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  • Public Library of Science  (131,866)
  • Cell Press  (76,245)
  • Irkutsk : Ross. Akad. Nauk, Sibirskoe Otd., Inst. Zemnoj Kory
  • Krefeld : Geologischer Dienst Nordhein-Westfalen
  • Public Library of Science (PLoS)
  • 2010-2014  (191,633)
  • 2005-2009  (43,166)
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  • 1
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    Multiple Sclerosis in the Mount Etna Region: Possible Role of Volcanogenic Trace Elements (2014)
    Public Library of Science
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    Publication Date: 2017-04-04
    Description: Background: Trace elements have been hypothesised to be involved in the pathogenesis of Multiple Sclerosis and volcanic degassing is the major natural sources of trace elements. Both incidence of Multiple Sclerosis in Catania and volcanic activity of Mount Etna have been significantly increased during the last 30 years. Due to prevailing trade winds direction, volcanic gases from Etna summit craters are mostly blown towards the eastern and southern sectors of the volcano. Objective: To evaluate the possible association between Multiple Sclerosis and exposure to volcanogenic trace elements. Methods: We evaluated prevalence and incidence of Multiple Sclerosis in four communities (47,234 inhabitants) located in the eastern flank and in two communities (52,210 inhabitants) located in the western flank of Mount Etna, respectively the most and least exposed area to crater gas emissions. Results: A higher prevalence was found in the population of the eastern flank compared to the population of the western one (137.6/100,000 versus 94.3/100,000; p-value 0.04). We found a borderline significantly higher incidence risk during the incidence study period (1980–2009) in the population of the eastern flank 4.6/100,000 (95% CI 3.1–5.9), compared with the western population 3.2/100,000 (95% CI 2.4–4.2) with a RR of 1.41 (95% CI 0.97–2.05; p-value 0.06). Incidence risks have increased over the time in both populations reaching a peak of 6.4/100,000 in the eastern flank and of 4.4/100.000 in the western flank during 2000–2009. Conclusion: We found a higher prevalence and incidence of Multiple Sclerosis among populations living in the eastern flank of Mount Etna. According to our data a possible role of TE cannot be ruled out as possible co-factor in the MS pathogenesis. However larger epidemiological study are needed to confirm this hypothesis.
    Description: Published
    Description: e74259
    Description: 6A. Monitoraggio ambientale, sicurezza e territorio
    Description: JCR Journal
    Description: open
    Keywords: Mt. Etna volcano ; Multiple Sclerosis ; trace elements ; volcanic activity ; 05. General::05.08. Risk::05.08.01. Environmental risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 2
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    Geosphere-biosphere interacions in bio-activity volcanic lakes: evidences from Hule and Rìo Cuarto (Costa Rica). (2014)
    Public Library of Science
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    Publication Date: 2020-02-24
    Description: Hule and Rı´o Cuarto are maar lakes located 11 and 18 km N of Poa´s volcano along a 27 km long fracture zone, in the Central Volcanic Range of Costa Rica. Both lakes are characterized by a stable thermic and chemical stratification and recently they were affected by fish killing events likely related to the uprising of deep anoxic waters to the surface caused by rollover phenomena. The vertical profiles of temperature, pH, redox potential, chemical and isotopic compositions of water and dissolved gases, as well as prokaryotic diversity estimated by DNA fingerprinting and massive 16S rRNA pyrosequencing along the water column of the two lakes, have highlighted that different bio-geochemical processes occur in these meromictic lakes. Although the two lakes host different bacterial and archaeal phylogenetic groups, water and gas chemistry in both lakes is controlled by the same prokaryotic functions, especially regarding the CO2-CH4 cycle. Addition of hydrothermal CO2 through the bottom of the lakes plays a fundamental priming role in developing a stable water stratification and fuelling anoxic bacterial and archaeal populations. Methanogens and methane oxidizers as well as autotrophic and heterotrophic aerobic bacteria responsible of organic carbon recycling resulted to be stratified with depth and strictly related to the chemical-physical conditions and availability of free oxygen, affecting both the CO2 and CH4 chemical concentrations and their isotopic compositions along the water column. Hule and Rı´o Cuarto lakes were demonstrated to contain a CO2 (CH4, N2)-rich gas reservoir mainly controlled by the interactions occurring between geosphere and biosphere. Thus, we introduced the term of bio-activity volcanic lakes to distinguish these lakes, which have analogues worldwide (e.g. Kivu: D.R.C.-Rwanda; Albano, Monticchio and Averno: Italy; Pavin: France) from volcanic lakes only characterized by geogenic CO2 reservoir such as Nyos and Monoun (Cameroon).
    Description: Published
    Description: e102456
    Description: 4V. Vulcani e ambiente
    Description: JCR Journal
    Description: open
    Keywords: bio activity, volcanic lakes, costa rica ; 03. Hydrosphere::03.04. Chemical and biological::03.04.06. Hydrothermal systems
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 3
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    Compositional discrimination of decompression and decomposition gas bubbles in bycaught seals and dolphins (2014)
    Public Library of Science
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    Publication Date: 2022-05-25
    Description: This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. The definitive version was published in PLoS One 8 (2013): e83994, doi:10.1371/journal.pone.0083994.
    Description: Gas bubbles in marine mammals entangled and drowned in gillnets have been previously described by computed tomography, gross examination and histopathology. The absence of bacteria or autolytic changes in the tissues of those animals suggested that the gas was produced peri- or post-mortem by a fast decompression, probably by quickly hauling animals entangled in the net at depth to the surface. Gas composition analysis and gas scoring are two new diagnostic tools available to distinguish gas embolisms from putrefaction gases. With this goal, these methods have been successfully applied to pathological studies of marine mammals. In this study, we characterized the flux and composition of the gas bubbles from bycaught marine mammals in anchored sink gillnets and bottom otter trawls. We compared these data with marine mammals stranded on Cape Cod, MA, USA. Fresh animals or with moderate decomposition (decomposition scores of 2 and 3) were prioritized. Results showed that bycaught animals presented with significantly higher gas scores than stranded animals. Gas composition analyses indicate that gas was formed by decompression, confirming the decompression hypothesis.
    Description: This study was funded by the Woods Hole Oceanographic Institution Marine Mammal Center, and Wick and Sloan Simmons.
    Repository Name: Woods Hole Open Access Server
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  • 4
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    Decadal changes in zooplankton of the Northeast U.S. continental shelf (2014)
    Public Library of Science
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    Publication Date: 2022-05-25
    Description: This article is distributed under the Creative Commons CC0 public domain dedication. The definitive version was published in PLoS One 9 (2014): e87720, doi:10.1371/journal.pone.0087720.
    Description: The abundance of the subarctic copepod, Calanus finmarchicus, and temperate, shelf copepod, Centropages typicus, was estimated from samples collected bi-monthly over the Northeast U.S. continental shelf (NEUS) from 1977–2010. Latitudinal variation in long term trends and seasonal patterns for the two copepod species were examined for four sub-regions: the Gulf of Maine (GOM), Georges Bank (GB), Southern New England (SNE), and Mid-Atlantic Bight (MAB). Results suggested that there was significant difference in long term variation between northern region (GOM and GB), and the MAB for both species. C. finmarchicus generally peaked in May – June throughout the entire study region and Cen. typicus had a more complex seasonal pattern. Time series analysis revealed that the peak time for Cen. typicus switched from November – December to January - March after 1985 in the MAB. The long term abundance of C. finmarchicus showed more fluctuation in the MAB than the GOM and GB, whereas the long term abundance of Cen. typicus was more variable in the GB than other sub-regions. Alongshore transport was significantly correlated with the abundance of C. finmarchicus, i.e., more water from north, higher abundance for C. finmarchicus. The abundance of Cen. typicus showed positive relationship with the Gulf Stream north wall index (GSNWI) in the GOM and GB, but the GSNWI only explained 12–15% of variation in Cen. typicus abundance. In general, the alongshore current was negatively correlated with the GSNWI, suggesting that Cen. typicus is more abundant when advection from the north is less. However, the relationship between Cen. typicus and alongshore transport was not significant. The present study highlights the importance of spatial scales in the study of marine populations: observed long term changes in the northern region were different from the south for both species.
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  • 5
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    A quantitative assessment of the role of the parasite Amoebophrya in the termination of Alexandrium fundyense blooms within a small coastal embayment (2014)
    Public Library of Science
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 8 (2013): e81150, doi:10.1371/journal.pone.0081150.
    Description: Parasitic dinoflagellates of the genus Amoebophrya infect free-living dinoflagellates, some of which can cause harmful algal blooms (HABs). High prevalence of Amoebophrya spp. has been linked to the decline of some HABs in marine systems. The objective of this study was to evaluate the impact of Amoebophrya spp. on the dynamics of dinoflagellate blooms in Salt Pond (MA, USA), particularly the harmful species Alexandrium fundyense. The abundance of Amoebophrya life stages was estimated 3–7 days per week through the full duration of an annual A. fundyense bloom using fluorescence in situ hybridization coupled with tyramide signal amplification (FISH- TSA). More than 20 potential hosts were recorded including Dinophysis spp., Protoperidinium spp. and Gonyaulax spp., but the only dinoflagellate cells infected by Amoebophrya spp. during the sampling period were A. fundyense. Maximum A. fundyense concentration co-occurred with an increase of infected hosts, followed by a massive release of Amoebophrya dinospores in the water column. On average, Amoebophrya spp. infected and killed ~30% of the A. fundyense population per day in the end phase of the bloom. The decline of the host A. fundyense population coincided with a dramatic life-cycle transition from vegetative division to sexual fusion. This transition occurred after maximum infected host concentrations and before peak infection percentages were observed, suggesting that most A. fundyense escaped parasite infection through sexual fusion. The results of this work highlight the importance of high frequency sampling of both parasite and host populations to accurately assess the impact of parasites on natural plankton assemblages.
    Description: L. Velo-Sua´rez was supported by a Marie Curie International Outgoing Fellowship (IOF; grant agreement: MOHAB PIOF-GA-252260). This work was supported in part by NSF grants OCE-0430724 and OCE-0911031 and National Institute of Environmental Health Sciences grants 1P50-ES01274201 and 1P01ES021923-01 to D.M. Anderson and D.J. McGillicuddy through the Woods Hole Center for Oceans and Human Health, National Park Service Cooperative Agreement H238015504 to D.M. Anderson.
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  • 6
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    Diving behavior of the reef manta ray links coral reefs with adjacent deep pelagic habitats (2014)
    Public Library of Science
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e88170, doi:10.1371/journal.pone.0088170.
    Description: Recent successful efforts to increase protection for manta rays has highlighted the lack of basic ecological information, including vertical and horizontal movement patterns, available for these species. We deployed pop-up satellite archival transmitting tags on nine reef manta rays, Manta alfredi, to determine diving behaviors and vertical habitat use. Transmitted and archived data were obtained from seven tagged mantas over deployment periods of 102–188 days, including three recovered tags containing 2.6 million depth, temperature, and light level data points collected every 10 or 15 seconds. Mantas frequented the upper 10 m during daylight hours and tended to occupy deeper water throughout the night. Six of the seven individuals performed a cumulative 76 deep dives (〉150 m) with one individual reaching 432 m, extending the known depth range of this coastal, reef-oriented species and confirming its role as an ecological link between epipelagic and mesopelagic habitats. Mean vertical velocities calculated from high-resolution dive data (62 dives 〉150 m) from three individuals suggested that mantas may use gliding behavior during travel and that this behavior may prove more efficient than continuous horizontal swimming. The behaviors in this study indicate manta rays provide a previously unknown link between the epi- and mesopelagic layers of an extremely oligotrophic marine environment and provide evidence of a third marine species that utilizes gliding to maximize movement efficiency.
    Description: inancial support was provided in part by KAUST baseline research funds (to MLB), KAUST award numbers USA00002 and KSA 00011 (to SRT), and the U.S. National Science Foundation (OCE 0825148 to SRT and GBS).
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  • 7
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    Identification of cinnabarinic acid as novel endogenous aryl hydrocarbon receptor ligand that drives IL-22 production (2014)
    Public Library of Science
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e87877, doi:10.1371/journal.pone.0087877.
    Description: The aryl hydrocarbon receptor (AHR) binds to environmental toxicants including synthetic halogenated aromatic hydrocarbons and is involved in a diverse array of biological processes. Recently, the AHR was shown to control host immunity by affecting the balance between inflammatory T cells that produce IL-17 (Th17) and IL-22 versus regulatory T cells (Treg) involved in tolerance. While environmental AHR ligands can mediate this effect, endogenous ligands are likely to be more relevant in host immune responses. We investigated downstream metabolites of tryptophan as potential AHR ligands because (1) tryptophan metabolites have been implicated in regulating the balance between Th17 and Treg cells and (2) many of the AHR ligands identified thus far are derivatives of tryptophan. We characterized the ability of tryptophan metabolites to bind and activate the AHR and to increase IL-22 production in human T cells. We report that the tryptophan metabolite, cinnabarinic acid (CA), is an AHR ligand that stimulates the differentiation of human and mouse T cells producing IL-22. We compare the IL-22-stimulating activity of CA to that of other tryptophan metabolites and define stimulation conditions that lead to CA production from immune cells. Our findings link tryptophan metabolism to AHR activation and define a novel endogenous AHR agonist with potentially broad biological functions.
    Description: This work was supported in part by National Institutes of Health (NIH) grants OD000329 and R01AI40312 (to JMM), R01ES006272 (to MEH), P42ES007381 (Superfund Research Program at Boston University to JS, DHS and MEH), R21CA134882 (to JS), NIH Training Grant T32 GM007175 (MML), and the Harvey V. Berneking Living Trust. BK is supported by Career Development Awards from the NIH/National Institute of Diabetes and Digestive and Kidney Diseases (DK083334) and the NASPGHAN Foundation. JEM is a recipient of the Human Frontiers Science Program Long-Term Fellowship (LT000231/2011-L). JMM is a recipient of the NIH Director's Pioneer Award Program, part of the NIH Roadmap for Medical Research, through grant DPI OD00329.
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  • 8
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    Shifts in the microbial community composition of Gulf Coast beaches following beach oiling (2014)
    Public Library of Science
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 8 (2013): e74265, doi:10.1371/journal.pone.0074265.
    Description: Microorganisms associated with coastal sands serve as a natural biofilter, providing essential nutrient recycling in nearshore environments and acting to maintain coastal ecosystem health. Anthropogenic stressors often impact these ecosystems, but little is known about whether these disturbances can be identified through microbial community change. The blowout of the Macondo Prospect reservoir on April 20, 2010, which released oil hydrocarbons into the Gulf of Mexico, presented an opportunity to examine whether microbial community composition might provide a sensitive measure of ecosystem disturbance. Samples were collected on four occasions, beginning in mid-June, during initial beach oiling, until mid-November from surface sand and surf zone waters at seven beaches stretching from Bay St. Louis, MS to St. George Island, FL USA. Oil hydrocarbon measurements and NOAA shoreline assessments indicated little to no impact on the two most eastern beaches (controls). Sequence comparisons of bacterial ribosomal RNA gene hypervariable regions isolated from beach sands located to the east and west of Mobile Bay in Alabama demonstrated that regional drivers account for markedly different bacterial communities. Individual beaches had unique community signatures that persisted over time and exhibited spatial relationships, where community similarity decreased as horizontal distance between samples increased from one to hundreds of meters. In contrast, sequence analyses detected larger temporal and less spatial variation among the water samples. Superimposed upon these beach community distance and time relationships, was increased variability in bacterial community composition from oil hydrocarbon contaminated sands. The increased variability was observed among the core, resident, and transient community members, indicating the occurrence of community-wide impacts rather than solely an overprinting of oil hydrocarbon-degrading bacteria onto otherwise relatively stable sand population structures. Among sequences classified to genus, Alcanivorax, Alteromonas, Marinobacter, Winogradskyella, and Zeaxanthinibacter exhibited the largest relative abundance increases in oiled sands.
    Description: Financial support for this work was provided by the University of Wisconsin-Milwaukee National Institute of Environmental Health Sciences program, grant ES-004184 to SLM and the Alfred P. Sloan Foundation's grant for the Rare Biosphere in the Built Environment MLS.
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  • 9
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    Vertebral bomb radiocarbon suggests extreme longevity in white sharks (2014)
    Public Library of Science
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    Publication Date: 2022-05-25
    Description: This article is distributed free of all copyright. The definitive version was published in PLoS One 9 (2014): e84006, doi:10.1371/journal.pone.0084006.
    Description: Conservation and management efforts for white sharks (Carcharodon carcharias) remain hampered by a lack of basic demographic information including age and growth rates. Sharks are typically aged by counting growth bands sequentially deposited in their vertebrae, but the assumption of annual deposition of these band pairs requires testing. We compared radiocarbon (Δ14C) values in vertebrae from four female and four male white sharks from the northwestern Atlantic Ocean (NWA) with reference chronologies documenting the marine uptake of 14C produced by atmospheric testing of thermonuclear devices to generate the first radiocarbon age estimates for adult white sharks. Age estimates were up to 40 years old for the largest female (fork length [FL]: 526 cm) and 73 years old for the largest male (FL: 493 cm). Our results dramatically extend the maximum age and longevity of white sharks compared to earlier studies, hint at possible sexual dimorphism in growth rates, and raise concerns that white shark populations are considerably more sensitive to human-induced mortality than previously thought.
    Description: This study was funded by the National Science Foundation (OCE 0825148 was awarded to SRT) and LLH was supported by the National Science Foundation Graduate Research Fellowship Program.
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  • 10
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    Strong depth-related zonation of megabenthos on a rocky continental margin (∼700–4000 m) off southern Tasmania, Australia (2014)
    Public Library of Science
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e85872, doi:10.1371/journal.pone.0085872.
