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  • Springer Nature  (109,086)
  • Public Library of Science (PLoS)
  • 2015-2019  (118,512)
  • 2019  (61,111)
  • 2016  (57,401)
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  • 2015-2019  (118,512)
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  • 1
    Publication Date: 2016-12-16
    Description: Slope failure like in the Hinlopen/Yermak Megaslide is one of the major geohazards in a changing Arctic environment. We analysed hydroacoustic and 2D high-resolution seismic data from the apparently intact continental slope immediately north of the Hinlopen/Yermak Megaslide for signs of past and future instabilities. Our new bathymetry and seismic data show clear evidence for incipient slope instability. Minor slide deposits and an internally-deformed sedimentary layer near the base of the gas hydrate stability zone imply an incomplete failure event, most probably about 30000 years ago, contemporaneous to or shortly after the Hinlopen/Yermak Megaslide. An active gas reservoir at the base of the gas hydrate stability zone demonstrate that over-pressured fluids might have played a key role in the initiation of slope failure at the studied slope, but more importantly also for the giant HYM slope failure. To date, it is not clear, if the studied slope is fully preconditioned to fail completely in future or if it might be slowly deforming and creeping at present. We detected widespread methane seepage on the adjacent shallow shelf areas not sealed by gas hydrates.
    Repository Name: EPIC Alfred Wegener Institut
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  • 2
    Publication Date: 2017-07-05
    Description: Little is known about the production of fluorescent dissolved organic matter (FDOM) in the anoxic oceanic sediments. In this study, sediment pore waters were sampled from four different sites in the Chukchi-East Siberian Seas area to examine the bulk dissolved organic carbon (DOC) and their optical properties. The production of FDOM, coupled with the increase of nutrients, was observed above the sulfate-methane-transition-zone (SMTZ). The presence of FDOM was concurrent with sulfate reduction and increased alkalinity (R2 〉 0.96, p 〈 0.0001), suggesting a link to organic matter degradation. This inference was supported by the positive correlation (R2 〉 0.95, p 〈 0.0001) between the net production of FDOM and the modeled degradation rates of particulate organic carbon sulfate reduction. The production of FDOM was more pronounced in a shallow shelf site S1 with a total net production ranging from 17.9 to 62.3 RU for different FDOM components above the SMTZ depth of ca. 4.1 mbsf, which presumably underwent more accumulation of particulate organic matter than the other three deeper sites. The sediments were generally found to be the sources of CDOM and FDOM to the overlying water column, unearthing a channel of generally bio-refractory and pre-aged DOM to the oceans.
    Repository Name: EPIC Alfred Wegener Institut
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  • 3
    Publication Date: 2021-02-16
    Description: The deglacial history of CO2 release from the deep North Pacific remains unresolved. This is due to conflicting indications about subarctic Pacific ventilation changes based on various marine proxies, especially for Heinrich Stadial 1 (HS-1) when a rapid atmospheric CO2 rise occurs. Here, we use a complex Earth System Model to investigate the deglacial North Pacific overturning and its control on ocean stratification. Our results show an enhanced intermediate-to-deep ocean stratification coeval with intensified North Pacific Intermediate Water (NPIW) formation during HS-1, compared to the Last Glacial Maximum. The stronger NPIW formation causes lower salinities and higher temperatures at intermediate depths. By lowering NPIW densities, this enlarges vertical density gradient and thus enhances intermediate-to-deep ocean stratification during HS-1. Physically, this process prevents the North Pacific deep waters from a better communication with the upper oceans, thus prolongs the existing isolation of glacial Pacific abyssal carbons during HS-1.
    Repository Name: EPIC Alfred Wegener Institut
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  • 4
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    Springer Nature
    In:  EPIC3Magnetic Resonance Materials in Physics, Biology and Medicine, Springer Nature, ISSN: 1352-8661
    Publication Date: 2019-05-27
    Description: An approach is presented for high-field MRI studies of the cardiovascular system (CVS) of a marine crustacean, the edible crab Cancer pagurus, submerged in highly conductive seawater. Structure and function of the CVS were investigated at 9.4 T. Cardiac motion was studied using self-gated CINE MRI. Imaging protocols and radio-frequency coil arrangements were tested for anatomical imaging. Haemolymph flow was quantified using phase-contrast angiography. Signal-to-noise-ratios and flow velocities in afferent and efferent branchial veins were compared with Student’s t test (n = 5). Seawater induced signal losses were dependent on imaging protocols and RF coil setup. Internal cardiac structures could be visualized with high spatial resolution within 8 min using a gradient-echo technique. Variations in haemolymph flow in different vessels could be determined over time. Maximum flow was similar within individual vessels and corresponded to literature values from Doppler measurements. Heart contractions were more pronounced in lateral and dorso-ventral directions than in the anterior–posterior direction. Choosing adequate imaging protocols in combination with a specific RF coil arrangement allows to monitor various parts of the crustacean CVS with exceptionally high spatial resolution despite the adverse effects of seawater at 9.4 T.
    Repository Name: EPIC Alfred Wegener Institut
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  • 5
    Publication Date: 2022-05-25
    Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Gruen, D. S., Wolfe, J. M., & Fournier, G. P.. Paleozoic diversification of terrestrial chitin-degrading bacterial lineages. BMC Evolutionary Biology, 19, (2019): 34, doi:10.1186/s12862-019-1357-8.
    Description: Background Establishing the divergence times of groups of organisms is a major goal of evolutionary biology. This is especially challenging for microbial lineages due to the near-absence of preserved physical evidence (diagnostic body fossils or geochemical biomarkers). Horizontal gene transfer (HGT) can serve as a temporal scaffold between microbial groups and other fossil-calibrated clades, potentially improving these estimates. Specifically, HGT to or from organisms with fossil-calibrated age estimates can propagate these constraints to additional groups that lack fossils. While HGT is common between lineages, only a small subset of HGT events are potentially informative for dating microbial groups. Results Constrained by published fossil-calibrated studies of fungal evolution, molecular clock analyses show that multiple clades of Bacteria likely acquired chitinase homologs via HGT during the very late Neoproterozoic into the early Paleozoic. These results also show that, following these HGT events, recipient terrestrial bacterial clades likely diversified ~ 300–500 million years ago, consistent with established timescales of arthropod and plant terrestrialization. Conclusions We conclude that these age estimates are broadly consistent with the dispersal of chitinase genes throughout the microbial world in direct response to the evolution and ecological expansion of detrital-chitin producing groups. The convergence of multiple lines of evidence demonstrates the utility of HGT-based dating methods in microbial evolution. The pattern of inheritance of chitinase genes in multiple terrestrial bacterial lineages via HGT processes suggests that these genes, and possibly other genes encoding substrate-specific enzymes, can serve as a “standard candle” for dating microbial lineages across the Tree of Life.
    Description: This work was supported by a National Science Foundation (NSF) Graduate Research Fellowship Program Award to DSG., and Simons Collaboration on the Origins of Life Award #339603 and NSF Integrated Earth Systems Program Award #1615426 to GPF. The funding agencies for this study had no role in study design, data collection, data analysis and interpretation, or in writing the manuscript.
    Keywords: Horizontal gene transfer ; Chitinase ; Chitin ; Bacteria ; Fungi ; Arthropods
    Repository Name: Woods Hole Open Access Server
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  • 6
    Publication Date: 2019-12-02
    Description: Seismological findings show a complex scenario of plume upwellings from a deep thermo-chemical anomaly (superplume) beneath the East African Rift System (EARS). It is unclear if these geophysical observations represent a true picture of the superplume and its influence on magmatism along the EARS. Thus, it is essential to find a geochemical tracer to establish where upwellings are connected to the deep-seated thermo-chemical anomaly. Here we identify a unique non-volatile superplume isotopic signature (‘C’) in the youngest (after 10 Ma) phase of widespread EARS rift-related magmatism where it extends into the Indian Ocean and the Red Sea. This is the first sound evidence that the superplume influences the EARS far from the low seismic velocities in the magma-rich northern half. Our finding shows for the first time that superplume mantle exists beneath the rift the length of Africa from the Red Sea to the Indian Ocean offshore southern Mozambique
    Repository Name: EPIC Alfred Wegener Institut
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  • 7
    Publication Date: 2022-05-26
    Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in ISME Journal (2019), doi:10.1038/s41396-019-0373-4.
    Description: The benthos in estuarine environments often experiences periods of regularly occurring hypoxic and anoxic conditions, dramatically impacting biogeochemical cycles. How oxygen depletion affects the growth of specific uncultivated microbial populations within these diverse benthic communities, however, remains poorly understood. Here, we applied H218O quantitative stable isotope probing (qSIP) in order to quantify the growth of diverse, uncultured bacterial populations in response to low oxygen concentrations in estuarine sediments. Over the course of 7- and 28-day incubations with redox conditions spanning from hypoxia to euxinia (sulfidic), 18O labeling of bacterial populations exhibited different patterns consistent with micro-aerophilic, anaerobic, facultative anaerobic, and aerotolerant anaerobic growth. 18O-labeled populations displaying anaerobic growth had a significantly non-random phylogenetic distribution, exhibited by numerous clades currently lacking cultured representatives within the Planctomycetes, Actinobacteria, Latescibacteria, Verrucomicrobia, and Acidobacteria. Genes encoding the beta-subunit of the dissimilatory sulfate reductase (dsrB) became 18O labeled only during euxinic conditions. Sequencing of these 18O-labeled dsrB genes showed that Acidobacteria were the dominant group of growing sulfate-reducing bacteria, highlighting their importance for sulfur cycling in estuarine sediments. Our findings provide the first experimental constraints on the redox conditions underlying increased growth in several groups of “microbial dark matter”, validating hypotheses put forth by earlier metagenomic studies.
    Description: This work was supported by a grant OR 417/1-1 from the Deutsche Forschungsgemeinschaft, and a Junior Researcher Fund grant from LMU Munich to WDO. This work was performed in part, through the Master’s Program in Geobiology and Paleontology (MGAP) at LMU Munich.
    Repository Name: Woods Hole Open Access Server
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  • 8
    Publication Date: 2022-05-26
    Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Trembath-Reichert, E., Butterfield, D. A., & Huber, J. A. Active subseafloor microbial communities from Mariana back-arc venting fluids share metabolic strategies across different thermal niches and taxa. Isme Journal, 13(9), (2019): 2264-2279, doi: 10.1038/s41396-019-0431-y.
    Description: There are many unknowns regarding the distribution, activity, community composition, and metabolic repertoire of microbial communities in the subseafloor of deep-sea hydrothermal vents. Here we provide the first characterization of subseafloor microbial communities from venting fluids along the central Mariana back-arc basin (15.5–18°N), where the slow-spreading rate, depth, and variable geochemistry along the back-arc distinguish it from other spreading centers. Results indicated that diverse Epsilonbacteraeota were abundant across all sites, with a population of high temperature Aquificae restricted to the northern segment. This suggests that differences in subseafloor populations along the back-arc are associated with local geologic setting and resultant geochemistry. Metatranscriptomics coupled to stable isotope probing revealed bacterial carbon fixation linked to hydrogen oxidation, denitrification, and sulfide or thiosulfate oxidation at all sites, regardless of community composition. NanoSIMS (nanoscale secondary ion mass spectrometry) incubations at 80 °C show only a small portion of the microbial community took up bicarbonate, but those autotrophs had the highest overall rates of activity detected across all experiments. By comparison, acetate was more universally utilized to sustain growth, but within a smaller range of activity. Together, results indicate that microbial communities in venting fluids from the Mariana back-arc contain active subseafloor communities reflective of their local conditions with metabolisms commonly shared across geologically disparate spreading centers throughout the ocean.
    Description: This work was funded by the NOAA Ocean Exploration and Research (OER) Program, the NSF Center for Dark Energy Biosphere Investigations (C-DEBI) (OCE-0939564), and NOAA/PMEL and JISAO under NOAA Cooperative Agreement NA15OAR4320063. ETR was supported by a NASA Postdoctoral Fellowship with the NASA Astrobiology Institute and a L’Oréal USA For Women in Science Fellowship. The data collected in this study includes work supported by the Schmidt Ocean Institute during cruise FK161129 aboard R/V Falkor. We thank the captains and crews of the R/V Falkor and ROV SuBastian. Critical support in cruise planning and sampling at sea was carried out by Andra Bobbitt, Bill Chadwick, Bob Embley, Ben Larson, and Kevin Roe. Caroline Fortunato, Connor Skennerton, Rika Anderson, Karthik Anantharaman, Jaclyn Saunders, Hank Yu, Lewis Ward, Elaina Graham, and Ben Tully aided bioinformatics pipeline development and Victoria Orphan and Yunbin Guan aided with NanoSIMS analysis. This is C-DEBI Contribution 470, JISAO Contribution 2018-0173, and PMEL Contribution 4867.
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  • 9
    Publication Date: 2022-05-26
    Description: Author Posting. © The Author(s), 2019. This is the author's version of the work. It is posted here by permission of Springer Nature for personal use, not for redistribution. The definitive version was published in Zakroff, C., Mooney, T.A. & Wirth, C. Ocean acidification responses in paralarval squid swimming behavior using a novel 3D tracking system. Hydrobiologia, 808(1),(2018):83-106, doi:10.1007/s10750-017-3342-9.
    Description: Chronic embryonic exposure to ocean acidification (OA) has been shown to degrade the aragonitic statolith of paralarval squid, Doryteuthis pealeii, a key structure for their swimming behavior. This study examined if day-of-hatching paralarval D. pealeii from eggs reared under chronic OA demonstrated measurable impairments to swimming activity and control. This required the development of a novel, cost-effective, and robust method for 3D motion tracking and analysis. Squid eggs were reared in pCO2 levels in a dose-dependent manner ranging from 400 - 2200 ppm. Initial 2D experiments showed paralarvae in higher acidification environments spent more time at depth. In 3D experiments, velocity, particularly positive and negative vertical velocities, significantly decreased from 400 to 1000 ppm pCO2, but showed non-significant decreases at higher concentrations. Activity and horizontal velocity decreased linearly with increasing pCO2, indicating a subtle impact to paralarval energetics. Patterns may have been obscured by notable individual variability in the paralarvae. Responses were also seen to vary between trials on cohort or potentially annual scales. Overall, paralarval swimming appeared resilient to OA, with effects being slight. The newly developed 3D tracking system provides a powerful and accessible method for future studies to explore similar questions in the larvae of aquatic taxa.
    Description: We thank D. Remsen, the MBL Marine Resources Center staff, and MBL Gemma crew for their support in acquiring squid. R. Galat and the facilities staff of the WHOI ESL provided system support. D. McCorkle, KYK Chan, and M. White provided valuable insight on the OA system. E. Moberg, A. Beet, and A. Solow assisted in the development and coding of the 3D model system. We also thank E. Bonk, K. Hoering, M. Lee, D. Weiler, and A. Schlunk for their assistance and input with the experiments. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. 1122374. This project is funded by NSF Grant No. 1220034.
