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   ISSN (Online) 1932-6203
   Published by PLoS Homepage  [13 journals]
  • Correction: Association of physical capacity with heart rate variability
           based on a short-duration measurement of resting pulse rate in older
           adults with obesity

    • Authors: Chun-De Liao Jau-Yih Tsauo Dun-Jen Hsiao Tsan-Hon Liou Shih-Wei Huang Li-Fong Lin
      Abstract: by Chun-De Liao, Jau-Yih Tsauo, Dun-Jen Hsiao, Tsan-Hon Liou, Shih-Wei Huang, Li-Fong Lin
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191842
  • Correction: Right-wing authoritarianism and stereotype-driven expectations
           interact in shaping intergroup trust in one-shot vs multiple-round social

    • Authors: Giorgia Ponsi Maria Serena Panasiti Salvatore Maria Aglioti Marco Tullio Liuzza
      Abstract: by Giorgia Ponsi, Maria Serena Panasiti, Salvatore Maria Aglioti, Marco Tullio Liuzza
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191811
  • Correction: Properties of halogenated and sulfonated porphyrins relevant
           for the selection of photosensitizers in anticancer and antimicrobial

    • Authors: Barbara Pucelik Robert Paczyński Grzegorz Dubin Mariette M. Pereira Luis G. Arnaut Janusz M. Dąbrowski
      Abstract: by Barbara Pucelik, Robert Paczyński, Grzegorz Dubin, Mariette M. Pereira, Luis G. Arnaut, Janusz M. Dąbrowski
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191777
  • Correction: Musicians have better memory than nonmusicians: A

    • Authors: Francesca Talamini Gianmarco Altoè Barbara Carretti Massimo Grassi
      Abstract: by Francesca Talamini, Gianmarco Altoè, Barbara Carretti, Massimo Grassi
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191776
  • Correction: Functional implications of hexameric assembly of RraA proteins
           from Vibrio vulnificus

    • Authors: Saemee Song Seokho Hong Jinyang Jang Ji-Hyun Yeom Nohra Park Jaejin Lee Yeri Lim Jun-Yeong Jeon Hyung-Kyoon Choi Minho Lee Nam-Chul Ha Kangseok Lee
      Abstract: by Saemee Song, Seokho Hong, Jinyang Jang, Ji-Hyun Yeom, Nohra Park, Jaejin Lee, Yeri Lim, Jun-Yeong Jeon, Hyung-Kyoon Choi, Minho Lee, Nam-Chul Ha, Kangseok Lee
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191775
  • Correction: Stakeholders' views and experiences of care and interventions
           for addressing frailty and pre-frailty: A meta-synthesis of qualitative

    • Authors: Barbara D’Avanzo Rachel Shaw Silvia Riva Joao Apostolo Elzbieta Bobrowicz-Campos Donata Kurpas Maria Bujnowska-Fedak Carol Holland
      Abstract: by Barbara D’Avanzo, Rachel Shaw, Silvia Riva, Joao Apostolo, Elzbieta Bobrowicz-Campos, Donata Kurpas, Maria Bujnowska-Fedak, Carol Holland
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191763
  • Correction: Shared acoustic codes underlie emotional communication in
           music and speech—Evidence from deep transfer learning

    • Authors: Eduardo Coutinho Björn Schuller
      Abstract: by Eduardo Coutinho, Björn Schuller
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191754
  • Correction: Identification of soil P fractions that are associated with P
           loss from surface runoff under various cropping systems and fertilizer
           rates on sloped farmland

    • Authors: Xinghua Li Baona Wang Tewu Yang Duanwei Zhu Zhongnan Nie Junchi Xu
      Abstract: by Xinghua Li, Baona Wang, Tewu Yang, Duanwei Zhu, Zhongnan Nie, Junchi Xu
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191753
  • Correction: Cardiovascular Effect of Incretin-Based Therapy in Patients
           with Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis

