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  • 1
    Journal cover
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    Public Library of Science (PLoS)
    Online: 1.2005 –
    Publisher: Public Library of Science (PLoS)
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 2
    Journal cover
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    Public Library of Science (PLoS)
    Online: 1.2003 –
    Publisher: Public Library of Science (PLoS)
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 3
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    Public Library of Science (PLoS)
    Online: 1.2010 –
    Publisher: Public Library of Science (PLoS)
    Topics: Biology
    Keywords: Biodiversität
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  • 4
    Journal cover
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    Public Library of Science (PLoS)
    Online: 1.2005 –
    Publisher: Public Library of Science (PLoS)
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 5
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    Public Library of Science (PLoS) | PubMed Central
    Online: 1.2009 –
    Publisher: Public Library of Science (PLoS) , PubMed Central
    Electronic ISSN: 2157-3999
    Topics: Medicine , Natural Sciences in General
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  • 6
    Publication Date: 2016-10-12
    Description: The rich fossil record of horses has made them a classic example of evolutionary processes. However, while the overall picture of equid evolution is well known, the details are surprisingly poorly understood, especially for the later Pliocene and Pleistocene, c. 3 million to 0.01 million years (Ma) ago, and nowhere more so than in the Americas. There is no consensus on the number of equid species or even the number of lineages that existed in these continents. Likewise, the origin of the endemic South American genus Hippidion is unresolved, as is the phylogenetic position of the “stilt-legged” horses of North America. Using ancient DNA sequences, we show that, in contrast to current models based on morphology and a recent genetic study, Hippidion was phylogenetically close to the caballine (true) horses, with origins considerably more recent than the currently accepted date of c. 10 Ma. Furthermore, we show that stilt-legged horses, commonly regarded as Old World migrants related to the hemionid asses of Asia, were in fact an endemic North American lineage. Finally, our data suggest that there were fewer horse species in late Pleistocene North America than have been named on morphological grounds. Both caballine and stilt-legged lineages may each have comprised a single, wide-ranging species.
    Type: Article , PeerReviewed
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  • 7
    Publication Date: 2019-02-01
    Description: Habitat-forming species sustain biodiversity and ecosystem functioning in harsh environments through the amelioration of physical stress. Nonetheless, their role in shaping patterns of species distribution under future climate scenarios is generally overlooked. Focusing on coastal systems, we assess how habitat-forming species can influence the ability of stress-sensitive species to exhibit plastic responses, adapt to novel environmental conditions, or track suitable climates. Here, we argue that habitat-former populations could be managed as a nature-based solution against climate-driven loss of biodiversity. Drawing from different ecological and biological disciplines, we identify a series of actions to sustain the resilience of marine habitat-forming species to climate change, as well as their effectiveness and reliability in rescuing stress-sensitive species from increasingly adverse environmental conditions.
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  • 8
  • 9
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    Public Library of Science (PLoS)
    Publication Date: 2016-09-22
    Description: © 2004 Jennifer J. Wernegreen. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in PLoS Biology 2 (2004): e68, doi:10.1371/journal.pbio.0020068.
    Description: Symbiosis, an interdependent relationship between two species, is an important driver of evolutionary novelty and ecological diversity. Microbial symbionts in particular have been major evolutionary catalysts throughout the 4 billion years of life on earth and have largely shaped the evolution of complex organisms. Endosymbiosis is a specifi c type of symbiosis in which one—typically microbial—partner lives within its host and represents the most intimate contact between interacting organisms. Mitochondria and chloroplasts, for example, result from endosymbiotic events of lasting significance that extended the range of acceptable habitats for life. The wide distribution of intracellular bacteria across diverse hosts and marine and terrestrial habitats testifies to the continued importance of endosymbiosis in evolution. Among multicellular organisms, insects as a group form exceptionally diverse associations with microbial associates, including bacteria that live exclusively within host cells and undergo maternal transmission to offspring. These microbes have piqued the interest of evolutionary biologists because they represent a wide spectrum of evolutionary strategies, ranging from obligate mutualism to reproductive parasitism (Buchner 1965; Ishikawa 2003) (Box 1; Table 1).
    Description: JJW gratefully acknowledges the support of the National Institutes of Health (R01 GM62626-01), the National Science Foundation (DEB 0089455), the National Aeronautics and Space Administration Astrobiology Institute (NNA04CC04A), and the Josephine Bay Paul and C. Michael Paul Foundation.
    Keywords: Endosymbiosis ; Endosymbiosis manipulation
    Repository Name: Woods Hole Open Access Server
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  • 10
    Publication Date: 2016-09-23
    Description: © 2005 Sullivan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in PLoS Biology 3 (2005): e144, doi:10.1371/journal.pbio.0030144.
    Description: The oceanic cyanobacteria Prochlorococcus are globally important, ecologically diverse primary producers. It is thought that their viruses (phages) mediate population sizes and affect the evolutionary trajectories of their hosts. Here we present an analysis of genomes from three Prochlorococcus phages: a podovirus and two myoviruses. The morphology, overall genome features, and gene content of these phages suggest that they are quite similar to T7-like (P-SSP7) and T4-like (P-SSM2 and P-SSM4) phages. Using the existing phage taxonomic framework as a guideline, we examined genome sequences to establish ‘‘core’’ genes for each phage group. We found the podovirus contained 15 of 26 core T7-like genes and the two myoviruses contained 43 and 42 of 75 core T4-like genes. In addition to these core genes, each genome contains a significant number of ‘‘cyanobacterial’’ genes, i.e., genes with significant best BLAST hits to genes found in cyanobacteria. Some of these, we speculate, represent ‘‘signature’’ cyanophage genes. For example, all three phage genomes contain photosynthetic genes (psbA, hliP) that are thought to help maintain host photosynthetic activity during infection, as well as an aldolase family gene (talC) that could facilitate alternative routes of carbon metabolism during infection. The podovirus genome also contains an integrase gene (int) and other features that suggest it is capable of integrating into its host. If indeed it is, this would be unprecedented among cultured T7-like phages or marine cyanophages and would have significant evolutionary and ecological implications for phage and host. Further, both myoviruses contain phosphate-inducible genes (phoH and pstS) that are likely to be important for phage and host responses to phosphate stress, a commonly limiting nutrient in marine systems. Thus, these marine cyanophages appear to be variations of two well-known phages—T7 and T4—but contain genes that, if functional, reflect adaptations for infection of photosynthetic hosts in low-nutrient oceanic environments.
    Description: This research was supported by the US DOE under grant numbers DEFG02– 99ER62814 and DE-FG02–02ER63445, and the National Science Foundation under grant number OCE-9820035 (to SWC).
    Keywords: Oceanic cyanobacteria ; Prochlorococcus phages
    Repository Name: Woods Hole Open Access Server
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  • 11
    Publication Date: 2016-09-22
    Description: © 2006 Bordenstein et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in PLoS Pathogens 2(2006): e43, doi:10.1371/journal.ppat.0020043.
    Description: By manipulating arthropod reproduction worldwide, the heritable endosymbiont Wolbachia has spread to pandemic levels. Little is known about the microbial basis of cytoplasmic incompatibility (CI) except that bacterial densities and percentages of infected sperm cysts associate with incompatibility strength. The recent discovery of a temperate bacteriophage (WO-B) of Wolbachia containing ankyrin-encoding genes and virulence factors has led to intensifying debate that bacteriophage WO-B induces CI. However, current hypotheses have not considered the separate roles that lytic and lysogenic phage might have on bacterial fitness and phenotype. Here we describe a set of quantitative approaches to characterize phage densities and its associations with bacterial densities and CI. We enumerated genome copy number of phage WO-B and Wolbachia and CI penetrance in supergroup A- and B-infected males of the parasitoid wasp Nasonia vitripennis. We report several findings: (1) variability in CI strength for A-infected males is positively associated with bacterial densities, as expected under the bacterial density model of CI, (2) phage and bacterial densities have a significant inverse association, as expected for an active lytic infection, and (3) CI strength and phage densities are inversely related in A-infected males; similarly, males expressing incomplete CI have significantly higher phage densities than males expressing complete CI. Ultrastructural analyses indicate that approximately 12% of the A Wolbachia have phage particles, and aggregations of these particles can putatively occur outside the Wolbachia cell. Physical interactions were observed between approximately 16% of the Wolbachia cells and spermatid tails. The results support a low to moderate frequency of lytic development in Wolbachia and an overall negative density relationship between bacteriophage and Wolbachia. The findings motivate a novel phage density model of CI in which lytic phage repress Wolbachia densities and therefore reproductive parasitism. We conclude that phage, Wolbachia, and arthropods form a tripartite symbiotic association in which all three are integral to understanding the biology of this widespread endosymbiosis. Clarifying the roles of lytic and lysogenic phage development in Wolbachia biology will effectively structure inquiries into this research topic.
    Description: This work was supported by grants from the NASA Astrobiology Institute (NNA04CC04A) and National Institutes of Health (R01 GM62626-01) to JJW, and by the Marine Biological Laboratory's Program in Global Infectious Diseases, funded by the Ellison Medical Foundation, to SRB.
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  • 12
    Publication Date: 2016-09-23
    Description: This is an open-access article distributed under the terms of the Creative Commons Public Domain dedication. The definitive version was published in PLoS Biology 4 (2006): e383, doi:10.1371/journal.pbio.0040383.
    Description: Presented here is the complete genome sequence of Thiomicrospira crunogena XCL-2, representative of ubiquitous chemolithoautotrophic sulfur-oxidizing bacteria isolated from deep-sea hydrothermal vents. This gammaproteobacterium has a single chromosome (2,427,734 base pairs), and its genome illustrates many of the adaptations that have enabled it to thrive at vents globally. It has 14 methyl-accepting chemotaxis protein genes, including four that may assist in positioning it in the redoxcline. A relative abundance of coding sequences (CDSs) encoding regulatory proteins likely control the expression of genes encoding carboxysomes, multiple dissolved inorganic nitrogen and phosphate transporters, as well as a phosphonate operon, which provide this species with a variety of options for acquiring these substrates from the environment. Thiom. crunogena XCL-2 is unusual among obligate sulfur-oxidizing bacteria in relying on the Sox system for the oxidation of reduced sulfur compounds. The genome has characteristics consistent with an obligately chemolithoautotrophic lifestyle, including few transporters predicted to have organic allocrits, and Calvin-Benson-Bassham cycle CDSs scattered throughout the genome.
    Description: This work was performed under the auspices of the United States Department of Energy by Lawrence Livermore National Laboratory, University of California, under contract W-7405-ENG-48. Genome closure was funded in part by a University of South Florida Innovative Teaching Grant (to KMS). KMS, SKF, and CAK gratefully acknowledge support from the United States Department of Agriculture Higher Education Challenge Grants Program (Award # 20053841115876). SMS kindly acknowledges support through a fellowship received from the Hanse Wissenschaftskolleg in Delmenhorst, Germany (http://www.h-w-k.de). MH was supported by a Woods Hole Oceanographic Institution postdoctoral scholarship.
    Repository Name: Woods Hole Open Access Server
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  • 13
    Publication Date: 2016-09-22
    Description: © 2006 Parfrey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in PLoS Genetics 2 (2006): e220, doi:10.1371/journal.pgen.0020220.
    Description: Perspectives on the classification of eukaryotic diversity have changed rapidly in recent years, as the four eukaryotic groups within the five-kingdom classification—plants, animals, fungi, and protists—have been transformed through numerous permutations into the current system of six ‘‘supergroups.’’ The intent of the supergroup classification system is to unite microbial and macroscopic eukaryotes based on phylogenetic inference. This supergroup approach is increasing in popularity in the literature and is appearing in introductory biology textbooks. We evaluate the stability and support for the current six-supergroup classification of eukaryotes based on molecular genealogies. We assess three aspects of each supergroup: (1) the stability of its taxonomy, (2) the support for monophyly (single evolutionary origin) in molecular analyses targeting a supergroup, and (3) the support for monophyly when a supergroup is included as an out-group in phylogenetic studies targeting other taxa. Our analysis demonstrates that supergroup taxonomies are unstable and that support for groups varies tremendously, indicating that the current classification scheme of eukaryotes is likely premature. We highlight several trends contributing to the instability and discuss the requirements for establishing robust clades within the eukaryotic tree of life.
    Description: This work is supported by the National Science Foundation Assembling the Tree of Life grant (043115) to DB, DJP, and LAK.
    Repository Name: Woods Hole Open Access Server
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  • 14
    Publication Date: 2019-07-18
    Description: Almost all animals and plants are inhabited by diverse communities of microorganisms, the microbiota, thereby forming an integrated entity, the metaorganism. Natural selection should favor hosts that shape the community composition of these microbes to promote a beneficial host-microbe symbiosis. Indeed, animal hosts often pose selective environments, which only a subset of the environmentally available microbes are able to colonize. How these microbes assemble after colonization to form the complex microbiota is less clear. Neutral models are based on the assumption that the alternatives in microbiota community composition are selectively equivalent and thus entirely shaped by random population dynamics and dispersal. Here, we use the neutral model as a null hypothesis to assess microbiata composition in host organisms, which does not rely on invoking any adaptive processes underlying microbial community assembly. We show that the overall microbiota community structure from a wide range of host organisms, in particular including previously understudied invertebrates, is in many cases consistent with neutral expectations. Our approach allows to identify individual microbes that are deviating from the neutral expectation and are therefore interesting candidates for further study. Moreover, using simulated communities, we demonstrate that transient community states may play a role in the deviations from the neutral expectation. Our findings highlight that the consideration of neutral processes and temporal changes in community composition are critical for an in-depth understanding of microbiota-host interactions.
