ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Articles  (629)
  • Rats  (629)
  • 2005-2009  (270)
  • 1990-1994  (359)
  • Physics  (629)
Collection
  • Articles  (629)
Source
Keywords
Publisher
Years
Year
Journal
Topic
  • 1
    Electronic Resource
    Electronic Resource
    Production of new trabecular bone in osteopenic ovariectomized rats by prostaglandin E2 (1992)
    Springer
    Calcified tissue international 50 (1992), S. 80-87 
    Details
    ISSN: 1432-0827
    Keywords: PGE2 ; Ovariectomy ; Rats ; New bone trabeculae ; Positive balance ; Accelerated bone turnover
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Serum chemistry and bone morphometry of the proximal tibial metaphysis were performed in 3-month-old double fluorescent-labeled, female Sprague-Dawley rats subjected to bilateral ovariectomy or sham surgery for 4 months prior to treatment with 0, 0.3, 1, 3, or 6 mg of prostaglandin E2 (PGE2)/kg/day subcutaneously for 30 days. The 4-month postovariectomized rats possessed an osteopenic proximal tibial metaphysis with 7% trabecular area compared with controls (19%). PGE2 treatment elevated osteocalcin levels and augmented proximal tibial metaphyseal bone area in ovariectomized and sham-operated rats. Osteopenic, ovariectomized rats treated with 6 mg PGE2/kg/day for 30 days restored bone area to levels of agematched sham-operated rats. Morphometric analyses showed increased woven and lamellar bone area, fluorescent-labeled perimeter (osteoblastic recruitment), mineral apposition rate (osteoblastic activity), bone formation rate (BFR/BV), and longitudinal bone growth. These dramatic bone changes were all significantly increased at the doseresponse manner. This study showed that in vivo PGE2 is a powerful activator of bone remodeling, it increases both bone resorption and bone formation, and produces an anabolic effect by shifting bone balance to the positive direction. Furthermore, PGE2-induced augmentation of metaphyseal bone area in ovariectomized rats was at least two times greater than in sham-operated rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00297302
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Effects of estrogen replacement on insulin-like growth factor I concentrations in serum and bone tissue and on interleukin 1 secretion from spleen macrophages in oophorectomized rats (1993)
    Springer
    Calcified tissue international 53 (1993), S. 111-116 
    Details
    ISSN: 1432-0827
    Keywords: Insulinlike growth factor I ; Interleukin 1 ; Oophorectomy ; Estrogen ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Oophorectomy (OOX) has been known to increase bone turnover, but its precise mechanism is not fully understood. In order to further investigate the mechanism, we determined insulinlike growth factor I (IGF-I) concentrations in serum and bone tissue and interleukin 1 (IL-1) release from spleen macrophages in oophorectomized rats because it has been demonstrated that IGF-I stimulates bone formation and IL-1 stimulates bone resorption. Female 8-week-old Wistar rats were divided into four groups: (1) control, (2) OOX, (3) OOX given estradiol, and (4) control given estradiol. Ten μg/kg of 17β-estradiol was given daily by subcutaneous injection. After 5 weeks of treatment, IGF-I concentrations in the extract from right femur and in serum were determined by specific radioimmunoassay. IL-1 activity released from lipopolysaccharide (LPS)-stimulated spleen macrophages was determined by bioassay. IGF-I contents in the femur and IGF-I concentrations in serum in oophorectomized rats were significantly higher than those in control rats. Treatment by estradiol inhibited the increase in IGF-I concentrations both in femur and in serum. IL-1 release from LPS-stimulated spleen macrophages in oophorectomized rats was increased, and treatment by estradiol also inhibited the stimulated IL-1 release. The ash weights and the calcium contents of left femur in oophorectomized rats were lower than those in control rats. These results suggest that both IGF-I and IL-1 may be involved in the mechanism of the regulation of bone turnover in oophorectomized rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01321888
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Humoral (immunological) responses in female albino rats during rotating magnetic field exposures (1991)
    Springer
    International journal of biometeorology 34 (1991), S. 239-241 
    Details
    ISSN: 1432-1254
    Keywords: Immunology ; Human serum albumin (HSA) ; Magnetic fields ; Rats ; Females
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract Experiments were designed to evaluate the primary and secondary humoral responses to a rotating magnetic field configuration, which is known to evoke significant biobehavioral changes. Ten days after inoculation with human serum albumin and 10 days before a booster, female rats were exposed to eigher a 0.5 Hz rotating magnetic field (RMF) or to room conditions (control). The lighting schedule was either continuous or involved a light-dark cycle (LD) of 12:12h. A third group of rats served as colony room controls. Group differences of low statistical significance were found when females were exposed to continuous lighting rather than the LD 12:12 light-dark cycle. However, the effects were considered trivial and not sufficient to explain the previously reported biobehavioral changes evoked by this field configuration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01041836
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Studies on organ weights in naproxen treated rats after intermittent exposure to simulated high altitude (1990)
    Springer
    International journal of biometeorology 34 (1990), S. 90-92 
    Details
    ISSN: 1432-1254
    Keywords: Rats ; Naproxen ; Hypoxia ; Organ weight
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract Rats were exposed intermittently for 8h per day over 6 days at simulated high altitude of 20 000 feet. One group of altitude-exposed animals was treated with naproxen, a prostaglandin inhibiting drug. Significant reduction in body weight gain was observed in both altitude-exposed and drug-treated altitude-exposed animals compared to the control group. Right and left ventricular weights and weights of the adrenal glands were increased significantly in altitude-exposed and altitude-exposed drug-treated animals. The weight of the spleen was increased significantly in altitude-exposed animals whereas no such increase of splenic weight was observed in drug-treated altitude-exposed group of animals. On the other hand, the weight of the liver was decreased significantly in both cases. In drug-treated altitude-exposed animals, the unaltered splenic weight was thought to be due to inhibition of the erythropoietic activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01093453
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    facet.materialart.
    Unknown
    Compartmentalized dendritic plasticity and input feature storage in neurons (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-03-28
    Description: Although information storage in the central nervous system is thought to be primarily mediated by various forms of synaptic plasticity, other mechanisms, such as modifications in membrane excitability, are available. Local dendritic spikes are nonlinear voltage events that are initiated within dendritic branches by spatially clustered and temporally synchronous synaptic input. That local spikes selectively respond only to appropriately correlated input allows them to function as input feature detectors and potentially as powerful information storage mechanisms. However, it is currently unknown whether any effective form of local dendritic spike plasticity exists. Here we show that the coupling between local dendritic spikes and the soma of rat hippocampal CA1 pyramidal neurons can be modified in a branch-specific manner through an N-methyl-d-aspartate receptor (NMDAR)-dependent regulation of dendritic Kv4.2 potassium channels. These data suggest that compartmentalized changes in branch excitability could store multiple complex features of synaptic input, such as their spatio-temporal correlation. We propose that this 'branch strength potentiation' represents a previously unknown form of information storage that is distinct from that produced by changes in synaptic efficacy both at the mechanistic level and in the type of information stored.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Losonczy, Attila -- Makara, Judit K -- Magee, Jeffrey C -- England -- Nature. 2008 Mar 27;452(7186):436-41. doi: 10.1038/nature06725.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Dr Ashburn, Virginia 20147, USA. losonczya@janelia.hhmi.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18368112" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/physiology ; Animals ; Cell Shape ; Dendrites/*physiology ; Ion Channel Gating ; Male ; Mice ; Models, Neurological ; Neuronal Plasticity/*physiology ; Pyramidal Cells/*cytology/*metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism ; Shal Potassium Channels/deficiency/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 6
    facet.materialart.
    Unknown
    Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-05-27
    Description: Relapse to cocaine use after prolonged abstinence is an important clinical problem. This relapse is often induced by exposure to cues associated with cocaine use. To account for the persistent propensity for relapse, it has been suggested that cue-induced cocaine craving increases over the first several weeks of abstinence and remains high for extended periods. We and others identified an analogous phenomenon in rats that was termed 'incubation of cocaine craving': time-dependent increases in cue-induced cocaine-seeking over the first months after withdrawal from self-administered cocaine. Cocaine-seeking requires the activation of glutamate projections that excite receptors for alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in the nucleus accumbens. Here we show that the number of synaptic AMPA receptors in the accumbens is increased after prolonged withdrawal from cocaine self-administration by the addition of new AMPA receptors lacking glutamate receptor 2 (GluR2). Furthermore, we show that these new receptors mediate the incubation of cocaine craving. Our results indicate that GluR2-lacking AMPA receptors could be a new target for drug development for the treatment of cocaine addiction. We propose that after prolonged withdrawal from cocaine, increased numbers of synaptic AMPA receptors combined with the higher conductance of GluR2-lacking AMPA receptors causes increased reactivity of accumbens neurons to cocaine-related cues, leading to an intensification of drug craving and relapse.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574981/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574981/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Conrad, Kelly L -- Tseng, Kuei Y -- Uejima, Jamie L -- Reimers, Jeremy M -- Heng, Li-Jun -- Shaham, Yavin -- Marinelli, Michela -- Wolf, Marina E -- DA00453/DA/NIDA NIH HHS/ -- DA015835/DA/NIDA NIH HHS/ -- DA020654/DA/NIDA NIH HHS/ -- DA09621/DA/NIDA NIH HHS/ -- Z01 DA000434-08/Intramural NIH HHS/ -- England -- Nature. 2008 Jul 3;454(7200):118-21. doi: 10.1038/nature06995. Epub 2008 May 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, Illinois 60064, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18500330" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cocaine ; Cocaine-Related Disorders/genetics/metabolism/*physiopathology ; Cues ; Gene Expression Regulation ; Male ; Nucleus Accumbens/*metabolism/physiopathology ; Rats ; Rats, Long-Evans ; Rats, Sprague-Dawley ; Receptors, AMPA/deficiency/genetics/*metabolism ; Self Administration ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 7
    facet.materialart.
    Unknown
    Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-04-11
    Description: Energy and glucose homeostasis are regulated by food intake and liver glucose production, respectively. The upper intestine has a critical role in nutrient digestion and absorption. However, studies indicate that upper intestinal lipids inhibit food intake as well in rodents and humans by the activation of an intestine-brain axis. In parallel, a brain-liver axis has recently been proposed to detect blood lipids to inhibit glucose production in rodents. Thus, we tested the hypothesis that upper intestinal lipids activate an intestine-brain-liver neural axis to regulate glucose homeostasis. Here we demonstrate that direct administration of lipids into the upper intestine increased upper intestinal long-chain fatty acyl-coenzyme A (LCFA-CoA) levels and suppressed glucose production. Co-infusion of the acyl-CoA synthase inhibitor triacsin C or the anaesthetic tetracaine with duodenal lipids abolished the inhibition of glucose production, indicating that upper intestinal LCFA-CoAs regulate glucose production in the preabsorptive state. Subdiaphragmatic vagotomy or gut vagal deafferentation interrupts the neural connection between the gut and the brain, and blocks the ability of upper intestinal lipids to inhibit glucose production. Direct administration of the N-methyl-d-aspartate ion channel blocker MK-801 into the fourth ventricle or the nucleus of the solitary tract where gut sensory fibres terminate abolished the upper-intestinal-lipid-induced inhibition of glucose production. Finally, hepatic vagotomy negated the inhibitory effects of upper intestinal lipids on glucose production. These findings indicate that upper intestinal lipids activate an intestine-brain-liver neural axis to inhibit glucose production, and thereby reveal a previously unappreciated pathway that regulates glucose homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Penny Y T -- Caspi, Liora -- Lam, Carol K L -- Chari, Madhu -- Li, Xiaosong -- Light, Peter E -- Gutierrez-Juarez, Roger -- Ang, Michelle -- Schwartz, Gary J -- Lam, Tony K T -- DK45024/DK/NIDDK NIH HHS/ -- DK47208/DK/NIDDK NIH HHS/ -- England -- Nature. 2008 Apr 24;452(7190):1012-6. doi: 10.1038/nature06852. Epub 2008 Apr 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Toronto General Hospital Research Institute, University Health Network, Toronto M5G 1L7, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18401341" target="_blank"〉PubMed〈/a〉
    Keywords: Acyl Coenzyme A/biosynthesis/metabolism ; Animals ; Brain/drug effects/*metabolism ; Dietary Fats/administration & dosage/metabolism/*pharmacology ; Fatty Acids/chemistry/metabolism ; Glucose/*biosynthesis/metabolism ; Homeostasis/drug effects ; Insulin/metabolism ; Intestines/drug effects/innervation/*metabolism ; *Lipid Metabolism ; Liver/drug effects/innervation/*metabolism ; Rats ; Satiety Response/drug effects ; Tetracaine/pharmacology ; Triazenes/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    Oligopotent stem cells are distributed throughout the mammalian ocular surface (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-10-03
    Description: The integrity of the cornea, the most anterior part of the eye, is indispensable for vision. Forty-five million individuals worldwide are bilaterally blind and another 135 million have severely impaired vision in both eyes because of loss of corneal transparency; treatments range from local medications to corneal transplants, and more recently to stem cell therapy. The corneal epithelium is a squamous epithelium that is constantly renewing, with a vertical turnover of 7 to 14 days in many mammals. Identification of slow cycling cells (label-retaining cells) in the limbus of the mouse has led to the notion that the limbus is the niche for the stem cells responsible for the long-term renewal of the cornea; hence, the corneal epithelium is supposedly renewed by cells generated at and migrating from the limbus, in marked opposition to other squamous epithelia in which each resident stem cell has in charge a limited area of epithelium. Here we show that the corneal epithelium of the mouse can be serially transplanted, is self-maintained and contains oligopotent stem cells with the capacity to generate goblet cells if provided with a conjunctival environment. Furthermore, the entire ocular surface of the pig, including the cornea, contains oligopotent stem cells (holoclones) with the capacity to generate individual colonies of corneal and conjunctival cells. Therefore, the limbus is not the only niche for corneal stem cells and corneal renewal is not different from other squamous epithelia. We propose a model that unifies our observations with the literature and explains why the limbal region is enriched in stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Majo, Francois -- Rochat, Ariane -- Nicolas, Michael -- Jaoude, Georges Abou -- Barrandon, Yann -- England -- Nature. 2008 Nov 13;456(7219):250-4. doi: 10.1038/nature07406. Epub 2008 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Stem Cell Dynamics, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne CH, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18830243" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*cytology ; Animals ; Cattle ; Cells, Cultured ; Child, Preschool ; Clone Cells ; Corneal Transplantation ; Epithelium, Corneal/*cytology/metabolism ; Female ; Gene Expression Regulation ; Humans ; Infant ; Keratinocytes/cytology/metabolism ; Male ; Mice ; Mice, SCID ; Models, Biological ; Multipotent Stem Cells/*cytology ; Proteins/metabolism ; Rats ; Swine
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    Crystal structure of the neurotrophin-3 and p75NTR symmetrical complex (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-07-04
    Description: Neurotrophins (NTs) are important regulators for the survival, differentiation and maintenance of different peripheral and central neurons. NTs bind to two distinct classes of glycosylated receptor: the p75 neurotrophin receptor (p75(NTR)) and tyrosine kinase receptors (Trks). Whereas p75(NTR) binds to all NTs, the Trk subtypes are specific for each NT. The question of whether NTs stimulate p75(NTR) by inducing receptor homodimerization is still under debate. Here we report the 2.6-A resolution crystal structure of neurotrophin-3 (NT-3) complexed to the ectodomain of glycosylated p75(NTR). In contrast to the previously reported asymmetric complex structure, which contains a dimer of nerve growth factor (NGF) bound to a single ectodomain of deglycosylated p75(NTR) (ref. 3), we show that NT-3 forms a central homodimer around which two glycosylated p75(NTR) molecules bind symmetrically. Symmetrical binding occurs along the NT-3 interfaces, resulting in a 2:2 ligand-receptor cluster. A comparison of the symmetrical and asymmetric structures reveals significant differences in ligand-receptor interactions and p75(NTR) conformations. Biochemical experiments indicate that both NT-3 and NGF bind to p75(NTR) with 2:2 stoichiometry in solution, whereas the 2:1 complexes are the result of artificial deglycosylation. We therefore propose that the symmetrical 2:2 complex reflects a native state of p75(NTR) activation at the cell surface. These results provide a model for NTs-p75(NTR) recognition and signal generation, as well as insights into coordination between p75(NTR) and Trks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gong, Yong -- Cao, Peng -- Yu, Hong-jun -- Jiang, Tao -- England -- Nature. 2008 Aug 7;454(7205):789-93. doi: 10.1038/nature07089. Epub 2008 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18596692" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Crystallography, X-Ray ; Dimerization ; Glycosylation ; Humans ; Ligands ; Models, Molecular ; Neurotrophin 3/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Rats ; Receptor, Nerve Growth Factor/*chemistry/genetics/*metabolism ; Spodoptera
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 10
    facet.materialart.
    Unknown
    Brain metabolism dictates the polarity of astrocyte control over arterioles (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-10-31
    Description: Calcium signalling in astrocytes couples changes in neural activity to alterations in cerebral blood flow by eliciting vasoconstriction or vasodilation of arterioles. However, the mechanism for how these opposite astrocyte influences provide appropriate changes in vessel tone within an environment that has dynamic metabolic requirements remains unclear. Here we show that the ability of astrocytes to induce vasodilations over vasoconstrictions relies on the metabolic state of the rat brain tissue. When oxygen availability is lowered and astrocyte calcium concentration is elevated, astrocyte glycolysis and lactate release are maximized. External lactate attenuates transporter-mediated uptake from the extracellular space of prostaglandin E(2), leading to accumulation and subsequent vasodilation. In conditions of low oxygen concentration extracellular adenosine also increases, which blocks astrocyte-mediated constriction, facilitating dilation. These data reveal the role of metabolic substrates in regulating brain blood flow and provide a mechanism for differential astrocyte control over cerebrovascular diameter during different states of brain activation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097022/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097022/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gordon, Grant R J -- Choi, Hyun B -- Rungta, Ravi L -- Ellis-Davies, Graham C R -- MacVicar, Brian A -- R01 GM053395/GM/NIGMS NIH HHS/ -- R01 GM053395-13/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Dec 11;456(7223):745-9. doi: 10.1038/nature07525. Epub 2008 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Brain Research Centre, Department of Psychiatry, University of British Columbia, British Columbia T2N 2B5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18971930" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine/metabolism/pharmacology ; Animals ; Arterioles/drug effects/*metabolism ; Astrocytes/*metabolism ; Brain/*blood supply/*metabolism ; Dinoprostone/metabolism ; Glycolysis ; Lactic Acid/metabolism ; Male ; Organic Anion Transporters/metabolism ; Oxygen/metabolism ; Pressure ; Prostaglandin-Endoperoxide Synthases/metabolism ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction/drug effects/*physiology ; Vasodilation/drug effects/*physiology ; Vasodilator Agents/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 11
    facet.materialart.
    Unknown
    A discontinuous hammerhead ribozyme embedded in a mammalian messenger RNA (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-07-11
    Description: Structured RNAs embedded in the untranslated regions (UTRs) of messenger RNAs can regulate gene expression. In bacteria, control of a metabolite gene is mediated by the self-cleaving activity of a ribozyme embedded in its 5' UTR. This discovery has raised the question of whether gene-regulating ribozymes also exist in eukaryotic mRNAs. Here we show that highly active hammerhead ribozymes are present in the 3' UTRs of rodent C-type lectin type II (Clec2) genes. Using a hammerhead RNA motif search with relaxed delimitation of the non-conserved regions, we detected ribozyme sequences in which the invariant regions, in contrast to the previously identified continuous hammerheads, occur as two fragments separated by hundreds of nucleotides. Notably, a fragment pair can assemble to form an active hammerhead ribozyme structure between the translation termination and the polyadenylation signals within the 3' UTR. We demonstrate that this hammerhead structure can self-cleave both in vitro and in vivo, and is able to reduce protein expression in mouse cells. These results indicate that an unrecognized mechanism of post-transcriptional gene regulation involving association of discontinuous ribozyme sequences within an mRNA may be modulating the expression of several CLEC2 proteins that function in bone remodelling and the immune response of several mammals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612532/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612532/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martick, Monika -- Horan, Lucas H -- Noller, Harry F -- Scott, William G -- R01 AI043393/AI/NIAID NIH HHS/ -- R01 AI043393-09/AI/NIAID NIH HHS/ -- R01 GM087721/GM/NIGMS NIH HHS/ -- R01043393/PHS HHS/ -- England -- Nature. 2008 Aug 14;454(7206):899-902. doi: 10.1038/nature07117. Epub 2008 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Biology of RNA, University of California, Santa Cruz, California 95064, USA. mmartick@yahoo.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18615019" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics ; Animals ; Down-Regulation ; Lectins, C-Type/genetics/metabolism ; Mice ; Models, Molecular ; NIH 3T3 Cells ; Nucleic Acid Conformation ; RNA, Catalytic/chemistry/*genetics/metabolism ; RNA, Messenger/chemistry/*genetics/metabolism ; Rats ; Reverse Transcriptase Polymerase Chain Reaction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 12
    facet.materialart.