    Keywords: Hypercapnia ; Cephalopod ; Larvae ; Movement analysis ; Stress physiology
    Repository Name: Woods Hole Open Access Server
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  • 10
    Publication Date: 2022-05-26
    Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Chen, R.; Park, H. A.; Mnatsakanyan, N.; Niu, Y.; Licznerski, P.; Wu, J.; Miranda, P.; Graham, M.; Tang, J.; Boon, A. J. W.; Cossu, G.; Mandemakers, W.; Bonifati, V.; Smith, P. J. S.; Alavian, K. N.; Jonas, E. A. Parkinson's disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth. Cell Death & Disease, 10(6), (2019):469, doi:10.1038/s41419-019-1679-x.
    Description: Familial Parkinson’s disease (PD) protein DJ-1 mutations are linked to early onset PD. We have found that DJ-1 binds directly to the F1FO ATP synthase β subunit. DJ-1’s interaction with the β subunit decreased mitochondrial uncoupling and enhanced ATP production efficiency while in contrast mutations in DJ-1 or DJ-1 knockout increased mitochondrial uncoupling, and depolarized neuronal mitochondria. In mesencephalic DJ-1 KO cultures, there was a progressive loss of neuronal process extension. This was ameliorated by a pharmacological reagent, dexpramipexole, that binds to ATP synthase, closing a mitochondrial inner membrane leak and enhancing ATP synthase efficiency. ATP synthase c-subunit can form an uncoupling channel; we measured, therefore, ATP synthase F1 (β subunit) and c-subunit protein levels. We found that ATP synthase β subunit protein level in the DJ-1 KO neurons was approximately half that found in their wild-type counterparts, comprising a severe defect in ATP synthase stoichiometry and unmasking c-subunit. We suggest that DJ-1 enhances dopaminergic cell metabolism and growth by its regulation of ATP synthase protein components.
    Description: The research was supported by NIH (NS081746) to E.A.J., W.M. and V.B. are supported by the Stichting Parkinson Fonds (The Netherlands).
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  • 11
    Publication Date: 2022-05-26
    Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Millette, N. C., Kelble, C., Linhoss, A., Ashby, S., & Visser, L. Using spatial variability in the rate of change of chlorophyll a to improve water quality management in a subtropical oligotrophic estuary. Estuaries and Coasts, 42(7), (2019): 1792-1803, doi:10.1007/s12237-019-00610-5.
    Description: Anthropogenic eutrophication threatens numerous aquatic ecosystems across the globe. Proactive management that prevents a system from becoming eutrophied is more effective and cheaper than restoring a eutrophic system, but detecting early warning signs and problematic nutrient sources in a relatively healthy system can be difficult. The goal of this study was to investigate if rates of change in chlorophyll a and nutrient concentrations at individual stations can be used to identify specific areas that need to be targeted for management. Biscayne Bay is a coastal embayment in southeast Florida with primarily adequate water quality that has experienced rapid human population growth over the last century. Water quality data collected at 48 stations throughout Biscayne Bay over a 20-year period (1995–2014) were examined to identify any water quality trends associated with eutrophication. Chlorophyll a and phosphate concentrations have increased throughout Biscayne Bay, which is a primary indicator of eutrophication. Moreover, chlorophyll a concentrations throughout the northern area, where circulation is restricted, and in nearshore areas of central Biscayne Bay are increasing at a higher rate compared to the rest of the Bay. This suggests increases in chlorophyll a are due to local nutrient sources from the watershed. These areas are also where recent seagrass die-offs have occurred, suggesting an urgent need for management intervention. This is in contrast with the state of Florida listing of Biscayne Bay as a medium priority impaired body of water.
    Description: Data provided by the SERC-FIU/SFWMD Water Quality Monitoring Network is supported by SFWMD/SERC Cooperative Agreement #4600000352 as well as EPA Agreement #X7-96410603-3. This research was also funded by a NOAA/Atlantic Oceanographic and Meteorological Laboratory grant to the Northern Gulf Institute (award number NA160AR4320199).
    Keywords: Chlorophyll a ; Eutrophication ; Oligotrophic ; Ecological indicators
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  • 12
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    Springer Nature
    In:  EPIC3Advances in Polar Ecology 2, The Ecosystem of Kongsfjorden, Svalbard, Switzerland, Springer Nature, 2, pp. 303-330, ISSN: 2468-5712
    Publication Date: 2023-06-21
    Description: Organisms in shallow waters at high latitudes are under pressure due to climate change. These areas are typically inhabited by microphytobenthos (MPB) communities, composed mainly of diatoms. Only sparse information is available on the ecophysiology and acclimation processes within MPBs from Arctic regions. The physico-chemical environment and the ecology and ecophysiology of benthic diatoms in Kongsfjorden (Svalbard, Norway) are addressed in this review. MPB biofilms cover extensive areas of sediment. They show high rates of primary production, stabilise sediment surfaces against erosion under hydrodynamic forces,and affect the exchange of oxygen and nutrients across the sediment-water interface. Additionally, this phototrophic community represents a key component in the functioning of the Kongsfjorden trophic web, particularly as a major food source for benthic suspension- or deposit-feeders. MPB in Kongsfjorden is confronted with pronounced seasonal variations in solar radiation, low temperatures, and hyposaline (meltwater) conditions in summer, as well as long periods of ice and snow cover in winter. From the few data available, it seems that these organisms can easily cope with these environmental extremes. The underlying physiological mechanisms that allow growth and photosynthesis to continue under widely varying abiotic parameters, along with vertical migration and heterotrophy, and biochemical features such as a pronounced fatty-acid metabolism and silicate incorporation are discussed. Existing gaps in our knowledge of benthic diatoms in Kongsfjorden, such as the chemical ecology of biotic interactions, need to be filled. In addition, since many of the underlying molecular acclimation mechanisms are poorly understood, modern approaches based on transcriptomics, proteomics, and/or metabolomics, in conjunction with cell biological and biochemical techniques, are urgently needed. Climate change models for the Arctic predict other multifactorial stressors, such as an increase in precipitation and permafrost thawing, with consequences for the shallow-water regions. Both precipitation and permafrost thawing are likely to increase nutrient-enriched, turbid freshwater runoff and may locally counteract the expected increase in coastal radiation availability. So far, complex interactions among factors, as well as the full genetic diversity and physiological plasticity of Arctic benthic diatoms, have only rarely been considered. The limited existing information is described and discussed in this review.
    Repository Name: EPIC Alfred Wegener Institut
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  • 13
    Publication Date: 2023-09-22
    Description: Effects of temperature changes on phytoplankton communities seem to be highly context-specific, but few studies have analyzed whether this context specificity depends on differences in the abiotic conditions or in species composition between studies. We present an experiment that allows disentangling the contribution of abiotic and biotic differences in shaping the response to two aspects of temperature change: permanent increase of mean temperature versus pulse disturbance in form of a heat wave. We used natural communities from six different sites of a floodplain system as well as artificially mixed communities from laboratory cultures and grew both, artificial and natural communities, in water from the six different floodplain lakes (sites). All 12 contexts (2 communities × 6 sites) were first exposed to three different temperature levels (12, 18, 24 °C, respectively) and afterward to temperature pulses (4 °C increase for 7 h day(-1)). Temperature-dependent changes in biomass and community composition depended on the initial composition of phytoplankton communities. Abiotic conditions had a major effect on biomass of phytoplankton communities exposed to different temperature conditions, however, the effect of biotic and abiotic conditions together was even more pronounced. Additionally, phytoplankton community responses to pulse temperature effects depended on the warming history. By disentangling abiotic and biotic effects, our study shows that temperature-dependent effects on phytoplankton communities depend on both, biotic and abiotic constraints.
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  • 14
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    Springer Nature
    In:  EPIC3Scientific Reports, Springer Nature, 9(1), pp. 12268-12268, ISSN: 2045-2322
    Publication Date: 2023-09-25
    Description: Identifying stabilizing factors in foodwebs is a long standing challenge with wide implications for community ecology and conservation. Here, we investigate the stability of spatially resolved meta-foodwebs with far-ranging super-predators for whom the whole meta-foodwebs appears to be a single habitat. By using a combination of generalized modeling with a master stability function approach, we are able to efficiently explore the asymptotic stability of large classes of realistic many-patch meta-foodwebs. We show that meta-foodwebs with far-ranging top predators are more stable than those with localized top predators. Moreover, adding far-ranging generalist top predators to a system can have a net stabilizing effect. These results highlight the importance of top predator conservation.
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  • 15
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    Springer Nature
    In:  EPIC3BIOspektrum, Springer Nature, 25(1), pp. 50-57, ISSN: 0947-0867
    Publication Date: 2024-05-03
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  • 16
    Publication Date: 2019-05-08
    Print ISSN: 1078-8956
    Electronic ISSN: 1546-170X
    Topics: Biology , Medicine
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  • 17
    Publication Date: 2019-08-26
    Print ISSN: 1465-7392
    Electronic ISSN: 1476-4679
    Topics: Biology , Medicine
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  • 18
    Publication Date: 2019-11-27
    Print ISSN: 1754-2189
    Electronic ISSN: 1750-2799
    Topics: Natural Sciences in General
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  • 19
    Publication Date: 2019-12-01
    Description: We evaluated whether the central nervous system (CNS) chooses muscle activations not only to achieve behavioral goals but also to minimize stresses and strains within joints. We analyzed the coordination between quadriceps muscles during locomotion in rats before and after imposing a lateral force on the patella. Vastus lateralis (VL) and vastus medialis (VM) in the rat produce identical knee torques but opposing mediolateral patellar forces. If the CNS regulates internal joint stresses, we predicted that after imposing a lateral patellar load by attaching a spring between the patella and lateral femur, the CNS would reduce the ratio between VL and VM activation to minimize net mediolateral patellar forces. Our results confirmed this prediction, showing that VL activation was reduced after attaching the spring whereas VM and rectus femoris (RF) activations were not significantly changed. This adaptation was reversed after the spring was detached. These changes were not observed immediately after attaching the spring but only developed after 3–5 days, suggesting that they reflected gradual processes rather than immediate compensatory reflexes. Overall, these results support the hypothesis that the CNS chooses muscle activations to regulate internal joint variables.
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
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  • 20
    Publication Date: 2019-09-23
    Print ISSN: 1471-0056
    Electronic ISSN: 1471-0064
    Topics: Biology , Medicine
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  • 21
    Publication Date: 2019-09-24
    Description: Pesticide use is one of the main causes of pollinator declines in agricultural ecosystems. Traditionally, most laboratory studies on bee ecotoxicology test acute exposure to single compounds. However, under field conditions, bees are often chronically exposed to a variety of chemicals, with potential synergistic effects. We studied the effects of field-realistic concentrations of three pesticides measured in pollen and nectar of commercial melon fields on the solitary bee Osmia bicornis L. We orally exposed females of this species throughout their life span to 8 treatments combining two neonicotinoid insecticides (acetamiprid, imidacloprid) and a triazole fungicide (myclobutanil) via pollen and sugar syrup. We measured pollen and syrup consumption, longevity, ovary maturation and thermogenesis. Although bees consumed larger amounts of syrup than pollen, pesticide intake via syrup and pollen were similar. At the tested concentrations, no synergistic effects emerged, and we found no effects on longevity and ovary maturation. However, all treatments containing imidacloprid resulted in suppressed syrup consumption and drastic decreases in thoracic temperature and bee activity. Our results have important implications for pesticide regulation. If we had measured only lethal effects we would have wrongly concluded that the pesticide combinations containing imidacloprid were safe to O. bicornis. The incorporation of tests specifically intended to detect sublethal effects in bee risk assessment schemes should be an urgent priority. In this way, the effects of pesticide exposure on the dynamics of bee populations in agroecosystems will be better assessed.
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
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  • 22
    Publication Date: 2019-02-27
    Description: Phosphorylation of the translation initiation factor eIF2α within the mediobasal hypothalamus is known to suppress food intake, but the role of the eIF2α phosphatases in regulating body weight is poorly understood. Mice deficient in active PPP1R15A, a stress-inducible eIF2α phosphatase, are healthy and more resistant to endoplasmic reticulum stress than wild type controls. We report that when female Ppp1r15a mutant mice are fed a high fat diet they gain less weight than wild type littermates owing to reduced food intake. This results in healthy leaner Ppp1r15a mutant animals with reduced hepatic steatosis and improved insulin sensitivity, albeit with a possible modest defect in insulin secretion. By contrast, no weight differences are observed between wild type and Ppp1r15a deficient mice fed a standard diet. We conclude that female mice lacking the C-terminal PP1-binding domain of PPP1R15A show reduced dietary intake and preserved glucose tolerance. Our data indicate that this results in reduced weight gain and protection from diet-induced obesity.
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
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  • 23
    Publication Date: 2016-03-17
    Description: Hepes simplex Virus type 1 (HSV-1) is an enveloped DNA virus that can cause lytic and latent infection. miRNAs post-transcriptionally regulate gene expression and our previous work has indicated that HSV-1 infection induces miR-101 expression in HeLa cells. The present study demonstrates that HSV-1-induced miR-101 is mainly derived from its precursor hsa-mir-101-2 and the HSV-1 immediate early gene ICP4 (infected-cell polypeptide 4) directly binds to the hsa-mir-101-2 promoter to activate its expression. RNA-binding protein G-rich sequence factor 1 (GRSF1) was identified as a new target of miR-101; GRSF1 binds to HSV-1 p40 mRNA and enhances its expression, facilitating viral proliferation. Together, ICP4 induces miR-101 expression, which downregulates GRSF1 expression and attenuates the replication of HSV-1. This allows host cells to maintain a permissive environment for viral replication by preventing lytic cell death. These findings indicate that HSV-1 early gene expression modulates host miRNAs to regulate molecular defense mechanisms. This study provides novel insight into host-virus interactions in HSV-1 infection and may contribute to the development of antiviral therapeutics.
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 24
    Publication Date: 2016-03-01
    Description: Distributed optical fibre sensors possess the unique capability of measuring the spatial and temporal map of environmental quantities that can be of great interest for several field applications. Although existing methods for performance enhancement have enabled important progresses in the field, they do not take full advantage of all information present in the measured data, still giving room for substantial improvement over the state-of-the-art. Here we propose and experimentally demonstrate an approach for performance enhancement that exploits the high level of similitude and redundancy contained on the multidimensional information measured by distributed fibre sensors. Exploiting conventional image and video processing, an unprecedented boost in signal-to-noise ratio and measurement contrast is experimentally demonstrated. The method can be applied to any white-noise-limited distributed fibre sensor and can remarkably provide a 100-fold improvement in the sensor performance with no hardware modification.
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 25
    Publication Date: 2019-08-06
    Description: Damage to the corticospinal tract is widely studied following unilateral subcortical stroke, whereas less is known about changes to other sensorimotor pathways. This may be due to the fact that many studies investigated morphological changes in the brain, where the majority of descending and ascending brain pathways are overlapping, and did not investigate the brainstem where they separate. Moreover, these pathways continue passing through separate regions in the spinal cord. Here, using a high-resolution structural MRI of both the brainstem and the cervical spinal cord, we were able to identify a number of microstructurally altered pathways, in addition to the corticospinal tract, post stroke. Moreover, decreases in ipsi-lesional corticospinal tract integrity and increases in contra-lesional medial reticulospinal tract integrity were correlated with motor impairment severity in individuals with stroke.