    Type: Article , PeerReviewed
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  • 15
    Publication Date: 2019-09-23
    Description: Aquatic ecosystems worldwide continue to experience unprecedented warming and ecological change. Warming increases metabolic rates of animals, plants, and microbes, accelerating their use of energy and materials, their population growth, and interaction rates. At a much larger biological scale, warming accelerates ecosystem-level processes, elevating fluxes of carbon and oxygen between biota and the atmosphere. Although these general effects of temperature at finer and broader biological scales are widely observed, they can lead to contradictory predictions for how warming affects the structure and function of ecological communities at the intermediate scale of biological organization. We experimentally tested the hypothesis that the presence of predators and their associated species interactions modify the temperature dependence of net ecosystem oxygen production and respiration. We tracked a series of independent freshwater ecosystems (370 L) over 9 weeks, and we found that at higher temperatures, cascading effects of predators on zooplankton prey and algae were stronger than at lower temperatures. When grazing was weak or absent, standing phytoplankton biomass declined by 85%–95% (〈1-fold) over the temperature gradient (19–30 °C), and by 3-fold when grazers were present and lacked predators. These temperature-dependent species interactions and consequent community biomass shifts occurred without signs of species loss or community collapse, and only modestly affected the temperature dependence of net ecosystem oxygen fluxes. The exponential increases in net ecosystem oxygen production and consumption were relatively insensitive to differences in trophic interactions among ecosystems. Furthermore, monotonic declines in phytoplankton standing stock suggested no threshold effects of warming across systems. We conclude that local changes in community structure, including temperature-dependent trophic cascades, may be compatible with prevailing and predictable effects of temperature on ecosystem functions related to fundamental effects of temperature on metabolism.
    Type: Article , PeerReviewed
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  • 16
    Publication Date: 2016-11-24
    Description: by James Alibhai, Richard A. Blanco, Marcelo A. Barria, Pedro Piccardo, Byron Caughey, V. Hugh Perry, Tom C. Freeman, Jean C. Manson Protein misfolding is common across many neurodegenerative diseases, with misfolded proteins acting as seeds for "prion-like" conversion of normally folded protein to abnormal conformations. A central hypothesis is that misfolded protein accumulation, spread, and distribution are restricted to specific neuronal populations of the central nervous system and thus predict regions of neurodegeneration. We examined this hypothesis using a highly sensitive assay system for detection of misfolded protein seeds in a murine model of prion disease. Misfolded prion protein (PrP) seeds were observed widespread throughout the brain, accumulating in all brain regions examined irrespective of neurodegeneration. Importantly, neither time of exposure nor amount of misfolded protein seeds present determined regions of neurodegeneration. We further demonstrate two distinct microglia responses in prion-infected brains: a novel homeostatic response in all regions and an innate immune response restricted to sites of neurodegeneration. Therefore, accumulation of misfolded prion protein alone does not define targeting of neurodegeneration, which instead results only when misfolded prion protein accompanies a specific innate immune response.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 17
    Publication Date: 2016-11-24
    Description: by Bo Ram Kim, Emily Van de Laar, Michael Cabanero, Shintaro Tarumi, Stefan Hasenoeder, Dennis Wang, Carl Virtanen, Takaya Suzuki, Bizhan Bandarchi, Shingo Sakashita, Nhu An Pham, Sharon Lee, Shaf Keshavjee, Thomas K. Waddell, Ming-Sound Tsao, Nadeem Moghal Although cancers are considered stem cell diseases, mechanisms involving stem cell alterations are poorly understood. Squamous cell carcinoma (SQCC) is the second most common lung cancer, and its pathogenesis appears to hinge on changes in the stem cell behavior of basal cells in the bronchial airways. Basal cells are normally quiescent and differentiate into mucociliary epithelia. Smoking triggers a hyperproliferative response resulting in progressive premalignant epithelial changes ranging from squamous metaplasia to dysplasia. These changes can regress naturally, even with chronic smoking. However, for unknown reasons, dysplasias have higher progression rates than earlier stages. We used primary human tracheobronchial basal cells to investigate how copy number gains in SOX2 and PIK3CA at 3q26-28, which co-occur in dysplasia and are observed in 94% of SQCCs, may promote progression. We find that SOX2 cooperates with PI3K signaling, which is activated by smoking, to initiate the squamous injury response in basal cells. This response involves SOX9 repression, and, accordingly, SOX2 and PI3K signaling levels are high during dysplasia, while SOX9 is not expressed. By contrast, during regeneration of mucociliary epithelia, PI3K signaling is low and basal cells transiently enter a SOX2 Lo SOX9 Hi state, with SOX9 promoting proliferation and preventing squamous differentiation. Transient reduction in SOX2 is necessary for ciliogenesis, although SOX2 expression later rises and drives mucinous differentiation, as SOX9 levels decline. Frequent coamplification of SOX2 and PIK3CA in dysplasia may, thus, promote progression by locking basal cells in a SOX2 Hi SOX9 Lo state with active PI3K signaling, which sustains the squamous injury response while precluding normal mucociliary differentiation. Surprisingly, we find that, although later in invasive carcinoma SOX9 is generally expressed at low levels, its expression is higher in a subset of SQCCs with less squamous identity and worse clinical outcome. We propose that early pathogenesis of most SQCCs involves stabilization of the squamous injury state in stem cells through copy number gains at 3q, with the pro-proliferative activity of SOX9 possibly being exploited in a subset of SQCCs in later stages.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 18
    Publication Date: 2016-11-24
    Description: by The PLOS ONE Staff
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 19
    Publication Date: 2016-11-24
    Description: by Elizabeth N. Davison, Benjamin O. Turner, Kimberly J. Schlesinger, Michael B. Miller, Scott T. Grafton, Danielle S. Bassett, Jean M. Carlson Individual differences in brain functional networks may be related to complex personal identifiers, including health, age, and ability. Dynamic network theory has been used to identify properties of dynamic brain function from fMRI data, but the majority of analyses and findings remain at the level of the group. Here, we apply hypergraph analysis, a method from dynamic network theory, to quantify individual differences in brain functional dynamics. Using a summary metric derived from the hypergraph formalism—hypergraph cardinality—we investigate individual variations in two separate, complementary data sets. The first data set (“multi-task”) consists of 77 individuals engaging in four consecutive cognitive tasks. We observe that hypergraph cardinality exhibits variation across individuals while remaining consistent within individuals between tasks; moreover, the analysis of one of the memory tasks revealed a marginally significant correspondence between hypergraph cardinality and age. This finding motivated a similar analysis of the second data set (“age-memory”), in which 95 individuals, aged 18–75, performed a memory task with a similar structure to the multi-task memory task. With the increased age range in the age-memory data set, the correlation between hypergraph cardinality and age correspondence becomes significant. We discuss these results in the context of the well-known finding linking age with network structure, and suggest that hypergraph analysis should serve as a useful tool in furthering our understanding of the dynamic network structure of the brain.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 20
    Publication Date: 2016-11-24
    Description: by Milen Nikolov, Caitlin A. Bever, Alexander Upfill-Brown, Busiku Hamainza, John M. Miller, Philip A. Eckhoff, Edward A. Wenger, Jaline Gerardin As more regions approach malaria elimination, understanding how different interventions interact to reduce transmission becomes critical. The Lake Kariba area of Southern Province, Zambia, is part of a multi-country elimination effort and presents a particular challenge as it is an interconnected region of variable transmission intensities. In 2012–13, six rounds of mass test-and-treat drug campaigns were carried out in the Lake Kariba region. A spatial dynamical model of malaria transmission in the Lake Kariba area, with transmission and climate modeled at the village scale, was calibrated to the 2012–13 prevalence survey data, with case management rates, insecticide-treated net usage, and drug campaign coverage informed by surveillance. The model captured the spatio-temporal trends of decline and rebound in malaria prevalence in 2012–13 at the village scale. Various interventions implemented between 2016–22 were simulated to compare their effects on reducing regional transmission and achieving and maintaining elimination through 2030. Simulations predict that elimination requires sustaining high coverage with vector control over several years. When vector control measures are well-implemented, targeted mass drug campaigns in high-burden areas further increase the likelihood of elimination, although drug campaigns cannot compensate for insufficient vector control. If infections are regularly imported from outside the region into highly receptive areas, vector control must be maintained within the region until importations cease. Elimination in the Lake Kariba region is possible, although human movement both within and from outside the region risk damaging the success of elimination programs.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
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  • 21
    Publication Date: 2016-11-24
    Description: by Florent Bocquelet, Thomas Hueber, Laurent Girin, Christophe Savariaux, Blaise Yvert Restoring natural speech in paralyzed and aphasic people could be achieved using a Brain-Computer Interface (BCI) controlling a speech synthesizer in real-time. To reach this goal, a prerequisite is to develop a speech synthesizer producing intelligible speech in real-time with a reasonable number of control parameters. We present here an articulatory-based speech synthesizer that can be controlled in real-time for future BCI applications. This synthesizer converts movements of the main speech articulators (tongue, jaw, velum, and lips) into intelligible speech. The articulatory-to-acoustic mapping is performed using a deep neural network (DNN) trained on electromagnetic articulography (EMA) data recorded on a reference speaker synchronously with the produced speech signal. This DNN is then used in both offline and online modes to map the position of sensors glued on different speech articulators into acoustic parameters that are further converted into an audio signal using a vocoder. In offline mode, highly intelligible speech could be obtained as assessed by perceptual evaluation performed by 12 listeners. Then, to anticipate future BCI applications, we further assessed the real-time control of the synthesizer by both the reference speaker and new speakers, in a closed-loop paradigm using EMA data recorded in real time. A short calibration period was used to compensate for differences in sensor positions and articulatory differences between new speakers and the reference speaker. We found that real-time synthesis of vowels and consonants was possible with good intelligibility. In conclusion, these results open to future speech BCI applications using such articulatory-based speech synthesizer.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
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  • 22
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    Public Library of Science (PLoS)
    Publication Date: 2016-11-24
    Description: by Shen Gu, Przemyslaw Szafranski, Zeynep Coban Akdemir, Bo Yuan, Mitchell L. Cooper, Maria A. Magriñá, Carlos A. Bacino, Seema R. Lalani, Amy M. Breman, Janice L. Smith, Ankita Patel, Rodger H. Song, Weimin Bi, Sau Wai Cheung, Claudia M. B. Carvalho, Paweł Stankiewicz, James R. Lupski Chromosomal insertions are genomic rearrangements with a chromosome segment inserted into a non-homologous chromosome or a non-adjacent locus on the same chromosome or the other homologue, constituting ~2% of nonrecurrent copy-number gains. Little is known about the molecular mechanisms of their formation. We identified 16 individuals with complex insertions among 56,000 individuals tested at Baylor Genetics using clinical array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH). Custom high-density aCGH was performed on 10 individuals with available DNA, and breakpoint junctions were fine-mapped at nucleotide resolution by long-range PCR and DNA sequencing in 6 individuals to glean insights into potential mechanisms of formation. We observed microhomologies and templated insertions at the breakpoint junctions, resembling the breakpoint junction signatures found in complex genomic rearrangements generated by replication-based mechanism(s) with iterative template switches. In addition, we analyzed 5 families with apparently balanced insertion in one parent detected by FISH analysis and found that 3 parents had additional small copy-number variants (CNVs) at one or both sides of the inserting fragments as well as at the inserted sites. We propose that replicative repair can result in interchromosomal complex insertions generated through chromothripsis-like chromoanasynthesis involving two or three chromosomes, and cause a significant fraction of apparently balanced insertions harboring small flanking CNVs.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 23
    Publication Date: 2016-11-24
    Description: by Weiming Tang, Songyuan Tang, Yilu Qin, Ye Zhang, Wei Zhang, Chuncheng Liu, Lai Sze Tso, Chongyi Wei, Ligang Yang, Shujie Huang, Bin Yang, Joseph Tucker Introduction China is amidst a sexual revolution, with changing sexual practices and behaviors. Sex–seeking mobile phone applications (gay apps) that allow multiple people to meet up quickly may facilitate group sex. This study was therefore undertaken to evaluate group sex among Chinese MSM and to better understand factors associated with group sex. Methods An online survey was conducted from September-October 2014, collecting data on socio-demographics, sexual behaviors, use of gay apps and occurrence of group sex among Chinese MSM. Univariate and multivariable logistic regressions were used to compare group sex and non-group sex participants. Results Of the 1,424 MSM, the majority were under 30 years old (77.5%), unmarried (83.9%), and were gay apps users (57.9%). Overall, 141 (9.9%) participants engaged in group sex in the last 12 months. Multivariate analyses showed that men living with HIV, engaged in condomless anal intercourse with men, and used gay apps were more likely to engage in group sex, with adjusted ORs of 3.74 (95% CI 1.92–7.28), 2.88 (95% CI 2.00–4.16) and 1.46 (95% CI: 1.00–2.13), respectively. Among gay app users, the likelihood of group sex increases with the number of sex partners and the number of sex acts with partners met through a gay app. Conclusions Chinese MSM who engage in group sex are also more likely to engage in other risky sexual behaviors, and gay app use may facilitate group sex. Further research is needed among MSM who engage in group sex in order to target interventions and surveillance.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 24
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    Public Library of Science (PLoS)
    Publication Date: 2016-11-24
    Description: by Mehdi Moussaïd, Kyanoush Seyed Yahosseini In many social systems, groups of individuals can find remarkably efficient solutions to complex cognitive problems, sometimes even outperforming a single expert. The success of the group, however, crucially depends on how the judgments of the group members are aggregated to produce the collective answer. A large variety of such aggregation methods have been described in the literature, such as averaging the independent judgments, relying on the majority or setting up a group discussion. In the present work, we introduce a novel approach for aggregating judgments—the transmission chain—which has not yet been consistently evaluated in the context of collective intelligence. In a transmission chain, all group members have access to a unique collective solution and can improve it sequentially. Over repeated improvements, the collective solution that emerges reflects the judgments of every group members. We address the question of whether such a transmission chain can foster collective intelligence for binary-choice problems. In a series of numerical simulations, we explore the impact of various factors on the performance of the transmission chain, such as the group size, the model parameters, and the structure of the population. The performance of this method is compared to those of the majority rule and the confidence-weighted majority. Finally, we rely on two existing datasets of individuals performing a series of binary decisions to evaluate the expected performances of the three methods empirically. We find that the parameter space where the transmission chain has the best performance rarely appears in real datasets. We conclude that the transmission chain is best suited for other types of problems, such as those that have cumulative properties.