    Unknown
    Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-12-19
    Description: Palmitoylation regulates diverse aspects of neuronal protein trafficking and function. Here a global characterization of rat neural palmitoyl-proteomes identifies most of the known neural palmitoyl proteins-68 in total, plus more than 200 new palmitoyl-protein candidates, with further testing confirming palmitoylation for 21 of these candidates. The new palmitoyl proteins include neurotransmitter receptors, transporters, adhesion molecules, scaffolding proteins, as well as SNAREs and other vesicular trafficking proteins. Of particular interest is the finding of palmitoylation for a brain-specific Cdc42 splice variant. The palmitoylated Cdc42 isoform (Cdc42-palm) differs from the canonical, prenylated form (Cdc42-prenyl), both with regard to localization and function: Cdc42-palm concentrates in dendritic spines and has a special role in inducing these post-synaptic structures. Furthermore, assessing palmitoylation dynamics in drug-induced activity models identifies rapidly induced changes for Cdc42 as well as for other synaptic palmitoyl proteins, suggesting that palmitoylation may participate broadly in the activity-driven changes that shape synapse morphology and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2610860/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2610860/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, Rujun -- Wan, Junmei -- Arstikaitis, Pamela -- Takahashi, Hideto -- Huang, Kun -- Bailey, Aaron O -- Thompson, James X -- Roth, Amy F -- Drisdel, Renaldo C -- Mastro, Ryan -- Green, William N -- Yates, John R 3rd -- Davis, Nicholas G -- El-Husseini, Alaa -- DA019695/DA/NIDA NIH HHS/ -- DA13602/DA/NIDA NIH HHS/ -- GM65525/GM/NIGMS NIH HHS/ -- NS043782/NS/NINDS NIH HHS/ -- P01 DA019695/DA/NIDA NIH HHS/ -- P01 DA019695-01A20001/DA/NIDA NIH HHS/ -- P01 DA019695-020001/DA/NIDA NIH HHS/ -- R01 DA013602/DA/NIDA NIH HHS/ -- R01 DA013602-01/DA/NIDA NIH HHS/ -- R01 DA013602-02/DA/NIDA NIH HHS/ -- R01 DA013602-02S1/DA/NIDA NIH HHS/ -- R01 DA013602-02S2/DA/NIDA NIH HHS/ -- R01 DA013602-03/DA/NIDA NIH HHS/ -- R01 DA013602-04/DA/NIDA NIH HHS/ -- R01 DA013602-05/DA/NIDA NIH HHS/ -- R01 NS032693/NS/NINDS NIH HHS/ -- R01 NS032693-08/NS/NINDS NIH HHS/ -- R01 NS043782/NS/NINDS NIH HHS/ -- R01 NS043782-01A2/NS/NINDS NIH HHS/ -- R01 NS043782-02/NS/NINDS NIH HHS/ -- R01 NS043782-03/NS/NINDS NIH HHS/ -- R01 NS043782-04/NS/NINDS NIH HHS/ -- R01 NS043782-05/NS/NINDS NIH HHS/ -- R56 NS043782/NS/NINDS NIH HHS/ -- R56 NS043782-06/NS/NINDS NIH HHS/ -- RR011823/RR/NCRR NIH HHS/ -- England -- Nature. 2008 Dec 18;456(7224):904-9. doi: 10.1038/nature07605.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver V6T 1Z3, British Columbia, Canada. rkang@interchange.ubc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19092927" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing/genetics ; Animals ; Cells, Cultured ; Cerebral Cortex/cytology/embryology ; Dendrites/metabolism ; *Lipoylation ; Models, Neurological ; Neurons/*metabolism ; Organ Specificity ; Proteome/metabolism ; *Proteomics ; Rats ; Synapses/*metabolism ; cdc42 GTP-Binding Protein/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 13
    facet.materialart.
    Unknown
    A phosphatase cascade by which rewarding stimuli control nucleosomal response (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-05-23
    Description: Dopamine orchestrates motor behaviour and reward-driven learning. Perturbations of dopamine signalling have been implicated in several neurological and psychiatric disorders, and in drug addiction. The actions of dopamine are mediated in part by the regulation of gene expression in the striatum, through mechanisms that are not fully understood. Here we show that drugs of abuse, as well as food reinforcement learning, promote the nuclear accumulation of 32-kDa dopamine-regulated and cyclic-AMP-regulated phosphoprotein (DARPP-32). This accumulation is mediated through a signalling cascade involving dopamine D1 receptors, cAMP-dependent activation of protein phosphatase-2A, dephosphorylation of DARPP-32 at Ser 97 and inhibition of its nuclear export. The nuclear accumulation of DARPP-32, a potent inhibitor of protein phosphatase-1, increases the phosphorylation of histone H3, an important component of nucleosomal response. Mutation of Ser 97 profoundly alters behavioural effects of drugs of abuse and decreases motivation for food, underlining the functional importance of this signalling cascade.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796210/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796210/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stipanovich, Alexandre -- Valjent, Emmanuel -- Matamales, Miriam -- Nishi, Akinori -- Ahn, Jung-Hyuck -- Maroteaux, Matthieu -- Bertran-Gonzalez, Jesus -- Brami-Cherrier, Karen -- Enslen, Herve -- Corbille, Anne-Gaelle -- Filhol, Odile -- Nairn, Angus C -- Greengard, Paul -- Herve, Denis -- Girault, Jean-Antoine -- DA10044/DA/NIDA NIH HHS/ -- MH74866/MH/NIMH NIH HHS/ -- P01 DA010044/DA/NIDA NIH HHS/ -- P01 DA010044-020002/DA/NIDA NIH HHS/ -- P01 DA010044-030002/DA/NIDA NIH HHS/ -- P01 DA010044-04/DA/NIDA NIH HHS/ -- P01 DA010044-040002/DA/NIDA NIH HHS/ -- P01 DA010044-05/DA/NIDA NIH HHS/ -- P01 DA010044-050002/DA/NIDA NIH HHS/ -- P01 DA010044-06/DA/NIDA NIH HHS/ -- P01 DA010044-060002/DA/NIDA NIH HHS/ -- P01 DA010044-07/DA/NIDA NIH HHS/ -- P01 DA010044-070002/DA/NIDA NIH HHS/ -- P01 DA010044-08/DA/NIDA NIH HHS/ -- P01 DA010044-080002/DA/NIDA NIH HHS/ -- P01 DA010044-09/DA/NIDA NIH HHS/ -- P01 DA010044-090002/DA/NIDA NIH HHS/ -- P01 DA010044-10/DA/NIDA NIH HHS/ -- P01 DA010044-100002/DA/NIDA NIH HHS/ -- P01 DA010044-11/DA/NIDA NIH HHS/ -- P01 DA010044-110005/DA/NIDA NIH HHS/ -- P01 DA010044-12/DA/NIDA NIH HHS/ -- P01 DA010044-120005/DA/NIDA NIH HHS/ -- P01 DA010044-129002/DA/NIDA NIH HHS/ -- P01 DA010044-13/DA/NIDA NIH HHS/ -- P01 DA010044-130005/DA/NIDA NIH HHS/ -- P01 DA010044-139002/DA/NIDA NIH HHS/ -- P01 DA010044-14/DA/NIDA NIH HHS/ -- P01 DA010044-140005/DA/NIDA NIH HHS/ -- P01 DA010044-149002/DA/NIDA NIH HHS/ -- P01 DA010044-14S1/DA/NIDA NIH HHS/ -- P50 MH074866/MH/NIMH NIH HHS/ -- P50 MH074866-010001/MH/NIMH NIH HHS/ -- P50 MH074866-019001/MH/NIMH NIH HHS/ -- P50 MH074866-020001/MH/NIMH NIH HHS/ -- P50 MH074866-029001/MH/NIMH NIH HHS/ -- P50 MH074866-030001/MH/NIMH NIH HHS/ -- P50 MH074866-039001/MH/NIMH NIH HHS/ -- P50 MH074866-040001/MH/NIMH NIH HHS/ -- P50 MH074866-049001/MH/NIMH NIH HHS/ -- P50 MH074866-050001/MH/NIMH NIH HHS/ -- P50 MH074866-059001/MH/NIMH NIH HHS/ -- England -- Nature. 2008 Jun 12;453(7197):879-84. doi: 10.1038/nature06994. Epub 2008 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Inserm, UMR-S 839, 75005 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18496528" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Dopamine/metabolism ; Dopamine and cAMP-Regulated Phosphoprotein 32/chemistry/genetics/*metabolism ; Food ; Histones/metabolism ; Learning ; Male ; Mice ; Mice, Inbred C57BL ; Motivation ; Motor Activity/physiology ; Neostriatum/cytology ; Neurons/metabolism ; Nucleosomes/*metabolism ; Phosphoprotein Phosphatases/antagonists & inhibitors/*metabolism ; Phosphorylation/drug effects ; Phosphoserine/metabolism ; Protein Transport ; Rats ; *Reward ; *Signal Transduction/drug effects ; Substance-Related Disorders
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 14
    facet.materialart.
    Unknown
    Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-05-02
    Description: Phosphoinositide 3-kinases (PI3Ks) signal downstream of multiple cell-surface receptor types. Class IA PI3K isoforms couple to tyrosine kinases and consist of a p110 catalytic subunit (p110alpha, p110beta or p110delta), constitutively bound to one of five distinct p85 regulatory subunits. PI3Ks have been implicated in angiogenesis, but little is known about potential selectivity among the PI3K isoforms and their mechanism of action in endothelial cells during angiogenesis in vivo. Here we show that only p110alpha activity is essential for vascular development. Ubiquitous or endothelial cell-specific inactivation of p110alpha led to embryonic lethality at mid-gestation because of severe defects in angiogenic sprouting and vascular remodelling. p110alpha exerts this critical endothelial cell-autonomous function by regulating endothelial cell migration through the small GTPase RhoA. p110alpha activity is particularly high in endothelial cells and preferentially induced by tyrosine kinase ligands (such as vascular endothelial growth factor (VEGF)-A). In contrast, p110beta in endothelial cells signals downstream of G-protein-coupled receptor (GPCR) ligands such as SDF-1alpha, whereas p110delta is expressed at low level and contributes only minimally to PI3K activity in endothelial cells. These results provide the first in vivo evidence for p110-isoform selectivity in endothelial PI3K signalling during angiogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Graupera, Mariona -- Guillermet-Guibert, Julie -- Foukas, Lazaros C -- Phng, Li-Kun -- Cain, Robert J -- Salpekar, Ashreena -- Pearce, Wayne -- Meek, Stephen -- Millan, Jaime -- Cutillas, Pedro R -- Smith, Andrew J H -- Ridley, Anne J -- Ruhrberg, Christiana -- Gerhardt, Holger -- Vanhaesebroeck, Bart -- BB/C505659/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/C505659/2/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0601093/Medical Research Council/United Kingdom -- G0601093(79633)/Medical Research Council/United Kingdom -- G0700711/Medical Research Council/United Kingdom -- Cancer Research UK/United Kingdom -- England -- Nature. 2008 May 29;453(7195):662-6. doi: 10.1038/nature06892. Epub 2008 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Cell Signalling, Institute of Cancer, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18449193" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Movement ; Cells, Cultured ; Class I Phosphatidylinositol 3-Kinases ; Endothelial Cells/*cytology/*enzymology ; Female ; Humans ; Mice ; *Neovascularization, Physiologic ; Phosphatidylinositol 3-Kinases/genetics/*metabolism ; RNA Interference ; Rats ; Signal Transduction/drug effects ; Vascular Endothelial Growth Factor A/pharmacology ; Wounds and Injuries ; rho GTP-Binding Proteins/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 15
    facet.materialart.
    Unknown
    A structural explanation for the binding of endocytic dileucine motifs by the AP2 complex (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-01-14
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340503/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340503/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kelly, Bernard T -- McCoy, Airlie J -- Spate, Kira -- Miller, Sharon E -- Evans, Philip R -- Honing, Stefan -- Owen, David J -- 090909/Wellcome Trust/United Kingdom -- MC_U105178845/Medical Research Council/United Kingdom -- England -- Nature. 2008 Dec 18;456(7224):976-79. doi: 10.1038/nature07422.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19140243" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Protein Complex 2/*chemistry/genetics/*metabolism ; Amino Acid Motifs ; Animals ; Antigens, CD4/*chemistry/*metabolism ; Binding Sites ; Conserved Sequence ; *Endocytosis ; Humans ; Leucine/*metabolism ; Mice ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Subunits/chemistry/genetics/metabolism ; Rats
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 16
    facet.materialart.
    Unknown
    The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-05-02
    Description: Lysosomes are the stomachs of the cell-terminal organelles on the endocytic pathway where internalized macromolecules are degraded. Containing a wide range of hydrolytic enzymes, lysosomes depend on maintaining acidic luminal pH values for efficient function. Although acidification is mediated by a V-type proton ATPase, a parallel anion pathway is essential to allow bulk proton transport. The molecular identity of this anion transporter remains unknown. Recent results of knockout experiments raise the possibility that ClC-7, a member of the CLC family of anion channels and transporters, is a contributor to this pathway in an osteoclast lysosome-like compartment, with loss of ClC-7 function causing osteopetrosis. Several mammalian members of the CLC family have been characterized in detail; some (including ClC-0, ClC-1 and ClC-2) function as Cl--conducting ion channels, whereas others act as Cl-/H+antiporters (ClC-4 and ClC-5). However, previous attempts at heterologous expression of ClC-7 have failed to yield evidence of functional protein, so it is unclear whether ClC-7 has an important function in lysosomal biology, and also whether this protein functions as a Cl- channel, a Cl-/H+ antiporter, or as something else entirely. Here we directly demonstrate an anion transport pathway in lysosomes that has the defining characteristics of a CLC Cl-/H+ antiporter and show that this transporter is the predominant route for Cl- through the lysosomal membrane. Furthermore, knockdown of ClC-7 expression by short interfering RNA can essentially ablate this lysosomal Cl-/H+ antiport activity and can strongly diminish the ability of lysosomes to acidify in vivo, demonstrating that ClC-7 is a Cl-/H+ antiporter, that it constitutes the major Cl- permeability of lysosomes, and that it is important in lysosomal acidification.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Graves, Austin R -- Curran, Patricia K -- Smith, Carolyn L -- Mindell, Joseph A -- Intramural NIH HHS/ -- England -- Nature. 2008 Jun 5;453(7196):788-92. doi: 10.1038/nature06907. Epub 2008 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Membrane Transport Biophysics Unit, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Building 35, MSC 3701, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18449189" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiporters/deficiency/genetics/*metabolism ; Chloride Channels/deficiency/genetics/*metabolism ; Chlorides/*metabolism ; Fluorescence ; HeLa Cells ; Humans ; Hydrogen-Ion Concentration ; Ion Transport ; Liver/cytology/metabolism ; Lysosomes/*metabolism ; Permeability ; Protons ; Rats
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 17
    facet.materialart.
    Unknown
    Neural correlates, computation and behavioural impact of decision confidence (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-08-12
    Description: Humans and other animals must often make decisions on the basis of imperfect evidence. Statisticians use measures such as P values to assign degrees of confidence to propositions, but little is known about how the brain computes confidence estimates about decisions. We explored this issue using behavioural analysis and neural recordings in rats in combination with computational modelling. Subjects were trained to perform an odour categorization task that allowed decision confidence to be manipulated by varying the distance of the test stimulus to the category boundary. To understand how confidence could be computed along with the choice itself, using standard models of decision-making, we defined a simple measure that quantified the quality of the evidence contributing to a particular decision. Here we show that the firing rates of many single neurons in the orbitofrontal cortex match closely to the predictions of confidence models and cannot be readily explained by alternative mechanisms, such as learning stimulus-outcome associations. Moreover, when tested using a delayed reward version of the task, we found that rats' willingness to wait for rewards increased with confidence, as predicted by the theoretical model. These results indicate that confidence estimates, previously suggested to require 'metacognition' and conscious awareness are available even in the rodent brain, can be computed with relatively simple operations, and can drive adaptive behaviour. We suggest that confidence estimation may be a fundamental and ubiquitous component of decision-making.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kepecs, Adam -- Uchida, Naoshige -- Zariwala, Hatim A -- Mainen, Zachary F -- England -- Nature. 2008 Sep 11;455(7210):227-31. doi: 10.1038/nature07200.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA. kepecs@cshl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18690210" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/*physiology ; Confidence Intervals ; Decision Making/*physiology ; Frontal Lobe/physiology ; Linear Models ; Male ; *Models, Neurological ; Neurons/*physiology ; Odors/analysis ; Rats ; Rats, Long-Evans ; Reward ; Smell/physiology ; Uncertainty
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 18
    facet.materialart.
    Unknown
    Deconstructing voltage sensor function and pharmacology in sodium channels (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-11-14
    Description: Voltage-activated sodium (Na(v)) channels are crucial for the generation and propagation of nerve impulses, and as such are widely targeted by toxins and drugs. The four voltage sensors in Na(v) channels have distinct amino acid sequences, raising fundamental questions about their relative contributions to the function and pharmacology of the channel. Here we use four-fold symmetric voltage-activated potassium (K(v)) channels as reporters to examine the contributions of individual S3b-S4 paddle motifs within Na(v) channel voltage sensors to the kinetics of voltage sensor activation and to forming toxin receptors. Our results uncover binding sites for toxins from tarantula and scorpion venom on each of the four paddle motifs in Na(v) channels, and reveal how paddle-specific interactions can be used to reshape Na(v) channel activity. One paddle motif is unique in that it slows voltage sensor activation, and toxins selectively targeting this motif impede Na(v) channel inactivation. This reporter approach and the principles that emerge will be useful in developing new drugs for treating pain and Na(v) channelopathies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587061/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587061/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bosmans, Frank -- Martin-Eauclaire, Marie-France -- Swartz, Kenton J -- ZIA NS003017-03/Intramural NIH HHS/ -- England -- Nature. 2008 Nov 13;456(7219):202-8. doi: 10.1038/nature07473.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19005548" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Ion Channel Gating/*drug effects ; Models, Molecular ; Mutagenesis ; Potassium Channels, Voltage-Gated/genetics/metabolism ; Protein Interaction Domains and Motifs/genetics/physiology ; Rats ; Recombinant Fusion Proteins/genetics/metabolism ; Scorpion Venoms/pharmacology ; Sodium Channels/genetics/*metabolism ; Spider Venoms/pharmacology ; Xenopus
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 19
    facet.materialart.
    Unknown
    Structural biology: Enzyme knocked for a loop (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mellgren, Ronald L -- England -- Nature. 2008 Nov 20;456(7220):337-8. doi: 10.1038/456337a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020611" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biocatalysis ; Calcium/metabolism ; Calcium-Binding Proteins/*chemistry/*metabolism ; Calpain/*antagonists & inhibitors/chemistry/*metabolism ; *Catalytic Domain ; Crystallography, X-Ray ; Models, Molecular ; Peptide Fragments/chemistry/metabolism ; Protein Binding ; Protein Multimerization ; Rats
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 20
    facet.materialart.
    Unknown
    TMEM16A confers receptor-activated calcium-dependent chloride conductance (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-08-30
    Description: Calcium (Ca(2+))-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remained largely unknown. Here we show that transmembrane protein 16A (TMEM16A, which we also call anoctamin 1 (ANO1)) is a bona fide Ca(2+)-activated chloride channel that is activated by intracellular Ca(2+) and Ca(2+)-mobilizing stimuli. With eight putative transmembrane domains and no apparent similarity to previously characterized channels, ANO1 defines a new family of ionic channels. The biophysical properties as well as the pharmacological profile of ANO1 are in full agreement with native Ca(2+)-activated chloride currents. ANO1 is expressed in various secretory epithelia, the retina and sensory neurons. Furthermore, knockdown of mouse Ano1 markedly reduced native Ca(2+)-activated chloride currents as well as saliva production in mice. We conclude that ANO1 is a candidate Ca(2+)-activated chloride channel that mediates receptor-activated chloride currents in diverse physiological processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Young Duk -- Cho, Hawon -- Koo, Jae Yeon -- Tak, Min Ho -- Cho, Yeongyo -- Shim, Won-Sik -- Park, Seung Pyo -- Lee, Jesun -- Lee, Byeongjun -- Kim, Byung-Moon -- Raouf, Ramin -- Shin, Young Ki -- Oh, Uhtaek -- Wellcome Trust/United Kingdom -- England -- Nature. 2008 Oct 30;455(7217):1210-5. doi: 10.1038/nature07313. Epub 2008 Aug 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18724360" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism/pharmacology ; Chloride Channels/chemistry/deficiency/genetics/*metabolism ; Chlorides/*metabolism ; Electric Conductivity ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Intracellular Space/drug effects/metabolism ; Ion Transport/drug effects ; Mice ; Oocytes/metabolism ; Pilocarpine/pharmacology ; RNA, Small Interfering/genetics/metabolism ; Rats ; Receptors, G-Protein-Coupled/*metabolism ; Salivation/drug effects ; Xenopus
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 21
    facet.materialart.
