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  • 1
    ISSN: 1435-9456
    Keywords: Key words Shape from shading ; Visual search ; Texture segregation ; Chimpanzees ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The perception of shape from shading was tested in two chimpanzees (Pan troglodytes) and five humans (Homo sapiens), using visual search tasks. Subjects were required to select and touch an odd item (target) from among uniform distractors. Humans found the target faster when shading was vertical than when it was horizontal, consistent with results of previous research. Both chimpanzees showed the opposite pattern: they found the target faster when shading was horizontal. The same difference in response was found in texture segregation tasks. This difference between the species could not be explained by head rotation or head shift parallel to the surface of the monitor. Furthermore, when the shaded shape was changed from a circle to a square, or the shading type was changed from gradual to stepwise, the difference in performance between vertical and horizontal shading disappeared in chimpanzees, but persisted in humans. These results suggest that chimpanzees process shading information in a different way from humans.
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  • 2
    ISSN: 1432-1432
    Keywords: Genome composition ; Coding sequences ; Isochores ; Humans ; Murids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The compositional distributions of coding sequences and DNA molecules (in the 50-100-kb range) are remarkably narrower in murids (rat and mouse) compared to humans (as well as to all other mammals explored so far). In murids, both distributions begin at higher and end at lower GC values. A comparison of homologous coding sequences from murids and humans revealed that their different compositional distributions are due to differences in GC levels in all three codon positions, particularly of genes located at both ends of the distribution. In turn, these differences are responsible for differences in both codon usage and amino acids. When GC levels at first+second codon positions and third codon positions, respectively, of murid genes are plotted against corresponding GC levels of homologous human genes, linear relationships (with very high correlation coefficients and slopes of about 0.78 and 0.60, respectively) are found. This indicates a conservation of the order of GC levels in homologous genes from humans and murids. (The same comparison for mouse and rat genes indicates a conservation of GC levels of homologous genes.) A similar linear relationship was observed when plotting GC levels of corresponding DNA fractions (as obtained by density gradient centrifugation in the presence of a sequence-specific ligand) from mouse and human. These findings indicate that orderly compositional changes affecting not only coding sequences but also noncoding sequences took place since the divergence of murids. Such directional fixations of mutations point to the existence of selective pressures affecting the genome as a whole.
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  • 3
    ISSN: 1432-1432
    Keywords: Alu source genes ; Humans ; Gorillas ; Retrotransposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A member of the young PV Alu sub-family is detected in chimpanzee DNA showing that the PV subfamily is not specific to human DNA. This particular Alu is absent from the orthologous loci in both human and gorilla DNAs, indicating that PV subfamily members transposed within the chimpanzee lineage following the divergence of chimpanzee from both gorilla and human. These findings and previous reports describing the transpositional activity of other Alu sequences within the human, gorilla, and chimpanzee lineages provide phylogenetic evidence for the existence of multiple Alu source genes. Sequences surrounding this particular Alu resemble known transcriptional control elements associated with RNA polymerase III, suggesting a mechanism by which cis-acting elements might be acquired upon retrotransposition.
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  • 4
    ISSN: 1432-1432
    Keywords: Humans ; Mitochondrial DNA ; Nuclear polymorphisms ; Heteroplasmy ; Genetic differentiation ; Sickle cell ; Rain forest refuges
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The identification of genetically coherent populations is essential for understanding human evolution. Among the culturally uniform ethnic groups of west Africa, there are two geographically distinct populations with high frequencies of sickle-cell hemoglobin (HbS). Although the HbS mutation in each group is found on distinguishable chromosomes 11, these populations have been assumed to be parts of a single population. Analysis of mitochondrial DNA (mtDNA) in these populations demonstrated that the two populations identified by alternative chromosomes 11 bearing HbS have distinct distributions of mitochondrial genotypes, i.e., they are maternally separate. These studies also showed that, contrary to expectation, the mtDNA of some individuals is heteroplasmic. For nuclear loci, a comparison of the frequency of alternative alleles established that these populations are genetically distinct. Both the mitochondrial and nuclear data indicate that these populations have been separate for approximately 50,000 years. Although HbS in the two populations is usually attributed to recent, independent mutations, the duration of the separation and the observed geographic distribution of the population allow for the possibility of an ancient origin of HbS. Assuming an ancient mutation and considering the known biogeography, we suggest that HbS protected selected populations from malaria in rain forest refuges during the most recent ice age.
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  • 5
    ISSN: 1432-1432
    Keywords: Humans ; Mouse ; Rat ; Codon usage ; Mutation bias ; Selection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A new statistical test has been developed to detect selection on silent sites. This test compares the codon usage within a gene and thus does not require knowledge of which genes are under the greatest selection, that there exist common trends in codon usage across genes, or that genes have the same mutation pattern. It also controls for mutational biases that might be introduced by the adjacent bases. The test was applied to 62 mammalian sequences, the significant codon usage biases were detected in all three species examined (humans, rats, and mice). However, these biases appear not to be the consequence of selection, but of the first base pair in the codon influencing the mutation pattern at the third position.
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  • 6
    ISSN: 0891-5849
    Keywords: Free radicals ; Humans ; Noninvasive analytical techniques ; Oxidative stress status
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 7
    ISSN: 1432-1254
    Keywords: Briths ; Humans ; Solar wind ; Geomagnetism ; Melatonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract Data obtained from the literature on the annual pattern of human conceptions and plasma melatonin at high latitudes indicated that simple annual rhythms do not exist. Instead, prominent semiannual rhythms are found, with equinoctial troughs and solsticial peaks. A prominent semiannual environmental event is the magnetic disturbance induced by the solar wind. The semiannual magnetic disturbances are worldwide, but most pronounced in the auroral zones where the corpuscular radiation enters the atmosphere. Magnetic indices that predominantly reflect these events were obtained from the literature and correlated with the melatonin and conception data. Significant and inverse correlations were found for Inuit conceptions and the melatonin data. The correlations obtained for 48 contiguous states of the United States indicated that only the extreme northern states exhibited this relationship. These data were compared with a previous correlational study in the United States which established that sunshine was correlated with conceptions in the middle latitude and southern states. An hypothesis of dual control by electromagnetic and magnetic energies is proposed: melatonin is a progonadal hormone in humans controlled by both factors, depending on their relative strength. Other studies are reviewed regarding the possible factors involved in determining the annual pattern of human conceptions. Demographic studies of geographic variation in temporal patterns of conceptions, with particular regard to variations of the magnetic fields on the earth's surface, may provide some insight into the efficacy of these different factors.