    Description: Assemblages of megabenthos are structured in seven depth-related zones between ~700 and 4000 m on the rocky and topographically complex continental margin south of Tasmania, southeastern Australia. These patterns emerge from analysis of imagery and specimen collections taken from a suite of surveys using photographic and in situ sampling by epibenthic sleds, towed video cameras, an autonomous underwater vehicle and a remotely operated vehicle (ROV). Seamount peaks in shallow zones had relatively low biomass and low diversity assemblages, which may be in part natural and in part due to effects of bottom trawl fishing. Species richness was highest at intermediate depths (1000–1300 m) as a result of an extensive coral reef community based on the bioherm-forming scleractinian Solenosmilia variabilis. However, megabenthos abundance peaked in a deeper, low diversity assemblage at 2000–2500 m. The S. variabilis reef and the deep biomass zone were separated by an extensive dead, sub-fossil S. variabilis reef and a relatively low biomass stratum on volcanic rock roughly coincident with the oxygen minimum layer. Below 2400 m, megabenthos was increasingly sparse, though punctuated by occasional small pockets of relatively high diversity and biomass. Nonetheless, megabenthic organisms were observed in the vast majority of photographs on all seabed habitats and to the maximum depths observed - a sandy plain below 3950 m. Taxonomic studies in progress suggest that the observed depth zonation is based in part on changing species mixes with depth, but also an underlying commonality to much of the seamount and rocky substrate biota across all depths. Although the mechanisms supporting the extraordinarily high biomass in 2000–2500 m depths remains obscure, plausible explanations include equatorwards lateral transport of polar production and/or a response to depth-stratified oxygen availability.
    Description: Components of this work were supported by the National Science Foundation, the Australian Department of Environment, Water, Heritage, and the Arts, the Australian Commonwealth Environmental Research Fund, a grant of ship time by the Australian National Research Facility, and the CSIRO Wealth from Oceans and Climate Adaptation Flagships.
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  • 11
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    Transcriptome data reveal syndermatan relationships and suggest the evolution of endoparasitism in Acanthocephala via an epizoic stage (2014)
    Public Library of Science
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e88618, doi:10.1371/journal.pone.0088618.
    Description: The taxon Syndermata comprises the biologically interesting wheel animals (“Rotifera”: Bdelloidea + Monogononta + Seisonidea) and thorny-headed worms (Acanthocephala), and is central for testing superordinate phylogenetic hypotheses (Platyzoa, Gnathifera) in the metazoan tree of life. Recent analyses of syndermatan phylogeny suggested paraphyly of Eurotatoria (free-living bdelloids and monogononts) with respect to endoparasitic acanthocephalans. Data of epizoic seisonids, however, were absent, which may have affected the branching order within the syndermatan clade. Moreover, the position of Seisonidea within Syndermata should help in understanding the evolution of acanthocephalan endoparasitism. Here, we report the first phylogenomic analysis that includes all four higher-ranked groups of Syndermata. The analyzed data sets comprise new transcriptome data for Seison spec. (Seisonidea), Brachionus manjavacas (Monogononta), Adineta vaga (Bdelloidea), and Paratenuisentis ambiguus (Acanthocephala). Maximum likelihood and Bayesian trees for a total of 19 metazoan species were reconstructed from up to 410 functionally diverse proteins. The results unanimously place Monogononta basally within Syndermata, and Bdelloidea appear as the sister group to a clade comprising epizoic Seisonidea and endoparasitic Acanthocephala. Our results support monophyly of Syndermata, Hemirotifera (Bdelloidea + Seisonidea + Acanthocephala), and Pararotatoria (Seisonidea + Acanthocephala), rejecting monophyly of traditional Rotifera and Eurotatoria. This serves as an indication that early acanthocephalans lived epizoically or as ectoparasites on arthropods, before their complex lifecycle with arthropod intermediate and vertebrate definite hosts evolved.
    Description: The work was funded by the Deutsche Forschungsgemeinschaft (DFG grant Ha2103/4-3, Priority Project "Deep Metazoan Phylogeny", SPP1174; www. dfg.de). Additional financial support came from the Center for Computational Sciences (SRFN) of Johannes Gutenberg University Mainz (http://www.csm.unimainz. de).
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  • 12
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    Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses (2014)
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e97338, doi:10.1371/journal.pone.0097338.
    Description: Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.
    Description: This work was supported by King Abdullah University for Science and Technology Global Collaborative Partners (GCR) program.
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  • 13
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    Capture of lipopolysaccharide (endotoxin) by the blood clot : a comparative study (2014)
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 8 (2013): e80192, doi:10.1371/journal.pone.0080192.
    Description: In vertebrates and arthropods, blood clotting involves the establishment of a plug of aggregated thrombocytes (the cellular clot) and an extracellular fibrillar clot formed by the polymerization of the structural protein of the clot, which is fibrin in mammals, plasma lipoprotein in crustaceans, and coagulin in the horseshoe crab, Limulus polyphemus. Both elements of the clot function to staunch bleeding. Additionally, the extracellular clot functions as an agent of the innate immune system by providing a passive anti-microbial barrier and microbial entrapment device, which functions directly at the site of wounds to the integument. Here we show that, in addition to these passive functions in immunity, the plasma lipoprotein clot of lobster, the coagulin clot of Limulus, and both the platelet thrombus and the fibrin clot of mammals (human, mouse) operate to capture lipopolysaccharide (LPS, endotoxin). The lipid A core of LPS is the principal agent of gram-negative septicemia, which is responsible for more than 100,000 human deaths annually in the United States and is similarly toxic to arthropods. Quantification using the Limulus Amebocyte Lysate (LAL) test shows that clots capture significant quantities of LPS and fluorescent-labeled LPS can be seen by microscopy to decorate the clot fibrils. Thrombi generated in the living mouse accumulate LPS in vivo. It is suggested that capture of LPS released from gram-negative bacteria entrapped by the blood clot operates to protect against the disease that might be caused by its systemic dispersal.
    Description: Grant # 0344360 from the National Science Foundation (PBA).
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  • 14
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    Comparison of bacterial communities in sands and water at beaches with bacterial water quality violations (2014)
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e90815, doi:10.1371/journal.pone.0090815.
    Description: Recreational water quality, as measured by culturable fecal indicator bacteria (FIB), may be influenced by persistent populations of these bacteria in local sands or wrack, in addition to varied fecal inputs from human and/or animal sources. In this study, pyrosequencing was used to generate short sequence tags of the 16S hypervariable region ribosomal DNA from shallow water samples and from sand samples collected at the high tide line and at the intertidal water line at sites with and without FIB exceedance events. These data were used to examine the sand and water bacterial communities to assess the similarity between samples, and to determine the impact of water quality exceedance events on the community composition. Sequences belonging to a group of bacteria previously identified as alternative fecal indicators were also analyzed in relationship to water quality violation events. We found that sand and water samples hosted distinctly different overall bacterial communities, and there was greater similarity in the community composition between coastal water samples from two distant sites. The dissimilarity between high tide and intertidal sand bacterial communities, although more similar to each other than to water, corresponded to greater tidal range between the samples. Within the group of alternative fecal indicators greater similarity was observed within sand and water from the same site, likely reflecting the anthropogenic contribution at each beach. This study supports the growing evidence that community-based molecular tools can be leveraged to identify the sources and potential impact of fecal pollution in the environment, and furthermore suggests that a more diverse bacterial community in beach sand and water may reflect a less contaminated site and better water quality.
    Description: This work was supported by the National Science Foundation grant OCE-0430724, and the National Institute of Environmental Health Sciences grant P0ES012742 to the Woods Hole Center for Ocean and Human Health. E. Halliday was partially supported by WHOI Academic Programs and grants from the WHOI Ocean Ventures Fund and the WHOI Coastal Ocean Institute.
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    Movement patterns of juvenile whale sharks tagged at an aggregation site in the Red Sea (2014)
    Public Library of Science
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e103536, doi:10.1371/journal.pone.0103536.
    Description: Conservation efforts aimed at the whale shark, Rhincodon typus, remain limited by a lack of basic information on most aspects of its ecology, including global population structure, population sizes and movement patterns. Here we report on the movements of 47 Red Sea whale sharks fitted with three types of satellite transmitting tags from 2009–2011. Most of these sharks were tagged at a single aggregation site near Al-Lith, on the central coast of the Saudi Arabian Red Sea. Individuals encountered at this site were all juveniles based on size estimates ranging from 2.5–7 m total length with a sex ratio of approximately 1:1. All other known aggregation sites for juvenile whale sharks are dominated by males. Results from tagging efforts showed that most individuals remained in the southern Red Sea and that some sharks returned to the same location in subsequent years. Diving data were recorded by 37 tags, revealing frequent deep dives to at least 500 m and as deep as 1360 m. The unique temperature-depth profiles of the Red Sea confirmed that several whale sharks moved out of the Red Sea while tagged. The wide-ranging horizontal movements of these individuals highlight the need for multinational, cooperative efforts to conserve R. typus populations in the Red Sea and Indian Ocean.
    Description: Financial support was provided in part by KAUST baseline research funds (to MLB), KAUST award nos. USA00002 and KSA 00011 (to SRT), and the United States National Science Foundation (OCE 0825148 to SRT and GBS).
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    Aggregation and Sedimentation of Thalassiosira weissflogii (diatom) in a Warmer and More Acidified Future Ocean (2014)
    Public Library of Science
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e112379, doi:10.1575/1912/6845.
    Description: Increasing Transparent Exopolymer Particle (TEP) formation during diatom blooms as a result of elevated temperature and pCO2 have been suggested to result in enhanced aggregation and carbon flux, therewith potentially increasing the sequestration of carbon by the ocean. We present experimental results on TEP and aggregate formation by Thalassiosira weissflogii (diatom) in the presence or absence of bacteria under two temperature and three pCO2 scenarios. During the aggregation phase of the experiment TEP formation was elevated at the higher temperature (20°C vs. 15°C), as predicted. However, in contrast to expectations based on the established relationship between TEP and aggregation, aggregation rates and sinking velocity of aggregates were depressed in warmer treatments, especially under ocean acidification conditions. If our experimental findings can be extrapolated to natural conditions, they would imply a reduction in carbon flux and potentially reduced carbon sequestration after diatom blooms in the future ocean.
    Description: This work was supported by National Science Foundation grants OCE-0926711 & OCE-1041038 to UP and Helmholtz Graduate School for Polar and Marine Research and Jacobs University Bremen to SS.
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    Assessing performance of Bayesian state-space models fit to Argos satellite telemetry locations processed with Kalman filtering (2014)
    Public Library of Science
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e92277, doi:10.1371/journal.pone.0092277.
    Description: Argos recently implemented a new algorithm to calculate locations of satellite-tracked animals that uses a Kalman filter (KF). The KF algorithm is reported to increase the number and accuracy of estimated positions over the traditional Least Squares (LS) algorithm, with potential advantages to the application of state-space methods to model animal movement data. We tested the performance of two Bayesian state-space models (SSMs) fitted to satellite tracking data processed with KF algorithm. Tracks from 7 harbour seals (Phoca vitulina) tagged with ARGOS satellite transmitters equipped with Fastloc GPS loggers were used to calculate the error of locations estimated from SSMs fitted to KF and LS data, by comparing those to “true” GPS locations. Data on 6 fin whales (Balaenoptera physalus) were used to investigate consistency in movement parameters, location and behavioural states estimated by switching state-space models (SSSM) fitted to data derived from KF and LS methods. The model fit to KF locations improved the accuracy of seal trips by 27% over the LS model. 82% of locations predicted from the KF model and 73% of locations from the LS model were 〈5 km from the corresponding interpolated GPS position. Uncertainty in KF model estimates (5.6±5.6 km) was nearly half that of LS estimates (11.6±8.4 km). Accuracy of KF and LS modelled locations was sensitive to precision but not to observation frequency or temporal resolution of raw Argos data. On average, 88% of whale locations estimated by KF models fell within the 95% probability ellipse of paired locations from LS models. Precision of KF locations for whales was generally higher. Whales’ behavioural mode inferred by KF models matched the classification from LS models in 94% of the cases. State-space models fit to KF data can improve spatial accuracy of location estimates over LS models and produce equally reliable behavioural estimates.
    Description: This research was primarily funded by Fundação para a Ciência e a Tecnologia (FCT), Fundo Regional da Ciência, Tecnologia (FRCT), through research projects TRACE-PTDC/MAR/74071/2006 and MAPCET-M2.1.2/F/012/2011 [FEDER], the Competitiveness Factors Operational (COMPETE), QREN European Social Fund, and Proconvergencia Açores/EU Program]. We acknowledge funds provided by FCT to LARSyS Associated Laboratory and IMAR-University of the Azores/the Thematic Area D & E of the Strategic Project PEst-OE/EEI/LA0009/2011–1012 and 2013–2014 (OE & Compete) and by the FRCT - Government of the Azores pluriannual funding. MAS was supported by an FCT postdoctoral grant (SFRH/BPD/29841/2006) and is currently supported by POPH, QREN European Social Fund and the Portuguese Ministry for Science and Education through an FCT Investigator grant. RP was supported by an FCT doctoral grant (SFRH/BD/41192/2007) and by the research grant from the Azores Regional Fund for Science and Technology (M3.1.5/F/115/2012). IJ was supported by the Natural Sciences and Engineering Research Council (NSERC) and the Canada Foundation for Innovation (CFI) through their support of the Ocean Tracking Network. DJFR is funded by the United Kingdom Department of Energy and Climate Change as part of their Offshore Energy Strategic Environmental Assessment program. DT is funded by Natural Environment Research Council and Marine Scotland.
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    Analysis, optimization and verification of Illumina-generated 16S rRNA gene amplicon surveys (2014)
    Public Library of Science
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e94249, doi:10.1371/journal.pone.0094249.
    Description: The exploration of microbial communities by sequencing 16S rRNA genes has expanded with low-cost, high-throughput sequencing instruments. Illumina-based 16S rRNA gene sequencing has recently gained popularity over 454 pyrosequencing due to its lower costs, higher accuracy and greater throughput. Although recent reports suggest that Illumina and 454 pyrosequencing provide similar beta diversity measures, it remains to be demonstrated that pre-existing 454 pyrosequencing workflows can transfer directly from 454 to Illumina MiSeq sequencing by simply changing the sequencing adapters of the primers. In this study, we modified 454 pyrosequencing primers targeting the V4-V5 hyper-variable regions of the 16S rRNA gene to be compatible with Illumina sequencers. Microbial communities from cows, humans, leeches, mice, sewage, and termites and a mock community were analyzed by 454 and MiSeq sequencing of the V4-V5 region and MiSeq sequencing of the V4 region. Our analysis revealed that reference-based OTU clustering alone introduced biases compared to de novo clustering, preventing certain taxa from being observed in some samples. Based on this we devised and recommend an analysis pipeline that includes read merging, contaminant filtering, and reference-based clustering followed by de novo OTU clustering, which produces diversity measures consistent with de novo OTU clustering analysis. Low levels of dataset contamination with Illumina sequencing were discovered that could affect analyses that require highly sensitive approaches. While moving to Illumina-based sequencing platforms promises to provide deeper insights into the breadth and function of microbial diversity, our results show that care must be taken to ensure that sequencing and processing artifacts do not obscure true microbial diversity.
    Description: This work was partially funded by an Emerging Frontiers in Research and Innovation – Multicellular and Inter-kingdom Signaling (EFRI-MIKS) grant awarded by the US National Science Foundation to Joerg Graf and NIH RO1 GM095390 to JG and HGM.
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    First autonomous bio-optical profiling float in the Gulf of Mexico reveals dynamic biogeochemistry in deep waters (2014)
    Public Library of Science
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    Publication Date: 2022-05-26
    Description: This is an open-access article, free of all copyright. The definitive version was published in PLoS One 9 (2014): e101658, doi:10.1371/journal.pone.0101658.
    Description: Profiling floats equipped with bio-optical sensors well complement ship-based and satellite ocean color measurements by providing highly-resolved time-series data on the vertical structure of biogeochemical processes in oceanic waters. This is the first study to employ an autonomous profiling (APEX) float in the Gulf of Mexico for measuring spatiotemporal variability in bio-optics and hydrography. During the 17-month deployment (July 2011 to December 2012), the float mission collected profiles of temperature, salinity, chlorophyll fluorescence, particulate backscattering (bbp), and colored dissolved organic matter (CDOM) fluorescence from the ocean surface to a depth of 1,500 m. Biogeochemical variability was characterized by distinct depth trends and local “hot spots”, including impacts from mesoscale processes associated with each of the water masses sampled, from ambient deep waters over the Florida Plain, into the Loop Current, up the Florida Canyon, and eventually into the Florida Straits. A deep chlorophyll maximum (DCM) occurred between 30 and 120 m, with the DCM depth significantly related to the unique density layer ρ = 1023.6 (R2 = 0.62). Particulate backscattering, bbp, demonstrated multiple peaks throughout the water column, including from phytoplankton, deep scattering layers, and resuspension. The bio-optical relationship developed between bbp and chlorophyll (R2 = 0.49) was compared to a global relationship and could significantly improve regional ocean-color algorithms. Photooxidation and autochthonous production contributed to CDOM distributions in the upper water column, whereas in deep water, CDOM behaved as a semi-conservative tracer of water masses, demonstrating a tight relationship with density (R2 = 0.87). In the wake of the Deepwater Horizon oil spill, this research lends support to the use of autonomous drifting profilers as a powerful tool for consideration in the design of an expanded and integrated observing network for the Gulf of Mexico.
    Description: This project was funded by Bureau of Ocean Energy Management (BOEM) Contract M10PC00112 to Leidos, Inc. with subcontract to ASB (www.boem.gov).
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    Optogenetic mapping of cerebellar inhibitory circuitry reveals spatially biased coordination of interneurons via electrical synapses (2014)
    Cell Press
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Cell 7 (2014): 1601–1613, doi:10.1016/j.celrep.2014.04.047.
