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  • 1
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    A core erythroid transcriptional network is repressed by a master regulator of myelo-lymphoid differentiation [Developmental Biology] (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-03-07
    Description: Two mechanisms that play important roles in cell fate decisions are control of a “core transcriptional network” and repression of alternative transcriptional programs by antagonizing transcription factors. Whether these two mechanisms operate together is not known. Here we report that GATA-1, SCL, and Klf1 form an erythroid core transcriptional network by co-occupying 〉300 genes. Importantly, we find that PU.1, a negative regulator of terminal erythroid differentiation, is a highly integrated component of this network. GATA-1, SCL, and Klf1 act to promote, whereas PU.1 represses expression of many of the core network genes. PU.1 also represses the genes encoding GATA-1, SCL, Klf1, and important GATA-1 cofactors. Conversely, in addition to repressing PU.1 expression, GATA-1 also binds to and represses 〉100 PU.1 myelo-lymphoid gene targets in erythroid progenitors. Mathematical modeling further supports that this dual mechanism of repressing both the opposing upstream activator and its downstream targets provides a synergistic, robust mechanism for lineage specification. Taken together, these results amalgamate two key developmental principles, namely, regulation of a core transcriptional network and repression of an alternative transcriptional program, thereby enhancing our understanding of the mechanisms that establish cellular identity.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 2
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    Genome-wide mapping of IBD segments in an Ashkenazi PD cohort identifies associated haplotypes (2014)
    Oxford University Press
    Details
    Publication Date: 2014-08-03
    Description: The recent series of large genome-wide association studies in European and Japanese cohorts established that Parkinson disease (PD) has a substantial genetic component. To further investigate the genetic landscape of PD, we performed a genome-wide scan in the largest to date Ashkenazi Jewish cohort of 1130 Parkinson patients and 2611 pooled controls. Motivated by the reduced disease allele heterogeneity and a high degree of identical-by-descent (IBD) haplotype sharing in this founder population, we conducted a haplotype association study based on mapping of shared IBD segments. We observed significant haplotype association signals at three previously implicated Parkinson loci: LRRK2 (OR = 12.05, P = 1.23 x 10 –56 ), MAPT (OR = 0.62, P = 1.78 x 10 –11 ) and GBA (multiple distinct haplotypes, OR 〉 8.28, P = 1.13 x 10 –11 and OR = 2.50, P = 1.22 x 10 –9 ). In addition, we identified a novel association signal on chr2q14.3 coming from a rare haplotype (OR = 22.58, P = 1.21 x 10 –10 ) and replicated it in a secondary cohort of 306 Ashkenazi PD cases and 2583 controls. Our results highlight the power of our haplotype association method, particularly useful in studies of founder populations, and reaffirm the benefits of studying complex diseases in Ashkenazi Jewish cohorts.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 3
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    Dependence of cortical plasticity on correlated activity of single neurons and on behavioral context (1992)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1992-09-04
    Description: It has not been possible to analyze the cellular mechanisms underlying learning in behaving mammals because of the difficulties in recording intracellularly from awake animals. Therefore, in the present study of neuronal plasticity in behaving monkeys, the net effect of a single neuron on another neuron (the "functional connection") was evaluated by cross-correlating the times of firing of the two neurons. When two neurons were induced to fire together within a short time window, the functional connection between them was potentiated, and when simultaneous firing was prevented, the connection was depressed. These modifications were strongly dependent on the behavioral context of the stimuli that induced them. The results indicate that changes in the temporal contingency between neurons are often necessary, but not sufficient, for cortical plasticity in the adult monkey: behavioral relevance is required.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ahissar, E -- Vaadia, E -- Ahissar, M -- Bergman, H -- Arieli, A -- Abeles, M -- New York, N.Y. -- Science. 1992 Sep 4;257(5075):1412-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Hebrew University, Hadassah Medical School, Jerusalem, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1529342" target="_blank"〉PubMed〈/a〉
    Keywords: Acoustic Stimulation ; Action Potentials ; Animals ; Auditory Cortex/*physiology ; Behavior, Animal/*physiology ; Conditioning (Psychology) ; Macaca fascicularis ; Neuronal Plasticity/*physiology ; Neurons/*physiology ; Synapses/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)
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  • 4
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    Reversal of experimental parkinsonism by lesions of the subthalamic nucleus (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-09-21
    Description: Although it is known that Parkinson's disease results from a loss of dopaminergic neurons in the substantia nigra, the resulting alterations in activity in the basal ganglia responsible for parkinsonian motor deficits are still poorly characterized. Recently, increased activity in the subthalamic nucleus has been implicated in the motor abnormalities. To test this hypothesis, the effects of lesions of the subthalamic nucleus were evaluated in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The lesions reduced all of the major motor disturbances in the contralateral limbs, including akinesia, rigidity, and tremor. This result supports the postulated role of excessive activity in the subthalamic nucleus in Parkinson's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bergman, H -- Wichmann, T -- DeLong, M R -- S RO1 NS15412-09/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 21;249(4975):1436-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Johns Hopkins Hospital, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2402638" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Brain/physiology/physiopathology ; Cercopithecus aethiops ; Disease Models, Animal ; Ibotenic Acid/pharmacology/therapeutic use ; Models, Neurological ; Parkinson Disease/physiopathology/*therapy ; Parkinson Disease, Secondary/chemically induced ; Periaqueductal Gray/drug effects/physiology/*physiopathology
    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)
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  • 5