    Electronic ISSN: 1932-6203
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  • 25
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    Publication Date: 2016-11-24
    Description: by Chee W. Chia, Michelle Shardell, Toshiko Tanaka, David D. Liu, Kristofer S. Gravenstein, Eleanor M. Simonsick, Josephine M. Egan, Luigi Ferrucci Introduction Low-calorie sweetener use for weight control has come under increasing scrutiny as obesity, especially abdominal obesity, remain entrenched despite substantial low-calorie sweetener use. We evaluated whether chronic low-calorie sweetener use is a risk factor for abdominal obesity. Participants and Methods We used 8268 anthropometric measurements and 3096 food diary records with detailed information on low-calorie sweetener consumption in all food products, from 1454 participants (741 men, 713 women) in the Baltimore Longitudinal Study of Aging collected from 1984 to 2012 with median follow-up of 10 years (range: 0–28 years). At baseline, 785 were low-calorie sweetener non-users (51.7% men) and 669 participants were low-calorie sweetener users (50.1% men). Time-varying low-calorie sweetener use was operationalized as the proportion of visits since baseline at which low-calorie sweetener use was reported. We used marginal structural models to determine the association between baseline and time-varying low-calorie sweetener use with longitudinal outcomes—body mass index, waist circumference, obesity and abdominal obesity—with outcome status assessed at the visit following low-calorie sweetener ascertainment to minimize the potential for reverse causality. All models were adjusted for year of visit, age, sex, age by sex interaction, race, current smoking status, dietary intake (caffeine, fructose, protein, carbohydrate, and fat), physical activity, diabetes status, and Dietary Approaches to Stop Hypertension score as confounders. Results With median follow-up of 10 years, low-calorie sweetener users had 0.80 kg/m 2 higher body mass index (95% confidence interval [CI], 0.17–1.44), 2.6 cm larger waist circumference (95% CI, 0.71–4.39), 36.7% higher prevalence (prevalence ratio = 1.37; 95% CI, 1.10–1.69) and 53% higher incidence (hazard ratio = 1.53; 95% CI 1.10–2.12) of abdominal obesity than low-calorie sweetener non-users. Conclusions Low-calorie sweetener use is independently associated with heavier relative weight, a larger waist, and a higher prevalence and incidence of abdominal obesity suggesting that low-calorie sweetener use may not be an effective means of weight control.
    Electronic ISSN: 1932-6203
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  • 26
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    Publication Date: 2016-11-24
    Description: by Ana L. M. Batista de Carvalho, Paula S. C. Medeiros, Francisco M. Costa, Vanessa P. Ribeiro, Joana B. Sousa, Carmen Diniz, Maria P. M. Marques The present work is aimed at evaluating the antitumour properties of a Pd(II) dinuclear complex with the biogenic polyamine spermine, by investigating: i) the anti-angiogenic and anti-migration properties of a Pd(II) dinuclear complex with spermine (Pd 2 Spm); ii) the anti-proliferative activity of Pd 2 Spm against a triple negative human breast carcinoma (MDA-MB-231); and finally iii) the putative interaction mediated by combination of Pd 2 Spm with Docetaxel. Anti-invasive (anti-angiogenic and anti-migratory) as well as anti-proliferative capacities were assessed, for different combination schemes and drug exposure times, using the CAM assay and VEGFR2 activity measurement, the Matrigel TM method and the SRB proliferation test. The results thus obtained evidence the ability of Pd 2 Spm to restrict angiogenesis and cell migration: Pd 2 Spm induced a marked inhibition of migration (43.8±12.2%), and a higher inhibition of angiogenesis (81.8±4.4% for total length values, at 4 μM) as compared to DTX at the clinical dosage 4x10 -2 μM (26.4±14.4%; n = 4 to 11). Combination of Pd 2 Spm/DTX was more effective as anti-invasive and anti-proliferative than DTX or Pd 2 Spm in sole administration, which is compatible with the occurrence of synergism: for the anti-angiogenic effect, IC 50(Pd2Spm/DTX) = 0.5/0.5x10 -2 μM vs IC 50(DTX) = 1.7x10 -2 μM and IC 50(Pd2Spm) = 1.6 μM. In conclusion, the reported effects of Pd 2 Spm on angiogenesis, migration and proliferation showed that this compound is a promising therapeutic agent against this type of breast cancer. Moreover, combined administration of Pd 2 Spm and DTX was found to trigger a substantial synergetic effect regarding angiogenesis inhibition as well as anti-migratory and anti-proliferative activities reinforcing the putative use of Pd(II) complexes in chemotherapeutic regimens. This is a significant outcome, aiming at the application of these combined strategies towards metastatic breast cancer (or other type of resistant cancers), justifying further studies that include pre-clinical trials.
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  • 27
    Publication Date: 2016-11-24
    Description: by Min Huang, Xuefeng Zhou, Xiaobing Xie, Chunrong Zhao, Jiana Chen, Fangbo Cao, Yingbin Zou The mechanism associated with improvement of soil nutritional status by oilseed rape crop, leading to better performance of rice crop, in rice-oilseed rape cropping systems is little known. The present study was aimed to test the hypothesis that earthworm casts produced during oilseed rape-growing season have positive effects on grain yield and fertilizer nitrogen (N) utilization in the subsequent flooded rice crop. A 15 N-tracing pot experiment was conducted to determine the effects of earthworm casts collected from oilseed rape fields on yield attributes in rice and the fate of fertilizer N. Soil treated with earthworm casts (soil: earthworm casts = 4: 1, w/w) (EC 1 ) produced 39% higher grain yield than soil only (EC 0 ). EC 1 had 18% more panicle number and 10% higher spikelet filling percentage than EC 0 . Aboveground biomass and harvest index were higher in EC 1 than in EC 0 by 20% and 15%, respectively. SPAD values in flag leaves were 10% and 22% higher under EC 1 than EC 0 at 15 and 20 days after heading, respectively. EC 1 had 19% higher total N uptake and 18% higher physiological N-use efficiency than EC 0 . These positive effects of earthworm casts on yield attributes offset negative effects of decreasing N rate from 0.74 g pot –1 (equivalent to the recommended field rate of 150 kg ha –1 ) to 0.44 g pot –1 (equivalent to 60% of the recommended rate). Fertilizer N retention rate was 7% higher while fertilizer N loss rate was 6% lower in EC 1 than in EC 0 . Our study suggests that earthworm casts produced during oilseed rape-growing season are expected to have the following benefits on the subsequent flooded rice system: (1) improving growth and physiological processes in rice plants and consequently increasing rice grain yield, and (2) increasing fertilizer N retention rate and hence decreasing fertilizer N loss rate and reducing environmental risk.
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  • 28
    Publication Date: 2016-11-24
    Description: by Julia Truthmann, Gert B. M. Mensink, Anja Bosy-Westphal, Christa Scheidt-Nave, Anja Schienkiewitz Objective The study examined potential changes in the proportion of metabolic health according to body size categories over time and across strata of sex and age, varying definitions of metabolic health. Methods We analysed data from national health interview and examination surveys 1997–99 and 2008–11 for adults aged 18–79 years (GNHIES98: N = 6,565; DEGS1: 6,860). Metabolic health as defined by ATPIII criteria was examined across body mass index categories. The Plourde and Karelis criteria were applied in relation to abdominal obesity. Results Proportions of adults with metabolic health by body size categories were largely stable over time, except for an increasing proportion of metabolically healthy persons with pre-obesity and metabolically healthy women without abdominal obesity. In both surveys proportions of adults meeting ATPIII criteria ranged from approximately 30% among men and women with obesity, to about two thirds of those with pre-obesity to about 93% among those with normal weight. According to Plourde and Karelis criteria proportions ranged from almost 30% among men and women without abdominal obesity to less than 10% among those with abdominal obesity. Proportions were consistently higher among younger than older age groups and less consistently higher among women than men. Conclusions Proportions of adults with metabolic health by body size categories were largely stable over time, except for an increasing proportion of metabolically healthy women without abdominal obesity. There is no evidence that metabolic health among adults with obesity increased in Germany over a period of ten years.
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  • 29
    Publication Date: 2016-11-24
    Description: by Shion Miyoshi, Shinji Sasada, Takehiro Izumo, Yuji Matsumoto, Takaaki Tsuchida Background Some trials recently demonstrated the benefit of targeted treatment for malignant disease; therefore, adequate tissues are needed to detect the targeted gene. Pleural biopsy using flex-rigid pleuroscopy and pleural effusion cell block analysis are both useful for diagnosis of malignancy and obtaining adequate samples. The purpose of our study was to compare the diagnostic utility between the two methods among patients with malignant pleural disease with effusion. Methods Data from patients who underwent flex-rigid pleuroscopy for diagnosis of pleural effusion suspicious for malignancy at the National Cancer Center Hospital, Japan between April 2011 and June 2014 were retrospectively reviewed. All procedures were performed under local anesthesia. At least 150 mL of pleural fluid was collected by pleuroscopy, followed by pleural biopsies from the abnormal site. Results Thirty-five patients who were finally diagnosed as malignant pleural disease were included in this study. Final diagnoses of malignancy were 24 adenocarcinoma, 1 combined adeno-small cell carcinoma, and 7 malignant pleural mesothelioma (MPM), and 3 metastatic breast cancer. The diagnostic yield was significantly higher by pleural biopsy than by cell block [94.2% (33/35) vs. 71.4% (25/35); p = 0.008]. All patients with positive results on cell block also had positive results on pleural biopsy. Eight patients with negative results on cell block had positive results on pleural biopsy (lung adenocarcinoma in 4, sarcomatoid MPM in 3, and metastatic breast cancer in 1). Two patients with negative results on both cell block and pleural biopsy were diagnosed was sarcomatoid MPM by computed tomography-guided needle biopsy and epithelioid MPM by autopsy. Conclusion Pleural biopsy using flex-rigid pleuroscopy was efficient in the diagnosis of malignant pleural diseases. Flex-rigid pleuroscopy with pleural biopsy and pleural effusion cell block analysis should be considered as the initial diagnostic approach for malignant pleural diseases presenting with effusion.
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  • 30
    Publication Date: 2016-11-24
    Description: by Hisayoshi Nozaki, Noriko Ueki, Nanako Isaka, Tokiko Saigo, Kayoko Yamamoto, Ryo Matsuzaki, Fumio Takahashi, Ken-ichi Wakabayashi, Masanobu Kawachi Volvox sect. Volvox is characterized by having unique morphological characteristics, such as thick cytoplasmic bridges between adult somatic cells in the spheroids and spiny zygote walls. Species of this section are found from various freshwater habitats. Recently, three species of Volvox sect. Volvox originating from rice paddies and a marsh were studied taxonomically based on molecular and morphological data of cultured materials. However, taxonomic studies have not been performed on cultured materials of this section originating from large lake water bodies. We studied a new morphological type of Volvox sect. Volvox (“ Volvox sp. Sagami”), using cultured materials originating from two large lakes and a pond in Japan. Volvox sp. Sagami produced monoecious sexual spheroids and may represent a new morphological species; it could be clearly distinguished from all previously described monoecious species of Volvox sect. Volvox by its small number of eggs or zygotes (5–25) in sexual spheroids, with short acute spines (up to 3 μm long) on the zygote walls and elongated anterior somatic cells in asexual spheroids. Based on sequences of internal transcribed spacer (ITS) regions of nuclear ribosomal DNA (rDNA; ITS-1, 5.8S rDNA and ITS-2) and plastid genes, however, the Volvox sp. Sagami lineage and its sister lineage (the monoecious species V . ferrisii ) showed very small genetic differences, which correspond to the variation within a single biological species in other volvocalean algae. Since V . ferrisii was different from Volvox sp. Sagami, by having approximately 100–200 zygotes in the sexual spheroids and long spines (6–8.5 μm long) on the zygote walls, as well as growing in Japanese rice paddies, these two morphologically distinct lineages might have diverged rapidly in the two different freshwater habitats. In addition, the swimming velocity during phototaxis of Volvox sp. Sagami spheroids originating from large lakes was significantly higher than that of V . ferrisii originating from rice paddies, suggesting adaptation of Volvox sp. Sagami to large water bodies.