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
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  • 26
    Publication Date: 2019-08-19
    Description: Migratory birds usually respond to climate change by modifying breeding and/or wintering areas, as well as by reproducing earlier. In addition, changes in winter habitat use or breeding phenology could have important carry-over effects on subsequent breeding success. Here, we studied age- and sex-dependent carry-over effects from wintering to the breeding stage of a small aerial insectivorous long-distance migratory bird, the barn swallows (Hirundo rustica) breeding in Denmark during 1984–2013. First, we used stable isotope analyses combined with ringing recoveries to identify wintering areas. Second, we found that environmental conditions as inferred by Normalized Difference Vegetation Index (NDVI) have improved at the wintering grounds. Third, we used confirmatory path analysis to quantify the indirect effect of winter conditions on subsequent breeding success. Males delayed onset of breeding and raised fewer fledglings in the first brood when ecological conditions during the previous winter improved. This response was age dependent, since yearlings did not respond to this environmental cue but the response was increasingly stronger as males aged. Females showed a similar response to winter conditions, although not statistically significant. These results highlight the importance of studying carry-over effects within the context of climate change, especially in relation to age of individuals.
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 27
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    Publication Date: 2016-07-12
    Description: by Eva R. M. Joosten, Shihab A. Shamma, Christian Lorenzi, Peter Neri Sound waveforms convey information largely via amplitude modulations (AM). A large body of experimental evidence has provided support for a modulation (bandpass) filterbank. Details of this model have varied over time partly reflecting different experimental conditions and diverse datasets from distinct task strategies, contributing uncertainty to the bandwidth measurements and leaving important issues unresolved. We adopt here a solely data-driven measurement approach in which we first demonstrate how different models can be subsumed within a common ‘cascade’ framework, and then proceed to characterize the cascade via system identification analysis using a single stimulus/task specification and hence stable task rules largely unconstrained by any model or parameters. Observers were required to detect a brief change in level superimposed onto random level changes that served as AM noise; the relationship between trial-by-trial noisy fluctuations and corresponding human responses enables targeted identification of distinct cascade elements. The resulting measurements exhibit a dynamic complex picture in which human perception of auditory modulations appears adaptive in nature, evolving from an initial lowpass to bandpass modes (with broad tuning, Q∼1) following repeated stimulus exposure.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
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  • 28
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    Publication Date: 2016-07-12
    Description: by Bihai Shi, Cui Zhang, Caihuan Tian, Jin Wang, Quan Wang, Tengfei Xu, Yan Xu, Carolyn Ohno, Robert Sablowski, Marcus G. Heisler, Klaus Theres, Ying Wang, Yuling Jiao Shoot branching requires the establishment of new meristems harboring stem cells; this phenomenon raises questions about the precise regulation of meristematic fate. In seed plants, these new meristems initiate in leaf axils to enable lateral shoot branching. Using live-cell imaging of leaf axil cells, we show that the initiation of axillary meristems requires a meristematic cell population continuously expressing the meristem marker SHOOT MERISTEMLESS ( STM ). The maintenance of STM expression depends on the leaf axil auxin minimum. Ectopic expression of STM is insufficient to activate axillary buds formation from plants that have lost leaf axil STM expressing cells. This suggests that some cells undergo irreversible commitment to a developmental fate. In more mature leaves, REVOLUTA ( REV ) directly up-regulates STM expression in leaf axil meristematic cells, but not in differentiated cells, to establish axillary meristems. Cell type-specific binding of REV to the STM region correlates with epigenetic modifications. Our data favor a threshold model for axillary meristem initiation, in which low levels of STM maintain meristematic competence and high levels of STM lead to meristem initiation.
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  • 29
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    Publication Date: 2016-07-12
    Description: by Lauren A. Richardson Our first ever Open Highlights explores recent Open Access research into the complex relationship between host and pathogen during the course of an infection, and the factors that determine its eventual outcome.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 30
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    Publication Date: 2016-07-12
    Description: by Cuncong Zhong, Anna Edlund, Youngik Yang, Jeffrey S. McLean, Shibu Yooseph Analyses of metagenome data (MG) and metatranscriptome data (MT) are often challenged by a paucity of complete reference genome sequences and the uneven/low sequencing depth of the constituent organisms in the microbial community, which respectively limit the power of reference-based alignment and de novo sequence assembly. These limitations make accurate protein family classification and abundance estimation challenging, which in turn hamper downstream analyses such as abundance profiling of metabolic pathways, identification of differentially encoded/expressed genes, and de novo reconstruction of complete gene and protein sequences from the protein family of interest. The profile hidden Markov model (HMM) framework enables the construction of very useful probabilistic models for protein families that allow for accurate modeling of position specific matches, insertions, and deletions. We present a novel homology detection algorithm that integrates banded Viterbi algorithm for profile HMM parsing with an iterative simultaneous alignment and assembly computational framework. The algorithm searches a given profile HMM of a protein family against a database of fragmentary MG/MT sequencing data and simultaneously assembles complete or near-complete gene and protein sequences of the protein family. The resulting program, HMM-GRASPx, demonstrates superior performance in aligning and assembling homologs when benchmarked on both simulated marine MG and real human saliva MG datasets. On real supragingival plaque and stool MG datasets that were generated from healthy individuals, HMM-GRASPx accurately estimates the abundances of the antimicrobial resistance (AMR) gene families and enables accurate characterization of the resistome profiles of these microbial communities. For real human oral microbiome MT datasets, using the HMM-GRASPx estimated transcript abundances significantly improves detection of differentially expressed (DE) genes. Finally, HMM-GRASPx was used to reconstruct comprehensive sets of complete or near-complete protein and nucleotide sequences for the query protein families. HMM-GRASPx is freely available online from http://sourceforge.net/projects/hmm-graspx.
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  • 31
    Publication Date: 2016-07-12
    Description: by Dazhe Meng, Manu Dubin, Pei Zhang, Edward J. Osborne, Oliver Stegle, Richard M. Clark, Magnus Nordborg The extent to which epigenetic variation affects complex traits in natural populations is not known. We addressed this question using transcriptome and DNA methylation data from a sample of 135 sequenced A. thaliana accessions. Across individuals, expression was significantly associated with cis -methylation for hundreds of genes, and many of these associations remained significant after taking SNP effects into account. The pattern of correlations differed markedly between gene body methylation and transposable element methylation. The former was usually positively correlated with expression, and the latter usually negatively correlated, although exceptions were found in both cases. Finally, we developed graphical models of causality that adapt to a sample with heavy population structure, and used them to show that while methylation appears to affect gene expression more often than expression affects methylation, there is also strong support for both being independently controlled. In conclusion, although we find clear evidence for epigenetic regulation, both the number of loci affected and the magnitude of the effects appear to be small compared to the effect of SNPs.
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  • 32
    Publication Date: 2016-07-12
    Description: by Minghua Nie, Emily Arner, John Prudden, Lana Schaffer, Steven Head, Michael N. Boddy Posttranslational modifications (PTMs) provide dynamic regulation of the cellular proteome, which is critical for both normal cell growth and for orchestrating rapid responses to environmental stresses, e.g. genotoxins. Key PTMs include ubiquitin, the Small Ubiquitin-like MOdifier SUMO, and phosphorylation. Recently, SUMO-targeted ubiquitin ligases (STUbLs) were found to integrate signaling through the SUMO and ubiquitin pathways. In general, STUbLs are recruited to target proteins decorated with poly-SUMO chains to ubiquitinate them and drive either their extraction from protein complexes, and/or their degradation at the proteasome. In fission yeast, reducing or preventing the formation of SUMO chains can circumvent the essential and DNA damage response functions of STUbL. This result indicates that whilst some STUbL "targets" have been identified, the crucial function of STUbL is to antagonize SUMO chain formation. Herein, by screening for additional STUbL suppressors, we reveal crosstalk between the serine/threonine phosphatase PP2A-Pab1 B55 and the SUMO pathway. A hypomorphic Pab1 B55 mutant not only suppresses STUbL dysfunction, but also mitigates the phenotypes associated with deletion of the SUMO protease Ulp2, or mutation of the STUbL cofactor Rad60. Together, our results reveal a novel role for PP2A-Pab1 B55 in modulating SUMO pathway output, acting in parallel to known critical regulators of SUMOylation homeostasis. Given the broad evolutionary functional conservation of the PP2A and SUMO pathways, our results could be relevant to the ongoing attempts to therapeutically target these factors.
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  • 33
    Publication Date: 2016-07-12
    Description: by Edoardo Pasolli, Duy Tin Truong, Faizan Malik, Levi Waldron, Nicola Segata Shotgun metagenomic analysis of the human associated microbiome provides a rich set of microbial features for prediction and biomarker discovery in the context of human diseases and health conditions. However, the use of such high-resolution microbial features presents new challenges, and validated computational tools for learning tasks are lacking. Moreover, classification rules have scarcely been validated in independent studies, posing questions about the generality and generalization of disease-predictive models across cohorts. In this paper, we comprehensively assess approaches to metagenomics-based prediction tasks and for quantitative assessment of the strength of potential microbiome-phenotype associations. We develop a computational framework for prediction tasks using quantitative microbiome profiles, including species-level relative abundances and presence of strain-specific markers. A comprehensive meta-analysis, with particular emphasis on generalization across cohorts, was performed in a collection of 2424 publicly available metagenomic samples from eight large-scale studies. Cross-validation revealed good disease-prediction capabilities, which were in general improved by feature selection and use of strain-specific markers instead of species-level taxonomic abundance. In cross-study analysis, models transferred between studies were in some cases less accurate than models tested by within-study cross-validation. Interestingly, the addition of healthy (control) samples from other studies to training sets improved disease prediction capabilities. Some microbial species (most notably Streptococcus anginosus ) seem to characterize general dysbiotic states of the microbiome rather than connections with a specific disease. Our results in modelling features of the “healthy” microbiome can be considered a first step toward defining general microbial dysbiosis. The software framework, microbiome profiles, and metadata for thousands of samples are publicly available at http://segatalab.cibio.unitn.it/tools/metaml.
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  • 34
    Publication Date: 2016-07-12
    Description: Path dependence in energy systems and economic development Nature Energy, Published online: 11 July 2016; doi:10.1038/nenergy.2016.98 Cheap energy can encourage economic growth but it can also force economies into specific energy-intensive futures. Roger Fouquet argues that path dependence in energy systems has profound implications for an economy and should be considered carefully before governments make choices about energy provision.
    Electronic ISSN: 2058-7546
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Published by Springer Nature
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  • 35
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    In: PLoS ONE
    Publication Date: 2016-07-12
    Description: by Anja S. Ziegler, Simon J. McIlroy, Poul Larsen, Mads Albertsen, Aviaja A. Hansen, Nicolas Heinen, Per Halkjær Nielsen Membrane fouling presents the greatest challenge to the application of membrane bioreactor (MBR) technology. Formation of biofilms on the membrane surface is the suggested cause, yet little is known of the composition or dynamics of the microbial community responsible. To gain an insight into this important question, we applied 16S rRNA gene amplicon sequencing with a curated taxonomy and fluorescent in situ hybridization to monitor the community of a pilot-scale MBR carrying out enhanced biological nitrogen and phosphorus removal with municipal wastewater. In order to track the dynamics of the fouling process, we concurrently investigated the communities of the biofilm, MBR bulk sludge, and the conventional activated sludge system used to seed the MBR system over several weeks from start-up. As the biofilm matured the initially abundant betaproteobacterial genera Limnohabitans , Hydrogenophaga and Malikia were succeeded by filamentous Chloroflexi and Gordonia as the abundant species. This study indicates that, although putative pioneer species appear, the biofilm became increasingly similar to the bulk community with time. This suggests that the microbial population in bulk water will largely determine the community structure of the mature biofilm.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 36
    Publication Date: 2016-07-12
    Description: by Petra E. Verburg, Graeme Tucker, Wendy Scheil, Jan Jaap H. M. Erwich, Gus A. Dekker, Claire Trelford Roberts Objectives Sexual inequality starts in utero . The contribution of biological sex to the developmental origins of health and disease is increasingly recognized. The aim of this study was to assess and interpret sexual dimorphisms for three major adverse pregnancy outcomes which affect the health of the neonate, child and potentially adult. Methods Retrospective population-based study of 574,358 South Australian singleton live births during 1981–2011. The incidence of three major adverse pregnancy outcomes [preterm birth (PTB), pregnancy induced hypertensive disorders (PIHD) and gestational diabetes mellitus (GDM)] in relation to fetal sex was compared according to traditional and fetus-at-risk (FAR) approaches. Results The traditional approach showed male predominance for PTB [20–24 weeks: Relative Risk (RR) M/F 1.351, 95%-CI 1.274–1.445], spontaneous PTB [25–29 weeks: RR M/F 1.118, 95%-CI 1.044–1.197%], GDM [RR M/F 1.042, 95%-CI 1.011–1.074], overall PIHD [RR M/F 1.053, 95%-CI 1.034–1.072] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044–1.105]. The FAR approach showed that males were at increased risk for PTB [20–24 weeks: RR M/F 1.273, 95%-CI 1.087–1.490], for spontaneous PTB [25–29 weeks: RR M/F 1.269, 95%-CI 1.143–1.410] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044–1.105%]. The traditional approach demonstrated female predominance for iatrogenic PTB [25–29 weeks: RR M/F 0.857, 95%-CI 0.780–0.941] and PIHD associated with PTB [25–29 weeks: RR M/F 0.686, 95%-CI 0.581–0.811]. The FAR approach showed that females were at increased risk for PIHD with PTB [25–29 weeks: RR M/F 0.779, 95%-CI 0.648–0.937]. Conclusions This study confirms the presence of sexual dimorphisms and presents a coherent framework based on two analytical approaches to assess and interpret the sexual dimorphisms for major adverse pregnancy outcomes. The mechanisms by which these occur remain elusive, but sex differences in placental gene expression and function are likely to play a key role. Further research on sex differences in placental function and maternal adaptation to pregnancy is required to delineate the causal molecular mechanisms in sex-specific pregnancy outcome. Identifying these mechanisms may inform fetal sex specific tailored antenatal and neonatal care.