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    Blood-brain barrier penetration and in vivo activity of an NGF conjugate (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-01-15
    Description: Nerve growth factor (NGF) is essential for the survival of both peripheral ganglion cells and central cholinergic neurons of the basal forebrain. The accelerated loss of central cholinergic neurons during Alzheimer's disease may be a determinant of dementia in these patients and may therefore suggest a therapeutic role for NGF. However, NGF does not significantly penetrate the blood-brain barrier, which makes its clinical utility dependent on invasive neurosurgical procedures. When conjugated to an antibody to the transferrin receptor, however, NGF crossed the blood-brain barrier after peripheral injection. This conjugated NGF increased the survival of both cholinergic and noncholinergic neurons of the medial septal nucleus that had been transplanted into the anterior chamber of the rat eye. This approach may prove useful for the treatment of Alzheimer's disease and other neurological disorders that are amenable to treatment by proteins that do not readily cross the blood-brain barrier.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Friden, P M -- Walus, L R -- Watson, P -- Doctrow, S R -- Kozarich, J W -- Backman, C -- Bergman, H -- Hoffer, B -- Bloom, F -- Granholm, A C -- NS29601-01/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 15;259(5093):373-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Alkermes, Inc., Cambridge, MA 02139.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8420006" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anterior Chamber/metabolism ; Antibodies/*metabolism ; *Blood-Brain Barrier ; Brain/blood supply/metabolism ; Capillaries ; Cell Line ; Cross-Linking Reagents ; Dose-Response Relationship, Drug ; Drug Carriers ; Immunohistochemistry ; Nerve Growth Factors/administration & dosage/*pharmacokinetics/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Transferrin/*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)
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  • 6
    Electronic Resource
    Electronic Resource
    Qualitative and quantitative detection of soluble nucleotides and their derivatives in cereal seedlings by means of proper chromatography
    Amsterdam : Elsevier
    Journal of Chromatography A 31 (1967), S. 279-281 
    Details
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/S0021-9673(01)86070-2
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  • 7
    Electronic Resource
    Electronic Resource
    Laser pyrolysis of explosives combined with mass spectral studies of the ignition zone
    Amsterdam : Elsevier
    Journal of Analytical and Applied Pyrolysis 24 (1992), S. 163-178 
    Details
    ISSN: 0165-2370
    Keywords: Explosives ; RDX. ; ignition zone ; laser ; mass spectrometry ; pyrolysis
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0165-2370(92)85027-I
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  • 8
    Electronic Resource
    Electronic Resource
    The chemistry of 3-mtro-1,2,4-triazol-5-one (NTO): thermal decomposition
    Amsterdam : Elsevier
    Thermochimica Acta 213 (1993), S. 165-175 
    Details
    ISSN: 0040-6031
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0040-6031(93)80014-2
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  • 9
    Electronic Resource
    Electronic Resource
    Toxicity of underground coal gasification condenser water and selected constituents to aquatic biota (1980)
    Springer
    Archives of environmental contamination and toxicology 9 (1980), S. 543-555 
    Details
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract The acute and embryo-larval toxicity of the Laramie Energy Technology Center's Hanna-3 underground coal gasification (UCG) condenser water and its constituents were studied in continuous-flow bioassays. The 96-hr LC50 dilution values for untreated Hanna-3 UCG condenser water were 0.1% for rainbow trout, 0.11% for fathead minnows and the 48-hr LC50 dilution forDaphnia pulicaria was 0.18%. Separate 96-hr acute tests with phenol, ammonia, and ammonia plus phenol showed that these two constituents, acting synergistically, were the major constituents affecting the acute toxicity of this coal conversion effluent to fishDaphnia pulicaria, on the other hand, was relatively insensitive to phenol exposure; the primary constituent of Hanna-3 UCG condenser water affecting this species was ammonia. A previously described model was used for predicting the toxicity of effluents with high concentrations of phenol and ammonia to confirm our hypothesis that the acute toxicity of Hanna-3 UCG condenser water to fish was primarily due to the presence of phenol and ammonia. Using the Hanna-3 concentrations of phenol and ammonia in this formula, it was calculated that the 96-hr LC50 values for rainbow trout and fathead minnows exposed to Hanna-3 condenser water would be 0.11% and 0.28%, respectively; values which are near the observed acute toxicity of Hanna-3 condenser water. In a 30-day embryo-larval exposure, fathead minnow egg hatchability, growth, and survival were significantly reduced at 0.04%, 0.02% and 0.01% Hanna-3 condenser water, respectively. At a Hanna-3 dilution of 0.01%, the phenol and un-ionized ammonia concentrations were calculated to be 0.23 mg/L and 0.14 mg/L, respectively. The phenol and un-ionized ammonia concentrations are within ranges expected to produce the long-term effects which were observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01056934
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  • 10
    Electronic Resource
    Electronic Resource
    Effects of naphthalene and benzene on fathead minnows and rainbow trout (1982)
    Springer
    Archives of environmental contamination and toxicology 11 (1982), S. 487-490 
    Details
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract Fathead minnows (FHM) and rainbow trout (RBT) were used in flow-through bioassays to determine the acute toxicity of benzene and naphthalene, and to determine the embryo-larval effects of naphthalene on FHM. On an acute basis, naphthalene was more toxic than benzene (naphthalene LC50 values were 1.6 mg/L for RBT and 7.9 mg/L for FHM; benzene LC50 values were 5.3 mg/L for RBT and 〉15.1 mg/L for FHM). In the embryo-larval test naphthalene significantly (α= 0.05) reduced FHM growth at concentrations as low as 0.85 mg/L. The highest concentration producing no effect was 0.45 mg/L naphthalene, which was 5.7% of the FHM 96-hr LC50. Based upon long-term no-effects naphthalene concentration, the best estimate of the maximum acceptable toxicant concentration (MATC) was 〉0.45 to 〈0.85 mg/L naphthalene.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01056076
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