    • Authors: Je-Yon Kim Seungwon Yang Jangik I. Lee Min Jung Chang
      Abstract: by Je-Yon Kim, Seungwon Yang, Jangik I. Lee, Min Jung Chang
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191744
  • Seasonal variation in environmental DNA detection in sediment and water

    • Authors: Andrew S. Buxton Jim J. Groombridge Richard A. Griffiths
      Abstract: by Andrew S. Buxton, Jim J. Groombridge, Richard A. GriffithsThe use of aquatic environmental DNA (eDNA) to detect the presence of species depends on the seasonal activity of the species in the sampled habitat. eDNA may persist in sediments for longer than it does in water, and analysing sediment could potentially extend the seasonal window for species assessment. Using the great crested newt as a model, we compare how detection probability changes across the seasons in eDNA samples collected from both pond water and pond sediments. Detection of both aquatic and sedimentary eDNA varied through the year, peaking in the summer (July), with its lowest point in the winter (January): in all seasons, detection probability of eDNA from water exceeded that from sediment. Detection probability of eDNA also varied between study areas, and according to great crested newt habitat suitability and sediment type. As aquatic and sedimentary eDNA show the same seasonal fluctuations, the patterns observed in both sample types likely reflect current or recent presence of the target species. However, given the low detection probabilities found in the autumn and winter we would not recommend using either aquatic or sedimentary eDNA for year-round sampling without further refinement and testing of the methods.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191737
  • Correction: Timing and rate of spheno-occipital synchondrosis closure and
           its relationship to puberty

    • Authors: Anwar Alhazmi Eduardo Vargas J. Martin Palomo Mark Hans Bruce Latimer Scott Simpson
      Abstract: by Anwar Alhazmi, Eduardo Vargas, J. Martin Palomo, Mark Hans, Bruce Latimer, Scott Simpson
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191703
  • Correction: Early postnatal vocalizations predict sociability and spatial
           memory in C57BL/6J mice: Individual differences in behavioral traits
           emerge early in development

    • Authors: Kaichi Yoshizaki Kohei Koike Ryuichi Kimura Noriko Osumi
      Abstract: by Kaichi Yoshizaki, Kohei Koike, Ryuichi Kimura, Noriko Osumi
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191702
  • Inflammatory-linked changes in CpG island methylation of three opioid
           peptide genes in a rat model for pain

    • Authors: Charlotte Louise Justine Jacobi Christoph Stein
      Abstract: by Charlotte Louise Justine Jacobi, Christoph SteinExpression of the opioid peptide genes proopiomelanocortin (Pomc), proenkephalin (Penk), and prodynorphin (Pdyn), in immune cells plays a key role in endogenous pain control. In a rat model of painful unilateral paw inflammation, we isolated cells from popliteal lymph nodes and evaluated the role of CpG island C5-methylation on the transcriptional activation of those genes. Using methylated DNA immunoprecipitation, we sorted gDNA into methylated (me) and non-me fractions and then determined the CpG island methylation status of each fraction via quantitative Real Time-PCR (qRT-PCR). In silico analysis by MethPrimer software identified one CpG island in Pdyn and three each in Pomc and Penk. No substantial changes in C5-methylation of any gene were observed. In conclusion, the CpG island methylation status does not seem to be a key regulator of opioid gene activation in immune cells during peripheral tissue inflammation.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191698
  • Optic flow detection is not influenced by visual-vestibular congruency