    Electronic ISSN: 1932-6203
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  • 37
    Publication Date: 2016-07-12
    Description: by Harald Schrem, Valentin Schneider, Marlene Kurok, Alon Goldis, Maren Dreier, Alexander Kaltenborn, Wilfried Gwinner, Marc Barthold, Jan Liebeneiner, Markus Winny, Jürgen Klempnauer, Moritz Kleine Background The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G-chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers. Patients and Methods 1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized-incidence-ratios (SIRs) of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G-chart analysis was applied to determine relevant differences in the frequency of cancer occurrences. Results Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33–3.21). Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46), post-transplant lymphoproliferative disorder (SIR = 8.36), prostate cancer (SIR = 2.22), bladder cancer (SIR = 3.24), thyroid cancer (SIR = 10.13) and melanoma (SIR = 3.08). Independent pre-transplant risk factors for cancer-free survival were age 62.6 years (p = 0.001, HR: 1.29), polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD) (p = 0.001, HR: 0.68), high body mass index in kg/m 2 (p
    Electronic ISSN: 1932-6203
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  • 38
    Publication Date: 2016-07-12
    Description: by Prasamit Saurav Baruah, Myriam Beauchemin, Josée Hébert, Richard Bertrand Bcl-xL proteins undergo dynamic phosphorylation/dephosphorylation on Ser49 and Ser62 residues during mitosis. The expression of Bcl-xL(S49A), (S62A) and dual (S49/62A) phosphorylation mutants in tumor cells lead to severe mitotic defects associated with multipolar spindle, chromosome lagging and bridging, and micro-, bi- and multi-nucleated cells. Because the above observations were made in tumor cells which already display genomic instability, we now address the question: will similar effects occur in normal human diploid cells? We studied normal human diploid BJ foreskin fibroblast cells expressing Bcl-xL (wild type), (S49A), (S49D), (S62A), (S62D) and the dual-site (S49/62A) and (S49/62D) mutants. Cells expressing S49 and/or S62 phosphorylation mutants showed reduced kinetics of cell population doubling. These effects on cell population doubling kinetics correlated with early outbreak of senescence with no impact on the cell death rate. Senescent cells displayed typical senescence-associated phenotypes including high-level of senescence-associated β-galactosidase activity, interleukin-6 (IL-6) secretion, tumor suppressor p53 and cyclin-dependent kinase inhibitor p21Waf1/Cip1 activation as well as γH2A.X-associated nuclear chromatin foci. Fluorescence in situ hybridization analysis and Giemsa-banded karyotypes revealed that the expression of Bcl-xL phosphorylation mutants in normal diploid BJ cells provoked chromosome instability and aneuploidy. These findings suggest that dynamic Bcl-xL(S49) and (S62) phosphorylation/dephosphorylation cycles are important in the maintenance of chromosome integrity during mitosis in normal cells. They could impact future strategies aiming to develop and identify compounds that could target not only the anti-apoptotic domain of Bcl-xL protein, but also its mitotic domain for cancer therapy.
    Electronic ISSN: 1932-6203
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  • 39
    Publication Date: 2016-07-12
    Description: by Vera Kloten, Martin Schlensog, Julian Eschenbruch, Janina Gasthaus, Janina Tiedemann, Jolein Mijnes, Timon Heide, Till Braunschweig, Ruth Knüchel, Edgar Dahl NDRG2 , a member of the N-myc downstream-regulated gene family, is thought to be a putative tumor suppressor gene with promising clinical impact in breast cancer. Since breast cancer comprises heterogeneous intrinsic subtypes with distinct clinical outcomes we investigated the pivotal role of NDRG2 in basal-type breast cancers. Based on subtype classified tumor (n = 45) and adjacent normal tissues (n = 17) we examined NDRG2 mRNA expression and CpG-hypermethylation, whose significance was further validated by independent data sets from The Cancer Genome Atlas (TCGA). In addition, NDRG2 protein expression was evaluated immunohistochemically using a tissue micro array (TMA, n = 211). In vitro , we investigated phenotypic effects caused by NDRG2 silencing in the basal A-like HCC1806 as well as NDRG2 over-expression in basal A-like BT20 compared to luminal-type MCF7 breast cancer cells. Our tissue collections demonstrated an overall low NDRG2 mRNA expression in breast cancer subtypes compared to normal breast tissue in line with an increased CpG-hypermethylation in breast cancer tissue. Independent TCGA data sets verified a significant (P
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  • 40
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    In: PLoS ONE
    Publication Date: 2016-07-12
    Description: by Viorica Ionut, Orison O. Woolcott, Hasmik J. Mkrtchyan, Darko Stefanovski, Morvarid Kabir, Malini S. Iyer, Huiwen Liu, Ana V. B. Castro, Qiang Wu, Josiane L. Broussard, Cathryn M. Kolka, Isaac Asare-Bediako, Richard N. Bergman Background Exenatide’s effects on glucose metabolism have been studied extensively in diabetes but not in pre-diabetes. Objective We examined the chronic effects of exenatide alone on glucose metabolism in pre-diabetic canines. Design and Methods After 10 weeks of high-fat diet (HFD), adult dogs received one injection of streptozotocin (STZ, 18.5 mg/kg). After induction of pre-diabetes, while maintained on HFD, animals were randomized to receive either exenatide (n = 7) or placebo (n = 7) for 12 weeks. β-Cell function was calculated from the intravenous glucose tolerance test (IVGTT, expressed as the acute insulin response, AIR G ), the oral glucose tolerance test (OGTT, insulinogenic index) and the graded-hyperglycemic clamp (clamp insulinogenic index). Whole-body insulin sensitivity was assessed by the IVGTT. At the end of the study, pancreatic islets were isolated to assess β-cell function in vitro . Results OGTT: STZ caused an increase in glycemia at 120 min by 22.0% (interquartile range, IQR, 31.5%) (P = 0.011). IVGTT: This protocol also showed a reduction in glucose tolerance by 48.8% (IQR, 36.9%) (P = 0.002). AIR G decreased by 54.0% (IQR, 40.7%) (P = 0.010), leading to mild fasting hyperglycemia (P = 0.039). Exenatide, compared with placebo, decreased body weight (P
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  • 41
    Publication Date: 2016-07-12
    Description: by Ha Young Kim, Eun Jin Jang, ByeongJu Park, Tae-Young Kim, Soon-Ae Shin, Yong-Chan Ha, Sunmee Jang Background Asian-specific prediction models for estimating individual risk of osteoporotic fractures are rare. We developed a Korean fracture risk prediction model using clinical risk factors and assessed validity of the final model. Methods A total of 718,306 Korean men and women aged 50–90 years were followed for 7 years in a national system-based cohort study. In total, 50% of the subjects were assigned randomly to the development dataset and 50% were assigned to the validation dataset. Clinical risk factors for osteoporotic fracture were assessed at the biennial health check. Data on osteoporotic fractures during the follow-up period were identified by ICD-10 codes and the nationwide database of the National Health Insurance Service (NHIS). Results During the follow-up period, 19,840 osteoporotic fractures were reported (4,889 in men and 14,951 in women) in the development dataset. The assessment tool called the Korean Fracture Risk Score (KFRS) is comprised of a set of nine variables, including age, body mass index, recent fragility fracture, current smoking, high alcohol intake, lack of regular exercise, recent use of oral glucocorticoid, rheumatoid arthritis, and other causes of secondary osteoporosis. The KFRS predicted osteoporotic fractures over the 7 years. This score was validated using an independent dataset. A close relationship with overall fracture rate was observed when we compared the mean predicted scores after applying the KFRS with the observed risks after 7 years within each 10th of predicted risk. Conclusion We developed a Korean specific prediction model for osteoporotic fractures. The KFRS was able to predict risk of fracture in the primary population without bone mineral density testing and is therefore suitable for use in both clinical setting and self-assessment. The website is available at http://www.nhis.or.kr.
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  • 42
    Publication Date: 2016-07-12
    Description: by Cecilia Ma, Eva Monsma This paper examines the factor structure and measurement invariance of the Task and Ego Orientation in Sport Questionnaire (TEOSQ) across American and Chinese samples. Results based on the mean and covariance structure analyses supported configural invariance, metric invariance and scalar invariance across groups. Latent means analyses revealed that American sample had significantly higher mean scores on task and ego orientations than the Chinese sample. The findings suggest that the TEOSQ is a valid and reliable instrument in assessing achievement motivation across these two diverse populations.
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  • 43
    Publication Date: 2016-07-12
    Description: by Lin Yang, Liangping Xia, Yan Wang, Shaodong Hong, Haiyang Chen, Shaobo Liang, Peijian Peng, Yong Chen Background Poor nutritional status is associated with progression and advanced disease in patients with cancer. The prognostic nutritional index (PNI) may represent a simple method of assessing host immunonutritional status. This study was designed to investigate the prognostic value of the PNI for distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC). Methods A training cohort of 1,168 patients with non-metastatic NPC from two institutions was retrospectively analyzed. The optimal PNI cutoff value for DMFS was identified using the online tool “Cutoff Finder”. DMFS was analyzed using stratified and adjusted analysis. Propensity score-matched analysis was performed to balance baseline characteristics between the high and low PNI groups. Subsequently, the prognostic value of the PNI for DMFS was validated in an external validation cohort of 756 patients with NPC. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of different prognostic scores. Results The optimal PNI cutoff value was determined to be 51. Low PNI was significantly associated with poorer DMFS than high PNI in univariate analysis (P
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  • 44
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    In: PLoS ONE
    Publication Date: 2016-07-12
    Description: by Hung Yuan Chen, Yen Ling Chiu, Shih Ping Hsu, Mei Fen Pai, Ju Yeh Yang, Yu Sen Peng Background Fractures are a common morbidity that lead to worse outcomes in dialysis patients. Fetuin A inhibits vascular calcification (VC), potentially promotes bone mineralization and its level positively correlates with bone mineral density in the general population. On the other hand, the presence of VC is associated with low bone volume in dialysis patients. Whether the fetuin A level and VC can predict the occurrence of fractures in dialysis patients remains unknown. Methods We performed this prospective, observational cohort study including 685 dialysis patients (629 hemodialysis and 56 peritoneal dialysis) from a single center in Taiwan for a median follow-up period of 3.4 years. The baseline fetuin A level and status of presence of aortic arch calcification (VC) and incidence of major fractures (hip, pelvis, humerus, proximal forearm, lower leg or vertebrae) were assessed using adjusted Cox proportional hazards models, recursive partitioning analysis and competing risk models. Results Overall, 177 of the patients had major fractures. The incidence rate of major fractures was 3.29 per 100 person-years. In adjusted analyses, the patients with higher baseline fetuin A levels had a lower incidence of fractures (adjusted hazard ratio (HR), 0.3; 95% CI, 0.18‒0.5, fetuin A tertile 3 vs . tertile 1 and HR, 0.52; 95% CI, 0.34‒0.78, tertile 2 vs . tertile 1). The presence of aortic arch calcification (VC) independently predicted the occurrence of fractures (adjusted HR, 1.95; 95% CI, 1.34‒2.84) as well. When accounting for death as an event in competing risk models, the patients with higher baseline fetuin A levels remained to have a lower incidence of fractures (SHR, 0.31; 95% CI, 0.17‒0.56, fetuin A tertile 3 vs . tertile 1 and 0.51; 95% CI, 0.32‒0.81, tertile 2 vs . tertile 1). Interpretations Lower baseline fetuin A levels and the presence of VC were independently linked to higher risk of incident fractures in prevalent dialysis patients.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 45
    Publication Date: 2016-07-10
    Description: Article Polycyclic and caged molecules are common in nature but present challenging targets for synthesis. Here, the authors report a route to caged diterpene cores and apply to the total synthesis of atropurpuran, with oxidative dearomatization/intramolecular Diels-Alder cascade, aldol and ketyl-olefin cyclizations as key steps. Nature Communications doi: 10.1038/ncomms12183 Authors: Jing Gong, Huan Chen, Xiao-Yu Liu, Zhi-Xiu Wang, Wei Nie, Yong Qin
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 46
    Publication Date: 2016-07-10
    Description: Article Copper (Cu) is an essential mineral nutrient but high concentrations in rice grain can cause toxicity. Here the authors provide evidence that natural variation in rice grain Cu concentration is caused by altered sequestration of Cu into root vacuoles due to a single amino acid substitution in the OsHMA4 transporter. Nature Communications doi: 10.1038/ncomms12138 Authors: Xin-Yuan Huang, Fenglin Deng, Naoki Yamaji, Shannon R.M. Pinson, Miho Fujii-Kashino, John Danku, Alex Douglas, Mary Lou Guerinot, David E. Salt, Jian Feng Ma
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 47
    Publication Date: 2016-07-10
    Description: Article Graphitic carbon nitride is a promising hydrogen evolution photocatalyst, although there is limited understanding of its mechanistic operation. Here, the authors employ molecular heptazine-based model catalysts to identify catalytically relevant defects and to rationally design a highly active carbon nitride photocatalyst. Nature Communications doi: 10.1038/ncomms12165 Authors: Vincent Wing-hei Lau, Igor Moudrakovski, Tiago Botari, Simon Weinberger, Maria B. Mesch, Viola Duppel, Jürgen Senker, Volker Blum, Bettina V. Lotsch
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 48
    Publication Date: 2016-07-10
    Description: Article Aurora B activation at the centromere is critical for faithful chromosome segregation in mammals. Here the authors show that Aurora B-mediated phosphorylation of histone H2AX at serine 121 is essential for Aurora B auto-activation circuitry at centromeres, ensuring proper chromosome segregation. Nature Communications doi: 10.1038/ncomms12059 Authors: Midori Shimada, Takahiro Goshima, Hiromi Matsuo, Yoshikazu Johmura, Mayumi Haruta, Kazuhiro Murata, Hiromitsu Tanaka, Masahito Ikawa, Keiko Nakanishi, Makoto Nakanishi
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
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  • 49
    Publication Date: 2016-07-10
    Description: Article Laser capture microscopy (LCM) coupled with global transcriptome profiling requires relatively large numbers of cells. Here, the authors show that LCM coupled with full-length mRNA-sequencing (LCM-seq) can sequence single cells, and that LCM-seq can provide biological insight on highly similar neuronal populations. Nature Communications doi: 10.1038/ncomms12139 Authors: Susanne Nichterwitz, Geng Chen, Julio Aguila Benitez, Marlene Yilmaz, Helena Storvall, Ming Cao, Rickard Sandberg, Qiaolin Deng, Eva Hedlund
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 50
    Publication Date: 2016-07-10
    Description: Article PDZ domain-containing proteins are known to function as intracellular scaffolds. Here, Egea-Jimenez et al . report the structure of the tandem PDZ domains of syntenin in complex with a Frizzled 7 peptide and PIP2, show that the ligands bind to syntenin cooperatively and illustrate the role of the complex for Frizzled 7 function. Nature Communications doi: 10.1038/ncomms12101 Authors: Antonio Luis Egea-Jimenez, Rodrigo Gallardo, Abel Garcia-Pino, Ylva Ivarsson, Anna Maria Wawrzyniak, Rudra Kashyap, Remy Loris, Joost Schymkowitz, Frederic Rousseau, Pascale Zimmermann
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 51
    Publication Date: 2016-07-12
    Description: A consolidated analysis of the physiologic and molecular responses induced under acid stress in the legume-symbiont model-soil bacterium 〈i〉Sinorhizobium meliloti〈/i〉 Scientific Reports, Published online: 11 July 2016; doi:10.1038/srep29278
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 52
    Publication Date: 2016-07-13
    Description: by Zhenyu Yuan, Heiko Praxenthaler, Nassif Tabaja, Rubben Torella, Anette Preiss, Dieter Maier, Rhett A. Kovall Notch is a conserved signaling pathway that specifies cell fates in metazoans. Receptor-ligand interactions induce changes in gene expression, which is regulated by the transcription factor CBF1/Su(H)/Lag-1 (CSL). CSL interacts with coregulators to repress and activate transcription from Notch target genes. While the molecular details of the activator complex are relatively well understood, the structure-function of CSL-mediated repressor complexes is poorly defined. In Drosophila , the antagonist Hairless directly binds Su(H) (the fly CSL ortholog) to repress transcription from Notch targets. Here, we determine the X-ray structure of the Su(H)-Hairless complex bound to DNA. Hairless binding produces a large conformational change in Su(H) by interacting with residues in the hydrophobic core of Su(H), illustrating the structural plasticity of CSL molecules to interact with different binding partners. Based on the structure, we designed mutants in Hairless and Su(H) that affect binding, but do not affect formation of the activator complex. These mutants were validated in vitro by isothermal titration calorimetry and yeast two- and three-hybrid assays. Moreover, these mutants allowed us to solely characterize the repressor function of Su(H) in vivo.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 53
    Publication Date: 2016-07-13
    Description: by Camille Attané, Marie-Line Peyot, Roxane Lussier, Dongwei Zhang, Erik Joly, S. R. Murthy Madiraju, Marc Prentki Many metabolic studies employ tissue-specific gene knockout mice, which requires breeding of floxed gene mice, available mostly on C57BL/6N (NN) genetic background, with cre or Flp recombinase-expressing mice, available on C57BL/6J (JJ) background, resulting in the generation of mixed C57BL/6NJ (NJ) genetic background mice. Recent awareness of many genetic differences between NN and JJ strains including the deletion of nicotinamide nucleotide transhydrogenase ( nnt ), necessitates examination of the consequence of mixed NJ background on glucose tolerance, beta cell function and other metabolic parameters. Male mice with NN and NJ genetic background were fed with normal or high fat diets (HFD) for 12 weeks and glucose and insulin homeostasis were studied. Genotype had no effect on body weight and food intake in mice fed normal or high fat diets. Insulinemia in the fed and fasted states and after a glucose challenge was lower in HFD-fed NJ mice, even though their glycemia and insulin sensitivity were similar to NN mice. NJ mice showed mild glucose intolerance. Moreover, glucose- but not KCl-stimulated insulin secretion in isolated islets was decreased in HFD-fed NJ vs NN mice without changes in insulin content and beta cell mass. Under normal diet, besides reduced fed insulinemia, NN and NJ mice presented similar metabolic parameters. However, HFD-fed NJ mice displayed lower fed and fasted insulinemia and glucose-induced insulin secretion in vivo and ex vivo , as compared to NN mice. These results strongly caution against using unmatched mixed genetic background C57BL/6 mice for comparisons, particularly under HFD conditions.