    Description: We used high-speed optogenetic mapping technology to examine the spatial organization of local inhibitory circuits formed by cerebellar interneurons. Transgenic mice expressing channelrhodopsin-2 exclusively in molecular layer interneurons allowed us to focally photostimulate these neurons, while measuring resulting responses in postsynaptic Purkinje cells. This approach revealed that interneurons converge upon Purkinje cells over a broad area and that at least seven interneurons form functional synapses with a single Purkinje cell. The number of converging interneurons was reduced by treatment with gap junction blockers, revealing that electrical synapses between interneurons contribute substantially to the spatial convergence. Remarkably, gap junction blockers affected convergence in sagittal slices, but not in coronal slices, indicating a sagittal bias in electrical coupling between interneurons. We conclude that electrical synapse networks spatially coordinate interneurons in the cerebellum and may also serve this function in other brain regions.
    Description: This work was supported by a CRP grant from the National Research Foundation of Singapore and by the World Class Institute (WCI) Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology of Korea (NRF grant number WCI 2009-003).
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    Swimming speed of larval snail does not correlate with size and ciliary beat frequency (2014)
    Public Library of Science
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 8 (2013): e82764, doi:10.1371/journal.pone.0082764.
    Description: Many marine invertebrates have planktonic larvae with cilia used for both propulsion and capturing of food particles. Hence, changes in ciliary activity have implications for larval nutrition and ability to navigate the water column, which in turn affect survival and dispersal. Using high-speed high-resolution microvideography, we examined the relationship between swimming speed, velar arrangements, and ciliary beat frequency of freely swimming veliger larvae of the gastropod Crepidula fornicata over the course of larval development. Average swimming speed was greatest 6 days post hatching, suggesting a reduction in swimming speed towards settlement. At a given age, veliger larvae have highly variable speeds (0.8–4 body lengths s−1) that are independent of shell size. Contrary to the hypothesis that an increase in ciliary beat frequency increases work done, and therefore speed, there was no significant correlation between swimming speed and ciliary beat frequency. Instead, there are significant correlations between swimming speed and visible area of the velar lobe, and distance between centroids of velum and larval shell. These observations suggest an alternative hypothesis that, instead of modifying ciliary beat frequency, larval C. fornicata modify swimming through adjustment of velum extension or orientation. The ability to adjust velum position could influence particle capture efficiency and fluid disturbance and help promote survival in the plankton.
    Description: K.Y.K. Chan was supported by the Postdoctoral Scholar 1 Program at the Woods Hole Oceanographic Institution (WHOI), with funding provided by the Coastal Ocean Institute, the Croucher Foundation, and the Royal Swedish Academy of Sciences. H. Jiang was supported by National Science Foundation grant NSF OCE-1129496 and an award from WHOI's Ocean Life Institute, and D.K. Padilla was supported by NSF IOS-0920032.
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    Indirect human impacts reverse centuries of carbon sequestration and salt marsh accretion (2014)
    Public Library of Science
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e93296, doi:10.1371/journal.pone.0093296.
    Description: Direct and indirect human impacts on coastal ecosystems have increased over the last several centuries, leading to unprecedented degradation of coastal habitats and loss of ecological services. Here we document a two-century temporal disparity between salt marsh accretion and subsequent loss to indirect human impacts. Field surveys, manipulative experiments and GIS analyses reveal that crab burrowing weakens the marsh peat base and facilitates further burrowing, leading to bank calving, disruption of marsh accretion, and a loss of over two centuries of sequestered carbon from the marsh edge in only three decades. Analogous temporal disparities exist in other systems and are a largely unrecognized obstacle in attaining sustainable ecosystem services in an increasingly human impacted world. In light of the growing threat of indirect impacts worldwide and despite uncertainties in the fate of lost carbon, we suggest that estimates of carbon emissions based only on direct human impacts may significantly underestimate total anthropogenic carbon emissions.
    Description: This research was made possible by a grant from the National Science Foundation Biological Oceanography Program and the Brown University Undergraduate Teaching and Research Award Program.
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    Humpback whale populations share a core skin bacterial community : towards a health index for marine mammals? (2014)
    Public Library of Science
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e90785, doi:10.1371/journal.pone.0090785.
    Description: Microbes are now well regarded for their important role in mammalian health. The microbiology of skin – a unique interface between the host and environment - is a major research focus in human health and skin disorders, but is less explored in other mammals. Here, we report on a cross-population study of the skin-associated bacterial community of humpback whales (Megaptera novaeangliae), and examine the potential for a core bacterial community and its variability with host (endogenous) or geographic/environmental (exogenous) specific factors. Skin biopsies or freshly sloughed skin from 56 individuals were sampled from populations in the North Atlantic, North Pacific and South Pacific oceans and bacteria were characterized using 454 pyrosequencing of SSU rRNA genes. Phylogenetic and statistical analyses revealed the ubiquity and abundance of bacteria belonging to the Flavobacteria genus Tenacibaculum and the Gammaproteobacteria genus Psychrobacter across the whale populations. Scanning electron microscopy of skin indicated that microbial cells colonize the skin surface. Despite the ubiquity of Tenacibaculum and Psychrobater spp., the relative composition of the skin-bacterial community differed significantly by geographic area as well as metabolic state of the animals (feeding versus starving during migration and breeding), suggesting that both exogenous and endogenous factors may play a role in influencing the skin-bacteria. Further, characteristics of the skin bacterial community from these free-swimming individuals were assembled and compared to two entangled and three dead individuals, revealing a decrease in the central or core bacterial community members (Tenacibaculum and Psychrobater spp.), as well as the emergence of potential pathogens in the latter cases. This is the first discovery of a cross-population, shared skin bacterial community. This research suggests that the skin bacteria may be connected to humpback health and immunity and could possibly serve as a useful index for health and skin disorder monitoring of threatened and endangered marine mammals.
    Description: A.A. was funded by a WHOI Ocean Life Institute post-doctoral scholar award, and this research was supported by a grant to A.A. and T.J.M. from Woods Hole Oceanographic Institution's (WHOI) Marine Mammal Center.
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    Genomic and metabolic diversity of Marine Group I Thaumarchaeota in the mesopelagic of two subtropical gyres (2014)
    Public Library of Science
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    Publication Date: 2022-05-26
    Description: The work is made available under the Creative Commons CC0 public domain dedication. The definitive version was published in PLoS One 9 (2014): e95380, doi:10.1371/journal.pone.0095380.
    Description: Marine Group I (MGI) Thaumarchaeota are one of the most abundant and cosmopolitan chemoautotrophs within the global dark ocean. To date, no representatives of this archaeal group retrieved from the dark ocean have been successfully cultured. We used single cell genomics to investigate the genomic and metabolic diversity of thaumarchaea within the mesopelagic of the subtropical North Pacific and South Atlantic Ocean. Phylogenetic and metagenomic recruitment analysis revealed that MGI single amplified genomes (SAGs) are genetically and biogeographically distinct from existing thaumarchaea cultures obtained from surface waters. Confirming prior studies, we found genes encoding proteins for aerobic ammonia oxidation and the hydrolysis of urea, which may be used for energy production, as well as genes involved in 3-hydroxypropionate/4-hydroxybutyrate and oxidative tricarboxylic acid pathways. A large proportion of protein sequences identified in MGI SAGs were absent in the marine cultures Cenarchaeum symbiosum and Nitrosopumilus maritimus, thus expanding the predicted protein space for this archaeal group. Identifiable genes located on genomic islands with low metagenome recruitment capacity were enriched in cellular defense functions, likely in response to viral infections or grazing. We show that MGI Thaumarchaeota in the dark ocean may have more flexibility in potential energy sources and adaptations to biotic interactions than the existing, surface-ocean cultures.
    Description: This work was supported by NSF grants EF-826924 (R.S.), OCE-821374 (R.S.) and OCE-1232982 (R.S. and B.K.S.); the DOE JGI 2010 Microbes Program grant CSP77 (R.S. and M.E.S.); National Institutes of Health grant 1UH2DK083993 (H.G.M.). Work conducted by the U.S. Department of Energy Joint Genome Institute is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. The contributions of S.K. were funded under Agreement No. HSHQDC-07-C-00020 awarded by the Department of Homeland Security (DHS) for the management and operation of the National Biodefense Analysis and Countermeasures Center (NBACC), a Federally Funded Research and Development Center.
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    The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP) : illuminating the functional diversity of eukaryotic life in the oceans through transcriptome sequencing (2014)
    Public Library of Science
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS Biology 12 (2014): e1001889, doi:10.1371/journal.pbio.1001889.
    Description: Microbial ecology is plagued by problems of an abstract nature. Cell sizes are so small and population sizes so large that both are virtually incomprehensible. Niches are so far from our everyday experience as to make their very definition elusive. Organisms that may be abundant and critical to our survival are little understood, seldom described and/or cultured, and sometimes yet to be even seen. One way to confront these problems is to use data of an even more abstract nature: molecular sequence data. Massive environmental nucleic acid sequencing, such as metagenomics or metatranscriptomics, promises functional analysis of microbial communities as a whole, without prior knowledge of which organisms are in the environment or exactly how they are interacting. But sequence-based ecological studies nearly always use a comparative approach, and that requires relevant reference sequences, which are an extremely limited resource when it comes to microbial eukaryotes. In practice, this means sequence databases need to be populated with enormous quantities of data for which we have some certainties about the source. Most important is the taxonomic identity of the organism from which a sequence is derived and as much functional identification of the encoded proteins as possible. In an ideal world, such information would be available as a large set of complete, well-curated, and annotated genomes for all the major organisms from the environment in question. Reality substantially diverges from this ideal, but at least for bacterial molecular ecology, there is a database consisting of thousands of complete genomes from a wide range of taxa, supplemented by a phylogeny-driven approach to diversifying genomics. For eukaryotes, the number of available genomes is far, far fewer, and we have relied much more heavily on random growth of sequence databases, raising the question as to whether this is fit for purpose.
    Description: This project was funded by the Gordon and Betty Moore Foundation (GBMF; Grants GBMF2637 and GBMF3111) to the National Center for Genome Resources (NCGR) and the National Center for Marine Algae and Microbiota (NCMA).
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    Assessing the health of the U.S. west coast with a regional-scale application of the Ocean Health Index (2014)
    Public Library of Science
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    Publication Date: 2022-05-26
    Description: This is an open-access article, free of all copyright. The definitive version was published in PLoS One 9 (2014): e98995, doi:10.1371/journal.pone.0098995.
    Description: Management of marine ecosystems increasingly demands comprehensive and quantitative assessments of ocean health, but lacks a tool to do so. We applied the recently developed Ocean Health Index to assess ocean health in the relatively data-rich US west coast region. The overall region scored 71 out of 100, with sub-regions scoring from 65 (Washington) to 74 (Oregon). Highest scoring goals included tourism and recreation (99) and clean waters (87), while the lowest scoring goals were sense of place (48) and artisanal fishing opportunities (57). Surprisingly, even in this well-studied area data limitations precluded robust assessments of past trends in overall ocean health. Nonetheless, retrospective calculation of current status showed that many goals have declined, by up to 20%. In contrast, near-term future scores were on average 6% greater than current status across all goals and sub-regions. Application of hypothetical but realistic management scenarios illustrate how the Index can be used to predict and understand the tradeoffs among goals and consequences for overall ocean health. We illustrate and discuss how this index can be used to vet underlying assumptions and decisions with local stakeholders and decision-makers so that scores reflect regional knowledge, priorities and values. We also highlight the importance of ongoing and future monitoring that will provide robust data relevant to ocean health assessment.
    Description: Beau and Heather Wrigley generously provided the founding grant. Additional financial and in-kind support was provided by the Pacific Life Foundation, Thomas W. Haas Fund of the New Hampshire Charitable Foundation, the Oak Foundation, Akiko Shiraki Dynner Fund for Ocean Exploration and Conservation, Darden Restaurants Inc. Foundation, Conservation International, New England Aquarium, National Geographic, and the University of California Santa Barbara's National Center for Ecological Analysis and Synthesis, which supported the Ecosystem Health Working Group as part of the Science of Ecosystem-Based Management project funded by the David and Lucile Packard Foundation. Individual authors also acknowledge support from the U.S. National Science Foundation.
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    Evolutionary strategies of viruses, bacteria and archaea in hydrothermal vent ecosystems revealed through metagenomics (2014)
    Public Library of Science
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e109696, doi:10.1371/journal.pone.0109696.
    Description: The deep-sea hydrothermal vent habitat hosts a diverse community of archaea and bacteria that withstand extreme fluctuations in environmental conditions. Abundant viruses in these systems, a high proportion of which are lysogenic, must also withstand these environmental extremes. Here, we explore the evolutionary strategies of both microorganisms and viruses in hydrothermal systems through comparative analysis of a cellular and viral metagenome, collected by size fractionation of high temperature fluids from a diffuse flow hydrothermal vent. We detected a high enrichment of mobile elements and proviruses in the cellular fraction relative to microorganisms in other environments. We observed a relatively high abundance of genes related to energy metabolism as well as cofactors and vitamins in the viral fraction compared to the cellular fraction, which suggest encoding of auxiliary metabolic genes on viral genomes. Moreover, the observation of stronger purifying selection in the viral versus cellular gene pool suggests viral strategies that promote prolonged host integration. Our results demonstrate that there is great potential for hydrothermal vent viruses to integrate into hosts, facilitate horizontal gene transfer, and express or transfer genes that manipulate the hosts’ functional capabilities.
    Description: Funding for sequencing of the viral metagenome was provided by the Gordon and Betty Moore Foundation. All other funding was provided by a NASA Astrobiology Institute grant through Cooperative Agreement NNA04CC09A to the Geophysical Laboratory at the Carnegie Institution for Science. R.A. was funded by a NSF Graduate Research Fellowship through NSF grant number DGE-0718124, an NSF IGERT grant to the University of Washington Astrobiology Program, and the ARCS Foundation.
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    The transcriptional response to oxidative stress during vertebrate development : effects of tert-butylhydroquinone and 2,3,7,8-tetrachlorodibenzo-p-dioxin (2014)
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 9 (2014): e113158, doi:10.1371/journal.pone.0113158.
    Description: Oxidative stress is an important mechanism of chemical toxicity, contributing to teratogenesis and to cardiovascular and neurodegenerative diseases. Developing animals may be especially sensitive to chemicals causing oxidative stress. The developmental expression and inducibility of anti-oxidant defenses through activation of NF-E2-related factor 2 (NRF2) affect susceptibility to oxidants, but the embryonic response to oxidants is not well understood. To assess the response to chemically mediated oxidative stress and how it may vary during development, zebrafish embryos, eleutheroembryos, or larvae at 1, 2, 3, 4, 5, and 6 days post fertilization (dpf) were exposed to DMSO (0.1%), tert-butylhydroquinone (tBHQ; 10 µM) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 2 nM) for 6 hr. Transcript abundance was assessed by real-time qRT-PCR and microarray. qRT-PCR showed strong (4- to 5-fold) induction of gstp1 by tBHQ as early as 1 dpf. tBHQ also induced gclc (2 dpf), but not sod1, nqo1, or cyp1a. TCDD induced cyp1a but none of the other genes. Microarray analysis showed that 1477 probes were significantly different among the DMSO-, tBHQ-, and TCDD-treated eleutheroembryos at 4 dpf. There was substantial overlap between genes induced in developing zebrafish and a set of marker genes induced by oxidative stress in mammals. Genes induced by tBHQ in 4-dpf zebrafish included those involved in glutathione synthesis and utilization, signal transduction, and DNA damage/stress response. The strong induction of hsp70 determined by microarray was confirmed by qRT-PCR and by use of transgenic zebrafish expressing enhanced green fluorescent protein (EGFP) under control of the hsp70 promoter. Genes strongly down-regulated by tBHQ included mitfa, providing a molecular explanation for the loss of pigmentation in tBHQ-exposed embryos. These data show that zebrafish embryos are responsive to oxidative stress as early as 1 dpf, that responsiveness varies with development in a gene-specific manner, and that the oxidative stress response is substantially conserved in vertebrate animals.
    Description: This research was supported in part by National Institutes of Health grants R01ES016366 (MEH), R01ES006272 (MEH), R01ES015912 (JJS), and F32ES017585 (ART-L), the Andrew W. Mellon Foundation Endowed Fund for Innovative Research, a WHOI (Woods Hole Oceanographic Institution) Postdoctoral Scholar award, and the Walter A. and Hope Noyes Smith endowed chair (MEH). AGM and MJC were supported in part by the Marine Biological Laboratory's Program in Global Infectious Disease, funded by the Ellison Medical Foundation.
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    Cyberdiversity: Improving the Informatic Value of Diverse Tropical Arthropod Inventories (2014)
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    In:  PLoS ONE vol. 9 no. 12, pp. e115750-e115750
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    Publication Date: 2024-01-12
    Keywords: Multidisciplinary
    Repository Name: National Museum of Natural History, Netherlands
    Type: info:eu-repo/semantics/article
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    Unisexual Reproduction Drives Meiotic Recombination and Phenotypic and Karyotypic Plasticity in Cryptococcus neoformans (2014)
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    Publication Date: 2014-12-12
    Description: by Sheng Sun, R. Blake Billmyre, Piotr A. Mieczkowski, Joseph Heitman In fungi, unisexual reproduction, where sexual development is initiated without the presence of two compatible mating type alleles, has been observed in several species that can also undergo traditional bisexual reproduction, including the important human fungal pathogens Cryptococcus neoformans and Candida albicans . While unisexual reproduction has been well characterized qualitatively, detailed quantifications are still lacking for aspects of this process, such as the frequency of recombination during unisexual reproduction, and how this compares with bisexual reproduction. Here, we analyzed meiotic recombination during α-α unisexual and a-α bisexual reproduction of C. neoformans . We found that meiotic recombination operates in a similar fashion during both modes of sexual reproduction. Specifically, we observed that in α-α unisexual reproduction, the numbers of crossovers along the chromosomes during meiosis, recombination frequencies at specific chromosomal regions, as well as meiotic recombination hot and cold spots, are all similar to those observed during a-α bisexual reproduction. The similarity in meiosis is also reflected by the fact that phenotypic segregation among progeny collected from the two modes of sexual reproduction is also similar, with transgressive segregation being observed in both. Additionally, we found diploid meiotic progeny were also produced at similar frequencies in the two modes of sexual reproduction, and transient chromosomal loss and duplication likely occurs frequently and results in aneuploidy and loss of heterozygosity that can span entire chromosomes. Furthermore, in both α-α unisexual and a-α bisexual reproduction, we observed biased allele inheritance in regions on chromosome 4, suggesting the presence of fragile chromosomal regions that might be vulnerable to mitotic recombination. Interestingly, we also observed a crossover event that occurred within the MAT locus during α-α unisexual reproduction. Our results provide definitive evidence that α-α unisexual reproduction is a meiotic process similar to a-α bisexual reproduction.
