10 research outputs found

    Positional variations among heterogeneous nucleosome maps give dynamical information on chromatin

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    Although nucleosome remodeling is essential to transcriptional regulation in eukaryotes, little is known about its genome-wide behavior. Since a number of nucleosome positioning maps in vivo have been recently determined, we examined if their comparisons might be used for obtaining a genome-wide profile of nucleosome remodeling. Using seven yeast maps, the local variability of nucleosomes, measured by the entropy, was significantly higher in a set of reported unstable nucleosomes. The binding sites of four transcription factors, known as the remodeling factors, were distinctively high both in entropy and linker ratio, whereas those of Yhp1, their potential inhibitor, showed the lowest values in both of them. Taken together, our map shows the general information of nucleosome dynamics reasonably well. The “nucleosome dynamics” map provides the new significant correlation with the degree of expression variety instead of their intensity. Furthermore, the associations with gene function and histone modification were also discussed here

    High cell density increases glioblastoma cell viability under glucose deprivation via degradation of the cystine/glutamate transporter xCT (SLC7A11)

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    The cystine/glutamate transporter system x c − consists of the light-chain subunit xCT (SLC7A11) and the heavy-chain subunit CD98 (4F2hc or SLC3A2) and exchanges extracellular cystine for intracellular glutamate at the plasma membrane. The imported cystine is reduced to cysteine and used for synthesis of GSH, one of the most important antioxidants in cancer cells. Because cancer cells have increased levels of reactive oxygen species, xCT, responsible for cystine–glutamate exchange, is overexpressed in many cancers, including glioblastoma. However, under glucose-limited conditions, xCT overexpression induces reactive oxygen species accumulation and cell death. Here we report that cell survival under glucose deprivation depends on cell density. We found that high cell density (HD) down-regulates xCT levels and increases cell viability under glucose deprivation. We also found that growth of glioblastoma cells at HD inactivates mTOR and that treatment of cells grown at low density with the mTOR inhibitor Torin 1 down-regulates xCT and inhibits glucose deprivation-induced cell death. The lysosome inhibitor bafilomycin A1 suppressed xCT down-regulation in HD-cultured glioblastoma cells and in Torin 1–treated cells grown at low density. Additionally, bafilomycin A1 exposure or ectopic xCT expression restored glucose deprivation–induced cell death at HD. These results suggest that HD inactivates mTOR and promotes lysosomal degradation of xCT, leading to improved glioblastoma cell viability under glucose-limited conditions. Our findings provide evidence that control of xCT protein expression via lysosomal degradation is an important mechanism for metabolic adaptation in glioblastoma cells

    Global population structure of the Serratia marcescens complex and identification of hospital-adapted lineages in the complex

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    International audienceSerratia marcescens is an important nosocomial pathogen causing various opportunistic infections, such as urinary tract infections, bacteremia and sometimes even hospital outbreaks. The recent emergence and spread of multidrug-resistant (MDR) strains further pose serious threats to global public health. This bacterium is also ubiquitously found in natural environments, but the genomic differences between clinical and environmental isolates are not clear, including those between S. marcescens and its close relatives. In this study, we performed a large-scale genome analysis of S. marcescens and closely related species (referred to as the ‘ S. marcescens complex’), including more than 200 clinical and environmental strains newly sequenced here. Our analysis revealed their phylogenetic relationships and complex global population structure, comprising 14 clades, which were defined based on whole-genome average nucleotide identity. Clades 10, 11, 12 and 13 corresponded to S. nematodiphila , S. marcescens sensu stricto , S. ureilytica and S. surfactantfaciens , respectively. Several clades exhibited distinct genome sizes and GC contents and a negative correlation of these genomic parameters was observed in each clade, which was associated with the acquisition of mobile genetic elements (MGEs), but different types of MGEs, plasmids or prophages (and other integrative elements), were found to contribute to the generation of these genomic variations. Importantly, clades 1 and 2 mostly comprised clinical or hospital environment isolates and accumulated a wide range of antimicrobial resistance genes, including various extended-spectrum ÎČ-lactamase and carbapenemase genes, and fluoroquinolone target site mutations, leading to a high proportion of MDR strains. This finding suggests that clades 1 and 2 represent hospital-adapted lineages in the S. marcescens complex although their potential virulence is currently unknown. These data provide an important genomic basis for reconsidering the classification of this group of bacteria and reveal novel insights into their evolution, biology and differential importance in clinical settings