    Electronic ISSN: 1932-6203
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  • 54
    Publication Date: 2016-07-13
    Description: by Jill A. Rahnert, Bin Zheng, Matthew B. Hudson, Myra E. Woodworth-Hobbs, S. Russ Price Muscle wasting associated with chronic diseases has been linked to decreased expression of PGC-1α and overexpression of PGC-1α counters muscle loss. CREB, in conjunction with the CREB-regulated transcription coactivator (CRTC2), is a positive modulator of PGC-1α transcription. We previously reported that PGC-1α expression is decreased in skeletal muscle of diabetic rats despite a high level of CREB phosphorylation (i.e., activation), suggesting that CRTC2-CREB signaling may be dysregulated. In this study, the relationship between CREB/CRTC signaling and PGC-1α expression was examined in L6 myotubes treated with dexamethasone (Dex, 48h) to induce atrophy. Dex decreased PGC-1α mRNA and protein as well as the levels of CRTC1 and CRTC2 in the nucleus. Dex also altered the nuclear levels of two known regulators of CRTC2 localization; the amount of calcinuerin catalytic A subunit (CnA) was decreased whereas SIK was increased. To assess PGC-1α transcription, muscle cells were transfected with a PGC-1α luciferase reporter plasmid (PGC-1α-Luc). Dex suppressed PGC-1α luciferase activity while both isobutylmethylxanthine (IBMX) and over-expression of CRTC1 or CRTC2 increased PGC-1α-Luc activity. Mutation of the CRE binding site from PGC-1α-Luc reporter attenuated the responses to both IBMX and the CRTC proteins. Consistent with the reporter gene results, overexpression of CRTC2 produced an increase in CRTC2 in the nucleus and in PGC-1α mRNA and PGC-1α protein. Overexpression of CRTC2 was not sufficient to prevent the decrease in PGC-1α mRNA or protein by Dex. In summary, these data suggest that attenuated CREB/CRTC signaling contributes to the decrease in PGC-1α expression during atrophy.
    Electronic ISSN: 1932-6203
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  • 55
    Publication Date: 2016-07-13
    Description: by Fatima Ochoa-Gonzalez, Alberto R. Cervantes-Villagrana, Julio C. Fernandez-Ruiz, Hilda S. Nava-Ramirez, Adriana C. Hernandez-Correa, Jose A. Enciso-Moreno, Julio E. Castañeda-Delgado
    Electronic ISSN: 1932-6203
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  • 56
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    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2016-07-13
    Description: by Abdessamad Ababou, Vassilis Koronakis Gram-negative bacteria such as E . coli use tripartite efflux pumps such as AcrAB-TolC to expel antibiotics and noxious compounds. A key feature of the inner membrane transporter component, AcrB, is a short stretch of residues known as the gate/switch loop that divides the proximal and distal substrate binding pockets. Amino acid substitutions of the gate loop are known to decrease antibiotic resistance conferred by AcrB. Here we present two new AcrB gate loop variants, the first stripped of its bulky side chains, and a second in which the gate loop is removed entirely. By determining the crystal structures of the variant AcrB proteins in the presence and absence of erythromycin and assessing their ability to confer erythromycin tolerance, we demonstrate that the gate loop is important for AcrB export activity but is not required for erythromycin binding.
    Electronic ISSN: 1932-6203
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  • 57
    Publication Date: 2016-07-13
    Description: by Shou-Chieh Wang, Chin-Chin Huang, Cheng-Huang Shen, Lei-Chen Lin, Pei-Wen Zhao, Shih-Ying Chen, Yu-Chiao Deng, Yi-Wen Liu Bladder cancer is highly recurrent after therapy, which has an enormous impact on the health and financial condition of the patient. It is worth developing diagnostic tools for bladder cancer. In our previous study, we found that the bladder carcinogen BBN increased urothelial global DNA CpG methylation and decreased GSTM1 protein expression in mice. Here, the correlation of BBN-decreased GSTM1 and GSTM gene CpG methylation status was analyzed in mice bladders. BBN treatment decreased the protein and mRNA expression of GSTM1, and the CpG methylation ratio of GSTM1 gene promoter was slightly increased in mice bladders. Unlike mouse GSTM1, the human GSTM1 gene tends to be deleted in bladder cancers. Among 7 human bladder cancer cell lines, GSTM1 gene is really null in 6 cell lines except one, T24 cells. The CpG methylation level of GSTM1 was 9.9% and 5-aza-dC did not significantly increase GSTM1 protein and mRNA expression in T24 cells; however, the GSTM5 gene was CpG hypermethylated (65.4%) and 5-aza-dC also did not affect the methylation ratio and mRNA expression. However, in other cell lines without GSTM1, 5-aza-dC increased GSTM5 expression and decreased its CpG DNA methylation ratio from 84.6% to 61.5% in 5637, and from 97.4% to 75% in J82 cells. In summary, two biomarkers of bladder tumor were provided. One is the GSTM1 gene which is down-regulated in mice bladder carcinogenesis and is usually deleted in human urothelial carcinoma, while the other is the GSTM5 gene, which is inactivated by DNA CpG methylation.
    Electronic ISSN: 1932-6203
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  • 58
    Publication Date: 2016-07-13
    Description: by Anna Moretti, Michele Ghidini, Carmine De Angelis, Matteo Lambertini, Chiara Cremolini, Martina Imbimbo, Rossana Berardi, Massimo Di Maio, Stefano Cascinu, Nicla La Verde Background and objectives Relevant heterogeneity exists among Postgraduate Schools in Medical Oncology, also within the same country. In order to provide a comprehensive overview of the landscape of Italian Postgraduate Schools in Medical Oncology, the Italian Association of Medical Oncology (AIOM) undertook an online survey, inviting all the residents to describe their daily activities and to express their overall satisfaction about their programs. Methods A team composed of five residents and three consultants in medical oncology prepared a 38 items questionnaire that was published online in a reserved section, accessible through a link sent by e-mail. Residents were invited to anonymously fill in the questionnaire that included the following sub-sections: quality of teaching, clinical and research activity, overall satisfaction. Results Three-hundred and eleven (57%) out of 547 invited residents filled in the questionnaire. Two-hundred and twenty-three (72%) participants declared that attending lessons was frequently difficult and 153 (49%) declared they did not gain substantial improvement in their knowledge from them. Fifty-five percent stated that they did not receive lessons on palliative care. Their overall judgment about didactic activity was low in 63% of the interviewed. The satisfaction for clinical activity was in 86% of cases good: 84% recognized that, during the training period, they acquired a progressive independence on patients' management. About research activity, the majority (79%) of participants in the survey was actively engaged in managing patients included in clinical trials but the satisfaction level for the involvement in research activities was quite low (54%). Overall, 246 residents (79%) gave a positive global judgment of their Medical Oncology Schools. Conclusions The landscape of Italian Postgraduate Schools in Medical Oncology is quite heterogeneous across the country. Some improvements in the organization of teaching and in the access to research opportunity are needed; the perception about clinical activity and the overall judgment of the programs are quite satisfactory.
    Electronic ISSN: 1932-6203
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  • 59
    Publication Date: 2016-07-13
    Description: by Jian Song, Zhangxiong Liu, Huilong Hong, Yansong Ma, Long Tian, Xinxiu Li, Ying-Hui Li, Rongxia Guan, Yong Guo, Li-Juan Qiu Soybean seed coat exists in a range of colors from yellow, green, brown, black, to bicolor. Classical genetic analysis suggested that soybean seed color was a moderately complex trait controlled by multi-loci. However, only a couple of loci could be detected using a single biparental segregating population. In this study, a combination of association mapping and bulk segregation analysis was employed to identify genes/loci governing this trait in soybean. A total of 14 loci, including nine novel and five previously reported ones, were identified using 176,065 coding SNPs selected from entire SNP dataset among 56 soybean accessions. Four of these loci were confirmed and further mapped using a biparental population developed from the cross between ZP95-5383 (yellow seed color) and NY279 (brown seed color), in which different seed coat colors were further dissected into simple trait pairs (green/yellow, green/black, green/brown, yellow/black, yellow/brown, and black/brown) by continuously developing residual heterozygous lines. By genotyping entire F 2 population using flanking markers located in fine-mapping regions, the genetic basis of seed coat color was fully dissected and these four loci could explain all variations of seed colors in this population. These findings will be useful for map-based cloning of genes as well as marker-assisted breeding in soybean. This work also provides an alternative strategy for systematically isolating genes controlling relative complex trait by association analysis followed by biparental mapping.
    Electronic ISSN: 1932-6203
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  • 60
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    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2016-07-13
    Description: by Yuki Murai, Yuko Yotsumoto When individuals are asked to reproduce intervals of stimuli that are intermixedly presented at various times, longer intervals are often underestimated and shorter intervals overestimated. This phenomenon may be attributed to the central tendency of time perception, and suggests that our brain optimally encodes a stimulus interval based on current stimulus input and prior knowledge of the distribution of stimulus intervals. Two distinct systems are thought to be recruited in the perception of sub- and supra-second intervals. Sub-second timing is subject to local sensory processing, whereas supra-second timing depends on more centralized mechanisms. To clarify the factors that influence time perception, the present study investigated how both sensory modality and timescale affect the central tendency. In Experiment 1, participants were asked to reproduce sub- or supra-second intervals, defined by visual or auditory stimuli. In the sub-second range, the magnitude of the central tendency was significantly larger for visual intervals compared to auditory intervals, while visual and auditory intervals exhibited a correlated and comparable central tendency in the supra-second range. In Experiment 2, the ability to discriminate sub-second intervals in the reproduction task was controlled across modalities by using an interval discrimination task. Even when the ability to discriminate intervals was controlled, visual intervals exhibited a larger central tendency than auditory intervals in the sub-second range. In addition, the magnitude of the central tendency for visual and auditory sub-second intervals was significantly correlated. These results suggest that a common modality-independent mechanism is responsible for the supra-second central tendency, and that both the modality-dependent and modality-independent components of the timing system contribute to the central tendency in the sub-second range.
    Electronic ISSN: 1932-6203
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  • 61
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    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2016-07-13
    Description: by Martin W. von Websky, Koji Kitamura, Isis Ludwig-Portugall, Christian Kurts, Maximilian von Laffert, Joel LeMaoult, Edgardo D. Carosella, Kareem Abu-Elmagd, Joerg C. Kalff, Nico Schäfer The non-classical MHC I paralogue HLA-G is expressed by cytotrophoblast cells and implicated with fetomaternal tolerance by downregulating the maternal adaptive and innate immune response against the fetus. HLA-G expression correlates with favorable graft outcome in humans and recently promising immunosuppressive effects of therapeutic HLA-G in experimental transplantation (skin allograft acceptance) were shown. Consequently, we examined this novel therapeutic approach in solid organ transplantation. In this study, therapeutic recombinant HLA-G5 was evaluated for the first time in a solid organ model of acute rejection (ACR) after orthotopic intestinal transplantation (ITX). Allogenic ITX was performed in rats (Brown Norway to Lewis) with and without HLA-G treatment. It was found that HLA-G treatment significantly reduced histologically proven ACR at both an early and late postoperative timepoint (POD 4/7), concomitant to a functionally preserved graft contractility at POD 7. Interestingly, graft infiltration by myeloperoxidase+ cells was significantly reduced at POD7 by HLA-G treatment. Moreover, HLA-G treatment showed an effect on the allogenic T-cell immune response as assessed by flow cytometry: The influx of recipient-derived CD8 + T-cells into the graft mesenteric lymphnodes at POD7 was significantly reduced while CD4 + populations were not affected. As a potential mechanism of action, an induction of T-reg populations in the mesenteric lymphnodes was postulated, but flow cytometric analysis of classical CD4 + /CD25 + /FoxP3 + T reg -cells showed no significant alteration by HLA-G treatment. The novel therapeutic approach using recombinant HLA-G5 reported herein demonstrates a significant immunosuppressive effect in this model of allogenic experimental intestinal transplantation. This effect may be mediated via inhibition of recipient-derived CD8 + T-cell populations either directly or by induction of non-classical T reg populations.