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    Echoes of the Past: Hereditarianism and A Troublesome Inheritance (2014)
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    Publication Date: 2014-12-12
    Description: by Marcus Feldman
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    The miR9863 Family Regulates Distinct Mla Alleles in Barley to Attenuate NLR Receptor-Triggered Disease Resistance and Cell-Death Signaling (2014)
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    Publication Date: 2014-12-12
    Description: by Jie Liu, Xiliu Cheng, Da Liu, Weihui Xu, Roger Wise, Qian-Hua Shen Barley ( Hordeum vulgare L.) Mla alleles encode coiled-coil (CC), nucleotide binding, leucine-rich repeat (NB-LRR) receptors that trigger isolate-specific immune responses against the powdery mildew fungus, Blumeria graminis f. sp. hordei ( Bgh ). How Mla or NB-LRR genes in grass species are regulated at post-transcriptional level is not clear. The microRNA family, miR9863, comprises four members that differentially regulate distinct Mla alleles in barley. We show that miR9863 members guide the cleavage of Mla1 transcripts in barley, and block or reduce the accumulation of MLA1 protein in the heterologous Nicotiana benthamiana expression system. Regulation specificity is determined by variation in a unique single-nucleotide-polymorphism (SNP) in mature miR9863 family members and two SNPs in the Mla miR9863-binding site that separates these alleles into three groups. Further, we demonstrate that 22-nt miR9863s trigger the biogenesis of 21-nt phased siRNAs (phasiRNAs) and together these sRNAs form a feed-forward regulation network for repressing the expression of group I Mla alleles. Overexpression of miR9863 members specifically attenuates MLA1, but not MLA10-triggered disease resistance and cell-death signaling. We propose a key role of the miR9863 family in dampening immune response signaling triggered by a group of MLA immune receptors in barley.
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    Global Analysis of Photosynthesis Transcriptional Regulatory Networks (2014)
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    Publication Date: 2014-12-12
    Description: by Saheed Imam, Daniel R. Noguera, Timothy J. Donohue Photosynthesis is a crucial biological process that depends on the interplay of many components. This work analyzed the gene targets for 4 transcription factors: FnrL, PrrA, CrpK and MppG (RSP_2888), which are known or predicted to control photosynthesis in Rhodobacter sphaeroides . Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identified 52 operons under direct control of FnrL, illustrating its regulatory role in photosynthesis, iron homeostasis, nitrogen metabolism and regulation of sRNA synthesis. Using global gene expression analysis combined with ChIP-seq, we mapped the regulons of PrrA, CrpK and MppG. PrrA regulates ∼34 operons encoding mainly photosynthesis and electron transport functions, while CrpK, a previously uncharacterized Crp-family protein, regulates genes involved in photosynthesis and maintenance of iron homeostasis. Furthermore, CrpK and FnrL share similar DNA binding determinants, possibly explaining our observation of the ability of CrpK to partially compensate for the growth defects of a ΔFnrL mutant. We show that the Rrf2 family protein, MppG, plays an important role in photopigment biosynthesis, as part of an incoherent feed-forward loop with PrrA. Our results reveal a previously unrealized, high degree of combinatorial regulation of photosynthetic genes and significant cross-talk between their transcriptional regulators, while illustrating previously unidentified links between photosynthesis and the maintenance of iron homeostasis.
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    The nphp-2 and arl-13 Genetic Modules Interact to Regulate Ciliogenesis and Ciliary Microtubule Patterning in C. elegans (2014)
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    Publication Date: 2014-12-12
    Description: by Simon R. F. Warburton-Pitt, Malan Silva, Ken C. Q. Nguyen, David H. Hall, Maureen M. Barr Cilia are microtubule-based cellular organelles that mediate signal transduction. Cilia are organized into several structurally and functionally distinct compartments: the basal body, the transition zone (TZ), and the cilia shaft. In vertebrates, the cystoprotein Inversin localizes to a portion of the cilia shaft adjacent to the TZ, a region termed the “Inversin compartment” (InvC). The mechanisms that establish and maintain the InvC are unknown. In the roundworm C. elegans, the cilia shafts of amphid channel and phasmid sensory cilia are subdivided into two regions defined by different microtubule ultrastructure: a proximal doublet-based region adjacent to the TZ, and a distal singlet-based region. It has been suggested that C. elegans cilia also possess an InvC, similarly to mammalian primary cilia. Here we explored the biogenesis, structure, and composition of the C. elegans ciliary doublet region and InvC. We show that the InvC is conserved and distinct from the doublet region. nphp-2 (the C. elegans Inversin homolog) and the doublet region genes arl-13 , klp-11, and unc-119 are redundantly required for ciliogenesis. InvC and doublet region genes can be sorted into two modules— nphp-2 + klp-11 and arl-13 + unc-119— which are both antagonized by the hdac-6 deacetylase. The genes of this network modulate the sizes of the NPHP-2 InvC and ARL-13 doublet region. Glutamylation, a tubulin post-translational modification, is not required for ciliary targeting of InvC and doublet region components; rather, glutamylation is modulated by nphp-2 , arl-13 , and unc-119 . The ciliary targeting and restricted localization of NPHP-2, ARL-13, and UNC-119 does not require TZ-, doublet region, and InvC-associated genes. NPHP-2 does require its calcium binding EF hand domain for targeting to the InvC. We conclude that the C. elegans InvC is distinct from the doublet region, and that components in these two regions interact to regulate ciliogenesis via cilia placement, ciliary microtubule ultrastructure, and protein localization.
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    Unexpected DNA Loss Mediated by the DNA Binding Activity of Ribonuclease A (2014)
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    In: PLoS ONE
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    Publication Date: 2014-12-12
    Description: by Federico Donà, Jonathan Houseley Ribonuclease A (RNase A) is widely used in molecular biology research both for analytical assays and for nucleic acid preparation. The catalytic mechanism of RNase A is well understood and absolutely precludes activity on DNA; however anecdotal reports of DNA degradation by RNase A are not uncommon. Here we describe a mechanism by which RNase A treatment can lead to apparent DNA degradation. This results from the surprising finding that RNase A remains functional in a phenol:chloroform mixture, to our knowledge the only enzyme that survives this highly denaturing solvent environment. Although RNase A does not cleave the DNA backbone it is capable of binding to DNA, forming stable RNase A-DNA complexes that partition to the interphase or organic phase during phenol:chloroform purification. The unexpected survival of the RNase A DNA-binding activity in phenol means that these complexes are not dissolved and a substantial amount of RNase A-bound DNA is permanently removed from the aqueous phase and lost on phase separation. This effect will impact DNA recovery from multiple procedures and is likely to represent a source of sequence bias in genome-wide studies. Our results also indicate that the results of analytical studies performed using RNase A must be considered with care.
    Electronic ISSN: 1932-6203
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    Screening for Vulnerability in Older Cancer Patients: The ONCODAGE Prospective Multicenter Cohort Study (2014)
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    In: PLoS ONE
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    Publication Date: 2014-12-12
    Description: by Pierre Soubeyran, Carine Bellera, Jean Goyard, Damien Heitz, Hervé Curé, Hubert Rousselot, Gilles Albrand, Véronique Servent, Olivier Saint Jean, Isabelle van Praagh, Jean-Emmanuel Kurtz, Stéphane Périn, Jean-Luc Verhaeghe, Catherine Terret, Christophe Desauw, Véronique Girre, Cécile Mertens, Simone Mathoulin-Pélissier, Muriel Rainfray Background Geriatric Assessment is an appropriate method for identifying older cancer patients at risk of life-threatening events during therapy. Yet, it is underused in practice, mainly because it is time- and resource-consuming. This study aims to identify the best screening tool to identify older cancer patients requiring geriatric assessment by comparing the performance of two short assessment tools the G8 and the Vulnerable Elders Survey (VES-13). Patients and Methods The diagnostic accuracy of the G8 and the (VES-13) were evaluated in a prospective cohort study of 1674 cancer patients accrued before treatment in 23 health care facilities. 1435 were eligible and evaluable. Outcome measures were multidimensional geriatric assessment (MGA), sensitivity (primary), specificity, negative and positive predictive values and likelihood ratios of the G8 and VES-13, and predictive factors of 1-year survival rate. Results Patient median age was 78.2 years (70-98) with a majority of females (69.8%), various types of cancer including 53.9% breast, and 75.8% Performance Status 0-1. Impaired MGA, G8, and VES-13 were 80.2%, 68.4%, and 60.2%, respectively. Mean time to complete G8 or VES-13 was about five minutes. Reproducibility of the two questionnaires was good. G8 appeared more sensitive (76.5% versus 68.7%, P  =  0.0046) whereas VES-13 was more specific (74.3% versus 64.4%, P
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    Impact of the Lab-Score on Antibiotic Prescription Rate in Children with Fever without Source: A Randomized Controlled Trial (2014)
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    In: PLoS ONE
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    Publication Date: 2014-12-12
    Description: by Laurence Lacroix, Sergio Manzano, Lynda Vandertuin, Florence Hugon, Annick Galetto-Lacour, Alain Gervaix Background The Lab-score, based on the combined determination of procalcitonin, C-reactive protein and urinary dipstick results, has been shown accurate in detecting serious bacterial infections (SBI) in children with fever without source (FWS) on retrospective cohorts. We aimed to prospectively assess the utility of the Lab-score in safely decreasing antibiotic prescriptions in children with FWS and to determine its diagnostic characteristics compared to common SBI biomarkers. Methods Randomized controlled trial in children 7 days to 36 months old with FWS, allocated either to the Lab-score group (Lab-score reported, blinded WBC count) or to the control group (WBC, bands and C-reactive protein determined, blinded procalcitonin and Lab-score), followed up until recovery. Demographic data, antibiotic prescription rate, admission rate and diagnostic properties of the Lab-score were analyzed. Results 271 children were analyzed. No statistically significant difference concerning antibiotic prescription rate was observed: 41.2% (54 of 131) in the Lab-score group and 42.1% (59 of 140) in the control group (p = 1.000). If recommendations based on the Lab-score had been strictly applied, a hypothetical 30.6% treatment rate would have been encountered, compared to the overall 41.7% observed rate (p = 0.0095). A Lab-score ≥3 showed the following characteristics: sensitivity 85.1% (95% CI: 76.5–93.6%), specificity 87.3% (95% CI: 82.7–91.8%), positive predictive value 68.7% (95% CI: 58.7–78.7%), negative predictive value 94.1% (95% CI: 91.5–97.9%), positive and negative likelihood ratios: 6.68 and 0.17 respectively. Area under the receiver operating characteristic curve was best for the Lab-score (0.911, 95% CI: 0.871–0.950). Discussion No difference regarding antibiotic treatment rate was observed when using the Lab-score, due to lack of adherence to the related recommendations. However, if strictly followed, a significant 26.5% reduction of antibiotic prescriptions would have been encountered. Medical education needs to be reinforced in order to observe rather than treat low-risk well-appearing children with FWS. Trial Registration ClinicalTrials.gov NCT02179398
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    A Common Control Group - Optimising the Experiment Design to Maximise Sensitivity (2014)
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    In: PLoS ONE
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    Publication Date: 2014-12-12
    Description: by Simon Bate, Natasha A. Karp Methods for choosing an appropriate sample size in animal experiments have received much attention in the statistical and biological literature. Due to ethical constraints the number of animals used is always reduced where possible. However, as the number of animals decreases so the risk of obtaining inconclusive results increases. By using a more efficient experimental design we can, for a given number of animals, reduce this risk. In this paper two popular cases are considered, where planned comparisons are made to compare treatments back to control and when researchers plan to make all pairwise comparisons. By using theoretical and empirical techniques we show that for studies where all pairwise comparisons are made the traditional balanced design, as suggested in the literature, maximises sensitivity. For studies that involve planned comparisons of the treatment groups back to the control group, which are inherently more sensitive due to the reduced multiple testing burden, the sensitivity is maximised by increasing the number of animals in the control group while decreasing the number in the treated groups.
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    Body Mass Index and Depressive Symptoms in Older Adults: A Cross-Lagged Panel Analysis (2014)
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    In: PLoS ONE
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    Publication Date: 2014-12-12
    Description: by Jinseok Kim, Jin-Won Noh, Jumin Park, Young Dae Kwon Background There are conflicting results about the association between body mass index (BMI) and depressive symptoms in older adults. The present study examined the relationship between weight and depressive symptoms over time in older adults in South Korea. Methods We used data from three waves of the Korean Longitudinal Study of Aging and ran a series of cross-lagged panel models to test the reciprocal relationship between depressive symptoms and obesity in older Korean adults. We assumed a temporally stable relationship between depressive symptoms and obesity and, thus imposed equality constraints over time. Results After controlling for the effect of depressive symptoms two years prior, underweight older adults had a higher depressive symptom score than those of normal weight. When controlling for obesity status from two years prior, older adults with higher levels of depressive symptoms were more likely to be underweight and less likely to be overweight than normal weight. The same patterns were observed in data from 2006 to 2008 and from 2008 to 2010. Conclusions These results show that there is a correlation between depressive symptoms and weight status. In middle-aged and elderly Asian populations, depression can lead to weight loss rather than obesity, and underweight may develop depressive symptoms.
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    Eaten Out of House and Home: Impacts of Grazing on Ground-Dwelling Reptiles in Australian Grasslands and Grassy Woodlands (2014)
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    Publication Date: 2014-12-12
    Description: by Brett Howland, Dejan Stojanovic, Iain J. Gordon, Adrian D. Manning, Don Fletcher, David B. Lindenmayer Large mammalian grazers can alter the biotic and abiotic features of their environment through their impacts on vegetation. Grazing at moderate intensity has been recommended for biodiversity conservation. Few studies, however, have empirically tested the benefits of moderate grazing intensity in systems dominated by native grazers. Here we investigated the relationship between (1) density of native eastern grey kangaroos, Macropus giganteus , and grass structure, and (2) grass structure and reptiles (i.e. abundance, richness, diversity and occurrence) across 18 grassland and grassy Eucalyptus woodland properties in south-eastern Australia. There was a strong negative relationship between kangaroo density and grass structure after controlling for tree canopy cover. We therefore used grass structure as a surrogate for grazing intensity. Changes in grazing intensity (i.e. grass structure) significantly affected reptile abundance, reptile species richness, reptile species diversity, and the occurrence of several ground-dwelling reptiles. Reptile abundance, species richness and diversity were highest where grazing intensity was low. Importantly, no species of reptile was more likely to occur at high grazing intensities. Legless lizards ( Delma impar , D. inornata ) were more likely to be detected in areas subject to moderate grazing intensity, whereas one species ( Hemiergis talbingoensis ) was less likely to be detected in areas subject to intense grazing and three species ( Menetia greyii , Morethia boulengeri , and Lampropholis delicata ) did not appear to be affected by grazing intensity. Our data indicate that to maximize reptile abundance, species richness, species diversity, and occurrence of several individual species of reptile, managers will need to subject different areas of the landscape to moderate and low grazing intensities and limit the occurrence and extent of high grazing.
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    Autonomous Inhibition of Apoptosis Correlates with Responsiveness of Colon Carcinoma Cell Lines to Ciglitazone (2014)
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    Publication Date: 2014-12-12
    Description: by David M. Baron, Ulrike Kaindl, Verena J. Haudek-Prinz, Editha Bayer, Clemens Röhrl, Christopher Gerner, Brigitte Marian Colorectal cancer is a leading cause of mortality worldwide. Resistance to therapy is common and often results in patients succumbing to the disease. The mechanisms of resistance are poorly understood. Cells basically have two possibilities to survive a treatment with potentially apoptosis-inducing substances. They can make use of their existing proteins to counteract the induced reactions or quickly upregulate protective factors to evade the apoptotic signal. To identify protein patterns involved in resistance to apoptosis, we studied two colorectal adenocarcinoma cell lines with different growth responses to low-molar concentrations of the thiazolidinedione Ciglitazone: HT29 cells underwent apoptosis, whereas SW480 cells increased cell number. Fluorescence detection and autoradiography scans of 2D-PAGE gels were performed in both cell lines to assess protein synthesis and turnover, respectively. To verify the data we performed shotgun analysis using the same treatment procedure as in 2D-experiments. Biological functions of the identified proteins were mainly associated with apoptosis regulation, chaperoning, intrinsic inflammation, and DNA repair. The present study suggests that different growth response of two colorectal carcinoma cell lines after treatment with Ciglitazone results from cell-specific protein synthesis and differences in protein regulation.
