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  • Articles  (9,452)
  • Public Library of Science (PLoS)  (9,424)
  • Nature Publishing Group
  • 2015-2019  (9,452)
  • 2016  (9,452)
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  • 2015-2019  (9,452)
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  • 1
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    Simulated leakage of high pCO2 water negatively impacts bivalve dominated infaunal communities from the Western Baltic Sea (2016)
    Nature Publishing Group
    In:  EPIC3Scientific Reports, Nature Publishing Group, 6(31447)
    Details
    Publication Date: 2016-11-24
    Description: Carbon capture and storage is promoted as a mitigation method counteracting the increase of atmospheric CO2 levels. However, at this stage, environmental consequences of potential CO2 leakage from sub-seabed storage sites are still largely unknown. In a 3-month-long mesocosm experiment, this study assessed the impact of elevated pCO2 levels (1,500 to 24,400 µatm) on Cerastoderma edule dominated benthic communities from the Baltic Sea. Mortality of C. edule was significantly increased in the highest treatment (24,400 µatm) and exceeded 50%. Furthermore, mortality of small size classes (0-1 cm) was significantly increased in treatment levels ≥6,600 µatm. First signs of external shell dissolution became visible at ≥1,500 µatm, holes were observed at 〉6,600 µatm. C. edule body condition decreased significantly at all treatment levels (1,500-24,400 µatm). Dominant meiofauna taxa remained unaffected in abundance. Densities of calcifying meiofauna taxa (i.e. Gastropoda and Ostracoda) decreased in high CO2 treatments (〉6,600 µatm), while the non - calcifying Gastrotricha significantly increased in abundance at 24,400 µatm. In addition, microbial community composition was altered at the highest pCO2 level. We conclude that strong CO2 leakage can alter benthic infauna community composition at multiple trophic levels, likely due to high mortality of the dominant macrofauna species C. edule.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 2
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    Seismic footprints of shallow dyke propagation at Etna, Italy (2016)
    Nature Publishing Group
    Details
    Publication Date: 2017-04-04
    Description: One of the key issues in forecasting volcanic eruptions is to detect signals that can track the propagation of dykes towards the surface. Continuous monitoring of active volcanoes helps significantly in achieving this goal. The seismic data presented here are unique, as they document surface faulting processes close (tens to a few hundred meters) to their source, namely the dyke tip. They originated nearby - and under - a seismic station that was subsequently destroyed by lava flows during eruptive activity at Etna volcano, Italy, in 2013. On February 20, a ~600 m-long and ~120 m wide NW-SE fracture field opened at an altitude between 2750 and 2900 m. The consequent rock dislocation caused the station to tilt and offset the seismic signal temporarily. Data acquisition continued until the arrival of the lava flow that led to the breakdown of the transmission system. Shallow ground fracturing and repeated low-frequency oscillations occurred during two stages in which the seismic signal underwent a maximum offset ~2.57 E+04 nm/s. Bridging instrumental recordings, fieldwork and conceptual modelling, these data are interpreted as the seismic footprints of a magmatic dyke intrusion that moved at speed ~0.02 m/s (first stage) and 0.46 m/s (second stage).
    Description: This work was supported by the MED-SUV project, which has received funding from the European Union’s Seventh Programme for research, technological development and demonstration under grant agreement No 308665.
    Description: Published
    Description: 11908
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: JCR Journal
    Description: restricted
    Keywords: dyke propagation ; Etna ; seismic signals ; ground fracturing ; conceptual modelling ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 3
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    A novel approach to estimate the eruptive potential and probability in open conduit volcanoes (2016)
    Nature Publishing Group
    Details
    Publication Date: 2017-04-04
    Description: In open conduit volcanoes, volatile-rich magma continuously enters into the feeding system nevertheless the eruptive activity occurs intermittently. From a practical perspective, the continuous steady input of magma in the feeding system is not able to produce eruptive events alone, but rather surplus of magma inputs are required to trigger the eruptive activity. The greater the amount of surplus of magma within the feeding system, the higher is the eruptive probability.Despite this observation, eruptive potential evaluations are commonly based on the regular magma supply, and in eruptive probability evaluations, generally any magma input has the same weight. Conversely, herein we present a novel approach based on the quantification of surplus of magma progressively intruded in the feeding system. To quantify the surplus of magma, we suggest to process temporal series of measurable parameters linked to the magma supply. We successfully performed a practical application on Mt Etna using the soil CO2 flux recorded over ten years.
    Description: Published
    Description: 30471
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: 5V. Sorveglianza vulcanica ed emergenze
    Description: JCR Journal
    Description: restricted
    Keywords: eruptive potential ; eruptive probability ; open conduit volcanoes ; Etna ; Soil CO2 flux ; 04. Solid Earth::04.08. Volcanology::04.08.99. General or miscellaneous ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 05. General::05.08. Risk::05.08.01. Environmental risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 4
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    Jurassic zircons from the Southwest Indian Ridge (2016)
    Nature Publishing Group
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 26260, doi:10.1038/srep26260.
    Description: The existence of ancient rocks in present mid-ocean ridges have long been observed but received less attention. Here we report the discovery of zircons with both reasonably young ages of about 5 Ma and abnormally old ages of approximate 180 Ma from two evolved gabbroic rocks that were dredged from the Southwest Indian Ridge (SWIR) in the Gallieni fracture zone. U–Pb and Lu–Hf isotope analyses of zircons were made using ion probe and conventional laser abrasion directly in petrographic thin sections. Young zircons and their host oxide gabbro have positive Hf isotope compositions (εHf = +15.7–+12.4), suggesting a highly depleted mantle beneath the SWIR. The spread εHf values (from−2.3 to−4.5) of abnormally old zircons, together with the unradiogenic Nd-Hf isotope of the host quartz diorite, appears to suggest an ancient juvenile magmatism along the rifting margin of the southern Gondwana prior to the opening of the Indian Ocean. A convincing explanation for the origin of the unusually old zircons is yet to surface, however, an update of the theory of plate tectonics would be expected with continuing discovery of ancient rocks in the mid-oceanic ridges and abyssal ocean basins.
    Description: This work was supported by the National Natural Science Foundation of China (41573046) to H.C. and the Chinese National Key Basic Research Program (2012CB417300) to H.Z.
    Repository Name: Woods Hole Open Access Server
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  • 5
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    An integrated Pan-European perspective on coastal Lagoons management through a mosaic-DPSIR approach (2016)
    Nature Publishing Group
    Details
    Publication Date: 2022-05-25
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 19400, doi:10.1038/srep19400.
    Description: A decision support framework for the management of lagoon ecosystems was tested using four European Lagoons: Ria de Aveiro (Portugal), Mar Menor (Spain), Tyligulskyi Liman (Ukraine) and Vistula Lagoon (Poland/Russia). Our aim was to formulate integrated management recommendations for European lagoons. To achieve this we followed a DPSIR (Drivers-Pressures-State Change-Impacts-Responses) approach, with focus on integrating aspects of human wellbeing, welfare and ecosystem sustainability. The most important drivers in each lagoon were identified, based on information gathered from the lagoons’ stakeholders, complemented by scientific knowledge on each lagoon as seen from a land-sea perspective. The DPSIR cycles for each driver were combined into a mosaic-DPSIR conceptual model to examine the interdependency between the multiple and interacting uses of the lagoon. This framework emphasizes the common links, but also the specificities of responses to drivers and the ecosystem services provided. The information collected was used to formulate recommendations for the sustainable management of lagoons within a Pan-European context. Several common management recommendations were proposed, but specificities were also identified. The study synthesizes the present conditions for the management of lagoons, thus analysing and examining the activities that might be developed in different scenarios, scenarios which facilitate ecosystem protection without compromising future generations.
    Description: This study was supported by the European Commission, under the 7th Framework Programme, through the collaborative research project LAGOONS (contract n° 283157); by European funds through COMPETE and by Portuguese funds through the national Foundation for Science and Technology – FCT (PEst-C/MAR/LA0017/2013). The post-Doc grant SFRH/BPD/41117/2007 (M Dolbeth) and the PhD grant SFRH/BD/79170/2011 (LP Sousa) supported by FCT are also acknowledged.
    Repository Name: Woods Hole Open Access Server
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  • 6
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    Nutrient enrichment induces dormancy and decreases diversity of active bacteria in salt marsh sediments (2016)
    Nature Publishing Group
    Details
    Publication Date: 2022-05-25
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 7 (2016): 12881, doi:10.1038/ncomms12881.
    Description: Microorganisms control key biogeochemical pathways, thus changes in microbial diversity, community structure and activity can affect ecosystem response to environmental drivers. Understanding factors that control the proportion of active microbes in the environment and how they vary when perturbed is critical to anticipating ecosystem response to global change. Increasing supplies of anthropogenic nitrogen to ecosystems globally makes it imperative that we understand how nutrient supply alters active microbial communities. Here we show that nitrogen additions to salt marshes cause a shift in the active microbial community despite no change in the total community. The active community shift causes the proportion of dormant microbial taxa to double, from 45 to 90%, and induces diversity loss in the active portion of the community. Our results suggest that perturbations to salt marshes can drastically alter active microbial communities, however these communities may remain resilient by protecting total diversity through increased dormancy.
    Repository Name: Woods Hole Open Access Server
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  • 7
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    Expansion and contraction of the Indo-Pacific tropical rain belt over the last three millennia (2016)
    Nature Publishing Group
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 34485, doi:10.1038/srep34485.
    Description: The seasonal north-south migration of the intertropical convergence zone (ITCZ) defines the tropical rain belt (TRB), a region of enormous terrestrial and marine biodiversity and home to 40% of people on Earth. The TRB is dynamic and has been shown to shift south as a coherent system during periods of Northern Hemisphere cooling. However, recent studies of Indo-Pacific hydroclimate suggest that during the Little Ice Age (LIA; AD 1400–1850), the TRB in this region contracted rather than being displaced uniformly southward. This behaviour is not well understood, particularly during climatic fluctuations less pronounced than those of the LIA, the largest centennial-scale cool period of the last millennium. Here we show that the Indo-Pacific TRB expanded and contracted numerous times over multi-decadal to centennial scales during the last 3,000 yr. By integrating precisely-dated stalagmite records of tropical hydroclimate from southern China with a newly enhanced stalagmite time series from northern Australia, our study reveals a previously unidentified coherence between the austral and boreal summer monsoon. State-of-the-art climate model simulations of the last millennium suggest these are linked to changes in the structure of the regional manifestation of the atmosphere’s meridional circulation.
    Description: Funded by grants from the US National Science Foundation (NSF) Paleo Perspectives on Climate Change (P2C2) program (AGS-1103413), the Center for Global and Regional Environmental Research, and Cornell College (to R.F.D.); and the NSF P2C2 program (AGS-1203704 and AGS-1602455) and the Penzance and John P. Chase Memorial Endowed Funds at WHOI (to C.C.U.).
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  • 8
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    Decrease in coccolithophore calcification and CO2 since the middle Miocene (2016)
    Nature Publishing Group
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 7 (2016): 10284, doi:10.1038/ncomms10284.
    Description: Marine algae are instrumental in carbon cycling and atmospheric carbon dioxide (CO2) regulation. One group, coccolithophores, uses carbon to photosynthesize and to calcify, covering their cells with chalk platelets (coccoliths). How ocean acidification influences coccolithophore calcification is strongly debated, and the effects of carbonate chemistry changes in the geological past are poorly understood. This paper relates degree of coccolith calcification to cellular calcification, and presents the first records of size-normalized coccolith thickness spanning the last 14 Myr from tropical oceans. Degree of calcification was highest in the low-pH, high-CO2 Miocene ocean, but decreased significantly between 6 and 4 Myr ago. Based on this and concurrent trends in a new alkenone εp record, we propose that decreasing CO2 partly drove the observed trend via reduced cellular bicarbonate allocation to calcification. This trend reversed in the late Pleistocene despite low CO2, suggesting an additional regulator of calcification such as alkalinity.
    Description: Funding for this research was provided by the European Research Council under grant UE-09-ERC-2009-STG-240222-PACE (HMS), the Principado de Asturias under award FC-13-COF13-044 (HMS) and a French ANR infrastructure project EMBRC-France (IP).
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  • 9
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    Extensive modulation of the fecal metagenome in children With Crohn’s disease during exclusive enteral nutrition (2016)
    Nature Publishing Group
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in American Journal of Gastroenterology 110 (2015): 1718–1729, doi:10.1038/ajg.2015.357.
    Description: Exploring associations between the gut microbiota and colonic inflammation and assessing sequential changes during exclusive enteral nutrition (EEN) may offer clues into the microbial origins of Crohn’s disease (CD). Fecal samples (n=117) were collected from 23 CD and 21 healthy children. From CD children fecal samples were collected before, during EEN, and when patients returned to their habitual diets. Microbiota composition and functional capacity were characterized using sequencing of the 16S rRNA gene and shotgun metagenomics. Microbial diversity was lower in CD than controls before EEN (P=0.006); differences were observed in 36 genera, 141 operational taxonomic units (OTUs), and 44 oligotypes. During EEN, the microbial diversity of CD children further decreased, and the community structure became even more dissimilar than that of controls. Every 10 days on EEN, 0.6 genus diversity equivalents were lost; 34 genera decreased and one increased during EEN. Fecal calprotectin correlated with 35 OTUs, 14 of which accounted for 78% of its variation. OTUs that correlated positively or negatively with calprotectin decreased during EEN. The microbiota of CD patients had a broader functional capacity than healthy controls, but diversity decreased with EEN. Genes involved in membrane transport, sulfur reduction, and nutrient biosynthesis differed between patients and controls. The abundance of genes involved in biotin (P=0.005) and thiamine biosynthesis decreased (P=0.017), whereas those involved in spermidine/putrescine biosynthesis (P=0.031), or the shikimate pathway (P=0.058), increased during EEN. Disease improvement following treatment with EEN is associated with extensive modulation of the gut microbiome.
    Description: The IBD team at Royal Hospital for Children, Glasgow, is supported by the Catherine McEwan Foundation and the Yorkhill IBD fund.
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  • 10
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    (Meta)genomic insights into the pathogenome of Cellulosimicrobium cellulans (2016)
    Nature Publishing Group
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 25527, doi:10.1038/srep25527.
    Description: Despite having serious clinical manifestations, Cellulosimicrobium cellulans remain under-reported with only three genome sequences available at the time of writing. Genome sequences of C. cellulans LMG16121, C. cellulans J36 and Cellulosimicrobium sp. strain MM were used to determine distribution of pathogenicity islands (PAIs) across C. cellulans, which revealed 49 potential marker genes with known association to human infections, e.g. Fic and VbhA toxin-antitoxin system. Oligonucleotide composition-based analysis of orthologous proteins (n = 791) across three genomes revealed significant negative correlation (P 〈 0.05) between frequency of optimal codons (Fopt) and gene G+C content, highlighting the G+C-biased gene conversion (gBGC) effect across Cellulosimicrobium strains. Bayesian molecular-clock analysis performed on three virulent PAI proteins (Fic; D-alanyl-D-alanine-carboxypeptidase; transposase) dated the divergence event at 300 million years ago from the most common recent ancestor. Synteny-based annotation of hypothetical proteins highlighted gene transfers from non-pathogenic bacteria as a key factor in the evolution of PAIs. Additonally, deciphering the metagenomic islands using strain MM’s genome with environmental data from the site of isolation (hot-spring biofilm) revealed (an)aerobic respiration as population segregation factor across the in situ cohorts. Using reference genomes and metagenomic data, our results highlight the emergence and evolution of PAIs in the genus Cellulosimicrobium.
    Description: The authors acknowledge funds from Department of Biotechnology (DBT) and National Bureau of Agriculturally Important Microorganisms (NBAIM). AS gratefully acknowledge National Bureau of Agriculturally Important Microorganisms (NBAIM) for providing research fellowship.
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  • 11
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    Coupled RNA-SIP and metatranscriptomics of active chemolithoautotrophic communities at a deep-sea hydrothermal vent (2016)
    Nature Publishing Group
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    Publication Date: 2022-05-25
    Description: © The International Society for Microbial Ecology, 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in ISME Journal 10 (2016): 1925–1938, doi:10.1038/ismej.2015.258.
    Description: The chemolithoautotrophic microbial community of the rocky subseafloor potentially provides a large amount of organic carbon to the deep ocean, yet our understanding of the activity and metabolic complexity of subseafloor organisms remains poorly described. A combination of metagenomic, metatranscriptomic, and RNA stable isotope probing (RNA-SIP) analyses were used to identify the metabolic potential, expression patterns, and active autotrophic bacteria and archaea and their pathways present in low-temperature hydrothermal fluids from Axial Seamount, an active submarine volcano. Metagenomic and metatranscriptomic results showed the presence of genes and transcripts for sulfur, hydrogen, and ammonium oxidation, oxygen respiration, denitrification, and methanogenesis, as well as multiple carbon fixation pathways. In RNA-SIP experiments across a range of temperatures under reducing conditions, the enriched 13C fractions showed differences in taxonomic and functional diversity. At 30 °C and 55 °C, Epsilonproteobacteria were dominant, oxidizing hydrogen and primarily reducing nitrate. Methanogenic archaea were also present at 55 °C, and were the only autotrophs present at 80 °C. Correspondingly, the predominant CO2 fixation pathways changed from the reductive tricarboxylic acid (rTCA) cycle to the reductive acetyl-CoA pathway with increasing temperature. By coupling RNA-SIP with meta-omics, this study demonstrates the presence and activity of distinct chemolithoautotrophic communities across a thermal gradient of a deep-sea hydrothermal vent.
    Description: This work was funded by the Gordon and Betty Moore Foundation Grant GBMF3297 and NSF Center for Dark Energy Biosphere Investigations (C-DEBI) (OCE-0939564). The data collected in this study is based upon work supported by the Schmidt Ocean Institute during cruise FK010-2013 aboard R/V Falkor.
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  • 12
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    Species-specific control of external superoxide levels by the coral holobiont during a natural bleaching event (2016)
    Nature Publishing Group
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 7 (2016): 13801, doi:10.1038/ncomms13801.