    Electronic ISSN: 1932-6203
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  • 62
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    In: PLoS ONE
    Publication Date: 2016-07-13
    Description: by Nayana Wijayathilaka, Madhava Meegaskumbura Vocalizing behavior of frogs and toads, once quantified, is useful for systematics, rapid species identification, behavioral experimentation and conservation monitoring. But yet, for many lineages vocalizations remain unknown or poorly quantified, especially in diversity rich tropical regions. Here we provide a quantitative acoustical analysis for all four Sri Lankan congeners of the genus Microhyla . Three of these species are endemic to the island, but Microhyla ornata is regionally widespread. Two of these endemics, M . karunaratnei (Critically Endangered) and M . zeylanica (Endangered), are highly threatened montane isolates; the other, M . mihintalei , is relatively common across the dry lowlands. We recorded and analyzed 100 advertisement calls from five calling males for each species, except for M . zeylanica , which only had 53 calls from three males suitable for analyses. All four species call in choruses and their vocal repertoires are simple compared to most frogs. Their calls contain multiple pulses and no frequency modulation. We quantified eight call characters. Call duration and number of pulses were higher for the two montane isolates (inhabiting cooler habitats at higher altitudes) compared to their lowland congeners. Microhyla zeylanica has the longest call duration (of 1.8 ± 0.12 s) and the highest number of pulses (of 61–92 pulses). The smallest of the species, Microhyla karunaratnei (16.2–18.3 mm), has the highest mean dominant frequency (3.3 ± 0.14 kHz) and pulse rate (77 ± 5.8 pulses per second). The calls separate well in the Principal Component space: PC1 axis is mostly explained by the number of pulses per call and call duration; PC2 is mostly explained by the pulse rate. A canonical means plot of a Discriminant Function analysis shows non-overlapping 95% confidence ellipses. This suggests that some call parameters can be used to distinguish these species effectively. We provide detailed descriptions for eight call properties and compare these with congeners for which data is available. This work provides a foundation for comparative bioacoustic analyses and species monitoring while facilitating the systematics of Microhyla across its range.
    Electronic ISSN: 1932-6203
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  • 63
    Publication Date: 2016-07-13
    Description: by Rozalia Korbut, Foojan Mehrdana, Per Walter Kania, Marianne Halberg Larsen, Dorte Frees, Inger Dalsgaard, Louise von Gersdorff Jørgensen Immersion-vaccines (bacterins) are routinely used for aquacultured rainbow trout to protect against Yersinia ruckeri (Yr). During immersion vaccination, rainbow trout take up and process the antigens, which induce protection. The zebrafish was used as a model organism to study uptake mechanisms and subsequent antigen transport in fish. A genetically modified Yr was developed to constitutively express green fluorescent protein (GFP) and was used for bacterin production. Larval, juvenile and adult transparent zebrafish (tra:nac mutant) received a bath in the bacterin for up to 30 minutes. Samples were taken after 1 min, 15 min, 30 min, 2 h, 12 h and 24 h. At each sampling point fish were used for live imaging of the uptake using a fluorescence stereomicroscope and for immunohistochemistry (IHC). In adult fish, the bacterin could be traced within 30 min in scale pockets, skin, oesophagus, intestine and fins. Within two hours post bath (pb) Yr-antigens were visible in the spleen and at 24 h in liver and kidney. Bacteria were associated with the gills, but uptake at this location was limited. Antigens were rarely detected in the blood and never in the nares. In juvenile fish uptake of the bacterin was seen in the intestine 30 min pb and in the nares 2 hpb but never in scale pockets. Antigens were detected in the spleen 12 hpb. Zebrafish larvae exhibited major Yr uptake only in the mid-intestine enterocytes 24 hpb. The different life stages of zebrafish varied with regard to uptake locations, however the gut was consistently a major uptake site. Zebrafish and rainbow trout tend to have similar uptake mechanisms following immersion or bath vaccination, which points towards zebrafish as a suitable model organism for this aquacultured species.
    Electronic ISSN: 1932-6203
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  • 64
    Publication Date: 2016-07-13
    Description: by Seema Thakur, Rajesh K. Grover, Sanjay Gupta, Ajay K. Yadav, Bhudev C. Das Of several subtypes of breast cancer, triple negative breast cancer (TNBC) is a highly aggressive tumor that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor receptor 2 and shows a worst prognosis. The small noncoding RNAs (miRNAs) considered as master regulator of gene expression play a key role in cancer initiation, progression and drug resistance and have emerged as attractive molecular biomarkers for diagnosis, prognosis and treatment targets in cancer. We have done expression profiling of selected miRNAs in paired serum and tissue samples of TNBC patients and corresponding cell lines and compared with that of other subtypes, in order to identify novel serum miRNA biomarkers for early detection and progression of TNBC. A total of 85 paired tumor tissues and sera with an equal number of adjacent normal tissue margins and normal sera from age matched healthy women including tissue and sera samples from 15 benign fibroadenomas were employed for the study. We report for the first time an extremely high prevalence (73.9%) of TNBC in premenopausal women below 35 years of age and a significant altered expression of a panel of three specific oncogenic miRNAs- miR-21, miR-221, miR-210, and three tumor suppressor miRNAs- miR-195, miR-145 and Let-7a in both tissues and corresponding sera of TNBC patients when compared with triple positive breast cancer (TPBC) patients. While miR-21, miR-221 and miR-210 showed significant over-expression, miR-195 and miR-145 were downregulated and well correlated with various clinicopathological and demographic risk factors, tumor grade, clinical stage and hormone receptor status. Interestingly, despite being a known tumor suppressor, Let-7a showed a significant overexpression in TNBCs. It is suggested that this panel of six miRNA signature may serve as a minimally invasive biomarker for an early detection of TNBC patients.
    Electronic ISSN: 1932-6203
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  • 65
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    In: PLoS ONE
    Publication Date: 2016-07-13
    Description: by Martin G. Schwacha, Meenakshi Rani, Susannah E. Nicholson, Aaron M. Lewis, Travis L. Holloway, Salvador Sordo, Andrew P. Cap Background Gamma delta T-cells have been shown to be important to the early immunoinflammatory response to injury, independent of infection. This unique T-cell population acts to regulate cell trafficking and the release of cytokines and growth factors. We propose this sterile inflammatory response is in part associated with damage associated molecular patterns (DAMPs) generated by major injury, such as burn, and mediated via toll-like receptors (TLRs). It is unknown whether DAMPs can activate resident γδ T-cells that reside in skin. Methods Gamma delta T-cells were isolated from the skin of male C57BL/6 mice by enzymatic digestion. Mitochondrial DAMPs (MTDs) were generated from mitochondria isolated from mouse livers by sonication and centrifugation. Dermal γδ T-cells were incubated with MTDs (0–500 μg/ml) for 24 hr and cells and supernatants were collected for analysis. Results MTDs activated dermal γδ T-cells, as evidenced by increased TLR2 and TLR4 expression following in vitro exposure. MTDs also induced the production of inflammatory cytokines (IL-1β, IL-6), and growth factors (PDGF and VEGF) by γδ T-cells. Conclusions These findings herein support the concept that MTDs released after tissue/cellular injury are capable of activating dermal γδ T-cells. We propose that the activation of this unique T-cell population is central in the initiation of sterile inflammation and also contributes to the subsequent healing processes.
    Electronic ISSN: 1932-6203
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  • 66
    Publication Date: 2016-07-13
    Description: by Tamaki Hayase Like various stressors, the addictive use of nicotine (NC) is associated with emotional symptoms such as anxiety and depression, although the underlying mechanisms have not yet been fully elucidated due to the complicated involvement of target neurotransmitter systems. In the elicitation of these emotional symptoms, the fundamental involvement of epigenetic mechanisms such as histone acetylation has recently been suggested. Furthermore, among the interacting neurotransmitter systems implicated in the effects of NC and stressors, the endocannabinoid (ECB) system is considered to contribute indispensably to anxiety and depression. In the present study, the epigenetic involvement of histone acetylation induced by histone deacetylase (HDAC) inhibitors was investigated in anxiety- and depression-related behavioral alterations caused by NC and/or immobilization stress (IM). Moreover, based on the contributing roles of the ECB system, the interacting influence of ECB ligands on the effects of HDAC inhibitors was evaluated in order to examine epigenetic therapeutic interventions. Anxiety-like (elevated plus-maze test) and depression-like (forced swimming test) behaviors, which were observed in mice treated with repeated (4 days) NC (subcutaneous 0.8 mg/kg) and/or IM (10 min), were blocked by the HDAC inhibitors sodium butyrate (SB) and valproic acid (VA). The cannabinoid type 1 (CB1) agonist ACPA (arachidonylcyclopropylamide; AC) also antagonized these behaviors. Conversely, the CB1 antagonist SR 141716A (SR), which counteracted the effects of AC, attenuated the anxiolytic-like effects of the HDAC inhibitors commonly in the NC and/or IM groups. SR also attenuated the antidepressant-like effects of the HDAC inhibitors, most notably in the IM group. From these results, the combined involvement of histone acetylation and ECB system was shown in anxiety- and depression-related behaviors. In the NC treatment groups, the limited influence of SR against the HDAC inhibitor-induced antidepressant-like effects may reflect the characteristic involvement of histone acetylation within the NC-related neurotransmitter systems other than the ECB system.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 67
    Publication Date: 2016-07-13
    Description: Decreased expression of Calpain-9 predicts unfavorable prognosis in patients with gastric cancer Scientific Reports, Published online: 12 July 2016; doi:10.1038/srep29604
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 68
    Publication Date: 2016-07-13
    Description: Electrical characterization of DNA supported on nitrocellulose membranes Scientific Reports, Published online: 12 July 2016; doi:10.1038/srep29089
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 69
    Publication Date: 2016-07-14
    Description: Development of near-zero water consumption cement materials via the geopolymerization of tektites and its implication for lunar construction Scientific Reports, Published online: 13 July 2016; doi:10.1038/srep29659
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 70
    Publication Date: 2016-07-14
    Description: Disentangling adaptive evolutionary radiations and the role of diet in promoting diversification on islands Scientific Reports, Published online: 13 July 2016; doi:10.1038/srep29803
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
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  • 71
    Publication Date: 2016-07-15
    Description: Article JAK inhibitors are currently undergoing evaluation in clinical trials for advanced breast cancer. Here, the authors show that JAK pathway inhibition increases metastasis in mouse models of breast cancer by impairing NK anti-tumour activity and that these side effects can be overcome by addition of IL-15. Nature Communications doi: 10.1038/ncomms12258 Authors: Alessia Bottos, Dagmar Gotthardt, Jason W. Gill, Albana Gattelli, Anna Frei, Alexandar Tzankov, Veronika Sexl, Aleksandra Wodnar-Filipowicz, Nancy E. Hynes
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 72
    Publication Date: 2016-07-15
    Description: Article Breast cancer is separated into multiple subtypes based on the expression of HER2 and hormone receptors. Here, the authors report the whole genome sequence of 64 HER2 positive tumours and show that these can be further separated into four groups with different gene expression profiles and genomic features. Nature Communications doi: 10.1038/ncomms12222 Authors: Anthony Ferrari, Anne Vincent-Salomon, Xavier Pivot, Anne-Sophie Sertier, Emilie Thomas, Laurie Tonon, Sandrine Boyault, Eskeatnaf Mulugeta, Isabelle Treilleux, Gaëtan MacGrogan, Laurent Arnould, Janice Kielbassa, Vincent Le Texier, Hélène Blanché, Jean-François Deleuze, Jocelyne Jacquemier, Marie-Christine Mathieu, Frédérique Penault-Llorca, Frédéric Bibeau, Odette Mariani, Cécile Mannina, Jean-Yves Pierga, Olivier Trédan, Thomas Bachelot, Hervé Bonnefoi, Gilles Romieu, Pierre Fumoleau, Suzette Delaloge, Maria Rios, Jean-Marc Ferrero, Carole Tarpin, Catherine Bouteille, Fabien Calvo, Ivo Glynne Gut, Marta Gut, Sancha Martin, Serena Nik-Zainal, Michael R. Stratton, Iris Pauporté, Pierre Saintigny, Daniel Birnbaum, Alain Viari, Gilles Thomas
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 73
    Publication Date: 2016-07-15
    Description: B Lymphocytes in Multiple Sclerosis: Bregs and BTLA/CD272 Expressing-CD19+ Lymphocytes Modulate Disease Severity Scientific Reports, Published online: 14 July 2016; doi:10.1038/srep29699
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
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  • 74
    Publication Date: 2016-07-15
    Description: Interferon regulatory factor 3 is a key regulation factor for inducing the expression of SAMHD1 in antiviral innate immunity Scientific Reports, Published online: 14 July 2016; doi:10.1038/srep29665
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
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  • 75
    Publication Date: 2016-07-15
    Description: by Mario Novkovic, Lucas Onder, Jovana Cupovic, Jun Abe, David Bomze, Viviana Cremasco, Elke Scandella, Jens V. Stein, Gennady Bocharov, Shannon J. Turley, Burkhard Ludewig Fibroblastic reticular cells (FRCs) form the cellular scaffold of lymph nodes (LNs) and establish distinct microenvironmental niches to provide key molecules that drive innate and adaptive immune responses and control immune regulatory processes. Here, we have used a graph theory-based systems biology approach to determine topological properties and robustness of the LN FRC network in mice. We found that the FRC network exhibits an imprinted small-world topology that is fully regenerated within 4 wk after complete FRC ablation. Moreover, in silico perturbation analysis and in vivo validation revealed that LNs can tolerate a loss of approximately 50% of their FRCs without substantial impairment of immune cell recruitment, intranodal T cell migration, and dendritic cell-mediated activation of antiviral CD8 + T cells. Overall, our study reveals the high topological robustness of the FRC network and the critical role of the network integrity for the activation of adaptive immune responses.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 76
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    Publication Date: 2016-07-15
    Description: by Jose L. Herrera, Ravi Srinivasan, John S. Brownstein, Alison P. Galvani, Lauren Ancel Meyers As infectious disease surveillance systems expand to include digital, crowd-sourced, and social network data, public health agencies are gaining unprecedented access to high-resolution data and have an opportunity to selectively monitor informative individuals. Contact networks, which are the webs of interaction through which diseases spread, determine whether and when individuals become infected, and thus who might serve as early and accurate surveillance sensors. Here, we evaluate three strategies for selecting sensors—sampling the most connected, random, and friends of random individuals—in three complex social networks—a simple scale-free network, an empirical Venezuelan college student network, and an empirical Montreal wireless hotspot usage network. Across five different surveillance goals—early and accurate detection of epidemic emergence and peak, and general situational awareness—we find that the optimal choice of sensors depends on the public health goal, the underlying network and the reproduction number of the disease ( R 0 ). For diseases with a low R 0 , the most connected individuals provide the earliest and most accurate information about both the onset and peak of an outbreak. However, identifying network hubs is often impractical, and they can be misleading if monitored for general situational awareness, if the underlying network has significant community structure, or if R 0 is high or unknown. Taking a theoretical approach, we also derive the optimal surveillance system for early outbreak detection but find that real-world identification of such sensors would be nearly impossible. By contrast, the friends-of-random strategy offers a more practical and robust alternative. It can be readily implemented without prior knowledge of the network, and by identifying sensors with higher than average, but not the highest, epidemiological risk, it provides reasonably early and accurate information.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 77
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    Publication Date: 2016-07-15
    Description: by Liying Guan, Xuehua Ma, Jingyan Zhang, Jia-Jia Liu, Yingchun Wang, Mei Ding Eukaryotic cells extend a variety of surface protrusions to direct cell motility. Formation of protrusions is mediated by coordinated actions between the plasma membrane and the underlying actin cytoskeleton. Here, we found that the single calponin homology (CH) domain-containing protein CHDP-1 induces the formation of cell protrusions in C . elegans . CHDP-1 is anchored to the cortex through its amphipathic helix. CHDP-1 associates through its CH domain with the small GTPase Rac1/CED-10, which is a key regulator of the actin cytoskeleton. CHDP-1 preferentially binds to the GTP-bound active form of the CED-10 protein and preserves the membrane localization of GTP-CED-10. Hence, by coupling membrane expansion to Rac1-mediated actin dynamics, CHDP-1 promotes the formation of cellular protrusions in vivo .
