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  • 1
    Publication Date: 2016-08-18
    Description: Circadian neuron feedback controls the Drosophila sleep–activity profile Nature 536, 7616 (2016). doi:10.1038/nature19097 Authors: Fang Guo, Junwei Yu, Hyung Jae Jung, Katharine C. Abruzzi, Weifei Luo, Leslie C. Griffith & Michael Rosbash Little is known about the ability of Drosophila circadian neurons to promote sleep. Here we show, using optogenetic manipulation and video recording, that a subset of dorsal clock neurons (DN1s) are potent sleep-promoting cells that release glutamate to directly inhibit key pacemaker neurons. The
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 2
    Publication Date: 2011-06-25
    Description: Author(s): T. H. Loftus, M. D. Swallows, W. C. Griffith, M. V. Romalis, B. R. Heckel, and E. N. Fortson We present measurements of Stark interference in the 6 1 S 0 →6 3 P 1 transition in 199 Hg , a process whereby a static electric field E mixes magnetic dipole and electric quadrupole couplings into an electric dipole transition, leading to E -linear energy shifts similar to those produced by a permanent atomi... [Phys. Rev. Lett. 106, 253002] Published Fri Jun 24, 2011
    Keywords: Atomic, Molecular, and Optical Physics
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
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  • 3
    Publication Date: 2012-06-30
    Description: The Journal of Physical Chemistry B DOI: 10.1021/jp303913e
    Electronic ISSN: 1520-5207
    Topics: Chemistry and Pharmacology , Physics
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  • 4
    Publication Date: 2012-04-19
    Description: Accounts of Chemical Research DOI: 10.1021/ar300027q
    Print ISSN: 0001-4842
    Electronic ISSN: 1520-4898
    Topics: Chemistry and Pharmacology
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  • 5
    Publication Date: 2012-05-11
    Description: The aggregation of α-synuclein (αSyn) is a neuropathologic hallmark of Parkinson's disease and other synucleinopathies. In Lewy bodies, αSyn is extensively phosphorylated, predominantly at serine 129 (S129). Recent studies in yeast have shown that, at toxic levels, αSyn disrupts Rab homeostasis, causing an initial endoplasmic reticulum-to-Golgi block that precedes a generalized trafficking collapse. However, whether αSyn phosphorylation modulates trafficking defects has not been evaluated. Here, we show that constitutive expression of αSyn in yeast impairs late-exocytic, early-endocytic and/or recycling trafficking. Although members of the casein kinase I (CKI) family phosphorylate αSyn at S129, they attenuate αSyn toxicity and trafficking defects by an S129 phosphorylation-independent mechanism. Surprisingly, phosphorylation of S129 modulates αSyn toxicity and trafficking defects in a manner strictly determined by genetic background. Abnormal endosome morphology, increased levels of the endosome marker Rab5 and co-localization of mammalian CKI with αSyn aggregates are observed in brain sections from αSyn-overexpressing mice and human synucleinopathies. Our results contribute to evidence that suggests αSyn-induced defects in endocytosis, exocytosis and/or recycling of vesicles involved in these cellular processes might contribute to the pathogenesis of synucleinopathies.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 6
    Publication Date: 2014-02-27
    Description: Journal of the American Chemical Society DOI: 10.1021/ja5006256
    Print ISSN: 0002-7863
    Electronic ISSN: 1520-5126
    Topics: Chemistry and Pharmacology
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  • 7
    Publication Date: 2014-09-20
    Description: Detailed models of the biomechanics of the heart are important both for developing improved interventions for patients with heart disease and also for patient risk stratification and treatment planning. For instance, stress distributions in the heart affect cardiac remodelling, but such distributions are not presently accessible in patients. Biomechanical models of the heart offer detailed three-dimensional deformation, stress and strain fields that can supplement conventional clinical data. In this work, we introduce dynamic computational models of the human left ventricle (LV) that are derived from clinical imaging data obtained from a healthy subject and from a patient with a myocardial infarction (MI). Both models incorporate a detailed invariant-based orthotropic description of the passive elasticity of the ventricular myocardium along with a detailed biophysical model of active tension generation in the ventricular muscle. These constitutive models are employed within a dynamic simulation framework that accounts for the inertia of the ventricular muscle and the blood that is based on an immersed boundary (IB) method with a finite element description of the structural mechanics. The geometry of the models is based on data obtained non-invasively by cardiac magnetic resonance (CMR). CMR imaging data are also used to estimate the parameters of the passive and active constitutive models, which are determined so that the simulated end-diastolic and end-systolic volumes agree with the corresponding volumes determined from the CMR imaging studies. Using these models, we simulate LV dynamics from end-diastole to end-systole. The results of our simulations are shown to be in good agreement with subject-specific CMR-derived strain measurements and also with earlier clinical studies on human LV strain distributions.