    Description: The reactive oxygen species superoxide (O2·−) is both beneficial and detrimental to life. Within corals, superoxide may contribute to pathogen resistance but also bleaching, the loss of essential algal symbionts. Yet, the role of superoxide in coral health and physiology is not completely understood owing to a lack of direct in situ observations. By conducting field measurements of superoxide produced by corals during a bleaching event, we show substantial species-specific variation in external superoxide levels, which reflect the balance of production and degradation processes. Extracellular superoxide concentrations are independent of light, algal symbiont abundance and bleaching status, but depend on coral species and bacterial community composition. Furthermore, coral-derived superoxide concentrations ranged from levels below bulk seawater up to ∼120 nM, some of the highest superoxide concentrations observed in marine systems. Overall, these results unveil the ability of corals and/or their microbiomes to regulate superoxide in their immediate surroundings, which suggests species-specific roles of superoxide in coral health and physiology.
    Description: This work was supported by a Postdoctoral Fellowship from the Ford Foundation (J.M.D.), the National Science Foundation under grants OCE 1225801 (J.M.D.) and OCE 1233612 (A.A.), the Ocean and Climate Change Institute of the Woods Hole Oceanographic Institution (C.M.H.), the Sidney Stern Memorial Trust (C.M.H. and A.A.) and an anonymous donor.
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  • 13
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    The intertropical convergence zone modulates intense hurricane strikes on the western North Atlantic margin (2016)
    Nature Publishing Group
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 21728, doi:10.1038/srep21728
    Description: Most Atlantic hurricanes form in the Main Development Region between 9°N to 20°N along the northern edge of the Intertropical Convergence Zone (ITCZ). Previous research has suggested that meridional shifts in the ITCZ position on geologic timescales can modulate hurricane activity, but continuous and long-term storm records are needed from multiple sites to assess this hypothesis. Here we present a 3000 year record of intense hurricane strikes in the northern Bahamas (Abaco Island) based on overwash deposits in a coastal sinkhole, which indicates that the ITCZ has likely helped modulate intense hurricane strikes on the western North Atlantic margin on millennial to centennial-scales. The new reconstruction closely matches a previous reconstruction from Puerto Rico, and documents a period of elevated intense hurricane activity on the western North Atlantic margin from 2500 to 1000 years ago when paleo precipitation proxies suggest that the ITCZ occupied a more northern position. Considering that anthropogenic warming is predicted to be focused in the northern hemisphere in the coming century, these results provide a prehistoric analog that an attendant northern ITCZ shift in the future may again return the western North Atlantic margin to an active hurricane interval.
    Description: This research was supported by NSF Awards: OCE-1519578, OCE-1356708, BCS-1118340.
    Keywords: Climate-change impacts ; Forest ecology ; Ocean sciences ; Palaeoclimate
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  • 14
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    Calcium phosphate mineralization is widely applied in crustacean mandibles (2016)
    Nature Publishing Group
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 22118, doi:10.1038/srep22118.
    Description: Crustaceans, like most mineralized invertebrates, adopted calcium carbonate mineralization for bulk skeleton reinforcement. Here, we show that a major part of the crustacean class Malacostraca (which includes lobsters, crayfishes, prawns and shrimps) shifted toward the formation of calcium phosphate as the main mineral at specified locations of the mandibular teeth. In these structures, calcium phosphate is not merely co-precipitated with the bulk calcium carbonate but rather creates specialized structures in which a layer of calcium phosphate, frequently in the form of crystalline fluorapatite, is mounted over a calcareous “jaw”. From a functional perspective, the co-existence of carbonate and phosphate mineralization demonstrates a biomineralization system that provides a versatile route to control the physico-chemical properties of skeletal elements. This system enables the deposition of amorphous calcium carbonate, amorphous calcium phosphate, calcite and apatite at various skeletal locations, as well as combinations of these minerals, to form graded composites materials. This study demonstrates the widespread occurrence of the dual mineralization strategy in the Malacostraca, suggesting that in terms of evolution, this feature of phosphatic teeth did not evolve independently in the different groups but rather represents an early common trait.
    Description: This study was supported in part by grants from the Israel Science Foundation (ISF, Grant 613/13) and the National Institute for Biotechnology in the Negev (NIBN).
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  • 15
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    Evidence for quorum sensing and differential metabolite production by a marine bacterium in response to DMSP (2016)
    Nature Publishing Group
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    Publication Date: 2022-05-25
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in The ISME Journal 10 (2016): 2304–2316, doi:10.1038/ismej.2016.6.
    Description: Microbes, the foundation of the marine foodweb, do not function in isolation, but rather rely on molecular level interactions among species to thrive. Although certain types of interactions between autotrophic and heterotrophic microorganisms have been well documented, the role of specific organic molecules in regulating inter-species relationships and supporting growth are only beginning to be understood. Here, we examine one such interaction by characterizing the metabolic response of a heterotrophic marine bacterium, Ruegeria pomeroyi DSS-3, to growth on dimethylsulfoniopropionate (DMSP), an abundant organosulfur metabolite produced by phytoplankton. When cultivated on DMSP, R. pomeroyi synthesized a quorum-sensing molecule, N-(3-oxotetradecanoyl)-l-homoserine lactone, at significantly higher levels than during growth on propionate. Concomitant with the production of a quorum-sensing molecule, we observed differential production of intra- and extracellular metabolites including glutamine, vitamin B2 and biosynthetic intermediates of cyclic amino acids. Our metabolomics data indicate that R. pomeroyi changes regulation of its biochemical pathways in a manner that is adaptive for a cooperative lifestyle in the presence of DMSP, in anticipation of phytoplankton-derived nutrients and higher microbial density. This behavior is likely to occur on sinking marine particles, indicating that this response may impact the fate of organic matter.
    Description: This research is funded in part by the Gordon and Betty Moore Foundation through Grant GBMF3304 as well as by the National Science Foundation (Grants OCE-0928424 and OCE-1154320).
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  • 16
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    Lipid remodelling is a widespread strategy in marine heterotrophic bacteria upon phosphorus deficiency (2016)
    Nature Publishing Group
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    Publication Date: 2022-05-26
    Description: © The International Society for Microbial Ecology, 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in ISME Journal 10 (2016): 968–978, doi:10.1038/ismej.2015.172.
    Description: Upon phosphorus (P) deficiency, marine phytoplankton reduce their requirements for P by replacing membrane phospholipids with alternative non-phosphorus lipids. It was very recently demonstrated that a SAR11 isolate also shares this capability when phosphate starved in culture. Yet, the extent to which this process occurs in other marine heterotrophic bacteria and in the natural environment is unknown. Here, we demonstrate that the substitution of membrane phospholipids for a variety of non-phosphorus lipids is a conserved response to P deficiency among phylogenetically diverse marine heterotrophic bacteria, including members of the Alphaproteobacteria and Flavobacteria. By deletion mutagenesis and complementation in the model marine bacterium Phaeobacter sp. MED193 and heterologous expression in recombinant Escherichia coli, we confirm the roles of a phospholipase C (PlcP) and a glycosyltransferase in lipid remodelling. Analyses of the Global Ocean Sampling and Tara Oceans metagenome data sets demonstrate that PlcP is particularly abundant in areas characterized by low phosphate concentrations. Furthermore, we show that lipid remodelling occurs seasonally and responds to changing nutrient conditions in natural microbial communities from the Mediterranean Sea. Together, our results point to the key role of lipid substitution as an adaptive strategy enabling heterotrophic bacteria to thrive in the vast P-depleted areas of the ocean.
    Description: This work was partially supported by grants STORM (CTM2009-09352/MAR), MALASPINA (CSD2008-00077), HOTMIX (CTM2011-30010/MAR), DOREMI (CTM2012-34294) and EcoBGM (CTM2013-48292-C3-3-R) funded by the Spanish Government, GAČR project GA13-11281S and MESOAQUA (228224) funded by the European Union Seventh Framework Program (FP7/2007-2013) and by the Natural Environment Research Council (NERC), UK (NE/M002233/1).
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    Punctuated shutdown of Atlantic Meridional Overturning Circulation during Greenland Stadial 1 (2016)
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 25902, doi:10.1038/srep25902.
    Description: The Greenland Stadial 1 (GS-1; ~12.9 to 11.65 kyr cal BP) was a period of North Atlantic cooling, thought to have been initiated by North America fresh water runoff that caused a sustained reduction of North Atlantic Meridional Overturning Circulation (AMOC), resulting in an antiphase temperature response between the hemispheres (the ‘bipolar seesaw’). Here we exploit sub-fossil New Zealand kauri trees to report the first securely dated, decadally-resolved atmospheric radiocarbon (14C) record spanning GS-1. By precisely aligning Southern and Northern Hemisphere tree-ring 14C records with marine 14C sequences we document two relatively short periods of AMOC collapse during the stadial, at ~12,920-12,640 cal BP and 12,050-11,900 cal BP. In addition, our data show that the interhemispheric atmospheric 14C offset was close to zero prior to GS-1, before reaching ‘near-modern’ values at ~12,660 cal BP, consistent with synchronous recovery of overturning in both hemispheres and increased Southern Ocean ventilation. Hence, sustained North Atlantic cooling across GS-1 was not driven by a prolonged AMOC reduction but probably due to an equatorward migration of the Polar Front, reducing the advection of southwesterly air masses to high latitudes. Our findings suggest opposing hemispheric temperature trends were driven by atmospheric teleconnections, rather than AMOC changes.
    Description: This work was part funded by the Foundation for Research, Science and Technology (FRST)—now Ministry for Business, Innovation & Employment (MBIE)-PROP-20224-SFK-UOA), a Royal Society of New Zealand grant, the Australian Research Council (FL100100195 and DP0664898) and the Natural Environment Research Council (NE/H009922/1, NE/I007660/1, NER/A/S/2001/01037 and NE/H007865/1).
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    Full circumpolar migration ensures evolutionary unity in the Emperor penguin (2016)
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 7 (2016): 11842, doi:10.1038/ncomms11842.
    Description: Defining reliable demographic models is essential to understand the threats of ongoing environmental change. Yet, in the most remote and threatened areas, models are often based on the survey of a single population, assuming stationarity and independence in population responses. This is the case for the Emperor penguin Aptenodytes forsteri, a flagship Antarctic species that may be at high risk continent-wide before 2100. Here, using genome-wide data from the whole Antarctic continent, we reveal that this top-predator is organized as one single global population with a shared demography since the late Quaternary. We refute the view of the local population as a relevant demographic unit, and highlight that (i) robust extinction risk estimations are only possible by including dispersal rates and (ii) colony-scaled population size is rather indicative of local stochastic events, whereas the species’ response to global environmental change is likely to follow a shared evolutionary trajectory.
    Description: This study was undertaken within the framework of the Programme 137 of the Institut Polaire Français Paul-Emile Victor (IPEV), with additional support from the French National Research Agency (ANR) ‘PICASO’ grant (ANR-2010-BLAN-1728-01, PI: Y.L.M.), from Marie Curie Intra European Fellowships (FP7-PEOPLE-IEF-2008, European Commission; project no. 235962 to CLB and FP7-PEOPLE-IEF-2010, European Commission; project no. 252252 to E.T.), from the Centre Scientifique de Monaco through budget allocated to the Laboratoire International Associé 647 ‘BioSensib’ (CSM/CNRS-University of Strasbourg), from the Centre National de la Recherche Scientifique (Programme Zone Atelier de Recherches sur l’Environnement Antarctique et Subantarctique) and from the British Antarctic Survey Ecosystems Programme, NERC (P.N.T.). Logistic and field costs of research were supported by IPEV (C.L.B.), the British Antarctic Survey Ecosystems Programme, NERC (P.N.T.), AWI (D.P.Z.), US NSF grant number NSF 0229638 (P.J.P.).
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    Coral reef soundscapes may not be detectable far from the reef (2016)
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 31862, doi:10.1038/srep31862.
    Description: Biological sounds produced on coral reefs may provide settlement cues to marine larvae. Sound fields are composed of pressure and particle motion, which is the back and forth movement of acoustic particles. Particle motion (i.e., not pressure) is the relevant acoustic stimulus for many, if not most, marine animals. However, there have been no field measurements of reef particle motion. To address this deficiency, both pressure and particle motion were recorded at a range of distances from one Hawaiian coral reef at dawn and mid-morning on three separate days. Sound pressure attenuated with distance from the reef at dawn. Similar trends were apparent for particle velocity but with considerable variability. In general, average sound levels were low and perhaps too faint to be used as an orientation cue except very close to the reef. However, individual transient sounds that exceeded the mean values, sometimes by up to an order of magnitude, might be detectable far from the reef, depending on the hearing abilities of the larva. If sound is not being used as a long-range cue, it might still be useful for habitat selection or other biological activities within a reef.
    Description: This work was funded by the Woods Hole Oceanographic Institution Ocean Ventures Fund, the PADI Foundation, the Woods Hole Oceanographic Institution Access To The Sea program, and the National Science Foundation grant OCE-1536782.
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    Bacterial diversity and community composition from seasurface to subseafloor (2016)
    Nature Publishing Group
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    Publication Date: 2022-05-26
    Description: © The International Society for Microbial Ecology, 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in ISME Journal 10 (2016): 979–989, doi:10.1038/ismej.2015.175.
    Description: We investigated compositional relationships between bacterial communities in the water column and those in deep-sea sediment at three environmentally distinct Pacific sites (two in the Equatorial Pacific and one in the North Pacific Gyre). Through pyrosequencing of the v4–v6 hypervariable regions of the 16S ribosomal RNA gene, we characterized 450 104 pyrotags representing 29 814 operational taxonomic units (OTUs, 97% similarity). Hierarchical clustering and non-metric multidimensional scaling partition the samples into four broad groups, regardless of geographic location: a photic-zone community, a subphotic community, a shallow sedimentary community and a subseafloor sedimentary community (greater than or equal to1.5 meters below seafloor). Abundance-weighted community compositions of water-column samples exhibit a similar trend with depth at all sites, with successive epipelagic, mesopelagic, bathypelagic and abyssopelagic communities. Taxonomic richness is generally highest in the water-column O2 minimum zone and lowest in the subseafloor sediment. OTUs represented by abundant tags in the subseafloor sediment are often present but represented by few tags in the water column, and represented by moderately abundant tags in the shallow sediment. In contrast, OTUs represented by abundant tags in the water are generally absent from the subseafloor sediment. These results are consistent with (i) dispersal of marine sedimentary bacteria via the ocean, and (ii) selection of the subseafloor sedimentary community from within the community present in shallow sediment.
    Description: This study was funded by the Biological Oceanography Program of the US National Science Foundation (grant OCE-0752336) and by the NSF-funded Center for Dark Energy Biosphere Investigations (grant NSF-OCE-0939564).
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    Prevalence of influenza A virus in live-captured North Atlantic gray seals : a possible wild reservoir (2016)
    Nature Publishing Group
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Emerging Microbes and Infections 5 (2016): e81, doi:10.1038/emi.2016.77.
    Description: Influenza A virus (IAV) has been associated with multiple unusual mortality events (UMEs) in North Atlantic pinnipeds, frequently attributed to spillover of virus from wild-bird reservoirs. To determine if endemic infection persists outside of UMEs, we undertook a multiyear investigation of IAV in healthy, live-captured Northwest Atlantic gray seals (Halichoerus grypus). From 2013 to 2015, we sampled 345 pups and 57 adults from Cape Cod, MA, USA and Nova Scotia, Canada consistently detecting IAV infection across all groups. There was an overall viral prevalence of 9.0% (95% confidence interval (CI): 6.4%–12.5%) in weaned pups and 5.3% (CI: 1.2%–14.6%) in adults, with seroprevalences of 19.3% (CI: 15.0%–24.5%) and 50% (CI: 33.7%–66.4%), respectively. Positive sera showed a broad reactivity to diverse influenza subtypes. IAV status did not correlate with measures of animal health nor impact animal movement or foraging. This study demonstrated that Northwest Atlantic gray seals are both permissive to and tolerant of diverse IAV, possibly representing an endemically infected wild reservoir population.
    Description: This work was supported in part by National Institute of Allergy and Infectious Diseases (NIAID), the Centers of Excellence for Influenza Research and Surveillance (CEIRS) HHSN272201400008C, MIT Sea Grant Project 2013-DOH-45-LEV, National Science and Engineering Research Council of Canada (NSERC), NMFS #17670-01, NMFS #10080-95 and FWS #53514-13003.
    Keywords: Gray seal ; Halichoerus grypus ; Influenza ; Pinniped ; Reservoir ; Telemetry
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    The size-distribution of Earth’s lakes (2016)
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 29633, doi:10.1038/srep29633.
    Description: Globally, there are millions of small lakes, but a small number of large lakes. Most key ecosystem patterns and processes scale with lake size, thus this asymmetry between area and abundance is a fundamental constraint on broad-scale patterns in lake ecology. Nonetheless, descriptions of lake size-distributions are scarce and empirical distributions are rarely evaluated relative to theoretical predictions. Here we develop expectations for Earth’s lake area-distribution based on percolation theory and evaluate these expectations with data from a global lake census. Lake surface areas ≥8.5 km2 are power-law distributed with a tail exponent (τ = 1.97) and fractal dimension (d = 1.38), similar to theoretical expectations (τ = 2.05; d = 4/3). Lakes 〈8.5 km2 are not power-law distributed. An independently developed regional lake census exhibits a similar transition and consistency with theoretical predictions. Small lakes deviate from the power-law distribution because smaller lakes are more susceptible to dynamical change and topographic behavior at sub-kilometer scales is not self-similar. Our results provide a robust characterization and theoretical explanation for the lake size-abundance relationship, and form a fundamental basis for understanding and predicting patterns in lake ecology at broad scales.
    Description: This paper is based on research supported by the National Science Foundation (OCE-1315201), the Swedish Research Council Formas, and the Carl Tryggers Foundation for Scientific Research.
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    Mitigation of coral reef warming across the central Pacific by the Equatorial Undercurrent : a past and future divide (2016)
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 21213, doi:10.1038/srep21213.
    Description: Global climate models (GCMs) predict enhanced warming and nutrient decline across the central tropical Pacific as trade winds weaken with global warming. Concurrent changes in circulation, however, have potential to mitigate these effects for equatorial islands. The implications for densely populated island nations, whose livelihoods depend on ecosystem services, are significant. A unique suite of in situ measurements coupled with state-of-the-art GCM simulations enables us to quantify the mitigation potential of the projected circulation change for three coral reef ecosystems under two future scenarios. Estimated historical trends indicate that over 100% of the large-scale warming to date has been offset locally by changes in circulation, while future simulations predict a warming mitigation effect of only 5–10% depending on the island. The pace and extent to which GCM projections overwhelm historical trends will play a key role in defining the fate of marine ecosystems and island communities across the tropical Pacific.