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    Correction: Molecular Determinants of Agonist Selectivity in Glutamate-Gated Chloride Channels Which Likely Explain the Agonist Selectivity of the Vertebrate Glycine and GABAA-ρ Receptors (2014)
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    Publication Date: 2014-12-12
    Description: by The PLOS ONE Staff
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    Circadian Mechanisms of Food Anticipatory Rhythms in Rats Fed Once or Twice Daily: Clock Gene and Endocrine Correlates (2014)
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    Publication Date: 2014-12-12
    Description: by Danica F. Patton, Ângela M. Katsuyama, Ilya Pavlovski, Mateusz Michalik, Zachary Patterson, Maksim Parfyonov, Andrea N. Smit, Elliott G. Marchant, John Chung, Alfonso Abizaid, Kai-Florian Storch, Horacio de la Iglesia, Ralph E. Mistlberger Circadian clocks in many brain regions and peripheral tissues are entrained by the daily rhythm of food intake. Clocks in one or more of these locations generate a daily rhythm of locomotor activity that anticipates a regular mealtime. Rats and mice can also anticipate two daily meals. Whether this involves 1 or 2 circadian clocks is unknown. To gain insight into how the circadian system adjusts to 2 daily mealtimes, male rats in a 12∶12 light-dark cycle were fed a 2 h meal either 4 h after lights-on or 4 h after lights-off, or a 1 h meal at both times. After 30 days, brain, blood, adrenal and stomach tissue were collected at 6 time points. Multiple clock genes from adrenals and stomachs were assayed by RT-PCR. Blood was assayed for corticosterone and ghrelin. Bmal1 expression was quantified in 14 brain regions by in situ hybridization. Clock gene rhythms in adrenal and stomach from day-fed rats oscillated in antiphase with the rhythms in night-fed rats, and at an intermediate phase in rats fed twice daily. Corticosterone and ghrelin in 1-meal rats peaked at or prior to the expected mealtime. In 2-meal rats, corticosterone peaked only prior the nighttime meal, while ghrelin peaked prior to the daytime meal and then remained elevated. The olfactory bulb, nucleus accumbens, dorsal striatum, cerebellum and arcuate nucleus exhibited significant daily rhythms of Bmal1 in the night-fed groups that were approximately in antiphase in the day-fed groups, and at intermediate levels (arrhythmic) in rats anticipating 2 daily meals. The dissociations between anticipatory activity and the peripheral clocks and hormones in rats anticipating 2 daily meals argue against a role for these signals in the timing of behavioral rhythms. The absence of rhythmicity at the tissue level in brain regions from rats anticipating 2 daily meals support behavioral evidence that circadian clock cells in these tissues may reorganize into two populations coupled to different meals.
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    Use of a Guinea Pig-Specific Transcriptome Array for Evaluation of Protective Immunity against Genital Chlamydial Infection following Intranasal Vaccination in Guinea Pigs (2014)
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    Publication Date: 2014-12-12
    Description: by Shradha Wali, Rishein Gupta, Ronald L. Veselenak, Yansong Li, Jieh-Juen Yu, Ashlesh K. Murthy, Andrew P. Cap, M. Neal Guentzel, James P. Chambers, Guangming Zhong, Roger G. Rank, Richard B. Pyles, Bernard P. Arulanandam Guinea pigs have been used as a second animal model to validate putative anti-chlamydial vaccine candidates tested in mice. However, the lack of guinea pig-specific reagents has limited the utility of this animal model in Chlamydia sp . vaccine studies. Using a novel guinea pig-specific transcriptome array, we determined correlates of protection in guinea pigs vaccinated with Chlamydia caviae ( C. caviae ) via the intranasal route, previously reported by us and others to provide robust antigen specific immunity against subsequent intravaginal challenge. C. caviae vaccinated guinea pigs resolved genital infection by day 3 post challenge. In contrast, mock vaccinated animals continued to shed viable Chlamydia up to day 18 post challenge. Importantly, at day 80 post challenge, vaccinated guinea pigs experienced significantly reduced genital pathology - a sequelae of genital chlamydial infections, in comparison to mock vaccinated guinea pigs. Sera from vaccinated guinea pigs displayed antigen specific IgG responses and increased IgG1 and IgG2 titers capable of neutralizing GPIC in vitro . Th1-cellular/inflammatory immune genes and Th2-humoral associated genes were also found to be elevated in vaccinated guinea pigs at day 3 post-challenge and correlated with early clearance of the bacterium. Overall, this study provides the first evidence of guinea pig-specific genes involved in anti-chlamydial vaccination and illustrates the enhancement of the utility of this animal model in chlamydial pathogenesis.
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    Correction: Genome-Wide Associations between Genetic and Epigenetic Variation Influence mRNA Expression and Insulin Secretion in Human Pancreatic Islets (2014)
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    Publication Date: 2014-12-13
    Description: by The PLOS Genetics Staff
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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    Evolutionary Phylodynamics of Korean Noroviruses Reveals a Novel GII.2/GII.10 Recombination Event (2014)
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    Publication Date: 2014-12-13
    Description: by Thoi Cong Truong, Van Thai Than, Wonyong Kim Viral gastroenteritis is the most common causal agent of public health problems worldwide. Noroviruses cause nonbacterial acute gastroenteritis in humans of all ages. In this study, we investigated the occurrence of norovirus infection in children with acute gastroenteritis admitted to university hospitals in South Korea. We also analyzed the genetic diversity of the viruses and identified novel recombination events among the identified viral strains. Of 502 children with acute gastroenteritis admitted to our three hospitals between January 2011 and March 2012, genotyping of human noroviruses was performed in 171 (34%) norovirus-positive samples. Of these samples, 170 (99.5%) were in genogroup II (GII), while only one (0.5%) was in genogroup I (GI). The most common GII strain was the GII.4-2006b variant (n = 96, 56.5%), followed by GII.6 (n = 23, 13.5%), GII.12 (n = 22, 12.9%), GII.3 (n = 20, 11.8%), GII.2 (n = 6, 3.5%), GII.b (n = 2, 1.2%), and GII.10 (n = 1, 0.6%). Potential recombination events (polymerase/capsid) were detected in 39 GII strains (22.9%), and the most frequent genotypes were GII.4/GII.12 (n = 12, 30.8%), GII.4/GII.6 (n = 12, 30.8%), GII.4/GII.3 (n = 8, 20.5%), GII.b/GII.3 (n = 3, 7.7%), GII.16/GII.2 (n = 2, 5.1%), GII.4/GII.2 (n = 1, 2.6%), and GII.2/GII.10 (n = 1, 2.6%). For the first time, a novel GII.2/GII.10 recombination was detected; we also identified the GII.16/GII.2 strain for the first time in South Korea. Our data provided important insights into new recombination events, which may prove valuable for predicting the emergence of circulating norovirus strains with global epidemic potential.
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    Paramagnetic Beads and Magnetically Mediated Strain Enhance Cardiomyogenesis in Mouse Embryoid Bodies (2014)
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    Publication Date: 2014-12-13
    Description: by Laura R. Geuss, Douglas C. Wu, Divya Ramamoorthy, Corinne D. Alford, Laura J. Suggs Mechanical forces play an important role in proper embryologic development, and similarly such forces can directly impact pluripotency and differentiation of mouse embryonic stem cells (mESC) in vitro . In addition, manipulation of the embryoid body (EB) microenvironment, such as by incorporation of microspheres or microparticles, can similarly influence fate determination. In this study, we developed a mechanical stimulation regimen using permanent neodymium magnets to magnetically attract cells within an EB. Arginine-Glycine-Aspartic Acid (RGD)-conjugated paramagnetic beads were incorporated into the interior of the EBs during aggregation, allowing us to exert force on individual cells using short-term magnetization. EBs were stimulated for one hour at different magnetic field strengths, subsequently exerting a range of force intensity on the cells at different stages of early EB development. Our results demonstrated that following exposure to a 0.2 Tesla magnetic field, ESCs respond to magnetically mediated strain by activating Protein Kinase A (PKA) and increasing phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) expression. The timing of stimulation can also be tailored to guide ESC differentiation: the combination of bone morphogenetic protein 4 (BMP4) supplementation with one hour of magnetic attraction on Day 3 enhances cardiomyogenesis by increasing contractile activity and the percentage of sarcomeric α-actin-expressing cells compared to control samples with BMP4 alone. Interestingly, we also observed that the beads alone had some impact on differentiation by increasingly slightly, albeit not significantly, the percentage of cardiomyocytes. Together these results suggest that magnetically mediated strain can be used to enhance the percentage of mouse ESC-derived cardiomyocytes over current differentiation protocols.
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    Efficacy and Safety of Crizotinib among Chinese EML4-ALK-Positive, Advanced-Stage Non-Small Cell Lung Cancer Patients (2014)
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    Publication Date: 2014-12-13
    Description: by Yabing Cao, Guangli Xiao, Xibin Qiu, Sheng Ye, Tongyu Lin Introduction We report the efficacy and safety of crizotinib treatment among Chinese patients with advanced-stage NSCLC. Methods We retrospectively analyzed patients with EML4-ALK positive advanced NSCLC who were treated with crizotinib from May 2012 to Aug 2013. Baseline clinical parameters, treatment protocol, response to therapy and survival were noted. The primary goal was to evaluate the efficacy of crizotinib in patients who were previously treated patients or who had poor ECOG performance status (PS). Results Forty patients were evaluable for safety and efficacy. Median age was 43 years, 100% had adenocarcinoma and stage IV disease, and 42.5% were female. Six patients received frontline treatment with crizotinib, 17 patients had 1 prior treatment, and 17 patients had more than 2 lines of prior treatment. Patients received a median of 5 cycles of treatment (range 1–15 cycles). After the first cycle, 92.5% (37/40) patients archived partial remission (PR). At the end of the follow-up period, the overall PR rate was 70% (28/40), and progression of disease (PD) occurred in 30% of patients (12/40). The median PFS was 28 weeks (95% CI 15.4 to 40.5 weeks), and median OS was 40 weeks (95% CI 38.6 to 49.3 weeks). The most frequent treatment-related AEs were vomiting (47.5%), vision disorder (27.5%) and increased ALT/AST (42%); most toxicities were Grade 1/2. Observed treatment-related Grade 3/4 AEs included increased ALT/AST (10%) and vomiting (5%). The EML4-ALK fusion rate and number of prior chemotherapy cycles did not appear to significantly affect the efficacy of crizotinib. However, PS 0–2 patients had improved PFS (50 weeks vs. 24 weeks, p = 0.015). Conclusions Crizotinib was safe, well-tolerated, and effective in Chinese patients with pre-treated ALK-rearranged NSCLC. QOL was improved and PS appears to have an effect on the efficacy of crizotinib, but prior treatment and ALK fusion rate do not.
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    Detection of DNA Sequences Refractory to PCR Amplification Using a Biophysical SERRS Assay (Surface Enhanced Resonant Raman Spectroscopy) (2014)
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    Publication Date: 2014-12-13
    Description: by Cécile Feuillie, Maxime M. Merheb, Benjamin Gillet, Gilles Montagnac, Isabelle Daniel, Catherine Hänni The analysis of ancient or processed DNA samples is often a great challenge, because traditional Polymerase Chain Reaction – based amplification is impeded by DNA damage. Blocking lesions such as abasic sites are known to block the bypass of DNA polymerases, thus stopping primer elongation. In the present work, we applied the SERRS-hybridization assay, a fully non-enzymatic method, to the detection of DNA refractory to PCR amplification. This method combines specific hybridization with detection by Surface Enhanced Resonant Raman Scattering (SERRS). It allows the detection of a series of double-stranded DNA molecules containing a varying number of abasic sites on both strands, when PCR failed to detect the most degraded sequences. Our SERRS approach can quickly detect DNA molecules without any need for DNA repair. This assay could be applied as a pre-requisite analysis prior to enzymatic reparation or amplification. A whole new set of samples, both forensic and archaeological, could then deliver information that was not yet available due to a high degree of DNA damage.
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    Accumulation of Oxidized LDL in the Tendon Tissues of C57BL/6 or Apolipoprotein E Knock-Out Mice That Consume a High Fat Diet: Potential Impact on Tendon Health (2014)
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    Publication Date: 2014-12-13
    Description: by Navdeep Grewal, Gail M. Thornton, Hayedeh Behzad, Aishwariya Sharma, Alex Lu, Peng Zhang, W. Darlene Reid, David J. Granville, Alex Scott Objective Clinical studies have suggested an association between dyslipidemia and tendon injuries or chronic tendon pain; the mechanisms underlying this association are not yet known. The objectives of this study were (1) to evaluate the impact of a high fat diet on the function of load-bearing tendons and on the distribution in tendons of oxidized low density lipoprotein (oxLDL), and (2) to examine the effect of oxLDL on tendon fibroblast proliferation and gene expression. Methods Gene expression ( Mmp2, Tgfb1 , Col1a1 , Col3a1 ), fat content (Oil Red O staining), oxLDL levels (immunohistochemistry) and tendon biomechanical properties were examined in mice (C57Bl/6 or ApoE -/-) receiving a standard or a high fat diet. Human tendon fibroblast proliferation and gene expression ( COL1A1 , COL3A1 , MMP2 ) were examined following oxLDL exposure. Results In both types of mice (C57Bl/6 or ApoE -/-), consumption of a high fat diet led to a marked increase in oxLDL deposition in the load-bearing extracellular matrix of the tendon. The consumption of a high fat diet also reduced the failure stress and load of the patellar tendon in both mouse types, and increased Mmp2 expression. ApoE -/- mice exhibited more pronounced reductions in tendon function than wild-type mice, and decreased expression of Col1a1 compared to wild type mice. Human tendon fibroblasts responded to oxLDL by increasing their proliferation and their mRNA levels of MMP2 , while decreasing their mRNA levels for COL1A1 and COL3A1 . Conclusion The consumption of a high fat diet resulted in deleterious changes in tendon function, and these changes may be explained in part by the effects of oxLDL, which induced a proliferative, matrix-degrading phenotype in human tenocytes.
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    Neuroprotective and Anti-Inflammatory Roles of the Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN) Inhibition in a Mouse Model of Temporal Lobe Epilepsy (2014)
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    Publication Date: 2014-12-13
    Description: by Valentina Grande, Giusi Manassero, Alessandro Vercelli Excitotoxic damage represents the major mechanism leading to cell death in many human neurodegenerative diseases such as ischemia, trauma and epilepsy. Caused by an excess of glutamate that acts on metabotropic and ionotropic excitatory receptors, excitotoxicity activates several death signaling pathways leading to an extensive neuronal loss and a consequent strong activation of astrogliosis. Currently, the search for a neuroprotective strategy is aimed to identify the level in the signaling pathways to block excitotoxicity avoiding the loss of important physiological functions and side effects. To this aim, PTEN can be considered an ideal candidate: downstream the excitatory receptors activated in excitotoxicity (whose inhibition was shown to be not clinically viable), it is involved in neuronal damage and in the first stage of the reactive astrogliosis in vivo . In this study, we demonstrated the involvement of PTEN in excitotoxicity through its pharmacological inhibition by dipotassium bisperoxo (picolinato) oxovanadate [bpv(pic)] in a model of temporal lobe epilepsy, obtained by intraperitoneal injection of kainate in 2-month-old C57BL/6J male mice. We have demonstrated that inhibition of PTEN by bpv(pic) rescues neuronal death and decreases the reactive astrogliosis in the CA3 area of the hippocampus caused by systemic administration of kainate. Moreover, the neurotoxin administration increases significantly the scanty presence of mitochondrial PTEN that is significantly decreased by the administration of the inhibitor 6 hr after the injection of kainate, suggesting a role of PTEN in mitochondrial apoptosis. Taken together, our results confirm the key role played by PTEN in the excitotoxic damage and the strong anti-inflammatory and neuroprotective potential of its inhibition.
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    Phlebotomy Treatment for Elimination of Perfluoroalkyl Acids in a Highly Exposed Family: A Retrospective Case-Series (2014)
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    Publication Date: 2014-12-13
    Description: by Stephen J. Genuis, Yanna Liu, Quentin I. T. Genuis, Jonathan W. Martin Background Perfluoroalkyl acids (PFAAs) are a family of commonly used synthetic chemicals that have become widespread environmental contaminants. In human serum, perfluorohexane sulfonate (PFHxS), perflurooctane sulfonate (PFOS), and perfluorooctanoate (PFOA) are most frequently detected, in part owing to their long elimination half-lives of between 3.8 yrs (PFOA) and 8.5 yrs (PFHxS). These PFAAs also cross the placenta and have been associated with developmental toxicity, and some are considered likely human carcinogens. Interventions to eliminate PFAAs in highly contaminated individuals would reduce future health risks, but minimal research has been conducted on methods to facilitate accelerated human clearance of these persistent substances. Methods Six patients with elevated serum concentrations from a single family were treated by intermittent phlebotomy over a 4–5 year period at intervals similar to, or less frequent than what is done for routine blood donation at Canadian Blood Services. The apparent elimination half-life (HL app ) for PFHxS, PFOS, and PFOA in this treated population was calculated in each patient and compared to the intrinsic elimination half-lives (HL in ) from a literature reference population of untreated fluorochemical manufacturing plant retirees (n = 26, age 〉55 yrs). Results For all three PFAAs monitored during phlebotomy, HL app in each of the family members (except the mother, who had a low rate of venesection) was significantly shorter than the geometric mean HL measured in the reference population, and in some cases were even shorter compared to the fastest eliminator in the reference population. Conclusion This study suggests significantly accelerated PFAA clearance with regular phlebotomy treatment, but the small sample size and the lack of controls in this clinical intervention precludes drawing firm conclusions. Given the minimal risks of intermittent phlebotomy, this may be an effective and safe clinical intervention to diminish the body burden of PFAAs in highly exposed people.