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  • 31
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    Publication Date: 2016-11-24
    Description: by Norio Kobayashi, Hiroaki Okae, Hitoshi Hiura, Hatsune Chiba, Yoshiki Shirakata, Kenshiro Hara, Kentaro Tanemura, Takahiro Arima DNA methylation plays important roles in the production and functioning of spermatozoa. Recent studies have suggested that DNA methylation patterns in spermatozoa can change with age, but the regions susceptible to age-related methylation changes remain to be fully elucidated. In this study, we conducted genome-scale DNA methylation profiling of spermatozoa obtained from C57BL/6N mice at 8 weeks (8w), 18 weeks (18w) and 17 months of age (17m). There was no substantial difference in the global DNA methylation patterns between 18w and 17m samples except for a slight increase of methylation levels in long interspersed nuclear elements in the 17m samples. We found that maternally methylated imprinting control regions (mICRs) and spermatogenesis-related gene promoters had 5–10% higher methylation levels in 8w samples than in 18w or 17m samples. Analysis of individual sequence reads suggested that these regions were fully methylated (80–100%) in a subset of 8w spermatozoa. These regions are also known to be highly methylated in a subset of postnatal spermatogonia, which might be the source of the increased DNA methylation in 8w spermatozoa. Another possible source was contamination by somatic cells. Although we carefully purified the spermatozoa, it was difficult to completely exclude the possibility of somatic cell contamination. Further studies are needed to clarify the source of the small increase in DNA methylation in the 8w samples. Overall, our findings suggest that DNA methylation patterns in mouse spermatozoa are relatively stable throughout reproductive life.
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  • 32
    Publication Date: 2016-11-24
    Description: by Hitoshi Nishimura, Takashi Miura, Masatoshi Minamisawa, Yasushi Ueki, Naoyuki Abe, Naoto Hashizume, Tomoaki Mochidome, Mikiko Harada, Kunihiko Shimizu, Wataru Shoin, Koji Yoshie, Yasutaka Oguchi, Soichiro Ebisawa, Hirohiko Motoki, Atsushi Izawa, Jun Koyama, Uichi Ikeda, Koichiro Kuwahara Background Reduced ankle–brachial index (ABI) is a predictor of cardiovascular events. However, the significance of high ABI remains poorly understood. This study aimed to assess the characteristics and outcomes of patients with high ABI. Methods The IMPACT-ABI study was a retrospective cohort study that enrolled and examined ABI in 3,131 patients hospitalized for cardiovascular disease between January 2005 and December 2012. From this cohort, 2,419 patients were identified and stratified into two groups: high ABI (〉 1.4; 2.6%) and normal ABI (1.0–1.4; 97.3%). The primary endpoint was the cumulative incidence of major adverse cardiovascular events (MACE), including cardiovascular-associated death, myocardial infarction, and stroke. Results Compared with the normal ABI group, patients in the high ABI group showed significantly lower body mass index (BMI) and hemoglobin level, but had higher incidence of chronic kidney disease and hemodialysis. Multivariate logistic regression analysis revealed that hemodialysis was the strongest predictor of high ABI (odds ratio, 6.18; 95% confidence interval (CI), 3.05–12.52; P 〈 0.001). During the follow-up (median, 4.7 years), 172 cases of MACE occurred. Cumulative MACE incidence in patients with high ABI was significantly increased compared to that in those with normal ABI (32.5% vs. 14.5%; P = 0.005). In traditional cardiovascular risk factors-adjusted multivariate Cox proportional hazard analysis, high ABI was an independent predictor of MACE (hazard ratio, 2.07; 95% CI, 1.02–4.20; P = 0.044). Conclusion Lower BMI, chronic kidney disease, and hemodialysis are more frequent in patients with high ABI. Hemodialysis is the strongest predictor of high ABI. High ABI is a parameter that independently predicts MACE.
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  • 33
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    Publication Date: 2016-11-24
    Description: by Iris Groman-Yaroslavski, Ehud Weiss, Dani Nadel Use-wear analysis of five glossed flint blades found at Ohalo II, a 23,000-years-old fisher-hunter-gatherers’ camp on the shore of the Sea of Galilee, Northern Israel, provides the earliest evidence for the use of composite cereal harvesting tools. The wear traces indicate that tools were used for harvesting near-ripe semi-green wild cereals, shortly before grains are ripe and disperse naturally. The studied tools were not used intensively, and they reflect two harvesting modes: flint knives held by hand and inserts hafted in a handle. The finds shed new light on cereal harvesting techniques some 8,000 years before the Natufian and 12,000 years before the establishment of sedentary farming communities in the Near East. Furthermore, the new finds accord well with evidence for the earliest ever cereal cultivation at the site and the use of stone-made grinding implements.
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  • 34
    Publication Date: 2016-11-24
    Description: by Victor M. Santana, Josu G. Alday, HyoHyeMi Lee, Katherine A. Allen, Rob H. Marrs A present challenge in fire ecology is to optimize management techniques so that ecological services are maximized and C emissions minimized. Here, we modeled the effects of different prescribed-burning rotation intervals and wildfires on carbon emissions (present and future) in British moorlands. Biomass-accumulation curves from four Calluna -dominated ecosystems along a north-south gradient in Great Britain were calculated and used within a matrix-model based on Markov Chains to calculate above-ground biomass-loads and annual C emissions under different prescribed-burning rotation intervals. Additionally, we assessed the interaction of these parameters with a decreasing wildfire return intervals. We observed that litter accumulation patterns varied between sites. Northern sites (colder and wetter) accumulated lower amounts of litter with time than southern sites (hotter and drier). The accumulation patterns of the living vegetation dominated by Calluna were determined by site-specific conditions. The optimal prescribed-burning rotation interval for minimizing annual carbon emissions also differed between sites: the optimal rotation interval for northern sites was between 30 and 50 years, whereas for southern sites a hump-backed relationship was found with the optimal interval either between 8 to 10 years or between 30 to 50 years. Increasing wildfire frequency interacted with prescribed-burning rotation intervals by both increasing C emissions and modifying the optimum prescribed-burning interval for minimum C emission. This highlights the importance of studying site-specific biomass accumulation patterns with respect to environmental conditions for identifying suitable fire-rotation intervals to minimize C emissions.
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  • 35
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    Publication Date: 2016-11-24
    Description: by S. H. Hosseini Nasab, Renate List, Katja Oberhofer, Sandro F. Fucentese, Jess G. Snedeker, William R. Taylor Background The posterior cruciate ligament (PCL) is the strongest ligament of the knee, serving as one of the major passive stabilizers of the tibio-femoral joint. However, despite a number of experimental and modelling approaches to understand the kinematics and kinetics of the ligament, the normal loading conditions of the PCL and its functional bundles are still controversially discussed. Objectives This study aimed to generate science-based evidence for understanding the functional loading of the PCL, including the anterolateral and posteromedial bundles, in the healthy knee joint through systematic review and statistical analysis of the literature. Data sources MEDLINE, EMBASE and CENTRAL Eligibility criteria for selecting studies Databases were searched for articles containing any numerical strain or force data on the healthy PCL and its functional bundles. Studied activities were as follows: passive flexion, flexion under 100N and 134N posterior tibial load, walking, stair ascent and descent, body-weight squatting and forward lunge. Method Statistical analysis was performed on the reported load data, which was weighted according to the number of knees tested to extract average strain and force trends of the PCL and identify deviations from the norms. Results From the 3577 articles retrieved by the initial electronic search, only 66 met all inclusion criteria. The results obtained by aggregating data reported in the eligible studies indicate that the loading patterns of the PCL vary with activity type, knee flexion angle, but importantly also the technique used for assessment. Moreover, different fibres of the PCL exhibit different strain patterns during knee flexion, with higher strain magnitudes reported in the anterolateral bundle. While during passive flexion the posteromedial bundle is either lax or very slightly elongated, it experiences higher strain levels during forward lunge and has a synergetic relationship with the anterolateral bundle. The strain patterns obtained for virtual fibres that connect the origin and insertion of the bundles in a straight line show similar trends to those of the real bundles but with different magnitudes. Conclusion This review represents what is now the best available understanding of the biomechanics of the PCL, and may help to improve programs for injury prevention, diagnosis methods as well as reconstruction and rehabilitation techniques.
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  • 36
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    Publication Date: 2016-11-24
    Description: by Sandra Janezic, Mojca Potocnik, Valerija Zidaric, Maja Rupnik Clostridium difficile is one of the most important human and animal pathogens. However, the bacterium is ubiquitous and can be isolated from various sources. Here we report the prevalence and characterization of C . difficile in less studied environmental samples, puddle water (n = 104) and soil (n = 79). C . difficile was detected in 14.4% of puddle water and in 36.7% of soil samples. Environmental strains displayed antimicrobial resistance patterns comparable to already published data of human and animal isolates. A total of 480 isolates were grouped into 34 different PCR ribotypes. More than half of these (52.9%; 18 of 34) were already described in humans or animals. However, 14 PCR ribotypes were new in our PCR ribotype library and all but one were non-toxigenic. The multilocus sequence analysis of these new PCR ribotypes revealed that non-toxigenic environmental isolates are phylogenetically distinct and belong to three highly divergent clades, two of which have not been described before. Our data suggest that environment is a potential reservoir of genetically diverse population of C . difficile .
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  • 37
    Publication Date: 2016-11-24
    Description: by Mats Leifels, Ibrahim Ahmed Hamza, Marion Krieger, Michael Wilhelm, Martin Mackowiak, Lars Jurzik Quantitative PCR methods are commonly used to monitor enteric viruses in the aquatic environment because of their high sensitivity, short reaction times and relatively low operational cost. However, conclusions for public health drawn from results of such molecular techniques are limited due to their inability to determine viral infectivity. Ethidium monoazide (EMA) and propidium monoazide (PMA) are capable to penetrate the damaged or compromised capsid of the inactivated viruses and bind to the viral nucleic acids. We assessed whether dye treatment is a suitable approach to improve the ability of qPCR to distinguish between infectious and non-infectious human adenovirus, enterovirus and rotavirus A in surface water of an urban river and sewage before and after UV disinfection. Like the gold standard of cell culture assays, pretreatment EMA-/PMA-qPCR succeeded in removing false positive results which would lead to an overestimation of the viral load if only qPCR of the environmental samples was considered. A dye pretreatment could therefore provide a rapid and relatively inexpensive tool to improve the efficacy of molecular quantification methods in regards to viral infectivity.
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  • 38
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    Publication Date: 2016-11-24
    Description: by Christoph Tappeiner, Ellinor Maurer, Pauline Sallin, Thomas Bise, Volker Enzmann, Markus Tschopp In contrast to the mammalian retina, the zebrafish retina exhibits the potential for lifelong retinal neurogenesis and regeneration even after severe damage. Previous studies have shown that the transforming growth factor beta (TGFβ) signaling pathway is activated during the regeneration of different tissues in the zebrafish and is needed for regeneration in the heart and the fin. In this study, we have investigated the role of the TGFβ pathway in the N-methyl-N-nitrosourea (MNU)-induced chemical model of rod photoreceptor de- and regeneration in adult zebrafish. Immunohistochemical staining for phosphorylated Smad3 was elevated during retinal regeneration, and phosphorylated Smad3 co-localized with proliferating cell nuclear antigen and glutamine synthetase, indicating TGFβ pathway activation in proliferating Müller glia. Inhibiting the TGFβ signaling pathway using a small molecule inhibitor (SB431542) resulted in accelerated recovery from retinal degeneration. Accordingly, we observed increased cell proliferation in the outer nuclear layer at days 3 to 8 after MNU treatment. In contrast to the observations in the heart and the fin, the inhibition of the TGFβ signaling pathway resulted in increased proliferation after the induction of retinal degeneration. A better understanding of the underlying pathways with the possibility to boost retinal regeneration in adult zebrafish may potentially help to stimulate such proliferation also in other species.