    Unknown
    Reversal of pathological pain through specific spinal GABAA receptor subtypes (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-01-19
    Description: Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment. A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology. Facilitation of spinal gamma-aminobutyric acid (GABA)ergic neurotransmission through modulation of GABA(A) receptors should be able to compensate for this loss. With the use of GABA(A)-receptor point-mutated knock-in mice in which specific GABA(A) receptor subtypes have been selectively rendered insensitive to benzodiazepine-site ligands, we show here that pronounced analgesia can be achieved by specifically targeting spinal GABA(A) receptors containing the alpha2 and/or alpha3 subunits. We show that their selective activation by the non-sedative ('alpha1-sparing') benzodiazepine-site ligand L-838,417 (ref. 13) is highly effective against inflammatory and neuropathic pain yet devoid of unwanted sedation, motor impairment and tolerance development. L-838,417 not only diminished the nociceptive input to the brain but also reduced the activity of brain areas related to the associative-emotional components of pain, as shown by functional magnetic resonance imaging in rats. These results provide a rational basis for the development of subtype-selective GABAergic drugs for the treatment of chronic pain, which is often refractory to classical analgesics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knabl, Julia -- Witschi, Robert -- Hosl, Katharina -- Reinold, Heiko -- Zeilhofer, Ulrike B -- Ahmadi, Seifollah -- Brockhaus, Johannes -- Sergejeva, Marina -- Hess, Andreas -- Brune, Kay -- Fritschy, Jean-Marc -- Rudolph, Uwe -- Mohler, Hanns -- Zeilhofer, Hanns Ulrich -- England -- Nature. 2008 Jan 17;451(7176):330-4. doi: 10.1038/nature06493.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nurnberg, D-91054 Erlangen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18202657" target="_blank"〉PubMed〈/a〉
    Keywords: Analgesics/administration & dosage/metabolism/pharmacology/therapeutic use ; Animals ; Brain/drug effects/physiology ; Capsaicin/pharmacology ; Chronic Disease/drug therapy ; Diazepam/administration & dosage/metabolism/pharmacology ; Disease Models, Animal ; Fluorobenzenes/metabolism/pharmacology ; Formaldehyde ; Ganglia, Spinal/cytology/metabolism ; Hot Temperature ; Inflammation/chemically induced/drug therapy ; Male ; Mice ; Neurons/drug effects/metabolism ; Organ Specificity ; Pain/chemically induced/*drug therapy/*metabolism/prevention & control ; Protein Isoforms/chemistry/metabolism ; Protein Subunits/chemistry/metabolism ; Rats ; Rats, Wistar ; Receptors, GABA-A/chemistry/genetics/*metabolism ; Spinal Cord/cytology/drug effects/*metabolism/physiopathology ; Triazoles/metabolism/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 22
    facet.materialart.
    Unknown
    Hippocampus-independent phase precession in entorhinal grid cells (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-05-16
    Description: Theta-phase precession in hippocampal place cells is one of the best-studied experimental models of temporal coding in the brain. Theta-phase precession is a change in spike timing in which the place cell fires at progressively earlier phases of the extracellular theta rhythm as the animal crosses the spatially restricted firing field of the neuron. Within individual theta cycles, this phase advance results in a compressed replication of the firing sequence of consecutively activated place cells along the animal's trajectory, at a timescale short enough to enable spike-time-dependent plasticity between neurons in different parts of the sequence. The neuronal circuitry required for phase precession has not yet been established. The fact that phase precession can be seen in hippocampal output stuctures such as the prefrontal cortex suggests either that efferent structures inherit the precession from the hippocampus or that it is generated locally in those structures. Here we show that phase precession is expressed independently of the hippocampus in spatially modulated grid cells in layer II of medial entorhinal cortex, one synapse upstream of the hippocampus. Phase precession is apparent in nearly all principal cells in layer II but only sparsely in layer III. The precession in layer II is not blocked by inactivation of the hippocampus, suggesting that the phase advance is generated in the grid cell network. The results point to possible mechanisms for grid formation and raise the possibility that hippocampal phase precession is inherited from entorhinal cortex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hafting, Torkel -- Fyhn, Marianne -- Bonnevie, Tora -- Moser, May-Britt -- Moser, Edvard I -- England -- Nature. 2008 Jun 26;453(7199):1248-52. doi: 10.1038/nature06957. Epub 2008 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory, Norwegian University of Science and Technology, NO-7489 Trondheim, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18480753" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Electroencephalography ; Entorhinal Cortex/*cytology/*physiology ; Hippocampus/cytology/physiology ; Male ; Models, Neurological ; Rats ; Rats, Long-Evans ; Running/physiology ; Theta Rhythm
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 23
    facet.materialart.
    Unknown
    Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-02-01
    Description: Understanding cellular response to environmental stress has broad implications for human disease. AMP-activated protein kinase (AMPK) orchestrates the regulation of energy-generating and -consuming pathways, and protects the heart against ischaemic injury and apoptosis. A role for circulating hormones such as adiponectin and leptin in the activation of AMPK has received recent attention. Whether local autocrine and paracrine factors within target organs such as the heart modulate AMPK is unknown. Here we show that macrophage migration inhibitory factor (MIF), an upstream regulator of inflammation, is released in the ischaemic heart, where it stimulates AMPK activation through CD74, promotes glucose uptake and protects the heart during ischaemia-reperfusion injury. Germline deletion of the Mif gene impairs ischaemic AMPK signalling in the mouse heart. Human fibroblasts with a low-activity MIF promoter polymorphism have diminished MIF release and AMPK activation during hypoxia. Thus, MIF modulates the activation of the cardioprotective AMPK pathway during ischaemia, functionally linking inflammation and metabolism in the heart. We anticipate that genetic variation in MIF expression may impact on the response of the human heart to ischaemia by the AMPK pathway, and that diagnostic MIF genotyping might predict risk in patients with coronary artery disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Edward J -- Li, Ji -- Leng, Lin -- McDonald, Courtney -- Atsumi, Toshiya -- Bucala, Richard -- Young, Lawrence H -- England -- Nature. 2008 Jan 31;451(7178):578-82. doi: 10.1038/nature06504.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Medicine Section of the Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18235500" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases ; Animals ; Anoxia/enzymology/genetics/metabolism ; Antigens, Differentiation, B-Lymphocyte/genetics/metabolism ; Coronary Artery Disease/genetics ; Enzyme Activation ; Genetic Predisposition to Disease ; Genotype ; Glucose/metabolism ; Histocompatibility Antigens Class II/genetics/metabolism ; Humans ; Macrophage Migration-Inhibitory Factors/deficiency/genetics/*metabolism/secretion ; Mice ; Multienzyme Complexes/*metabolism ; Myocardial Ischemia/enzymology/genetics/*metabolism ; Myocardial Reperfusion Injury/physiopathology/prevention & control ; Myocardium/enzymology/metabolism ; Polymorphism, Genetic/genetics ; Promoter Regions, Genetic/genetics ; Protein-Serine-Threonine Kinases/*metabolism ; Rats ; Signal Transduction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 24
    facet.materialart.
    Unknown
    Metabolism: food alert (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-04-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thaler, Joshua P -- Cummings, David E -- England -- Nature. 2008 Apr 24;452(7190):941-2. doi: 10.1038/452941a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18432230" target="_blank"〉PubMed〈/a〉
    Keywords: Acyl Coenzyme A/metabolism ; Animals ; Brain/drug effects/*metabolism ; Dietary Fats/administration & dosage/metabolism/*pharmacology ; Fatty Acids/metabolism ; Glucose/*biosynthesis/metabolism ; Homeostasis/drug effects ; Insulin/metabolism ; Intestines/drug effects/innervation/*metabolism ; Liver/drug effects/innervation/*metabolism ; Rats ; Satiety Response/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 25
    facet.materialart.
    Unknown
    MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-12-02
    Description: MicroRNAs comprise a broad class of small non-coding RNAs that control expression of complementary target messenger RNAs. Dysregulation of microRNAs by several mechanisms has been described in various disease states including cardiac disease. Whereas previous studies of cardiac disease have focused on microRNAs that are primarily expressed in cardiomyocytes, the role of microRNAs expressed in other cell types of the heart is unclear. Here we show that microRNA-21 (miR-21, also known as Mirn21) regulates the ERK-MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function. miR-21 levels are increased selectively in fibroblasts of the failing heart, augmenting ERK-MAP kinase activity through inhibition of sprouty homologue 1 (Spry1). This mechanism regulates fibroblast survival and growth factor secretion, apparently controlling the extent of interstitial fibrosis and cardiac hypertrophy. In vivo silencing of miR-21 by a specific antagomir in a mouse pressure-overload-induced disease model reduces cardiac ERK-MAP kinase activity, inhibits interstitial fibrosis and attenuates cardiac dysfunction. These findings reveal that microRNAs can contribute to myocardial disease by an effect in cardiac fibroblasts. Our results validate miR-21 as a disease target in heart failure and establish the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thum, Thomas -- Gross, Carina -- Fiedler, Jan -- Fischer, Thomas -- Kissler, Stephan -- Bussen, Markus -- Galuppo, Paolo -- Just, Steffen -- Rottbauer, Wolfgang -- Frantz, Stefan -- Castoldi, Mirco -- Soutschek, Jurgen -- Koteliansky, Victor -- Rosenwald, Andreas -- Basson, M Albert -- Licht, Jonathan D -- Pena, John T R -- Rouhanifard, Sara H -- Muckenthaler, Martina U -- Tuschl, Thomas -- Martin, Gail R -- Bauersachs, Johann -- Engelhardt, Stefan -- R01 CA059998/CA/NCI NIH HHS/ -- R01 CA78711/CA/NCI NIH HHS/ -- England -- Nature. 2008 Dec 18;456(7224):980-4. doi: 10.1038/nature07511. Epub 2008 Nov 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine I, Interdisziplinares Zentrum fur Klinische Forschung (IZKF), University of Wuerzburg, 97080 Wuerzburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19043405" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cardiomyopathies/*genetics/*metabolism/pathology/therapy ; Cell Line ; Cell Survival ; Cells, Cultured ; Disease Models, Animal ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fibroblasts/*metabolism ; Gene Silencing ; Humans ; *MAP Kinase Signaling System ; Male ; Mice ; Mice, Transgenic ; MicroRNAs/*genetics ; Myocytes, Cardiac/cytology/metabolism ; Rats
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 26
    facet.materialart.
    Unknown
    Single-nucleotide mutation rate increases close to insertions/deletions in eukaryotes (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-07-22
    Description: Mutation hotspots are commonly observed in genomic sequences and certain human disease loci, but general mechanisms for their formation remain elusive. Here we investigate the distribution of single-nucleotide changes around insertions/deletions (indels) in six independent genome comparisons, including primates, rodents, fruitfly, rice and yeast. In each of these genomic comparisons, nucleotide divergence (D) is substantially elevated surrounding indels and decreases monotonically to near-background levels over several hundred bases. D is significantly correlated with both size and abundance of nearby indels. In comparisons of closely related species, derived nucleotide substitutions surrounding indels occur in significantly greater numbers in the lineage containing the indel than in the one containing the ancestral (non-indel) allele; the same holds within species for single-nucleotide mutations surrounding polymorphic indels. We propose that heterozygosity for an indel is mutagenic to surrounding sequences, and use yeast genome-wide polymorphism data to estimate the increase in mutation rate. The consistency of these patterns within and between species suggests that indel-associated substitution is a general mutational mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tian, Dacheng -- Wang, Qiang -- Zhang, Pengfei -- Araki, Hitoshi -- Yang, Sihai -- Kreitman, Martin -- Nagylaki, Thomas -- Hudson, Richard -- Bergelson, Joy -- Chen, Jian-Qun -- England -- Nature. 2008 Sep 4;455(7209):105-8. doi: 10.1038/nature07175. Epub 2008 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Pharmaceutical Biotechnology, Department of Biology, Nanjing University, Nanjing 210093, China. dtian@nju.edu.cn〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18641631" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Computational Biology ; Drosophila melanogaster/genetics ; Eukaryotic Cells/*metabolism ; *Evolution, Molecular ; Genome/*genetics ; Genomics ; Humans ; Macaca mulatta/genetics ; Mice ; Models, Genetic ; Mutagenesis, Insertional/*genetics ; Oryza/genetics ; Pan troglodytes/genetics ; Point Mutation/*genetics ; Rats ; Saccharomyces cerevisiae/genetics ; Sequence Alignment ; Sequence Deletion/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 27
    facet.materialart.
    Unknown
    Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-11-21
    Description: The Ca(2+)-dependent cysteine proteases, calpains, regulate cell migration, cell death, insulin secretion, synaptic function and muscle homeostasis. Their endogenous inhibitor, calpastatin, consists of four inhibitory repeats, each of which neutralizes an activated calpain with exquisite specificity and potency. Despite the physiological importance of this interaction, the structural basis of calpain inhibition by calpastatin is unknown. Here we report the 3.0 A structure of Ca(2+)-bound m-calpain in complex with the first calpastatin repeat, both from rat, revealing the mechanism of exclusive specificity. The structure highlights the complexity of calpain activation by Ca(2+), illustrating key residues in a peripheral domain that serve to stabilize the protease core on Ca(2+) binding. Fully activated calpain binds ten Ca(2+) atoms, resulting in several conformational changes allowing recognition by calpastatin. Calpain inhibition is mediated by the intimate contact with three critical regions of calpastatin. Two regions target the penta-EF-hand domains of calpain and the third occupies the substrate-binding cleft, projecting a loop around the active site thiol to evade proteolysis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847431/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847431/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moldoveanu, Tudor -- Gehring, Kalle -- Green, Douglas R -- P01 CA069381/CA/NCI NIH HHS/ -- P01 CA069381-140010/CA/NCI NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 AI040646/AI/NIAID NIH HHS/ -- R01 AI040646-14/AI/NIAID NIH HHS/ -- R01 AI044828/AI/NIAID NIH HHS/ -- R01 AI044828-12/AI/NIAID NIH HHS/ -- R01 AI047891/AI/NIAID NIH HHS/ -- R01 AI047891-12/AI/NIAID NIH HHS/ -- R37 GM052735/GM/NIGMS NIH HHS/ -- R37 GM052735-19/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Nov 20;456(7220):404-8. doi: 10.1038/nature07353.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, St Jude Children's Research Hospital, 332 N Lauderdale, Memphis, Tennessee 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020622" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biocatalysis ; Calcium/metabolism ; Calcium-Binding Proteins/*chemistry/genetics/*metabolism ; Calpain/antagonists & inhibitors/*chemistry/*metabolism ; *Catalytic Domain ; Crystallography, X-Ray ; EF Hand Motifs ; Enzyme Activation ; Protein Binding ; Protein Multimerization ; Protein Processing, Post-Translational ; Rats ; Structure-Activity Relationship ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 28
    facet.materialart.
    Unknown
    The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-06-20
    Description: Cues that reliably predict rewards trigger the thoughts and emotions normally evoked by those rewards. Humans and other animals will work, often quite hard, for these cues. This is termed conditioned reinforcement. The ability to use conditioned reinforcers to guide our behaviour is normally beneficial; however, it can go awry. For example, corporate icons, such as McDonald's Golden Arches, influence consumer behaviour in powerful and sometimes surprising ways, and drug-associated cues trigger relapse to drug seeking in addicts and animals exposed to addictive drugs, even after abstinence or extinction. Yet, despite their prevalence, it is not known how conditioned reinforcers control human or other animal behaviour. One possibility is that they act through the use of the specific rewards they predict; alternatively, they could control behaviour directly by activating emotions that are independent of any specific reward. In other words, the Golden Arches may drive business because they evoke thoughts of hamburgers and fries, or instead, may be effective because they also evoke feelings of hunger or happiness. Moreover, different brain circuits could support conditioned reinforcement mediated by thoughts of specific outcomes versus more general affective information. Here we have attempted to address these questions in rats. Rats were trained to learn that different cues predicted different rewards using specialized conditioning procedures that controlled whether the cues evoked thoughts of specific outcomes or general affective representations common to different outcomes. Subsequently, these rats were given the opportunity to press levers to obtain short and otherwise unrewarded presentations of these cues. We found that rats were willing to work for cues that evoked either outcome-specific or general affective representations. Furthermore the orbitofrontal cortex, a prefrontal region important for adaptive decision-making, was critical for the former but not for the latter form of conditioned reinforcement.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727745/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727745/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burke, Kathryn A -- Franz, Theresa M -- Miller, Danielle N -- Schoenbaum, Geoffrey -- R01 DA015718/DA/NIDA NIH HHS/ -- R01 DA015718-06A2/DA/NIDA NIH HHS/ -- England -- Nature. 2008 Jul 17;454(7202):340-4. doi: 10.1038/nature06993. Epub 2008 Jun 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Neuroscience, University of Maryland School of Medicine, 20 Penn Street, HSF-2 S251 Baltimore, Maryland 21201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18563088" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/*physiology ; Conditioning, Classical/physiology ; Cues ; Frontal Lobe/drug effects/*physiology ; Happiness ; Male ; Neurotoxins/pharmacology ; Prefrontal Cortex/drug effects/physiology ; Rats ; *Reward
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 29
    facet.materialart.
    Unknown
    On the nature of partial agonism in the nicotinic receptor superfamily (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-07-18
    Description: Partial agonists are ligands that bind to receptors but produce only a small maximum response even at concentrations where all receptors are occupied. In the case of ligand-activated ion channels, it has been supposed since 1957 that partial agonists evoke a small response because they are inefficient at eliciting the change of conformation between shut and open states of the channel. We have investigated partial agonists for two members of the nicotinic superfamily-the muscle nicotinic acetylcholine receptor and the glycine receptor-and find that the open-shut reaction is similar for both full and partial agonists, but the response to partial agonists is limited by an earlier conformation change ('flipping') that takes place while the channel is still shut. This has implications for the interpretation of structural studies, and in the future, for the design of partial agonists for therapeutic use.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629928/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629928/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lape, Remigijus -- Colquhoun, David -- Sivilotti, Lucia G -- 074491/Wellcome Trust/United Kingdom -- G0400869/Medical Research Council/United Kingdom -- G0400869(72542)/Medical Research Council/United Kingdom -- England -- Nature. 2008 Aug 7;454(7205):722-7. doi: 10.1038/nature07139. Epub 2008 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University College London, Medical Sciences Building, Gower Street, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18633353" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; *Drug Partial Agonism ; Glycine/pharmacology ; Humans ; Membrane Potentials/drug effects ; Muscles/metabolism ; Nicotinic Agonists/*pharmacology ; Protein Conformation ; Protein Subunits/agonists/chemistry/genetics/metabolism ; Quaternary Ammonium Compounds/pharmacology ; Rats ; Receptors, Glycine/agonists/chemistry/genetics/metabolism ; Receptors, Nicotinic/chemistry/genetics/*metabolism ; Structure-Activity Relationship ; Taurine/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 30
    facet.materialart.
    Unknown
    Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-11-21
    Description: Calpains are non-lysosomal calcium-dependent cysteine proteinases that selectively cleave proteins in response to calcium signals and thereby control cellular functions such as cytoskeletal remodelling, cell cycle progression, gene expression and apoptotic cell death. In mammals, the two best-characterized members of the calpain family, calpain 1 and calpain 2 (micro-calpain and m-calpain, respectively), are ubiquitously expressed. The activity of calpains is tightly controlled by the endogenous inhibitor calpastatin, which is an intrinsically unstructured protein capable of reversibly binding and inhibiting four molecules of calpain, but only in the presence of calcium. To date, the mechanism of inhibition by calpastatin and the basis for its absolute specificity have remained speculative. It was not clear how this unstructured protein inhibits calpains without being cleaved itself, nor was it known how calcium induced changes that facilitated the binding of calpastatin to calpain. Here we report the 2.4-A-resolution crystal structure of the calcium-bound calpain 2 heterodimer bound by one of the four inhibitory domains of calpastatin. Calpastatin is seen to inhibit calpain by occupying both sides of the active site cleft. Although the inhibitor passes through the active site cleft it escapes cleavage in a novel manner by looping out and around the active site cysteine. The inhibitory domain of calpastatin recognizes multiple lower affinity sites present only in the calcium-bound form of the enzyme, resulting in an interaction that is tight, specific and calcium dependent. This crystal structure, and that of a related complex, also reveal the conformational changes that calpain undergoes on binding calcium, which include opening of the active site cleft and movement of the domains relative to each other to produce a more compact enzyme.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanna, Rachel A -- Campbell, Robert L -- Davies, Peter L -- England -- Nature. 2008 Nov 20;456(7220):409-12. doi: 10.1038/nature07451.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020623" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Calcium-Binding Proteins/*chemistry/*metabolism ; Calpain/*antagonists & inhibitors/*chemistry/metabolism ; Catalytic Domain ; Crystallography, X-Ray ; Models, Molecular ; Protein Binding ; Protein Multimerization ; Rats ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 31
    facet.materialart.
    Unknown
    Science & music: the neural roots of music (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trainor, Laurel -- England -- Nature. 2008 May 29;453(7195):598-9. doi: 10.1038/453598a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉McMaster Institute for Music and the Mind, and the Auditory Development Lab at McMaster University, 1280 Main Street West, Hamilton, Ontario L854L8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18509429" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Auditory Perception/*physiology ; Biological Evolution ; Brain/*physiology ; Child ; Dancing/physiology/psychology ; Ear/anatomy & histology/physiology ; Emotions/physiology ; Hearing/*physiology ; Humans ; Infant ; Music/*psychology ; Pitch Perception/physiology ; Rats ; Vestibule, Labyrinth/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 32
    facet.materialart.