    Description: Support provided by NSF OCE-1031971 (ALC and KBK). KBK also acknowledges support from NSF OCE-1233282, the DoD Strategic Environmental Research and Development Program (SERDP), the WHOI Ocean and Climate Change Institute Moltz Fellowship, and the Alfred P. Sloan Foundation. Funding for the Pacific Reef Assessment and Monitoring Program, was provided by NOAA’s Coral Reef Conservation Program.
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    A distinct and active bacterial community in cold oxygenated fluids circulating beneath the western flank of the Mid-Atlantic ridge (2016)
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 22541, doi:10.1038/srep22541.
    Description: The rock-hosted, oceanic crustal aquifer is one of the largest ecosystems on Earth, yet little is known about its indigenous microorganisms. Here we provide the first phylogenetic and functional description of an active microbial community residing in the cold oxic crustal aquifer. Using subseafloor observatories, we recovered crustal fluids and found that the geochemical composition is similar to bottom seawater, as are cell abundances. However, based on relative abundances and functional potential of key bacterial groups, the crustal fluid microbial community is heterogeneous and markedly distinct from seawater. Potential rates of autotrophy and heterotrophy in the crust exceeded those of seawater, especially at elevated temperatures (25°C) and deeper in the crust. Together, these results reveal an active, distinct, and diverse bacterial community engaged in both heterotrophy and autotrophy in the oxygenated crustal aquifer, providing key insight into the role of microbial communities in the ubiquitous cold dark subseafloor biosphere. An Author Correction to this article was published on 16 April 2020
    Description: This work was supported by NSF OCE1062006 to JAH, NSF OCE1061934 to PRG, and NSF OCE1061827 to BTG. The Center for Dark Energy Biosphere Investigations (C-DEBI) (OCE-0939564), a National Science Foundation-funded Science and Technology Centers of Excellence also supported the participation of CGW, THL, JPC, JAH, BT, and CHH, as well as JLM and UJ through C-DEBI Postdoctoral Fellowships.
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    CO2 and fire influence tropical ecosystem stability in response to climate change (2016)
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 29587, doi:10.1038/srep29587.
    Description: Interactions between climate, fire and CO2 are believed to play a crucial role in controlling the distributions of tropical woodlands and savannas, but our understanding of these processes is limited by the paucity of data from undisturbed tropical ecosystems. Here we use a 28,000-year integrated record of vegetation, climate and fire from West Africa to examine the role of these interactions on tropical ecosystem stability. We find that increased aridity between 28–15 kyr B.P. led to the widespread expansion of tropical grasslands, but that frequent fires and low CO2 played a crucial role in stabilizing these ecosystems, even as humidity changed. This resulted in an unstable ecosystem state, which transitioned abruptly from grassland to woodlands as gradual changes in CO2 and fire shifted the balance in favor of woody plants. Since then, high atmospheric CO2 has stabilized tropical forests by promoting woody plant growth, despite increased aridity. Our results indicate that the interactions between climate, CO2 and fire can make tropical ecosystems more resilient to change, but that these systems are dynamically unstable and potentially susceptible to abrupt shifts between woodland and grassland dominated states in the future.
    Description: This work was supported by NSF grants EAR0601998, EAR0602355, AGS0402010, ATM0401908, ATM0214525, ATM0096232 and AGS1243125 and a Chevron Centennial Fellowship at the University of Texas at Austin awarded to T.M.S.
    Keywords: Climate-change ecology ; Palaeoclimate
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    Metatranscriptomics reveals temperature-driven functional changes in microbiome impacting cheese maturation rate (2016)
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 21871, doi:10.1038/srep21871.
    Description: Traditional cheeses harbour complex microbial consortia that play an important role in shaping typical sensorial properties. However, the microbial metabolism is considered difficult to control. Microbial community succession and the related gene expression were analysed during ripening of a traditional Italian cheese, identifying parameters that could be modified to accelerate ripening. Afterwards, we modulated ripening conditions and observed consistent changes in microbial community structure and function. We provide concrete evidence of the essential contribution of non-starter lactic acid bacteria in ripening-related activities. An increase in the ripening temperature promoted the expression of genes related to proteolysis, lipolysis and amino acid/lipid catabolism and significantly increases the cheese maturation rate. Moreover, temperature-promoted microbial metabolisms were consistent with the metabolomic profiles of proteins and volatile organic compounds in the cheese. The results clearly indicate how processing-driven microbiome responses can be modulated in order to optimize production efficiency and product quality.
    Description: F.D.F. was supported by a grant from Regione Campania within the program “POR CAMPANIA FSE 2007/2013” - project CARINA (Safety sustainability and competitiveness of the agro-food production in Campania) – CUP B25B09000080007.
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    Identification of differentially expressed genes from multipotent epithelia at the onset of an asexual development (2016)
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 27357, doi:10.1038/srep27357.
    Description: Organisms that have evolved alternative modes of reproduction, complementary to the sexual mode, are found across metazoans. The chordate Botryllus schlosseri is an emerging model for asexual development studies. Botryllus can rebuild its entire body from a portion of adult epithelia in a continuous and stereotyped process called blastogenesis. Anatomy and ontogenies of blastogenesis are well described, however molecular signatures triggering this developmental process are entirely unknown. We isolated tissues at the site of blastogenesis onset and from the same epithelia where this process is never triggered. We linearly amplified an ultra-low amount of mRNA (〈10ng) and generated three transcriptome datasets. To provide a conservative landscape of transcripts differentially expressed between blastogenic vs. non-blastogenic epithelia we compared three different mapping and analysis strategies with a de novo assembled transcriptome and partially assembled genome as references, additionally a self-mapping strategy on the dataset. A subset of differentially expressed genes were analyzed and validated by in situ hybridization. The comparison of different analyses allowed us to isolate stringent sets of target genes, including transcripts with potential involvement in the onset of a non-embryonic developmental pathway. The results provide a good entry point to approach regenerative event in a basal chordate.
    Description: This work was supported by AFM Telethon grant (#16611), IRG Marie Curie grant (#276974), ANR (ANR-14-CE02-0019-01) and IDEX Super (INDIBIO). L.R. was supported by an UPMC-EMREGENCE grant and by a FRM grant (#FDT20140931163). A.C. was supported by a FRM grant (ING 20140129231).
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    Mechanisms of increased Trichodesmium fitness under iron and phosphorus co-limitation in the present and future ocean (2016)
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 7 (2016): 12081, doi:10.1038/ncomms12081.
    Description: Nitrogen fixation by cyanobacteria supplies critical bioavailable nitrogen to marine ecosystems worldwide; however, field and lab data have demonstrated it to be limited by iron, phosphorus and/or CO2. To address unknown future interactions among these factors, we grew the nitrogen-fixing cyanobacterium Trichodesmium for 1 year under Fe/P co-limitation following 7 years of both low and high CO2 selection. Fe/P co-limited cell lines demonstrated a complex cellular response including increased growth rates, broad proteome restructuring and cell size reductions relative to steady-state growth limited by either Fe or P alone. Fe/P co-limitation increased abundance of a protein containing a conserved domain previously implicated in cell size regulation, suggesting a similar role in Trichodesmium. Increased CO2 further induced nutrient-limited proteome shifts in widespread core metabolisms. Our results thus suggest that N2-fixing microbes may be significantly impacted by interactions between elevated CO2 and nutrient limitation, with broad implications for global biogeochemical cycles in the future ocean.
    Description: Grant support was provided by U.S. National Science Foundation OCE 1260490 to D.A.H., E.A.W. and F.-X.F., and OCE OA 1220484 and G.B. Moore Foundation 3782 and 3934 to M.A.S.
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    Dynamic Reweighting of Auditory Modulation Filters (2016)
    Public Library of Science (PLoS)
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    Publication Date: 2016-07-12
    Description: by Eva R. M. Joosten, Shihab A. Shamma, Christian Lorenzi, Peter Neri Sound waveforms convey information largely via amplitude modulations (AM). A large body of experimental evidence has provided support for a modulation (bandpass) filterbank. Details of this model have varied over time partly reflecting different experimental conditions and diverse datasets from distinct task strategies, contributing uncertainty to the bandwidth measurements and leaving important issues unresolved. We adopt here a solely data-driven measurement approach in which we first demonstrate how different models can be subsumed within a common ‘cascade’ framework, and then proceed to characterize the cascade via system identification analysis using a single stimulus/task specification and hence stable task rules largely unconstrained by any model or parameters. Observers were required to detect a brief change in level superimposed onto random level changes that served as AM noise; the relationship between trial-by-trial noisy fluctuations and corresponding human responses enables targeted identification of distinct cascade elements. The resulting measurements exhibit a dynamic complex picture in which human perception of auditory modulations appears adaptive in nature, evolving from an initial lowpass to bandpass modes (with broad tuning, Q∼1) following repeated stimulus exposure.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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    Two-Step Regulation of a Meristematic Cell Population Acting in Shoot Branching in Arabidopsis (2016)
    Public Library of Science (PLoS)
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    Publication Date: 2016-07-12
    Description: by Bihai Shi, Cui Zhang, Caihuan Tian, Jin Wang, Quan Wang, Tengfei Xu, Yan Xu, Carolyn Ohno, Robert Sablowski, Marcus G. Heisler, Klaus Theres, Ying Wang, Yuling Jiao Shoot branching requires the establishment of new meristems harboring stem cells; this phenomenon raises questions about the precise regulation of meristematic fate. In seed plants, these new meristems initiate in leaf axils to enable lateral shoot branching. Using live-cell imaging of leaf axil cells, we show that the initiation of axillary meristems requires a meristematic cell population continuously expressing the meristem marker SHOOT MERISTEMLESS ( STM ). The maintenance of STM expression depends on the leaf axil auxin minimum. Ectopic expression of STM is insufficient to activate axillary buds formation from plants that have lost leaf axil STM expressing cells. This suggests that some cells undergo irreversible commitment to a developmental fate. In more mature leaves, REVOLUTA ( REV ) directly up-regulates STM expression in leaf axil meristematic cells, but not in differentiated cells, to establish axillary meristems. Cell type-specific binding of REV to the STM region correlates with epigenetic modifications. Our data favor a threshold model for axillary meristem initiation, in which low levels of STM maintain meristematic competence and high levels of STM lead to meristem initiation.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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    Understanding Disease Tolerance and Resilience (2016)
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    Publication Date: 2016-07-12
    Description: by Lauren A. Richardson Our first ever Open Highlights explores recent Open Access research into the complex relationship between host and pathogen during the course of an infection, and the factors that determine its eventual outcome.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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    Metagenome and Metatranscriptome Analyses Using Protein Family Profiles (2016)
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    Publication Date: 2016-07-12
    Description: by Cuncong Zhong, Anna Edlund, Youngik Yang, Jeffrey S. McLean, Shibu Yooseph Analyses of metagenome data (MG) and metatranscriptome data (MT) are often challenged by a paucity of complete reference genome sequences and the uneven/low sequencing depth of the constituent organisms in the microbial community, which respectively limit the power of reference-based alignment and de novo sequence assembly. These limitations make accurate protein family classification and abundance estimation challenging, which in turn hamper downstream analyses such as abundance profiling of metabolic pathways, identification of differentially encoded/expressed genes, and de novo reconstruction of complete gene and protein sequences from the protein family of interest. The profile hidden Markov model (HMM) framework enables the construction of very useful probabilistic models for protein families that allow for accurate modeling of position specific matches, insertions, and deletions. We present a novel homology detection algorithm that integrates banded Viterbi algorithm for profile HMM parsing with an iterative simultaneous alignment and assembly computational framework. The algorithm searches a given profile HMM of a protein family against a database of fragmentary MG/MT sequencing data and simultaneously assembles complete or near-complete gene and protein sequences of the protein family. The resulting program, HMM-GRASPx, demonstrates superior performance in aligning and assembling homologs when benchmarked on both simulated marine MG and real human saliva MG datasets. On real supragingival plaque and stool MG datasets that were generated from healthy individuals, HMM-GRASPx accurately estimates the abundances of the antimicrobial resistance (AMR) gene families and enables accurate characterization of the resistome profiles of these microbial communities. For real human oral microbiome MT datasets, using the HMM-GRASPx estimated transcript abundances significantly improves detection of differentially expressed (DE) genes. Finally, HMM-GRASPx was used to reconstruct comprehensive sets of complete or near-complete protein and nucleotide sequences for the query protein families. HMM-GRASPx is freely available online from http://sourceforge.net/projects/hmm-graspx.
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    Limited Contribution of DNA Methylation Variation to Expression Regulation in Arabidopsis thaliana (2016)
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    Publication Date: 2016-07-12
    Description: by Dazhe Meng, Manu Dubin, Pei Zhang, Edward J. Osborne, Oliver Stegle, Richard M. Clark, Magnus Nordborg The extent to which epigenetic variation affects complex traits in natural populations is not known. We addressed this question using transcriptome and DNA methylation data from a sample of 135 sequenced A. thaliana accessions. Across individuals, expression was significantly associated with cis -methylation for hundreds of genes, and many of these associations remained significant after taking SNP effects into account. The pattern of correlations differed markedly between gene body methylation and transposable element methylation. The former was usually positively correlated with expression, and the latter usually negatively correlated, although exceptions were found in both cases. Finally, we developed graphical models of causality that adapt to a sample with heavy population structure, and used them to show that while methylation appears to affect gene expression more often than expression affects methylation, there is also strong support for both being independently controlled. In conclusion, although we find clear evidence for epigenetic regulation, both the number of loci affected and the magnitude of the effects appear to be small compared to the effect of SNPs.
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    Functional Crosstalk between the PP2A and SUMO Pathways Revealed by Analysis of STUbL Suppressor, razor 1-1 (2016)
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    Publication Date: 2016-07-12
    Description: by Minghua Nie, Emily Arner, John Prudden, Lana Schaffer, Steven Head, Michael N. Boddy Posttranslational modifications (PTMs) provide dynamic regulation of the cellular proteome, which is critical for both normal cell growth and for orchestrating rapid responses to environmental stresses, e.g. genotoxins. Key PTMs include ubiquitin, the Small Ubiquitin-like MOdifier SUMO, and phosphorylation. Recently, SUMO-targeted ubiquitin ligases (STUbLs) were found to integrate signaling through the SUMO and ubiquitin pathways. In general, STUbLs are recruited to target proteins decorated with poly-SUMO chains to ubiquitinate them and drive either their extraction from protein complexes, and/or their degradation at the proteasome. In fission yeast, reducing or preventing the formation of SUMO chains can circumvent the essential and DNA damage response functions of STUbL. This result indicates that whilst some STUbL "targets" have been identified, the crucial function of STUbL is to antagonize SUMO chain formation. Herein, by screening for additional STUbL suppressors, we reveal crosstalk between the serine/threonine phosphatase PP2A-Pab1 B55 and the SUMO pathway. A hypomorphic Pab1 B55 mutant not only suppresses STUbL dysfunction, but also mitigates the phenotypes associated with deletion of the SUMO protease Ulp2, or mutation of the STUbL cofactor Rad60. Together, our results reveal a novel role for PP2A-Pab1 B55 in modulating SUMO pathway output, acting in parallel to known critical regulators of SUMOylation homeostasis. Given the broad evolutionary functional conservation of the PP2A and SUMO pathways, our results could be relevant to the ongoing attempts to therapeutically target these factors.
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    Machine Learning Meta-analysis of Large Metagenomic Datasets: Tools and Biological Insights (2016)
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    Publication Date: 2016-07-12
    Description: by Edoardo Pasolli, Duy Tin Truong, Faizan Malik, Levi Waldron, Nicola Segata Shotgun metagenomic analysis of the human associated microbiome provides a rich set of microbial features for prediction and biomarker discovery in the context of human diseases and health conditions. However, the use of such high-resolution microbial features presents new challenges, and validated computational tools for learning tasks are lacking. Moreover, classification rules have scarcely been validated in independent studies, posing questions about the generality and generalization of disease-predictive models across cohorts. In this paper, we comprehensively assess approaches to metagenomics-based prediction tasks and for quantitative assessment of the strength of potential microbiome-phenotype associations. We develop a computational framework for prediction tasks using quantitative microbiome profiles, including species-level relative abundances and presence of strain-specific markers. A comprehensive meta-analysis, with particular emphasis on generalization across cohorts, was performed in a collection of 2424 publicly available metagenomic samples from eight large-scale studies. Cross-validation revealed good disease-prediction capabilities, which were in general improved by feature selection and use of strain-specific markers instead of species-level taxonomic abundance. In cross-study analysis, models transferred between studies were in some cases less accurate than models tested by within-study cross-validation. Interestingly, the addition of healthy (control) samples from other studies to training sets improved disease prediction capabilities. Some microbial species (most notably Streptococcus anginosus ) seem to characterize general dysbiotic states of the microbiome rather than connections with a specific disease. Our results in modelling features of the “healthy” microbiome can be considered a first step toward defining general microbial dysbiosis. The software framework, microbiome profiles, and metadata for thousands of samples are publicly available at http://segatalab.cibio.unitn.it/tools/metaml.
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    Dynamics of the Fouling Layer Microbial Community in a Membrane Bioreactor (2016)
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    Publication Date: 2016-07-12
    Description: by Anja S. Ziegler, Simon J. McIlroy, Poul Larsen, Mads Albertsen, Aviaja A. Hansen, Nicolas Heinen, Per Halkjær Nielsen Membrane fouling presents the greatest challenge to the application of membrane bioreactor (MBR) technology. Formation of biofilms on the membrane surface is the suggested cause, yet little is known of the composition or dynamics of the microbial community responsible. To gain an insight into this important question, we applied 16S rRNA gene amplicon sequencing with a curated taxonomy and fluorescent in situ hybridization to monitor the community of a pilot-scale MBR carrying out enhanced biological nitrogen and phosphorus removal with municipal wastewater. In order to track the dynamics of the fouling process, we concurrently investigated the communities of the biofilm, MBR bulk sludge, and the conventional activated sludge system used to seed the MBR system over several weeks from start-up. As the biofilm matured the initially abundant betaproteobacterial genera Limnohabitans , Hydrogenophaga and Malikia were succeeded by filamentous Chloroflexi and Gordonia as the abundant species. This study indicates that, although putative pioneer species appear, the biofilm became increasingly similar to the bulk community with time. This suggests that the microbial population in bulk water will largely determine the community structure of the mature biofilm.