    Print ISSN: 0272-4960
    Electronic ISSN: 1464-3634
    Topics: Mathematics
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  • 8
    Publication Date: 2014-12-30
    Description: Net ecosystem production (NEP) and the overall organic carbon budget for the estuaries along the east coast of the United States are estimated. We focus on the open estuarine waters, excluding the fringing wetlands. We developed empirical models relating NEP to loading ratios of dissolved inorganic nitrogen to total organic carbon, and carbon burial in the sediment to estuarine water residence time and total nitrogen input across the landward boundary. Output from a data-constrained water quality model was used to estimate inputs of total nitrogen and organic carbon to the estuaries across the landward boundary, including fluvial and tidal-wetland sources. Organic carbon export from the estuaries to the continental shelf was computed by difference, assuming steady state. Uncertainties in the budget were estimated by allowing uncertainties in the supporting model relations. Collectively, U.S. east coast estuaries are net heterotrophic, with the area-integrated NEP of −1.5 (−2.8, −1.0) Tg C yr −1 (best estimate and 95% confidence interval) and area-normalized NEP of −3.2 (−6.1, −2.3) mol C m −2  yr −1 . East coast estuaries serve as a source of organic carbon to the shelf, exporting 3.4 (2.0, 4.3) Tg C yr −1 or 7.6 (4.4, 9.5) mol C m −2  yr −1 . Organic carbon inputs from fluvial and tidal-wetland sources for the region are estimated at 5.4 (4.6, 6.5) Tg C yr −1 or 12 (10, 14) mol C m −2  yr −1 and carbon burial in the open estuarine waters at 0.50 (0.33, 0.78) Tg C yr −1 or 1.1 (0.73, 1.7) mol C m −2  yr −1 . Our results highlight the importance of estuarine systems in the overall coastal budget of organic carbon, suggesting that in the aggregate, U.S. east coast estuaries assimilate (via respiration and burial) ~40% of organic carbon inputs from fluvial and tidal-wetland sources and allow ~60% to be exported to the shelf.
    Print ISSN: 0886-6236
    Electronic ISSN: 1944-9224
    Topics: Biology , Chemistry and Pharmacology , Geography , Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 9
    Publication Date: 2003-11-01
    Description: Mutations in MeCP2, which encodes a protein that has been proposed to function as a global transcriptional repressor, are the cause of Rett syndrome (RT T), an X-linked progressive neurological disorder. Although the selective inactivation of MeCP2 in neurons is sufficient to confer a Rett-like phenotype in mice, the specific functions of MeCP2 in postmitotic neurons are not known. We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene. Membrane depolarization triggers the calcium-dependent phosphorylation and release of MeCP2 from BDNF promoter III, thereby facilitating transcription. These studies indicate that MeCP2 plays a key role in the control of neuronal activity-dependent gene regulation and suggest that the deregulation of this process may underlie the pathology of RT T.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Wen G -- Chang, Qiang -- Lin, Yingxi -- Meissner, Alexander -- West, Anne E -- Griffith, Eric C -- Jaenisch, Rudolf -- Greenberg, Michael E -- HD 18655/HD/NICHD NIH HHS/ -- NS28829/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):885-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593183" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain-Derived Neurotrophic Factor/*genetics ; Calcium/*metabolism ; Cell Membrane/physiology ; Cells, Cultured ; *Chromosomal Proteins, Non-Histone ; Cloning, Molecular ; CpG Islands ; DNA Methylation ; DNA-Binding Proteins/*metabolism ; Electrophoretic Mobility Shift Assay ; *Gene Expression Regulation ; Gene Silencing ; Histones/metabolism ; Methyl-CpG-Binding Protein 2 ; Methylation ; Mice ; Mice, Knockout ; Neurons/metabolism/physiology ; Phosphorylation ; Potassium Chloride/pharmacology ; Precipitin Tests ; Promoter Regions, Genetic ; Rats ; *Repressor Proteins ; Rett Syndrome/genetics ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 1997-06-27
    Description: Long-term potentiation (LTP), a cellular model of learning and memory, requires calcium-dependent protein kinases. Induction of LTP increased the phosphorus-32 labeling of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPA-Rs), which mediate rapid excitatory synaptic transmission. This AMPA-R phosphorylation appeared to be catalyzed by Ca2+- and calmodulin-dependent protein kinase II (CaM-KII): (i) it correlated with the activation and autophosphorylation of CaM-KII, (ii) it was blocked by the CaM-KII inhibitor KN-62, and (iii) its phosphorus-32 peptide map was the same as that of GluR1 coexpressed with activated CaM-KII in HEK-293 cells. This covalent modulation of AMPA-Rs in LTP provides a postsynaptic molecular mechanism for synaptic plasticity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barria, A -- Muller, D -- Derkach, V -- Griffith, L C -- Soderling, T R -- NS27037/NS/NINDS NIH HHS/ -- R01 GM054408/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1997 Jun 27;276(5321):2042-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health Sciences University, Portland, OR 97201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9197267" target="_blank"〉PubMed〈/a〉
    Keywords: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/pharmacology ; 2-Amino-5-phosphonovalerate/pharmacology ; Animals ; Calcium/metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*metabolism ; Cell Line ; Enzyme Inhibitors/pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; Hippocampus/*metabolism ; Humans ; In Vitro Techniques ; *Long-Term Potentiation/drug effects ; Male ; Peptide Mapping ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/*metabolism ; Synaptic Transmission/drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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