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  • 8
    ISSN: 1432-0878
    Keywords: Skeletal muscles ; Ultrastructure ; Exercise ; Glycogen ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Distribution of glycogen particles in semithin and ultrathin sections of biopsy samples from human muscles subjected to either short- or long-term running were investigated using PAS and Periodic Acid-ThioSemiCarbazide-Silver Proteinate (PA-TSC-SP) staining methods. Glycogen particles were predominantly found immediately under the sarcolemma or aligned along the myofibrillar Iband. After long-term exhaustive exercise type-1 fibers with a few or no glycogen particles in the core of the fibers were frequently observed. The subsarcolemmal glycogen stores of these “depleted” type-1 fibers were about three times as large as after exhaustive short-time exercise. Another indication of utilization of subsarcolemmal glycogen stores during anaerobic exercise was that many particles displayed a pale, rudimentary shape. This observation suggests fragmental metabolization of glycogen. Thus, depending on type of exercise and type of fiber differential and sequential glycogen utilization patterns can be observed.
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  • 9
    ISSN: 1573-9686
    Keywords: Work of breathing ; Inspiratory pressure-time integral ; Respiratory modeling ; Dogs ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract We hypothesized that the viscoelastic properties of the respiratory system should have significant implications for the energetically optimal frequency of breathing, in view of the fact that these properties cause marked dependencies of overall system resistance and elastance on frequency. To test our hypothesis we simulated two models of canine and human respiratory system mechanics during sinusoidal breathing and calculated the inspiratory work ( $$\dot W$$ ) and pressure-time integral (PTI) per minute under both resting and exercise conditions. The two models were a two-compartment viscoelastic model and a single-compartment model. Requiring minute alveolar ventilation to be fixed, we found that both models predicted almost identical optimum breathing frequencies. The calculated PTI was very insensitive to increases in breathing frequency above the optimal frequencies, while $$\dot W$$ was found to increase slowly with frequency above its optimum. In contrast, both $$\dot W$$ and PTI increased sharply as frequency decreased below their respective optima. A sensitivity analysis showed that the model predictions were very insensitive to the elastance and resistance values chosen to characterize tissue viscoelasticity. We conclude that the $$\dot W$$ criterion for choosing the frequency of breathing is compatible with observations in nature, whereas the optimal frequency predictions of the PTI are rather too high. Both criteria allow for a fairly wide margin of choice in frequency above the optimum values without incurring excessive additional energy expenditure. Furthermore, contrary to our expectations, the viscoelastic properties of the respiratory system tissues do not pose a noticeable problem to the respiratory controller in terms of energy expenditure.
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  • 10
    ISSN: 1573-0832
    Keywords: Assessment ; Cancer ; Humans ; Hydrazines ; Mushroom
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract This assessment focuses on the concentrations of some chemicals present in theAgaricus bisporus mushroom, the cancer-inducing doses of these chemicals or mushroom used in the animal experiments, the total amounts of these chemicals or mushroom needed to induce cancer in these mice, and the estimated total amounts of these chemicals or mushroom needed to induce cancer in humans. By adding the estimated amounts of chemicals needed to induce cancer and by comparing it with the amount of raw mushroom needed to induce the same effect, it becomes obvious that we have accounted for less than 2% of the carcinogenic components of theAgaricus bisporus mushroom. Since some unavailable data handicapped this assessment, it should be regarded as tentative and subject to further adjustment.
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  • 11
    Publication Date: 2018-04-17
    Description: © The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in International Journal of Environmental Research and Public Health 15 (2018): 723, doi:10.3390/ijerph15040723.
    Description: There has been a massive increase in recent years of the use of lead (Pb) isotopes in attempts to better understand sources and pathways of Pb in the environment and in man or experimental animals. Unfortunately, there have been many cases where the quality of the isotopic data, especially that obtained by quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS), are questionable, resulting in questionable identification of potential sources, which, in turn, impacts study interpretation and conclusions. We present several cases where the isotopic data have compromised interpretation because of the use of only the major isotopes 208Pb/206Pb and 207Pb/206Pb, or their graphing in other combinations. We also present some examples comparing high precision data from thermal ionization (TIMS) or multi-collector plasma mass spectrometry (MC-ICP-MS) to illustrate the deficiency in the Q-ICP-MS data. In addition, we present cases where Pb isotopic ratios measured on Q-ICP-MS are virtually impossible for terrestrial samples. We also evaluate the Pb isotopic data for rat studies, which had concluded that Pb isotopic fractionation occurs between different organs and suggest that this notion of biological fractionation of Pb as an explanation for isotopic differences is not valid. Overall, the brief review of these case studies shows that Q-ICP-MS as commonly practiced is not a suitable technique for precise and accurate Pb isotopic analysis in the environment and health fields
    Keywords: Lead isotopes ; ICP-MS ; TIMS ; MC-ICP-MS ; Environment ; Humans ; Rats ; Fractionation
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 12
    Publication Date: 2017-01-04
    Description: The primary objective of this publication is to share with a wider audience the valuable information and extensive dialogue that took place amongst over 140 individuals who attended the second in a series of planned workshops on the science and management of coastal landforms in Massachusetts. This workshop took place at the Woods Hole Oceanographic Institution on January 24, 2001. The individuals who attended this workshop are actively engaged in planning, managing, regulating, engineering, educating, and studying coastal landforms and their beneficial functions. This workshop titled, Can Humans & Coastal Landforms Co-exist?’, was a natural follow-up to a previous workshop, Coastal Landform Management in Massachusetts, held at WHOI October 9-10, 1997 (proceedings published as WHOI Technical Report #WHOI-98-16). The workshop had a very practical, applied focus, providing state-of-the-art scientific understanding of coastal landform function, case history management and regulation of human activities proposed on coastal landforms, a multi-faceted mock conservation commission hearing presented by practicing technical consultants and attorneys that involved all attendees acting as regulators in breakout sessions, and, at the conclusion of the workshop, an open discussion on all issues related to the science and management of coastal landforms, including future research needs.
    Description: Funding for these proceedings was provided by WHOI Sea Grant and the NOAA National Sea Grant College Program Office, Department of Commerce, under NOAA Grant No. M10-2, Woods Hole Oceanographic Institution Sea Grant Project No. NA86R60075.