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  • 39
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    Publication Date: 2016-11-24
    Description: by Sanjay Swaminathan, Ju Qiu, Adam W. Rupert, Zonghui Hu, Jeanette Higgins, Robin L. Dewar, Randy Stevens, Catherine A. Rehm, Julia A. Metcalf, Brad T. Sherman, Michael W. Baseler, H. Clifford Lane, Tomozumi Imamichi Objective IL-15 has been postulated to play an important role in HIV-1 infection, yet there are conflicting reports regarding its expression levels in these patients. We sought to measure the level of IL-15 in a large, well characterised cohort of HIV-1 infected patients and correlate this with well known markers of inflammation, including CRP, D-dimer, sCD163 and sCD14. Design and Methods IL-15 levels were measured in 501 people (460 patients with HIV-1 infection and 41 uninfected controls). The HIV-1 infected patients were divided into 4 groups based on viral load: 100,000 copies/ml. The Mann Whitney test (non-parametric) was used to identify significant relationships between different patient groups. Results IL-15 levels were significantly higher in patients with viral loads 〉100,000 copies/ml (3.02 ± 1.53 pg/ml) compared to both uninfected controls (1.69 ± 0.37 pg/ml, p
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  • 40
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    Publication Date: 2016-11-24
    Description: by Brendan A. Palmer, Liam J. Fanning Hepatitis C virus is a positive-sense single-stranded RNA virus. The gene junction partitioning the viral glycoproteins E1 and E2 displays concurrent sequence evolution with the 3′-end of E1 highly conserved and the 5′-end of E2 highly heterogeneous. This gene junction is also believed to contain structured RNA elements, with a growing body of evidence suggesting that such structures can act as an additional level of viral replication and transcriptional control. We have previously used ultradeep pyrosequencing to analyze an amplicon library spanning the E1/E2 gene junction from a treatment naïve patient where samples were collected over 10 years of chronic HCV infection. During this timeframe maintenance of an in-frame insertion, recombination and humoral immune targeting of discrete virus sub-populations was reported. In the current study, we present evidence of epistatic evolution across the E1/E2 gene junction and observe the development of co-varying networks of codons set against a background of a complex virome with periodic shifts in population dominance. Overtime, the number of codons actively mutating decreases for all virus groupings. We identify strong synonymous co-variation between codon sites in a group of sequences harbouring a 3 bp in-frame insertion and propose that synonymous mutation acts to stabilize the RNA structural backbone.
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  • 41
    Publication Date: 2016-11-24
    Description: by Sidney Grosprêtre, Julien Duclay, Alain Martin In humans, the amount of spinal homonymous recurrent inhibition during voluntary contraction is usually assessed by using a peripheral nerve stimulation paradigm. This method consists of conditioning the maximal M-wave (SM stimulus) with prior reflex stimulation (S1), with 10 ms inter-stimulus interval (ISI). The decrease observed between unconditioned (S1 only) and conditioned (S1+SM) reflex size is then attributed to recurrent inhibition. However, during a voluntary contraction, a superimposed SM stimulation leads to a maximal M-wave followed by a voluntary (V) wave at similar latency than the H-reflex. This wave can therefore interfere with the conditioned H-reflex when two different stimulation intensities are used (S1 and SM), leading to misinterpretation of the data. The aim of the present study was to assess if conditioning V-wave response instead of H-reflex, by applying SM for both stimuli (test and conditioning), can be used as an index of recurrent inhibition. Conditioned and unconditioned responses of soleus and medial gastrocnemius muscles were recorded in twelve subjects at 25% and at 50% of maximal voluntary contraction at the usual ISI of 10 ms and an optimal inter-stimulus of 15 ms determined upon M- and V-wave latencies. Conditioned H-reflex (obtained with S1+SM paradigm) was significantly lower than the unconditioned by ~30% on average, meaning that the amount of inhibition was 70%. This amount of recurrent inhibition was significantly lower at higher force level with both methods. Regardless of the level of force or the conditioning ISI, results obtained with V-wave conditioning (SM+SM) were similar at both force levels, linearly correlated and proportional to those obtained with H conditioning. Then, V-wave conditioning appears to be a reliable index of homonymous recurrent inhibition during voluntary contraction.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 42
    Publication Date: 2016-11-29
    Description: by Ariel B. Rydeen, Joshua S. Waxman Although retinoic acid (RA) teratogenicity has been investigated for decades, the mechanisms underlying RA-induced outflow tract (OFT) malformations are not understood. Here, we show zebrafish embryos deficient for Cyp26a1 and Cyp26c1 enzymes, which promote RA degradation, have OFT defects resulting from two mechanisms: first, a failure of second heart field (SHF) progenitors to join the OFT, instead contributing to the pharyngeal arch arteries (PAAs), and second, a loss of first heart field (FHF) ventricular cardiomyocytes due to disrupted cell polarity and extrusion from the heart tube. Molecularly, excess RA signaling negatively regulates fibroblast growth factor 8a ( fgf8a ) expression and positively regulates matrix metalloproteinase 9 ( mmp9 ) expression. Although restoring Fibroblast growth factor (FGF) signaling can partially rescue SHF addition in Cyp26 deficient embryos, attenuating matrix metalloproteinase (MMP) function can rescue both ventricular SHF addition and FHF integrity. These novel findings indicate a primary effect of RA-induced OFT defects is disruption of the extracellular environment, which compromises both SHF recruitment and FHF ventricular integrity.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 43
    Publication Date: 2016-11-29
    Description: by Edgar D. Coelho, Joel P. Arrais, José Luís Oliveira De novo experimental drug discovery is an expensive and time-consuming task. It requires the identification of drug-target interactions (DTIs) towards targets of biological interest, either to inhibit or enhance a specific molecular function. Dedicated computational models for protein simulation and DTI prediction are crucial for speed and to reduce the costs associated with DTI identification. In this paper we present a computational pipeline that enables the discovery of putative leads for drug repositioning that can be applied to any microbial proteome, as long as the interactome of interest is at least partially known. Network metrics calculated for the interactome of the bacterial organism of interest were used to identify putative drug-targets. Then, a random forest classification model for DTI prediction was constructed using known DTI data from publicly available databases, resulting in an area under the ROC curve of 0.91 for classification of out-of-sampling data. A drug-target network was created by combining 3,081 unique ligands and the expected ten best drug targets. This network was used to predict new DTIs and to calculate the probability of the positive class, allowing the scoring of the predicted instances. Molecular docking experiments were performed on the best scoring DTI pairs and the results were compared with those of the same ligands with their original targets. The results obtained suggest that the proposed pipeline can be used in the identification of new leads for drug repositioning. The proposed classification model is available at http://bioinformatics.ua.pt/software/dtipred/.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 44
    Publication Date: 2016-11-29
    Description: by Florian Aspart, Josef Ladenbauer, Klaus Obermayer Transcranial brain stimulation and evidence of ephaptic coupling have recently sparked strong interests in understanding the effects of weak electric fields on the dynamics of brain networks and of coupled populations of neurons. The collective dynamics of large neuronal populations can be efficiently studied using single-compartment (point) model neurons of the integrate-and-fire (IF) type as their elements. These models, however, lack the dendritic morphology required to biophysically describe the effect of an extracellular electric field on the neuronal membrane voltage. Here, we extend the IF point neuron models to accurately reflect morphology dependent electric field effects extracted from a canonical spatial “ball-and-stick” (BS) neuron model. Even in the absence of an extracellular field, neuronal morphology by itself strongly affects the cellular response properties. We, therefore, derive additional components for leaky and nonlinear IF neuron models to reproduce the subthreshold voltage and spiking dynamics of the BS model exposed to both fluctuating somatic and dendritic inputs and an extracellular electric field. We show that an oscillatory electric field causes spike rate resonance, or equivalently, pronounced spike to field coherence. Its resonance frequency depends on the location of the synaptic background inputs. For somatic inputs the resonance appears in the beta and gamma frequency range, whereas for distal dendritic inputs it is shifted to even higher frequencies. Irrespective of an external electric field, the presence of a dendritic cable attenuates the subthreshold response at the soma to slowly-varying somatic inputs while implementing a low-pass filter for distal dendritic inputs. Our point neuron model extension is straightforward to implement and is computationally much more efficient compared to the original BS model. It is well suited for studying the dynamics of large populations of neurons with heterogeneous dendritic morphology with (and without) the influence of weak external electric fields.
    Print ISSN: 1553-734X
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  • 45
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    Public Library of Science (PLoS)
    Publication Date: 2016-11-29
    Description: by The PLOS Genetics Staff
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 46
    Publication Date: 2016-11-29
    Description: by Anders Gammelmark, Michael S. Nielsen, Søren Lundbye-Christensen, Anne Tjønneland, Erik B. Schmidt, Kim Overvad Background The 5-lipoxygenase pathway (5-LOX) has been implicated in the development of cardiovascular disease and studies have suggested that genetic polymorphisms related to key enzymes in this pathway may confer risk of myocardial infarction (MI). This study investigated the association of pre-selected genetic polymorphisms in four candidate genes of 5-LOX (arachidonate 5-lipoxygenase and its activating protein ( ALOX-5 and FLAP ), leukotriene A4 hydroxylase ( LTA4-H ) and leukotriene C4 synthase ( LTC4-S )) with incident MI. Methods In a Danish cohort including 57,053 participants, aged 50–64 at enrolment and recruited from 1993–97, we conducted a case-cohort study including cases with incident MI and a randomly selected sub cohort of 3,000 participants. Cases were identified from national registries through July 2013. A total of 22 SNPs were selected and genotyped using the commercially available KASP ™ assay. A tandem-repeat polymorphism, located in the ALOX-5 gene, was genotyped by multi-titre plate sequencing. Haplotypes were inferred using PHASE 2.1. Results During a median follow-up of 17.0 years we identified 3,089 cases of incident MI. In FLAP , two SNPs were negatively associated with incident MI (rs9551963 & rs17222842) while one SNP (rs2247570) located in LTA4-H , was associated with higher risk of MI when comparing subjects with two copies of the variant allele to homozygotes for the wild type. However, only rs17222842 remained significantly associated with MI after correcting for multiple testing. Furthermore, the promoter polymorphism rs59439148 was associated with risk of MI in men. For male carriers of two variant alleles we found a hazard ratio of 1.63 (95% CI: 1.06;2.52) compared to homozygotes for the wild type. Previously described haplotypes (Hap-A -B, -E and -K) were not associated with MI in our population. Conclusion In conclusion, some common polymorphisms in the 5-lipoxygenase pathway were modestly associated with incident MI, suggesting a potential role for this pathway in the development of cardiovascular disease.
    Electronic ISSN: 1932-6203
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  • 47
    Publication Date: 2016-11-29
    Description: by Graham C. Smith, Richard J. Delahay, Robbie A. McDonald, Richard Budgey Bovine tuberculosis (bTB) causes substantial economic losses to cattle farmers and taxpayers in the British Isles. Disease management in cattle is complicated by the role of the European badger ( Meles meles ) as a host of the infection. Proactive, non-selective culling of badgers can reduce the incidence of disease in cattle but may also have negative effects in the area surrounding culls that have been associated with social perturbation of badger populations. The selective removal of infected badgers would, in principle, reduce the number culled, but the effects of selective culling on social perturbation and disease outcomes are unclear. We used an established model to simulate non-selective badger culling, non-selective badger vaccination and a selective trap and vaccinate or remove (TVR) approach to badger management in two distinct areas: South West England and Northern Ireland. TVR was simulated with and without social perturbation in effect. The lower badger density in Northern Ireland caused no qualitative change in the effect of management strategies on badgers, although the absolute number of infected badgers was lower in all cases. However, probably due to differing herd density in Northern Ireland, the simulated badger management strategies caused greater variation in subsequent cattle bTB incidence. Selective culling in the model reduced the number of badgers killed by about 83% but this only led to an overall benefit for cattle TB incidence if there was no social perturbation of badgers. We conclude that the likely benefit of selective culling will be dependent on the social responses of badgers to intervention but that other population factors including badger and cattle density had little effect on the relative benefits of selective culling compared to other methods, and that this may also be the case for disease management in other wild host populations.
    Electronic ISSN: 1932-6203
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  • 48
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    Publication Date: 2016-11-29
    Description: by Wei Qin, Xiaoyu Zhang, Shuna Yang, Yue Li, Junliang Yuan, Lei Yang, Shujuan Li, Wenli Hu Background Severe stroke patients have poor clinical outcome which may be associated with development of multiple organ dysfunction syndrome (MODS). Therefore, the aim of our study was to investigate independent risk factors for development of MODS in severe stroke patients. Methods Ninety seven severe stroke patients were prospective recruited from Jan 2011 to Jun 2015. The development of MODS was identified by Sequential Organ Failure Assessment (SOFA) score (score ≥ 3, at least two organs), which was assessed on day 1, 4, 7, 10 and 14 after admission. Baseline characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow coma score (GCS) and cerebral imaging parameters were collected at admission. Cox regression was performed to determine predictors for the development of MODS. Medical complications after admission and in-hospital mortality were also investigated. Results 33 (34%) patients were in MODS group and 64 (66%) were in non-MODS group within 14 days after admission. Patients in MODS group had more smoker (51.5% vs 28.1%, p = 0.023), higher NIHSS score (23.48 ± 6.12 vs 19.81 ± 4.83, p = 0.004), higher APACHE II score (18.70 ± 5.18 vs 15.64 ± 4.36, p = 0.003) and lower GCS score (6.33 ± 2.48 vs 8.14 ± 2.73, p = 0.002). They also had higher rate of infarction in multi vascular territories (36.4% vs 10.9%, p = 0.003). The most common complication in all patients was pulmonary infection, while complication scores were comparable between two groups. Patients with MODS had higher in-hospital mortality (69.7% vs 9.4%, p = 0.000). In Cox regression, NIHSS score (RR = 1.084, 95% CI 1.019–1.153) and infarction in multi vascular territories (RR = 2.345 95% CI 1.105–4.978) were independent risk factors for development of MODS. Conclusions In acute phase of stroke, NIHSS score and infarction in multi vascular territories predicted MODS in severe stroke patients. Moreover, patients with MODS had higher in-hospital mortality, suggesting that early identification of MODS is critical important.