    Unknown
    A novel route for ATP acquisition by the remnant mitochondria of Encephalitozoon cuniculi (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-05-02
    Description: Mitochondria use transport proteins of the eukaryotic mitochondrial carrier family (MCF) to mediate the exchange of diverse substrates, including ATP, with the host cell cytosol. According to classical endosymbiosis theory, insertion of a host-nuclear-encoded MCF transporter into the protomitochondrion was the key step that allowed the host cell to harvest ATP from the enslaved endosymbiont. Notably the genome of the microsporidian Encephalitozoon cuniculi has lost all of its genes for MCF proteins. This raises the question of how the recently discovered microsporidian remnant mitochondrion, called a mitosome, acquires ATP to support protein import and other predicted ATP-dependent activities. The E. cuniculi genome does contain four genes for an unrelated type of nucleotide transporter used by plastids and bacterial intracellular parasites, such as Rickettsia and Chlamydia, to import ATP from the cytosol of their eukaryotic host cells. The inference is that E. cuniculi also uses these proteins to steal ATP from its eukaryotic host to sustain its lifestyle as an obligate intracellular parasite. Here we show that, consistent with this hypothesis, all four E. cuniculi transporters can transport ATP, and three of them are expressed on the surface of the parasite when it is living inside host cells. The fourth transporter co-locates with mitochondrial Hsp70 to the E. cuniculi mitosome. Thus, uniquely among eukaryotes, the traditional relationship between mitochondrion and host has been subverted in E. cuniculi, by reductive evolution and analogous gene replacement. Instead of the mitosome providing the parasite cytosol with ATP, the parasite cytosol now seems to provide ATP for the organelle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsaousis, Anastasios D -- Kunji, Edmund R S -- Goldberg, Alina V -- Lucocq, John M -- Hirt, Robert P -- Embley, T Martin -- MC_U105663139/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2008 May 22;453(7194):553-6. doi: 10.1038/nature06903. Epub 2008 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cell and Molecular Biosciences, Catherine Cookson Building, Framlington Place, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18449191" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/*metabolism ; Animals ; Biological Transport ; Carrier Proteins/genetics/immunology/metabolism ; Cell Line ; Encephalitozoon cuniculi/*cytology/genetics/*metabolism ; Escherichia coli/genetics/metabolism ; Fungal Proteins/genetics/immunology/metabolism ; Genome, Fungal/genetics ; Genome, Mitochondrial/genetics ; Mitochondria/genetics/*metabolism ; Models, Biological ; Molecular Sequence Data ; Rabbits ; Rats ; Symbiosis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 33
    facet.materialart.
    Unknown
    Rapid strengthening of thalamo-amygdala synapses mediates cue-reward learning (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-05-13
    Description: What neural changes underlie individual differences in goal-directed learning? The lateral amygdala (LA) is important for assigning emotional and motivational significance to discrete environmental cues, including those that signal rewarding events. Recognizing that a cue predicts a reward enhances an animal's ability to acquire that reward; however, the cellular and synaptic mechanisms that underlie cue-reward learning are unclear. Here we show that marked changes in both cue-induced neuronal firing and input-specific synaptic strength occur with the successful acquisition of a cue-reward association within a single training session. We performed both in vivo and ex vivo electrophysiological recordings in the LA of rats trained to self-administer sucrose. We observed that reward-learning success increased in proportion to the number of amygdala neurons that responded phasically to a reward-predictive cue. Furthermore, cue-reward learning induced an AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid)-receptor-mediated increase in the strength of thalamic, but not cortical, synapses in the LA that was apparent immediately after the first training session. The level of learning attained by individual subjects was highly correlated with the degree of synaptic strength enhancement. Importantly, intra-LA NMDA (N-methyl-d-aspartate)-receptor blockade impaired reward-learning performance and attenuated the associated increase in synaptic strength. These findings provide evidence of a connection between LA synaptic plasticity and cue-reward learning, potentially representing a key mechanism underlying goal-directed behaviour.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759353/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759353/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tye, Kay M -- Stuber, Garret D -- de Ridder, Bram -- Bonci, Antonello -- Janak, Patricia H -- R01 DA015096/DA/NIDA NIH HHS/ -- R01 DA015096-06/DA/NIDA NIH HHS/ -- R01DA115096/DA/NIDA NIH HHS/ -- England -- Nature. 2008 Jun 26;453(7199):1253-7. doi: 10.1038/nature06963. Epub 2008 May 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California 94608, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18469802" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/*cytology/physiology ; Animals ; *Cues ; Excitatory Postsynaptic Potentials ; Learning/*physiology ; Male ; Models, Neurological ; N-Methylaspartate/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/metabolism ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism ; *Reward ; Synapses/*metabolism ; Thalamus/*cytology/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 34
    facet.materialart.
    Unknown
    S-Nitrosylation of histone deacetylase 2 induces chromatin remodelling in neurons (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-08-30
    Description: Brain-derived neurotrophic factor (BDNF) and other neurotrophins have a vital role in the development of the rat and mouse nervous system by influencing the expression of many specific genes that promote differentiation, cell survival, synapse formation and, later, synaptic plasticity. Although nitric oxide (NO) is known to be an important mediator of BDNF signalling in neurons, the mechanisms by which neurotrophins influence gene expression during development and plasticity remain largely unknown. Here we show that BDNF triggers NO synthesis and S-nitrosylation of histone deacetylase 2 (HDAC2) in neurons, resulting in changes to histone modifications and gene activation. S-nitrosylation of HDAC2 occurs at Cys 262 and Cys 274 and does not affect deacetylase activity. In contrast, nitrosylation of HDAC2 induces its release from chromatin, which increases acetylation of histones surrounding neurotrophin-dependent gene promoters and promotes transcription. Notably, nitrosylation of HDAC2 in embryonic cortical neurons regulates dendritic growth and branching, possibly by the activation of CREB (cyclic-AMP-responsive-element-binding protein)-dependent genes. Thus, by stimulating NO production and S-nitrosylation of HDAC2, neurotrophic factors promote chromatin remodelling and the activation of genes that are associated with neuronal development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nott, Alexi -- Watson, P Marc -- Robinson, James D -- Crepaldi, Luca -- Riccio, Antonella -- G0500792/Medical Research Council/United Kingdom -- G117/533/Medical Research Council/United Kingdom -- G120/934/Medical Research Council/United Kingdom -- MC_U122663296/Medical Research Council/United Kingdom -- England -- Nature. 2008 Sep 18;455(7211):411-5. doi: 10.1038/nature07238. Epub 2008 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory for Molecular and Cell Biology, and Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18754010" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain-Derived Neurotrophic Factor/pharmacology ; Chromatin/*metabolism ; *Chromatin Assembly and Disassembly ; Cysteine/metabolism ; Cytoplasm/metabolism ; Dendrites/metabolism ; Female ; Histone Deacetylase 2 ; Histone Deacetylases/genetics/*metabolism ; Male ; Mice ; Nerve Growth Factors/metabolism ; Neurons/cytology/enzymology/*metabolism ; Nitric Oxide/biosynthesis/metabolism ; Nuclear Proteins/metabolism ; Rats ; Repressor Proteins/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 35
    facet.materialart.
    Unknown
    FcRn-mediated antibody transport across epithelial cells revealed by electron tomography (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-09-27
    Description: The neonatal Fc receptor (FcRn) transports maternal IgG across epithelial barriers, thereby providing the fetus or newborn with humoral immunity before its immune system is fully functional. In newborn rats, FcRn transfers IgG from milk to blood by apical-to-basolateral transcytosis across intestinal epithelial cells. The pH difference between the apical (pH 6.0-6.5) and basolateral (pH 7.4) sides of intestinal epithelial cells facilitates the efficient unidirectional transport of IgG, because FcRn binds IgG at pH 6.0-6.5 but not at pH 7 or more. As milk passes through the neonatal intestine, maternal IgG is removed by FcRn-expressing cells in the proximal small intestine (duodenum and jejunum); remaining proteins are absorbed and degraded by FcRn-negative cells in the distal small intestine (ileum). Here we use electron tomography to make jejunal transcytosis visible directly in space and time, developing new labelling and detection methods to map individual nanogold-labelled Fc within transport vesicles and simultaneously to characterize these vesicles by immunolabelling. Combining electron tomography with a non-perturbing endocytic label allowed us to conclusively identify receptor-bound ligands, resolve interconnecting vesicles, determine whether a vesicle was microtubule-associated, and accurately trace FcRn-mediated transport of IgG. Our results present a complex picture in which Fc moves through networks of entangled tubular and irregular vesicles, only some of which are microtubule-associated, as it migrates to the basolateral surface. New features of transcytosis are elucidated, including transport involving multivesicular body inner vesicles/tubules and exocytosis through clathrin-coated pits. Markers for early, late and recycling endosomes each labelled vesicles in different and overlapping morphological classes, revealing spatial complexity in endo-lysosomal trafficking.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773227/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773227/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Wanzhong -- Ladinsky, Mark S -- Huey-Tubman, Kathryn E -- Jensen, Grant J -- McIntosh, J Richard -- Bjorkman, Pamela J -- 2 R37 AI041239-06A1/AI/NIAID NIH HHS/ -- R37 AI041239/AI/NIAID NIH HHS/ -- R37 AI041239-06A1/AI/NIAID NIH HHS/ -- RR000592/RR/NCRR NIH HHS/ -- England -- Nature. 2008 Sep 25;455(7212):542-6. doi: 10.1038/nature07255.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology 114-96, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18818657" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Antibodies/*metabolism ; Electrons ; Epithelial Cells/*metabolism ; Gold ; Histocompatibility Antigens Class I/*metabolism ; Humans ; Imaging, Three-Dimensional ; Immunity, Maternally-Acquired ; Immunoglobulin G/metabolism ; Intestines/*cytology/metabolism ; Jejunum/cytology ; Protein Transport ; Rats ; Receptors, Fc/*metabolism ; Tomography
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 36
    facet.materialart.
    Unknown
    Amygdala intercalated neurons are required for expression of fear extinction (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-07-11
    Description: Congruent findings from studies of fear learning in animals and humans indicate that research on the circuits mediating fear constitutes our best hope of understanding human anxiety disorders. In mammals, repeated presentations of a conditioned stimulus that was previously paired to a noxious stimulus leads to the gradual disappearance of conditioned fear responses. Although much evidence suggests that this extinction process depends on plastic events in the amygdala, the underlying mechanisms remain unclear. Intercalated (ITC) amygdala neurons constitute probable mediators of extinction because they receive information about the conditioned stimulus from the basolateral amygdala (BLA), and contribute inhibitory projections to the central nucleus (CEA), the main output station of the amygdala for conditioned fear responses. Thus, after extinction training, ITC cells could reduce the impact of conditioned-stimulus-related BLA inputs to the CEA by means of feed-forward inhibition. Here we test the hypothesis that ITC neurons mediate extinction by lesioning them with a toxin that selectively targets cells expressing micro-opioid receptors (microORs). Electron microscopic observations revealed that the incidence of microOR-immunoreactive synapses is much higher in ITC cell clusters than in the BLA or CEA and that microORs typically have a post-synaptic location in ITC cells. In keeping with this, bilateral infusions of the microOR agonist dermorphin conjugated to the toxin saporin in the vicinity of ITC neurons caused a 34% reduction in the number of ITC cells but no significant cell loss in surrounding nuclei. Moreover, ITC lesions caused a marked deficit in the expression of extinction that correlated negatively with the number of surviving ITC neurons but not CEA cells. Because ITC cells exhibit an unusual pattern of receptor expression, these findings open new avenues for the treatment of anxiety disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528060/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528060/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Likhtik, Ekaterina -- Popa, Daniela -- Apergis-Schoute, John -- Fidacaro, George A -- Pare, Denis -- F31 MH076415-02/MH/NIMH NIH HHS/ -- F31 MH76415/MH/NIMH NIH HHS/ -- R01 MH073610/MH/NIMH NIH HHS/ -- R01 MH073610-04/MH/NIMH NIH HHS/ -- R01MH-073610/MH/NIMH NIH HHS/ -- England -- Nature. 2008 Jul 31;454(7204):642-5. doi: 10.1038/nature07167. Epub 2008 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, New Jersey 07102, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18615014" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/cytology/*physiology/ultrastructure ; Animals ; Conditioning (Psychology)/physiology ; Extinction, Psychological/*physiology ; Fear/*physiology ; Freezing Reaction, Cataleptic/drug effects/physiology ; Immunotoxins/pharmacology ; Interneurons/cytology/drug effects/*physiology/ultrastructure ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid/drug effects/metabolism ; Ribosome Inactivating Proteins, Type 1/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 37
    facet.materialart.
    Unknown
    Activity-dependent regulation of inhibitory synapse development by Npas4 (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-09-26
    Description: Neuronal activity regulates the development and maturation of excitatory and inhibitory synapses in the mammalian brain. Several recent studies have identified signalling networks within neurons that control excitatory synapse development. However, less is known about the molecular mechanisms that regulate the activity-dependent development of GABA (gamma-aminobutyric acid)-releasing inhibitory synapses. Here we report the identification of a transcription factor, Npas4, that plays a role in the development of inhibitory synapses by regulating the expression of activity-dependent genes, which in turn control the number of GABA-releasing synapses that form on excitatory neurons. These findings demonstrate that the activity-dependent gene program regulates inhibitory synapse development, and suggest a new role for this program in controlling the homeostatic balance between synaptic excitation and inhibition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637532/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637532/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Yingxi -- Bloodgood, Brenda L -- Hauser, Jessica L -- Lapan, Ariya D -- Koon, Alex C -- Kim, Tae-Kyung -- Hu, Linda S -- Malik, Athar N -- Greenberg, Michael E -- HD18655/HD/NICHD NIH HHS/ -- NS27572/NS/NINDS NIH HHS/ -- NS48276/NS/NINDS NIH HHS/ -- P01 NS047572/NS/NINDS NIH HHS/ -- P01 NS047572-01A10001/NS/NINDS NIH HHS/ -- P01 NS047572-020001/NS/NINDS NIH HHS/ -- P01 NS047572-030001/NS/NINDS NIH HHS/ -- P01 NS047572-040001/NS/NINDS NIH HHS/ -- P01 NS047572-050001/NS/NINDS NIH HHS/ -- R01 MH091220/MH/NIMH NIH HHS/ -- R01 NS048276/NS/NINDS NIH HHS/ -- R01 NS048276-01/NS/NINDS NIH HHS/ -- R01 NS048276-02/NS/NINDS NIH HHS/ -- R01 NS048276-03/NS/NINDS NIH HHS/ -- R01 NS048276-04/NS/NINDS NIH HHS/ -- R01 NS048276-05/NS/NINDS NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Oct 30;455(7217):1198-204. doi: 10.1038/nature07319. Epub 2008 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉F. M. Kirby Neurobiology Center, Children's Hospital and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18815592" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Brain-Derived Neurotrophic Factor/metabolism ; Cells, Cultured ; Electrophysiology ; Gene Expression Regulation ; Hippocampus/cytology ; Mice ; Neurons/metabolism ; Rats ; Synapses/*metabolism ; Transcription Factors/genetics/*metabolism ; Transfection ; gamma-Aminobutyric Acid/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 38
    facet.materialart.
    Unknown
    Neuroscience: greasy proteins of the neuron (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Linder, Maurine E -- England -- Nature. 2008 Dec 18;456(7224):887-8. doi: 10.1038/456887a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19092922" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing/genetics ; Animals ; *Lipoylation ; Neurons/*metabolism ; Proteome/*metabolism ; *Proteomics ; Rats ; Synapses/*metabolism ; cdc42 GTP-Binding Protein/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 39
    facet.materialart.
    Unknown
    Behavioural report of single neuron stimulation in somatosensory cortex (2007)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2007
    Description: Understanding how neural activity in sensory cortices relates to perception is a central theme of neuroscience. Action potentials of sensory cortical neurons can be strongly correlated to properties of sensory stimuli and reflect the subjective judgements of an individual about stimuli. Microstimulation experiments have established a direct link from sensory activity to behaviour, suggesting that small neuronal populations can influence sensory decisions. However, microstimulation does not allow identification and quantification of the stimulated cellular elements. The sensory impact of individual cortical neurons therefore remains unknown. Here we show that stimulation of single neurons in somatosensory cortex affects behavioural responses in a detection task. We trained rats to respond to microstimulation of barrel cortex at low current intensities. We then initiated short trains of action potentials in single neurons by juxtacellular stimulation. Animals responded significantly more often in single-cell stimulation trials than in catch trials without stimulation. Stimulation effects varied greatly between cells, and on average in 5% of trials a response was induced. Whereas stimulation of putative excitatory neurons led to weak biases towards responding, stimulation of putative inhibitory neurons led to more variable and stronger sensory effects. Reaction times for single-cell stimulation were long and variable. Our results demonstrate that single neuron activity can cause a change in the animal's detection behaviour, suggesting a much sparser cortical code for sensations than previously anticipated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Houweling, Arthur R -- Brecht, Michael -- England -- Nature. 2008 Jan 3;451(7174):65-8. Epub 2007 Dec 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bernstein Center for Computational Neuroscience and Humboldt University Berlin, Philippstrasse 13, House 6, 10115 Berlin, Germany. arthur.houweling@bccn-berlin.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18094684" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Behavior, Animal/*physiology ; Electric Stimulation ; Neurons/*physiology ; Pyramidal Cells/metabolism ; Rats ; Reaction Time ; Somatosensory Cortex/*cytology/*physiology ; Touch/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 40
    facet.materialart.
    Unknown
    Clustering of InsP3 receptors by InsP3 retunes their regulation by InsP3 and Ca2+ (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-04-07
    Description: The versatility of Ca2+ signals derives from their spatio-temporal organization. For Ca2+ signals initiated by inositol-1,4,5-trisphosphate (InsP3), this requires local interactions between InsP3 receptors (InsP3Rs) mediated by their rapid stimulation and slower inhibition by cytosolic Ca2+. This allows hierarchical recruitment of Ca2+ release events as the InsP3 concentration increases. Single InsP3Rs respond first, then clustered InsP3Rs open together giving a local 'Ca2+ puff', and as puffs become more frequent they ignite regenerative Ca2+ waves. Using nuclear patch-clamp recording, here we demonstrate that InsP3Rs are initially randomly distributed with an estimated separation of 1 m. Low concentrations of InsP3 cause InsP3Rs to aggregate rapidly and reversibly into small clusters of about four closely associated InsP3Rs. At resting cytosolic [Ca2+], clustered InsP3Rs open independently, but with lower open probability, shorter open time, and less InsP3 sensitivity than lone InsP3Rs. Increasing cytosolic [Ca2+] reverses the inhibition caused by clustering, InsP3R gating becomes coupled, and the duration of multiple openings is prolonged. Clustering both exposes InsP3Rs to local Ca2+ rises and increases the effects of Ca2+. Dynamic regulation of clustering by InsP3 retunes InsP3R sensitivity to InsP3 and Ca2+, facilitating hierarchical recruitment of the elementary events that underlie all InsP3-evoked Ca2+ signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702691/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702691/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taufiq-Ur-Rahman -- Skupin, Alexander -- Falcke, Martin -- Taylor, Colin W -- 085295/Wellcome Trust/United Kingdom -- BBE0046601/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Apr 2;458(7238):655-9. doi: 10.1038/nature07763.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Tennis Court Road, Cambridge CB2 1PD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19348050" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; *Calcium Signaling ; Cell Line ; Cytosol/metabolism ; Inositol 1,4,5-Trisphosphate/*metabolism ; Inositol 1,4,5-Trisphosphate Receptors/*metabolism ; Ion Channel Gating ; Patch-Clamp Techniques ; Protein Transport ; Rats
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 41
    facet.materialart.
    Unknown
    Cell biology: Another way to get rid of fat (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-05-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zechner, Rudolf -- Madeo, Frank -- England -- Nature. 2009 Apr 30;458(7242):1118-9. doi: 10.1038/4581118a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407787" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy/*physiology ; Cholesterol/metabolism ; Fatty Acids/*metabolism ; Fatty Liver/metabolism/pathology ; Hepatocytes/cytology/metabolism ; *Lipid Metabolism ; Lipolysis ; Mice ; Rats ; Triglycerides/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 42
    facet.materialart.
    Unknown
    Synaptic depression enables neuronal gain control (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-01-16
    Description: To act as computational devices, neurons must perform mathematical operations as they transform synaptic and modulatory input into output firing rate. Experiments and theory indicate that neuronal firing typically represents the sum of synaptic inputs, an additive operation, but multiplication of inputs is essential for many computations. Multiplication by a constant produces a change in the slope, or gain, of the input-output relationship, amplifying or scaling down the sensitivity of the neuron to changes in its input. Such gain modulation occurs in vivo, during contrast invariance of orientation tuning, attentional scaling, translation-invariant object recognition, auditory processing and coordinate transformations. Moreover, theoretical studies highlight the necessity of gain modulation in several of these tasks. Although potential cellular mechanisms for gain modulation have been identified, they often rely on membrane noise and require restrictive conditions to work. Because nonlinear components are used to scale signals in electronics, we examined whether synaptic nonlinearities are involved in neuronal gain modulation. We used synaptic stimulation and the dynamic-clamp technique to investigate gain modulation in granule cells in acute slices of rat cerebellum. Here we show that when excitation is mediated by synapses with short-term depression (STD), neuronal gain is controlled by an inhibitory conductance in a noise-independent manner, allowing driving and modulatory inputs to be multiplied together. The nonlinearity introduced by STD transforms inhibition-mediated additive shifts in the input-output relationship into multiplicative gain changes. When granule cells were driven with bursts of high-frequency mossy fibre input, as observed in vivo, larger inhibition-mediated gain changes were observed, as expected with greater STD. Simulations of synaptic integration in more complex neocortical neurons suggest that STD-based gain modulation can also operate in neurons with large dendritic trees. Our results establish that neurons receiving depressing excitatory inputs can act as powerful multiplicative devices even when integration of postsynaptic conductances is linear.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689940/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689940/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rothman, Jason S -- Cathala, Laurence -- Steuber, Volker -- Silver, R Angus -- 064413/Wellcome Trust/United Kingdom -- BB/F005369/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0400598/Medical Research Council/United Kingdom -- G0400598(71261)/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Feb 19;457(7232):1015-8. doi: 10.1038/nature07604. Epub 2009 Jan 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19145233" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dendrites/physiology ; Excitatory Postsynaptic Potentials/physiology ; Long-Term Synaptic Depression/*physiology ; Models, Neurological ; Neocortex/cytology ; Nerve Fibers/physiology ; Neurons/cytology/*physiology ; Pyramidal Cells/cytology ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Synapses/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 43
    facet.materialart.