    Keywords: Coastal ; Landforms ; Humans
    Repository Name: Woods Hole Open Access Server
    Type: Technical Report
    Format: 1574993 bytes
    Format: application/pdf
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  • 13
    ISSN: 0306-4565
    Keywords: Humans ; exercise ; hyperthermia ; oesophageal temperature
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
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  • 14
    ISSN: 0027-5107
    Keywords: Cotinine ; Genetic monitoring ; Hprt mutation ; Humans ; Lymphocytes ; Pregnancy ; Smoking ; Tobacco
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
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  • 15
    ISSN: 0196-9781
    Keywords: Autocrine feedback mechanism ; Cholecystokinin ; Feeding ; Humans ; Radioimmunoassay
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
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  • 16
    ISSN: 0168-1591
    Keywords: Fear ; Handling ; Humans ; Poultry ; Productivity
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
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  • 17
    ISSN: 0168-1591
    Keywords: Cats ; Foraging ; Humans ; Livestock ; Predators ; Vampire bats
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
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  • 18
    ISSN: 0196-9781
    Keywords: ACTH ; Aging ; Attention ; Cognition ; Humans ; MSH ; Peptide ; Visual retention
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
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  • 19
    Electronic Resource
    Amsterdam : Elsevier
    Peptides 4 (1983), S. 451-455 
    ISSN: 0196-9781
    Keywords: Biliary system ; Cat ; Guinea-pig ; Humans ; Mucosa ; Rabbit ; Radioimmunoassay ; Respiratory system ; Skin ; Substance P ; Sympathetic nervous system ; Urinary system
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
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  • 20
    Electronic Resource
    Amsterdam : Elsevier
    Peptides 5 (1984), S. 319-323 
    ISSN: 0196-9781
    Keywords: Blood flow ; Circulation ; Electromagnetic flowmetry ; Humans ; VIP
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
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  • 21
    ISSN: 0196-9781
    Keywords: Angiotensin II ; Blood ; Humans ; Radioimmunoassay ; Rats ; [des-Leu^1^0]-angiotensin I
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
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  • 22
    ISSN: 0921-8734
    Keywords: Ageing ; Humans ; Skin cells ; Telomeres
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
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  • 23
    ISSN: 0921-8734
    Keywords: Aging ; Humans ; Ionizing radiation ; Single cell electrophoresis
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
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  • 24
    ISSN: 0165-7992
    Keywords: Cytochrome P-450 ; Dogs ; Humans ; Monkeys ; P-448-H ; Rats
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
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  • 25
    ISSN: 0162-3095
    Keywords: Assortative mating ; Genetic similarity ; Heritability ; Humans ; Kin recognition
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
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  • 26
    Electronic Resource
    Amsterdam : Elsevier
    Ethology and Sociobiology 8 (1987), S. 215-220 
    ISSN: 0162-3095
    Keywords: Humans ; Paternity confidence ; Relatedness
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
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  • 27
    Publication Date: 2011-01-14
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804163/" 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/PMC3804163/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sprang, Stephen R -- R56 DK046371/DK/NIDDK NIH HHS/ -- England -- Nature. 2011 Jan 13;469(7329):172-3. doi: 10.1038/469172a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21228868" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic Agonists/chemistry/metabolism/*pharmacology ; Adrenergic Antagonists/chemistry/metabolism/*pharmacology ; Animals ; Crystallography, X-Ray ; Drug Partial Agonism ; Heterotrimeric GTP-Binding Proteins/*metabolism ; Humans ; Models, Molecular ; Protein Conformation/drug effects ; Protein Stability/drug effects ; Receptors, Adrenergic, beta-1/*chemistry/*metabolism ; Receptors, Adrenergic, beta-2/*chemistry/*metabolism ; Viral Proteins/chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 28
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    Nature Publishing Group (NPG)
    Publication Date: 2011-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2011 Mar 17;471(7338):266. doi: 10.1038/471266a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21412289" target="_blank"〉PubMed〈/a〉
    Keywords: Artifacts ; Fatigue Syndrome, Chronic/*etiology/*virology ; Humans ; Patients/psychology ; Reproducibility of Results ; *Xenotropic murine leukemia virus-related virus/isolation & ; purification/pathogenicity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 29
    Publication Date: 2014-03-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gorkin, David U -- Ren, Bing -- U01 ES017166/ES/NIEHS NIH HHS/ -- England -- Nature. 2014 Mar 20;507(7492):309-10. doi: 10.1038/nature13212. Epub 2014 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Institute for Cancer Research, La Jolla, California 92093, USA. ; 1] Ludwig Institute for Cancer Research, La Jolla, California 92093, USA. [2] Department of Cellular and Molecular Medicine, University of California, La Jolla, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24646989" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Homeodomain Proteins/*genetics ; Humans ; Introns/*genetics ; Male ; Mixed Function Oxygenases/*genetics ; Obesity/*genetics ; Oxo-Acid-Lyases/*genetics ; Proteins/*genetics ; Transcription Factors/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 30
    Publication Date: 2014-07-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gostin, Lawrence O -- England -- Nature. 2014 Jul 10;511(7508):147-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25013878" target="_blank"〉PubMed〈/a〉
    Keywords: Diabetes Mellitus/prevention & control ; *Health ; Heart Diseases/prevention & control ; Humans ; International Cooperation ; *Internationality ; Neoplasms/prevention & control ; *Preventive Medicine ; Stroke/prevention & control ; World Health Organization
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 31
    Publication Date: 2014-08-27
    Description: Aberrant activation of oncogenes or loss of tumour suppressor genes opposes malignant transformation by triggering a stable arrest in cell growth, which is termed cellular senescence. This process is finely tuned by both cell-autonomous and non-cell-autonomous mechanisms that regulate the entry of tumour cells to senescence. Whether tumour-infiltrating immune cells can oppose senescence is unknown. Here we show that at the onset of senescence, PTEN null prostate tumours in mice are massively infiltrated by a population of CD11b(+)Gr-1(+) myeloid cells that protect a fraction of proliferating tumour cells from senescence, thus sustaining tumour growth. Mechanistically, we found that Gr-1(+) cells antagonize senescence in a paracrine manner by interfering with the senescence-associated secretory phenotype of the tumour through the secretion of interleukin-1 receptor antagonist (IL-1RA). Strikingly, Pten-loss-induced cellular senescence was enhanced in vivo when Il1ra knockout myeloid cells were adoptively transferred to PTEN null mice. Therapeutically, docetaxel-induced senescence and efficacy were higher in PTEN null tumours when the percentage of tumour-infiltrating CD11b(+)Gr-1(+) myeloid cells was reduced using an antagonist of CXC chemokine receptor 2 (CXCR2). Taken together, our findings identify a novel non-cell-autonomous network, established by innate immunity, that controls senescence evasion and chemoresistance. Targeting this network provides novel opportunities for cancer therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Di Mitri, Diletta -- Toso, Alberto -- Chen, Jing Jing -- Sarti, Manuela -- Pinton, Sandra -- Jost, Tanja Rezzonico -- D'Antuono, Rocco -- Montani, Erica -- Garcia-Escudero, Ramon -- Guccini, Ilaria -- Da Silva-Alvarez, Sabela -- Collado, Manuel -- Eisenberger, Mario -- Zhang, Zhe -- Catapano, Carlo -- Grassi, Fabio -- Alimonti, Andrea -- England -- Nature. 