    • Authors: Vivian Holten Paul R. MacNeilage
      Abstract: by Vivian Holten, Paul R. MacNeilageOptic flow patterns generated by self-motion relative to the stationary environment result in congruent visual-vestibular self-motion signals. Incongruent signals can arise due to object motion, vestibular dysfunction, or artificial stimulation, which are less common. Hence, we are predominantly exposed to congruent rather than incongruent visual-vestibular stimulation. If the brain takes advantage of this probabilistic association, we expect observers to be more sensitive to visual optic flow that is congruent with ongoing vestibular stimulation. We tested this expectation by measuring the motion coherence threshold, which is the percentage of signal versus noise dots, necessary to detect an optic flow pattern. Observers seated on a hexapod motion platform in front of a screen experienced two sequential intervals. One interval contained optic flow with a given motion coherence and the other contained noise dots only. Observers had to indicate which interval contained the optic flow pattern. The motion coherence threshold was measured for detection of laminar and radial optic flow during leftward/rightward and fore/aft linear self-motion, respectively. We observed no dependence of coherence thresholds on vestibular congruency for either radial or laminar optic flow. Prior studies using similar methods reported both decreases and increases in coherence thresholds in response to congruent vestibular stimulation; our results do not confirm either of these prior reports. While methodological differences may explain the diversity of results, another possibility is that motion coherence thresholds are mediated by neural populations that are either not modulated by vestibular stimulation or that are modulated in a manner that does not depend on congruency.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191693
  • Electroacupuncture at Guanyuan (CV 4), Zusanli (ST 36) and Baihui (DU 20)
           regulate the aging-related changes in gene expression profile of the
           hippocampus in sub-acutely aging rats

    • Authors: Jianmin Liu Jing Liu Guang’an Wang Guangya Liu Huanjiao Zhou Yun Fan Fengxia Liang Hua Wang
      Abstract: by Jianmin Liu, Jing Liu, Guang’an Wang, Guangya Liu, Huanjiao Zhou, Yun Fan, Fengxia Liang, Hua WangTo investigate the molecular mechanisms of sub-acutely aging and demonstrate the effect of electroacupuncture (EA) at the Guanyuan (CV 4), Zusanli (ST 36) and Baihui (DU 20) acupoint on the sub-acutely aging brain, cDNA microarrays and bioinformatics analyses were carried out. Thirty Sprague-Dawley (SD) male rats were selected and randomly divided into three groups: the control group (C), the sub-acutely aging model group (M) and the electroacupuncture group (M+EA). Sub-acutely aging model rats were obtained by D-galactose s.c. injection continuously for 40 days. Total RNA was extracted from the hippocampus area of brains in three groups for cDNA microarrays. The data of different groups were compared and analyzed by differential expression analysis, Gene ontology (GO) term enrichment, Kyoto Encyclopedia of Genes Genomes (KEGG) pathway enrichment and quantitative real-time PCR. According to the results, 4052 DE genes were identified in our study. Among them, there were 3079 differentially expressed (DE) genes between group M and group C, and these genes are associated with the aging of rats. Moreover, 983 genes were expressed differently in group M+EA compared with group M, revealing that points stimuli could regulate gene expression in brain with aging. Gene ontology (GO) term enrichment and KEGG enrichment were performed to further classify the differential expression genes. Important GO terms and KEGG pathways connected with sub-acutely aging EA effects were identified. At last, 3 significant differentially expressed genes were selected for real-time quantitative PCR to clarify the cDNA microarray results. In conclusion, the cDNA microarray data first compared and analyzed the differences of gene expression profile in the hippocampus of rats in different groups, which contribute to our knowledge on the molecular mechanisms of EA towards sub-acutely aging.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191623
  • Crystal structure of a UDP-GlcNAc epimerase for surface polysaccharide
           biosynthesis in Acinetobacter baumannii