    Unknown
    Central control of fever and female body temperature by RANKL/RANK (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-11-27
    Description: Receptor-activator of NF-kappaB ligand (TNFSF11, also known as RANKL, OPGL, TRANCE and ODF) and its tumour necrosis factor (TNF)-family receptor RANK are essential regulators of bone remodelling, lymph node organogenesis and formation of a lactating mammary gland. RANKL and RANK are also expressed in the central nervous system. However, the functional relevance of RANKL/RANK in the brain was entirely unknown. Here we report that RANKL and RANK have an essential role in the brain. In both mice and rats, central RANKL injections trigger severe fever. Using tissue-specific Nestin-Cre and GFAP-Cre rank(floxed) deleter mice, the function of RANK in the fever response was genetically mapped to astrocytes. Importantly, Nestin-Cre and GFAP-Cre rank(floxed) deleter mice are resistant to lipopolysaccharide-induced fever as well as fever in response to the key inflammatory cytokines IL-1beta and TNFalpha. Mechanistically, RANKL activates brain regions involved in thermoregulation and induces fever via the COX2-PGE(2)/EP3R pathway. Moreover, female Nestin-Cre and GFAP-Cre rank(floxed) mice exhibit increased basal body temperatures, suggesting that RANKL and RANK control thermoregulation during normal female physiology. We also show that two children with RANK mutations exhibit impaired fever during pneumonia. These data identify an entirely novel and unexpected function for the key osteoclast differentiation factors RANKL/RANK in female thermoregulation and the central fever response in inflammation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanada, Reiko -- Leibbrandt, Andreas -- Hanada, Toshikatsu -- Kitaoka, Shiho -- Furuyashiki, Tomoyuki -- Fujihara, Hiroaki -- Trichereau, Jean -- Paolino, Magdalena -- Qadri, Fatimunnisa -- Plehm, Ralph -- Klaere, Steffen -- Komnenovic, Vukoslav -- Mimata, Hiromitsu -- Yoshimatsu, Hironobu -- Takahashi, Naoyuki -- von Haeseler, Arndt -- Bader, Michael -- Kilic, Sara Sebnem -- Ueta, Yoichi -- Pifl, Christian -- Narumiya, Shuh -- Penninger, Josef M -- England -- Nature. 2009 Nov 26;462(7272):505-9. doi: 10.1038/nature08596.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940926" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/drug effects/metabolism ; Body Temperature Regulation/*drug effects/*physiology ; Child ; Dinoprostone/metabolism ; Female ; Fever/*chemically induced/complications/*metabolism ; Gene Expression Profiling ; Humans ; Injections, Intraventricular ; Male ; Mice ; Mice, Inbred C57BL ; Pneumonia/complications/metabolism ; RANK Ligand/administration & dosage/antagonists & ; inhibitors/metabolism/*pharmacology ; Rats ; Rats, Wistar ; Receptor Activator of Nuclear Factor-kappa B/genetics/*metabolism ; Receptors, Prostaglandin E/metabolism ; Receptors, Prostaglandin E, EP3 Subtype ; *Sex Characteristics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 44
    facet.materialart.
    Unknown
    Toxicity testing gets a makeover (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2009 Sep 10;461(7261):158. doi: 10.1038/461158a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741676" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Use Alternatives/economics/*methods/trends ; Animals ; Chemical Industry/economics/*methods ; Cosmetics/adverse effects/toxicity ; Europe ; Humans ; Mice ; Rats ; Toxicity Tests/economics/*methods/trends ; Toxicology/economics/*methods/trends ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 45
    facet.materialart.
    Unknown
    Dendritic encoding of sensory stimuli controlled by deep cortical interneurons (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-01-20
    Description: The computational power of single neurons is greatly enhanced by active dendritic conductances that have a large influence on their spike activity. In cortical output neurons such as the large pyramidal cells of layer 5 (L5), activation of apical dendritic calcium channels leads to plateau potentials that increase the gain of the input/output function and switch the cell to burst-firing mode. The apical dendrites are innervated by local excitatory and inhibitory inputs as well as thalamic and corticocortical projections, which makes it a formidable task to predict how these inputs influence active dendritic properties in vivo. Here we investigate activity in populations of L5 pyramidal dendrites of the somatosensory cortex in awake and anaesthetized rats following sensory stimulation using a new fibre-optic method for recording dendritic calcium changes. We show that the strength of sensory stimulation is encoded in the combined dendritic calcium response of a local population of L5 pyramidal cells in a graded manner. The slope of the stimulus-response function was under the control of a particular subset of inhibitory neurons activated by synaptic inputs predominantly in L5. Recordings from single apical tuft dendrites in vitro showed that activity in L5 pyramidal neurons disynaptically coupled via interneurons directly blocks the initiation of dendritic calcium spikes in neighbouring pyramidal neurons. The results constitute a functional description of a cortical microcircuit in awake animals that relies on the active properties of L5 pyramidal dendrites and their very high sensitivity to inhibition. The microcircuit is organized so that local populations of apical dendrites can adaptively encode bottom-up sensory stimuli linearly across their full dynamic range.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murayama, Masanori -- Perez-Garci, Enrique -- Nevian, Thomas -- Bock, Tobias -- Senn, Walter -- Larkum, Matthew E -- England -- Nature. 2009 Feb 26;457(7233):1137-41. doi: 10.1038/nature07663. Epub 2009 Jan 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physiologisches Institut, Universitat Bern, Buhlplatz 5, CH-3012 Bern, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19151696" target="_blank"〉PubMed〈/a〉
    Keywords: Anesthesia ; Animals ; Calcium/metabolism ; Dendrites/*physiology ; Electric Stimulation ; Excitatory Postsynaptic Potentials/physiology ; Female ; Interneurons/*physiology ; Models, Neurological ; Rats ; Rats, Wistar ; Somatosensory Cortex/*cytology/*physiology ; Wakefulness/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 46
    facet.materialart.
    Unknown
    Integration of neuronal clones in the radial cortical columns by EphA and ephrin-A signalling (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-09-18
    Description: The cerebral cortex is a laminated sheet of neurons composed of the arrays of intersecting radial columns. During development, excitatory projection neurons originating from the proliferative units at the ventricular surface of the embryonic cerebral vesicles migrate along elongated radial glial fibres to form a cellular infrastructure of radial (vertical) ontogenetic columns in the overlaying cortical plate. However, a subpopulation of these clonally related neurons also undergoes a short lateral shift and transfers from their parental to the neighbouring radial glial fibres, and intermixes with neurons originating from neighbouring proliferative units. This columnar organization acts as the primary information processing unit in the cortex. The molecular mechanisms, role and significance of this lateral dispersion for cortical development are not understood. Here we show that an Eph receptor A (EphA) and ephrin A (Efna) signalling-dependent shift in the allocation of clonally related neurons is essential for the proper assembly of cortical columns. In contrast to the relatively uniform labelling of the developing cortical plate by various molecular markers and retrograde tracers in wild-type mice, we found alternating labelling of columnar compartments in Efna knockout mice that are caused by impaired lateral dispersion of migrating neurons rather than by altered cell production or death. Furthermore, in utero electroporation showed that lateral dispersion depends on the expression levels of EphAs and ephrin-As during neuronal migration. This so far unrecognized mechanism for lateral neuronal dispersion seems to be essential for the proper intermixing of neuronal types in the cortical columns, which, when disrupted, might contribute to neuropsychiatric disorders associated with abnormal columnar organization.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874978/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874978/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Torii, Masaaki -- Hashimoto-Torii, Kazue -- Levitt, Pat -- Rakic, Pasko -- R01 DA022785/DA/NIDA NIH HHS/ -- R01 DA022785-03/DA/NIDA NIH HHS/ -- R01 DA023999/DA/NIDA NIH HHS/ -- R01 DA023999-01A1/DA/NIDA NIH HHS/ -- R01 DA023999-02/DA/NIDA NIH HHS/ -- R01 NS014841/NS/NINDS NIH HHS/ -- R01 NS014841-30/NS/NINDS NIH HHS/ -- R01 NS014841-31/NS/NINDS NIH HHS/ -- R01 NS038296/NS/NINDS NIH HHS/ -- R01 NS038296-09/NS/NINDS NIH HHS/ -- R01 NS038296-10/NS/NINDS NIH HHS/ -- England -- Nature. 2009 Sep 24;461(7263):524-8. doi: 10.1038/nature08362. Epub 2009 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA. masaaki.torii@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759535" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Movement ; Cerebral Cortex/anatomy & histology/cytology/*embryology/metabolism ; Ephrins/deficiency/genetics/*metabolism ; Mice ; Mice, Knockout ; Neocortex/cytology/metabolism ; Neurons/*cytology/*metabolism ; Organogenesis ; Rats ; Receptors, Eph Family/deficiency/genetics/*metabolism ; *Signal Transduction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 47
    facet.materialart.
    Unknown
    Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-12-05
    Description: Many organisms can enter a dormant state or diapause to survive harsh environmental conditions for extended durations. When Caenorhabditis elegans larvae enter dauer they arrest feeding but remain active and motile, yet become stress-resistant, extremely long-lived and non-ageing. Entry into dauer is associated with a reduction in insulin-like signalling, the accumulation of nutritive resources and a concomitant global change in metabolism, yet the precise molecular and physiological processes that enable long-term survival in the absence of caloric intake remain largely unknown. We show here that C. elegans larvae that lack LKB1/AMPK (AMP-activated protein kinase) signalling enter dauer normally, but then rapidly consume their stored energy and prematurely expire following vital organ failure. We found that this signalling pathway acts in adipose-like tissues to downregulate triglyceride hydrolysis so that these lipid reserves are rationed to last the entire duration of the arrest. Indeed, the downregulation of adipose triglyceride lipase (ATGL-1) activity suppresses both the rapid depletion of stored lipids and reduced life span of AMPK mutant dauers, while AMPK directly phosphorylates ATGL-1. Finally, we show that the slow release of energy during dauer is critical for appropriate long-term osmoregulation, which fails as triglyceride resources become depleted. These mechanisms may be essential for survival through diapause, hibernation, or long-term fasting in diverse organisms and may also underlie AMPK-dependent life span extension.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Narbonne, Patrick -- Roy, Richard -- England -- Nature. 2009 Jan 8;457(7226):210-4. doi: 10.1038/nature07536. Epub 2008 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052547" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/chemistry/deficiency/genetics/*metabolism ; Adaptation, Physiological/*physiology ; Animals ; Caenorhabditis elegans/*growth & development/*metabolism ; Caenorhabditis elegans Proteins/antagonists & inhibitors/genetics/*metabolism ; Fasting/physiology ; Larva/metabolism/physiology ; Life Cycle Stages/*physiology ; Lipase/antagonists & inhibitors/metabolism ; *Lipid Metabolism ; Longevity/genetics/physiology ; Phosphorylation ; Protein-Serine-Threonine Kinases/deficiency/genetics/*metabolism ; Rats ; Signal Transduction ; Subcutaneous Tissue/metabolism ; Survival Analysis ; Time Factors ; Triglycerides/metabolism ; Water-Electrolyte Balance/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 48
    facet.materialart.
    Unknown
    Toxicology for the twenty-first century (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hartung, Thomas -- England -- Nature. 2009 Jul 9;460(7252):208-12. doi: 10.1038/460208a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Environmental Health Sciences at the Johns Hopkins University Bloomberg School of Public Health, USA. thartung@jhsph.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587762" target="_blank"〉PubMed〈/a〉
    Keywords: Adverse Drug Reaction Reporting Systems ; Animals ; False Positive Reactions ; History, 20th Century ; Humans ; Models, Animal ; Rats ; Reproducibility of Results ; Research Design ; Toxicity Tests ; Toxicology/history/*methods/*trends
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 49
    facet.materialart.
    Unknown
    Chemical regulators have overreached (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-08-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hartung, Thomas -- Rovida, Costanza -- England -- Nature. 2009 Aug 27;460(7259):1080-1. doi: 10.1038/4601080a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. thartung@jhsph.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19713914" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chemical Industry/*economics/*standards ; European Union ; Humans ; Rats ; Reproduction/drug effects ; Toxicity Tests/*economics/methods
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 50
    facet.materialart.
    Unknown
    Time to sequence the 'red and the dead' (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-04-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nicholls, Henry -- England -- Nature. 2009 Apr 16;458(7240):812-3. doi: 10.1038/458812a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19369991" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conservation of Natural Resources/methods/trends ; *Extinction, Biological ; Genomics/instrumentation/*trends ; Humans ; Museums ; Rats ; Selection, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 51
    facet.materialart.
    Unknown
    Compound vesicle fusion increases quantal size and potentiates synaptic transmission (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-03-13
    Description: Exocytosis at synapses involves fusion between vesicles and the plasma membrane. Although compound fusion between vesicles was proposed to occur at ribbon-type synapses, whether it exists, how it is mediated, and what role it plays at conventional synapses remain unclear. Here we report the existence of compound fusion, its underlying mechanism, and its role at a nerve terminal containing conventional active zones in rats and mice. We found that high potassium application and high frequency firing induced giant capacitance up-steps, reflecting exocytosis of vesicles larger than regular ones, followed by giant down-steps, reflecting bulk endocytosis. These intense stimuli also induced giant vesicle-like structures, as observed with electron microscopy, and giant miniature excitatory postsynaptic currents (mEPSCs), reflecting more transmitter release. Calcium and its sensor for vesicle fusion, synaptotagmin, were required for these giant events. After high frequency firing, calcium/synaptotagmin-dependent mEPSC size increase was paralleled by calcium/synaptotagmin-dependent post-tetanic potentiation. These results suggest a new route of exocytosis and endocytosis composed of three steps. First, calcium/synaptotagmin mediates compound fusion between vesicles. Second, exocytosis of compound vesicles increases quantal size, which increases synaptic strength and contributes to the generation of post-tetanic potentiation. Third, exocytosed compound vesicles are retrieved via bulk endocytosis. We suggest that this vesicle cycling route be included in models of synapses in which only vesicle fusion with the plasma membrane is considered.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768540/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768540/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Liming -- Xue, Lei -- Xu, Jianhua -- McNeil, Benjamin D -- Bai, Li -- Melicoff, Ernestina -- Adachi, Roberto -- Wu, Ling-Gang -- Z99 NS999999/Intramural NIH HHS/ -- England -- Nature. 2009 May 7;459(7243):93-7. doi: 10.1038/nature07860.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Neurological Disorders and Stroke, 35 Convent Drive, Building 35, Room 2B-1012, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19279571" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Excitatory Postsynaptic Potentials ; Exocytosis/physiology ; Mice ; Rats ; Rats, Wistar ; Synaptic Transmission/*physiology ; Synaptic Vesicles/metabolism/*physiology ; Synaptotagmin II/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 52
    facet.materialart.
    Unknown
    Structural insight into the autoinhibition mechanism of AMP-activated protein kinase (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-05-29
    Description: The AMP-activated protein kinase (AMPK) is characterized by its ability to bind to AMP, which enables it to adjust enzymatic activity by sensing the cellular energy status and maintain the balance between ATP production and consumption in eukaryotic cells. It also has important roles in the regulation of cell growth and proliferation, and in the establishment and maintenance of cell polarity. These important functions have rendered AMPK an important drug target for obesity, type 2 diabetes and cancer treatments. However, the regulatory mechanism of AMPK activity by AMP binding remains unsolved. Here we report the crystal structures of an unphosphorylated fragment of the AMPK alpha-subunit (KD-AID) from Schizosaccharomyces pombe that contains both the catalytic kinase domain and an autoinhibitory domain (AID), and of a phosphorylated kinase domain from Saccharomyces cerevisiae (Snf1-pKD). The AID binds, from the 'backside', to the hinge region of its kinase domain, forming contacts with both amino-terminal and carboxy-terminal lobes. Structural analyses indicate that AID binding might constrain the mobility of helix alphaC, hence resulting in an autoinhibited KD-AID with much lower kinase activity than that of the kinase domain alone. AMP activates AMPK both allosterically and by inhibiting dephosphorylation. Further in vitro kinetic studies demonstrate that disruption of the KD-AID interface reverses the autoinhibition and these AMPK heterotrimeric mutants no longer respond to the change in AMP concentration. The structural and biochemical data have shown the primary mechanism of AMPK autoinhibition and suggest a conformational switch model for AMPK activation by AMP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Lei -- Jiao, Zhi-Hao -- Zheng, Li-Sha -- Zhang, Yuan-Yuan -- Xie, Shu-Tao -- Wang, Zhi-Xin -- Wu, Jia-Wei -- England -- Nature. 2009 Jun 25;459(7250):1146-9. doi: 10.1038/nature08075. Epub 2009 May 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MOE Key Laboratory of Bioinformatics, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19474788" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/*chemistry/*metabolism ; Adenosine Monophosphate/metabolism ; Amino Acid Sequence ; Animals ; *Models, Molecular ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Protein Structure, Tertiary ; Rats ; Saccharomyces cerevisiae/*enzymology ; Schizosaccharomyces/*enzymology ; Sequence Alignment
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 53
    facet.materialart.
    Unknown
    Neuroscience: Rethinking rehab (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-03-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schnabel, Jim -- England -- Nature. 2009 Mar 5;458(7234):25-7. doi: 10.1038/458025a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19262648" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Animals ; *Evidence-Based Practice ; Humans ; Magnetic Resonance Imaging ; Prefrontal Cortex/drug effects/physiology/*physiopathology ; *Psychotherapy, Group ; Rats ; Religion and Psychology ; Stress, Psychological/complications/physiopathology/psychology ; Substance-Related Disorders/drug ; therapy/*physiopathology/psychology/*rehabilitation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 54
    facet.materialart.
    Unknown
    Activation of CaMKII in single dendritic spines during long-term potentiation (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-03-20
    Description: Calcium/calmodulin-dependent kinase II (CaMKII) plays a central part in long-term potentiation (LTP), which underlies some forms of learning and memory. Here we monitored the spatiotemporal dynamics of CaMKII activation in individual dendritic spines during LTP using two-photon fluorescence lifetime imaging microscopy, in combination with two-photon glutamate uncaging. Induction of LTP and associated spine enlargement in single spines triggered transient ( approximately 1 min) CaMKII activation restricted to the stimulated spines. CaMKII in spines was specifically activated by NMDA receptors and L-type voltage-sensitive calcium channels, presumably by nanodomain Ca(2+) near the channels, in response to glutamate uncaging and depolarization, respectively. The high degree of compartmentalization and channel specificity of CaMKII signalling allow stimuli-specific spatiotemporal patterns of CaMKII signalling and may be important for synapse-specificity of synaptic plasticity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719773/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719773/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Seok-Jin R -- Escobedo-Lozoya, Yasmin -- Szatmari, Erzsebet M -- Yasuda, Ryohei -- AS1398/Autism Speaks/ -- R01 MH080047/MH/NIMH NIH HHS/ -- R01 MH080047-01/MH/NIMH NIH HHS/ -- R01 MH080047-02/MH/NIMH NIH HHS/ -- R01MH08004/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Mar 19;458(7236):299-304. doi: 10.1038/nature07842.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295602" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/antagonists & inhibitors/metabolism ; Calcium Channels, L-Type/metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/*metabolism ; Cell Line ; Cells, Cultured ; Chelating Agents/pharmacology ; Dendritic Spines/*enzymology/*physiology ; Enzyme Activation/drug effects ; Fluorescence ; Fluorescence Resonance Energy Transfer ; Glutamic Acid/metabolism ; Hippocampus/cytology ; Humans ; Kinetics ; Long-Term Potentiation/*physiology ; Photons ; Rats ; Receptors, N-Methyl-D-Aspartate/metabolism ; Synapses/metabolism ; Synaptic Potentials/physiology ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 55
    facet.materialart.
    Unknown
    Neuroscience: Making connections (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lehrer, Jonah -- England -- Nature. 2009 Jan 29;457(7229):524-7. doi: 10.1038/457524a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19177102" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Attachment Sites, Microbiological/genetics ; Brain/*cytology/physiology ; Color ; Humans ; Integrases/metabolism ; Luminescent Proteins/genetics/metabolism ; Mice ; Microscopy, Fluorescence/*methods ; Microtomy/*methods ; Muscle Fibers, Skeletal/physiology ; Neural Pathways/*metabolism ; Neurons/*metabolism ; Neurosciences/*methods ; Rats ; Staining and Labeling/*methods ; Synapses/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 56
    facet.materialart.
