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  • 1
    Publication Date: 2012-09-19
    Description: Protein posttranslational modifications (PTMs), particularly phosphorylation, dramatically expand the complexity of cellular regulatory networks. Although cysteine (Cys) in various proteins can be subject to multiple PTMs, its phosphorylation was previously considered a rare PTM with almost no regulatory role assigned. We report here that phosphorylation occurs to a reactive cysteine...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2016-07-06
    Description: Visual working memory is the cognitive system that holds visual information active to make it resistant to interference from new perceptual input. Information about simple stimuli—colors and orientations—is encoded into working memory rapidly: In under 100 ms, working memory ‟fills up,” revealing a stark capacity limit. However, for real-world objects,...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 3
    Publication Date: 2016-08-18
    Description: The ADP-ribosylating enzymes are encoded in many pathogenic bacteria in order to affect essential functions of the host. In this study, we show that Neisseria gonorrhoeae possess a locus that corresponds to the ADP-ribosyltransferase NarE, a previously characterized enzyme in N. meningitidis . The 291 bp coding sequence of gonococcal narE shares 100% identity with part of the coding sequence of the meningococcal narE gene due to a frameshift previously described, thus leading to a 49-amino-acid deletion at the N-terminus of gonococcal NarE protein. However, we found a promoter region and a GTG start codon, which allowed expression of the protein as demonstrated by RT-PCR and western blot analyses. Using a gonococcal NarE–6xHis fusion protein, we demonstrated that the gonococcal enzyme underwent auto-ADP-ribosylation but to a lower extent than meningococcal NarE. We also observed that gonoccocal NarE exhibited ADP-ribosyltransferase activity using agmatine and cell-free host proteins as ADP-ribose acceptors, but its activity was inhibited by human β-defensins. Taken together, our results showed that NarE of Neisseria gonorrhoeae is a functional enzyme that possesses key features of bacterial ADP-ribosylating enzymes.
    Keywords: Physiology & Biochemistry
    Print ISSN: 0378-1097
    Electronic ISSN: 1574-6968
    Topics: Biology
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  • 4
    Publication Date: 2016-02-24
    Description: ACS Sustainable Chemistry & Engineering DOI: 10.1021/acssuschemeng.5b01581
    Electronic ISSN: 2168-0485
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 5
  • 6
    Publication Date: 2019
    Description: Abstract Dissolved organic carbon (DOC) transport and export from headwater forests into freshwaters in highly dynamic tropical catchments are still understudied. Here we present a DOC analysis (2017) in a pristine and small (~2.6 km2) tropical catchment of Costa Rica. Storm flows governed a rapid surface and lateral allochthonous DOC transport (62.2% of the annual DOC export). Cross‐correlation analysis of rainfall and stream discharge indicated that DOC transport occurred on average ~1.25 hr after the rainfall maxima, with large contributions of event water, ranging from 42.4±0.3% up to 98.2±0.3% of the total discharge. Carbon export flux (annual mean=6.7±0.1 g C · m‐2 · year‐1) was greater than values reported in subtropical and temperate catchments. Specific ultraviolet absorbance indicated a mixture of hydrophobic humic and hydrophilic nonhumic matter during both baseflow and storm events. Our results highlight the rapid storm‐driven DOC transport and export as well as low biogeochemical attenuation during baseflow episodes in a climate sensitive hot spot. By understanding the key factors controlling the amount of organic carbon transported to streams in dynamic tropical landscapes, better global‐ and catchment‐scale model assessments, conservation practices, and water treatment innovations can be identified.