    Electronic ISSN: 1932-6203
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  • 49
    Publication Date: 2016-11-29
    Description: by Liza Bronner Murrison, Neil Martinson, Rachael M. Moloney, Regina Msandiwa, Mondiwana Mashabela, Jonathan M. Samet, Jonathan E. Golub Setting Although there is ample evidence that smoking increases the risk of tuberculosis (TB), the magnitude of impact on TB risk among HIV-infected persons is poorly described. Given that a high proportion of patients with TB are co-infected with HIV in South Africa, the risks arising from the intersection of smoking, TB, and HIV/AIDS have key relevance for tobacco control policies. Objective To evaluate the association of pulmonary tuberculosis (PTB) with current tobacco smoking among men with HIV in South Africa. Design Case-control study of antiretroviral therapy naïve men with confirmed HIV-infection in Johannesburg. Cases had laboratory-confirmed PTB and controls had no evidence of active TB. Participants were interviewed to collect detailed smoking histories. Results We enrolled 146 men diagnosed with PTB and 133 controls. Overall, 33% of participants were currently smoking, defined as smoking a cigarette within 2 months (34% cases vs. 32% controls, p = 0.27). Median CD4 count was lower (60 vs. 81 cells/mm3, P = 0.03) and median viral load was higher (173 vs. 67 copies/ul per thousand, P
    Electronic ISSN: 1932-6203
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  • 50
    Publication Date: 2016-11-29
    Description: by Graham Nugent, Ivor J. Yockney, E. Jackie Whitford, Martin L. Cross, Frank E. Aldwell, Bryce M. Buddle Oral-delivery Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine in a lipid matrix has been shown to confer protection against M . bovis infection and reduce the severity of tuberculosis (TB) when fed to brushtail possums ( Trichosurus vulpecula ), the major wildlife vector of bovine TB in New Zealand. Here we demonstrate the feasibility of aerial delivery of this live vaccine in bait form to an M . bovis -infected wild possum population, and subsequently assess vaccine uptake and field efficacy. Pre-trial studies indicated a resident possum population at very low density ( 5 baits available per possum. Blood sampling conducted two months later provided some evidence of vaccine uptake. A necropsy survey conducted one year later identified a lower prevalence of culture-confirmed M . bovis infection and/or gross TB lesions among adult possums in vaccinated areas (1.1% prevalence; 95% CI, 0–3.3%, n = 92) than in unvaccinated areas (5.6%; 0.7–10.5%, n = 89); P = 0.098. Although not statistically different, the 81% efficacy in protecting possums against natural infection calculated from these data is within the range of previous estimates of vaccine efficacy in trials where BCG vaccine was delivered manually. We conclude that, with further straightforward refinement to improve free-choice uptake, aerial delivery of oral BCG vaccine is likely to be effective in controlling TB in wild possums. We briefly discuss contexts in which this could potentially become an important complementary tool in achieving national eradication of TB from New Zealand wildlife.
    Electronic ISSN: 1932-6203
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  • 51
    Publication Date: 2016-11-29
    Description: by Yan Yu Both obesity (body mass index ≥ 30) and educational attainment have increased dramatically in the United States since the 1970s. This study analyzed the influences of educational inequalities in obesity and population improvements in education on national obesity trends between 1970 and 2010. For non-Hispanic white and black males and females aged 25–74 years, educational differences in the probability of being obese were estimated from the 1971–2012 National Health and Nutrition Examination Surveys, and population distributions of age and educational groups, from the 1970 Census and 2010 American Community Survey. In the total population, obesity increased from 15.7% to 38.8%, and there were increases in the greater obese probabilities of non-college graduates relative to four-year college graduates. The increase in obesity would have been lower by 10% (2.2 percentage points) if educational inequalities in obesity had stayed at their 1970 values and lower by one third (7.9 points) if obesity inequalities had been eliminated. Obesity inequalities were larger for females than males and for whites than blacks, and obesity did not differ by education among black males. As a result, the impact of obesity inequalities on the obesity trend was largest among white females (a 47% reduction in the obesity increase if obesity inequalities had been eliminated), and virtually zero among black males. On the other hand, without educational improvements, the obesity increase would have been 9% more in the total population, 23% more among white females and not different in the other three subpopulations. Results indicate that obesity inequalities made sizable contributions to the obesity trends, and the obesity reductions associated with educational improvements were more limited.
    Electronic ISSN: 1932-6203
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  • 52
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    Publication Date: 2016-11-30
    Description: by Sung Sik Nam, Mohamed-Slim Alouini, Seyeong Choi In this paper, we propose a modified dynamic decode-and-forward (MoDDF) relaying protocol to meet the critical requirements for user equipment (UE) relays in next-generation cellular systems (e.g., LTE-Advanced and beyond). The proposed MoDDF realizes the fast jump-in relaying and the sequential decoding with an application of random codeset to encoding and re-encoding process at the source and the multiple UE relays, respectively. A subframe-by-subframe decoding based on the accumulated (or buffered) messages is employed to achieve energy, information, or mixed combining. Finally, possible early termination of decoding at the end user can lead to the higher spectral efficiency and more energy saving by reducing the frequency of redundant subframe transmission and decoding. These attractive features eliminate the need of directly exchanging control messages between multiple UE relays and the end user, which is an important prerequisite for the practical UE relay deployment.
    Electronic ISSN: 1932-6203
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  • 53
    Publication Date: 2016-11-30
    Description: by Ida M. Smith, Adam Baker, Jeffrey E. Christensen, Teun Boekhout, Hanne Frøkiær, Nils Arneborg, Lene Jespersen Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo . The aim of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii strain with probiotic effects documented in clinical trials, we evaluated the ability of K . marxianus to modulate human dendritic cell (DC) function in vitro . Further, we assessed yeast induced DC modulation of naive T cells toward effector responses dominated by secretion of IFNγ and IL-17 versus induction of a T reg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K . marxianus and S . boulardii induced distinct levels of DC cytokine secretion, primarily driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S . boulardii induced a potent IFNγ response indicating T H 1 mobilization. In contrast, K . marxianus induced a response dominated by Foxp3 + T reg cells, a characteristic that may benefit human health in conditions characterized by excessive inflammation and positions K . marxianus as a strong candidate for further development as a novel yeast probiotic.
    Electronic ISSN: 1932-6203
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  • 54
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    Publication Date: 2016-11-30
    Description: by Jordan V. Pino, Robert V. Rohli, Kristine L. DeLong, Grant L. Harley, Jill C. Trepanier Observations of pre-1950 tropical cyclones are sparse due to observational limitations; therefore, the hurricane database HURDAT2 (1851–present) maintained by the National Oceanic and Atmospheric Administration may be incomplete. Here we provide additional documentation for HURDAT2 from historical United States Army fort records (1820–1915) and other archived documents for 28 landfalling tropical cyclones, 20 of which are included in HURDAT2, along the northern Gulf of Mexico coast. One event that occurred in May 1863 is not currently documented in the HURDAT2 database but has been noted in other studies. We identify seven tropical cyclones that occurred before 1851, three of which are potential tropical cyclones. We corroborate the pre-HURDAT2 storms with a tree-ring reconstruction of hurricane impacts from the Florida Keys (1707–2009). Using this information, we suggest landfall locations for the July 1822 hurricane just west of Mobile, Alabama and 1831 hurricane near Last Island, Louisiana on 18 August. Furthermore, we model the probable track of the August 1831 hurricane using the weighted average distance grid method that incorporates historical tropical cyclone tracks to supplement report locations.
    Electronic ISSN: 1932-6203
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  • 55
    Publication Date: 2016-11-30
    Description: by Seth C. Inzaule, Raph L. Hamers, Cissy Kityo, Tobias F. Rinke de Wit, Maria Roura Background Long-term success of HIV antiretroviral therapy requires near-perfect adherence, maintained throughout one’s lifetime. However, perceptions towards ART and patterns of adherence may change during the life course. We assessed challenges to long-term adherence in adolescents and adults in three regional HIV treatment centers in Uganda. Methods We conducted 24 in-depth interviews and 2 focus group discussions with a total of 33 health-care providers and expert clients (HIV patients on long-term ART who assist with adherence support of fellow patients). Interview topics included experiences with patients on long-term treatment with either declining adherence or persistent poor adherence. Transcribed texts were coded and analyzed based on the social-ecological framework highlighting differences and commonalities between adolescents and adults. Results The overarching themes in adolescents were unstructured treatment holidays, delays in disclosure of HIV status by caretakers, stigma, which was mainly experienced in boarding schools, and diminishing or lack of clinical support. In particular, there was minimal support for early and gradual disclosure for caretakers to the infected children, diminishing clinical support for young adults during transition to adult-based care and declining peer-to-peer support group activities. The predominating theme in adults was challenges with treatment access among temporary economic migrants. Common themes to adults and adolescents were challenges with disclosure in intimate relationships, treatment related factors including side effects, supply of single tablets in place of fixed-dose combined drugs, supply of drug brands with unfavorable taste and missed opportunities for counseling due to shortage of staff. Conclusion Adherence counseling and support should be adapted differently for adolescents and adults and to the emerging life course challenges in long-term treated patients. Programs should also address constraints experienced by temporary economic migrants to ensure continuity of treatment within the host country.
    Electronic ISSN: 1932-6203
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  • 56
    Publication Date: 2016-11-30
    Description: by Shu Zhu, Yongjun Wang, Weiqiang Chen, Wei Li, Angelina Wang, Sarabeth Wong, Guoqiang Bao, Jianhua Li, Huan Yang, Kevin J. Tracey, John D’Angelo, Haichao Wang Human serum amyloid A (SAA) has been demonstrated as a chemoattractant and proinflammatory mediator of lethal systemic inflammatory diseases. In the circulation, it can be sequestered by a high-density lipoprotein, HDL, which carries cholesterol, triglycerides, phospholipids and apolipoproteins (Apo-AI). The capture of SAA by HDL results in the displacement of Apo-AI, and the consequent inhibition of SAA’s chemoattractant activities. It was previously unknown whether HDL similarly inhibits SAA-induced sPLA 2 expression, as well as the resultant HMGB1 release, nitric oxide (NO) production and autophagy activation. Here we provided compelling evidence that human SAA effectively upregulated the expression and secretion of both sPLA 2 -IIE and sPLA 2 -V in murine macrophages, which were attenuated by HDL in a dose-dependent fashion. Similarly, HDL dose-dependently suppressed SAA-induced HMGB1 release, NO production, and autophagy activation. In both RAW 264.7 cells and primary macrophages, HDL inhibited SAA-induced secretion of several cytokines (e.g., IL-6) and chemokines (e.g., MCP-1 and RANTES) that were likely dependent on functional TLR4 signaling. Collectively, these findings suggest that HDL counter-regulates SAA-induced upregulation and secretion of sPLA 2 -IIE/V in addition to other TLR4-dependent cytokines and chemokines in macrophage cultures.
    Electronic ISSN: 1932-6203
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  • 57
    Publication Date: 2016-11-30
    Description: by Kosuke Saito, Mayumi Ueta, Keiko Maekawa, Chie Sotozono, Shigeru Kinoshita, Yoshiro Saito Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are drug-induced acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface. Even after recovery from skin symptoms, some SJS/TEN patients continue to suffer with severe ocular complications (SOCs). Therefore, this study aims to understand the pathophysiology of chronic SOCs. Because plasma lipid profiling has emerged as a useful tool to understand pathophysiological alterations in the body, we performed plasma lipid profiling of 17 patients who suffered from SJS/TEN-associated chronic SOCs. A lipidomics approach yielded 386 lipid molecules and demonstrated that plasma levels of inflammatory oxylipins increased in patients with SJS/TEN-associated chronic SOCs. In addition, oxidized phosphatidylcholines and ether-type diacylglycerols increased in the patients with chronic SOCs, while phosphoglycerolipids decreased. When we compared these lipidomic profiles with those of patients with atopic dermatitis, we found that patients with chronic SOCs, specifically, had decreased levels of ether-type phosphatidylcholines (ePCs) containing arachidonic acid (AA), such as PC(18:0e/20:4) and PC(20:0e/20:4). To confirm our finding, we recruited additional patients, who suffered from SOC associated with SJS/TEN (up to 51 patients), and validated the decreased plasma levels of AA-containing ePCs. Our study provides insight into the alterations of plasma lipidomic profiles in chronic SOCs and into the pathophysiology of SJS/TEN-associated chronic SOCs.