    IODP expedition 317 : exploring the record of sea-level change off New Zealand

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    Expedition 317 investigated the record of global sea-level change (eustasy) within continental margin sedimentary sequences and how eustasy interacts with local forcing to produce preserved sedimentary architectures. The Canterbury Basin, on the eastern margin of the South Island of New Zealand, was selected to study these complex interactions because of high rates of Neogene sediment supply from the uplifting Southern Alps. This sediment input results in a high frequency (~0.1–0.5 My periods) record of depositional cyclicity that is modulated by the presence of strong ocean currents. The expedition recovered sediments as old as Eocene but focused on the sequence stratigraphy of the late Miocene to Recent, when global sea-level change was dominated by glacioeustasy. A transect of three sites was drilled on the continental shelf (Sites U1353, U1354, and U1351), plus one on the continental slope (Site U1352). The transect samples the shallow-water environment most directly affected by relative sea-level change. Lithologic boundaries, provisionally correlative with seismic sequence boundaries, have been identified in cores from each site. Continental slope Site U1352 provides a record of ocean circulation and fronts during the last ~35 My. The early Oligocene (~30 Ma) Marshall Paraconformity was the deepest target of Expedition 317 and is hypothesized to represent intensified current erosion or non-deposition associated with the initiation of thermohaline circulation in the region. Expedition 317 involved operational challenges for JOIDES Resolution, including shallow-water, continental-shelf drilling and deep penetrations. Despite these challenges, Expedition 317 set a number of records for scientific ocean drilling penetration and water-depth.11 page(s

    Proceedings of the Integrated Ocean Drilling Program. Canterbury Basin Sea Level

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    [Extract - Foreword] The Integrated Ocean Drilling Program (IODP) is now in the latter half of its decadal program (2003–2013). As envisioned in the Initial Science Plan (ISP), IODP expeditions take advantage of three scientific ocean drilling platforms that enable us to cover unprecedented areas of wide oceans, from ice-covered shallow water to full ocean depths. Drilling miles of depth below seafloor, now part of IODP capabilities, is the major advance from the program predecessors, the Deep Sea Drilling Project and the Ocean Drilling Program. The living Earth is a dynamic system that is continuously evolving. IODP seeks to understand this complex and unique system through scientific ocean drilling, sampling, and experimenting in deep holes, along with advancement of related scientific disciplines. IODP is an international collaboration among scientists and nations with keen aspirations to attain the scientific goals of the ISP. IODP currently includes participating members from 24 nations. The Proceedings present the scientific and engineering results of IODP drilling projects, each designed to better understand the past, present, and future of the Earth system. IODP expeditions begin with scientists who submit research drilling proposals to test new and innovative ideas, then the proposals progress to international scientific advisors (Science Advisory Structure) who nurture, evaluate, rank, and prioritize proposals. Scientists also schedule the science operations, select science party members from scores of international scientists qualified to participate, plan platform operations, ready the drillship, and choose borehole locations. The science party, collectively and individually, conducts science on board and on shore. The co-chief scientists on each expedition are responsible for synthesizing the scientific results as hallmark of expedition. Ocean-drilling achievements help us to understand and interpret phenomena in various parts of the Earth system. Achievements in the two legacy drilling programs have validated the scientific concepts behind plate tectonics, contributed to the understanding of ocean circulation changes, and extended our knowledge of long- and short-term climate change. IODP is truly an expansion and extension of the scientific research conducted by the legacy programs, engaging in cutting-edge research concerning topics of global importance. IODP drilling platform operations are conducted by three Implementing Organizations (IOs). Riserless platform operations are conducted by the U.S. Implementing Organization (USIO), comprising the Consortium for Ocean Leadership, Inc., Texas A&M University through the Texas A&M Research Foundation, and Lamont-Doherty Earth Observatory of Columbia University. Riser platform operations are conducted by the Japan Agency for Marine-Earth Science and Technology through Japan's Center for Deep Earth Exploration in cooperation with the Center for Advanced Marine Core Research at Kochi University. Mission-specific platform operations are conducted by the European Consortium for Ocean Research Drilling (ECORD) Science Operator (ESO), comprising the British Geological Survey, Bremen University, and the European Petrophysics Consortium. The European IO currently represents the ocean-drilling efforts of 16 nations in Europe, plus Canada. The discoveries presented in this volume build upon layers of knowledge and science developed over roughly the last fifty years. Expedition Proceedings are published by IODP Management International for IODP under the sponsorship of the U.S. National Science Foundation (NSF), Japan's Ministry of Education, Culture, Sports, Science and Technology, and other IODP members. The material is based upon research supported under Contract OCE-0432224 from NSF