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    Sexual Dimorphism in Adverse Pregnancy Outcomes - A Retrospective Australian Population Study 1981-2011 (2016)
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    Publication Date: 2016-07-12
    Description: by Petra E. Verburg, Graeme Tucker, Wendy Scheil, Jan Jaap H. M. Erwich, Gus A. Dekker, Claire Trelford Roberts Objectives Sexual inequality starts in utero . The contribution of biological sex to the developmental origins of health and disease is increasingly recognized. The aim of this study was to assess and interpret sexual dimorphisms for three major adverse pregnancy outcomes which affect the health of the neonate, child and potentially adult. Methods Retrospective population-based study of 574,358 South Australian singleton live births during 1981–2011. The incidence of three major adverse pregnancy outcomes [preterm birth (PTB), pregnancy induced hypertensive disorders (PIHD) and gestational diabetes mellitus (GDM)] in relation to fetal sex was compared according to traditional and fetus-at-risk (FAR) approaches. Results The traditional approach showed male predominance for PTB [20–24 weeks: Relative Risk (RR) M/F 1.351, 95%-CI 1.274–1.445], spontaneous PTB [25–29 weeks: RR M/F 1.118, 95%-CI 1.044–1.197%], GDM [RR M/F 1.042, 95%-CI 1.011–1.074], overall PIHD [RR M/F 1.053, 95%-CI 1.034–1.072] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044–1.105]. The FAR approach showed that males were at increased risk for PTB [20–24 weeks: RR M/F 1.273, 95%-CI 1.087–1.490], for spontaneous PTB [25–29 weeks: RR M/F 1.269, 95%-CI 1.143–1.410] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044–1.105%]. The traditional approach demonstrated female predominance for iatrogenic PTB [25–29 weeks: RR M/F 0.857, 95%-CI 0.780–0.941] and PIHD associated with PTB [25–29 weeks: RR M/F 0.686, 95%-CI 0.581–0.811]. The FAR approach showed that females were at increased risk for PIHD with PTB [25–29 weeks: RR M/F 0.779, 95%-CI 0.648–0.937]. Conclusions This study confirms the presence of sexual dimorphisms and presents a coherent framework based on two analytical approaches to assess and interpret the sexual dimorphisms for major adverse pregnancy outcomes. The mechanisms by which these occur remain elusive, but sex differences in placental gene expression and function are likely to play a key role. Further research on sex differences in placental function and maternal adaptation to pregnancy is required to delineate the causal molecular mechanisms in sex-specific pregnancy outcome. Identifying these mechanisms may inform fetal sex specific tailored antenatal and neonatal care.
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    Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control (2016)
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    Publication Date: 2016-07-12
    Description: by Harald Schrem, Valentin Schneider, Marlene Kurok, Alon Goldis, Maren Dreier, Alexander Kaltenborn, Wilfried Gwinner, Marc Barthold, Jan Liebeneiner, Markus Winny, Jürgen Klempnauer, Moritz Kleine Background The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G-chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers. Patients and Methods 1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized-incidence-ratios (SIRs) of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G-chart analysis was applied to determine relevant differences in the frequency of cancer occurrences. Results Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33–3.21). Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46), post-transplant lymphoproliferative disorder (SIR = 8.36), prostate cancer (SIR = 2.22), bladder cancer (SIR = 3.24), thyroid cancer (SIR = 10.13) and melanoma (SIR = 3.08). Independent pre-transplant risk factors for cancer-free survival were age 62.6 years (p = 0.001, HR: 1.29), polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD) (p = 0.001, HR: 0.68), high body mass index in kg/m 2 (p
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    Dynamic Bcl-xL (S49) and (S62) Phosphorylation/Dephosphorylation during Mitosis Prevents Chromosome Instability and Aneuploidy in Normal Human Diploid Fibroblasts (2016)
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    Publication Date: 2016-07-12
    Description: by Prasamit Saurav Baruah, Myriam Beauchemin, Josée Hébert, Richard Bertrand Bcl-xL proteins undergo dynamic phosphorylation/dephosphorylation on Ser49 and Ser62 residues during mitosis. The expression of Bcl-xL(S49A), (S62A) and dual (S49/62A) phosphorylation mutants in tumor cells lead to severe mitotic defects associated with multipolar spindle, chromosome lagging and bridging, and micro-, bi- and multi-nucleated cells. Because the above observations were made in tumor cells which already display genomic instability, we now address the question: will similar effects occur in normal human diploid cells? We studied normal human diploid BJ foreskin fibroblast cells expressing Bcl-xL (wild type), (S49A), (S49D), (S62A), (S62D) and the dual-site (S49/62A) and (S49/62D) mutants. Cells expressing S49 and/or S62 phosphorylation mutants showed reduced kinetics of cell population doubling. These effects on cell population doubling kinetics correlated with early outbreak of senescence with no impact on the cell death rate. Senescent cells displayed typical senescence-associated phenotypes including high-level of senescence-associated β-galactosidase activity, interleukin-6 (IL-6) secretion, tumor suppressor p53 and cyclin-dependent kinase inhibitor p21Waf1/Cip1 activation as well as γH2A.X-associated nuclear chromatin foci. Fluorescence in situ hybridization analysis and Giemsa-banded karyotypes revealed that the expression of Bcl-xL phosphorylation mutants in normal diploid BJ cells provoked chromosome instability and aneuploidy. These findings suggest that dynamic Bcl-xL(S49) and (S62) phosphorylation/dephosphorylation cycles are important in the maintenance of chromosome integrity during mitosis in normal cells. They could impact future strategies aiming to develop and identify compounds that could target not only the anti-apoptotic domain of Bcl-xL protein, but also its mitotic domain for cancer therapy.
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    Abundant NDRG2 Expression Is Associated with Aggressiveness and Unfavorable Patients’ Outcome in Basal-Like Breast Cancer (2016)
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    Publication Date: 2016-07-12
    Description: by Vera Kloten, Martin Schlensog, Julian Eschenbruch, Janina Gasthaus, Janina Tiedemann, Jolein Mijnes, Timon Heide, Till Braunschweig, Ruth Knüchel, Edgar Dahl NDRG2 , a member of the N-myc downstream-regulated gene family, is thought to be a putative tumor suppressor gene with promising clinical impact in breast cancer. Since breast cancer comprises heterogeneous intrinsic subtypes with distinct clinical outcomes we investigated the pivotal role of NDRG2 in basal-type breast cancers. Based on subtype classified tumor (n = 45) and adjacent normal tissues (n = 17) we examined NDRG2 mRNA expression and CpG-hypermethylation, whose significance was further validated by independent data sets from The Cancer Genome Atlas (TCGA). In addition, NDRG2 protein expression was evaluated immunohistochemically using a tissue micro array (TMA, n = 211). In vitro , we investigated phenotypic effects caused by NDRG2 silencing in the basal A-like HCC1806 as well as NDRG2 over-expression in basal A-like BT20 compared to luminal-type MCF7 breast cancer cells. Our tissue collections demonstrated an overall low NDRG2 mRNA expression in breast cancer subtypes compared to normal breast tissue in line with an increased CpG-hypermethylation in breast cancer tissue. Independent TCGA data sets verified a significant (P
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    Exenatide Treatment Alone Improves β-Cell Function in a Canine Model of Pre-Diabetes (2016)
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    Publication Date: 2016-07-12
    Description: by Viorica Ionut, Orison O. Woolcott, Hasmik J. Mkrtchyan, Darko Stefanovski, Morvarid Kabir, Malini S. Iyer, Huiwen Liu, Ana V. B. Castro, Qiang Wu, Josiane L. Broussard, Cathryn M. Kolka, Isaac Asare-Bediako, Richard N. Bergman Background Exenatide’s effects on glucose metabolism have been studied extensively in diabetes but not in pre-diabetes. Objective We examined the chronic effects of exenatide alone on glucose metabolism in pre-diabetic canines. Design and Methods After 10 weeks of high-fat diet (HFD), adult dogs received one injection of streptozotocin (STZ, 18.5 mg/kg). After induction of pre-diabetes, while maintained on HFD, animals were randomized to receive either exenatide (n = 7) or placebo (n = 7) for 12 weeks. β-Cell function was calculated from the intravenous glucose tolerance test (IVGTT, expressed as the acute insulin response, AIR G ), the oral glucose tolerance test (OGTT, insulinogenic index) and the graded-hyperglycemic clamp (clamp insulinogenic index). Whole-body insulin sensitivity was assessed by the IVGTT. At the end of the study, pancreatic islets were isolated to assess β-cell function in vitro . Results OGTT: STZ caused an increase in glycemia at 120 min by 22.0% (interquartile range, IQR, 31.5%) (P = 0.011). IVGTT: This protocol also showed a reduction in glucose tolerance by 48.8% (IQR, 36.9%) (P = 0.002). AIR G decreased by 54.0% (IQR, 40.7%) (P = 0.010), leading to mild fasting hyperglycemia (P = 0.039). Exenatide, compared with placebo, decreased body weight (P
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    Development of a Korean Fracture Risk Score (KFRS) for Predicting Osteoporotic Fracture Risk: Analysis of Data from the Korean National Health Insurance Service (2016)
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    Publication Date: 2016-07-12
    Description: by Ha Young Kim, Eun Jin Jang, ByeongJu Park, Tae-Young Kim, Soon-Ae Shin, Yong-Chan Ha, Sunmee Jang Background Asian-specific prediction models for estimating individual risk of osteoporotic fractures are rare. We developed a Korean fracture risk prediction model using clinical risk factors and assessed validity of the final model. Methods A total of 718,306 Korean men and women aged 50–90 years were followed for 7 years in a national system-based cohort study. In total, 50% of the subjects were assigned randomly to the development dataset and 50% were assigned to the validation dataset. Clinical risk factors for osteoporotic fracture were assessed at the biennial health check. Data on osteoporotic fractures during the follow-up period were identified by ICD-10 codes and the nationwide database of the National Health Insurance Service (NHIS). Results During the follow-up period, 19,840 osteoporotic fractures were reported (4,889 in men and 14,951 in women) in the development dataset. The assessment tool called the Korean Fracture Risk Score (KFRS) is comprised of a set of nine variables, including age, body mass index, recent fragility fracture, current smoking, high alcohol intake, lack of regular exercise, recent use of oral glucocorticoid, rheumatoid arthritis, and other causes of secondary osteoporosis. The KFRS predicted osteoporotic fractures over the 7 years. This score was validated using an independent dataset. A close relationship with overall fracture rate was observed when we compared the mean predicted scores after applying the KFRS with the observed risks after 7 years within each 10th of predicted risk. Conclusion We developed a Korean specific prediction model for osteoporotic fractures. The KFRS was able to predict risk of fracture in the primary population without bone mineral density testing and is therefore suitable for use in both clinical setting and self-assessment. The website is available at http://www.nhis.or.kr.
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    Testing Cross-Cultural Generalizability of the Task and Ego Orientation in Sport Questionnaire across American and Chinese Samples (2016)
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    Publication Date: 2016-07-12
    Description: by Cecilia Ma, Eva Monsma This paper examines the factor structure and measurement invariance of the Task and Ego Orientation in Sport Questionnaire (TEOSQ) across American and Chinese samples. Results based on the mean and covariance structure analyses supported configural invariance, metric invariance and scalar invariance across groups. Latent means analyses revealed that American sample had significantly higher mean scores on task and ego orientations than the Chinese sample. The findings suggest that the TEOSQ is a valid and reliable instrument in assessing achievement motivation across these two diverse populations.
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    Low Prognostic Nutritional Index (PNI) Predicts Unfavorable Distant Metastasis-Free Survival in Nasopharyngeal Carcinoma: A Propensity Score-Matched Analysis (2016)
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    Publication Date: 2016-07-12
    Description: by Lin Yang, Liangping Xia, Yan Wang, Shaodong Hong, Haiyang Chen, Shaobo Liang, Peijian Peng, Yong Chen Background Poor nutritional status is associated with progression and advanced disease in patients with cancer. The prognostic nutritional index (PNI) may represent a simple method of assessing host immunonutritional status. This study was designed to investigate the prognostic value of the PNI for distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC). Methods A training cohort of 1,168 patients with non-metastatic NPC from two institutions was retrospectively analyzed. The optimal PNI cutoff value for DMFS was identified using the online tool “Cutoff Finder”. DMFS was analyzed using stratified and adjusted analysis. Propensity score-matched analysis was performed to balance baseline characteristics between the high and low PNI groups. Subsequently, the prognostic value of the PNI for DMFS was validated in an external validation cohort of 756 patients with NPC. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of different prognostic scores. Results The optimal PNI cutoff value was determined to be 51. Low PNI was significantly associated with poorer DMFS than high PNI in univariate analysis (P
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    Relationship between Fetuin A, Vascular Calcification and Fracture Risk in Dialysis Patients (2016)
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    Publication Date: 2016-07-12
    Description: by Hung Yuan Chen, Yen Ling Chiu, Shih Ping Hsu, Mei Fen Pai, Ju Yeh Yang, Yu Sen Peng Background Fractures are a common morbidity that lead to worse outcomes in dialysis patients. Fetuin A inhibits vascular calcification (VC), potentially promotes bone mineralization and its level positively correlates with bone mineral density in the general population. On the other hand, the presence of VC is associated with low bone volume in dialysis patients. Whether the fetuin A level and VC can predict the occurrence of fractures in dialysis patients remains unknown. Methods We performed this prospective, observational cohort study including 685 dialysis patients (629 hemodialysis and 56 peritoneal dialysis) from a single center in Taiwan for a median follow-up period of 3.4 years. The baseline fetuin A level and status of presence of aortic arch calcification (VC) and incidence of major fractures (hip, pelvis, humerus, proximal forearm, lower leg or vertebrae) were assessed using adjusted Cox proportional hazards models, recursive partitioning analysis and competing risk models. Results Overall, 177 of the patients had major fractures. The incidence rate of major fractures was 3.29 per 100 person-years. In adjusted analyses, the patients with higher baseline fetuin A levels had a lower incidence of fractures (adjusted hazard ratio (HR), 0.3; 95% CI, 0.18‒0.5, fetuin A tertile 3 vs . tertile 1 and HR, 0.52; 95% CI, 0.34‒0.78, tertile 2 vs . tertile 1). The presence of aortic arch calcification (VC) independently predicted the occurrence of fractures (adjusted HR, 1.95; 95% CI, 1.34‒2.84) as well. When accounting for death as an event in competing risk models, the patients with higher baseline fetuin A levels remained to have a lower incidence of fractures (SHR, 0.31; 95% CI, 0.17‒0.56, fetuin A tertile 3 vs . tertile 1 and 0.51; 95% CI, 0.32‒0.81, tertile 2 vs . tertile 1). Interpretations Lower baseline fetuin A levels and the presence of VC were independently linked to higher risk of incident fractures in prevalent dialysis patients.
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    Structure and Function of the Su(H)-Hairless Repressor Complex, the Major Antagonist of Notch Signaling in Drosophila melanogaster (2016)
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    Publication Date: 2016-07-13
    Description: by Zhenyu Yuan, Heiko Praxenthaler, Nassif Tabaja, Rubben Torella, Anette Preiss, Dieter Maier, Rhett A. Kovall Notch is a conserved signaling pathway that specifies cell fates in metazoans. Receptor-ligand interactions induce changes in gene expression, which is regulated by the transcription factor CBF1/Su(H)/Lag-1 (CSL). CSL interacts with coregulators to repress and activate transcription from Notch target genes. While the molecular details of the activator complex are relatively well understood, the structure-function of CSL-mediated repressor complexes is poorly defined. In Drosophila , the antagonist Hairless directly binds Su(H) (the fly CSL ortholog) to repress transcription from Notch targets. Here, we determine the X-ray structure of the Su(H)-Hairless complex bound to DNA. Hairless binding produces a large conformational change in Su(H) by interacting with residues in the hydrophobic core of Su(H), illustrating the structural plasticity of CSL molecules to interact with different binding partners. Based on the structure, we designed mutants in Hairless and Su(H) that affect binding, but do not affect formation of the activator complex. These mutants were validated in vitro by isothermal titration calorimetry and yeast two- and three-hybrid assays. Moreover, these mutants allowed us to solely characterize the repressor function of Su(H) in vivo.
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    Differential Insulin Secretion of High-Fat Diet-Fed C57BL/6NN and C57BL/6NJ Mice: Implications of Mixed Genetic Background in Metabolic Studies (2016)
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    Publication Date: 2016-07-13
    Description: by Camille Attané, Marie-Line Peyot, Roxane Lussier, Dongwei Zhang, Erik Joly, S. R. Murthy Madiraju, Marc Prentki Many metabolic studies employ tissue-specific gene knockout mice, which requires breeding of floxed gene mice, available mostly on C57BL/6N (NN) genetic background, with cre or Flp recombinase-expressing mice, available on C57BL/6J (JJ) background, resulting in the generation of mixed C57BL/6NJ (NJ) genetic background mice. Recent awareness of many genetic differences between NN and JJ strains including the deletion of nicotinamide nucleotide transhydrogenase ( nnt ), necessitates examination of the consequence of mixed NJ background on glucose tolerance, beta cell function and other metabolic parameters. Male mice with NN and NJ genetic background were fed with normal or high fat diets (HFD) for 12 weeks and glucose and insulin homeostasis were studied. Genotype had no effect on body weight and food intake in mice fed normal or high fat diets. Insulinemia in the fed and fasted states and after a glucose challenge was lower in HFD-fed NJ mice, even though their glycemia and insulin sensitivity were similar to NN mice. NJ mice showed mild glucose intolerance. Moreover, glucose- but not KCl-stimulated insulin secretion in isolated islets was decreased in HFD-fed NJ vs NN mice without changes in insulin content and beta cell mass. Under normal diet, besides reduced fed insulinemia, NN and NJ mice presented similar metabolic parameters. However, HFD-fed NJ mice displayed lower fed and fasted insulinemia and glucose-induced insulin secretion in vivo and ex vivo , as compared to NN mice. These results strongly caution against using unmatched mixed genetic background C57BL/6 mice for comparisons, particularly under HFD conditions.