2014 Nov 6;515(7525):134-7. doi: 10.1038/nature13638. Epub 2014 Aug 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona CH6500, Switzerland [2]. ; 1] Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona CH6500, Switzerland [2] Faculty of Biology and Medicine, University of Lausanne UNIL, Lausanne CH1011, Switzerland. ; Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona CH6500, Switzerland. ; Institute for Research in Biomedicine (IRB), Bellinzona CH6500, Switzerland. ; 1] Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona CH6500, Switzerland [2] Molecular Oncology Unit, CIEMAT, 28040 Madrid, Spain. ; Laboratory of Stem Cells in Cancer and Aging, (stemCHUS) Health Research Institute of Santiago de Compostela (IDIS), Clinical University Hospital (CHUS), E15706 Santiago de Compostela, Spain. ; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland 21231-1000, USA. ; Divisions of BioStatistics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland 21231-1000, USA. ; 1] Institute for Research in Biomedicine (IRB), Bellinzona CH6500, Switzerland [2] Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan I-20100, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25156255" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Aging/drug effects ; *Cell Movement ; Disease Progression ; Drug Resistance, Neoplasm ; Humans ; Immunity, Innate ; Interleukin 1 Receptor Antagonist Protein/deficiency/metabolism/secretion ; Interleukin-1alpha/immunology/metabolism ; Male ; Mice ; Myeloid Cells/*cytology/*metabolism/transplantation ; PTEN Phosphohydrolase/deficiency/genetics/metabolism ; Prostatic Neoplasms/drug therapy/immunology/metabolism/*pathology ; Receptors, Chemokine/*metabolism ; Receptors, Interleukin-8B/antagonists & inhibitors ; Taxoids/pharmacology ; Tumor Escape ; Tumor Microenvironment
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 32
    Publication Date: 2014-11-11
    Description: beta-catenin is a multi-functional protein that has an important role in the mature central nervous system; its dysfunction has been implicated in several neuropsychiatric disorders, including depression. Here we show that in mice beta-catenin mediates pro-resilient and anxiolytic effects in the nucleus accumbens, a key brain reward region, an effect mediated by D2-type medium spiny neurons. Using genome-wide beta-catenin enrichment mapping, we identify Dicer1-important in small RNA (for example, microRNA) biogenesis--as a beta-catenin target gene that mediates resilience. Small RNA profiling after excising beta-catenin from nucleus accumbens in the context of chronic stress reveals beta-catenin-dependent microRNA regulation associated with resilience. Together, these findings establish beta-catenin as a critical regulator in the development of behavioural resilience, activating a network that includes Dicer1 and downstream microRNAs. We thus present a foundation for the development of novel therapeutic targets to promote stress resilience.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257892/" 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/PMC4257892/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dias, Caroline -- Feng, Jian -- Sun, Haosheng -- Shao, Ning Yi -- Mazei-Robison, Michelle S -- Damez-Werno, Diane -- Scobie, Kimberly -- Bagot, Rosemary -- LaBonte, Benoit -- Ribeiro, Efrain -- Liu, XiaoChuan -- Kennedy, Pamela -- Vialou, Vincent -- Ferguson, Deveroux -- Pena, Catherine -- Calipari, Erin S -- Koo, Ja Wook -- Mouzon, Ezekiell -- Ghose, Subroto -- Tamminga, Carol -- Neve, Rachael -- Shen, Li -- Nestler, Eric J -- P50 MH096890/MH/NIMH NIH HHS/ -- R00 MH094405/MH/NIMH NIH HHS/ -- England -- Nature. 2014 Dec 4;516(7529):51-5. doi: 10.1038/nature13976. Epub 2014 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. ; Department of Psychiatry, University of Texas Southwestern, Dallas, Texas 75390, USA. ; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383518" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/genetics ; Animals ; DEAD-box RNA Helicases/*genetics/metabolism ; Depression/physiopathology ; Gene Expression Profiling ; *Gene Expression Regulation ; Genome-Wide Association Study ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; MicroRNAs/*genetics/metabolism ; Neurons/metabolism ; *Resilience, Psychological ; Ribonuclease III/*genetics/metabolism ; Signal Transduction ; Stress, Physiological/*genetics ; beta Catenin/genetics/*metabolism
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  • 33
    Publication Date: 2014-09-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burchard, Esteban G -- England -- Nature. 2014 Sep 18;513(7518):301-2. doi: 10.1038/513301a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California, San Francisco, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25230631" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; African Americans/genetics/statistics & numerical data ; Asthma/mortality ; *Biomedical Research/manpower/methods ; Clinical Trials as Topic/ethics/standards ; Continental Population Groups/genetics/statistics & numerical data ; Gene-Environment Interaction ; Humans ; Male ; Minority Groups/statistics & numerical data ; *Patient Selection/ethics
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  • 34
    Publication Date: 2014-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watson-Capps, Jana J -- Cech, Thomas R -- England -- Nature. 2014 Oct 16;514(7522):297-8. doi: 10.1038/514297a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BioFrontiers Institute at the University of Colorado Boulder, USA. ; University of Colorado Boulder and director of the BioFrontiers Institute.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25318508" target="_blank"〉PubMed〈/a〉
    Keywords: Drug Industry/manpower/*organization & administration ; Entrepreneurship ; Humans ; Laboratories/manpower/*organization & administration ; *Public-Private Sector Partnerships ; Translational Medical Research ; Universities/manpower/*organization & administration
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  • 35
    Publication Date: 2014-11-28
    Description: There have been no major advances for the treatment of metastatic urothelial bladder cancer (UBC) in the last 30 years. Chemotherapy is still the standard of care. Patient outcomes, especially for those in whom chemotherapy is not effective or is poorly tolerated, remain poor. One hallmark of UBC is the presence of high rates of somatic mutations. These alterations may enhance the ability of the host immune system to recognize tumour cells as foreign owing to an increased number of antigens. However, these cancers may also elude immune surveillance and eradication through the expression of programmed death-ligand 1 (PD-L1; also called CD274 or B7-H1) in the tumour microenvironment. Therefore, we examined the anti-PD-L1 antibody MPDL3280A, a systemic cancer immunotherapy, for the treatment of metastatic UBC. MPDL3280A is a high-affinity engineered human anti-PD-L1 monoclonal immunoglobulin-G1 antibody that inhibits the interaction of PD-L1 with PD-1 (PDCD1) and B7.1 (CD80). Because PD-L1 is expressed on activated T cells, MPDL3280A was engineered with a modification in the Fc domain that eliminates antibody-dependent cellular cytotoxicity at clinically relevant doses to prevent the depletion of T cells expressing PD-L1. Here we show that MPDL3280A has noteworthy activity in metastatic UBC. Responses were often rapid, with many occurring at the time of the first response assessment (6 weeks) and nearly all were ongoing at the data cutoff. This phase I expansion study, with an adaptive design that allowed for biomarker-positive enriched cohorts, demonstrated that tumours expressing PD-L1-positive tumour-infiltrating immune cells had particularly high response rates. Moreover, owing to the favourable toxicity profile, including a lack of renal toxicity, patients with UBC, who are often older and have a higher incidence of renal impairment, may be better able to tolerate MPDL3280A versus chemotherapy. These results suggest that MPDL3280A may have an important role in treating UBC-the drug received breakthrough designation status by the US Food and Drug Administration (FDA) in June 2014.