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 78
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    Publication Date: 2016-07-15
    Description: by Masashi Naito, Masaki Mori, Masayo Inagawa, Kohei Miyata, Naohiro Hashimoto, Sakae Tanaka, Hiroshi Asahara Cell differentiation status is defined by the gene expression profile, which is coordinately controlled by epigenetic mechanisms. Cell type-specific DNA methylation patterns are established by chromatin modifiers including de novo DNA methyltransferases, such as Dnmt3a and Dnmt3b . Since the discovery of the myogenic master gene MyoD , myogenic differentiation has been utilized as a model system to study tissue differentiation. Although knowledge about myogenic gene networks is accumulating, there is only a limited understanding of how DNA methylation controls the myogenic gene program. With an aim to elucidate the role of DNA methylation in muscle development and regeneration, we investigate the consequences of mutating Dnmt3a in muscle precursor cells in mice. Pax3 promoter-driven Dnmt3a -conditional knockout (cKO) mice exhibit decreased organ mass in the skeletal muscles, and attenuated regeneration after cardiotoxin-induced muscle injury. In addition, Dnmt3a -null satellite cells (SCs) exhibit a striking loss of proliferation in culture. Transcriptome analysis reveals dysregulated expression of p57Kip2 , a member of the Cip/Kip family of cyclin-dependent kinase inhibitors (CDKIs), in the Dnmt3a -KO SCs. Moreover, RNAi-mediated depletion of p57Kip2 replenishes the proliferation activity of the SCs, thus establishing a role for the Dnmt3a - p57Kip2 axis in the regulation of SC proliferation. Consistent with these findings, Dnmt3a -cKO muscles exhibit fewer Pax7 + SCs, which show increased expression of p57Kip2 protein. Thus, Dnmt3a is found to maintain muscle homeostasis by epigenetically regulating the proliferation of SCs through p57Kip2 .
    Print ISSN: 1553-7390
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  • 79
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    Publication Date: 2016-07-15
    Description: by William Zerges
    Print ISSN: 1553-7390
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  • 80
    Publication Date: 2016-07-15
    Description: by Wenjun Ji, Zhou Shi, Jingyi Huang, Shuo Li
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 81
    Publication Date: 2016-07-15
    Description: by Sheetal Prakash Silal, Francesca Little, Karen Irma Barnes, Lisa Jane White
    Electronic ISSN: 1932-6203
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  • 82
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    In: PLoS ONE
    Publication Date: 2016-07-15
    Description: by Christian Vinueza-Burgos, María Cevallos, Lenin Ron-Garrido, Sophie Bertrand, Lieven De Zutter Salmonella is frequently found in poultry and represent an important source for human gastrointestinal infections worldwide. The aim of this study was to investigate the prevalence, genotypes and antimicrobial resistance of Salmonella serotypes in broilers from Ecuador. Caeca content from 388 at random selected broiler batches were collected in 6 slaughterhouses during 1 year and analyzed by the ISO 6579/Amd1 protocol for the isolation for Salmonella . Isolates were serotyped and genotypic variation was acceded by pulsed field gel electrophoresis. MIC values for sulfamethoxazole, gentamicin, ciprofloxacin, ampicillin, cefotaxime, ceftazidime, tetracycline, streptomycin, trimethropim, chloramphenicol, colistin, florfenicol, kanamycin and nalidixic acid were obtained. Presence of bla CTX-M , bla TEM, bla SHV and bla CMY ; and mcr-1 plasmid genes was investigated in resistant strains to cefotaxime and colistin respectively. Prevalence at batch level was 16.0%. The most common serotype was S . Infantis (83.9%) followed by S . Enteritidis (14.5%) and S . Corvallis (1.6%). The pulsed field gel electrophoresis analysis showed that S . Corvallis, S . Enteritidis and S . Infantis isolates belonged to 1, 2 and 12 genotypes respectively. S . Infantis isolates showed high resistance rates to 12 antibiotics ranging from 57.7% (kanamycin) up to 98.1% (nalidixic acid and sulfamethoxazole). All S . Enteritidis isolates showed resistance to colistin. High multiresistant patterns were found for all the serotypes. The bla CTX-M gene was present in 33 S . Infantis isolates while mcr-1 was negative in 10 colistin resistant isolates. This study provides the first set of scientific data on prevalence and multidrug-resistant Salmonella coming from commercial poultry in Ecuador.
    Electronic ISSN: 1932-6203
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  • 83
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    In: PLoS ONE
    Publication Date: 2016-07-15
    Description: by Chun-Ta Huang, Yu-Chung Chuang, Yi-Ju Tsai, Wen-Je Ko, Chong-Jen Yu Background Severe sepsis is a potentially deadly illness and always requires intensive care. Do-not-resuscitate (DNR) orders remain a debated issue in critical care and limited data exist about its impact on care of septic patients, particularly in East Asia. We sought to assess outcome of severe sepsis patients with regard to DNR status in Taiwan. Methods A retrospective cohort study was conducted in intensive care units (ICUs) between 2008 and 2010. All severe sepsis patients were included for analysis. Primary outcome was association between DNR orders and ICU mortality. Volume of interventions was used as proxy indicator to indicate aggressiveness of care. Results Sixty-seven (9.4%) of 712 patients had DNR orders on ICU admission, and these patients were older and had higher disease severity compared with patients without DNR orders. Notably, DNR patients experienced high ICU mortality (90%). Multivariate analysis revealed that the presence of DNR orders was independently associated with ICU mortality (odds ratio: 6.13; 95% confidence interval: 2.66–14.10). In propensity score-matched cohort, ICU mortality rate (91%) in the DNR group was statistically higher than that (62%) in the non-DNR group (p
    Electronic ISSN: 1932-6203
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  • 84
    Publication Date: 2016-07-15
    Description: by Abbas Mirvakili, Mohammad Hossein Dadgarnia, Mohammad Hossein Baradaranfar, Saeid Atighechi, Vahid Zand, Abdollah Ansari
    Electronic ISSN: 1932-6203
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  • 85
    Publication Date: 2016-07-15
    Description: by Julie M. Butler, Karen E. Field, Karen P. Maruska Fishes use multimodal signals during both inter- and intra-sexual displays to convey information about their sex, reproductive state, and social status. These complex behavioral displays can include visual, auditory, olfactory, tactile, and hydrodynamic signals, and the relative role of each sensory channel in these complex multi-sensory interactions is a common focus of neuroethology. The mechanosensory lateral line system of fishes detects near-body water movements and is implicated in a variety of behaviors including schooling, rheotaxis, social communication, and prey detection. Cobalt chloride is commonly used to chemically ablate lateral line neuromasts, thereby eliminating water-movement cues to test for mechanosensory-mediated behavioral functions. However, cobalt acts as a nonspecific calcium channel antagonist and could potentially disrupt function of all superficially located sensory receptor cells, including those for chemosensing. Here, we examined whether CoCl 2 treatment used to ablate the lateral line system also impairs olfaction in three freshwater fishes, the African cichlid fish Astatotilapia burtoni , goldfish Carassius auratus , and the Mexican blind cavefish Astyanax mexicanus . To examine the impact of CoCl 2 on the activity of peripheral receptors, we quantified DASPEI fluorescence intensity of the olfactory epithelium from fish exposed to control and CoCl 2 solutions. In addition, we examined brain activation in olfactory processing regions of A . burtoni immersed in either control or cobalt solutions. All three species exposed to CoCl 2 had decreased DASPEI staining of the olfactory epithelium, and in A . burtoni , cobalt treatment caused reduced neural activation in olfactory processing regions of the brain. To our knowledge this is the first empirical evidence demonstrating that the same CoCl 2 treatment used to ablate the lateral line system also impairs olfactory function. These data have important implications for the use of CoCl 2 in future research and suggest that previous studies using CoCl 2 should be reinterpreted in the context of both impaired mechanoreception and olfaction.
    Electronic ISSN: 1932-6203
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  • 86
    Publication Date: 2016-07-15
    Description: by Tsugiko Kurita, Kotaro Sakurai, Youji Takeda, Toru Horinouchi, Ichiro Kusumi Objective Surgical intervention can result in complete seizure remission rates of up to 80% in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). However, certain patients cannot be treated surgically for various reasons. We analyzed the very long-term clinical outcomes of patients with TLE-HS who could not be treated surgically. Methods Subjects were selected from among patients with TLE-HS who were actively followed up for 〉10 years and treated with medication without surgical treatment. Patient medical records were used to retrospectively study seizure frequency, various clinical factors, and social adjustment. Patients who were seizure-free or had only aura were classified into Group 1; the others were classified into Group 2. Clinical factors including both patient and disease-specific factors were compared between the two groups. Current social adjustment, including the education, work, and economic status of each patient, was also investigated. Results Forty-one (41) subjects met the criteria for analysis, of which 12 (29%) were classified into Group 1. The average age of patients in Group 1 was higher than that of Group 2 (p = 0.0468). Group 2 included a significantly higher rate of patients who had more than one seizure per week at the onset (p = 0.0328), as well as a greater mean number of anti-epileptic drugs taken (p = 0.0024). Regarding social adjustment, Group 2 contained significantly fewer current jobholders than Group 1 (p = 0.0288). Conclusions After very long-term follow-up periods, 29% of patients with TLE-HS had a good outcome through treatment with anticonvulsant medications. Older patients tended to have fewer seizures, and seizure frequency at the onset was the only factor that predicted outcome.
    Electronic ISSN: 1932-6203
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  • 87
    Publication Date: 2016-07-15
    Description: by Ingebjørg Helena Nymo, Marit Seppola, Sascha Al Dahouk, Kathrine Ryvold Bakkemo, María Pilar Jiménez de Bagüés, Jacques Godfroid, Anett Kristin Larsen Pathology has not been observed in true seals infected with Brucella pinnipedialis . A lack of intracellular survival and multiplication of B . pinnipedialis in hooded seal ( Cystophora cristata ) macrophages in vitro indicates a lack of chronic infection in hooded seals. Both epidemiology and bacteriological patterns in the hooded seal point to a transient infection of environmental origin, possibly through the food chain. To analyse the potential role of fish in the transmission of B . pinnipedialis , Atlantic cod ( Gadus morhua ) were injected intraperitoneally with 7.5 x 10 7 bacteria of a hooded seal field isolate. Samples of blood, liver, spleen, muscle, heart, head kidney, female gonads and feces were collected on days 1, 7, 14 and 28 post infection to assess the bacterial load, and to determine the expression of immune genes and the specific antibody response. Challenged fish showed an extended period of bacteremia through day 14 and viable bacteria were observed in all organs sampled, except muscle, until day 28. Neither gross lesions nor mortality were recorded. Anti- Brucella antibodies were detected from day 14 onwards and the expression of hepcidin, cathelicidin, interleukin (IL)-1β, IL-10, and interferon (IFN)-γ genes were significantly increased in spleen at day 1 and 28. Primary mononuclear cells isolated from head kidneys of Atlantic cod were exposed to B . pinnipedialis reference (NCTC 12890) and hooded seal (17a-1) strain. Both bacterial strains invaded mononuclear cells and survived intracellularly without any major reduction in bacterial counts for at least 48 hours. Our study shows that the B . pinnipedialis strain isolated from hooded seal survives in Atlantic cod, and suggests that Atlantic cod could play a role in the transmission of B . pinnipedialis to hooded seals in the wild.
    Electronic ISSN: 1932-6203
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  • 88
    Publication Date: 2016-07-15
    Description: by Muskan Jain, Rituraj Batth, Sumita Kumari, Ananda Mustafiz The glyoxalase pathway is ubiquitously found in all the organisms ranging from prokaryotes to eukaryotes. It acts as a major pathway for detoxification of methylglyoxal (MG), which deleteriously affects the biological system in stress conditions. The first important enzyme of this system is Glyoxalase I (GLYI). It is a metalloenzyme which requires divalent metal ions for its activity. This divalent metal ion can be either Zn 2+ as found in most of eukaryotes or Ni 2+ as seen in prokaryotes. In the present study, we have found three active GLYI enzymes (AtGLYI2, AtGLYI3 and AtGLYI6) belonging to different metal activation classes coexisting in Arabidopsis thaliana . These enzymes have been found to efficiently complement the GLYI yeast mutants. These three enzymes have been characterized in terms of their activity, metal dependency, kinetic parameters and their role in conferring tolerance to multiple abiotic stresses in E . coli and yeast. AtGLYI2 was found to be Zn 2+ dependent whereas AtGLYI3 and AtGLYI6 were Ni 2+ dependent. Enzyme activity of Zn 2+ dependent enzyme, AtGLYI2, was observed to be exceptionally high (~250–670 fold) as compared to Ni 2+ dependent enzymes, AtGLYI3 and AtGLYI6. The activity of these GLYI enzymes correlated well to their role in stress tolerance. Heterologous expression of these enzymes in E . coli led to better tolerance against various stress conditions. This is the first report of a higher eukaryotic species having multiple active GLYI enzymes belonging to different metal activation classes.