    Electronic ISSN: 1932-6203
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    Glucocorticoids Alter CRTC-CREB Signaling in Muscle Cells: Impact on PGC-1α Expression and Atrophy Markers (2016)
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    Publication Date: 2016-07-13
    Description: by Jill A. Rahnert, Bin Zheng, Matthew B. Hudson, Myra E. Woodworth-Hobbs, S. Russ Price Muscle wasting associated with chronic diseases has been linked to decreased expression of PGC-1α and overexpression of PGC-1α counters muscle loss. CREB, in conjunction with the CREB-regulated transcription coactivator (CRTC2), is a positive modulator of PGC-1α transcription. We previously reported that PGC-1α expression is decreased in skeletal muscle of diabetic rats despite a high level of CREB phosphorylation (i.e., activation), suggesting that CRTC2-CREB signaling may be dysregulated. In this study, the relationship between CREB/CRTC signaling and PGC-1α expression was examined in L6 myotubes treated with dexamethasone (Dex, 48h) to induce atrophy. Dex decreased PGC-1α mRNA and protein as well as the levels of CRTC1 and CRTC2 in the nucleus. Dex also altered the nuclear levels of two known regulators of CRTC2 localization; the amount of calcinuerin catalytic A subunit (CnA) was decreased whereas SIK was increased. To assess PGC-1α transcription, muscle cells were transfected with a PGC-1α luciferase reporter plasmid (PGC-1α-Luc). Dex suppressed PGC-1α luciferase activity while both isobutylmethylxanthine (IBMX) and over-expression of CRTC1 or CRTC2 increased PGC-1α-Luc activity. Mutation of the CRE binding site from PGC-1α-Luc reporter attenuated the responses to both IBMX and the CRTC proteins. Consistent with the reporter gene results, overexpression of CRTC2 produced an increase in CRTC2 in the nucleus and in PGC-1α mRNA and PGC-1α protein. Overexpression of CRTC2 was not sufficient to prevent the decrease in PGC-1α mRNA or protein by Dex. In summary, these data suggest that attenuated CREB/CRTC signaling contributes to the decrease in PGC-1α expression during atrophy.
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    Correction: Metformin Induces Cell Cycle Arrest, Reduced Proliferation, Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients (2016)
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    Publication Date: 2016-07-13
    Description: by Fatima Ochoa-Gonzalez, Alberto R. Cervantes-Villagrana, Julio C. Fernandez-Ruiz, Hilda S. Nava-Ramirez, Adriana C. Hernandez-Correa, Jose A. Enciso-Moreno, Julio E. Castañeda-Delgado
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    Structures of Gate Loop Variants of the AcrB Drug Efflux Pump Bound by Erythromycin Substrate (2016)
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    Publication Date: 2016-07-13
    Description: by Abdessamad Ababou, Vassilis Koronakis Gram-negative bacteria such as E . coli use tripartite efflux pumps such as AcrAB-TolC to expel antibiotics and noxious compounds. A key feature of the inner membrane transporter component, AcrB, is a short stretch of residues known as the gate/switch loop that divides the proximal and distal substrate binding pockets. Amino acid substitutions of the gate loop are known to decrease antibiotic resistance conferred by AcrB. Here we present two new AcrB gate loop variants, the first stripped of its bulky side chains, and a second in which the gate loop is removed entirely. By determining the crystal structures of the variant AcrB proteins in the presence and absence of erythromycin and assessing their ability to confer erythromycin tolerance, we demonstrate that the gate loop is important for AcrB export activity but is not required for erythromycin binding.
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    Gene Expression and DNA Methylation Status of Glutathione S -Transferase Mu1 and Mu5 in Urothelial Carcinoma (2016)
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    Publication Date: 2016-07-13
    Description: by Shou-Chieh Wang, Chin-Chin Huang, Cheng-Huang Shen, Lei-Chen Lin, Pei-Wen Zhao, Shih-Ying Chen, Yu-Chiao Deng, Yi-Wen Liu Bladder cancer is highly recurrent after therapy, which has an enormous impact on the health and financial condition of the patient. It is worth developing diagnostic tools for bladder cancer. In our previous study, we found that the bladder carcinogen BBN increased urothelial global DNA CpG methylation and decreased GSTM1 protein expression in mice. Here, the correlation of BBN-decreased GSTM1 and GSTM gene CpG methylation status was analyzed in mice bladders. BBN treatment decreased the protein and mRNA expression of GSTM1, and the CpG methylation ratio of GSTM1 gene promoter was slightly increased in mice bladders. Unlike mouse GSTM1, the human GSTM1 gene tends to be deleted in bladder cancers. Among 7 human bladder cancer cell lines, GSTM1 gene is really null in 6 cell lines except one, T24 cells. The CpG methylation level of GSTM1 was 9.9% and 5-aza-dC did not significantly increase GSTM1 protein and mRNA expression in T24 cells; however, the GSTM5 gene was CpG hypermethylated (65.4%) and 5-aza-dC also did not affect the methylation ratio and mRNA expression. However, in other cell lines without GSTM1, 5-aza-dC increased GSTM5 expression and decreased its CpG DNA methylation ratio from 84.6% to 61.5% in 5637, and from 97.4% to 75% in J82 cells. In summary, two biomarkers of bladder tumor were provided. One is the GSTM1 gene which is down-regulated in mice bladder carcinogenesis and is usually deleted in human urothelial carcinoma, while the other is the GSTM5 gene, which is inactivated by DNA CpG methylation.
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    What Medical Oncologist Residents Think about the Italian Speciality Schools: A Survey of the Italian Association of Medical Oncology (AIOM) on Educational, Clinical and Research Activities (2016)
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    Publication Date: 2016-07-13
    Description: by Anna Moretti, Michele Ghidini, Carmine De Angelis, Matteo Lambertini, Chiara Cremolini, Martina Imbimbo, Rossana Berardi, Massimo Di Maio, Stefano Cascinu, Nicla La Verde Background and objectives Relevant heterogeneity exists among Postgraduate Schools in Medical Oncology, also within the same country. In order to provide a comprehensive overview of the landscape of Italian Postgraduate Schools in Medical Oncology, the Italian Association of Medical Oncology (AIOM) undertook an online survey, inviting all the residents to describe their daily activities and to express their overall satisfaction about their programs. Methods A team composed of five residents and three consultants in medical oncology prepared a 38 items questionnaire that was published online in a reserved section, accessible through a link sent by e-mail. Residents were invited to anonymously fill in the questionnaire that included the following sub-sections: quality of teaching, clinical and research activity, overall satisfaction. Results Three-hundred and eleven (57%) out of 547 invited residents filled in the questionnaire. Two-hundred and twenty-three (72%) participants declared that attending lessons was frequently difficult and 153 (49%) declared they did not gain substantial improvement in their knowledge from them. Fifty-five percent stated that they did not receive lessons on palliative care. Their overall judgment about didactic activity was low in 63% of the interviewed. The satisfaction for clinical activity was in 86% of cases good: 84% recognized that, during the training period, they acquired a progressive independence on patients' management. About research activity, the majority (79%) of participants in the survey was actively engaged in managing patients included in clinical trials but the satisfaction level for the involvement in research activities was quite low (54%). Overall, 246 residents (79%) gave a positive global judgment of their Medical Oncology Schools. Conclusions The landscape of Italian Postgraduate Schools in Medical Oncology is quite heterogeneous across the country. Some improvements in the organization of teaching and in the access to research opportunity are needed; the perception about clinical activity and the overall judgment of the programs are quite satisfactory.
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    Identification and Validation of Loci Governing Seed Coat Color by Combining Association Mapping and Bulk Segregation Analysis in Soybean (2016)
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    Publication Date: 2016-07-13
    Description: by Jian Song, Zhangxiong Liu, Huilong Hong, Yansong Ma, Long Tian, Xinxiu Li, Ying-Hui Li, Rongxia Guan, Yong Guo, Li-Juan Qiu Soybean seed coat exists in a range of colors from yellow, green, brown, black, to bicolor. Classical genetic analysis suggested that soybean seed color was a moderately complex trait controlled by multi-loci. However, only a couple of loci could be detected using a single biparental segregating population. In this study, a combination of association mapping and bulk segregation analysis was employed to identify genes/loci governing this trait in soybean. A total of 14 loci, including nine novel and five previously reported ones, were identified using 176,065 coding SNPs selected from entire SNP dataset among 56 soybean accessions. Four of these loci were confirmed and further mapped using a biparental population developed from the cross between ZP95-5383 (yellow seed color) and NY279 (brown seed color), in which different seed coat colors were further dissected into simple trait pairs (green/yellow, green/black, green/brown, yellow/black, yellow/brown, and black/brown) by continuously developing residual heterozygous lines. By genotyping entire F 2 population using flanking markers located in fine-mapping regions, the genetic basis of seed coat color was fully dissected and these four loci could explain all variations of seed colors in this population. These findings will be useful for map-based cloning of genes as well as marker-assisted breeding in soybean. This work also provides an alternative strategy for systematically isolating genes controlling relative complex trait by association analysis followed by biparental mapping.
    Electronic ISSN: 1932-6203
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    Timescale- and Sensory Modality-Dependency of the Central Tendency of Time Perception (2016)
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    Publication Date: 2016-07-13
    Description: by Yuki Murai, Yuko Yotsumoto When individuals are asked to reproduce intervals of stimuli that are intermixedly presented at various times, longer intervals are often underestimated and shorter intervals overestimated. This phenomenon may be attributed to the central tendency of time perception, and suggests that our brain optimally encodes a stimulus interval based on current stimulus input and prior knowledge of the distribution of stimulus intervals. Two distinct systems are thought to be recruited in the perception of sub- and supra-second intervals. Sub-second timing is subject to local sensory processing, whereas supra-second timing depends on more centralized mechanisms. To clarify the factors that influence time perception, the present study investigated how both sensory modality and timescale affect the central tendency. In Experiment 1, participants were asked to reproduce sub- or supra-second intervals, defined by visual or auditory stimuli. In the sub-second range, the magnitude of the central tendency was significantly larger for visual intervals compared to auditory intervals, while visual and auditory intervals exhibited a correlated and comparable central tendency in the supra-second range. In Experiment 2, the ability to discriminate sub-second intervals in the reproduction task was controlled across modalities by using an interval discrimination task. Even when the ability to discriminate intervals was controlled, visual intervals exhibited a larger central tendency than auditory intervals in the sub-second range. In addition, the magnitude of the central tendency for visual and auditory sub-second intervals was significantly correlated. These results suggest that a common modality-independent mechanism is responsible for the supra-second central tendency, and that both the modality-dependent and modality-independent components of the timing system contribute to the central tendency in the sub-second range.
    Electronic ISSN: 1932-6203
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    Recombinant HLA-G as Tolerogenic Immunomodulant in Experimental Small Bowel Transplantation (2016)
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    Publication Date: 2016-07-13
    Description: by Martin W. von Websky, Koji Kitamura, Isis Ludwig-Portugall, Christian Kurts, Maximilian von Laffert, Joel LeMaoult, Edgardo D. Carosella, Kareem Abu-Elmagd, Joerg C. Kalff, Nico Schäfer The non-classical MHC I paralogue HLA-G is expressed by cytotrophoblast cells and implicated with fetomaternal tolerance by downregulating the maternal adaptive and innate immune response against the fetus. HLA-G expression correlates with favorable graft outcome in humans and recently promising immunosuppressive effects of therapeutic HLA-G in experimental transplantation (skin allograft acceptance) were shown. Consequently, we examined this novel therapeutic approach in solid organ transplantation. In this study, therapeutic recombinant HLA-G5 was evaluated for the first time in a solid organ model of acute rejection (ACR) after orthotopic intestinal transplantation (ITX). Allogenic ITX was performed in rats (Brown Norway to Lewis) with and without HLA-G treatment. It was found that HLA-G treatment significantly reduced histologically proven ACR at both an early and late postoperative timepoint (POD 4/7), concomitant to a functionally preserved graft contractility at POD 7. Interestingly, graft infiltration by myeloperoxidase+ cells was significantly reduced at POD7 by HLA-G treatment. Moreover, HLA-G treatment showed an effect on the allogenic T-cell immune response as assessed by flow cytometry: The influx of recipient-derived CD8 + T-cells into the graft mesenteric lymphnodes at POD7 was significantly reduced while CD4 + populations were not affected. As a potential mechanism of action, an induction of T-reg populations in the mesenteric lymphnodes was postulated, but flow cytometric analysis of classical CD4 + /CD25 + /FoxP3 + T reg -cells showed no significant alteration by HLA-G treatment. The novel therapeutic approach using recombinant HLA-G5 reported herein demonstrates a significant immunosuppressive effect in this model of allogenic experimental intestinal transplantation. This effect may be mediated via inhibition of recipient-derived CD8 + T-cell populations either directly or by induction of non-classical T reg populations.
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    An Acoustic Analysis of the Genus Microhyla (Anura: Microhylidae) of Sri Lanka (2016)
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    Publication Date: 2016-07-13
    Description: by Nayana Wijayathilaka, Madhava Meegaskumbura Vocalizing behavior of frogs and toads, once quantified, is useful for systematics, rapid species identification, behavioral experimentation and conservation monitoring. But yet, for many lineages vocalizations remain unknown or poorly quantified, especially in diversity rich tropical regions. Here we provide a quantitative acoustical analysis for all four Sri Lankan congeners of the genus Microhyla . Three of these species are endemic to the island, but Microhyla ornata is regionally widespread. Two of these endemics, M . karunaratnei (Critically Endangered) and M . zeylanica (Endangered), are highly threatened montane isolates; the other, M . mihintalei , is relatively common across the dry lowlands. We recorded and analyzed 100 advertisement calls from five calling males for each species, except for M . zeylanica , which only had 53 calls from three males suitable for analyses. All four species call in choruses and their vocal repertoires are simple compared to most frogs. Their calls contain multiple pulses and no frequency modulation. We quantified eight call characters. Call duration and number of pulses were higher for the two montane isolates (inhabiting cooler habitats at higher altitudes) compared to their lowland congeners. Microhyla zeylanica has the longest call duration (of 1.8 ± 0.12 s) and the highest number of pulses (of 61–92 pulses). The smallest of the species, Microhyla karunaratnei (16.2–18.3 mm), has the highest mean dominant frequency (3.3 ± 0.14 kHz) and pulse rate (77 ± 5.8 pulses per second). The calls separate well in the Principal Component space: PC1 axis is mostly explained by the number of pulses per call and call duration; PC2 is mostly explained by the pulse rate. A canonical means plot of a Discriminant Function analysis shows non-overlapping 95% confidence ellipses. This suggests that some call parameters can be used to distinguish these species effectively. We provide detailed descriptions for eight call properties and compare these with congeners for which data is available. This work provides a foundation for comparative bioacoustic analyses and species monitoring while facilitating the systematics of Microhyla across its range.
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    Antigen Uptake during Different Life Stages of Zebrafish ( Danio rerio ) Using a GFP-Tagged Yersinia ruckeri (2016)
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    Publication Date: 2016-07-13
    Description: by Rozalia Korbut, Foojan Mehrdana, Per Walter Kania, Marianne Halberg Larsen, Dorte Frees, Inger Dalsgaard, Louise von Gersdorff Jørgensen Immersion-vaccines (bacterins) are routinely used for aquacultured rainbow trout to protect against Yersinia ruckeri (Yr). During immersion vaccination, rainbow trout take up and process the antigens, which induce protection. The zebrafish was used as a model organism to study uptake mechanisms and subsequent antigen transport in fish. A genetically modified Yr was developed to constitutively express green fluorescent protein (GFP) and was used for bacterin production. Larval, juvenile and adult transparent zebrafish (tra:nac mutant) received a bath in the bacterin for up to 30 minutes. Samples were taken after 1 min, 15 min, 30 min, 2 h, 12 h and 24 h. At each sampling point fish were used for live imaging of the uptake using a fluorescence stereomicroscope and for immunohistochemistry (IHC). In adult fish, the bacterin could be traced within 30 min in scale pockets, skin, oesophagus, intestine and fins. Within two hours post bath (pb) Yr-antigens were visible in the spleen and at 24 h in liver and kidney. Bacteria were associated with the gills, but uptake at this location was limited. Antigens were rarely detected in the blood and never in the nares. In juvenile fish uptake of the bacterin was seen in the intestine 30 min pb and in the nares 2 hpb but never in scale pockets. Antigens were detected in the spleen 12 hpb. Zebrafish larvae exhibited major Yr uptake only in the mid-intestine enterocytes 24 hpb. The different life stages of zebrafish varied with regard to uptake locations, however the gut was consistently a major uptake site. Zebrafish and rainbow trout tend to have similar uptake mechanisms following immersion or bath vaccination, which points towards zebrafish as a suitable model organism for this aquacultured species.
    Electronic ISSN: 1932-6203
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    Identification of Specific miRNA Signature in Paired Sera and Tissue Samples of Indian Women with Triple Negative Breast Cancer (2016)
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    Publication Date: 2016-07-13
    Description: by Seema Thakur, Rajesh K. Grover, Sanjay Gupta, Ajay K. Yadav, Bhudev C. Das Of several subtypes of breast cancer, triple negative breast cancer (TNBC) is a highly aggressive tumor that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor receptor 2 and shows a worst prognosis. The small noncoding RNAs (miRNAs) considered as master regulator of gene expression play a key role in cancer initiation, progression and drug resistance and have emerged as attractive molecular biomarkers for diagnosis, prognosis and treatment targets in cancer. We have done expression profiling of selected miRNAs in paired serum and tissue samples of TNBC patients and corresponding cell lines and compared with that of other subtypes, in order to identify novel serum miRNA biomarkers for early detection and progression of TNBC. A total of 85 paired tumor tissues and sera with an equal number of adjacent normal tissue margins and normal sera from age matched healthy women including tissue and sera samples from 15 benign fibroadenomas were employed for the study. We report for the first time an extremely high prevalence (73.9%) of TNBC in premenopausal women below 35 years of age and a significant altered expression of a panel of three specific oncogenic miRNAs- miR-21, miR-221, miR-210, and three tumor suppressor miRNAs- miR-195, miR-145 and Let-7a in both tissues and corresponding sera of TNBC patients when compared with triple positive breast cancer (TPBC) patients. While miR-21, miR-221 and miR-210 showed significant over-expression, miR-195 and miR-145 were downregulated and well correlated with various clinicopathological and demographic risk factors, tumor grade, clinical stage and hormone receptor status. Interestingly, despite being a known tumor suppressor, Let-7a showed a significant overexpression in TNBCs. It is suggested that this panel of six miRNA signature may serve as a minimally invasive biomarker for an early detection of TNBC patients.