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Powles, Thomas -- Eder, Joseph Paul -- Fine, Gregg D -- Braiteh, Fadi S -- Loriot, Yohann -- Cruz, Cristina -- Bellmunt, Joaquim -- Burris, Howard A -- Petrylak, Daniel P -- Teng, Siew-leng -- Shen, Xiaodong -- Boyd, Zachary -- Hegde, Priti S -- Chen, Daniel S -- Vogelzang, Nicholas J -- England -- Nature. 2014 Nov 27;515(7528):558-62. doi: 10.1038/nature13904.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Barts Cancer Institute, Queen Mary University of London, Barts Experimental Cancer Medicine Centre, London EC1M 6BQ, UK. ; Yale Cancer Center, 333 Cedar Street, WWW211, New Haven, Connecticut 06520, USA. ; Genentech, Inc. 1 DNA Way, South San Francisco, California 94080, USA. ; Comprehensive Cancer Centers of Nevada, 3730 S. Eastern Avenue, Las Vegas, Nevada 89169, USA. ; Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France. ; Vall d'Hebron Institute of Oncology (VHIO) and Vall d'Hebron University Hospital. Passeig Vall d'Hebron, 119-129, 08035, Barcelona, Spain. ; Bladder Cancer Center, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02215, USA. ; Sarah Cannon Research Institute, 3322 West End Avenue, Suite 900, Nashville, Tennessee 37203, USA. ; University of Nevada School of Medicine and US Oncology/Comprehensive Cancer Centers of Nevada, 3730 S. Eastern Avenue, Las Vegas, Nevada 89169, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25428503" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/adverse effects/*therapeutic use ; Antigens, CD274/metabolism ; Female ; Humans ; *Immunotherapy ; Male ; Middle Aged ; Treatment Outcome ; Urinary Bladder Neoplasms/*therapy
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  • 36
    Publication Date: 2014-03-05
    Description: Filoviruses are emerging pathogens and causative agents of viral haemorrhagic fever. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, exceeding 90% (ref. 1). Licensed therapeutic or vaccine products are not available to treat filovirus diseases. Candidate therapeutics previously shown to be efficacious in non-human primate disease models are based on virus-specific designs and have limited broad-spectrum antiviral potential. Here we show that BCX4430, a novel synthetic adenosine analogue, inhibits infection of distinct filoviruses in human cells. Biochemical, reporter-based and primer-extension assays indicate that BCX4430 inhibits viral RNA polymerase function, acting as a non-obligate RNA chain terminator. Post-exposure intramuscular administration of BCX4430 protects against Ebola virus and Marburg virus disease in rodent models. Most importantly, BCX4430 completely protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. In addition, BCX4430 exhibits broad-spectrum antiviral activity against numerous viruses, including bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses and flaviviruses. This is the first report, to our knowledge, of non-human primate protection from filovirus disease by a synthetic drug-like small molecule. We provide additional pharmacological characterizations supporting the potential development of BCX4430 as a countermeasure against human filovirus diseases and other viral diseases representing major public health threats.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warren, Travis K -- Wells, Jay -- Panchal, Rekha G -- Stuthman, Kelly S -- Garza, Nicole L -- Van Tongeren, Sean A -- Dong, Lian -- Retterer, Cary J -- Eaton, Brett P -- Pegoraro, Gianluca -- Honnold, Shelley -- Bantia, Shanta -- Kotian, Pravin -- Chen, Xilin -- Taubenheim, Brian R -- Welch, Lisa S -- Minning, Dena M -- Babu, Yarlagadda S -- Sheridan, William P -- Bavari, Sina -- HHSN272201100016I/PHS HHS/ -- HHSN272201100019I/PHS HHS/ -- HHSN27220110005I/PHS HHS/ -- England -- Nature. 2014 Apr 17;508(7496):402-5. doi: 10.1038/nature13027. Epub 2014 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Maryland 21702, USA. ; BioCryst Pharmaceuticals Inc., Durham, North Carolina 27703, USA. ; 1] BioCryst Pharmaceuticals Inc., Durham, North Carolina 27703, USA [2] Wilco Consulting, LLC, Durham, North Carolina 27712, USA. ; MedExpert Consulting, Inc., Indialantic, Florida 32903, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24590073" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine/*analogs & derivatives ; Administration, Oral ; Animals ; Antiviral Agents/administration & dosage/chemistry/pharmacokinetics/*pharmacology ; DNA-Directed RNA Polymerases/antagonists & inhibitors/metabolism ; Disease Models, Animal ; Ebolavirus/drug effects ; Filoviridae/*drug effects/enzymology ; Filoviridae Infections/*prevention & control/*virology ; Hemorrhagic Fever, Ebola/prevention & control/virology ; Humans ; Injections, Intramuscular ; Macaca fascicularis/virology ; Marburg Virus Disease/prevention & control/virology ; Marburgvirus/drug effects ; Purine Nucleosides/administration & ; dosage/chemistry/pharmacokinetics/*pharmacology ; RNA/biosynthesis ; Time Factors
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  • 37
    Publication Date: 2011-07-22
    Description: Most proteins must fold into defined three-dimensional structures to gain functional activity. But in the cellular environment, newly synthesized proteins are at great risk of aberrant folding and aggregation, potentially forming toxic species. To avoid these dangers, cells invest in a complex network of molecular chaperones, which use ingenious mechanisms to prevent aggregation and promote efficient folding. Because protein molecules are highly dynamic, constant chaperone surveillance is required to ensure protein homeostasis (proteostasis). Recent advances suggest that an age-related decline in proteostasis capacity allows the manifestation of various protein-aggregation diseases, including Alzheimer's disease and Parkinson's disease. Interventions in these and numerous other pathological states may spring from a detailed understanding of the pathways underlying proteome maintenance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hartl, F Ulrich -- Bracher, Andreas -- Hayer-Hartl, Manajit -- England -- Nature. 2011 Jul 20;475(7356):324-32. doi: 10.1038/nature10317.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. uhartl@biochem.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21776078" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Disease ; Humans ; Molecular Chaperones/classification/*metabolism ; *Protein Folding ; Proteins/*metabolism ; Proteome/metabolism ; Ribosomes/metabolism
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  • 38
    Publication Date: 2010-12-24
    Description: In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-trans-synaptic labelling with genetics to control the location, number and type of 'starter' cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odour preference or associative memory. The trans-synaptic labelling method described here should be widely applicable to mapping connections throughout the mouse nervous system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073090/" 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/PMC3073090/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miyamichi, Kazunari -- Amat, Fernando -- Moussavi, Farshid -- Wang, Chen -- Wickersham, Ian -- Wall, Nicholas R -- Taniguchi, Hiroki -- Tasic, Bosiljka -- Huang, Z Josh -- He, Zhigang -- Callaway, Edward M -- Horowitz, Mark A -- Luo, Liqun -- R01 MH063912/MH/NIMH NIH HHS/ -- R01 NS050835/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Apr 14;472(7342):191-6. doi: 10.1038/nature09714. Epub 2010 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉HHMI/Department of Biology, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21179085" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/anatomy & histology/cytology/physiology ; Animals ; Axons/physiology ; Bias (Epidemiology) ; Brain Mapping ; HEK293 Cells ; Humans ; Mice ; Mice, Transgenic ; *Neuroanatomical Tract-Tracing Techniques ; Odors/analysis ; Olfactory Bulb/anatomy & histology/cytology/physiology ; Olfactory Pathways/anatomy & histology/*cytology/*physiology ; Olfactory Perception/genetics/*physiology ; Olfactory Receptor Neurons/cytology/physiology ; Rabies virus/physiology ; Synapses/genetics/*metabolism