    • Authors: Bhumika S. Shah Heather E. Ashwood Stephen J. Harrop Daniel N. Farrugia Ian T. Paulsen Bridget C. Mabbutt
      Abstract: by Bhumika S. Shah, Heather E. Ashwood, Stephen J. Harrop, Daniel N. Farrugia, Ian T. Paulsen, Bridget C. MabbuttWith new strains of Acinetobacter baumannii undergoing genomic analysis, it has been possible to define regions of genomic plasticity (RGPs), encoding specific adaptive elements. For a selected RGP from a community-derived isolate of A. baumannii, we outline sequences compatible with biosynthetic machinery of surface polysaccharides, specifically enzymes utilized in the dehydration and conversion of UDP-N-acetyl-D-glucosamine (UDP-D-GlcNAc). We have determined the crystal structure of one of these, the epimerase Ab-WbjB. This dehydratase belongs to the ‘extended’ short-chain dehydrogenase/reductase (SDR) family, related in fold to previously characterised enzymes CapE and FlaA1. Our 2.65Å resolution structure of Ab-WbjB shows a hexamer, organised into a trimer of chain pairs, with coenzyme NADP+ occupying each chain. Specific active-site interactions between each coenzyme and a lysine quaternary group of a neighbouring chain interconnect adjacent dimers, so stabilising the hexameric form. We show UDP-GlcNAc to be a specific substrate for Ab-WbjB, with binding evident by ITC (Ka = 0.23 μmol-1). The sequence of Ab-WbjB shows variation from the consensus active-site motifs of many SDR enzymes, demonstrating a likely catalytic role for a specific threonine sidechain (as an alternative to tyrosine) in the canonical active site chemistry of these epimerases.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191610
  • qPortal: A platform for data-driven biomedical research

    • Authors: Christopher Mohr Andreas Friedrich David Wojnar Erhan Kenar Aydin Can Polatkan Marius Cosmin Codrea Stefan Czemmel Oliver Kohlbacher Sven Nahnsen
      Abstract: by Christopher Mohr, Andreas Friedrich, David Wojnar, Erhan Kenar, Aydin Can Polatkan, Marius Cosmin Codrea, Stefan Czemmel, Oliver Kohlbacher, Sven NahnsenModern biomedical research aims at drawing biological conclusions from large, highly complex biological datasets. It has become common practice to make extensive use of high-throughput technologies that produce big amounts of heterogeneous data. In addition to the ever-improving accuracy, methods are getting faster and cheaper, resulting in a steadily increasing need for scalable data management and easily accessible means of analysis.We present qPortal, a platform providing users with an intuitive way to manage and analyze quantitative biological data. The backend leverages a variety of concepts and technologies, such as relational databases, data stores, data models and means of data transfer, as well as front-end solutions to give users access to data management and easy-to-use analysis options. Users are empowered to conduct their experiments from the experimental design to the visualization of their results through the platform. Here, we illustrate the feature-rich portal by simulating a biomedical study based on publically available data. We demonstrate the software’s strength in supporting the entire project life cycle. The software supports the project design and registration, empowers users to do all-digital project management and finally provides means to perform analysis. We compare our approach to Galaxy, one of the most widely used scientific workflow and analysis platforms in computational biology. Application of both systems to a small case study shows the differences between a data-driven approach (qPortal) and a workflow-driven approach (Galaxy).qPortal, a one-stop-shop solution for biomedical projects offers up-to-date analysis pipelines, quality control workflows, and visualization tools. Through intensive user interactions, appropriate data models have been developed. These models build the foundation of our biological data management system and provide possibilities to annotate data, query metadata for statistics and future re-analysis on high-performance computing systems via coupling of workflow management systems. Integration of project and data management as well as workflow resources in one place present clear advantages over existing solutions.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191603
  • Prognostic and predictive role of EGFR pathway alterations in biliary
           cancer patients treated with chemotherapy and anti-EGFR