    Print ISSN: 2169-8953
    Electronic ISSN: 2169-8961
    Topics: Biology , Geosciences
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 7
    Publication Date: 2019
    Description: In this work we have detected that the occurrence of strong surface wind events associated to convection (CSSWE) during austral spring in northeastern Argentina (NEA) is related to the activity of the leading pattern of intraseasonal (IS) activity of OLR anomalies in South America, the SIS pattern. CSSWE are favoured when the SIS index is positive, related to a cyclonic IS anomaly in upper levels favouring ascent in NEA, and also in lower levels related to northerly advection in NEA. Abstract The relationship between intraseasonal variability (IS; 10–90 days) and days which registered convection‐associated strong surface wind events (CSSWE) over northeastern Argentina (NEA) was studied. The climatological behaviour of these strong wind events showed a higher duration and occurrence in austral spring. CSSWE were categorized as a function of the wet and dry phases of the spring‐season intraseasonal (spring‐SIS) index, which describes the activity of the leading pattern of IS‐filtered outgoing longwave radiation (IS‐OLR) during that season in eastern South America. A modulation of the IS variability over localized and mesoscale phenomena as the CSSWE was found, showing significant peaks of wind variability in that timescale, and especially the submonthly timescale. The CSSWE were categorized according to the phases of the spring‐SIS pattern and most of them occurred before or during a wet phase, especially for the longer CSSWE. Moreover, the detection of CSSWE days during and before a dry phase was scarce. Rossby wave trains were observed to organize the circulation on intraseasonal timescales that configure regional cyclonic anomalies in such way that favours the development of CSSWE, promoting mid‐level ascents over NEA and northerly advection of humidity to the region. Together with the composites of IS‐OLR anomalies and the spectra of wind velocity, they support the fact that the higher‐frequency IS variability is the primary influence for the development of CSSWE.
    Print ISSN: 0899-8418
    Electronic ISSN: 1097-0088
    Topics: Geosciences , Physics
    Published by Wiley
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  • 8
    Publication Date: 2011-04-13
    Description: Nucleolar stress, characterized by loss of nucleolar integrity, has not been described in the cardiac context. In addition to ribosome biogenesis, nucleoli are critical for control of cell proliferation and stress responses. Our group previously demonstrated induction of the nucleolar protein nucleostemin (NS) in response to cardiac pathological insult. NS interacts with nucleophosmin (NPM), a marker of nucleolar stress with cytoprotective properties. The dynamic behavior of NS and NPM reveal that nucleolar disruption is an early event associated with stress response in cardiac cells. Rapid translocation of NS and NPM to the nucleoplasm and suppression of new preribosomal RNA synthesis occurs in both neonatal rat cardiomyocytes (NRCM) and cardiac progenitor cells (CPC) upon exposure to doxorubicin or actinomycin D. Silencing of NS significantly increases cell death resulting from doxorubicin treatment in CPC, whereas NPM knockdown alone induces cell death. Overexpression of either NS or NPM significantly decreases caspase 8 activity in cultured cardiomyocytes challenged with doxorubicin. The presence of altered nucleolar structures resulting from myocardial infarction in mice supports the model of nucleolar stress as a general response to pathological injury. Collectively, these findings serve as the initial description of myocardial nucleolar stress and establish the postulate that nucleoli acts as sensors of stress, regulating the cellular response to pathological insults.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
    Publication Date: 2014-08-01
    Description: Haematopoietic stem cells (HSCs) self-renew for life, thereby making them one of the few blood cells that truly age. Paradoxically, although HSCs numerically expand with age, their functional activity declines over time, resulting in degraded blood production and impaired engraftment following transplantation. While many drivers of HSC ageing have been proposed, the reason why HSC function degrades with age remains unknown. Here we show that cycling old HSCs in mice have heightened levels of replication stress associated with cell cycle defects and chromosome gaps or breaks, which are due to decreased expression of mini-chromosome maintenance (MCM) helicase components and altered dynamics of DNA replication forks. Nonetheless, old HSCs survive replication unless confronted with a strong replication challenge, such as transplantation. Moreover, once old HSCs re-establish quiescence, residual replication stress on ribosomal DNA (rDNA) genes leads to the formation of nucleolar-associated gammaH2AX signals, which persist owing to ineffective H2AX dephosphorylation by mislocalized PP4c phosphatase rather than ongoing DNA damage. Persistent