    Unknown
    Regulation of cortical microcircuits by unitary GABA-mediated volume transmission (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-10-30
    Description: GABA (gamma-aminobutyric acid) is predominantly released by local interneurons in the cerebral cortex to particular subcellular domains of the target cells. This suggests that compartmentalized, synapse-specific action of GABA is required in cortical networks for phasic inhibition. However, GABA released at the synaptic cleft diffuses to receptors outside the postsynaptic density and thus tonically activates extrasynaptic GABA(A) and GABA(B) receptors, which include subtypes of both receptor families especially sensitive to low concentrations of GABA. The synaptic and extrasynaptic action of GABA corroborates the idea that neurons of the brain use synaptic (or wiring) transmission and non-synaptic (or volume) transmission for communication. However, re-uptake mechanisms restrict the spatial extent of extrasynaptic GABA-mediated effects, and it has been proposed that the concerted action of several presynaptic interneurons, the sustained firing of individual cells or an increase in release-site density is required to reach ambient GABA levels sufficient to activate extrasynaptic receptors. Here we show that individual neurogliaform cells release enough GABA for volume transmission within the axonal cloud and, thus, that neurogliaform cells do not require synapses to produce inhibitory responses in the overwhelming majority of nearby neurons. Neurogliaform cells suppress connections between other neurons acting on presynaptic terminals that do not receive synapses at all in the cerebral cortex. They also reach extrasynaptic, delta-subunit-containing GABA(A) (GABA(Adelta)) receptors responsible for tonic inhibition. We show that GABA(Adelta) receptors are localized to neurogliaform cells preferentially among cortical interneurons. Neurosteroids, which are modulators of GABA(Adelta) receptors, alter unitary GABA-mediated effects between neurogliaform cells. In contrast to the specifically placed synapses formed by other interneurons, the output of neurosteroid-sensitive neurogliaform cells represents the ultimate form of the lack of spatial specificity in GABA-mediated systems, leading to long-lasting network hyperpolarization combined with widespread suppression of communication in the local circuit.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771344/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771344/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olah, Szabolcs -- Fule, Miklos -- Komlosi, Gergely -- Varga, Csaba -- Baldi, Rita -- Barzo, Pal -- Tamas, Gabor -- NS535915/NS/NINDS NIH HHS/ -- R01 NS035915/NS/NINDS NIH HHS/ -- R01 NS035915-06/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Oct 29;461(7268):1278-81. doi: 10.1038/nature08503.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Kozep fasor 52, Szeged H-6726, Hungary.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19865171" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/metabolism ; Interneurons/metabolism ; Models, Neurological ; Neuroglia/cytology/metabolism/secretion ; Paracrine Communication ; Rats ; Rats, Wistar ; Receptors, GABA-A/metabolism ; Receptors, GABA-B/metabolism ; Somatosensory Cortex/*cytology/*physiology ; Synapses/metabolism ; gamma-Aminobutyric Acid/*metabolism/secretion
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 57
    facet.materialart.
    Unknown
    Frequency of gamma oscillations routes flow of information in the hippocampus (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-11-20
    Description: Gamma oscillations are thought to transiently link distributed cell assemblies that are processing related information, a function that is probably important for network processes such as perception, attentional selection and memory. This 'binding' mechanism requires that spatially distributed cells fire together with millisecond range precision; however, it is not clear how such coordinated timing is achieved given that the frequency of gamma oscillations varies substantially across space and time, from approximately 25 to almost 150 Hz. Here we show that gamma oscillations in the CA1 area of the hippocampus split into distinct fast and slow frequency components that differentially couple CA1 to inputs from the medial entorhinal cortex, an area that provides information about the animal's current position, and CA3, a hippocampal subfield essential for storage of such information. Fast gamma oscillations in CA1 were synchronized with fast gamma in medial entorhinal cortex, and slow gamma oscillations in CA1 were coherent with slow gamma in CA3. Significant proportions of cells in medial entorhinal cortex and CA3 were phase-locked to fast and slow CA1 gamma waves, respectively. The two types of gamma occurred at different phases of the CA1 theta rhythm and mostly on different theta cycles. These results point to routeing of information as a possible function of gamma frequency variations in the brain and provide a mechanism for temporal segregation of potentially interfering information from different sources.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colgin, Laura Lee -- Denninger, Tobias -- Fyhn, Marianne -- Hafting, Torkel -- Bonnevie, Tora -- Jensen, Ole -- Moser, May-Britt -- Moser, Edvard I -- England -- Nature. 2009 Nov 19;462(7271):353-7. doi: 10.1038/nature08573.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory, MTFS, Olav Kyrres gate 9, Norwegian University of Science and Technology, NO-7489 Trondheim, Norway. laura.colgin@ntnu.no〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19924214" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Hippocampus/*physiology ; Male ; Neural Pathways/*physiology ; Neurons/*physiology ; Rats ; Rats, Long-Evans ; Synaptic Transmission/physiology ; *Theta Rhythm
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 58
    facet.materialart.
    Unknown
    Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-10-16
    Description: The tissues of the central nervous system are effectively shielded from the blood circulation by specialized vessels that are impermeable not only to cells, but also to most macromolecules circulating in the blood. Despite this seemingly absolute seclusion, central nervous system tissues are subject to immune surveillance and are vulnerable to autoimmune attacks. Using intravital two-photon imaging in a Lewis rat model of experimental autoimmune encephalomyelitis, here we present in real-time the interactive processes between effector T cells and cerebral structures from their first arrival to manifest autoimmune disease. We observed that incoming effector T cells successively scanned three planes. The T cells got arrested to leptomeningeal vessels and immediately monitored the luminal surface, crawling preferentially against the blood flow. After diapedesis, the cells continued their scan on the abluminal vascular surface and the underlying leptomeningeal (pial) membrane. There, the T cells encountered phagocytes that effectively present antigens, foreign as well as myelin proteins. These contacts stimulated the effector T cells to produce pro-inflammatory mediators, and provided a trigger to tissue invasion and the formation of inflammatory infiltrations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bartholomaus, Ingo -- Kawakami, Naoto -- Odoardi, Francesca -- Schlager, Christian -- Miljkovic, Djordje -- Ellwart, Joachim W -- Klinkert, Wolfgang E F -- Flugel-Koch, Cassandra -- Issekutz, Thomas B -- Wekerle, Hartmut -- Flugel, Alexander -- England -- Nature. 2009 Nov 5;462(7269):94-8. doi: 10.1038/nature08478. Epub 2009 Oct 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Neurobiology, 82152 Martinsried, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19829296" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/immunology ; Antigens/immunology ; Cell Movement ; Cells, Cultured ; Central Nervous System Diseases/*immunology/*pathology ; Encephalomyelitis, Autoimmune, Experimental/*immunology/*pathology ; Meninges/*blood supply/*immunology/pathology ; Mice ; Ovalbumin/immunology ; Phagocytes/immunology ; Rats ; Rats, Inbred Lew ; T-Lymphocytes/*immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 59
    facet.materialart.
    Unknown
    Hippocampal theta oscillations are travelling waves (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-06-03
    Description: Theta oscillations clock hippocampal activity during awake behaviour and rapid eye movement (REM) sleep. These oscillations are prominent in the local field potential, and they also reflect the subthreshold membrane potential and strongly modulate the spiking of hippocampal neurons. The prevailing view is that theta oscillations are synchronized throughout the hippocampus, despite the lack of conclusive experimental evidence. In contrast, here we show that in freely behaving rats, theta oscillations in area CA1 are travelling waves that propagate roughly along the septotemporal axis of the hippocampus. Furthermore, we find that spiking in the CA1 pyramidal cell layer is modulated in a consistent travelling wave pattern. Our results demonstrate that theta oscillations pattern hippocampal activity not only in time, but also across anatomical space. The presence of travelling waves indicates that the instantaneous output of the hippocampus is topographically organized and represents a segment, rather than a point, of physical space.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lubenov, Evgueniy V -- Siapas, Athanassios G -- England -- Nature. 2009 May 28;459(7246):534-9. doi: 10.1038/nature08010.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, California 91125, USA. lubenov@caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19489117" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Hippocampus/cytology/*physiology ; Male ; Models, Neurological ; Pyramidal Cells/physiology ; Rats ; Rats, Long-Evans ; *Theta Rhythm
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 60
    facet.materialart.
    Unknown
    Autophagy regulates lipid metabolism (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-04-03
    Description: The intracellular storage and utilization of lipids are critical to maintain cellular energy homeostasis. During nutrient deprivation, cellular lipids stored as triglycerides in lipid droplets are hydrolysed into fatty acids for energy. A second cellular response to starvation is the induction of autophagy, which delivers intracellular proteins and organelles sequestered in double-membrane vesicles (autophagosomes) to lysosomes for degradation and use as an energy source. Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. Here we show a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). Lipid droplets and autophagic components associated during nutrient deprivation, and inhibition of autophagy in cultured hepatocytes and mouse liver increased triglyceride storage in lipid droplets. This study identifies a critical function for autophagy in lipid metabolism that could have important implications for human diseases with lipid over-accumulation such as those that comprise the metabolic syndrome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676208/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676208/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Singh, Rajat -- Kaushik, Susmita -- Wang, Yongjun -- Xiang, Youqing -- Novak, Inna -- Komatsu, Masaaki -- Tanaka, Keiji -- Cuervo, Ana Maria -- Czaja, Mark J -- K01 DK087776/DK/NIDDK NIH HHS/ -- P01 AG031782/AG/NIA NIH HHS/ -- P01 AG031782-01A1/AG/NIA NIH HHS/ -- P30 AG038072/AG/NIA NIH HHS/ -- R01 AG021904/AG/NIA NIH HHS/ -- R01 AG021904-07/AG/NIA NIH HHS/ -- R01 DK061498/DK/NIDDK NIH HHS/ -- R01 DK061498-05/DK/NIDDK NIH HHS/ -- England -- Nature. 2009 Apr 30;458(7242):1131-5. doi: 10.1038/nature07976. Epub 2009 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19339967" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy/drug effects/*physiology ; Cell Line ; Cholesterol/metabolism ; Dietary Fats/pharmacology ; Fatty Acids/*metabolism ; Food Deprivation ; Hepatocytes/cytology/drug effects/metabolism ; *Lipid Metabolism/drug effects ; Lipolysis/drug effects ; Liver/cytology/drug effects/metabolism ; Lysosomes/metabolism ; Mice ; Microtubule-Associated Proteins/deficiency/genetics ; Oxidation-Reduction ; Phagosomes/metabolism ; Rats ; Triglycerides/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 61
    facet.materialart.
    Unknown
    The postsynaptic function of type II cochlear afferents (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-10-23
    Description: The mammalian cochlea is innervated by two classes of sensory neurons. Type I neurons make up 90-95% of the cochlear nerve and contact single inner hair cells to provide acoustic analysis as we know it. In contrast, the far less numerous type II neurons arborize extensively among outer hair cells (OHCs) and supporting cells. Their scarcity and smaller calibre axons have made them the subject of much speculation, but little experimental progress for the past 50 years. Here we record from type II fibres near their terminal arbors under OHCs to show that they receive excitatory glutamatergic synaptic input. The type II peripheral arbor conducts action potentials, but the small and infrequent glutamatergic excitation indicates a requirement for strong acoustic stimulation. Furthermore, we show that type II neurons are excited by ATP. Exogenous ATP depolarized type II neurons, both directly and by evoking glutamatergic synaptic input. These results prove that type II neurons function as cochlear afferents, and can be modulated by ATP. The lesser magnitude of synaptic drive dictates a fundamentally different role in auditory signalling from that of type I afferents.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785502/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785502/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weisz, Catherine -- Glowatzki, Elisabeth -- Fuchs, Paul -- P30 DC005211/DC/NIDCD NIH HHS/ -- R01 DC000276/DC/NIDCD NIH HHS/ -- R01 DC000276-26/DC/NIDCD NIH HHS/ -- R01 DC006476/DC/NIDCD NIH HHS/ -- R01 DC006476-06/DC/NIDCD NIH HHS/ -- R01 DC006476-07/DC/NIDCD NIH HHS/ -- R01 DC006476-08/DC/NIDCD NIH HHS/ -- T32 DC000023/DC/NIDCD NIH HHS/ -- England -- Nature. 2009 Oct 22;461(7267):1126-9. doi: 10.1038/nature08487.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Department of Neuroscience, The Center for Hearing and Balance and the Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19847265" target="_blank"〉PubMed〈/a〉
    Keywords: Acoustic Stimulation ; Adenosine Triphosphate/metabolism/pharmacology ; Afferent Pathways/*cytology/*physiology ; Animals ; Auditory Perception ; Cochlea/cytology/*innervation ; Excitatory Postsynaptic Potentials/physiology ; Glutamic Acid/metabolism ; Hair Cells, Auditory, Outer/cytology/metabolism ; Neuronal Tract-Tracers ; Rats ; Rats, Sprague-Dawley ; Sensory Receptor Cells/*cytology/drug effects/*metabolism ; Synapses/drug effects/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 62
    facet.materialart.
    Unknown
    X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-12-01
    Description: Ionotropic glutamate receptors mediate most excitatory neurotransmission in the central nervous system and function by opening a transmembrane ion channel upon binding of glutamate. Despite their crucial role in neurobiology, the architecture and atomic structure of an intact ionotropic glutamate receptor are unknown. Here we report the crystal structure of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-sensitive, homotetrameric, rat GluA2 receptor at 3.6 A resolution in complex with a competitive antagonist. The receptor harbours an overall axis of two-fold symmetry with the extracellular domains organized as pairs of local dimers and with the ion channel domain exhibiting four-fold symmetry. A symmetry mismatch between the extracellular and ion channel domains is mediated by two pairs of conformationally distinct subunits, A/C and B/D. Therefore, the stereochemical manner in which the A/C subunits are coupled to the ion channel gate is different from the B/D subunits. Guided by the GluA2 structure and site-directed cysteine mutagenesis, we suggest that GluN1 and GluN2A NMDA (N-methyl-d-aspartate) receptors have a similar architecture, with subunits arranged in a 1-2-1-2 pattern. We exploit the GluA2 structure to develop mechanisms of ion channel activation, desensitization and inhibition by non-competitive antagonists and pore blockers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861655/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861655/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sobolevsky, Alexander I -- Rosconi, Michael P -- Gouaux, Eric -- F32 NS049767-05/NS/NINDS NIH HHS/ -- R01 NS038631/NS/NINDS NIH HHS/ -- R01 NS038631-06/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Dec 10;462(7274):745-56. doi: 10.1038/nature08624. Epub .〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19946266" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Crystallization ; Crystallography, X-Ray ; Ion Channel Gating ; Models, Molecular ; Potassium Channels/chemistry/metabolism ; Protein Conformation ; Protein Subunits/chemistry/metabolism ; Rats ; Receptors, AMPA/antagonists & inhibitors/*chemistry/*metabolism ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 63
    facet.materialart.
    Unknown
    Neuroscience: Excitatory view of a receptor (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-12-17
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225193/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225193/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wollmuth, Lonnie P -- Traynelis, Stephen F -- R01 MH066892/MH/NIMH NIH HHS/ -- R01 MH066892-08/MH/NIMH NIH HHS/ -- England -- Nature. 2009 Dec 10;462(7274):729-31. doi: 10.1038/462729a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010675" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crystallography, X-Ray ; Ion Channel Gating ; Models, Molecular ; Protein Conformation ; Protein Subunits/chemistry/metabolism ; Rats ; Receptors, AMPA/antagonists & inhibitors/*chemistry/*metabolism ; Receptors, N-Methyl-D-Aspartate/chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 64
    facet.materialart.
    Unknown
    Type II fatty acid synthesis is not a suitable antibiotic target for Gram-positive pathogens (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-03-06
    Description: Antimicrobial drugs targeting the reportedly essential type II fatty acid synthesis (FASII) pathway have been recently acclaimed for their efficacy against infections caused by multiresistant Gram-positive bacteria. Our findings show that the strategy for antibiotic development based on FASII pathway targets is fundamentally flawed by the fact that exogenous fatty acids fully bypass inhibition of this pathway in both in vitro and in vivo conditions. We demonstrate that major Gram-positive pathogens-such as streptococci, pneumococci, enterococci and staphylococci-overcome drug-induced FASII pathway inhibition when supplied with exogenous fatty acids, and human serum proves to be a highly effective source of fatty acids. For opportunist pathogen Streptococcus agalactiae, growth in serum leads to an overall decrease of FASII gene expression. No antibiotic inhibitor could have a stronger effect than the inactivation of the target gene, so we challenged the role of FASII using deletion mutants. Our results unequivocally show that the FASII target enzymes are dispensable in vivo during S. agalactiae infection. The results of this study largely compromise the use of FASII-based antimicrobials for treating sepsis caused by Gram-positive pathogens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brinster, Sophie -- Lamberet, Gilles -- Staels, Bart -- Trieu-Cuot, Patrick -- Gruss, Alexandra -- Poyart, Claire -- England -- Nature. 2009 Mar 5;458(7234):83-6. doi: 10.1038/nature07772.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19262672" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/*pharmacology ; *Drug Resistance, Bacterial ; Fatty Acids/analysis/*biosynthesis/chemistry/pharmacology ; Gene Expression Regulation, Bacterial/drug effects ; Genes, Bacterial/genetics ; Gram-Positive Bacteria/*drug effects/genetics/metabolism/pathogenicity ; Humans ; Mice ; Mice, Inbred C57BL ; Microbial Sensitivity Tests ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sepsis/drug therapy/microbiology ; Serum/chemistry/microbiology ; Streptococcal Infections/drug therapy/microbiology ; Streptococcus agalactiae/drug effects/enzymology/genetics/metabolism ; Substrate Specificity ; Virulence/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 65
    facet.materialart.
    Unknown
    Helical extension of the neuronal SNARE complex into the membrane (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-07-03
    Description: Neurotransmission relies on synaptic vesicles fusing with the membrane of nerve cells to release their neurotransmitter content into the synaptic cleft, a process requiring the assembly of several members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family. SNAREs represent an evolutionarily conserved protein family that mediates membrane fusion in the secretory and endocytic pathways of eukaryotic cells. On membrane contact, these proteins assemble in trans between the membranes as a bundle of four alpha-helices, with the energy released during assembly being thought to drive fusion. However, it is unclear how the energy is transferred to the membranes and whether assembly is conformationally linked to fusion. Here, we report the X-ray structure of the neuronal SNARE complex, consisting of rat syntaxin 1A, SNAP-25 and synaptobrevin 2, with the carboxy-terminal linkers and transmembrane regions at 3.4 A resolution. The structure shows that assembly proceeds beyond the already known core SNARE complex, resulting in a continuous helical bundle that is further stabilized by side-chain interactions in the linker region. Our results suggest that the final phase of SNARE assembly is directly coupled to membrane merger.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108252/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108252/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stein, Alexander -- Weber, Gert -- Wahl, Markus C -- Jahn, Reinhard -- P01 GM072694/GM/NIGMS NIH HHS/ -- P01 GM072694-01/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Jul 23;460(7254):525-8. doi: 10.1038/nature08156. Epub 2009 Jul 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571812" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crystallography, X-Ray ; Membrane Proteins/*chemistry ; Mice ; *Models, Molecular ; Neurons/*metabolism ; Protein Stability ; Protein Structure, Quaternary ; Rats ; SNARE Proteins/*chemistry/*metabolism ; Synapses/metabolism ; Syntaxin 1/chemistry ; Transition Temperature ; Vesicle-Associated Membrane Protein 2/chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 66
    facet.materialart.
    Unknown
    Nicotine binding to brain receptors requires a strong cation-pi interaction (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-03-03
    Description: Nicotine addiction begins with high-affinity binding of nicotine to acetylcholine (ACh) receptors in the brain. The end result is over 4,000,000 smoking-related deaths annually worldwide and the largest source of preventable mortality in developed countries. Stress reduction, pleasure, improved cognition and other central nervous system effects are strongly associated with smoking. However, if nicotine activated ACh receptors found in muscle as potently as it does brain ACh receptors, smoking would cause intolerable and perhaps fatal muscle contractions. Despite extensive pharmacological, functional and structural studies of ACh receptors, the basis for the differential action of nicotine on brain compared with muscle ACh receptors has not been determined. Here we show that at the alpha4beta2 brain receptors thought to underlie nicotine addiction, the high affinity for nicotine is the result of a strong cation-pi interaction to a specific aromatic amino acid of the receptor, TrpB. In contrast, the low affinity for nicotine at the muscle-type ACh receptor is largely due to the fact that this key interaction is absent, even though the immediate binding site residues, including the key amino acid TrpB, are identical in the brain and muscle receptors. At the same time a hydrogen bond from nicotine to the backbone carbonyl of TrpB is enhanced in the neuronal receptor relative to the muscle type. A point mutation near TrpB that differentiates alpha4beta2 and muscle-type receptors seems to influence the shape of the binding site, allowing nicotine to interact more strongly with TrpB in the neuronal receptor. ACh receptors are established therapeutic targets for Alzheimer's disease, schizophrenia, Parkinson's disease, smoking cessation, pain, attention-deficit hyperactivity disorder, epilepsy, autism and depression. Along with solving a chemical mystery in nicotine addiction, our results provide guidance for efforts to develop drugs that target specific types of nicotinic receptors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755585/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755585/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xiu, Xinan -- Puskar, Nyssa L -- Shanata, Jai A P -- Lester, Henry A -- Dougherty, Dennis A -- NS 11756/NS/NINDS NIH HHS/ -- NS 34407/NS/NINDS NIH HHS/ -- R01 DA017279/DA/NIDA NIH HHS/ -- R01 NS011756/NS/NINDS NIH HHS/ -- R01 NS011756-33/NS/NINDS NIH HHS/ -- England -- Nature. 2009 Mar 26;458(7237):534-7. doi: 10.1038/nature07768. Epub 2009 Mar 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19252481" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/chemistry/metabolism ; Animals ; Binding Sites ; Brain/*metabolism ; Cations/metabolism ; Halogenation ; Mice ; Models, Molecular ; Nicotine/chemistry/*metabolism ; Nicotinic Agonists/metabolism ; Oocytes/metabolism ; Organ Specificity ; Protein Binding ; Protein Conformation ; Rats ; Receptors, Nicotinic/chemistry/genetics/*metabolism ; Smoking/adverse effects ; Substance-Related Disorders/metabolism ; Tryptophan/chemistry/metabolism ; Xenopus laevis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 67
    facet.materialart.