    • Authors: Caterina Peraldo-Neia Giuliana Cavalloni Elisabetta Fenocchio Celeste Cagnazzo Loretta Gammaitoni Stefano Cereda Guglielmo Nasti Maria Antonietta Satolli Giuseppe Aprile Michele Reni Antonio Avallone Rosella Spadi Tiziana Venesio Vittoria Martin Claudio Doglioni Milo Frattini Massimo Aglietta Francesco Leone
      Abstract: by Caterina Peraldo-Neia, Giuliana Cavalloni, Elisabetta Fenocchio, Celeste Cagnazzo, Loretta Gammaitoni, Stefano Cereda, Guglielmo Nasti, Maria Antonietta Satolli, Giuseppe Aprile, Michele Reni, Antonio Avallone, Rosella Spadi, Tiziana Venesio, Vittoria Martin, Claudio Doglioni, Milo Frattini, Massimo Aglietta, Francesco LeoneThe association of anti-EGFR to gemcitabine and oxaliplatin (GEMOX) chemotherapy did not improve survival in biliary tract carcinoma (BTC) patients. Multiple mechanisms might be involved in the resistance to anti-EGFR. Here, we explored the mutation profile of EGFR extracellular domain (ECD), of tyrosine kinase domain (TKD), and its amplification status. EGFR mutational status of exons 12, 18–21 was analyzed in 57 tumors by Sanger sequencing. EGFR amplification was evaluated in 37 tumors by Fluorescent In Situ Hybridization (FISH). Kaplan-Meier curves were calculated using the log-rank test. Six patients had mutations in exon 12 of EGFR ECD and 7 in EGFR TKD. Neither EGFR ECD nor TKD mutations affected progression free survival (PFS) or overall survival (OS) in the entire population. In the panitumumab plus GEMOX (P-GEMOX) arm, ECD mutated patients had a worse OS, while EGFR TKD mutated patients had a trend towards shorter PFS and OS. Overall, the presence of mutations in EGFR or in its transducers did not affect PFS or OS, while the extrahepatic cholangiocarcinoma (ECC) mutated patients had a worse prognosis compared to WT. Nineteen out of 37 tumors were EGFR amplified, but the amplification did not correlate with survival. ECC EGFR amplified patients had improved OS, whereas the amplification significantly correlated with poor PFS (p = 0.03) in gallbladder carcinoma patients. The high molecular heterogeneity is a predominant feature of BTC: the alterations found in this work seem to have a prognostic impact rather than a predictive role towards anti-EGFR therapy.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191593
  • High-level production and purification in a functional state of an
           extrasynaptic gamma-aminobutyric acid type A receptor containing α4β3δ

    • Authors: Xiaojuan Zhou Rooma Desai Yinghui Zhang Wojciech J. Stec Keith W. Miller Youssef Jounaidi
      Abstract: by Xiaojuan Zhou, Rooma Desai, Yinghui Zhang, Wojciech J. Stec, Keith W. Miller, Youssef JounaidiThe inhibitory γ-aminobutyric acid type A receptors are implicated in numerous physiological processes, including cognition and inhibition of neurotransmission, rendering them important molecular targets for many classes of drugs. Functionally, the entire GABAAR family of receptors can be subdivided into phasic, fast acting synaptic receptors, composed of α-, β- and γ-subunits, and tonic extrasynaptic receptors, many of which contain the δ-subunit in addition to α- and β-subunits. Whereas the subunit arrangement of the former group is agreed upon, that of the αβδ GABAARs remains unresolved by electrophysiological and pharmacological research. To resolve such issues will require biophysical techniques that demand quantities of receptor that have been previously unavailable. Therefore, we have engineered a stable cell line with tetracycline inducible expression of human α4-, β3- and N-terminally Flag-tagged δ-subunits. This cell line achieved a specific activity between 15 and 20 pmol [3H]muscimol sites/mg of membrane protein, making it possible to obtain 1 nmole of purified α4β3δ GABAAR from sixty 15–cm culture dishes. When induced, these cells exhibited agonist–induced currents with characteristics comparable to those previously reported for this receptor and a pharmacology that included strong modulation by etomidate and the δ-subunit-specific ligand, DS2. Immunoaffinity purification and reconstitution in CHAPS/asolectin micelles resulted in the retention of equilibrium allosteric interactions between the separate agonist, anesthetic and DS2 sites. Moreover, all three subunits retained glycosylation. The establishment of this well–characterized cell line will allow molecular level studies of tonic receptors to be undertaken.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191583
  • An energy-efficient failure detector for vehicular cloud computing