nucleolar gammaH2AX also acts as a histone modification marking the transcriptional silencing of rDNA genes and decreased ribosome biogenesis in quiescent old HSCs. Our results identify replication stress as a potent driver of functional decline in old HSCs, and highlight the MCM DNA helicase as a potential molecular target for rejuvenation therapies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456040/" 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/PMC4456040/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flach, Johanna -- Bakker, Sietske T -- Mohrin, Mary -- Conroy, Pauline C -- Pietras, Eric M -- Reynaud, Damien -- Alvarez, Silvia -- Diolaiti, Morgan E -- Ugarte, Fernando -- Forsberg, E Camilla -- Le Beau, Michelle M -- Stohr, Bradley A -- Mendez, Juan -- Morrison, Ciaran G -- Passegue, Emmanuelle -- F32 HL106989/HL/NHLBI NIH HHS/ -- R01 CA184014/CA/NCI NIH HHS/ -- R01 HL092471/HL/NHLBI NIH HHS/ -- R01 HL115158/HL/NHLBI NIH HHS/ -- T32 AI007334/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Aug 14;512(7513):198-202. doi: 10.1038/nature13619. Epub 2014 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Department of Medicine, Hem/Onc Division, University of California San Francisco, San Francisco, California 94143, USA [2] Institute of Experimental Cancer Research, Comprehensive Cancer Center, 89081 Ulm, Germany. ; The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Department of Medicine, Hem/Onc Division, University of California San Francisco, San Francisco, California 94143, USA. ; Center for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland. ; Spanish National Cancer Research Centre (CNIO), E-28049 Madrid, Spain. ; Department of Pathology, University of California San Francisco, San Francisco, California 94143, USA. ; Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California 95064, USA. ; Section of Hematology/Oncology and the Comprehensive Cancer Center, University of Chicago, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079315" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Aging/genetics/*physiology ; Cell Proliferation ; DNA Damage/genetics ; DNA Replication/*physiology ; DNA, Ribosomal/genetics ; Female ; Gene Expression Regulation ; Hematopoietic Stem Cells/cytology/*pathology ; Histones/genetics/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Minichromosome Maintenance Proteins/genetics ; *Stress, Physiological
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2014-02-28
    Description: Sirtuins can promote deacetylation of a wide range of substrates in diverse cellular compartments and regulate many cellular processes(1),(2). Recently Narayan et al., reported that SIRT2 was required for necroptosis based on their findings that SIRT2 inhibition, knock-down or knock-out prevented necroptosis. We sought to confirm and explore the role of SIRT2 in necroptosis and tested four different sources of the SIRT2 inhibitor AGK2, three independent siRNAs against SIRT2, and cells from two independently generated Sirt2-/- mouse strains, however we were unable to show that inhibiting or depleting SIRT2 protected cells from necroptosis. Furthermore, Sirt2-/- mice succumbed to TNF induced Systemic Inflammatory Response Syndrome (SIRS) more rapidly than wild type mice while Ripk3-/- mice were resistant. Our results therefore question the importance of SIRT2 in the necroptosis cell death pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005920/" 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/PMC4005920/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Newton, Kim -- Hildebrand, Joanne M -- Shen, Zhirong -- Rodriguez, Diego -- Alvarez-Diaz, Silvia -- Petersen, Sean -- Shah, Saumil -- Dugger, Debra L -- Huang, Chunzi -- Auwerx, Johan -- Vandenabeele, Peter -- Green, Douglas R -- Ashkenazi, Avi -- Dixit, Vishva M -- Kaiser, William J -- Strasser, Andreas -- Degterev, Alexei -- Silke, John -- P30 CA021765/CA/NCI NIH HHS/ -- R01 AI044828/AI/NIAID NIH HHS/ -- R01 CA169291/CA/NCI NIH HHS/ -- England -- Nature. 2014 Feb 27;506(7489):E4-6. doi: 10.1038/nature13024.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genentech, Inc., South San Francisco, California 94080, USA. ; 1] The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia. ; National Institute of Biological Sciences, Zhongguancun Life Science Park, Beijing 102206, China. ; Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; Department of Biochemistry, Tufts University, Boston, Massachusetts 02111, USA. ; Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA. ; Laboratory of Integrative and Systems Physiology, EPFL, CH-1015 Lausanne, Switzerland. ; 1] Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Gent, Belgium [2] Department of Biomedical Molecular Biology, Ghent University, 9052 Gent, Belgium [3] Methusalem BOF09/01M00709, Ghent University, 9052 Gent, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24572428" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Humans ; Male ; Necrosis/*enzymology ; Sirtuin 2/*genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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