    Unknown
    A cytosolic protein catalyzes the release of GDP from p21ras (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-04-06
    Description: The rate of release of guanine nucleotides from the ras proteins (Ras) is extremely slow in the presence of Mg2+. It seemed likely, therefore that a factor might exist to accelerate the release of guanosine diphosphate (GDP), and hence the exchange of GDP for guanosine triphosphate (GTP). Such a factor has now been discovered in rat brain cytosol. Brain cytosol was found to catalyze, by orders of magnitude, the release of guanine nucleotides from recombinant v-H-Ras protein bound with [alpha-32P]GDP. This effect occurred even in the presence of a large excess of Mg2+, but was destroyed by heat or by incubation of the cytosol for an hour at 37 degrees C in the absence of phosphatase inhibitors. The effect was observed with either v-H-Ras or c-H-Ras, but not with p25rab3A, a small G protein with about 30% similarity to Ras. The effect could not be mimicked by addition of recombinant Ras-GAP or purified GEF, a guanine nucleotide exchange factor involved in the regulation of eukaryotic protein synthesis. By gel filtration chromatography, the factor appears to possess a molecular size between 100,000 and 160,000 daltons. This protein (Ras-guanine nucleotide-releasing factor, or Ras-GRF) may be involved in the activation of p21ras.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolfman, A -- Macara, I G -- CA 43551/CA/NCI NIH HHS/ -- ES 01247/ES/NIEHS NIH HHS/ -- GM 41220/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Apr 6;248(4951):67-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics, University of Rochester Medical Center, NY 14642.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2181667" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding, Competitive ; Brain/metabolism ; Cholic Acids ; Cytosol/*metabolism ; Guanine Nucleotides/*metabolism ; Guanosine 5'-O-(3-Thiotriphosphate) ; Guanosine Diphosphate/*metabolism ; Guanosine Triphosphate/analogs & derivatives/metabolism ; Hot Temperature ; Immunosorbent Techniques ; Kinetics ; Magnesium Chloride/pharmacology ; Molecular Weight ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins p21(ras) ; Rats ; Thionucleotides/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 68
    facet.materialart.
    Unknown
    New transplant method evades immune attack (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-09-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Skerrett, P J -- New York, N.Y. -- Science. 1990 Sep 14;249(4974):1248.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2119053" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diabetes Mellitus, Experimental/*surgery ; Graft Enhancement, Immunologic ; Immune Tolerance ; *Islets of Langerhans Transplantation ; Rats ; T-Lymphocytes/immunology ; Thymus Gland/surgery ; Transplantation, Heterotopic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 69
    facet.materialart.
    Unknown
    Autophosphorylation of protein kinase C at three separated regions of its primary sequence (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-07-27
    Description: The major autophosphorylation sites of the rat beta II isozyme of protein kinase C were identified. The modified threonine and serine residues were found in the amino-terminal peptide, the carboxyl-terminal tail, and the hinge region between the regulatory lipid-binding domain and the catalytic kinase domain. Because this autophosphorylation follows an intrapeptide mechanism, extraordinary flexibility of the protein is necessary to phosphorylate the three regions. Comparison of the sequences surrounding the modified residues showed no obvious recognition motif nor any similarity to substrate phosphorylation sites, suggesting that proximity to the active site may be the primary criterion for their phosphorylation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flint, A J -- Paladini, R D -- Koshland, D E Jr -- DK09765/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1990 Jul 27;249(4967):408-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2377895" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Brain/enzymology ; Cloning, Molecular ; Isoenzymes/genetics/*metabolism ; Molecular Sequence Data ; Peptide Fragments/isolation & purification/metabolism ; Phosphorylation ; Protein Conformation ; Protein Kinase C/genetics/*metabolism ; Rats ; Recombinant Proteins/metabolism ; Signal Transduction ; Trypsin
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 70
    facet.materialart.
    Unknown
    Protection from chemotherapy-induced alopecia in a rat model (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-09-28
    Description: Alopecia (hair loss) is among the most distressing side effects of cancer chemotherapy. Little progress has been made, however, in its prevention or treatment, partly because of the lack of suitable experimental model. In recent work on the treatment of myelogenous leukemia in the rat, the following observations were made: (i) treatment of 8-day-old rats with cytosine arabinoside consistently produced alopecia, and (ii) ImuVert, a biologic response modifier derived from the bacterium Serratia marcescens, uniformly produced complete protection against the alopecia. In subsequent experiments, both cyclophosphamide and doxorubicin also produced alopecia in this model, and the doxorubicin-induced alopecia was prevented by treatment with ImuVert. The potential relevance of these observations to chemotherapy-induced alopecia in the clinical setting should be examined.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hussein, A M -- Jimenez, J J -- McCall, C A -- Yunis, A A -- DK07114/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 28;249(4976):1564-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Miami School of Medicine, FL 33101.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2218498" target="_blank"〉PubMed〈/a〉
    Keywords: Alopecia/chemically induced/*prevention & control ; Animals ; Biological Products ; Cytarabine/therapeutic use/*toxicity ; Disease Models, Animal ; Immunologic Factors/*therapeutic use ; Leukemia, Experimental/*drug therapy ; Rats ; Rats, Inbred F344 ; Skin/drug effects/pathology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 71
    facet.materialart.
    Unknown
    Autoradiographic imaging of phosphoinositide turnover in the brain (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-08-17
    Description: With [3H]cytidine as a precursor, phosphoinositide turnover can be localized in brain slices by selective autoradiography of the product [3H]cytidine diphosphate diacylglycerol, which is membrane-bound. In the cerebellum, glutamatergic stimulation elicits an increase of phosphoinositide turnover only in Purkinje cells and the molecular layer. In the hippocampus, both glutamatergic and muscarinic cholinergic stimulation increase phosphoinositide turnover, but with distinct localizations. Cholinergic stimulation affects CA1, CA3, CA4, and subiculum, whereas glutamatergic effects are restricted to the subiculum and CA3. Imaging phosphoinositide turnover in brain slices, which are amenable to electrophysiologic studies, will permit a dynamic localized analysis of regulation of this second messenger in response to synaptic stimulation of specific neuronal pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hwang, P M -- Bredt, D S -- Snyder, S H -- DA-00074/DA/NIDA NIH HHS/ -- GM-07309/GM/NIGMS NIH HHS/ -- MH-18501/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):802-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1975122" target="_blank"〉PubMed〈/a〉
    Keywords: Alanine/analogs & derivatives/pharmacology ; Animals ; Autoradiography ; Brain/*metabolism ; Carbachol/pharmacology ; Cerebellum/drug effects/metabolism ; Cycloleucine/analogs & derivatives/pharmacology ; Cytidine/metabolism ; Cytidine Diphosphate Diglycerides/metabolism ; Glutamates/physiology ; Glutamic Acid ; Hippocampus/drug effects/metabolism ; Neomycin/pharmacology ; Phosphatidylinositols/*metabolism ; Pirenzepine/pharmacology ; Purkinje Cells/metabolism ; Rats ; Receptors, Muscarinic/drug effects/physiology ; Tissue Distribution
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 72
    facet.materialart.
    Unknown
    D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-12-07
    Description: The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinson's disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinson's disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This treatment also increases dynorphin mRNA in striatonigral neurons. Thus, the differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D1 and D2 dopamine receptor subtypes, respectively.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gerfen, C R -- Engber, T M -- Mahan, L C -- Susel, Z -- Chase, T N -- Monsma, F J Jr -- Sibley, D R -- New York, N.Y. -- Science. 1990 Dec 7;250(4986):1429-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2147780" target="_blank"〉PubMed〈/a〉
    Keywords: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology ; Animals ; Cerebral Cortex/physiology ; Corpus Striatum/drug effects/*metabolism ; Ergolines/pharmacology ; Gene Expression Regulation ; Globus Pallidus/drug effects/*metabolism ; Hydroxydopamines/pharmacology ; Models, Neurological ; Neurons/drug effects/*metabolism ; Oligonucleotide Probes ; Oxidopamine ; Quinpirole ; RNA, Messenger/drug effects/*genetics ; Rats ; Receptors, Dopamine/*genetics ; Receptors, Dopamine D1 ; Receptors, Dopamine D2 ; Substantia Nigra/drug effects/*metabolism ; Thalamus/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 73
    facet.materialart.
    Unknown
    Light pulses that shift rhythms induce gene expression in the suprachiasmatic nucleus (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-06-08
    Description: Lighting cycles synchronize (entrain) mammalian circadian rhythms by altering activity of cells in the suprachiasmatic nucleus (SCN) of the hypothalamus, a circadian pacemaker. Exposure of hamsters and rats to light pulses at those phases of the circadian rhythm during which light can shift the rhythm caused increased immunoreactivity for the product of the immediate-early gene c-fos in cells in the region of the SCN that receives retinal fibers. Light pulses also increased messenger RNA for the Fos protein and for the immediate-early protein NGFI-A in the rat SCN. Similar increases in mRNA for NGFI-A were seen in the SCN of hamsters. Thus cells in this portion of the SCN undergo alterations in gene expression in response to retinal illumination, but only at times in the circadian cycle when light is capable of influencing entrainment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rusak, B -- Robertson, H A -- Wisden, W -- Hunt, S P -- New York, N.Y. -- Science. 1990 Jun 8;248(4960):1237-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, Dalhousie University, Halifax, Nova Scotia, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2112267" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Circadian Rhythm ; Cricetinae ; Darkness ; *Gene Expression ; Light ; Nerve Growth Factors/*genetics ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins c-fos ; *Proto-Oncogenes ; RNA, Messenger/*analysis/genetics ; Rats ; Suprachiasmatic Nucleus/*physiology/radiation effects ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 74
    facet.materialart.
    Unknown
    Molecular cloning and expression of a complementary DNA for inositol 1,4,5-trisphosphate 3-kinase (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-04-06
    Description: A complementary DNA (cDNA) clone that encodes inositol 1,4,5-trisphosphate 3-kinase was isolated from a rat brain cDNA expression library with the use of monoclonal antibodies. This clone had an open reading frame that would direct the synthesis of a protein consisting of 449 amino acids and with a molecular mass of 49,853 daltons. The putative protein revealed a potential calmodulin-binding site and six regions with amino acid compositions (PEST regions) common to proteins that are susceptible to calpain. Expression of the cDNA in COS cells resulted in an approximately 150-fold increase in inositol 1,4,5-trisphosphate 3-kinase activity of these cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, K Y -- Kim, H K -- Lee, S Y -- Moon, K H -- Sim, S S -- Kim, J W -- Chung, H K -- Rhee, S G -- New York, N.Y. -- Science. 1990 Apr 6;248(4951):64-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2157285" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Brain/enzymology ; Calcium/metabolism ; Calmodulin/metabolism ; Calpain/antagonists & inhibitors/pharmacology ; Cell Line ; *Cloning, Molecular ; Codon ; DNA/*genetics ; *Gene Expression ; Molecular Sequence Data ; Molecular Weight ; Phosphotransferases/*genetics/metabolism ; *Phosphotransferases (Alcohol Group Acceptor) ; Plasmids ; Rats ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 75
    facet.materialart.
    Unknown
    Phencyclidine, dizocilpine, and cerebrocortical neurons (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-01-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allen, H L -- Iversen, L L -- New York, N.Y. -- Science. 1990 Jan 12;247(4939):221.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2403696" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/drug effects/*ultrastructure ; Dibenzocycloheptenes/administration & dosage/*pharmacology ; Dizocilpine Maleate ; Male ; Neurons/drug effects/*ultrastructure ; Phencyclidine/*pharmacology ; Rats ; Vacuoles/drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 76
    facet.materialart.
    Unknown
    Identification of a specialized adenylyl cyclase that may mediate odorant detection (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-12-07
    Description: The mammalian olfactory system may transduce odorant information via a G protein-mediated adenosine 3',5'-monophosphate (cAMP) cascade. A newly discovered adenylyl cyclase, termed type III, has been cloned, and its expression was localized to olfactory neurons. The type III protein resides in the sensory neuronal cilia, which project into the nasal lumen and are accessible to airborne odorants. The enzymatic activity of the type III adenylyl cyclase appears to differ from nonsensory cyclases. The large difference seen between basal and stimulated activity for the type III enzyme could allow considerable modulation of the intracellular cAMP concentration. This property may represent one mechanism of achieving sensitivity in odorant perception.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bakalyar, H A -- Reed, R R -- 5T32CA09339/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 7;250(4986):1403-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2255909" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/genetics/*physiology ; Amino Acid Sequence ; Animals ; Brain/enzymology/physiology ; Cell Line ; Clone Cells ; Cloning, Molecular ; Gene Library ; Glycosylation ; Isoenzymes/genetics/*physiology ; Macromolecular Substances ; Molecular Sequence Data ; Molecular Weight ; Neurons, Afferent/enzymology/physiology ; Nose/enzymology/physiology ; *Odors ; Protein Conformation ; Rats ; *Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 77
    facet.materialart.
    Unknown
    Endogenous cholecystokinin reduces feeding in young rats (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-03-30
    Description: The hypothesis that endogenous cholecystokinin (CCK) released from the small intestine during feeding causes satiety was tested in rat pups, 9 to 12 days old. Intragastric administration of soybean trypsin inhibitor, a procedure that releases CCK from the small intestine, decreased the subsequent intake of a test meal. This effect was reversed by prior treatment with MK-329, a selective antagonist of CCK at alimentary-type CCK (CCK-A) receptors. Thus, endogenous, small intestinal CCK can cause satiety in the neonatal rat and this effect involves CCK-A receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weller, A -- Smith, G P -- Gibbs, J -- MH00149/MH/NIMH NIH HHS/ -- MH40010/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 1990 Mar 30;247(4950):1589-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry, Cornell University Medical College, White Plains, NY.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2321020" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Benzodiazepinones/pharmacology ; Cholecystokinin/antagonists & inhibitors/*physiology ; Devazepide ; Eating/*physiology ; Intestine, Small/*metabolism ; Rats ; Rats, Inbred Strains ; Receptors, Cholecystokinin/drug effects/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 78
    facet.materialart.
    Unknown
    Identification of the DNA binding site for NGFI-B by genetic selection in yeast (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-05-31
    Description: An in vivo selection system for isolating targets of DNA binding proteins in yeast was developed and used to identify the DNA binding site for the NGFI-B protein, a member of the steroid-thyroid hormone receptor superfamily. The feasibility of the technique was verified by selecting DNA fragments that contained binding sites for GCN4, a well-characterized yeast transcriptional activator. The DNA binding domain of NGFI-B, expressed as part of a LexA-NGFI-B-GAL4 chimeric activator, was then used to isolate a rat genomic DNA fragment that contained an NGFI-B binding site. The NGFI-B response element (NBRE) is similar to but functionally distinct from elements recognized by the estrogen and thyroid hormone receptors and the hormone receptor-like proteins COUP-TF, CF1, and H-2RIIBP. Cotransfection experiments in mammalian cells demonstrated that NGFI-B can activate transcription from the NBRE with or without its putative ligand binding domain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, T E -- Fahrner, T J -- Johnston, M -- Milbrandt, J -- NS01018/NS/NINDS NIH HHS/ -- P01 CA49712/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1991 May 31;252(5010):1296-300.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1925541" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/metabolism ; Base Sequence ; Binding Sites ; Cloning, Molecular ; DNA, Fungal/*metabolism ; DNA-Binding Proteins/genetics/*metabolism/pharmacology ; Fungal Proteins/metabolism ; Molecular Sequence Data ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; Plasmids ; *Protein Kinases ; Rats ; Receptors, Cytoplasmic and Nuclear ; Receptors, Steroid ; Repressor Proteins ; Saccharomyces cerevisiae/*genetics ; *Saccharomyces cerevisiae Proteins ; *Serine Endopeptidases ; Transcription Factors/genetics/*metabolism/pharmacology ; Transcription, Genetic ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 79
    facet.materialart.
    Unknown
    Space may be bad for your health (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-09-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, E -- New York, N.Y. -- Science. 1991 Sep 27;253(5027):1491.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1896859" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; Models, Biological ; Monitoring, Physiologic ; Motion Sickness/*etiology ; Rats ; Scyphozoa ; *Space Flight ; *Weightlessness
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 80
    facet.materialart.
    Unknown
    Split anergy in a CD8+ T cell: receptor-dependent cytolysis in the absence of interleukin-2 production (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-03-08
    Description: Engagement of the antigen-specific receptor (TCR) of CD4+ T lymphocytes without a second (costimulatory) signal prevents the subsequent production of interleukin-2 (IL-2) by these cells. Because IL-2 is a key immunoregulatory lymphokine and is also produced by a subset of CD8+ T cells that are able to kill target cells, the effect of engaging the TCR of one such clone in the absence of costimulatory signals was examined. The capacity for TCR-dependent IL-2 production was lost, indicating comparable costimulator-dependent signaling requirements for IL-2 production in CD4+ and CD8+ T cells. However, TCR-mediated cytotoxicity was not impaired, implying that costimulation is required for only certain TCR-dependent effector functions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Otten, G R -- Germain, R N -- New York, N.Y. -- Science. 1991 Mar 8;251(4998):1228-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1900952" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/immunology ; Antigen-Presenting Cells/immunology ; Antigens, CD8 ; Antigens, Differentiation, T-Lymphocyte/*immunology ; Female ; Interleukin-2/biosynthesis/*physiology ; Kinetics ; Lymphocyte Activation ; Mice ; Mice, Inbred Strains ; Ovalbumin/immunology ; Rats ; Receptors, Antigen, T-Cell/*immunology ; Spleen/immunology/radiation effects ; T-Lymphocytes/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 81
    facet.materialart.
    Unknown
    Modulation of cardiac sodium channels by cAMP receptors on the myocyte surface (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-09-13
    Description: The phosphorylation of the cardiac sodium channel by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase A leads to its inactivation. It was shown that extracellular cAMP can also modulate the sodium channel of rat, guinea pig, and frog ventricular myocytes in a rapid (less than 50 milliseconds), reversible, and dose-dependent manner. The decrease in the sodium current was accompanied by a 10- to 15-millivolt shift in the steady-state availability of the sodium channel toward more negative potentials and was inhibited by guanosine-5'-O-(2-thiodiphosphate) or pertussis toxin, suggesting that the extracellular modulation of the sodium channel by cAMP is mediated by a membrane-delimited mechanism that includes a pertussis toxin-sensitive G protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sorbera, L A -- Morad, M -- HL16152/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1991 Sep 13;253(5025):1286-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Pennsylvania, Philadelphia 19104.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1653970" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cyclic AMP/*pharmacology ; Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology ; Guanosine Diphosphate/analogs & derivatives/pharmacology ; Guinea Pigs ; Heart/drug effects/*physiology ; Isoproterenol/pharmacology ; Kinetics ; Membrane Potentials/drug effects ; Pertussis Toxin ; Rana pipiens ; Rats ; Receptors, Cyclic AMP/drug effects/*physiology ; Sodium Channels/drug effects/*physiology ; Thionucleotides/pharmacology ; Virulence Factors, Bordetella/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 82
    facet.materialart.
    Unknown
    Cloning and expression of a cocaine-sensitive rat dopamine transporter (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-10-25
    Description: The action of dopamine and other monoamine neurotransmitters at synapses is terminated predominantly by high-affinity reuptake into presynaptic terminals by specific sodium-dependent neurotransmitter transport proteins. A complementary DNA encoding a rat dopamine transporter has been isolated that exhibits high sequence similarity with the previously cloned norepinephrine and gamma-aminobutyric acid transporters. Transient expression of the complementary DNA in HeLa cells confirms the cocaine sensitivity of this transporter.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kilty, J E -- Lorang, D -- Amara, S G -- New York, N.Y. -- Science. 1991 Oct 25;254(5031):578-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Yale University, New Haven, CT 06510.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1948035" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Carrier Proteins/drug effects/*genetics/metabolism ; Cloning, Molecular ; Cocaine/*pharmacology ; Dopamine/*metabolism ; Dopamine Plasma Membrane Transport Proteins ; Gene Expression ; HeLa Cells ; Humans ; Kinetics ; *Membrane Glycoproteins ; *Membrane Transport Proteins ; Molecular Sequence Data ; *Nerve Tissue Proteins ; Oligodeoxyribonucleotides ; Polymerase Chain Reaction/methods ; Rats ; Sequence Homology, Nucleic Acid ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 83
    facet.materialart.