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  • 58
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    Publication Date: 2016-11-30
    Description: by Patricia Gomez-Gutierrez, Pedro M. Campos, Miguel Vega, Juan J. Perez In the present study, we report the discovery of a novel allosteric inhibitory site for p38α, a subclass of the mitogen-activated protein kinases (MAPK) family. The putative site was discovered after inspection of the crystallographic structure of the p38α-MK2 complex. MK2 (MAPK-activated protein kinase 2) is an interesting protein playing a dual role as modulator and substrate of p38α. This intriguing behavior is due to the ability of the two proteins to form distinctive heterodimers when p38α is phosphorylated or not. We hypothesized that the regulatory action of MK2 is due to its capability to keep p38α in an inactive conformation and consequently, we investigated the atomic structure of the p38α-MK2 complex to understand such regulatory behavior at the molecular level. After inspection of the complex structure, two peptides designed from the MK2 regulatory loop in contact with p38α with sequences Tyr 1 -Ser 2 -Asn 3 -His 4 -Gly 5 -Leu 6 (peptide-1) and [Phe 0 ]-peptide-1 (peptide-2) in their zwitterionic form were investigated for their phosphorylation inhibitory capability in vitro . Since both peptides exhibited inhibitory capability of the p38α kinase mediated phosphorylation of MEF2A, in a subsequent step we pursued the discovery of small molecule peptidomimetics. For this purpose we characterized in detail the peptide-p38α interaction using molecular dynamics simulations, leading to the definition of a pharmacophore for the peptide-protein interaction. This hypothesis was used as query for a in silico screening, leading to the discovery of a fused ring compound with micromolar inhibitory activity. Site-directed mutagenesis studies support that the compound binds to the putative novel allosteric site in p38α.
    Electronic ISSN: 1932-6203
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  • 59
    Publication Date: 2016-11-30
    Description: by Ángel Herráiz-Adillo, Vicente Martínez-Vizcaíno, Iván Cavero-Redondo, Celia Álvarez-Bueno, Miriam Garrido-Miguel, Blanca Notario-Pacheco Background Peripheral arterial disease (PAD) is an indicator of widespread atherosclerosis. However, most individuals with PAD, in spite of being at high cardiovascular risk, are asymptomatic. This fact, together with the limitations of the Doppler ankle-brachial index (ABI), contributes to PAD underdiagnose. The aim of this study was to compare oscillometric ABI and Doppler ABI to diagnose peripheral arterial disease, and also to examine the influence of oscillometric errors and calcified legs on the PAD diagnoses. Methods and Findings We measured the ankle-brachial indexes of 90 volunteers (n = 180 legs, age 70 ± 14 years, 43% diabetics) using both oscillometer OMRON-M3 and Doppler. For concordance analyses we used the Bland and Altman method, and also estimated the intraclass correlation coefficient. Receiver Operating Characteristic Curves were used to examine the diagnostic performance of both methods. The ABI means were 1.06 ± 0.14 and 1.04 ± 0.16 (p = 0.034) measured by oscillometer and Doppler ABIs respectively, with limits of agreement of ± 0.20 and intraclass correlation coefficient = 0.769. Oscillometer yielded 23 “error” measurements, and also overestimated the measurements in low ankle pressures. Using Doppler as gold standard, oscillometer performance for diagnosis of PAD showed an Area Under Curve = 0.944 (sensitivity: 66.7%, specificity: 96.8%). Moreover, when considered calcified legs and oscillometric “error” readings as arteriopathy equivalents, sensitivity rose to 78.2%, maintaining specificity in 96%. The best oscillometer cut-off point was 0.96 (sensitivity: 87%, specificity: 91%, positive likelihood ratio: 9.66 and negative likelihood ratio: 0.14). Conclusion Despite its limitations, oscillometric ABI could be a useful tool for the diagnosis of PAD, particularly when considering calcified legs and oscillometric “errors” readings as peripheral arterial disease equivalents.
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  • 60
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    Public Library of Science (PLoS)
    Publication Date: 2016-12-01
    Description: by Hiruy S. Meharena, Xiaorui Fan, Lalima G. Ahuja, Malik M. Keshwani, Christopher L. McClendon, Angela M. Chen, Joseph A. Adams, Susan S. Taylor Eukaryotic protein kinases regulate most cellular functions by phosphorylating targeted protein substrates through a highly conserved catalytic core. In the active state, the catalytic core oscillates between open, intermediate, and closed conformations. Currently, the intramolecular interactions that regulate the active state mechanics are not well understood. Here, using cAMP-dependent protein kinase as a representative model coupled with biochemical, biophysical, and computational techniques, we define a set of highly conserved electrostatic and hydrophobic interactions working harmoniously to regulate these mechanics. These include the previously identified salt bridge between a lysine from the β3-strand and a glutamate from the αC-helix as well as an electrostatic interaction between the phosphorylated activation loop and αC-helix and an ensemble of hydrophobic residues of the Regulatory spine and Shell. Moreover, for over three decades it was thought that the highly conserved β3-lysine was essential for phosphoryl transfer, but our findings show that the β3-lysine is not required for phosphoryl transfer but is essential for the active state mechanics.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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    Public Library of Science (PLoS)
    Publication Date: 2016-12-01
    Description: by Elif Tekin, David Hunt, Mitchell G. Newberry, Van M. Savage Modern models that derive allometric relationships between metabolic rate and body mass are based on the architectural design of the cardiovascular system and presume sibling vessels are symmetric in terms of radius, length, flow rate, and pressure. Here, we study the cardiovascular structure of the human head and torso and of a mouse lung based on three-dimensional images processed via our software Angicart. In contrast to modern allometric theories, we find systematic patterns of asymmetry in vascular branching, potentially explaining previously documented mismatches between predictions (power-law or concave curvature) and observed empirical data (convex curvature) for the allometric scaling of metabolic rate. To examine why these systematic asymmetries in vascular branching might arise, we construct a mathematical framework to derive predictions based on local, junction-level optimality principles that have been proposed to be favored in the course of natural selection and development. The two most commonly used principles are material-cost optimizations (construction materials or blood volume) and optimization of efficient flow via minimization of power loss. We show that material-cost optimization solutions match with distributions for asymmetric branching across the whole network but do not match well for individual junctions. Consequently, we also explore random branching that is constrained at scales that range from local (junction-level) to global (whole network). We find that material-cost optimizations are the strongest predictor of vascular branching in the human head and torso, whereas locally or intermediately constrained random branching is comparable to material-cost optimizations for the mouse lung. These differences could be attributable to developmentally-programmed local branching for larger vessels and constrained random branching for smaller vessels.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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    Publication Date: 2016-12-01
    Description: by Mitchell V. Palmer, Tyler C. Thacker, W. Ray Waters The hallmark lesion of tuberculosis in humans and animals is the granuloma. The granuloma represents a distinct host cellular immune response composed of epithelioid macrophages, lymphocytes, and multinucleated giant cells, often surrounding a caseous necrotic core. Within the granuloma, host-pathogen interactions determine disease outcome. Factors within the granulomas such as cytokines and chemokines drive cell recruitment, activity, function and ultimately the success or failure of the host’s ability to control infection. Hence, an understanding of the granuloma-level cytokine response is necessary to understand tuberculosis pathogenesis. In-situ cytokine expression patterns were measured using a novel in situ hybridization assay, known as RNAScope ® in granulomas of the lungs, tracheobronchial lymph nodes and caudal mediastinal lymph nodes of cattle experimentally infected with Mycobacterium bovis via aerosol exposure. In spite of microscopic morphological similarities, significant differences were seen between late stage granulomas of the lung compared to those of the tracheobronchial lymph nodes for IL-17A, IFN-γ, TGF-β, IL10 and IL-22 but not for TNF-α. Additionally, significant differences were noted between granulomas from two different thoracic lymph nodes that both receive afferent lymphatics from the lungs (i.e., tracheobronchial and caudal mediastinal lymph nodes) for TNF-α, IL-17A, IFN-γ, TGF-β and IL-10 but not for IL-22. These findings show that granuloma morphology alone is not a reliable indicator of granuloma function as granulomas of similar morphologies can have disparate cytokine expression patterns. Moreover, anatomically distinct lymph nodes (tracheobronchial vs caudal mediastinal) differ in cytokine expression patterns even when both receive afferent lymphatics from a lung containing tuberculoid granulomas. These findings show that selection of tissue and anatomic location are critical factors in assessing host immune response to M . bovis and should be considered carefully.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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    Publication Date: 2016-12-01
    Description: by Antoine Abrieux, Amel Mhamdi, Kaouther K. Rabhi, Julie Egon, Stéphane Debernard, Line Duportets, Hélène Tricoire-Leignel, Sylvia Anton, Christophe Gadenne Neonicotinoid insecticides are widely used to protect plants against pest insects, and insecticide residues remaining in the environment affect both target and non-target organisms. Whereas low doses of neonicotinoids have been shown to disturb the behaviour of pollinating insects, recent studies have revealed that a low dose of the neonicotinoid clothianidin can improve behavioural and neuronal sex pheromone responses in a pest insect, the male moth Agrotis ipsilon , and thus potentially improve reproduction. As male moth behaviour depends also on its physiological state and previous experience with sensory signals, we wondered if insecticide effects would be dependent on plasticity of olfactory-guided behaviour. We investigated, using wind tunnel experiments, whether a brief pre-exposure to the sex pheromone could enhance the behavioural response to this important signal in the moth A . ipsilon at different ages (sexually immature and mature males) and after different delays (2 h and 24 h), and if the insecticide clothianidin would interfere with age effects or the potential pre-exposure-effects. Brief pre-exposure to the pheromone induced an age-independent significant increase of sex pheromone responses 24 h later, whereas sex pheromone responses did not increase significantly 2 h after exposure. However, response delays were significantly shorter compared to naïve males already two hours after exposure. Oral treatment with clothianidin increased sex pheromone responses in sexually mature males, confirming previous results, but did not influence responses in young immature males. Males treated with clothianidin after pre-exposure at day 4 responded significantly more to the sex pheromone at day 5 than males treated with clothianidin only and than males pre-exposed only, revealing an additive effect of experience and the insecticide. Plasticity of sensory systems has thus to be taken into account when investigating the effects of sublethal doses of insecticides on behaviour.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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    Publication Date: 2016-12-01
    Description: by Stjepko Cermak, Marko Kosicek, Aleksandra Mladenovic-Djordjevic, Kosara Smiljanic, Selma Kanazir, Silva Hecimovic Proper function of lysosomes is particularly important in neurons, as they cannot dilute accumulated toxic molecules and aggregates by cell division. Thus, impairment of lysosomal function plays an important role in neuronal degeneration and in the pathogenesis of numerous neurodegenerative diseases. In this work we analyzed how inhibition and/or loss of the major lysosomal proteases, the cysteine cathepsins B and L (CtsB/L), affects lysosomal function, cholesterol metabolism and degradation of the key Alzheimer's disease (AD) proteins. Here, we show that cysteine CtsB/L, and not the aspartyl cathepsin D (CtsD), represent a major lysosomal protease(s) that control lysosomal function, intracellular cholesterol trafficking and AD-like amyloidogenic features. Intriguingly, accumulation of free cholesterol in late endosomes/lysosomes upon CtsB/L inhibition resembled a phenotype characteristic for the rare neurodegenerative disorder Niemann-Pick type C (NPC). CtsB/L inhibition and not the inhibition of CtsD led to lysosomal impairment assessed by decreased degradation of EGF receptor, enhanced LysoTracker staining and accumulation of several lysosomal proteins LC3II, NPC1 and NPC2. By measuring the levels of NPC1 and ABCA1, the two major cholesterol efflux proteins, we showed that CtsB/L inhibition or genetic depletion caused accumulation of the NPC1 in lysosomes and downregulation of ABCA1 protein levels and its expression. Furthermore, we revealed that CtsB/L are involved in degradation of the key Alzheimer’s proteins: amyloid-β peptides (Aβ) and C-terminal fragments of the amyloid precursor protein (APP) and in degradation of β-secretase (BACE1). Our results imply CtsB/L as major regulators of lysosomal function and demonstrate that CtsB/L may play an important role in intracellular cholesterol trafficking and in degradation of the key AD proteins. Our findings implicate that enhancing the activity or levels of CtsB/L could provide a promising and a common strategy for maintaining lysosomal function and for preventing and/or treating neurodegenerative diseases.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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    Publication Date: 2016-12-01
    Description: by The PLOS ONE Staff
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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    Publication Date: 2016-12-01