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    The Duration of Hypotension Determines the Evolution of Bacteremia-Induced Acute Kidney Injury in the Intensive Care Unit (2014)
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    Publication Date: 2014-12-13
    Description: by Karin Janssen van Doorn, Walter Verbrugghe, Kristien Wouters, Hilde Jansens, Philippe G. Jorens Background Exploration of the impact of severe hypotension on the evolution of acute kidney injury in septic patients. Methods and Results We reviewed the hemodynamic parameters of 137 adults with septic shock and proven blood stream infection in the ICU. Severe hypotension was defined as a mean arterial blood pressure (MAP) ≤65 mmHg. The influence of the duration of severe hypotension on the evolution of acute kidney injury was evaluated according to the RIFLE classification, with day 0 defined as the day of a positive blood stream infection. After bloodstream infection, the probability for a patient to be in Failure was significantly higher than before blood stream infection (OR = 1.94, p = 0.0276). Patients have a significantly higher risk of evolving to Failure if the duration of severe hypotension is longer (OR = 1.02 for each 10 minutes increase in duration of a MAP
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    Correction: Population Genetics of the São Tomé Caecilian (Gymnophiona: Dermophiidae: Schistometopum thomense) Reveals Strong Geographic Structuring (2014)
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    Publication Date: 2014-12-16
    Description: by The PLOS ONE Staff
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    Correction: Mycobacterium tuberculosis Requires the ECF Sigma Factor SigE to Arrest Phagosome Maturation (2014)
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    Publication Date: 2014-12-16
    Description: by The PLOS ONE Staff
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    Correction: Molecular Phylogenetics and Systematics of the Bivalve Family Ostreidae Based on rRNA Sequence-Structure Models and Multilocus Species Tree (2014)
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    Publication Date: 2014-12-16
    Description: by The PLOS ONE Staff
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    Identification of Neonatal White Matter on DTI: Influence of More Inclusive Thresholds for Atlas Segmentation (2014)
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    Publication Date: 2014-12-16
    Description: by Rachel L. Vassar, Naama Barnea-Goraly, Jessica Rose Purpose Semi-automated diffusion tensor imaging (DTI) analysis of white matter (WM) microstructure offers a clinically feasible technique to assess neonatal brain development and provide early prognosis, but is limited by variable methods and insufficient evidence regarding optimal parameters. The purpose of this research was to investigate the influence of threshold values on semi-automated, atlas-based brain segmentation in very-low-birth-weight (VLBW) preterm infants at near-term age. Materials and Methods DTI scans were analyzed from 45 VLBW preterm neonates at near-term-age with no brain abnormalities evident on MRI. Brain regions were selected with a neonatal brain atlas and threshold values: trace 0.15, FA〉0.20, and FA〉0.25. Relative regional volumes, FA, axial diffusivity (AD), and radial diffusivity (RD) were compared for twelve WM regions. Results Near-term brain regions demonstrated differential effects from segmentation with the three FA thresholds. Regional DTI values and volumes selected in the PLIC, CereP, and RLC varied the least with the application of different FA thresholds. Overall, application of higher FA thresholds significantly reduced brain region volume selected, increased variability, and resulted in higher FA and lower RD values. The lower threshold FA〉0.15 selected 78±21% of original volumes segmented by the atlas, compared to 38±12% using threshold FA〉0.25. Conclusion Results indicate substantial and differential effects of atlas-based DTI threshold parameters on regional volume and diffusion scalars. A lower, more inclusive FA threshold than typically applied for adults is suggested for consistent analysis of WM regions in neonates.
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    Urinary Excretion of Fatty Acid-Binding Protein 4 is Associated with Albuminuria and Renal Dysfunction (2014)
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    Publication Date: 2014-12-16
    Description: by Yusuke Okazaki, Masato Furuhashi, Marenao Tanaka, Tomohiro Mita, Takahiro Fuseya, Shutaro Ishimura, Yuki Watanabe, Kyoko Hoshina, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura Background Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is expressed in not only adipocytes and macrophages but also peritubular capillaries in the normal kidney. We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP), in the glomerulus is associated with progression of proteinuria and renal dysfunction. However, urinary excretion of FABP4 has not been investigated. Methods Subjects who participated in the Tanno-Sobetsu Study, a study with a population-based cohort design, in 2011 (n = 392, male/female: 166/226) were enrolled. Urinary FABP4 (U-FABP4) and urinary albumin-to-creatinine ratio (UACR) were measured. Change in estimated glomerular filtration rate (eGFR) was followed up one year later. Results In 93 (23.7%) of the 392 subjects, U-FABP4 level was below the sensitivity of the assay. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. U-FABP4 level was positively correlated with age, systolic blood pressure and levels of serum FABP4 (S-FABP4), triglycerides, hemoglobin A1c (HbA1c), urinary FABP1 (U-FABP1) and UACR (r = 0.360, p
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    Age-Related Longitudinal Changes in Metabolic Energy Expenditure during Walking in Boys with Duchenne Muscular Dystrophy (2014)
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    Publication Date: 2014-12-16
    Description: by Merel-Anne Brehm, Jiska C. E. Kempen, Anneke J. van der Kooi, Imelda J. M. de Groot, Janneke C. van den Bergen, Jan J. G. M. Verschuuren, Erik H. Niks, Jaap Harlaar Objective The aim of this study was to evaluate age-related changes in metabolic walking energy expenditure in ambulant boys affected by Duchenne muscular dystrophy over a follow-up period of 12 months. Methods At baseline (T1) and 12 months later (T2), metabolic walking energy expenditure was assessed during a 6-minute walk test at comfortable speed in 14 ambulant boys with Duchenne (age range: 6.0-12.5 years, mean 8.2). Outcome measures derived from the assessment included the 6-minute comfortable walking distance (m) and net-nondimensional energy cost relative to speed-matched control cost (SMC-EC, %). Statistical comparisons were made using a two-way repeated measures ANOVA (factors: time (T1 versus T2) and age ( 0.158), and also there were no interaction effects (p〉0.248). Conclusions The results of our small study suggest that the natural course of walking performance in ambulant boys with Duchenne is characterized by a decrease in comfortable walking distance and an increase in walking energy cost. The rate of energy cost seems to increase with age, while walking distance decreases, which is opposite from the trend in typically developing children.
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    Hepatic Farnesoid X-Receptor Isoforms α2 and α4 Differentially Modulate Bile Salt and Lipoprotein Metabolism in Mice (2014)
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    Publication Date: 2014-12-16
    Description: by Marije Boesjes, Vincent W. Bloks, Jurre Hageman, Trijnie Bos, Theo H. van Dijk, Rick Havinga, Henk Wolters, Johan W. Jonker, Folkert Kuipers, Albert K. Groen The nuclear receptor FXR acts as an intracellular bile salt sensor that regulates synthesis and transport of bile salts within their enterohepatic circulation. In addition, FXR is involved in control of a variety of crucial metabolic pathways. Four FXR splice variants are known, i.e. FXRα1-4. Although these isoforms show differences in spatial and temporal expression patterns as well as in transcriptional activity, the physiological relevance hereof has remained elusive. We have evaluated specific roles of hepatic FXRα2 and FXRα4 by stably expressing these isoforms using liver-specific self-complementary adeno-associated viral vectors in total body FXR knock-out mice. The hepatic gene expression profile of the FXR knock-out mice was largely normalized by both isoforms. Yet, differential effects were also apparent; FXRα2 was more effective in reducing elevated HDL levels and transrepressed hepatic expression of Cyp8b1, the regulator of cholate synthesis. The latter coincided with a switch in hydrophobicity of the bile salt pool. Furthermore, FXRα2-transduction caused an increased neutral sterol excretion compared to FXRα4 without affecting intestinal cholesterol absorption. Our data show, for the first time, that hepatic FXRα2 and FXRα4 differentially modulate bile salt and lipoprotein metabolism in mice.
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    Mitochondrial COI and 16sRNA Evidence for a Single Species Hypothesis of E. vitis, J. formosana and E. onukii in East Asia (2014)
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    Publication Date: 2014-12-16
    Description: by Jian-Yu Fu, Bao-Yu Han, Qiang Xiao Tea green leafhopper is one of the most damaging tea pests in main tea production regions of East Asia. For lack of recognized morphological characters, the dominant species of tea green leafhoppers in Mainland China, Taiwan and Japan have always been named as Empoasca vitis Göthe, Jacobiasca formosana Paoli and Empoasca onukii MATSUDA, respectively. Furthermore, nothing is known about the genetic relationships among them. In this study, we collected six populations from Mainland China, four populations from Japan and one population from Taiwan, and examined the genetic distances in the COI and 16sRNA regions of mtDNA among them. The results showed that the genetic distances based on single gene or the combined sequences among eleven leafhopper populations were 0.3–1.2%, which were all less than the species boundary of 2%. Moreover, there were at least two haplotypes shared by two distinct populations from different regions. The phylogenetic analysis based on single gene or combined sets also supported that tea green leafhoppers from Mainland China, Taiwan and Japan were closely related to each other, and there were at least two specimens from different regions clustered ahead of those from the same region. Therefore, we propose that the view of recognizing the dominant species of tea green leafhoppers in three adjacent tea production regions of East Asia as different species is unreliable or questionable and suggest that they are a single species.
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    Correction: A Natural Plasmid Uniquely Encodes Two Biosynthetic Pathways Creating a Potent Anti-MRSA Antibiotic (2014)
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    Publication Date: 2014-12-16
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    Correction: Endogenous Retrovirus EAV-HP Linked to Blue Egg Phenotype in Mapuche Fowl (2014)
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    Description: by The PLOS ONE Staff
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    Metabolism of Skin-Absorbed Resveratrol into Its Glucuronized Form in Mouse Skin (2014)
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    Publication Date: 2014-12-16
    Description: by Itsuo Murakami, Romanas Chaleckis, Tomáš Pluskal, Ken Ito, Kousuke Hori, Masahiro Ebe, Mitsuhiro Yanagida, Hiroshi Kondoh Resveratrol (RESV) is a plant polyphenol, which is thought to have beneficial metabolic effects in laboratory animals as well as in humans. Following oral administration, RESV is immediately catabolized, resulting in low bioavailability. This study compared RESV metabolites and their tissue distribution after oral uptake and skin absorption. Metabolomic analysis of various mouse tissues revealed that RESV can be absorbed and metabolized through skin. We detected sulfated and glucuronidated RESV metabolites, as well as dihydroresveratrol. These metabolites are thought to have lower pharmacological activity than RESV. Similar quantities of most RESV metabolites were observed 4 h after oral or skin administration, except that glucuronidated RESV metabolites were more abundant in skin after topical RESV application than after oral administration. This result is consistent with our finding of glucuronidated RESV metabolites in cultured skin cells. RESV applied to mouse ears significantly suppressed inflammation in the TPA inflammation model. The skin absorption route could be a complementary, potent way to achieve therapeutic effects with RESV.
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    Intranasal Administration of Recombinant TRAIL Down-Regulates CXCL-1/KC in an Ovalbumin-Induced Airway Inflammation Murine Model (2014)
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    Description: by Veronica Tisato, Chiara Garrovo, Stefania Biffi, Francesca Petrera, Rebecca Voltan, Fabio Casciano, Germana Meroni, Chiara Agnoletto, Giorgio Zauli, Paola Secchiero Ovalbumin (OVA)-sensitized BALB/c mice were i.n. instilled with recombinant TNF-related apoptosis inducing ligand (TRAIL) 24 hours before OVA challenge. The total number of leukocytes and the levels of the chemokine CXCL-1/KC significantly increased in the bronchoalveolar lavage (BAL) fluids of allergic animals with respect to control littermates, but not in the BAL of mice i.n. pretreated with recombinant TRAIL before OVA challenge. In particular, TRAIL pretreatment significantly reduced the BAL percentage of both eosinophils and neutrophils. On the other hand, when TRAIL was administrated simultaneously to OVA challenge its effect on BAL infiltration was attenuated. Overall, the results show that the i.n. pretreatment with TRAIL down-modulated allergic airway inflammation.
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    Correction: Combined Treatment of Xenon and Hypothermia in Newborn Rats - Additive or Synergistic Effect? (2014)
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    Improved HIV Awareness and Perceived Empowerment to Negotiate Safe Sex among Married Women in Ethiopia between 2005 and 2011 (2014)
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    Publication Date: 2014-12-16
    Description: by Zaake De Coninck, Ibrahim A. Feyissa, Anna Mia Ekström, Gaetano Marrone Introduction The HIV prevalence rate in Ethiopia for married (or cohabiting) women is 3 times that found amongst women who have never been married. While marriage used to be seen as a protective factor against HIV, evidence suggests that this is no longer necessarily the case. This study analyses the trend and socio-demographic determinants of HIV awareness and safe sex negotiation among married women in Ethiopia between 2005 and 2011. Methods Data from Ethiopian Demographic and Health Surveys conducted in 2005 and in 2011 were analysed. Socio-demographic variables as well as ‘survey year’ were selected to assess their interaction with selected HIV awareness and safe sex negotiation indicators. Multivariable regression analyses were performed. Odds ratios and confidence intervals were computed. Results A significant increase in knowledge of HIV and ability to negotiate safer sex occurred between 2005 and 2011 reflecting a positive trend in gender empowerment amongst married Ethiopian women. Some of these advancements were striking, for instance respondents were 3.6 times more likely to have “Heard of AIDS” in 2011 than in 2005. HIV awareness and safer sex negotiation were significantly associated with higher education, higher socioeconomic status, those who had heard of HIV, those of the Orthodox Christian faith, and (to some extent) those living in rural areas. Conclusion HIV awareness has increased significantly in Ethiopia over the last decade but married women are still disproportionately susceptible to HIV. Community programmes, already effective in Ethiopia, also need to target this vulnerable sub-group of women.
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    Protoporphyrins Enhance Oligomerization and Enzymatic Activity of HtrA1 Serine Protease (2014)
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    Description: by Hakryul Jo, Victoria Patterson, Sean Stoessel, Chia-Yi Kuan, Josephine Hoh High temperature requirement protein A1 (HtrA1), a secreted serine protease of the HtrA family, is associated with a multitude of human diseases. However, the exact functions of HtrA1 in these diseases remain poorly understood. We seek to unravel the mechanisms of HtrA1 by elucidating its interactions with chemical or biological modulators. To this end, we screened a small molecule library of 500 bioactive compounds to identify those that alter the formation of extracellular HtrA1 complexes in the cell culture medium. An initial characterization of two novel hits from this screen showed that protoporphyrin IX (PPP-IX), a precursor in the heme biosynthetic pathway, and its metalloporphyrin (MPP) derivatives fostered the oligomerization of HtrA1 by binding to the protease domain. As a result of the interaction with MPPs, the proteolytic activity of HtrA1 against Fibulin-5, a specific HtrA1 substrate in age-related macular degeneration (AMD), was increased. This physical interaction could be abolished by the missense mutations of HtrA1 found in patients with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Furthermore, knockdown of HtrA1 attenuated apoptosis induced by PPP-IX. These results suggest that PPP-IX, or its derivatives, and HtrA1 may function as co-factors whereby porphyrins enhance oligomerization and the protease activity of HtrA1, while active HtrA1 elevates the pro-apoptotic actions of porphyrin derivatives. Further analysis of this interplay may shed insights into the pathogenesis of diseases such as AMD, CARASIL and protoporphyria, as well as effective therapeutic development.
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    Dissociable Neural Mechanisms Underlying the Modulation of Pain and Anxiety? An fMRI Pilot Study (2014)
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    Description: by Katja Wiech, Robert Edwards, Graham Lorimer Moseley, Chantal Berna, Markus Ploner, Irene Tracey The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC), which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a “behavioral control” paradigm, which involves the ability to terminate a noxious stimulus, and a “safety signaling” paradigm, which involves visual cues that signal the threat (or absence of threat) that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings.
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    Acoustic Telemetry Reveals Large-Scale Migration Patterns of Walleye in Lake Huron (2014)
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    Description: by Todd A. Hayden, Christopher M. Holbrook, David G. Fielder, Christopher S. Vandergoot, Roger A. Bergstedt, John M. Dettmers, Charles C. Krueger, Steven J. Cooke Fish migration in large freshwater lacustrine systems such as the Laurentian Great Lakes is not well understood. The walleye ( Sander vitreus ) is an economically and ecologically important native fish species throughout the Great Lakes. In Lake Huron walleye has recently undergone a population expansion as a result of recovery of the primary stock, stemming from changing food web dynamics. During 2011 and 2012, we used acoustic telemetry to document the timing and spatial scale of walleye migration in Lake Huron and Saginaw Bay. Spawning walleye ( n  = 199) collected from a tributary of Saginaw Bay were implanted with acoustic tags and their migrations were documented using acoustic receivers ( n  = 140) deployed throughout U.S. nearshore waters of Lake Huron. Three migration pathways were described using multistate mark-recapture models. Models were evaluated using the Akaike Information Criterion. Fish sex did not influence migratory behavior but did affect migration rate and walleye were detected on all acoustic receiver lines. Most (95%) tagged fish migrated downstream from the riverine tagging and release location to Saginaw Bay, and 37% of these fish emigrated from Saginaw Bay into Lake Huron. Remarkably, 8% of walleye that emigrated from Saginaw Bay were detected at the acoustic receiver line located farthest from the release location more than 350 km away. Most (64%) walleye returned to the Saginaw River in 2012, presumably for spawning. Our findings reveal that fish from this stock use virtually the entirety of U.S. nearshore waters of Lake Huron.