    Expedition 317 summary

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    Integrated Ocean Drilling Program (IODP) Expedition 317 was devoted to understanding the relative importance of global sea level (eustasy) versus local tectonic and sedimentary processes in controlling continental margin sedimentary cycles. The expedition recovered sediments from the Eocene to recent period, with a particular focus on the sequence stratigraphy of the late Miocene to recent, when global sea level change was dominated by glacioeustasy. Drilling in the Canterbury Basin, on the eastern margin of the South Island of New Zealand, takes advantage of high rates of Neogene sediment supply, which preserves a high-frequency (0.1-0.5 m.y.) record of depositional cyclicity. Because of its proximity to an uplifting mountain chain (the Southern Alps) and strong ocean currents, the Canterbury Basin provides an opportunity to study the complex interactions between processes responsible for the preserved sequence stratigraphic record. Currents have locally built large, elongate sediment drifts within the prograding Neogene section. These elongate drifts were not drilled during Expedition 317, but currents are inferred to have strongly influenced deposition across the basin, including locations lacking prominent mounded drifts. Upper Miocene to recent sedimentary sequences were cored in a transect of three sites on the continental shelf (landward to basinward, Sites U1353, U1354, and U1351) and one on the continental slope (Site U1352). The transect provides a stratigraphic record of depositional cycles across the shallow-water environment most directly affected by relative sea level change. Lithologic boundaries provisionally correlative with seismic sequence boundaries were identified in cores from each site, providing insight into the origins of seismically resolvable sequences. This record will be used to estimate the timing and amplitude of global sea level change and to document the sedimentary processes that operate during sequence formation. Sites U1353 and U1354 provide significant double-cored, high-recovery sections through the Holocene, allowing for high-resolution study of recent glacial cycles in a continental shelf setting. Continental slope Site U1352 represents a complete section from modern slope terrigenous sediment to hard Eocene limestone, with all the associated lithologic, biostratigraphic, physical, geochemical, and microbiological transitions. This site also provides a record of ocean circulation and fronts during the last approximately 35 m. The early Oligocene ( approximately 30 Ma) Marshall Paraconformity was the deepest drilling target of Expedition 317 and was hypothesized to represent intensified current erosion or nondeposition associated with the initiation of thermohaline circulation following the separation of Australia and Antarctica. Expedition 317 set a number of scientific ocean drilling records: (1) deepest hole drilled in a single expedition and second deepest hole in the history of scientific ocean drilling (Hole U1352C, 1927 m); (2) deepest hole and second deepest hole drilled by the R/V JOIDES Resolution on a continental shelf (Hole U1351B, 1030 m; Hole U1353B, 614 m); (3) shallowest water depth for a site drilled by the JOIDES Resolution for scientific purposes (Site U1353, 84.7 m water depth); and (4) deepest sample taken during scientific ocean drilling for microbiological studies (Site U1352, 1925 m). Expedition 317 supplements previous drilling of sedimentary successions for sequence stratigraphic and sea level objectives, particularly drilling on the New Jersey margin (Ocean Drilling Program [ODP] Legs 150, 150X, 174A, and 174AX and IODP Expedition 313) and in the Bahamas (ODP Leg 166), but includes an expanded Pliocene section. Completion of at least one transect across a geographically and tectonically distinct siliciclastic margin was the necessary next step in deciphering continental margin stratigraphy. Expedition 317 also complements ODP Leg 181, the focus of which was drift development in more distal parts of the Eastern New Zealand Oceanic Sedimentary System ( ENZOSS).86 page(s

    Activation and Reaction Volumes in Solution. 3

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