    Unknown
    Exchange of conduction pathways between two related K+ channels (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-02-22
    Description: The structure of the ion conduction pathway or pore of voltage-gated ion channels is unknown, although the linker between the membrane spanning segments S5 and S6 has been suggested to form part of the pore in potassium channels. To test whether this region controls potassium channel conduction, a 21-amino acid segment of the S5-S6 linker was transplanted from the voltage-activated potassium channel NGK2 to another potassium channel DRK1, which has very different pore properties. In the resulting chimeric channel, the single channel conductance and blockade by external and internal tetraethylammonium (TEA) ion were characteristic of the donor NGK2 channel. Thus, this 21-amino acid segment controls the essential biophysical properties of the pore and may form the conduction pathway of these potassium channels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hartmann, H A -- Kirsch, G E -- Drewe, J A -- Taglialatela, M -- Joho, R H -- Brown, A M -- NS08805/NS/NINDS NIH HHS/ -- NS23877/NS/NINDS NIH HHS/ -- NS28407/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1991 Feb 22;251(4996):942-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2000495" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Brain/physiology ; Chimera ; Cloning, Molecular ; Female ; Ion Channel Gating ; Membrane Potentials ; Molecular Sequence Data ; Oligonucleotide Probes ; Oocytes/physiology ; Polymerase Chain Reaction ; Potassium Channels/drug effects/genetics/*physiology ; Rats ; Restriction Mapping ; Sequence Homology, Nucleic Acid ; Tetraethylammonium ; Tetraethylammonium Compounds/pharmacology ; Xenopus
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 84
    facet.materialart.
    Unknown
    Engineers open a dialogue with neurons (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-07-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amato, I -- New York, N.Y. -- Science. 1991 Jul 5;253(5015):34.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2063204" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biomedical Engineering ; Electric Stimulation ; Electrodes, Implanted ; *Neurons ; Rats
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 85
    facet.materialart.
    Unknown
    Protein kinase activity closely associated with a reconstituted calcium-activated potassium channel (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-08-02
    Description: Modulation of the activity of potassium and other ion channels is an essential feature of nervous system function. The open probability of a large conductance Ca(2+)-activated K+ channel from rat brain, incorporated into planar lipid bilayers, is increased by the addition of adenosine triphosphate (ATP) to the cytoplasmic side of the channel. This modulation takes place without the addition of protein kinase, requires Mg2+, and is mimicked by an ATP analog that serves as a substrate for protein kinases but not by a nonhydrolyzable ATP analog. Addition of protein phosphatase 1 reverses the modulation by MgATP. Thus, there may be an endogenous protein kinase activity firmly associated with this K+ channel. Some ion channels may exist in a complex that contains regulatory protein kinases and phosphatases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chung, S K -- Reinhart, P H -- Martin, B L -- Brautigan, D -- Levitan, I B -- DK31374/DK/NIDDK NIH HHS/ -- NS17910/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1991 Aug 2;253(5019):560-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Department of Biochemistry, Brandeis University, Waltham, MA 02254.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1857986" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/pharmacology ; Animals ; Brain/*physiology ; Calcium/*pharmacology ; Kinetics ; Lipid Bilayers ; Potassium Channels/drug effects/metabolism/*physiology ; Protein Kinases/*metabolism ; Rats
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 86
    facet.materialart.
    Unknown
    Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-03-22
    Description: Defensins (molecular weight 3500 to 4000) act in the mammalian immune response by permeabilizing the plasma membranes of a broad spectrum of target organisms, including bacteria, fungi, and enveloped viruses. The high-resolution crystal structure of defensin HNP-3 (1.9 angstrom resolution, R factor 0.19) reveals a dimeric beta sheet that has an architecture very different from other lytic peptides. The dimeric assembly suggests mechanisms by which defensins might bind to and permeabilize the lipid bilayer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hill, C P -- Yee, J -- Selsted, M E -- Eisenberg, D -- New York, N.Y. -- Science. 1991 Mar 22;251(5000):1481-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Eisenberg, Molecular Biology Institute, Los Angeles, CA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2006422" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Blood Proteins/chemistry/*ultrastructure ; Cell Membrane Permeability ; Crystallography ; Defensins ; Guinea Pigs ; Humans ; Macromolecular Substances ; Membrane Proteins/chemistry/ultrastructure ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; Protein Conformation ; Rabbits ; Rats ; Structure-Activity Relationship ; X-Ray Diffraction ; *alpha-Defensins
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 87
    facet.materialart.
    Unknown
    Modulation of the time course of fast EPSCs and glutamate channel kinetics by aniracetam (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-10-11
    Description: It is generally accepted that glutamate serves as the neurotransmitter at most excitatory synapses in the mammalian central nervous system (CNS). Synaptic release of glutamate may trigger a fast and a slow excitatory postsynaptic current (EPSC). The slow EPSC is mediated by N-methyl-D-aspartate (NMDA) receptor channels, whereas the fast EPSC is mediated by non-NMDA receptor channels. The nootropic agent aniracetam selectively and reversibly slows the desensitization kinetics of non-NMDA channels and lengthens their single-channel open times. Antiracetam also modulates the kinetics of the fast EPSC in a manner that mirrors its action on the kinetics of the non-NMDA channels. These results support the hypothesis that the properties of the non-NMDA glutamate channels rather than the rate of neurotransmitter clearance are the primary determinants of the kinetics of the fast EPSC in the mammalian CNS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tang, C M -- Shi, Q Y -- Katchman, A -- Lynch, G -- NS28158/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1991 Oct 11;254(5029):288-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, University of Pennsylvania, Philadelphia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1681589" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/*drug effects ; Animals ; Glutamates/*physiology ; Glutamic Acid ; Kinetics ; Pyrrolidinones/*pharmacology ; Rats ; Receptors, Glutamate ; Receptors, N-Methyl-D-Aspartate/drug effects ; Receptors, Neurotransmitter/drug effects ; Synapses/*drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 88
    facet.materialart.
    Unknown
    Requirement of nuclear prolactin for interleukin-2--stimulated proliferation of T lymphocytes (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-07-05
    Description: Prolactin (PRL) is necessary for the proliferation of cloned T lymphocytes in response to interleukin-2 (IL-2). Translocation of PRL into the nucleus occurs during IL-2--stimulated mitogenesis. Therefore, the function of intranuclear PRL in T cell proliferation was tested. Eukaryotic expression vectors were prepared to express wild-type PRL [PRL(WT)], PRL that lacks the signal sequence for translocation into the endoplasmic reticulum [PRL(ER-)], and chimeric PRL in which the signal peptide was replaced with the sequence that directs the nuclear translocation of the SV40 large T antigen [PRL(NT+)]. Expression of these constructs in a T cell line (Nb2) responsive to PRL and IL-2 resulted in localization of PRL in the extracellular milieu, cytoplasm, or nucleus, respectively. Stimulation with IL-2 alone resulted in a five- to tenfold increase in the incorporation of [3H]thymidine by cells expressing PRL(NT+) or PRL(WT) as compared to PRL(ER-) or the parental Nb2 cells. Only the PRL(NT+) clone proliferated continuously with IL-2 stimulation in the presence of antiserum to PRL. These results demonstrate that nuclear PRL is necessary for IL-2--stimulated proliferation and suggest that a peptide hormone can function in the nucleus without binding to its cell surface receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clevenger, C V -- Altmann, S W -- Prystowsky, M B -- GM-13901/GM/NIGMS NIH HHS/ -- GM-36962/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1991 Jul 5;253(5015):77-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2063207" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Biological Transport, Active ; Cell Cycle/drug effects ; Cell Nucleus/metabolism ; Drug Synergism ; Genetic Vectors ; In Vitro Techniques ; Interleukin-2/pharmacology ; Lymphocyte Activation/*drug effects ; Molecular Sequence Data ; Prolactin/pharmacokinetics/*pharmacology ; Rats ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 89
    facet.materialart.
    Unknown
    Control of alternative splicing by the differential binding of U1 small nuclear ribonucleoprotein particle (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-03-01
    Description: Cellular factors controlling alternative splicing of precursor messenger RNA are largely unknown, even though this process plays a central role in specifying the diversity of proteins in the eukaryotic cell. For the identification of such factors, a segment of the rat preprotachykinin gene was used in which differential expression of neuropeptides gamma and K is dependent on alternative splicing of the fourth exon (E4). Sequence variants of the three-exon segment, (E3-E4-E5) were created, resulting in a sensitive assay for factors mediating the splicing switch between E4-skipping and E4-inclusion. A dinucleotide mutation in the 5' splice site of E4 that increase base-pairing of this site to U1 small nuclear RNA resulted in uniform selection of E4, whereas a control mutation that destroyed base-pairing resulted in uniform E4-skipping. Affinity selection of spliceosomes formed on these functionally distinct substrates revealed that the extreme difference in splicing was mediated by differential binding of the U1 small nuclear ribonucleoprotein particle (snRNP) to the 5' splice site of E4. These data show that, apart from its established role in selecting 5' splice sites, U1 snRNP plays a fundamental role in 3' exon selection and provides insight into possible mechanisms of alternative splicing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuo, H C -- Nasim, F H -- Grabowski, P J -- GM-39695/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1991 Mar 1;251(4997):1045-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Biochemistry, Brown University, Providence, RI 02912.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1825520" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; DNA Mutational Analysis ; Exons ; Hydrogen Bonding ; Macromolecular Substances ; Molecular Sequence Data ; Protein Precursors/*genetics ; *RNA Splicing ; RNA, Messenger/*metabolism ; RNA, Small Nuclear/*physiology ; Rats ; Ribonucleoproteins/chemistry/*physiology ; Ribonucleoproteins, Small Nuclear ; Structure-Activity Relationship ; Tachykinins/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 90
    facet.materialart.
    Unknown
    Maintenance of normoglycemia in diabetic mice by subcutaneous xenografts of encapsulated islets (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-12-20
    Description: The goal of islet transplantation in human diabetes is to maintain the islet grafts in the recipients without the use of immunosuppression. One approach is to encapsulate the donor islets in permselective membranes. Hollow fibers fabricated from an acrylic copolymer were used to encapsulate small numbers of rat islets that were immobilized in an alginate hydrogel for transplantation in diabetic mice. The fibers were biocompatible, prevented rejection, and maintained normoglycemia when transplanted intraperitoneally; hyperglycemia returned when the fibers were removed at 60 days. Normoglycemia was also maintained by subcutaneous implants that had an appropriately constructed outer surface on the fibers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lacy, P E -- Hegre, O D -- Gerasimidi-Vazeou, A -- Gentile, F T -- Dionne, K E -- DK01226/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1991 Dec 20;254(5039):1782-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1763328" target="_blank"〉PubMed〈/a〉
    Keywords: *Acrylic Resins ; Animals ; Animals, Newborn ; Blood Glucose/*metabolism ; Diabetes Mellitus, Experimental/blood/*surgery ; In Vitro Techniques ; Insulin/secretion ; Islets of Langerhans/*secretion ; Islets of Langerhans Transplantation/*physiology ; Male ; Membranes, Artificial ; Mice ; Mice, Inbred C57BL ; *Polyvinyl Chloride ; Rats ; Rats, Inbred WF ; Time Factors ; Transplantation, Heterologous
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 91
    facet.materialart.
    Unknown
    Identification of Ets- and notch-related subunits in GA binding protein (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-08-16
    Description: Recombinant cDNA clones that encode two distinct subunits of the transcription factor GA binding protein (GABP) have been isolated. The predicted amino acid sequence of one subunit, GABP alpha, exhibits similarity to the sequence of the product of the ets-1 protooncogene in a region known to encompass the Ets DNA binding domain. The sequence of the second subunit, GABP beta, contains four 33-amino acid repeats located close to the NH2-terminus of the subunit. The sequences of these repeats are similar to repeats in several transmembrane proteins, including Notch from Drosophila melanogaster and Glp-1 and Lin-12 from Caenorhabditis elegans. Avid, sequence-specific binding to DNA required the presence of both polypeptides, revealing a conceptual convergence of nuclear transforming proteins and membrane-anchored proteins implicated in developmentally regulated signal transduction processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉LaMarco, K -- Thompson, C C -- Byers, B P -- Walton, E M -- McKnight, S L -- New York, N.Y. -- Science. 1991 Aug 16;253(5021):789-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Research Laboratories, Carnegie Institution of Washington, Department of Embryology, Baltimore, MD 21210.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1876836" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Blotting, Northern ; Cloning, Molecular ; DNA-Binding Proteins/*chemistry/genetics ; GA-Binding Protein Transcription Factor ; Gene Expression ; Molecular Sequence Data ; Nuclear Proteins/chemistry/genetics ; Peptides/chemistry ; Proto-Oncogene Protein c-ets-1 ; Proto-Oncogene Proteins/chemistry ; Proto-Oncogene Proteins c-ets ; RNA, Messenger/genetics ; Rats ; Recombinant Proteins ; Transcription Factors/*chemistry/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 92
    facet.materialart.
    Unknown
    More pieces in the dioxin puzzle (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-10-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, L -- New York, N.Y. -- Science. 1991 Oct 18;254(5030):377.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1656528" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinogens/*toxicity ; Dioxins/*toxicity ; Dose-Response Relationship, Drug ; Models, Theoretical ; Rats ; Receptors, Aryl Hydrocarbon ; Receptors, Drug/metabolism ; Risk
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 93
    facet.materialart.
    Unknown
    Convergence of Ets- and notch-related structural motifs in a heteromeric DNA binding complex (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-08-16
    Description: Analysis of the heteromeric DNA binding protein GABP has revealed the interaction of two distinct peptide sequence motifs normally associated with proteins located in different cellular compartments. The alpha subunit of GABP contains an 85-amino acid segment related to the Ets family of DNA binding proteins. The ETS domain of GABP alpha facilitates weak binding to DNA and, together with an adjacent segment of 37 amino acids, mediates stable interaction with GABP beta. The beta subunit of GABP contains four imperfect repeats of a sequence present in several transmembrane proteins including the product of the Notch gene of Drosophila melanogaster. These amino-terminal repeats of GABP beta mediate stable interaction with GABP alpha and, when complexed with GABP alpha, directly contact DNA. These observations provide evidence for a distinct biochemical role for the 33-amino acid repeats, and suggest that they may serve as a module for the generation of specific dimerization interfaces.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, C C -- Brown, T A -- McKnight, S L -- New York, N.Y. -- Science. 1991 Aug 16;253(5021):762-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Research Laboratories, Carnegie Institution of Washington, Department of Embryology, Baltimore, MD 21210.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1876833" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Cross-Linking Reagents ; DNA/metabolism ; DNA-Binding Proteins/*chemistry/metabolism ; GA-Binding Protein Transcription Factor ; Macromolecular Substances ; Molecular Sequence Data ; Molecular Weight ; Multigene Family ; Nuclear Proteins/*chemistry/metabolism ; Oligonucleotides/chemistry ; Proto-Oncogene Proteins/chemistry ; Proto-Oncogene Proteins c-ets ; Rats ; Recombinant Proteins ; Structure-Activity Relationship ; Transcription Factors/*chemistry/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 94
    facet.materialart.
    Unknown
    Stimulation of protein tyrosine phosphorylation by NMDA receptor activation (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-08-23
    Description: The N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptors, plays a key role in synaptic plasticity in the nervous system. After NMDA receptor activation, calcium entry into the postsynaptic neuron is a critical initial event. However, the subsequent mechanisms by which the NMDA receptor signal is processed are incompletely understood. Stimulation of cultured rat hippocampal cells with glutamate resulted in the rapid and transient tyrosine phosphorylation of a 39-kilodalton protein (p39). Tyrosine phosphorylation of p39 was triggered by the NMDA receptor and required an influx of Ca2+ from the extracellular medium. Because p39 was found to be highly related or identical to the microtubule-associated protein 2 kinase, the NMDA receptor signal may be processed by a sequential activation of protein kinases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bading, H -- Greenberg, M E -- CA 43855/CA/NCI NIH HHS/ -- NS 28829/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1991 Aug 23;253(5022):912-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1715095" target="_blank"〉PubMed〈/a〉
    Keywords: 2-Amino-5-phosphonovalerate/pharmacology ; Animals ; Calcium/metabolism ; Calcium-Calmodulin-Dependent Protein Kinases ; Cells, Cultured ; Glutamates/pharmacology ; Glutamic Acid ; Hippocampus/drug effects/metabolism ; Immunoblotting ; Kinetics ; Phosphoproteins/*metabolism ; Phosphorylation ; Phosphotyrosine ; Protein Kinases/metabolism ; Rats ; Receptors, N-Methyl-D-Aspartate/*metabolism ; Tyrosine/*analogs & derivatives/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 95
    facet.materialart.
    Unknown
    New vector delivers genes to lung cells (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-04-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoffman, M -- New York, N.Y. -- Science. 1991 Apr 19;252(5004):374.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2017677" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoviridae/*genetics ; Animals ; Emphysema/therapy ; Genetic Therapy ; *Genetic Vectors ; Humans ; *Lung ; Rats ; *Transfection ; alpha 1-Antitrypsin/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 96
    facet.materialart.
    Unknown
    EPA moves to reassess the risk of dioxin (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-05-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, L -- New York, N.Y. -- Science. 1991 May 17;252(5008):911.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2035022" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinogenicity Tests ; *Carcinogens ; Dioxins/*toxicity ; Humans ; National Institute for Occupational Safety and Health (U.S.) ; Neoplasms, Experimental/chemically induced ; Rats ; Risk Factors ; United States ; *United States Environmental Protection Agency
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 97
    facet.materialart.
    Unknown
    Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801 (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-01-04
    Description: The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is an important mediator of several forms of neural and behavioral plasticity. The present studies examined whether NMDA receptors might be involved in the development of opiate tolerance and dependence, two examples of behavioral plasticity. The noncompetitive NMDA receptor antagonist MK-801 attenuated the development of tolerance to the analgesic effect of morphine without affecting acute morphine analgesia. In addition, MK-801 attenuated the development of morphine dependence as assessed by naloxone-precipitated withdrawal. These results suggest that NMDA receptors may be important in the development of opiate tolerance and dependence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trujillo, K A -- Akil, H -- DA02265/DA/NIDA NIH HHS/ -- DA05336/DA/NIDA NIH HHS/ -- MH422251/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 1991 Jan 4;251(4989):85-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mental Health Research Institute, University of Michigan, Ann Arbor 48109-0720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1824728" target="_blank"〉PubMed〈/a〉
    Keywords: *Analgesia ; Animals ; Behavior, Animal/drug effects ; Dizocilpine Maleate/*pharmacology ; Drug Tolerance ; Male ; *Morphine ; Naloxone/pharmacology ; Pain Measurement ; Rats ; Rats, Inbred Strains ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*physiology ; *Substance-Related Disorders
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 98
    facet.materialart.
    Unknown
    The brain as "sexual organ" (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbons, A -- New York, N.Y. -- Science. 1991 Aug 30;253(5023):957-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1887226" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*anatomy & histology/physiology ; Corpus Callosum/anatomy & histology/physiology ; Female ; Humans ; Hypothalamus/*anatomy & histology/physiology ; Male ; Rats ; *Sex Characteristics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 99
    facet.materialart.
    Unknown
    Clusters of coupled neuroblasts in embryonic neocortex (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-04-26
    Description: The neocortex of the brain develops from a simple germinal layer into a complex multilayer structure. To investigate cellular interactions during early neocortical development, whole-cell patch clamp recordings were made from neuroblasts in the ventricular zone of fetal rats. During early corticogenesis, neuroblasts are physiologically coupled by gap junctions into clusters of 15 to 90 cells. The coupled cells form columns within the ventricular zone and, by virtue of their membership in clusters, have low apparent membrane resistances and generate large responses to the inhibitory neurotransmitter gamma-aminobutyric acid. As neuronal migration out of the ventricular zone progresses, the number of cells within the clusters decreases. These clusters allow direct cell to cell interaction at the earliest stages of corticogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lo Turco, J J -- Kriegstein, A R -- NS07280/NS/NINDS NIH HHS/ -- NS12151/NS/NINDS NIH HHS/ -- NS21223/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1991 Apr 26;252(5005):563-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1850552" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/cytology/embryology/*physiology ; Electric Conductivity ; Electrophysiology/methods ; Embryo, Mammalian ; Evoked Potentials/drug effects ; In Vitro Techniques ; Membrane Potentials/drug effects ; Neurons/cytology/drug effects/*physiology ; Rats ; Receptors, GABA-A/physiology ; gamma-Aminobutyric Acid/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 100
    facet.materialart.
    Unknown
    High probability opening of NMDA receptor channels by L-glutamate (1992)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1992-01-24
    Description: Synaptic plasticity can be triggered by calcium flux into neurons through synaptically activated N-methyl-D-aspartate (NMDA) receptor channels. The amplitude and time course of the resulting intracellular calcium transient depend on the number of open NMDA receptor channels and the kinetics of their activation. Short applications of L-glutamate to outside-out patches from hippocampal neurons in the presence and absence of MK-801 revealed that about 30 percent of L-glutamate-bound channels are open at the peak of the current. This high probability of opening suggests that very few channels are required to guarantee a large, localized postsynaptic calcium transient.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jahr, C E -- NS21419/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1992 Jan 24;255(5043):470-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute L474, Oregon Health Sciences University, Portland 97201.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1346477" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Cells, Cultured ; Dizocilpine Maleate/pharmacology ; Glutamates/*physiology ; Glutamic Acid ; Hippocampus/physiology ; In Vitro Techniques ; *Ion Channel Gating ; Rats ; Receptors, N-Methyl-D-Aspartate/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...