    • Authors: Jiaxi Liu Zhibo Wu Jian Dong Jin Wu Dongxin Wen
      Abstract: by Jiaxi Liu, Zhibo Wu, Jian Dong, Jin Wu, Dongxin WenFailure detectors are one of the fundamental components for maintaining the high availability of vehicular cloud computing. In vehicular cloud computing, lots of RSUs are deployed along the road to improve the connectivity. Many of them are equipped with solar battery due to the unavailability or excess expense of wired electrical power. So it is important to reduce the battery consumption of RSU. However, the existing failure detection algorithms are not designed to save battery consumption RSU. To solve this problem, a new energy-efficient failure detector 2E-FD has been proposed specifically for vehicular cloud computing. 2E-FD does not only provide acceptable failure detection service, but also saves the battery consumption of RSU. Through the comparative experiments, the results show that our failure detector has better performance in terms of speed, accuracy and battery consumption.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191577
  • Influence of early stress on memory reconsolidation: Implications for
           post-traumatic stress disorder treatment

    • Authors: Hélène Villain Aïcha Benkahoul Philippe Birmes Barbara Ferry Pascal Roullet
      Abstract: by Hélène Villain, Aïcha Benkahoul, Philippe Birmes, Barbara Ferry, Pascal RoulletPost-traumatic stress disorder (PTSD) is a common consequence of exposure to a life-threatening event. Currently, pharmacological treatments are limited by high rates of relapse, and novel treatment approaches are needed. We have recently demonstrated that propranolol, a β-adrenergic antagonist, inhibited aversive memory reconsolidation in animals. Following this, in an open-label study 70% of patients with PTSD treated with propranolol during reactivation of traumatic memory exhibited full remission. However, the reason why 30% of these patients did not respond positively to propranolol treatment is still unclear. One of the major candidates as factor of treatment resistance is the patient's early-life traumatic history. To test the role of this factor, mice with pre- or postnatal stress are being tested in fear conditioning and in a new behavioral task, the "city-like", specifically designed as a mouse model of PTSD. After reactivation of the traumatic event, mice received propranolol injection to block the noradrenergic system during memory reconsolidation. Results show that, in the “city-like” test, control mice strongly avoided the shock compartment but also the compartments containing cues associated with the electric shocks. Injection of propranolol after reactivation greatly reduced the memory of the traumatic event, but this effect was not present when mice had received pre- or postnatal stress. Moreover, propranolol produced only a very weak effect in the fear conditioning test, and never changed the corticosterone level whatever the behavioral experiment. Taken together our results suggest that our new behavioural paradigm is well adapted to PTSD study in mice, and that early stress exposure may have an impact on propranolol PTSD treatment outcome. These data are critical to understanding the effect of propranolol treatment, in order to improve the therapeutic protocol currently used in humans.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191563
  • Using a model comparison approach to describe the assembly pathway for
           histone H1

    • Authors: Carlos Contreras Minaya Villasana Michael J. Hendzel Gustavo Carrero
      Abstract: by Carlos Contreras, Minaya Villasana, Michael J. Hendzel, Gustavo CarreroHistones H1 or linker histones are highly dynamic proteins that diffuse throughout the cell nucleus and associate with chromatin (DNA and associated proteins). This binding interaction of histone H1 with the chromatin is thought to regulate chromatin organization and DNA accessibility to transcription factors and has been proven to involve a kinetic process characterized by a population that associates weakly with chromatin and rapidly dissociates and another population that resides at a binding site for up to several minutes before dissociating. When considering differences between these two classes of interactions in a mathematical model for the purpose of describing and quantifying the dynamics of histone H1, it becomes apparent that there could be several assembly pathways that explain the kinetic data obtained in living cells. In this work, we model these different pathways using systems of reaction-diffusion equations and carry out a model comparison analysis using FRAP (fluorescence recovery after photobleaching) experimental data from different histone H1 variants to determine the most feasible mechanism to explain histone H1 binding to chromatin. The analysis favors four different chromatin assembly pathways for histone H1 which share common features and provide meaningful biological information on histone H1 dynamics. We show, using perturbation analysis, that the explicit consideration of high- and low-affinity associations of histone H1 with chromatin in the favored assembly pathways improves the interpretation of histone H1 experimental FRAP data. To illustrate the results, we use one of the favored models to assess the kinetic changes of histone H1 after core histone hyperacetylation, and conclude that this post-transcriptional modification does not affect significantly the transition of histone H1 from a weakly bound state to a tightly bound state.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191562
  • Aerial ULV control of Aedes aegypti with naled (Dibrom) inside simulated
           rural village and urban cryptic habitats