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  • 39
    Publication Date: 2011-02-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Edwards, Aled M -- Isserlin, Ruth -- Bader, Gary D -- Frye, Stephen V -- Willson, Timothy M -- Yu, Frank H -- England -- Nature. 2011 Feb 10;470(7333):163-5. doi: 10.1038/470163a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Toronto, Toronto, Ontario M5G 1L7, Canada. aled.edwards@utoronto.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21307913" target="_blank"〉PubMed〈/a〉
    Keywords: *Bibliometrics ; Biomedical Research/*instrumentation/methods/*statistics & numerical data/trends ; Human Genome Project ; Humans ; Ion Channels ; Protein Kinases ; Receptors, Cytoplasmic and Nuclear
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  • 40
    Publication Date: 2011-01-05
    Description: During mitosis, adherent animal cells undergo a drastic shape change, from essentially flat to round. Mitotic cell rounding is thought to facilitate organization within the mitotic cell and be necessary for the geometric requirements of division. However, the forces that drive this shape change remain poorly understood in the presence of external impediments, such as a tissue environment. Here we use cantilevers to track cell rounding force and volume. We show that cells have an outward rounding force, which increases as cells enter mitosis. We find that this mitotic rounding force depends both on the actomyosin cytoskeleton and the cells' ability to regulate osmolarity. The rounding force itself is generated by an osmotic pressure. However, the actomyosin cortex is required to maintain this rounding force against external impediments. Instantaneous disruption of the actomyosin cortex leads to volume increase, and stimulation of actomyosin contraction leads to volume decrease. These results show that in cells, osmotic pressure is balanced by inwardly directed actomyosin cortex contraction. Thus, by locally modulating actomyosin-cortex-dependent surface tension and globally regulating osmotic pressure, cells can control their volume, shape and mechanical properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stewart, Martin P -- Helenius, Jonne -- Toyoda, Yusuke -- Ramanathan, Subramanian P -- Muller, Daniel J -- Hyman, Anthony A -- England -- Nature. 2011 Jan 13;469(7329):226-30. doi: 10.1038/nature09642. Epub 2011 Jan 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ETH Zurich, Department of Biosystems Science and Engineering, CH-4058 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21196934" target="_blank"〉PubMed〈/a〉
    Keywords: Actomyosin/*metabolism ; Animals ; Cell Shape/drug effects/*physiology ; Cell Size/drug effects ; Cytochalasin D/pharmacology ; Cytoskeleton/drug effects/*metabolism ; HeLa Cells ; Humans ; Hydrostatic Pressure ; Microscopy, Atomic Force ; *Mitosis ; Models, Biological ; Osmolar Concentration ; Osmotic Pressure ; Prophase
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  • 41
    Publication Date: 2014-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koroshetz, Walter J -- England -- Nature. 2014 Jun 26;510(7506):S4. doi: 10.1038/510S4a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉US National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24964024" target="_blank"〉PubMed〈/a〉
    Keywords: *Blood Pressure/drug effects ; Exercise/physiology ; Humans ; Hypertension/complications/drug therapy/*therapy ; Risk ; Stroke/complications/*physiopathology/*prevention & control
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  • 42
    Publication Date: 2014-08-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mecke, Sven -- England -- Nature. 2014 Jul 31;511(7511):534. doi: 10.1038/511534c.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Philipps-Universitat Marburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079546" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Bufonidae/*physiology ; *Conservation of Natural Resources ; Humans ; *Introduced Species
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  • 43
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Apr 10;508(7495):150.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24724184" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbon Dioxide/*chemistry ; Catalysis ; Chelating Agents/therapeutic use ; Copper/*chemistry ; Ethanol/*chemical synthesis/chemistry ; Hepatolenticular Degeneration/drug therapy/metabolism ; Humans ; Mice ; Neoplasms/*drug therapy/genetics/*metabolism/pathology ; Proto-Oncogene Proteins B-raf/genetics ; Renewable Energy
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  • 44
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    Nature Publishing Group (NPG)
    Publication Date: 2014-05-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Qiu, Jane -- England -- Nature. 2014 May 8;509(7499):142-3. doi: 10.1038/509142a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805323" target="_blank"〉PubMed〈/a〉
    Keywords: Avalanches/mortality/*statistics & numerical data ; Humans ; *Islands/epidemiology ; Japan ; Russia
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  • 45
    Publication Date: 2014-07-22
    Description: A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486207/" 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/PMC4486207/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whelan, Robert -- Watts, Richard -- Orr, Catherine A -- Althoff, Robert R -- Artiges, Eric -- Banaschewski, Tobias -- Barker, Gareth J -- Bokde, Arun L W -- Buchel, Christian -- Carvalho, Fabiana M -- Conrod, Patricia J -- Flor, Herta -- Fauth-Buhler, Mira -- Frouin, Vincent -- Gallinat, Juergen -- Gan, Gabriela -- Gowland, Penny -- Heinz, Andreas -- Ittermann, Bernd -- Lawrence, Claire -- Mann, Karl -- Martinot, Jean-Luc -- Nees, Frauke -- Ortiz, Nick -- Paillere-Martinot, Marie-Laure -- Paus, Tomas -- Pausova, Zdenka -- Rietschel, Marcella -- Robbins, Trevor W -- Smolka, Michael N -- Strohle, Andreas -- Schumann, Gunter -- Garavan, Hugh -- IMAGEN Consortium -- MH082116/MH/NIMH NIH HHS/ -- P20 GM103644/GM/NIGMS NIH HHS/ -- P20GM103644/GM/NIGMS NIH HHS/ -- P50 DA036114/DA/NIDA NIH HHS/ -- P50DA036114/DA/NIDA NIH HHS/ -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2014 Aug 14;512(7513):185-9. doi: 10.1038/nature13402. Epub 2014 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Psychiatry, University of Vermont, Burlington, Vermont 05401, USA [2] Department of Psychology, University College Dublin, Dublin 4, Ireland. ; Department of Radiology, University of Vermont, Burlington, Vermont 05401, USA. ; Vermont Center for Children, Youth, and Families, University of Vermont, Burlington, Vermont 05401, USA. ; 1] Department of Pediatrics, University of Vermont, Burlington, Vermont 05401, USA [2] Department of Psychology, University of Vermont, Burlington, Vermont 05401, USA. ; 1] Institut National de la Sante et de la Recherche Medicale, INSERM CEA Unit 1000 "Imaging &Psychiatry", University Paris Sud, 91400 Orsay, France [2] Department of Psychiatry, Orsay Hospital, 4 place du General Leclerc, 91400 Orsay, France. ; Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. ; Institute of Psychiatry, King's College London, London SE5 8AF, UK. ; Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland. ; 1] Department of Systems Neuroscience, Universitatsklinikum Hamburg Eppendorf, 20246 