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    Healthy Dietary Interventions and Lipoprotein (a) Plasma Levels: Results from the Omni Heart Trial (2014)
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    Description: by Bernhard Haring, Moritz C. Wyler von Ballmoos, Lawrence J. Appel, Frank M. Sacks Background Increased lipoprotein(a) [Lp(a)] levels are associated with atherosclerotic cardiovascular disease. Studies of dietary interventions on changes in Lp(a) are sparse. We aimed to compare the effects of three healthy dietary interventions differing in macronutrient content on Lp(a) concentration. Methods Secondary analysis of a randomized, 3-period crossover feeding study including 155 (89 blacks; 66 whites) individuals. Participants were given DASH-type healthy diets rich in carbohydrates [Carb], in protein [Prot] or in unsaturated fat [Unsat Fat] for 6 weeks each. Plasma Lp(a) concentration was assessed at baseline and after each diet. Results Compared to baseline, all interventional diets increased mean Lp(a) by 2 to 5 mg/dl. Unsat Fat increased Lp(a) less than Prot with a difference of 1.0 mg/dl (95% CI, −0.5, 2.5; p = 0.196) in whites and 3.7 mg/dl (95% CI, 2.4, 5.0; p
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    Post Diagnosis Diet Quality and Colorectal Cancer Survival in Women (2014)
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    Description: by Teresa T. Fung, Rutendo Kashambwa, Kaori Sato, Stephanie E. Chiuve, Charles S. Fuchs, Kana Wu, Edward Giovannucci, Shuji Ogino, Frank B. Hu, Jeffrey A. Meyerhardt Background Dietary factors are known to influence colorectal cancer (CRC) risk, however, their association with CRC survival is unclear. Therefore, we prospectively examined the association between diet quality scores, dietary patterns and colorectal cancer (CRC) survival. Methods 1201 women diagnosed with stage I–III CRC between 1986 and 2008, were followed through 2010. Diet was assessed via a food frequency questionnaire administered at least 6 months after diagnosis. We computed the Alternate Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean Diet score (aMED) and Dietary Approaches to Stop Hypertension score (DASH) and derived two dietary patterns, Western (unhealthy) and prudent (healthy), by principal component analysis for each woman. Results During follow-up, we documented 435 deaths, including 162 from CRC. After adjusting for potential confounders, only a higher AHEI-2010 score was significantly associated with lower overall mortality (HR comparing extreme quintiles = 0.71, 95% CI 0.52–0.98, p trend = 0.01) as well as borderline significantly with lower risk of CRC mortality by the trend test (HR Q5 vs Q1 = 0.72, 95% CI = 0.43–1.21, p trend = 0.07). When AHEI-2010 components were examined separately, inverse associations for overall mortality were primarily accounted for by moderate alcohol intake (HR comparing abstainers vs 5–15 g/d = 1.30, 95%CI = 1.05–1.61) and lower intake of sugar sweetened beverages and fruit juices combined (HR for each additional serving = 1.11, 95% CI = 1.01–1.23). No other diet quality score or dietary pattern was associated with overall or CRC-specific mortality. Conclusion Higher AHEI-2010 score may be associated with lower overall mortality, moderate alcohol consumption and lower consumption of sugar sweetened beverages and juices combined appeared to account for most of the observed associations.
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    Mesothelin Expression in Triple Negative Breast Carcinomas Correlates Significantly with Basal-Like Phenotype, Distant Metastases and Decreased Survival (2014)
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    Publication Date: 2014-12-16
    Description: by Gary Tozbikian, Edi Brogi, Kyuichi Kadota, Jeffrey Catalano, Muzaffar Akram, Sujata Patil, Alice Y. Ho, Jorge S. Reis-Filho, Britta Weigelt, Larry Norton, Prasad S. Adusumilli, Hannah Yong Wen Mesothelin is a cell surface associated antigen expressed on mesothelial cells and in some malignant neoplasms. Mesothelin-targeted therapies are in phase I/II clinical trials. The clinicopathologic and prognostic significance of mesothelin expression in triple negative breast carcinomas (TNBC) has not been fully assessed. We evaluated the expression of mesothelin and of basal markers in tissue microarrays of 226 TNBC and 88 non-TNBC and assessed the clinicopathologic features of mesothelin-expressing breast carcinomas. Furthermore, we investigated the impact of mesothelin expression on the disease-free and overall survival of patients with TNBC. We found that mesothelin expression is significantly more frequent in TNBC than in non-TNBC (36% vs 16%, respectively; p = 0.0006), and is significantly correlated with immunoreactivity for basal keratins, but not for EGFR. Mesothelin-positive and mesothelin-negative TNBC were not significantly different by patients’ race, tumor size, histologic grade, tumor subtype, lymphovascular invasion and lymph node metastases. Patients with mesothelin-positive TNBC were older than patients with mesothelin-negative TNBC, developed more distant metastases with a shorter interval, and had significantly lower overall and disease-free survival. Based on our results, patients with mesothelin-positive TNBC could benefit from mesothelin-targeted therapies.
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    Correction: Human Papillomavirus and Cystic Node Metastasis in Oropharyngeal Cancer and Cancer of Unknown Primary Origin (2014)
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    Correction: Tempol, a Superoxide Dismutase Mimetic Agent, Ameliorates Cisplatin-Induced Nephrotoxicity through Alleviation of Mitochondrial Dysfunction in Mice (2014)
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    Correction: A New Recombinant BCG Vaccine Induces Specific Th17 and Th1 Effector Cells with Higher Protective Efficacy against Tuberculosis (2014)
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    Temporal Changes in Population Structure of a Marine Planktonic Diatom (2014)
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    Publication Date: 2014-12-16
    Description: by Sylvie V. M. Tesson, Marina Montresor, Gabriele Procaccini, Wiebe H. C. F. Kooistra A prevailing question in phytoplankton research addresses changes of genetic diversity in the face of huge population sizes and apparently unlimited dispersal capabilities. We investigated population genetic structure of the pennate planktonic marine diatom Pseudo-nitzschia multistriata at the LTER station MareChiara in the Gulf of Naples (Italy) over four consecutive years and explored possible changes over seasons and from year to year. A total of 525 strains were genotyped using seven microsatellite markers, for a genotypic diversity of 75.05%, comparable to that found in other Pseudo-nitzschia species. Evidence from Bayesian clustering analysis (BA) identified two genetically distinct clusters, here interpreted as populations, and several strains that could not be assigned with ≥90% probability to either population, here interpreted as putative hybrids. Principal Component Analysis (PCA) recovered these two clusters in distinct clouds with most of the putative hybrids located in-between. Relative proportions of the two populations and the putative hybrids remained similar within years, but changed radically between 2008 and 2009 and between 2010 and 2011, when the 2008-population apparently became the dominant one again. Strains from the two populations are inter-fertile, and so is their offspring. Inclusion of genotypes of parental strains and their offspring shows that the majority of the latter could not be assigned to any of the two parental populations. Therefore, field strains classified by BA as the putative hybrids could be biological hybrids. We hypothesize that P. multistriata population dynamics in the Gulf of Naples follows a meta-population-like model, including establishment of populations by cell inocula at the beginning of each growth season and remixing and dispersal governed by moving and mildly turbulent water masses.
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    A Survey of Management Practices That Influence Performance and Welfare of Dairy Calves Reared in Southern Brazil (2014)
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    Publication Date: 2014-12-16
    Description: by Maria J. Hötzel, Cibele Longo, Lucas F. Balcão, Clarissa S. Cardoso, João H. C. Costa Here we report dairy calf management practices used by 242 smallholder family farmers in the South of Brazil. Data were collected via a semi-structured questionnaire with farmers, inspection of the production environment and an in-depth interview with a sample of 26 farmers. Herds had an average of 22.3 lactating cows and an average milk production of 12.7 L/cow/day. Calves were dehorned in 98% of the farms, with a hot iron in 95%. Male calves were castrated in 71% of the farms; methods were surgery (68%), emasculator (29%), or rubber rings (3%). No pain control was used for these interventions. In 51% of the farms all newborn male calves were reared, sold or donated to others; in 35% all newborn males were killed on the farm. Calves were separated from the dam up to 12 h after birth in 78% of the farms, and left to nurse colostrum from the dam without intervention in 55% of the farms. The typical amount of milk fed to calves was 4 L/day until a median age of 75 days. In 40% of the farms milk was provided in a bucket, in 49% with bottles, and in 11% calves suckled from a cow. Solid feeding in the milk-feeding period started at a median age of 10 days. Calves were housed individually in 70% of the farms; in 81% of the farms calves were housed in indoor pens, in 6% in outdoor hutches and in 13% they were kept on pasture. Diarrhoea was reported as the main cause of calf mortality in 71% of the farms. Farmers kept no records of calf disease, mortality, or use of medicines. Changing the scenario identified in this survey is essential to support the sustainable development of dairy production, an activity of great economic and social relevance for the region.
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    Planning Study of Flattening Filter Free Beams for Volumetric Modulated Arc Therapy in Squamous Cell Carcinoma of the Scalp (2014)
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    Publication Date: 2014-12-16
    Description: by Youqun Lai, Liwan Shi, Qin Lin, Lirong Fu, Huiming Ha Purpose Flattening filter free (FFF) beams show the potential for a higher dose rate and lower peripheral dose. We investigated the planning study of FFF beams with their role for volumetric modulated arc therapy (VMAT) in squamous cell carcinoma of the scalp. Methods and Materials One patient with squamous cell carcinoma which had involvement of entire scalp was subjected to VMAT using TrueBeam linear accelerator. As it was a rare skin malignancy, CT data of 7 patients with brain tumors were also included in this study, and their entire scalps were outlined as target volumes. Three VMAT plans were employed with RapidArc form: two half-field full-arcs VMAT using 6 MV standard beams (HFF-VMAT-FF), eight half-field quarter-arcs VMAT using 6 MV standard beams (HFQ-VMAT-FF), and HFQ-VMAT using FFF beams (HFQ-VMAT-FFF). Prescribed dose was 25×2 Gy (50 Gy). Plan quality and efficiency were assessed for all plans. Results There were no statistically significant differences among the three VMAT plans in target volume coverage, conformity, and homogeneity. For HFQ-VMAT-FF plans, there was a significant decrease by 12.6% in the mean dose to the brain compared with HFF-VMAT-FF. By the use of FFF beams, the mean dose to brain in HFQ-VMAT-FFF plans was further decreased by 7.4% compared with HFQ-VMAT-FF. Beam delivery times were similar for each technique. Conclusions The HFQ-VMAT-FF plans showed the superiority in dose distributions compared with HFF-VMAT-FF. HFQ-VMAT-FFF plans might provide further normal tissue sparing, particularly in the brain, showing their potential for radiation therapy in squamous cell carcinoma of the scalp.
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    Light-Promoted Rhodopsin Expression and Starvation Survival in the Marine Dinoflagellate Oxyrrhis marina (2014)
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    Publication Date: 2014-12-16
    Description: by Zhiling Guo, Huan Zhang, Senjie Lin The discovery of microbial rhodopsins in marine proteobacteria changed the dogma that photosynthesis is the only pathway to use the solar energy for biological utilization in the marine environment. Although homologs of these rhodopsins have been identified in dinoflagellates, the diversity of the encoding genes and their physiological roles remain unexplored. As an initial step toward addressing the gap, we conducted high-throughput transcriptome sequencing on Oxyrrhis marina to retrieve rhodopsin transcripts, rapid amplification of cDNA ends to isolate full-length cDNAs of dominant representatives, and quantitative reverse-transcription PCR to investigate their expression under varying conditions. Our phylogenetic analyses showed that O . marina contained both the proton-pumping type (PR) and sensory type (SR) rhodopsins, and the transcriptome data showed that the PR type dominated over the SR type. We compared rhodopsin gene expression for cultures kept under light: dark cycle and continuous darkness in a time course of 24 days without feeding. Although both types of rhodopsin were expressed under the two conditions, the expression levels of PR were much higher than SR, consistent with the transcriptomic data. Furthermore, relative to cultures kept in the dark, rhodopsin expression levels and cell survival rate were both higher in cultures grown in the light. This is the first report of light-dependent promotion of starvation survival and concomitant promotion of PR expression in a eukaryote. While direct evidence needs to come from functional test on rhodopsins in vitro or gene knockout/knockdown experiments, our results suggest that the proton-pumping rhodopsin might be responsible for the light-enhanced survival of O . marina , as previously demonstrated in bacteria.
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    Comparison of Modic Changes in the Lumbar and Cervical Spine, in 3167 Patients with and without Spinal Pain (2014)
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    Publication Date: 2014-12-16
    Description: by Li Sheng-yun, Suyou Letu, Chen Jian, Maiwulanjiang Mamuti, Liu Jun-hui, Shan Zhi, Wang Chong-yan, Fan Shunwu, Fengdong Zhao Background Context There are few comparisons of Modic changes (MCs) in the lumbar and cervical spine. Purpose Compare the prevalence of MCs in the lumbar and cervical spine, and determine how MC prevalence depends on spinal pain, age, disc degeneration, spinal level, and the presence or absence of kyphosis. Study Design Retrospective clinical survey. Materials and Methods Magnetic resonance images (MRIs) were compared from five patient groups: 1. 1223 patients with low-back pain/radiculopathy only; 2. 1023 patients with neck pain/radiculopathy only; 3. 497 patients with concurrent low-back and neck symptoms; 4. 304 asymptomatic subjects with lumbar MRIs; and 5. 120 asymptomatic subjects with cervical MRIs. Results The prevalence of MCs was higher in those with spinal pain than in those without, both in the lumbar spine (21.0% vs 10.5%) and cervical spine (8.8% vs 3.3%). Type II MCs were most common and Type III were least common in all groups. The prevalence of lumbar MCs in people with back pain was little affected by the presence of concurrent neck pain, and the same was true for the prevalence of cervical MCs in people with neck pain with or without concurrent back pain. When symptomatic patients were reclassified into two groups (back pain, neck pain), the prevalence of lumbar MCs in people with back pain was greater than that of cervical MCs in people with neck pain. The prevalence of lumbar and cervical MCs increased with age, disc degeneration, (descending) spinal level, and increased kyphosis. Conclusions There is a significantly higher prevalence of MCs in patients with back and neck pain. The reported association with increased kyphosis (flat back) is novel.
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    Correction: Clinical Practice Guidelines and Consensus Statements in Oncology – An Assessment of Their Methodological Quality (2014)
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    Publication Date: 2014-12-18
    Description: by The PLOS ONE Staff
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 83
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    Range of Movement in Ray I of Manus and Pes and the Prehensility of the Autopodia in the Early Permian to Late Cretaceous Non-Anomodont Synapsida (2014)
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    Publication Date: 2014-12-18
    Description: by Susanna B. Kümmell, Eberhard Frey The mobility of ray I was analysed in seventy-eight Early Permian to Late Cretaceous specimens of non-mammalian Synapsida and one extant mammal. In all non-mammaliamorph Synapsida investigated, ray I formed a digital arcade. The first phalanx was maximally extendable to the zero position in the metapodiophalangeal joint I. Metapodiale I was the functional equivalent to a basal phalanx of digits II–V. In contrast, there was no digital arcade in ray I in Mesozoic Mammaliamorpha. Phalanx 1 I was dorsally extendable and metapodiale I was functionally part of the metapodium. During the propulsion phase, autopodial rotation occurred in the majority of Synapsida with abducted limb posture. Regarding ray I, the reduction of autopodial rotation can be estimated, e.g., from the decrease of lateral rotation and medial abduction of the first phalanx in the metapodiophalangeal joint I. Autopodial rotation was high in Titanophoneus and reduced in derived Cynodontia. In Mammaliamorpha the mobility of the first ray suggests autopodial rolling in an approximately anterior direction. Most non-mammaliamorph Therapsida and probably some Mesozoic Mammaliamorpha had prehensile autopodia with an opposable ray I. In forms with a pronounced relief of the respective joints, ray I could be opposed to 90° against ray III. A strong transverse arch in the row of distalia supported the opposition movement of ray I and resulted in a convergence of the claws of digits II–V just by flexing those digits. A tight articular coherence in the digital joints of digits II–V during strong flexion supported a firm grip capacity. Usually the grip capacity was more pronounced in the manus than in the pes. Prehensile autopodia of carnivorous Therapsida may have been utilized to hold prey while biting, thus helping to avoid fractures of the laterally compressed fangs.
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    Molecular Epidemiology of Carbapenem Non-Susceptible Acinetobacter baumannii in France (2014)
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    Publication Date: 2014-12-18
    Description: by Katy Jeannot, Laure Diancourt, Sophie Vaux, Michelle Thouverez, Amandina Ribeiro, Bruno Coignard, Patrice Courvalin, Sylvain Brisse Carbapenem-resistant Acinetobacter baumannii have emerged globally. The objective of this study was to investigate the epidemiology, clonal diversity and resistance mechanisms of imipenem non-susceptible A. baumannii isolates in France. Between December 2010 and August 2011, 132 notifications were collected, including 37 outbreaks corresponding to 242 cases (2 to 55 per cluster). Multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and characterisation of carbapenemase-encoding genes were performed on 110 non-repetitive isolates. Gene bla OXA-23 was the most frequently detected (82%), followed by bla OXA-24 (11%) and bla OXA-58 (7%). Eleven sequence types (ST) were distinguished, among which sequence types ST1, ST2 (64%), ST20, ST25, ST85 and ST107. Isolates from epidemiological clusters had the same ST and resistance genes, indicating probable transmission within centres. In contrast, PFGE types of isolates differed among centres, arguing against transmission among centers. This study provides the first epidemiological snapshot of the population of A. baumannii with reduced susceptibility to carbapenems from France, and further underlines the predominance of international clones.
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  • 85
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    Comparison of Texture Features Derived from Static and Respiratory-Gated PET Images in Non-Small Cell Lung Cancer (2014)
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    Publication Date: 2014-12-18
    Description: by Stephen Yip, Keisha McCall, Michalis Aristophanous, Aileen B. Chen, Hugo J. W. L. Aerts, Ross Berbeco Background PET-based texture features have been used to quantify tumor heterogeneity due to their predictive power in treatment outcome. We investigated the sensitivity of texture features to tumor motion by comparing static (3D) and respiratory-gated (4D) PET imaging. Methods Twenty-six patients (34 lesions) received 3D and 4D [ 18 F]FDG-PET scans before the chemo-radiotherapy. The acquired 4D data were retrospectively binned into five breathing phases to create the 4D image sequence. Texture features, including Maximal correlation coefficient (MCC), Long run low gray (LRLG), Coarseness, Contrast, and Busyness, were computed within the physician-defined tumor volume. The relative difference (δ 3D-4D ) in each texture between the 3D- and 4D-PET imaging was calculated. Coefficient of variation (CV) was used to determine the variability in the textures between all 4D-PET phases. Correlations between tumor volume, motion amplitude, and δ 3D-4D were also assessed. Results 4D-PET increased LRLG ( = 1%–2%, p
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  • 86
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    Relating Specific Emotions to Intrinsic Motivation: On the Moderating Role of Positive and Negative Emotion Differentiation (2014)
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    Publication Date: 2014-12-18
    Description: by Leen Vandercammen, Joeri Hofmans, Peter Theuns Despite the fact that studies on self-determination theory have traditionally disregarded the explicit role of emotions in the motivation eliciting process, research attention for the affective antecedents of motivation is growing. We add to this emerging research field by testing the moderating role of emotion differentiation –individual differences in the extent to which people can differentiate between specific emotions– on the relationship between twelve specific emotions and intrinsic motivation. To this end, we conducted a daily diary study ( N  = 72) and an experience sampling study ( N  = 34). Results showed that the relationship between enthusiasm, cheerfulness, optimism, contentedness, gloominess, miserableness, uneasiness (in both studies 1 and 2), calmness, relaxation, tenseness, depression, worry (only in Study 1) on one hand and intrinsic motivation on the other hand was moderated by positive emotion differentiation for the positive emotions and by negative emotion differentiation for the negative emotions. Altogether, these findings suggest that for people who are unable to distinguish between different specific positive emotions the relationship between those specific positive emotions and intrinsic motivation is stronger, whereas the relationship between specific negative emotions and intrinsic motivation is weaker for people who are able to distinguish between the different specific negative emotions. Theoretical and practical implications are discussed.