    Electronic ISSN: 1932-6203
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    Dermal γδ T-Cells Can Be Activated by Mitochondrial Damage-Associated Molecular Patterns (2016)
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    Publication Date: 2016-07-13
    Description: by Martin G. Schwacha, Meenakshi Rani, Susannah E. Nicholson, Aaron M. Lewis, Travis L. Holloway, Salvador Sordo, Andrew P. Cap Background Gamma delta T-cells have been shown to be important to the early immunoinflammatory response to injury, independent of infection. This unique T-cell population acts to regulate cell trafficking and the release of cytokines and growth factors. We propose this sterile inflammatory response is in part associated with damage associated molecular patterns (DAMPs) generated by major injury, such as burn, and mediated via toll-like receptors (TLRs). It is unknown whether DAMPs can activate resident γδ T-cells that reside in skin. Methods Gamma delta T-cells were isolated from the skin of male C57BL/6 mice by enzymatic digestion. Mitochondrial DAMPs (MTDs) were generated from mitochondria isolated from mouse livers by sonication and centrifugation. Dermal γδ T-cells were incubated with MTDs (0–500 μg/ml) for 24 hr and cells and supernatants were collected for analysis. Results MTDs activated dermal γδ T-cells, as evidenced by increased TLR2 and TLR4 expression following in vitro exposure. MTDs also induced the production of inflammatory cytokines (IL-1β, IL-6), and growth factors (PDGF and VEGF) by γδ T-cells. Conclusions These findings herein support the concept that MTDs released after tissue/cellular injury are capable of activating dermal γδ T-cells. We propose that the activation of this unique T-cell population is central in the initiation of sterile inflammation and also contributes to the subsequent healing processes.
    Electronic ISSN: 1932-6203
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    Putative Epigenetic Involvement of the Endocannabinoid System in Anxiety- and Depression-Related Behaviors Caused by Nicotine as a Stressor (2016)
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    Publication Date: 2016-07-13
    Description: by Tamaki Hayase Like various stressors, the addictive use of nicotine (NC) is associated with emotional symptoms such as anxiety and depression, although the underlying mechanisms have not yet been fully elucidated due to the complicated involvement of target neurotransmitter systems. In the elicitation of these emotional symptoms, the fundamental involvement of epigenetic mechanisms such as histone acetylation has recently been suggested. Furthermore, among the interacting neurotransmitter systems implicated in the effects of NC and stressors, the endocannabinoid (ECB) system is considered to contribute indispensably to anxiety and depression. In the present study, the epigenetic involvement of histone acetylation induced by histone deacetylase (HDAC) inhibitors was investigated in anxiety- and depression-related behavioral alterations caused by NC and/or immobilization stress (IM). Moreover, based on the contributing roles of the ECB system, the interacting influence of ECB ligands on the effects of HDAC inhibitors was evaluated in order to examine epigenetic therapeutic interventions. Anxiety-like (elevated plus-maze test) and depression-like (forced swimming test) behaviors, which were observed in mice treated with repeated (4 days) NC (subcutaneous 0.8 mg/kg) and/or IM (10 min), were blocked by the HDAC inhibitors sodium butyrate (SB) and valproic acid (VA). The cannabinoid type 1 (CB1) agonist ACPA (arachidonylcyclopropylamide; AC) also antagonized these behaviors. Conversely, the CB1 antagonist SR 141716A (SR), which counteracted the effects of AC, attenuated the anxiolytic-like effects of the HDAC inhibitors commonly in the NC and/or IM groups. SR also attenuated the antidepressant-like effects of the HDAC inhibitors, most notably in the IM group. From these results, the combined involvement of histone acetylation and ECB system was shown in anxiety- and depression-related behaviors. In the NC treatment groups, the limited influence of SR against the HDAC inhibitor-induced antidepressant-like effects may reflect the characteristic involvement of histone acetylation within the NC-related neurotransmitter systems other than the ECB system.
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    Topological Small-World Organization of the Fibroblastic Reticular Cell Network Determines Lymph Node Functionality (2016)
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    Publication Date: 2016-07-15
    Description: by Mario Novkovic, Lucas Onder, Jovana Cupovic, Jun Abe, David Bomze, Viviana Cremasco, Elke Scandella, Jens V. Stein, Gennady Bocharov, Shannon J. Turley, Burkhard Ludewig Fibroblastic reticular cells (FRCs) form the cellular scaffold of lymph nodes (LNs) and establish distinct microenvironmental niches to provide key molecules that drive innate and adaptive immune responses and control immune regulatory processes. Here, we have used a graph theory-based systems biology approach to determine topological properties and robustness of the LN FRC network in mice. We found that the FRC network exhibits an imprinted small-world topology that is fully regenerated within 4 wk after complete FRC ablation. Moreover, in silico perturbation analysis and in vivo validation revealed that LNs can tolerate a loss of approximately 50% of their FRCs without substantial impairment of immune cell recruitment, intranodal T cell migration, and dendritic cell-mediated activation of antiviral CD8 + T cells. Overall, our study reveals the high topological robustness of the FRC network and the critical role of the network integrity for the activation of adaptive immune responses.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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    Disease Surveillance on Complex Social Networks (2016)
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    Publication Date: 2016-07-15
    Description: by Jose L. Herrera, Ravi Srinivasan, John S. Brownstein, Alison P. Galvani, Lauren Ancel Meyers As infectious disease surveillance systems expand to include digital, crowd-sourced, and social network data, public health agencies are gaining unprecedented access to high-resolution data and have an opportunity to selectively monitor informative individuals. Contact networks, which are the webs of interaction through which diseases spread, determine whether and when individuals become infected, and thus who might serve as early and accurate surveillance sensors. Here, we evaluate three strategies for selecting sensors—sampling the most connected, random, and friends of random individuals—in three complex social networks—a simple scale-free network, an empirical Venezuelan college student network, and an empirical Montreal wireless hotspot usage network. Across five different surveillance goals—early and accurate detection of epidemic emergence and peak, and general situational awareness—we find that the optimal choice of sensors depends on the public health goal, the underlying network and the reproduction number of the disease ( R 0 ). For diseases with a low R 0 , the most connected individuals provide the earliest and most accurate information about both the onset and peak of an outbreak. However, identifying network hubs is often impractical, and they can be misleading if monitored for general situational awareness, if the underlying network has significant community structure, or if R 0 is high or unknown. Taking a theoretical approach, we also derive the optimal surveillance system for early outbreak detection but find that real-world identification of such sensors would be nearly impossible. By contrast, the friends-of-random strategy offers a more practical and robust alternative. It can be readily implemented without prior knowledge of the network, and by identifying sensors with higher than average, but not the highest, epidemiological risk, it provides reasonably early and accurate information.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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    The Calponin Family Member CHDP-1 Interacts with Rac/CED-10 to Promote Cell Protrusions (2016)
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    Publication Date: 2016-07-15
    Description: by Liying Guan, Xuehua Ma, Jingyan Zhang, Jia-Jia Liu, Yingchun Wang, Mei Ding Eukaryotic cells extend a variety of surface protrusions to direct cell motility. Formation of protrusions is mediated by coordinated actions between the plasma membrane and the underlying actin cytoskeleton. Here, we found that the single calponin homology (CH) domain-containing protein CHDP-1 induces the formation of cell protrusions in C . elegans . CHDP-1 is anchored to the cortex through its amphipathic helix. CHDP-1 associates through its CH domain with the small GTPase Rac1/CED-10, which is a key regulator of the actin cytoskeleton. CHDP-1 preferentially binds to the GTP-bound active form of the CED-10 protein and preserves the membrane localization of GTP-CED-10. Hence, by coupling membrane expansion to Rac1-mediated actin dynamics, CHDP-1 promotes the formation of cellular protrusions in vivo .
    Print ISSN: 1553-7390
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    Dnmt3a Regulates Proliferation of Muscle Satellite Cells via p57Kip2 (2016)
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    Publication Date: 2016-07-15
    Description: by Masashi Naito, Masaki Mori, Masayo Inagawa, Kohei Miyata, Naohiro Hashimoto, Sakae Tanaka, Hiroshi Asahara Cell differentiation status is defined by the gene expression profile, which is coordinately controlled by epigenetic mechanisms. Cell type-specific DNA methylation patterns are established by chromatin modifiers including de novo DNA methyltransferases, such as Dnmt3a and Dnmt3b . Since the discovery of the myogenic master gene MyoD , myogenic differentiation has been utilized as a model system to study tissue differentiation. Although knowledge about myogenic gene networks is accumulating, there is only a limited understanding of how DNA methylation controls the myogenic gene program. With an aim to elucidate the role of DNA methylation in muscle development and regeneration, we investigate the consequences of mutating Dnmt3a in muscle precursor cells in mice. Pax3 promoter-driven Dnmt3a -conditional knockout (cKO) mice exhibit decreased organ mass in the skeletal muscles, and attenuated regeneration after cardiotoxin-induced muscle injury. In addition, Dnmt3a -null satellite cells (SCs) exhibit a striking loss of proliferation in culture. Transcriptome analysis reveals dysregulated expression of p57Kip2 , a member of the Cip/Kip family of cyclin-dependent kinase inhibitors (CDKIs), in the Dnmt3a -KO SCs. Moreover, RNAi-mediated depletion of p57Kip2 replenishes the proliferation activity of the SCs, thus establishing a role for the Dnmt3a - p57Kip2 axis in the regulation of SC proliferation. Consistent with these findings, Dnmt3a -cKO muscles exhibit fewer Pax7 + SCs, which show increased expression of p57Kip2 protein. Thus, Dnmt3a is found to maintain muscle homeostasis by epigenetically regulating the proliferation of SCs through p57Kip2 .
    Print ISSN: 1553-7390
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    Gene Regulation in Developing Chloroplasts Disentangled (2016)
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    Publication Date: 2016-07-15
    Description: by William Zerges
    Print ISSN: 1553-7390
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    Correction: In Situ Measurement of Some Soil Properties in Paddy Soil Using Visible and Near-Infrared Spectroscopy (2016)
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    Publication Date: 2016-07-15
    Description: by Wenjun Ji, Zhou Shi, Jingyi Huang, Shuo Li
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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    Correction: Hitting a Moving Target: A Model for Malaria Elimination in the Presence of Population Movement (2016)
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    Publication Date: 2016-07-15
    Description: by Sheetal Prakash Silal, Francesca Little, Karen Irma Barnes, Lisa Jane White
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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    Prevalence and Diversity of Salmonella Serotypes in Ecuadorian Broilers at Slaughter Age (2016)
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    Publication Date: 2016-07-15
    Description: by Christian Vinueza-Burgos, María Cevallos, Lenin Ron-Garrido, Sophie Bertrand, Lieven De Zutter Salmonella is frequently found in poultry and represent an important source for human gastrointestinal infections worldwide. The aim of this study was to investigate the prevalence, genotypes and antimicrobial resistance of Salmonella serotypes in broilers from Ecuador. Caeca content from 388 at random selected broiler batches were collected in 6 slaughterhouses during 1 year and analyzed by the ISO 6579/Amd1 protocol for the isolation for Salmonella . Isolates were serotyped and genotypic variation was acceded by pulsed field gel electrophoresis. MIC values for sulfamethoxazole, gentamicin, ciprofloxacin, ampicillin, cefotaxime, ceftazidime, tetracycline, streptomycin, trimethropim, chloramphenicol, colistin, florfenicol, kanamycin and nalidixic acid were obtained. Presence of bla CTX-M , bla TEM, bla SHV and bla CMY ; and mcr-1 plasmid genes was investigated in resistant strains to cefotaxime and colistin respectively. Prevalence at batch level was 16.0%. The most common serotype was S . Infantis (83.9%) followed by S . Enteritidis (14.5%) and S . Corvallis (1.6%). The pulsed field gel electrophoresis analysis showed that S . Corvallis, S . Enteritidis and S . Infantis isolates belonged to 1, 2 and 12 genotypes respectively. S . Infantis isolates showed high resistance rates to 12 antibiotics ranging from 57.7% (kanamycin) up to 98.1% (nalidixic acid and sulfamethoxazole). All S . Enteritidis isolates showed resistance to colistin. High multiresistant patterns were found for all the serotypes. The bla CTX-M gene was present in 33 S . Infantis isolates while mcr-1 was negative in 10 colistin resistant isolates. This study provides the first set of scientific data on prevalence and multidrug-resistant Salmonella coming from commercial poultry in Ecuador.
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    High Mortality in Severe Sepsis and Septic Shock Patients with Do-Not-Resuscitate Orders in East Asia (2016)
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    Publication Date: 2016-07-15
    Description: by Chun-Ta Huang, Yu-Chung Chuang, Yi-Ju Tsai, Wen-Je Ko, Chong-Jen Yu Background Severe sepsis is a potentially deadly illness and always requires intensive care. Do-not-resuscitate (DNR) orders remain a debated issue in critical care and limited data exist about its impact on care of septic patients, particularly in East Asia. We sought to assess outcome of severe sepsis patients with regard to DNR status in Taiwan. Methods A retrospective cohort study was conducted in intensive care units (ICUs) between 2008 and 2010. All severe sepsis patients were included for analysis. Primary outcome was association between DNR orders and ICU mortality. Volume of interventions was used as proxy indicator to indicate aggressiveness of care. Results Sixty-seven (9.4%) of 712 patients had DNR orders on ICU admission, and these patients were older and had higher disease severity compared with patients without DNR orders. Notably, DNR patients experienced high ICU mortality (90%). Multivariate analysis revealed that the presence of DNR orders was independently associated with ICU mortality (odds ratio: 6.13; 95% confidence interval: 2.66–14.10). In propensity score-matched cohort, ICU mortality rate (91%) in the DNR group was statistically higher than that (62%) in the non-DNR group (p
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    Correction: Role of Platelet Parameters on Sudden Sensorineural Hearing Loss: A Case-Control Study in Iran (2016)
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    Publication Date: 2016-07-15
    Description: by Abbas Mirvakili, Mohammad Hossein Dadgarnia, Mohammad Hossein Baradaranfar, Saeid Atighechi, Vahid Zand, Abdollah Ansari
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    Cobalt Chloride Treatment Used to Ablate the Lateral Line System Also Impairs the Olfactory System in Three Freshwater Fishes (2016)
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    Publication Date: 2016-07-15
    Description: by Julie M. Butler, Karen E. Field, Karen P. Maruska Fishes use multimodal signals during both inter- and intra-sexual displays to convey information about their sex, reproductive state, and social status. These complex behavioral displays can include visual, auditory, olfactory, tactile, and hydrodynamic signals, and the relative role of each sensory channel in these complex multi-sensory interactions is a common focus of neuroethology. The mechanosensory lateral line system of fishes detects near-body water movements and is implicated in a variety of behaviors including schooling, rheotaxis, social communication, and prey detection. Cobalt chloride is commonly used to chemically ablate lateral line neuromasts, thereby eliminating water-movement cues to test for mechanosensory-mediated behavioral functions. However, cobalt acts as a nonspecific calcium channel antagonist and could potentially disrupt function of all superficially located sensory receptor cells, including those for chemosensing. Here, we examined whether CoCl 2 treatment used to ablate the lateral line system also impairs olfaction in three freshwater fishes, the African cichlid fish Astatotilapia burtoni , goldfish Carassius auratus , and the Mexican blind cavefish Astyanax mexicanus . To examine the impact of CoCl 2 on the activity of peripheral receptors, we quantified DASPEI fluorescence intensity of the olfactory epithelium from fish exposed to control and CoCl 2 solutions. In addition, we examined brain activation in olfactory processing regions of A . burtoni immersed in either control or cobalt solutions. All three species exposed to CoCl 2 had decreased DASPEI staining of the olfactory epithelium, and in A . burtoni , cobalt treatment caused reduced neural activation in olfactory processing regions of the brain. To our knowledge this is the first empirical evidence demonstrating that the same CoCl 2 treatment used to ablate the lateral line system also impairs olfactory function. These data have important implications for the use of CoCl 2 in future research and suggest that previous studies using CoCl 2 should be reinterpreted in the context of both impaired mechanoreception and olfaction.
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    Very Long-Term Outcome of Non-Surgically Treated Patients with Temporal Lobe Epilepsy with Hippocampal Sclerosis: A Retrospective Study (2016)
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    Publication Date: 2016-07-15
    Description: by Tsugiko Kurita, Kotaro Sakurai, Youji Takeda, Toru Horinouchi, Ichiro Kusumi Objective Surgical intervention can result in complete seizure remission rates of up to 80% in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). However, certain patients cannot be treated surgically for various reasons. We analyzed the very long-term clinical outcomes of patients with TLE-HS who could not be treated surgically. Methods Subjects were selected from among patients with TLE-HS who were actively followed up for 〉10 years and treated with medication without surgical treatment. Patient medical records were used to retrospectively study seizure frequency, various clinical factors, and social adjustment. Patients who were seizure-free or had only aura were classified into Group 1; the others were classified into Group 2. Clinical factors including both patient and disease-specific factors were compared between the two groups. Current social adjustment, including the education, work, and economic status of each patient, was also investigated. Results Forty-one (41) subjects met the criteria for analysis, of which 12 (29%) were classified into Group 1. The average age of patients in Group 1 was higher than that of Group 2 (p = 0.0468). Group 2 included a significantly higher rate of patients who had more than one seizure per week at the onset (p = 0.0328), as well as a greater mean number of anti-epileptic drugs taken (p = 0.0024). Regarding social adjustment, Group 2 contained significantly fewer current jobholders than Group 1 (p = 0.0288). Conclusions After very long-term follow-up periods, 29% of patients with TLE-HS had a good outcome through treatment with anticonvulsant medications. Older patients tended to have fewer seizures, and seizure frequency at the onset was the only factor that predicted outcome.