    • Authors: Seth C. Britch Kenneth J. Linthicum Robert L. Aldridge Mark S. Breidenbaugh Mark D. Latham Peter H. Connelly Mattie J. E. Rush Jennifer L. Remmers Jerry D. Kerce Charles A. Silcox US Navy Entomology Center of Excellence Team
      Abstract: by Seth C. Britch, Kenneth J. Linthicum, Robert L. Aldridge, Mark S. Breidenbaugh, Mark D. Latham, Peter H. Connelly, Mattie J. E. Rush, Jennifer L. Remmers, Jerry D. Kerce, Charles A. Silcox, US Navy Entomology Center of Excellence Team We conducted aerial fixed wing ultra low volume (ULV) spray trials with naled to investigate penetration of exposed and simulated cryptic habitat within opened buildings, partially sealed buildings, and outdoor locations targeting sentinel adult Aedes aegypti mosquitoes in north central Florida. Mortality was observed in open and closed buildings and outdoors, even in mosquitoes placed in cryptic habitats. Observations on the impact of building type, mosquito exposure method such as placement in cryptic habitat, and spray nozzle size on mosquito mortality are described and analyzed.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191555
  • Using daily text messages to improve adherence to infant micronutrient
           powder (MNP) packets in rural western China: A cluster-randomized
           controlled trial

    • Authors: Xu Wang Renfu Luo Chengfang Liu Linxiu Zhang Ai Yue Alexis Medina Scott Rozelle
      Abstract: by Xu Wang, Renfu Luo, Chengfang Liu, Linxiu Zhang, Ai Yue, Alexis Medina, Scott RozelleObjective To evaluate the effectiveness of daily text messages as a means to improve caregivers’ adherence to infant micronutrient powder (MNP) in rural Shaanxi Province of China. Methodology 638 infants aged 6–11 months in 234 villages were involved in a cluster-randomized controlled trial (RCT). All caregivers were given free infant MNP packets at baseline in April 2013 and the follow-up survey was in July 2013. We randomly assigned 318 infants in 117 villages to treatment group (receiving daily text message) and 320 infants in the other 117 villages as control group. Results On average, daily text messages increased the number of MNP packets fed (marginal effect = 4.63; 95% confidence interval (CI) = 0.16, 9.10). The text message is more likely to increase the consumption of MNP packets if the primary caregiver was the mother (marginal effect = 12.19; 95% CI = 0.69, 23.68). Receiving the text message appears to significantly increase the likelihood of full adherence when the primary caregiver can either check (odds ratio = 2.93; 95% CI = 1.34, 6.40) or knows how to send (odds ratio = 3.26; 95% CI = 1.53, 6.97) text messages. Conclusion Daily text messages improved the consumption of infant MNP packets. However, the impact was not large enough to increase the probability of caregivers being fully adherent to the feeding instruction, which is to feed 5–7 packets per week as recommended. In addition, when the mother is the caregiver and when the caregiver can check or knows how to send text messages there is greater adherence by the primary caregivers. Trial registration
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191549
  • KANSL1 variation is not a major contributing factor in self-limited focal
           epilepsy syndromes of childhood