    Description: by Yuichi Mizutani, Yasuaki Niizuma, Ken Yoda Telomeres are nucleotide sequences located at the ends of chromosomes that promote genome stability. Changes in telomere length (dynamics) are related to fitness or life expectancy, and telomere dynamics during the development phase are likely to be affected by growth and stress factors. Here, we examined telomere dynamics of black-tailed gull chicks ( Larus crassirostris ) in nests with and without siblings. We found that the initial telomere lengths of singletons at hatching were longer than those of siblings, indicating that singletons are higher-quality chicks than siblings in terms of telomere length. Other factors likely affecting individual quality (i.e., sex, laying date, laying order of eggs, and clutch size) were not related to telomere lengths. Within broods, initial telomere lengths were longer in older chicks than in younger chicks, suggesting that maternal effects, which vary with laying sequence, influence the initial lengths. Additionally, telomeres of chicks with a sibling showed more attrition between hatching and fledging than those of singleton chicks, suggesting that being raised with siblings can cause a sustained competitive environment that leads to telomere loss. High growth rates were associated with a low degree of telomere shortening observed in older siblings, perhaps because slower growth reflects higher food stress and/or higher aerobic metabolism from increased begging effort. Our results show that developmental telomere attrition was an inevitable consequence in two-chick nests in the pre- and post-hatching microenvironments due to the combination of social stress within the nest and maternal effects. The results of our study shed light on telomere dynamics in early life, which may represent an important physiological undercurrent of life-history traits.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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    Publication Date: 2016-12-01
    Description: by Juliana Rechetelo, Anthony Grice, April Elizabeth Reside, Britta Denise Hardesty, James Moloney Understanding movement patterns and home range of species is paramount in ecology; it is particularly important for threatened taxa as it can provide valuable information for conservation management. To address this knowledge gap for a range-restricted endangered bird, we estimated home range size, daily movement patterns and habitat use of a granivorous subspecies in northeast Australia, the black-throated finch ( Poephila cincta cincta ; BTF) using radio-tracking and re-sighting of colour banded birds. Little is known about basic aspects of its ecology including movement patterns and home range sizes. From 2011–2014 we colour-banded 102 BTF and radio-tracked 15 birds. We generated home ranges (calculated using kernel and Minimum Convex Polygons techniques of the 15 tracked BTF). More than 50% of the re-sightings occurred within 200 m of the banding site (n = 51 out of 93 events) and within 100 days of capture. Mean home-range estimates with kernel (50%, 95% probability) and Minimum Convex Polygons were 10.59 ha, 50.79 ha and 46.27 ha, respectively. Home range size differed between two capture sites but no seasonal differences were observed. BTF home ranges overlapped four habitat types among eight available. Habitat selection was different from random at Site 1 (χ 2 = 373.41, df = 42, p
    Electronic ISSN: 1932-6203
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    Publication Date: 2016-12-01
    Description: by Janice M Leung, Andrea Malagoli, Antonella Santoro, Giulia Besutti, Guido Ligabue, Riccardo Scaglioni, Darlene Dai, Cameron Hague, Jonathon Leipsic, Don D. Sin, SF Paul Man, Giovanni Guaraldi Background Chronic obstructive pulmonary disease (COPD) and emphysema are common amongst patients with human immunodeficiency virus (HIV). We sought to determine the clinical factors that are associated with emphysema progression in HIV. Methods 345 HIV-infected patients enrolled in an outpatient HIV metabolic clinic with ≥2 chest computed tomography scans made up the study cohort. Images were qualitatively scored for emphysema based on percentage involvement of the lung. Emphysema progression was defined as any increase in emphysema score over the study period. Univariate analyses of clinical, respiratory, and laboratory data, as well as multivariable logistic regression models, were performed to determine clinical features significantly associated with emphysema progression. Results 17.4% of the cohort were emphysema progressors. Emphysema progression was most strongly associated with having a low baseline diffusion capacity of carbon monoxide (DLCO) and having combination centrilobular and paraseptal emphysema distribution. In adjusted models, the odds ratio (OR) for emphysema progression for every 10% increase in DLCO percent predicted was 0.58 (95% confidence interval [CI] 0.41–0.81). The equivalent OR (95% CI) for centrilobular and paraseptal emphysema distribution was 10.60 (2.93–48.98). Together, these variables had an area under the curve (AUC) statistic of 0.85 for predicting emphysema progression. This was an improvement over the performance of spirometry (forced expiratory volume in 1 second to forced vital capacity ratio), which predicted emphysema progression with an AUC of only 0.65. Conclusion Combined paraseptal and centrilobular emphysema distribution and low DLCO could identify HIV patients who may experience emphysema progression.
    Electronic ISSN: 1932-6203
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    Publication Date: 2016-12-01
    Description: by James B. Koprich, Tom H. Johnston, Gabriela Reyes, Vanessa Omana, Jonathan M. Brotchie Recent failures in clinical trials for disease modification in Parkinson’s disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration. The present study was defined to begin the development of such a model in cynomolgus macaque. We have validated surgical and vector parameters to define a means to provide a robust over-expression of alpha-synuclein which is associated with Lewy-like pathology and robust degeneration of the nigrostriatal pathway. Thus, an AAV1/2 vector incorporating strong transcription and transduction regulatory elements was used to deliver the gene for the human A53T mutation of alpha-synuclein. When injected into 4 sites within each substantia nigra (7 μl per site, 1.7 x 10 12 gp/ml), this vector provided expression lasting at least 4 months, and a 50% loss of nigral dopaminergic neurons and a 60% reduction in striatal dopamine. Further studies will be required to develop this methodology into a validated model of value as a drug development platform.
    Electronic ISSN: 1932-6203
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  • 70
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    Public Library of Science (PLoS)
    Publication Date: 2016-12-01
    Description: by Coralie Lheure, Philippe Alain Grange, Guillaume Ollagnier, Philippe Morand, Nathalie Désiré, Sophie Sayon, Stéphane Corvec, Jöel Raingeaud, Anne-Geneviève Marcelin, Vincent Calvez, Amir Khammari, Frédéric Batteux, Brigitte Dréno, Nicolas Dupin Background Propionibacterium acnes ( P . acnes ) is an anaerobic, Gram-positive bacteria encountered in inflammatory acne lesions, particularly in the pilosebaceous follicle. P . acnes triggers a strong immune response involving keratinocytes, sebocytes and monocytes, the target cells during acne development. Lipoteicoic acid and peptidoglycan induce the inflammatory reaction, but no P . acnes surface protein interacting with Toll-like receptors has been identified. P . acnes surface proteins have been extracted by lithium stripping and shown to induce CXCL8 production by keratinocytes. Methodology and principal findings Far-western blotting identified two surface proteins, of 24.5- and 27.5-kDa in size, specifically recognized by TLR2. These proteins were characterized, by LC-MS/MS, as CAMP factor 1 devoid of its signal peptide sequence, as shown by N-terminal sequencing. Purified CAMP factor 1 induces CXCL8 production by activating the CXCL8 gene promoter, triggering the synthesis of CXCL8 mRNA. Antibodies against TLR2 significantly decreased the CXCL8 response. For the 27 P . acnes strains used in this study, CAMP1-TLR2 binding intensity was modulated and appeared to be strong in type IB and II strains, which produced large amounts of CXCL8, whereas most of the type IA 1 and IA 2 strains presented little or no CAMP1-TLR2 binding and low levels of CXCL8 production. The nucleotide sequence of CAMP factor displays a major polymorphism, defining two distinct genetic groups corresponding to CAMP factor 1 with 14 amino-acid changes from strains phylotyped II with moderate and high levels of CAMP1-TLR2 binding activity, and CAMP factor 1 containing 0, 1 or 2 amino-acid changes from strains phylotyped IA 1 , IA 2 , or IB presenting no, weak or moderate CAMP1-TLR2 binding. Conclusions Our findings indicate that CAMP factor 1 may contribute to P . acnes virulence, by amplifying the inflammation reaction through direct interaction with TLR2.
    Electronic ISSN: 1932-6203
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  • 71
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    Public Library of Science (PLoS)
    Publication Date: 2016-12-01
    Description: by Tomasz Łęga, Paulina Weiher, Michał Obuchowski, Dawid Nidzworski Effective vaccination against influenza virus infection is a serious problem mainly due to antigenic variability of the virus. Among many of investigated antigens, the extracellular domain of the M2 protein (M2e) features high homology in all strains of influenza A viruses and antibodies against M2e and is protective in animal models; this makes it a potential candidate for generation of a universal influenza vaccine. However, due to the low immunogenicity of the M2e, formulation of a vaccine based on this antigen requires some modification to induce effective immune responses. In this work we evaluated the possible use of Bacillus subtilis spores as a carrier of the Influenza A M2e antigen in mucosal vaccination. A tandem repeat of 4 consensus sequences coding for human—avian—swine—human M2e (M2eH-A-S-H) peptide was fused to spore coat proteins and stably exposed on the spore surface, as demonstrated by the immunostaining of intact, recombinant spores. Oral immunization of mice with recombinant endospores carrying M2eH-A-S-H elicited specific antibody production without the addition of adjuvants. Bacillus subtilis endospores can serve as influenza antigen carriers. Recombinant spores constructed in this work showed low immunogenicity although were able to induce antibody production. The System of influenza antigen administration presented in this work is attractive mainly due to the omitting time-consuming and cost-intensive immunogen production and purification. Therefore modification should be made to increase the immunogenicity of the presented system.
    Electronic ISSN: 1932-6203
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  • 72
    Publication Date: 2016-12-01
    Description: by Yuecheng Huang, Wuyi Cheng, Sida Luo, Yun Luo, Chengchen Ma, Tailin He The features of the asynchronous correlation between accident indices and the factors that influence accidents can provide an effective reference for warnings of coal mining accidents. However, what are the features of this correlation? To answer this question, data from the China coal price index and the number of deaths from coal mining accidents were selected as the sample data. The fluctuation modes of the asynchronous correlation between the two data sets were defined according to the asynchronous correlation coefficients, symbolization, and sliding windows. We then built several directed and weighted network models, within which the fluctuation modes and the transformations between modes were represented by nodes and edges. Then, the features of the asynchronous correlation between these two variables could be studied from a perspective of network topology. We found that the correlation between the price index and the accidental deaths was asynchronous and fluctuating. Certain aspects, such as the key fluctuation modes, the subgroups characteristics, the transmission medium, the periodicity and transmission path length in the network, were analyzed by using complex network theory, analytical methods and spectral analysis method. These results provide a scientific reference for generating warnings for coal mining accidents based on economic indices.
    Electronic ISSN: 1932-6203
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  • 73
    Publication Date: 2016-12-02
    Description: by Biyun Ching, Jia M. Woo, Kum C. Hiong, Mel V. Boo, Wai P. Wong, Shit F. Chew, Yuen K. Ip This study aimed to obtain the coding cDNA sequences of voltage-gated Na + channel ( scn ) α -subunit ( scna ) and β -subunit ( scnb ) isoforms from, and to quantify their transcript levels in, the main electric organ (EO), Hunter’s EO, Sach’s EO and the skeletal muscle (SM) of the electric eel, Electrophorus electricus , which can generate both high and low voltage electric organ discharges (EODs). The full coding sequences of two scna ( scn4aa and scn4ab ) and three scnb ( scn1b , scn2b and scn4b ) were identified for the first time (except scn4aa ) in E . electricus . In adult fish, the scn4aa transcript level was the highest in the main EO and the lowest in the Sach’s EO, indicating that it might play an important role in generating high voltage EODs. For scn4ab /Scn4ab, the transcript and protein levels were unexpectedly high in the EOs, with expression levels in the main EO and the Hunter’s EO comparable to those of scn4aa . As the key domains affecting the properties of the channel were mostly conserved between Scn4aa and Scn4ab, Scn4ab might play a role in electrogenesis. Concerning scnb , the transcript level of scn4b was much higher than those of scn1b and scn2b in the EOs and the SM. While the transcript level of scn4b was the highest in the main EO, protein abundance of Scn4b was the highest in the SM. Taken together, it is unlikely that Scna could function independently to generate EODs in the EOs as previously suggested. It is probable that different combinations of Scn4aa/Scn4ab and various Scnb isoforms in the three EOs account for the differences in EODs produced in E . electricus . In general, the transcript levels of various scn isoforms in the EOs and the SM were much higher in adult than in juvenile, and the three EOs of the juvenile fish could be functionally indistinct.
    Electronic ISSN: 1932-6203
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  • 74
    Publication Date: 2016-12-02
    Description: by The PLOS ONE Staff
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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    Publication Date: 2016-12-02
    Description: by Vipin Shankar, Hiroki Hori, Kentaro Kihira, Lei Qi, Hidemi Toyoda, Shotaro Iwamoto, Yoshihiro Komada
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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    Publication Date: 2016-12-02
    Description: by Marina Voinson, Sylvain Billiard, Alexandra Alvergne
    Electronic ISSN: 1932-6203
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  • 77
    Publication Date: 2016-12-02
    Description: by The PLOS ONE Staff
    Electronic ISSN: 1932-6203
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  • 78
    Publication Date: 2016-12-02
    Description: by Ryosuke Asano, Kenichi Ito, Toshikazu Yoshida
    Electronic ISSN: 1932-6203
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    Publication Date: 2016-12-02
    Description: by Grégory Lacraz, André-Jean Rouleau, Vanessa Couture, Thomas Söllradl, Geneviève Drouin, Noémie Veillette, Michel Grandbois, Guillaume Grenier
    Electronic ISSN: 1932-6203
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