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    Experimental Challenge of Atlantic Cod ( Gadus morhua ) with a Brucella pinnipedialis Strain from Hooded Seal ( Cystophora cristata ) (2016)
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    Publication Date: 2016-07-15
    Description: by Ingebjørg Helena Nymo, Marit Seppola, Sascha Al Dahouk, Kathrine Ryvold Bakkemo, María Pilar Jiménez de Bagüés, Jacques Godfroid, Anett Kristin Larsen Pathology has not been observed in true seals infected with Brucella pinnipedialis . A lack of intracellular survival and multiplication of B . pinnipedialis in hooded seal ( Cystophora cristata ) macrophages in vitro indicates a lack of chronic infection in hooded seals. Both epidemiology and bacteriological patterns in the hooded seal point to a transient infection of environmental origin, possibly through the food chain. To analyse the potential role of fish in the transmission of B . pinnipedialis , Atlantic cod ( Gadus morhua ) were injected intraperitoneally with 7.5 x 10 7 bacteria of a hooded seal field isolate. Samples of blood, liver, spleen, muscle, heart, head kidney, female gonads and feces were collected on days 1, 7, 14 and 28 post infection to assess the bacterial load, and to determine the expression of immune genes and the specific antibody response. Challenged fish showed an extended period of bacteremia through day 14 and viable bacteria were observed in all organs sampled, except muscle, until day 28. Neither gross lesions nor mortality were recorded. Anti- Brucella antibodies were detected from day 14 onwards and the expression of hepcidin, cathelicidin, interleukin (IL)-1β, IL-10, and interferon (IFN)-γ genes were significantly increased in spleen at day 1 and 28. Primary mononuclear cells isolated from head kidneys of Atlantic cod were exposed to B . pinnipedialis reference (NCTC 12890) and hooded seal (17a-1) strain. Both bacterial strains invaded mononuclear cells and survived intracellularly without any major reduction in bacterial counts for at least 48 hours. Our study shows that the B . pinnipedialis strain isolated from hooded seal survives in Atlantic cod, and suggests that Atlantic cod could play a role in the transmission of B . pinnipedialis to hooded seals in the wild.
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    Arabidopsis thaliana Contains Both Ni 2+ and Zn 2+ Dependent Glyoxalase I Enzymes and Ectopic Expression of the Latter Contributes More towards Abiotic Stress Tolerance in E . coli (2016)
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    Publication Date: 2016-07-15
    Description: by Muskan Jain, Rituraj Batth, Sumita Kumari, Ananda Mustafiz The glyoxalase pathway is ubiquitously found in all the organisms ranging from prokaryotes to eukaryotes. It acts as a major pathway for detoxification of methylglyoxal (MG), which deleteriously affects the biological system in stress conditions. The first important enzyme of this system is Glyoxalase I (GLYI). It is a metalloenzyme which requires divalent metal ions for its activity. This divalent metal ion can be either Zn 2+ as found in most of eukaryotes or Ni 2+ as seen in prokaryotes. In the present study, we have found three active GLYI enzymes (AtGLYI2, AtGLYI3 and AtGLYI6) belonging to different metal activation classes coexisting in Arabidopsis thaliana . These enzymes have been found to efficiently complement the GLYI yeast mutants. These three enzymes have been characterized in terms of their activity, metal dependency, kinetic parameters and their role in conferring tolerance to multiple abiotic stresses in E . coli and yeast. AtGLYI2 was found to be Zn 2+ dependent whereas AtGLYI3 and AtGLYI6 were Ni 2+ dependent. Enzyme activity of Zn 2+ dependent enzyme, AtGLYI2, was observed to be exceptionally high (~250–670 fold) as compared to Ni 2+ dependent enzymes, AtGLYI3 and AtGLYI6. The activity of these GLYI enzymes correlated well to their role in stress tolerance. Heterologous expression of these enzymes in E . coli led to better tolerance against various stress conditions. This is the first report of a higher eukaryotic species having multiple active GLYI enzymes belonging to different metal activation classes.
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    Whole Mitochondrial Genome Sequencing and Re-Examination of a Cytoplasmic Male Sterility-Associated Gene in Boro-Taichung-Type Cytoplasmic Male Sterile Rice (2016)
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    Publication Date: 2016-07-15
    Description: by Tomohiko Kazama, Kinya Toriyama Nuclear genome substitutions between subspecies can lead to cytoplasmic male sterility (CMS) through incompatibility between nuclear and mitochondrial genomes. Boro-Taichung (BT)-type CMS rice was obtained by substituting the nuclear genome of Oryza sativa subsp. indica cultivar Chinsurah Boro II with that of Oryza sativa subsp. japonica cultivar Taichung 65. In BT-type CMS rice, the mitochondrial gene orf79 is associated with male sterility. A complete sequence of the Boro-type mitochondrial genome responsible for BT-type CMS has not been determined to date. Here, we used pyrosequencing to construct the Boro-type mitochondrial genome. The contiguous sequences were assembled into five circular DNA molecules, four of which could be connected into a single circle. The two resulting subgenomic circles were unable to form a reliable master circle, as recombination between them was scarcely detected. We also found an unequal abundance of DNA molecules for the two loci of atp6 . These results indicate the presence of multi-partite DNA molecules in the Boro-type mitochondrial genome. Expression patterns were investigated for Boro-type mitochondria-specific orf s, which were not found in the mitochondria from the standard japonica cultivar Nipponbare. Restorer of fertility 1 (RF1)-dependent RNA processing has been observed in orf79 -containing RNA but was not detected in other Boro-type mitochondria-specific orf s, supporting the conclusion that orf79 is a unique CMS-associated gene in Boro-type mitochondria.
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    Incident Infection and Resistance Mutation Analysis of Dried Blood Spots Collected in a Field Study of HIV Risk Groups, 2007-2010 (2016)
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    Publication Date: 2016-07-15
    Description: by Xierong Wei, Amanda J. Smith, David W. Forrest, Gabriel A. Cardenas, Dano W. Beck, Marlene LaLota, Lisa R. Metsch, Catlainn Sionean, S. Michele Owen, Jeffrey A. Johnson Objective To assess the utility of cost-effective dried blood spot (DBS) field sampling for incidence and drug resistance surveillance of persons at high risk for HIV infection. Methods We evaluated DBS collected in 2007–2010 in non-clinical settings by finger-stick from HIV-positive heterosexuals at increased risk of HIV infection (n = 124), men who have sex with men (MSM, n = 110), and persons who inject drugs (PWID, n = 58). Relative proportions of recent-infection findings among risk groups were assessed at avidity index (AI) cutoffs of ≤25%, ≤30%, and ≤35%, corresponding to an infection mean duration of recency (MDR) of 220.6, 250.4, and 278.3 days, respectively. Drug resistance mutation prevalence was compared among the risk groups and avidity indices. Results HIV antibody avidity testing of all self-reported ARV-naïve persons (n = 186) resulted in 9.7%, 11.3% and 14.0% with findings within the 221, 250, and 278-day MDRs, respectively. The proportion of ARV-naïve MSM, heterosexuals, and PWID reporting only one risk category who had findings below the suggested 30% AI was 23.1%, 6.9% and 3.6% (p
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    Retrospection-Simulation-Revision: Approach to the Analysis of the Composition and Characteristics of Medical Waste at a Disaster Relief Site (2016)
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    Publication Date: 2016-07-15
    Description: by Li Zhang, Lihua Wu, Feng Tian, Zheng Wang A large amount of medical waste is produced during disaster relief, posing a potential hazard to the habitat and the environment. A comprehensive understanding of the composition and characteristics of medical waste that requires management is one of the most basic steps in the development of a plan for medical waste management. Unfortunately, limited reliable information is available in the open literature on the characteristics of the medical waste that is generated at disaster relief sites. This paper discusses the analysis of the composition and characteristics of medical waste at a disaster relief site using the retrospection-simulation-revision method. For this study, we obtained 35 medical relief records of the Wenchuan Earthquake, Sichuan, May 2008 from a field cabin hospital. We first present a retrospective analysis of the relief medical records, and then, we simulate the medical waste generated in the affected areas. We ultimately determine the composition and characteristics of medical waste in the affected areas using untreated medical waste to revise the composition of the simulated medical waste. The results from 35 cases showed that the medical waste generated from disaster relief consists of the following: plastic (43.2%), biomass (26.3%), synthetic fiber (15.3%), rubber (6.6%), liquid (6.6%), inorganic salts (0.3%) and metals (1.7%). The bulk density of medical relief waste is 249 kg/m 3 , and the moisture content is 44.75%. The data should be provided to assist the collection, segregation, storage, transportation, disposal and contamination control of medical waste in affected areas. In this paper, we wish to introduce this research method of restoring the medical waste generated in disaster relief to readers and researchers. In addition, we hope more disaster relief agencies will become aware of the significance of medical case recording and storing. This may be very important for the environmental evaluation of medical waste in disaster areas, as well as for medical waste management and disposal.
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    Co-Expression of Cancer Stem Cell Markers Corresponds to a Pro-Tumorigenic Expression Profile in Pancreatic Adenocarcinoma (2016)
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    Publication Date: 2016-07-15
    Description: by Jan Skoda, Marketa Hermanova, Tomas Loja, Pavel Nemec, Jakub Neradil, Petr Karasek, Renata Veselska Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Its dismal prognosis is often attributed to the presence of cancer stem cells (CSCs) that have been identified in PDAC using various markers. However, the co-expression of all of these markers has not yet been evaluated. Furthermore, studies that compare the expression levels of CSC markers in PDAC tumor samples and in cell lines derived directly from those tumors are lacking. Here, we analyzed the expression of putative CSC markers—CD24, CD44, epithelial cell adhesion molecule (EpCAM), CD133, and nestin—by immunofluorescence, flow cytometry and quantitative PCR in 3 PDAC-derived cell lines and by immunohistochemistry in 3 corresponding tumor samples. We showed high expression of the examined CSC markers among all of the cell lines and tumor samples, with the exception of CD24 and CD44, which were enriched under in vitro conditions compared with tumor tissues. The proportions of cells positive for the remaining markers were comparable to those detected in the corresponding tumors. Co-expression analysis using flow cytometry revealed that CD24 + /CD44 + /EpCAM + /CD133 + cells represented a significant population of the cells (range, 43 to 72%) among the cell lines. The highest proportion of CD24 + /CD44 + /EpCAM + /CD133 + cells was detected in the cell line derived from the tumor of a patient with the shortest survival. Using gene expression profiling, we further identified the specific pro-tumorigenic expression profile of this cell line compared with the profiles of the other two cell lines. Together, CD24 + /CD44 + /EpCAM + /CD133 + cells are present in PDAC cell lines derived from primary tumors, and their increased proportion corresponds with a pro-tumorigenic gene expression profile.
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    Mapping Global Potential Risk of Mango Sudden Decline Disease Caused by Ceratocystis fimbriata (2016)
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    Publication Date: 2016-07-15
    Description: by Tarcísio Visintin da Silva Galdino, Sunil Kumar, Leonardo S. S. Oliveira, Acelino C. Alfenas, Lisa G. Neven, Abdullah M. Al-Sadi, Marcelo C. Picanço The Mango Sudden Decline (MSD), also referred to as Mango Wilt, is an important disease of mango in Brazil, Oman and Pakistan. This fungus is mainly disseminated by the mango bark beetle, Hypocryphalus mangiferae (Stebbing), by infected plant material, and the infested soils where it is able to survive for long periods. The best way to avoid losses due to MSD is to prevent its establishment in mango production areas. Our objectives in this study were to: (1) predict the global potential distribution of MSD, (2) identify the mango growing areas that are under potential risk of MSD establishment, and (3) identify climatic factors associated with MSD distribution. Occurrence records were collected from Brazil, Oman and Pakistan where the disease is currently known to occur in mango. We used the correlative maximum entropy based model (MaxEnt) algorithm to assess the global potential distribution of MSD. The MaxEnt model predicted suitable areas in countries where the disease does not already occur in mango, but where mango is grown. Among these areas are the largest mango producers in the world including India, China, Thailand, Indonesia, and Mexico. The mean annual temperature, precipitation of coldest quarter, precipitation seasonality, and precipitation of driest month variables contributed most to the potential distribution of MSD disease. The mango bark beetle vector is known to occur beyond the locations where MSD currently exists and where the model predicted suitable areas, thus showing a high likelihood for disease establishment in areas predicted by our model. Our study is the first to map the potential risk of MSD establishment on a global scale. This information can be used in designing strategies to prevent introduction and establishment of MSD disease, and in preparation of efficient pest risk assessments and monitoring programs.
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    Novel Bioluminescent Binding Assays for Ligand–Receptor Interaction Studies of the Fibroblast Growth Factor Family (2016)
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    Publication Date: 2016-07-15
    Description: by Ge Song, Xiao-Xia Shao, Qing-Ping Wu, Zeng-Guang Xu, Ya-Li Liu, Zhan-Yun Guo We recently developed novel bioluminescent binding assays for several protein/peptide hormones to study their interactions with receptors using the so far brightest NanoLuc reporter. To validate the novel bioluminescent binding assay using a variety of protein/peptide hormones, in the present work we applied it to the fibroblast growth factor (FGF) family using the prototype member FGF2 as an example. A fully active recombinant FGF2 retaining a unique exposed cysteine (Cys) residue was chemically conjugated with an engineered NanoLuc carrying a unique exposed Cys residue at the C-terminus via formation of an intermolecular disulfide linkage. The NanoLuc-conjugated FGF2 (FGF2-Luc) retained high binding affinity to the overexpressed FGFR1 and the endogenous FGF receptor with the calculated dissociation constants of 161 ± 21 pM ( n = 3) and 25 ± 4 pM ( n = 3), respectively. In competition binding assays using FGF2-Luc as a tracer, receptor-binding potencies of wild-type or mutant FGF2s were accurately quantified. Thus, FGF2-Luc represents a novel non-radioactive tracer for the quantitative measurement of ligand–receptor interactions in the FGF family. These data suggest that the novel bioluminescent binding assay can be applied to a variety of protein/peptide hormones for ligand–receptor interaction studies.
    Electronic ISSN: 1932-6203
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    Sex in the City: Breeding Behavior of Urban Peregrine Falcons in the Midwestern US (2016)
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    Publication Date: 2016-07-16
    Description: by Isabel C. Caballero, John M. Bates, Mary Hennen, Mary V. Ashley Peregrine falcons ( Falco peregrinus ) were extirpated from most of the continental United States by widespread use of the pesticide DDT in the 1960s. Populations have rebounded with banning of the pesticide and successful implementation of captive breeding and hacking programs. An essentially new population of Midwestern peregrines now exists that is comprised almost entirely of urban-nesting birds. The new population is considered to be of mixed ancestry, occurs at relatively high densities, and has nest sites in close proximity, factors that could influence breeding behaviors including mate fidelity, nest-site fidelity, extra-pair paternity, and natal dispersal. We investigated these behaviors using a combination of field observations and DNA microsatellite genotyping. Data for eleven microsatellite DNA markers, including eight newly developed for the species, were analyzed from a total of 350 birds from nine Midwestern cities, representing 149 broods collected at 20 nest sites. To document breeding behavior, parentage was inferred by likelihood techniques when both parents were sampled and by parental genotype reconstruction when only one parent was sampled. In cases where neither parent was sampled, a sibship reconstruction approach was used. We found high mate fidelity and nest-site fidelity in urban peregrines; in 122 nesting attempts made by long-term breeders, only 12 (9.8%) mate changes and six (4.9%) nest-site changes occurred. Only one brood (of 35 tested) revealed extra-pair paternity and involved a male tending two offspring of a recently acquired mate. Natal dispersal patterns indicated that female peregrines dispersed on average 226 km, almost twice the distance of males (average 124 km). Despite the novel environment of cities, our results suggest that monogamous breeding, nest fidelity, and female natal dispersal are high in urban peregrines, not unlike other raptors living in non-urban habitats.
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    Long-Term Treatment with Liraglutide, a Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist, Has No Effect on β-Amyloid Plaque Load in Two Transgenic APP/PS1 Mouse Models of Alzheimer’s Disease (2016)
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    Publication Date: 2016-07-16
    Description: by Henrik H. Hansen, Katrine Fabricius, Pernille Barkholt, Pernille Kongsbak-Wismann, Chantal Schlumberger, Jacob Jelsing, Dick Terwel, Annelies Termont, Charles Pyke, Lotte Bjerre Knudsen, Niels Vrang One of the major histopathological hallmarks of Alzheimer’s disease (AD) is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1) receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP) and presenilin-1 (PS1) are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds. In this study, effects of long-term liraglutide treatment were therefore determined in two double APP/PS1 transgenic mouse models of Alzheimer’s disease carrying different clinical APP/PS1 mutations, i . e . the ‘London’ (hAPP Lon/ PS1 A246E ) and ‘Swedish’ mutation variant (hAPP Swe /PS1 ΔE9 ) of APP, with co-expression of distinct PS1 variants. Liraglutide was administered in 5 month-old hAPP Lon/ PS1 A246E mice for 3 months (100 or 500 ng/kg/day, s.c.), or 7 month-old hAPP Swe /PS1 ΔE9 mice for 5 months (500 ng/kg/day, s.c.). In both models, regional plaque load was quantified throughout the brain using stereological methods. Vehicle-dosed hAPP Swe /PS1 ΔE9 mice exhibited considerably higher cerebral plaque load than hAPP Lon/ PS1 A246E control mice. Compared to vehicle-dosed transgenic controls, liraglutide treatment had no effect on the plaque levels in hAPP Lon /PS1 A246E and hAPP Swe /PS1 ΔE9 mice. In conclusion, long-term liraglutide treatment exhibited no effect on cerebral plaque load in two transgenic mouse models of low- and high-grade amyloidosis, which suggests differential sensitivity to long-term liraglutide treatment in various transgenic mouse models mimicking distinct pathological hallmarks of AD.
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    GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing (2016)
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    Publication Date: 2016-07-16
    Description: by Ye Fang, Yun Ding, Wei P. Feinstein, David M. Koppelman, Juana Moreno, Mark Jarrell, J. Ramanujam, Michal Brylinski Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249.