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  • 87
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    Effective Use of the Built Environment to Manage Behavioural and Psychological Symptoms of Dementia: A Systematic Review (2014)
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    Publication Date: 2014-12-18
    Description: by Lesley J. J. Soril, Laura E. Leggett, Diane L. Lorenzetti, James Silvius, Duncan Robertson, Lynne Mansell, Jayna Holroyd-Leduc, Tom W. Noseworthy, Fiona M. Clement Objective To determine the effectiveness of built environment interventions in managing behavioural and psychological symptoms of dementia (BPSD) among residents in long-term care settings. Methods Systematic review of literature published from 1995–2013. Studies were included if they: were randomized controlled trials, quasi-experimental trials, or comparative cohort studies; were in long-term or specialized dementia care; included residents with dementia and BPSD; and examined effectiveness of a built environment intervention on frequency and/or severity of BPSD. Quality of included studies was assessed using the Downs and Black Checklist. Study design, patient population, intervention, and outcomes were extracted and narratively synthesized. Results Five low to moderate quality studies were included. Three categories of interventions were identified: change/redesign of existing physical space, addition of physical objects to environment, and type of living environment. One of the two studies that examined change/redesign of physical spaces reported improvements in BPSD. The addition of physical objects to an existing environment (n = 1) resulted in no difference in BPSD between treatment and control groups. The two studies that examined relocation to a novel living environment reported decreased or no difference in the severity and/or frequency of BPSD post-intervention. No studies reported worsening of BPSD following a built environment intervention. Conclusions The range of built environment interventions is broad, as is the complex and multi-dimensional nature of BPSD. There is inconclusive evidence to suggest a built environment intervention which is clinically superior in long-term care settings. Further high-quality methodological and experimental studies are required to demonstrate the feasibility and effectiveness of such interventions.
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  • 88
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    Correction: The White Ceiling Heuristic and the Underestimation of Asian-American Income (2014)
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    Publication Date: 2014-12-18
    Description: by The PLOS ONE Staff
    Electronic ISSN: 1932-6203
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  • 89
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    Vertical and Horizontal Genetic Connectivity in Chromis verater, an Endemic Damselfish Found on Shallow and Mesophotic Reefs in the Hawaiian Archipelago and Adjacent Johnston Atoll (2014)
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    Publication Date: 2014-12-18
    Description: by Kimberly A. Tenggardjaja, Brian W. Bowen, Giacomo Bernardi Understanding vertical and horizontal connectivity is a major priority in research on mesophotic coral ecosystems (30–150 m). However, horizontal connectivity has been the focus of few studies, and data on vertical connectivity are limited to sessile benthic mesophotic organisms. Here we present patterns of vertical and horizontal connectivity in the Hawaiian Islands-Johnston Atoll endemic threespot damselfish, Chromis verater , based on 319 shallow specimens and 153 deep specimens. The mtDNA markers cytochrome b and control region were sequenced to analyze genetic structure: 1) between shallow (
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  • 90
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    A Novel GJA8 Mutation (p.V44A) Causing Autosomal Dominant Congenital Cataract (2014)
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    Publication Date: 2014-12-18
    Description: by Yanan Zhu, Hao Yu, Wei Wang, Xiaohua Gong, Ke Yao Purpose To examine the mechanism by which a novel connexin 50 (Cx50) mutation, Cx50 V44A, in a Chinese family causes suture-sparing autosomal dominant congenital nuclear cataracts. Methods Family history and clinical data were recorded and direct gene sequencing was used to identify the disease-causing mutation. The Cx50 gene was cloned from a human lens cDNA library. Connexin protein distributions were assessed by fluorescence microscopy. Hemichannel functions were analyzed by dye uptake assay. Formation of functional channels was assessed by dye transfer experiments. Results Direct sequencing of the candidate GJA8 gene revealed a novel c.131T〉C transition in exon 2, which cosegregated with the disease in the family and resulted in the substitution of a valine residue with alanine at codon 44 (p. V44A) in the extracellular loop 1 of the Cx50 protein. Both Cx50 and Cx50V44A formed functional gap junctions, as shown by the neurobiotin transfer assay. However, unlike wild-type Cx50, Cx50V44A was unable to form open hemichannels in dye uptake experiments. Conclusion This work identified a unique congenital cataract in the Chinese population, caused by the novel mutation Cx50V44A, and it showed that the V44A mutation specifically impairs the gating of the hemichannels but not the gap junction channels. The dysfunctional hemichannels resulted in the development of human congenital cataracts.
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    The Effect of 17β-Estradiol on Cutaneous Wound Healing in Protein-Malnourished Ovariectomized Female Mouse Model (2014)
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    Publication Date: 2014-12-18
    Description: by Kanae Mukai, Emi Komatsu, Yukari Nakajima, Tamae Urai, Nasruddin, Junko Sugama, Toshio Nakatani Cutaneous wound healing is delayed by protein malnutrition (PM). On the other hand, estrogen promotes cutaneous wound healing by its anti-inflammatory and cell proliferation effects. Therefore, we hypothesized that estrogen administration in protein-malnourished ovariectomized (OVX) female mice might improve the inflammatory response and promote cutaneous wound healing as well as normal nutrition. To test this hypothesis, we used full-thickness excisional wounds in Control SHAM, PM SHAM, PM OVX and PM OVX+17β-estradiol mice. The Control diet included 200 g/kg protein and the PM diet included 30 g/kg protein. The ratio of wound area in the Control SHAM group was significantly smaller than those in the three PM groups. In addition, microscopic findings also showed that the ratio of collagen fibers, the ratio of myofibroblasts and the number of new blood vessels in the Control SHAM group were significantly greater than those in the three PM groups. However, the number of Ym1-positive cells as an anti-inflammatory M2-like macrophage marker in the PM OVX+17β-estradiol group was significantly higher than those in the other three groups. These results indicate that the appearance of anti-inflammatory M2-like macrophages was promoted by estrogen administration; however, it could not promote cutaneous wound healing upon a low-protein diet. Therefore, it may be confirmed that nutrition is more important for promoting cutaneous wound healing than estrogen administration.
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  • 92
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    Correction: Quantitative Analysis of Cytokinesis In Situ during C. elegans Postembryonic Development (2014)
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    Publication Date: 2014-12-18
    Description: by The PLOS ONE Staff
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  • 93
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    A Computational Model of Afterimage Rotation in the Peripheral Drift Illusion Based on Retinal ON/OFF Responses (2014)
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    Publication Date: 2014-12-18
    Description: by Yuichiro Hayashi, Shin Ishii, Hidetoshi Urakubo Human observers perceive illusory rotations after the disappearance of circularly repeating patches containing dark-to-light luminance. This afterimage rotation is a very powerful phenomenon, but little is known about the mechanisms underlying it. Here, we use a computational model to show that the afterimage rotation can be explained by a combination of fast light adaptation and the physiological architecture of the early visual system, consisting of ON- and OFF-type visual pathways. In this retinal ON/OFF model, the afterimage rotation appeared as a rotation of focus lines of retinal ON/OFF responses. Focus lines rotated clockwise on a light background, but counterclockwise on a dark background. These findings were consistent with the results of psychophysical experiments, which were also performed by us. Additionally, the velocity of the afterimage rotation was comparable with that observed in our psychophysical experiments. These results suggest that the early visual system (including the retina) is responsible for the generation of the afterimage rotation, and that this illusory rotation may be systematically misinterpreted by our high-level visual system.
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    Correction: Cell-Permeable Parkin Proteins Suppress Parkinson Disease-Associated Phenotypes in Cultured Cells and Animals (2014)
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    Publication Date: 2014-12-18
    Description: by The PLOS ONE Staff
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  • 95
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    Correction: Medium Effects on Minimum Inhibitory Concentrations of Nylon-3 Polymers against E. coli (2014)
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    Publication Date: 2014-12-18
    Description: by The PLOS ONE Staff
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  • 96
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    Unexpected Effects of Low Doses of a Neonicotinoid Insecticide on Behavioral Responses to Sex Pheromone in a Pest Insect (2014)
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    Publication Date: 2014-12-18
    Description: by Kaouther K. Rabhi, Kali Esancy, Anouk Voisin, Lucille Crespin, Julie Le Corre, Hélène Tricoire-Leignel, Sylvia Anton, Christophe Gadenne In moths, which include many agricultural pest species, males are attracted by female-emitted sex pheromones. Although integrated pest management strategies are increasingly developed, most insect pest treatments rely on widespread use of neurotoxic chemicals, including neonicotinoid insecticides. Residual accumulation of low concentrations of these insecticides in the environment is known to be harmful to beneficial insects such as honey bees. This environmental stress probably acts as an “info-disruptor” by modifying the chemical communication system, and therefore decreases chances of reproduction in target insects that largely rely on olfactory communication. However, low doses of pollutants could on the contrary induce adaptive processes in the olfactory pathway, thus enhancing reproduction. Here we tested the effects of acute oral treatments with different low doses of the neonicotinoid clothianidin on the behavioral responses to sex pheromone in the moth Agrotis ipsilon using wind tunnel experiments. We show that low doses of clothianidin induce a biphasic effect on pheromone-guided behavior. Surprisingly, we found a hormetic-like effect, improving orientation behavior at the LD20 dose corresponding to 10 ng clothianidin. On the contrary, a negative effect, disturbing orientation behavior, was elicited by a treatment with a dose below the LD0 dose corresponding to 0.25 ng clothianidin. No clothianidin effect was observed on behavioral responses to plant odor. Our results indicate that risk assessment has to include unexpected effects of residues on the life history traits of pest insects, which could then lead to their adaptation to environmental stress.
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    Obesity and Its Relationship with Hypertension among Adults 50 Years and Older in Jinan, China (2014)
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    Publication Date: 2014-12-18
    Description: by Shu-Kang Wang, Wei Ma, Shumei Wang, Xiang-Ren Yi, Hong-Ying Jia, Fuzhong Xue Background The relationship between obesity and hypertension varies with geographical area, race and definitions of obesity. Our study aimed to investigate the prevalence of obesity using standard Chinese criteria based on the body mass index (BMI) and the waist circumference (WC) and to examine the association between obesity and hypertension among middle-aged and elderly people in Jinan city. Methods This cross-sectional study examined 1,870 subjects from the blocks randomly selected from among the 6 communities of Jinan, China in 2011–2012. The Student's t-test was used to compare numerical data, and the χ 2 test was used to compare categorical data. Multivariate logistic regression analyses were performed to assess the effects of general and central obesity on hypertension after adjusting for age or for education level, smoking, alcohol consumption, and continuous age. Results The prevalence of general obesity among people age 50 years and older was 21.1% (17.0% for males and 23.1% for females), and the prevalence of central obesity was 77.8% for men and 78.7% for women. For men, compared with a normal BMI, the ORs and 95% CIs for overweight and general obesity were 1.853 (1.252, 2.744) and 3.422 (1.894, 6.182), respectively, after adjusting for age, smoking, alcohol consumption and educational level. Compared with a normal WC, the ORs and 95% CIs for central obesity were 2.334 (1.573, 3.465) and 2.318 (1.544, 3.479), respectively, for men. For women, compared with a normal BMI, the ORs and 95% CIs were 1.942 (1.473, 2.599) and 4.011 (2.817, 5.712), respectively, after adjusting for age, smoking, alcohol consumption and educational level. Compared with a normal WC, the ORs and 95% CIs for central obesity were 2.488 (1.865, 3.319) and 2.379 (1.773, 3.192), respectively, for women. Conclusions The relationship between hypertension and general obesity was stronger than the relationship between hypertension and either overweight or central obesity in both genders.
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    p-Cresol Affects Reactive Oxygen Species Generation, Cell Cycle Arrest, Cytotoxicity and Inflammation/Atherosclerosis-Related Modulators Production in Endothelial Cells and Mononuclear Cells (2014)
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    Publication Date: 2014-12-18
    Description: by Mei-Chi Chang, Hsiao-Hua Chang, Chiu-Po Chan, Sin-Yuet Yeung, Hsiang-Chi Hsien, Bor-Ru Lin, Chien-Yang Yeh, Wan-Yu Tseng, Shui-Kuan Tseng, Jiiang-Huei Jeng Aims Cresols are present in antiseptics, coal tar, some resins, pesticides, and industrial solvents. Cresol intoxication leads to hepatic injury due to coagulopathy as well as disturbance of hepatic circulation in fatal cases. Patients with uremia suffer from cardiovascular complications, such as atherosclerosis, thrombosis, hemolysis, and bleeding, which may be partly due to p-cresol toxicity and its effects on vascular endothelial and mononuclear cells. Given the role of reactive oxygen species (ROS) and inflammation in vascular thrombosis, the objective of this study was to evaluate the effect of p-cresol on endothelial and mononuclear cells. Methods EA.hy926 (EAHY) endothelial cells and U937 cells were exposed to different concentrations of p-cresol. Cytotoxicity was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5 -diphenyltetrazolium bromide (MTT) assay and trypan blue dye exclusion technique, respectively. Cell cycle distribution was analyzed by propidium iodide flow cytometry. Endothelial cell migration was studied by wound closure assay. ROS level was measured by 2′,7′-dichlorofluorescein diacetate (DCF) fluorescence flow cytometry. Prostaglandin F 2α (PGF 2α ), plasminogen activator inhibitor-1 (PAI-1), soluble urokinase plasminogen activator receptor (suPAR), and uPA production were determined by Enzyme-linked immunosorbant assay (ELISA). Results Exposure to 100–500 µM p-cresol decreased EAHY cell number by 30–61%. P-cresol also decreased the viability of U937 mononuclear cells. The inhibition of EAHY and U937 cell growth by p-cresol was related to induction of S-phase cell cycle arrest. Closure of endothelial wounds was inhibited by p-cresol (〉100 µM). P-cresol (〉50 µM) also stimulated ROS production in U937 cells and EAHY cells but to a lesser extent. Moreover, p-cresol markedly stimulated PAI-1 and suPAR, but not PGF 2α , and uPA production in EAHY cells. Conclusions p-Cresol may contribute to atherosclerosis and thrombosis in patients with uremia and cresol intoxication possibly due to induction of ROS, endothelial/mononuclear cell damage and production of inflammation/atherosclerosis-related molecules.
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    Quantitative Genetics Model as the Unifying Model for Defining Genomic Relationship and Inbreeding Coefficient (2014)
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    Publication Date: 2014-12-18
    Description: by Chunkao Wang, Yang Da The traditional quantitative genetics model was used as the unifying approach to derive six existing and new definitions of genomic additive and dominance relationships. The theoretical differences of these definitions were in the assumptions of equal SNP effects (equivalent to across-SNP standardization), equal SNP variances (equivalent to within-SNP standardization), and expected or sample SNP additive and dominance variances. The six definitions of genomic additive and dominance relationships on average were consistent with the pedigree relationships, but had individual genomic specificity and large variations not observed from pedigree relationships. These large variations may allow finding least related genomes even within the same family for minimizing genomic relatedness among breeding individuals. The six definitions of genomic relationships generally had similar numerical results in genomic best linear unbiased predictions of additive effects (GBLUP) and similar genomic REML (GREML) estimates of additive heritability. Predicted SNP dominance effects and GREML estimates of dominance heritability were similar within definitions assuming equal SNP effects or within definitions assuming equal SNP variance, but had differences between these two groups of definitions. We proposed a new measure of genomic inbreeding coefficient based on parental genomic co-ancestry coefficient and genomic additive correlation as a genomic approach for predicting offspring inbreeding level. This genomic inbreeding coefficient had the highest correlation with pedigree inbreeding coefficient among the four methods evaluated for calculating genomic inbreeding coefficient in a Holstein sample and a swine sample.
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    Lewis Carroll's Doublets Net of English Words: Network Heterogeneity in a Complex System (2014)
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    Publication Date: 2014-12-18
    Description: by Hsieh Fushing, Chen Chen, Yin-Chen Hsieh, Patrick Farrell Lewis Carroll's English word game Doublets is represented as a system of networks with each node being an English word and each connectivity edge confirming that its two ending words are equal in letter length, but different by exactly one letter. We show that this system, which we call the Doublets net, constitutes a complex body of linguistic knowledge concerning English word structure that has computable multiscale features. Distributed morphological, phonological and orthographic constraints and the language's local redundancy are seen at the node level. Phonological communities are seen at the network level. And a balancing act between the language's global efficiency and redundancy is seen at the system level. We develop a new measure of intrinsic node-to-node distance and a computational algorithm, called community geometry, which reveal the implicit multiscale structure within binary networks. Because the Doublets net is a modular complex cognitive system, the community geometry and computable multi-scale structural information may provide a foundation for understanding computational learning in many systems whose network structure has yet to be fully analyzed.
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