    Electronic ISSN: 1932-6203
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  • 89
    Publication Date: 2016-07-15
    Description: by Tomohiko Kazama, Kinya Toriyama Nuclear genome substitutions between subspecies can lead to cytoplasmic male sterility (CMS) through incompatibility between nuclear and mitochondrial genomes. Boro-Taichung (BT)-type CMS rice was obtained by substituting the nuclear genome of Oryza sativa subsp. indica cultivar Chinsurah Boro II with that of Oryza sativa subsp. japonica cultivar Taichung 65. In BT-type CMS rice, the mitochondrial gene orf79 is associated with male sterility. A complete sequence of the Boro-type mitochondrial genome responsible for BT-type CMS has not been determined to date. Here, we used pyrosequencing to construct the Boro-type mitochondrial genome. The contiguous sequences were assembled into five circular DNA molecules, four of which could be connected into a single circle. The two resulting subgenomic circles were unable to form a reliable master circle, as recombination between them was scarcely detected. We also found an unequal abundance of DNA molecules for the two loci of atp6 . These results indicate the presence of multi-partite DNA molecules in the Boro-type mitochondrial genome. Expression patterns were investigated for Boro-type mitochondria-specific orf s, which were not found in the mitochondria from the standard japonica cultivar Nipponbare. Restorer of fertility 1 (RF1)-dependent RNA processing has been observed in orf79 -containing RNA but was not detected in other Boro-type mitochondria-specific orf s, supporting the conclusion that orf79 is a unique CMS-associated gene in Boro-type mitochondria.
    Electronic ISSN: 1932-6203
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  • 90
    Publication Date: 2016-07-15
    Description: by Xierong Wei, Amanda J. Smith, David W. Forrest, Gabriel A. Cardenas, Dano W. Beck, Marlene LaLota, Lisa R. Metsch, Catlainn Sionean, S. Michele Owen, Jeffrey A. Johnson Objective To assess the utility of cost-effective dried blood spot (DBS) field sampling for incidence and drug resistance surveillance of persons at high risk for HIV infection. Methods We evaluated DBS collected in 2007–2010 in non-clinical settings by finger-stick from HIV-positive heterosexuals at increased risk of HIV infection (n = 124), men who have sex with men (MSM, n = 110), and persons who inject drugs (PWID, n = 58). Relative proportions of recent-infection findings among risk groups were assessed at avidity index (AI) cutoffs of ≤25%, ≤30%, and ≤35%, corresponding to an infection mean duration of recency (MDR) of 220.6, 250.4, and 278.3 days, respectively. Drug resistance mutation prevalence was compared among the risk groups and avidity indices. Results HIV antibody avidity testing of all self-reported ARV-naïve persons (n = 186) resulted in 9.7%, 11.3% and 14.0% with findings within the 221, 250, and 278-day MDRs, respectively. The proportion of ARV-naïve MSM, heterosexuals, and PWID reporting only one risk category who had findings below the suggested 30% AI was 23.1%, 6.9% and 3.6% (p
    Electronic ISSN: 1932-6203
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  • 91
    Publication Date: 2016-07-15
    Description: by Li Zhang, Lihua Wu, Feng Tian, Zheng Wang A large amount of medical waste is produced during disaster relief, posing a potential hazard to the habitat and the environment. A comprehensive understanding of the composition and characteristics of medical waste that requires management is one of the most basic steps in the development of a plan for medical waste management. Unfortunately, limited reliable information is available in the open literature on the characteristics of the medical waste that is generated at disaster relief sites. This paper discusses the analysis of the composition and characteristics of medical waste at a disaster relief site using the retrospection-simulation-revision method. For this study, we obtained 35 medical relief records of the Wenchuan Earthquake, Sichuan, May 2008 from a field cabin hospital. We first present a retrospective analysis of the relief medical records, and then, we simulate the medical waste generated in the affected areas. We ultimately determine the composition and characteristics of medical waste in the affected areas using untreated medical waste to revise the composition of the simulated medical waste. The results from 35 cases showed that the medical waste generated from disaster relief consists of the following: plastic (43.2%), biomass (26.3%), synthetic fiber (15.3%), rubber (6.6%), liquid (6.6%), inorganic salts (0.3%) and metals (1.7%). The bulk density of medical relief waste is 249 kg/m 3 , and the moisture content is 44.75%. The data should be provided to assist the collection, segregation, storage, transportation, disposal and contamination control of medical waste in affected areas. In this paper, we wish to introduce this research method of restoring the medical waste generated in disaster relief to readers and researchers. In addition, we hope more disaster relief agencies will become aware of the significance of medical case recording and storing. This may be very important for the environmental evaluation of medical waste in disaster areas, as well as for medical waste management and disposal.
    Electronic ISSN: 1932-6203
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  • 92
    Publication Date: 2016-07-15
    Description: by Jan Skoda, Marketa Hermanova, Tomas Loja, Pavel Nemec, Jakub Neradil, Petr Karasek, Renata Veselska Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Its dismal prognosis is often attributed to the presence of cancer stem cells (CSCs) that have been identified in PDAC using various markers. However, the co-expression of all of these markers has not yet been evaluated. Furthermore, studies that compare the expression levels of CSC markers in PDAC tumor samples and in cell lines derived directly from those tumors are lacking. Here, we analyzed the expression of putative CSC markers—CD24, CD44, epithelial cell adhesion molecule (EpCAM), CD133, and nestin—by immunofluorescence, flow cytometry and quantitative PCR in 3 PDAC-derived cell lines and by immunohistochemistry in 3 corresponding tumor samples. We showed high expression of the examined CSC markers among all of the cell lines and tumor samples, with the exception of CD24 and CD44, which were enriched under in vitro conditions compared with tumor tissues. The proportions of cells positive for the remaining markers were comparable to those detected in the corresponding tumors. Co-expression analysis using flow cytometry revealed that CD24 + /CD44 + /EpCAM + /CD133 + cells represented a significant population of the cells (range, 43 to 72%) among the cell lines. The highest proportion of CD24 + /CD44 + /EpCAM + /CD133 + cells was detected in the cell line derived from the tumor of a patient with the shortest survival. Using gene expression profiling, we further identified the specific pro-tumorigenic expression profile of this cell line compared with the profiles of the other two cell lines. Together, CD24 + /CD44 + /EpCAM + /CD133 + cells are present in PDAC cell lines derived from primary tumors, and their increased proportion corresponds with a pro-tumorigenic gene expression profile.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 93
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    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2016-07-15
    Description: by Tarcísio Visintin da Silva Galdino, Sunil Kumar, Leonardo S. S. Oliveira, Acelino C. Alfenas, Lisa G. Neven, Abdullah M. Al-Sadi, Marcelo C. Picanço The Mango Sudden Decline (MSD), also referred to as Mango Wilt, is an important disease of mango in Brazil, Oman and Pakistan. This fungus is mainly disseminated by the mango bark beetle, Hypocryphalus mangiferae (Stebbing), by infected plant material, and the infested soils where it is able to survive for long periods. The best way to avoid losses due to MSD is to prevent its establishment in mango production areas. Our objectives in this study were to: (1) predict the global potential distribution of MSD, (2) identify the mango growing areas that are under potential risk of MSD establishment, and (3) identify climatic factors associated with MSD distribution. Occurrence records were collected from Brazil, Oman and Pakistan where the disease is currently known to occur in mango. We used the correlative maximum entropy based model (MaxEnt) algorithm to assess the global potential distribution of MSD. The MaxEnt model predicted suitable areas in countries where the disease does not already occur in mango, but where mango is grown. Among these areas are the largest mango producers in the world including India, China, Thailand, Indonesia, and Mexico. The mean annual temperature, precipitation of coldest quarter, precipitation seasonality, and precipitation of driest month variables contributed most to the potential distribution of MSD disease. The mango bark beetle vector is known to occur beyond the locations where MSD currently exists and where the model predicted suitable areas, thus showing a high likelihood for disease establishment in areas predicted by our model. Our study is the first to map the potential risk of MSD establishment on a global scale. This information can be used in designing strategies to prevent introduction and establishment of MSD disease, and in preparation of efficient pest risk assessments and monitoring programs.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 94
    Publication Date: 2016-07-15
    Description: by Ge Song, Xiao-Xia Shao, Qing-Ping Wu, Zeng-Guang Xu, Ya-Li Liu, Zhan-Yun Guo We recently developed novel bioluminescent binding assays for several protein/peptide hormones to study their interactions with receptors using the so far brightest NanoLuc reporter. To validate the novel bioluminescent binding assay using a variety of protein/peptide hormones, in the present work we applied it to the fibroblast growth factor (FGF) family using the prototype member FGF2 as an example. A fully active recombinant FGF2 retaining a unique exposed cysteine (Cys) residue was chemically conjugated with an engineered NanoLuc carrying a unique exposed Cys residue at the C-terminus via formation of an intermolecular disulfide linkage. The NanoLuc-conjugated FGF2 (FGF2-Luc) retained high binding affinity to the overexpressed FGFR1 and the endogenous FGF receptor with the calculated dissociation constants of 161 ± 21 pM ( n = 3) and 25 ± 4 pM ( n = 3), respectively. In competition binding assays using FGF2-Luc as a tracer, receptor-binding potencies of wild-type or mutant FGF2s were accurately quantified. Thus, FGF2-Luc represents a novel non-radioactive tracer for the quantitative measurement of ligand–receptor interactions in the FGF family. These data suggest that the novel bioluminescent binding assay can be applied to a variety of protein/peptide hormones for ligand–receptor interaction studies.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 95
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    Unknown
    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2016-07-16
    Description: by Isabel C. Caballero, John M. Bates, Mary Hennen, Mary V. Ashley Peregrine falcons ( Falco peregrinus ) were extirpated from most of the continental United States by widespread use of the pesticide DDT in the 1960s. Populations have rebounded with banning of the pesticide and successful implementation of captive breeding and hacking programs. An essentially new population of Midwestern peregrines now exists that is comprised almost entirely of urban-nesting birds. The new population is considered to be of mixed ancestry, occurs at relatively high densities, and has nest sites in close proximity, factors that could influence breeding behaviors including mate fidelity, nest-site fidelity, extra-pair paternity, and natal dispersal. We investigated these behaviors using a combination of field observations and DNA microsatellite genotyping. Data for eleven microsatellite DNA markers, including eight newly developed for the species, were analyzed from a total of 350 birds from nine Midwestern cities, representing 149 broods collected at 20 nest sites. To document breeding behavior, parentage was inferred by likelihood techniques when both parents were sampled and by parental genotype reconstruction when only one parent was sampled. In cases where neither parent was sampled, a sibship reconstruction approach was used. We found high mate fidelity and nest-site fidelity in urban peregrines; in 122 nesting attempts made by long-term breeders, only 12 (9.8%) mate changes and six (4.9%) nest-site changes occurred. Only one brood (of 35 tested) revealed extra-pair paternity and involved a male tending two offspring of a recently acquired mate. Natal dispersal patterns indicated that female peregrines dispersed on average 226 km, almost twice the distance of males (average 124 km). Despite the novel environment of cities, our results suggest that monogamous breeding, nest fidelity, and female natal dispersal are high in urban peregrines, not unlike other raptors living in non-urban habitats.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 96
    Publication Date: 2016-07-16
    Description: by Henrik H. Hansen, Katrine Fabricius, Pernille Barkholt, Pernille Kongsbak-Wismann, Chantal Schlumberger, Jacob Jelsing, Dick Terwel, Annelies Termont, Charles Pyke, Lotte Bjerre Knudsen, Niels Vrang One of the major histopathological hallmarks of Alzheimer’s disease (AD) is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1) receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP) and presenilin-1 (PS1) are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds. In this study, effects of long-term liraglutide treatment were therefore determined in two double APP/PS1 transgenic mouse models of Alzheimer’s disease carrying different clinical APP/PS1 mutations, i . e . the ‘London’ (hAPP Lon/ PS1 A246E ) and ‘Swedish’ mutation variant (hAPP Swe /PS1 ΔE9 ) of APP, with co-expression of distinct PS1 variants. Liraglutide was administered in 5 month-old hAPP Lon/ PS1 A246E mice for 3 months (100 or 500 ng/kg/day, s.c.), or 7 month-old hAPP Swe /PS1 ΔE9 mice for 5 months (500 ng/kg/day, s.c.). In both models, regional plaque load was quantified throughout the brain using stereological methods. Vehicle-dosed hAPP Swe /PS1 ΔE9 mice exhibited considerably higher cerebral plaque load than hAPP Lon/ PS1 A246E control mice. Compared to vehicle-dosed transgenic controls, liraglutide treatment had no effect on the plaque levels in hAPP Lon /PS1 A246E and hAPP Swe /PS1 ΔE9 mice. In conclusion, long-term liraglutide treatment exhibited no effect on cerebral plaque load in two transgenic mouse models of low- and high-grade amyloidosis, which suggests differential sensitivity to long-term liraglutide treatment in various transgenic mouse models mimicking distinct pathological hallmarks of AD.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 97
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    Public Library of Science (PLoS)
    In: PLoS ONE
    Publication Date: 2016-07-16
    Description: by Ye Fang, Yun Ding, Wei P. Feinstein, David M. Koppelman, Juana Moreno, Mark Jarrell, J. Ramanujam, Michal Brylinski Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 98
    Publication Date: 2016-07-16
    Description: by Rinske Loeffen, René van Oerle, Mathie P. G. Leers, Johannes A. Kragten, Harry Crijns, Henri M. H. Spronk, Hugo ten Cate Objective In acute coronary syndrome (ACS) cardiac cell damage is preceded by thrombosis. Therefore, plasma coagulation markers may have additional diagnostic relevance in ACS. By using novel coagulation assays this study aims to gain more insight into the relationship between the coagulation system and ACS. Methods We measured plasma thrombin generation, factor XIa and D-dimer levels in plasma from ACS (n = 104) and non-ACS patients (n = 42). Follow-up measurements (n = 73) were performed at 1 and 6 months. Associations between coagulation markers and recurrent cardiovascular events were calculated by logistic regression analysis. Results Thrombin generation was significantly enhanced in ACS compared to non-ACS patients: peak height 148±53 vs. 122±42 nM. There was a significantly diminished ETP reduction (32 vs. 41%) and increased intrinsic coagulation activation (25 vs. 7%) in ACS compared to non-ACS patients. Furthermore, compared to non-ACS patients factor XIa and D-dimer levels were significantly elevated in ACS patients: 1.9±1.1 vs. 1.4±0.7 pM and 495(310–885) vs. 380(235–540) μg/L. Within the ACS spectrum, ST-elevated myocardial infarction patients had the highest prothrombotic profile. During the acute event, thrombin generation was significantly increased compared to 1 and 6 months afterwards: peak height 145±52 vs. 100±44 vs. 98±33 nM. Both peak height and factor XIa levels on admission predicted recurrent cardiovascular events (OR: 4.9 [95%CI 1.2–20.9] and 4.5 [1.1–18.9]). Conclusion ACS patients had an enhanced prothrombotic profile, demonstrated by an increased thrombin generation potential, factor XIa and D-dimer levels. This study is the first to demonstrate the positive association between factor XIa, thrombin generation and recurrent cardiovascular events.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 99
    Publication Date: 2016-07-16
    Description: Tetraspanin CD82 Regulates the Spatiotemporal Dynamics of PKCα in Acute Myeloid Leukemia Scientific Reports, Published online: 15 July 2016; doi:10.1038/srep29859
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 100
    Publication Date: 2016-07-16
    Description: Adiponectin enhances bone marrow mesenchymal stem cell resistance to flow shear stress through AMP-activated protein kinase signaling Scientific Reports, Published online: 15 July 2016; doi:10.1038/srep28752
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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