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    Factor XIa and Thrombin Generation Are Elevated in Patients with Acute Coronary Syndrome and Predict Recurrent Cardiovascular Events (2016)
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    Publication Date: 2016-07-16
    Description: by Rinske Loeffen, René van Oerle, Mathie P. G. Leers, Johannes A. Kragten, Harry Crijns, Henri M. H. Spronk, Hugo ten Cate Objective In acute coronary syndrome (ACS) cardiac cell damage is preceded by thrombosis. Therefore, plasma coagulation markers may have additional diagnostic relevance in ACS. By using novel coagulation assays this study aims to gain more insight into the relationship between the coagulation system and ACS. Methods We measured plasma thrombin generation, factor XIa and D-dimer levels in plasma from ACS (n = 104) and non-ACS patients (n = 42). Follow-up measurements (n = 73) were performed at 1 and 6 months. Associations between coagulation markers and recurrent cardiovascular events were calculated by logistic regression analysis. Results Thrombin generation was significantly enhanced in ACS compared to non-ACS patients: peak height 148±53 vs. 122±42 nM. There was a significantly diminished ETP reduction (32 vs. 41%) and increased intrinsic coagulation activation (25 vs. 7%) in ACS compared to non-ACS patients. Furthermore, compared to non-ACS patients factor XIa and D-dimer levels were significantly elevated in ACS patients: 1.9±1.1 vs. 1.4±0.7 pM and 495(310–885) vs. 380(235–540) μg/L. Within the ACS spectrum, ST-elevated myocardial infarction patients had the highest prothrombotic profile. During the acute event, thrombin generation was significantly increased compared to 1 and 6 months afterwards: peak height 145±52 vs. 100±44 vs. 98±33 nM. Both peak height and factor XIa levels on admission predicted recurrent cardiovascular events (OR: 4.9 [95%CI 1.2–20.9] and 4.5 [1.1–18.9]). Conclusion ACS patients had an enhanced prothrombotic profile, demonstrated by an increased thrombin generation potential, factor XIa and D-dimer levels. This study is the first to demonstrate the positive association between factor XIa, thrombin generation and recurrent cardiovascular events.
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    A Cross-Sectional Study of Ageing and Cardiovascular Function over the Baboon Lifespan (2016)
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    Publication Date: 2016-07-19
    Description: by Kristen R. Yeung, Christine L. Chiu, Suzanne Pears, Scott J. Heffernan, Angela Makris, Annemarie Hennessy, Joanne M. Lind Background Ageing is associated with changes at the molecular and cellular level that can alter cardiovascular function and ultimately lead to disease. The baboon is an ideal model for studying ageing due to the similarities in genetic, anatomical, physiological and biochemical characteristics with humans. The aim of this cross-sectional study was to investigate the changes in cardiovascular profile of baboons over the course of their lifespan. Methods Data were collected from 109 healthy baboons ( Papio hamadryas ) at the Australian National Baboon Colony. A linear regression model, adjusting for sex, was used to analyse the association between age and markers of ageing with P 〈 0.01 considered significant. Results Male (n = 49, 1.5–28.5 years) and female (n = 60, 1.8–24.6 years) baboons were included in the study. Age was significantly correlated with systolic (R 2 = 0.23, P 〈 0.001) and diastolic blood pressure (R 2 = 0.44, P 〈 0.001), with blood pressure increasing with age. Age was also highly correlated with core augmentation index (R 2 = 0.17, P 〈 0.001) and core pulse pressure (R 2 = 0.30, P 〈 0.001). Creatinine and urea were significantly higher in older animals compared to young animals (P 〈 0.001 for both). Older animals (〉12 years) had significantly shorter telomeres when compared to younger (
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    Correction: Relationship between Concentrations of Lutein and StARD3 among Pediatric and Geriatric Human Brain Tissue (2016)
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    Publication Date: 2016-07-19
    Description: by Emanuela Jirayu Tanprasertsuk, Binxing Li, Paul S. Bernstein, Rohini Vishwanathan, Mary Ann Johnson, Leonard Poon, Elizabeth J. Johnson
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    Correction: Psychological Distress in the Hospital Setting: A Comparison between Native Dutch and Immigrant Patients (2016)
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    Publication Date: 2016-07-19
    Description: by Gertrud L. G. Haverkamp, Bart Torensma, Anton C. M. Vergouwen, Adriaan Honig
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    Correction: Fibrous Hydrogels for Cell Encapsulation: A Modular and Supramolecular Approach (2016)
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    Publication Date: 2016-07-19
    Description: by The PLOS ONE Staff
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  • 89
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    Fragment Length of Circulating Tumor DNA (2016)
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    Publication Date: 2016-07-19
    Description: by Hunter R. Underhill, Jacob O. Kitzman, Sabine Hellwig, Noah C. Welker, Riza Daza, Daniel N. Baker, Keith M. Gligorich, Robert C. Rostomily, Mary P. Bronner, Jay Shendure Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA) may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring background of cell-free DNA derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences in fragment length size between ctDNAs and normal cell-free DNA are defined. Human ctDNA in rat plasma derived from human glioblastoma multiforme stem-like cells in the rat brain and human hepatocellular carcinoma in the rat flank were found to have a shorter principal fragment length than the background rat cell-free DNA (134–144 bp vs. 167 bp, respectively). Subsequently, a similar shift in the fragment length of ctDNA in humans with melanoma and lung cancer was identified compared to healthy controls. Comparison of fragment lengths from cell-free DNA between a melanoma patient and healthy controls found that the BRAF V600E mutant allele occurred more commonly at a shorter fragment length than the fragment length of the wild-type allele (132–145 bp vs. 165 bp, respectively). Moreover, size-selecting for shorter cell-free DNA fragment lengths substantially increased the EGFR T790M mutant allele frequency in human lung cancer. These findings provide compelling evidence that experimental or bioinformatic isolation of a specific subset of fragment lengths from cell-free DNA may improve detection of ctDNA.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
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    Correction: Temporal Expression of Peripheral Blood Leukocyte Biomarkers in a Macaca fascicularis Infection Model of Tuberculosis; Comparison with Human Datasets and Analysis with Parametric/Non-parametric Tools for Improved Diagnostic Biomarker Id (2016)
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    Publication Date: 2016-07-19
    Description: by Sajid Javed, Leanne Marsay, Alice Wareham, Kuiama S. Lewandowski, Ann Williams, Michael J. Dennis, Sally Sharpe, Richard Vipond, Nigel Silman, Graham Ball, Karen E. Kempsell
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    qiRNApredictor: A Novel Computational Program for the Prediction of qiRNAs in Neurospora crassa (2016)
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    Publication Date: 2016-07-19
    Description: by Haiyou Deng, Quan Liu, Wei Cao, Rong Gui, Chengzhang Ma, Ming Yi, Yuangen Yao Recently, a new type of small interfering RNAs (qiRNAs) of typically 20~21 nucleotides was found in Neurospora crassa and rice and has been shown to regulate gene silencing in the DNA damage response. Identification of qiRNAs is fundamental for dissecting regulatory functions and molecular mechanisms. In contrast to other expensive and time-consuming experimental methods, the computational prediction of qiRNAs is a conveniently rapid method for gaining valuable information for a subsequent experimental verification. However, no tool existed to date for the prediction of qiRNAs. To this purpose, we developed the novel qiRNA prediction software package qiRNApredictor. This software demonstrates a promising sensitivity of 93.55% and a specificity of 71.61% from the leave-one-out validation. These studies might be beneficial for further experimental investigation. Furthermore, the local package of qiRNApredictor was implemented and made freely available to the academic community at Supplementary material.
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    Correction: Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence (2016)
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    Publication Date: 2016-07-19
    Description: by Abhirami A. Ananth, Lee-Hwa Tai, Casey Lansdell, Almohanad A. Alkayyal, Katherine E. Baxter, Leonard Angka, Jiqing Zhang, Christiano Tanese de Souza, Kyle B Stephenson, Kelley Parato, Jonathan L Bramson, John C Bell, Brian D Lichty, Rebecca C Auer
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  • 93
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    Repeated Closed Head Injury in Mice Results in Sustained Motor and Memory Deficits and Chronic Cellular Changes (2016)
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    Publication Date: 2016-07-19
    Description: by Amanda N. Bolton Hall, Binoy Joseph, Jennifer M. Brelsfoard, Kathryn E. Saatman Millions of mild traumatic brain injuries (TBIs) occur every year in the United States, with many people subject to multiple head injuries that can lead to chronic behavioral dysfunction. We previously reported that mild TBI induced using closed head injuries (CHI) repeated at 24h intervals produced more acute neuron death and glial reactivity than a single CHI, and increasing the length of time between injuries to 48h reduced the cumulative acute effects of repeated CHI. To determine whether repeated CHI is associated with behavioral dysfunction or persistent cellular damage, mice receiving either five CHI at 24h intervals, five CHI at 48h intervals, or five sham injuries at 24h intervals were evaluated across a 10 week period after injury. Animals with repeated CHI exhibited motor coordination and memory deficits, but not gait abnormalities when compared to sham animals. At 10wks post-injury, no notable neuron loss or glial reactivity was observed in the cortex, hippocampus, or corpus callosum. Argyrophilic axons were found in the pyramidal tract of some injured animals, but neither silver stain accumulation nor inflammatory responses in the injury groups were statistically different from the sham group in this region. However, argyrophilic axons, microgliosis and astrogliosis were significantly increased within the optic tract of injured animals. Repeated mild CHI also resulted in microgliosis and a loss of neurofilament protein 200 in the optic nerve. Lengthening the inter-injury interval from 24h to 48h did not effectively reduce these behavioral or cellular responses. These results suggest that repeated mild CHI results in persistent behavioral dysfunction and chronic pathological changes within the visual system, neither of which was significantly attenuated by lengthening the inter-injury interval from 24h to 48h.
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    AG490 and PF431396 Sensitive Tyrosine Kinase Control the Population Heterogeneity of Basal STAT1 Activity in Ube1l Deficient Cells (2016)
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    Publication Date: 2016-07-19
    Description: by Hesung Now, Joo-Yeon Yoo A population often contains distinct sub-populations, thereby increasing the complexity of the overall heterogeneity. However, the cellular origin and biological relevance of sub-populations in cell population have not been clearly identified. Here we demonstrated the novel roles of ISGylation, which is an IFN-induced post-translational modification, controlling heterogeneity at the population level in cultured adherent cells. Without UBE1L, an E1 enzyme of ISGylation, mouse embryonic fibroblasts (MEF) exhibited low viral resistance despite high STAT1 and ISG expression compared with the wild-type MEF. We observe that Ube1l −/− MEF populations consist of two behaviorally distinguishable sub-populations with distinct basal STAT1 activity, while wild-type MEF populations are unimodal. This population heterogeneity in Ube1l knock-out cells was perturbed by tyrosine kinase inhibitors, AG490 and PF431396. In contrast, the neutralization of type I IFN did not affect population heterogeneity. Based on these results, we concluded that UBE1L functions to adjust basal immunological states with the regulation of population heterogeneity.
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    Systemic Absorption of Catechins after Intraruminal or Intraduodenal Application of a Green Tea Extract in Cows (2016)
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    Publication Date: 2016-07-19
    Description: by Silvia Wein, Birgit Beyer, Annika Gohlke, Ralf Blank, Cornelia C. Metges, Siegfried Wolffram Green tea catechins have various potential health benefits in humans including anti-inflammatory, anti-oxidative and hepato-protective effects. If present in the circulation, they might have similar effects in ruminants, which are exposed to oxidative stress and fatty liver disease such as dairy cows during the periparturient phase. However, the bioavailability of a substance is a prerequisite for any post absorptive effect in vivo . This study aimed to investigate the appearance of catechins from a green tea extract (GTE) in cattle plasma after intraruminal and intraduodenal administration because absorption is of major importance regarding the bioavailability of catechins. The studies were performed in 5 rumen-fistulated non-lactating heifers and 6 duodenally fistulated lactating dairy cows, respectively, equipped with indwelling catheters placed in a jugular vein. The GTE was applied intraruminally (10 and 50 mg/kg BW, heifers) or duodenally (10, 20 and 30 mg/kg BW, dairy cows) in a cross‐over design with a 2 d washout period between different dosages. Blood samples were drawn following the GTE administration at various pre-defined time intervals. The concentration of the major GTE catechins (gallocatechin, epigallocatechin, catechin, epicatechin, epigallocatechin-gallate, epicatechin-gallate) in plasma samples were analysed by HPLC with electrochemical detection. Irrespective of the dose, almost none of the catechins originally contained in the GTE were detected in plasma samples after intraruminal application. In contrast, intraduodenal administration of GTE resulted in increased plasma concentrations of epicatechin, epigallocatechin, epigallocatechin gallate in a dose‐dependent manner. Thus, we can conclude that intraruminally or orally administered catechins are intensively metabolized by ruminal microorganisms.
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    Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Colorectal Liver Metastasis: A Systematic Review and Meta-Analysis (2016)
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    Publication Date: 2016-07-19
    Description: by Haowen Tang, Bingmin Li, Aiqun Zhang, Wenping Lu, Canhong Xiang, Jiahong Dong Background and Objective Inflammation is deemed to play critical roles in tumor progression and metastasis, and an increased neutrophil-lymphocyte ratio (NLR) has been reported to correlate with poor survivals in various malignancies. However, association between NLR elevation and survival outcome in patients with colorectal liver metastasis (CRLM) remains controversial. The aim of this study was to investigate the prognostic significance of elevated NLR in CRLM. Methods The meta-analysis was conducted in adherence to the MOOSE guidelines. PubMed, Embase, Cochrane Library, Web of Science and the Chinese SinoMed were systematically searched to identify eligible studies from the initiation of the databases to May, 2016. Overall survival (OS) and recurrence free survival (RFS) were pooled by using hazard ratio (HR) with corresponding 95% confidence interval (CI). Correlation between NLR values and clinicopathological features was synthesized by using odds ratio (OR) with corresponding 95% CI. Results A total of 1685 patients from 8 studies (9 cohorts) were analyzed, consisting 347 (20.59%) in high pretreatment NLR value group and 1338 (79.41%) in low pretreatment NLR value one. The results demonstrated that elevated pretreatment NLR was significantly related to poor OS (HR 2.17, 95% CI 1.82–2.58) and RFS (HR 1.96, 95% CI 1.64–2.35) in patients with CRLM. Conclusion The result of this systematic review and meta-analysis indicated that an elevated pretreatment NLR was closely correlated with poor long-term survival (OS and RFS) in CRLM patients. NLR can be routinely monitored and serve as a useful and cost-effective marker with strong prognostic significance in patients with CRLM.
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    Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome (2016)
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    Publication Date: 2016-07-19
    Description: by Peter C. Rowe, Kevin R. Fontaine, Megan Lauver, Samantha E. Jasion, Colleen L. Marden, Malini Moni, Carol B. Thompson, Richard L. Violand Chronic fatigue syndrome (CFS) is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress. In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals. In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls. We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15 minute period of passive supine straight leg raise (true neuromuscular strain) or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline. Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0–10 scale, and summed to create a composite symptom score. Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04) and concentration difficulties (P = 0.02) as well as increased composite symptom scores (all P = 0.03) during the maneuver. After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001) and for the composite symptom score (P = 0.005). During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls. We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours. These findings support our preliminary observations that increased mechanical sensitivity may be a contributor to the provocation of symptoms in this disorder.
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    Interaction of the Chromatin Remodeling Protein hINO80 with DNA (2016)
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    Publication Date: 2016-07-19
    Description: by Shweta Mendiratta, Shipra Bhatia, Shruti Jain, Taniya Kaur, Vani Brahmachari The presence of a highly conserved DNA binding domain in INO80 subfamily predicted that INO80 directly interacts with DNA and we demonstrated its DNA binding activity in vitro . Here we report the consensus motif recognized by the DBINO domain identified by SELEX method and demonstrate the specific interaction of INO80 with the consensus motif. We show that INO80 significantly down regulates the reporter gene expression through its binding motif, and the repression is dependent on the presence of INO80 but not YY1 in the cell. The interaction is lost if specific residues within the consensus motif are altered. We identify a large number of potential target sites of INO80 in the human genome through in silico analysis that can grouped into three classes; sites that contain the recognition sequence for INO80 and YY1, only YY1 and only INO80. We demonstrate the binding of INO80 to a representative set of sites in HEK cells and the correlated repressive histone modifications around the binding motif. In the light of the role of INO80 in homeotic gene regulation in Drosophila as an Enhancer of trithorax and polycomb protein (ETP) that can modify the effect of both repressive complexes like polycomb as well as the activating complex like trithorax, it remains to be seen if INO80 can act as a recruiter of chromatin modifying complexes.
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    Role of Mitochondrial Dynamics in Neuronal Development: Mechanism for Wolfram Syndrome (2016)
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    Publication Date: 2016-07-20
    Description: by Michal Cagalinec, Mailis Liiv, Zuzana Hodurova, Miriam Ann Hickey, Annika Vaarmann, Merle Mandel, Akbar Zeb, Vinay Choubey, Malle Kuum, Dzhamilja Safiulina, Eero Vasar, Vladimir Veksler, Allen Kaasik Deficiency of the protein Wolfram syndrome 1 (WFS1) is associated with multiple neurological and psychiatric abnormalities similar to those observed in pathologies showing alterations in mitochondrial dynamics. The aim of this study was to examine the hypothesis that WFS1 deficiency affects neuronal function via mitochondrial abnormalities. We show that down-regulation of WFS1 in neurons leads to dramatic changes in mitochondrial dynamics (inhibited mitochondrial fusion, altered mitochondrial trafficking, and augmented mitophagy), delaying neuronal development. WFS1 deficiency induces endoplasmic reticulum (ER) stress, leading to inositol 1,4,5-trisphosphate receptor (IP 3 R) dysfunction and disturbed cytosolic Ca 2+ homeostasis, which, in turn, alters mitochondrial dynamics. Importantly, ER stress, impaired Ca 2+ homeostasis, altered mitochondrial dynamics, and delayed neuronal development are causatively related events because interventions at all these levels improved the downstream processes. Our data shed light on the mechanisms of neuronal abnormalities in Wolfram syndrome and point out potential therapeutic targets. This work may have broader implications for understanding the role of mitochondrial dynamics in neuropsychiatric diseases.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
    Published by Public Library of Science (PLoS)
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    Correction: Identification of a 3 rd Na + Binding Site of the Glycine Transporter, GlyT2 (2016)
    Public Library of Science (PLoS)
    In: PLoS ONE
    Details
    Publication Date: 2016-07-20
    Description: by Nandhitha Subramanian, Amanda J. Scopelliti, Jane E. Carland, Renae M. Ryan, Megan L. O’Mara, Robert J. Vandenberg
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
    Published by Public Library of Science (PLoS)
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