Hamburg, Germany [2] Department of Psychology, Stanford University, Stanford, California 94305, USA. ; 1] Institute of Psychiatry, King's College London, London SE5 8AF, UK [2] Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal H3T 1C5, Canada. ; 1] Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany [2] Department of Addictive Behaviour and Addiction Medicine, Heidelberg University, 68159 Mannheim, Germany. ; 14 CEA, DSV, I2BM, Neurospin bat 145, 91191 Gif-Sur-Yvette, France. ; 1] Department of Systems Neuroscience, Universitatsklinikum Hamburg Eppendorf, 20246 Hamburg, Germany [2] Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Charite-Universitatsmedizin Berlin 10117, Germany. ; Department of Psychiatry and Neuroimaging Center, Technische Universitat Dresden, 01062 Dresden, Germany. ; School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD, UK. ; Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Charite-Universitatsmedizin Berlin 10117, Germany. ; Physikalisch-Technische Bundesanstalt (PTB), 10587 Berlin, Germany. ; School of Psychology, University of Nottingham, Nottingham NG7 2RD, UK. ; 1] Institut National de la Sante et de la Recherche Medicale, INSERM CEA Unit 1000 "Imaging &Psychiatry", University Paris Sud, 91400 Orsay, France [2] AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, 75006 Paris, France. ; 1] Department of Psychiatry, University of Vermont, Burlington, Vermont 05401, USA [2] Neuroscience Graduate Program, University of Vermont, Burlington, Vermont 05401, USA. ; 1] Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Charite-Universitatsmedizin Berlin 10117, Germany [2] AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, 75006 Paris, France. ; 1] Rotman Research Institute, University of Toronto, Toronto, Ontario M5R 0A3, Canada [2] Montreal Neurological Institute, McGill University, H3A 2B4, Canada. ; The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 0A4, Canada. ; Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge CB2 1TN, UK. ; 1] Institute of Psychiatry, King's College London, London SE5 8AF, UK [2] MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, London WC2R 2LS, UK. ; 1] Department of Psychiatry, University of Vermont, Burlington, Vermont 05401, USA [2] Department of Psychology, University of Vermont, Burlington, Vermont 05401, USA [3] Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043041" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Alcohol Drinking/*psychology ; Alcoholism/genetics/prevention & control/*psychology ; Artificial Intelligence ; Brain/physiology ; Cognition/physiology ; Environment ; Humans ; Life Change Events ; Longitudinal Studies ; *Models, Theoretical ; Personality/physiology ; Polymorphism, Single Nucleotide ; Psychology ; Reproducibility of Results ; Risk Factors
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  • 46
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    Nature Publishing Group (NPG)
    Publication Date: 2014-03-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kraus, Virginia Byers -- England -- Nature. 2014 Mar 27;507(7493):441-2. doi: 10.1038/507441a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina 27701-2047, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670760" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; Male ; Osteoarthritis/*metabolism/*pathology ; *Signal Transduction
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  • 47
    Publication Date: 2014-07-22
    Description: Metabotropic glutamate receptors are class C G-protein-coupled receptors which respond to the neurotransmitter glutamate. Structural studies have been restricted to the amino-terminal extracellular domain, providing little understanding of the membrane-spanning signal transduction domain. Metabotropic glutamate receptor 5 is of considerable interest as a drug target in the treatment of fragile X syndrome, autism, depression, anxiety, addiction and movement disorders. Here we report the crystal structure of the transmembrane domain of the human receptor in complex with the negative allosteric modulator, mavoglurant. The structure provides detailed insight into the architecture of the transmembrane domain of class C receptors including the precise location of the allosteric binding site within the transmembrane domain and key micro-switches which regulate receptor signalling. This structure also provides a model for all class C G-protein-coupled receptors and may aid in the design of new small-molecule drugs for the treatment of brain disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dore, Andrew S -- Okrasa, Krzysztof -- Patel, Jayesh C -- Serrano-Vega, Maria -- Bennett, Kirstie -- Cooke, Robert M -- Errey, James C -- Jazayeri, Ali -- Khan, Samir -- Tehan, Ben -- Weir, Malcolm -- Wiggin, Giselle R -- Marshall, Fiona H -- England -- Nature. 2014 Jul 31;511(7511):557-62. doi: 10.1038/nature13396. Epub 2014 Jul 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, UK [2]. ; Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25042998" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Binding Sites ; Crystallography, X-Ray ; HEK293 Cells ; Humans ; *Models, Molecular ; Protein Structure, Tertiary ; Receptor, Metabotropic Glutamate 5/*chemistry ; Rhodopsin/chemistry
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  • 48
    Publication Date: 2013-11-22
    Description: The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians, there is no consensus with regard to which specific Old World populations they are closest to. Here we sequence the draft genome of an approximately 24,000-year-old individual (MA-1), from Mal'ta in south-central Siberia, to an average depth of 1x. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic and Mesolithic European hunter-gatherers, and the Y chromosome of MA-1 is basal to modern-day western Eurasians and near the root of most Native American lineages. Similarly, we find autosomal evidence that MA-1 is basal to modern-day western Eurasians and genetically closely related to modern-day Native Americans, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought. Furthermore, we estimate that 14 to 38% of Native American ancestry may originate through gene flow from this ancient population. This is likely to have occurred after the divergence of Native American ancestors from east Asian ancestors, but before the diversification of Native American populations in the New World. Gene flow from the MA-1 lineage into Native American ancestors could explain why several crania from the First Americans have been reported as bearing morphological characteristics that do not resemble those of east Asians. Sequencing of another south-central Siberian, Afontova Gora-2 dating to approximately 17,000 years ago, revealed similar autosomal genetic signatures as MA-1, suggesting that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures in modern-day Native Americans derive not only from post-Columbian admixture, as commonly thought, but also from a mixed ancestry of the First Americans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105016/" 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/PMC4105016/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raghavan, Maanasa -- Skoglund, Pontus -- Graf, Kelly E -- Metspalu, Mait -- Albrechtsen, Anders -- Moltke, Ida -- Rasmussen, Simon -- Stafford, Thomas W Jr -- Orlando, Ludovic -- Metspalu, Ene -- Karmin, Monika -- Tambets, Kristiina -- Rootsi, Siiri -- Magi, Reedik -- Campos, Paula F -- Balanovska, Elena -- Balanovsky, Oleg -- Khusnutdinova, Elza -- Litvinov, Sergey -- Osipova, Ludmila P -- Fedorova, Sardana A -- Voevoda, Mikhail I -- DeGiorgio, Michael -- Sicheritz-Ponten, Thomas -- Brunak, Soren -- Demeshchenko, Svetlana -- Kivisild, Toomas -- Villems, Richard -- Nielsen, Rasmus -- Jakobsson, Mattias -- Willerslev, Eske -- R01 HG003229/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Jan 2;505(7481):87-91. doi: 10.1038/nature12736. Epub 2013 Nov 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark [2]. ; 1] Department of Evolutionary Biology, Uppsala University, Norbyvagen 18D, Uppsala 752 36, Sweden [2]. ; Center for the Study of the First Americans, Texas A&M University, TAMU-4352, College Station, Texas 77845-4352, USA. ; 1] Estonian Biocentre, Evolutionary Biology group, Tartu 51010, Estonia [2] Department of Integrative Biology, University of California, Berkeley, California 94720, USA [3] Department of Evolutionary Biology, University of Tartu, Tartu 51010, Estonia. ; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, Copenhagen 2200, Denmark. ; 1] The Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, Copenhagen 2200, Denmark [2] Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA. ; Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby 2800, Denmark. ; 1] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark [2] AMS 14C Dating Centre, Department of Physics and Astronomy, University of Aarhus, Ny Munkegade 120, Aarhus DK-8000, Denmark. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; Department of Evolutionary Biology, University of Tartu, Tartu 51010, Estonia. ; 1] Estonian Biocentre, Evolutionary Biology group, Tartu 51010, Estonia [2] Department of Evolutionary Biology, University of Tartu, Tartu 51010, Estonia. ; Estonian Biocentre, Evolutionary Biology group, Tartu 51010, Estonia. ; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. ; Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moskvorechie Street 1, Moscow 115479, Russia. ; 1] Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moskvorechie Street 1, Moscow 115479, Russia [2] Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkina Street 3, Moscow 119991, Russia. ; 1] Institute of Biochemistry and Genetics, Ufa Scientific Centre, Russian Academy of Sciences, Ufa, Bashkorostan 450054, Russia [2] Biology Department, Bashkir State University, Ufa, Bashkorostan 450074, Russia. ; 1] Estonian Biocentre, Evolutionary Biology group, Tartu 51010, Estonia [2] Institute of Biochemistry and Genetics, Ufa Scientific Centre, Russian Academy of Sciences, Ufa, Bashkorostan 450054, Russia. ; The Institute of Cytology and Genetics, Center for Brain Neurobiology and Neurogenetics, Siberian Branch of the Russian Academy of Sciences, Lavrentyeva Avenue, Novosibirsk 630090, Russia. ; Department of Molecular Genetics, Yakut Research Center of Complex Medical Problems, Russian Academy of Medical Sciences and North-Eastern Federal University, Yakutsk, Sakha (Yakutia) 677010, Russia. ; 1] The Institute of Cytology and Genetics, Center for Brain Neurobiology and Neurogenetics, Siberian Branch of the Russian Academy of Sciences, Lavrentyeva Avenue, Novosibirsk 630090, Russia [2] Institute of Internal Medicine, Siberian Branch of the Russian Academy of Medical Sciences, Borisa Bogatkova 175/1, Novosibirsk 630089, Russia. ; Department of Integrative Biology, University of California, Berkeley, California 94720, USA. ; 1] Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby 2800, Denmark [2] Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby 2800, Denmark. ; The State Hermitage Museum, 2, Dvortsovaya Ploshchad, St. Petersberg 190000, Russia. ; 1] Estonian Biocentre, Evolutionary Biology group, Tartu 51010, Estonia [2] Department of Biological Anthropology, University of Cambridge, Cambridge CB2 1QH, UK. ; 1] Estonian Biocentre, Evolutionary Biology group, Tartu 51010, Estonia [2] Department of Evolutionary Biology, University of Tartu, Tartu 51010, Estonia [3] Estonian Academy of Sciences, Tallinn 10130, Estonia. ; 1] Department of Evolutionary Biology, Uppsala University, Norbyvagen 18D, Uppsala 752 36, Sweden [2] Science for Life Laboratory, Uppsala University, Norbyvagen 18D, 752 36 Uppsala, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24256729" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Asia/ethnology ; Asian Continental Ancestry Group/*genetics ; Chromosomes, Human, Y/genetics ; DNA, Mitochondrial/genetics ; Emigration and Immigration ; European Continental Ancestry Group/*genetics ; Gene Flow/genetics ; Genome, Human/*genetics ; Genome, Mitochondrial/genetics ; Haplotypes/genetics ; Humans ; Indians, North American/classification/*ethnology/*genetics ; Male ; *Phylogeny ; Phylogeography ; Siberia/ethnology ; Skeleton
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  • 49
    Publication Date: 2014-07-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyer, Michelle N -- England -- Nature. 2014 Jul 17;511(7509):265. doi: 10.1038/511265a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25030132" target="_blank"〉PubMed〈/a〉
    Keywords: Data Mining ; *Ethics, Research ; Humans ; Social Media/ethics/*statistics & numerical data ; Social Sciences/*ethics/*methods
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  • 50
    Publication Date: 2014-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krug, Robert M -- England -- Nature. 2014 Dec 18;516(7531):338-9. doi: 10.1038/516338a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biosciences, Center for Infectious Disease, Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25519129" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA-Directed RNA Polymerases/*chemistry/metabolism ; Humans ; Influenza A virus/*enzymology ; Influenza B virus/*enzymology ; RNA/biosynthesis ; Virus Replication
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  • 51
    Publication Date: 2014-07-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- Maher, Brendan -- England -- Nature. 2014 Jul 3;511(7507):13-4. doi: 10.1038/511013a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24990722" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Genetic Engineering ; Humans ; Influenza A Virus, H1N1 Subtype/*genetics/*pathogenicity ; Influenza A Virus, H5N1 Subtype/genetics/pathogenicity ; Influenza, Human/transmission/*virology ; National Institute of Allergy and Infectious Diseases (U.S.)/legislation & ; jurisprudence ; Risk Assessment ; United States ; Universities
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  • 52
    Publication Date: 2014-09-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smaglik, Paul -- Kaplan, Karen -- Kelly, Shirana -- Penny, Dan -- England -- Nature. 2014 Sep 11;513(7517):267-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25215388" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; Humans ; *Job Satisfaction ; Research/*economics
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  • 53
    Publication Date: 2014-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- Morello, Lauren -- England -- Nature. 2014 Oct 16;514(7522):284-5. doi: 10.1038/514284a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25318501" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; Disease Outbreaks/*statistics & numerical data ; Female ; Hemorrhagic Fever, Ebola/*epidemiology/mortality/*transmission ; Humans ; Male
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  • 54
    Publication Date: 2014-03-05
    Description: Recognition of modified histones by 'reader' proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific 'Ser 31' residue in a composite pocket formed by the tandem bromo-PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142212/" 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/PMC4142212/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wen, Hong -- Li, Yuanyuan -- Xi, Yuanxin -- Jiang, Shiming -- Stratton, Sabrina -- Peng, Danni -- Tanaka, Kaori -- Ren, Yongfeng -- Xia, Zheng -- Wu, Jun -- Li, Bing -- Barton, Michelle C -- Li, Wei -- Li, Haitao -- Shi, Xiaobing -- CA016672/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- R01 GM090077/GM/NIGMS NIH HHS/ -- R01 HG007538/HG/NHGRI NIH HHS/ -- R01GM090077/GM/NIGMS NIH HHS/ -- R01HG007538/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Apr 10;508(7495):263-8. doi: 10.1038/nature13045. Epub 2014 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Center for Cancer Epigenetics, Center for Genetics and Genomics, and Center for Stem Cell and Developmental Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [3]. ; 1] MOE Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China [2] Department of Basic Medical Sci