    • Authors: Kenneth A. Myers Amelia McGlade Bernd A. Neubauer Dennis Lal Samuel F. Berkovic Ingrid E. Scheffer Michael S. Hildebrand
      Abstract: by Kenneth A. Myers, Amelia McGlade, Bernd A. Neubauer, Dennis Lal, Samuel F. Berkovic, Ingrid E. Scheffer, Michael S. HildebrandBackground KANSL1 haploinsufficiency causes Koolen-de Vries syndrome (KdVS), characterized by dysmorphic features and intellectual disability; amiable personality, congenital malformations and seizures also commonly occur. The epilepsy phenotypic spectrum in KdVS is broad, but most individuals have focal seizures with some having a phenotype resembling the self-limited focal epilepsies of childhood (SFEC). We hypothesized that variants in KANSL1 contribute to pathogenesis of SFEC. Materials and methods We screened KANSL1 for single nucleotide variants in 90 patients with SFEC. We then screened a cohort of 208 patients with two specific SFEC syndromes, childhood epilepsy with centrotemporal spikes (CECTS) and atypical childhood epilepsy with centrotemporal spikes (ACECTS) for KANSL1 variants. The second cohort was also used to evaluate minor allelic variants that appeared overrepresented in the initial cohort. Results One variant, p.Lys104Thr, was predicted damaging and appeared overrepresented in our 90-patient cohort compared to Genome Aggregation Database (gnomAD) allele frequency (0.217 to 0.116, with no homozygotes in gnomAD). However, there was no difference in p.Lys104Thr allele frequency in the follow-up CECTS/ACECTS cohort and controls. Four rare KANSL1 variants of uncertain significance were identified in the CECTS/ACECTS cohort. Discussion Our data do not support a major role for KANSL1 variants in pathogenesis of SFEC.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191546
  • Leisure-time physical activity and prevalence of non-communicable
           pathologies and prescription medication in Spain

    • Authors: Pablo Fernandez-Navarro María Teresa Aragones Victoria Ley
      Abstract: by Pablo Fernandez-Navarro, María Teresa Aragones, Victoria LeyOur aims were to describe physical activity (PA) behaviour in Spain and to examine its association with the prevalence of some of the major non-communicable diseases and with the use of prescription medication. Individualized secondary data retrieved from the 2014 European Health Interview Survey (EHIS) for Spain were used to conduct a cross-sectional epidemiological study (n = 18926). PA was assessed by two different measures: a specific designed variable for EHIS and a leisure time PA frequency-based query of the national survey. Diseases analyzed were hypertension, diabetes, hypercholesterolemia, depression and anxiety. The use of prescription medication was also included in the study. Weighted percentages were computed and contingency tables were calculated to describe PA by levels of the traits and sociodemographic characteristics. Chi-square test was used to compare percentages between groups and weighted logistic regression models were used to assess the relationship between PA and the prevalence of the disease. About 73% of the Spanish population performs no PA at all or only occasionally during their leisure time, and only one third meets minimum PA international guidelines (≥ 150min/week). Men are considerably more active than women and less PA is observed as the education level decreases and as age increases. The risk of the diseases evaluated was up to three times higher among inactive individuals. This study provides national population-based estimations highlighting the impact of PA in Spain, not only in the prevalence of some of the major non-communicable diseases but also in reducing prescription medication, and the potential sex and socioeconomic influence.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191542
  • Hexokinase II may be dispensable for CD4 T cell responses against a virus

    • Authors: Siva Karthik Varanasi Ujjaldeep Jaggi Nissim Hay Barry T. Rouse
      Abstract: by Siva Karthik Varanasi, Ujjaldeep Jaggi, Nissim Hay, Barry T. RouseActivation of CD4 T cells leads to their metabolic reprogramming which includes enhanced glycolysis, catalyzed through hexokinase enzymes. Studies in some systems indicate that the HK2 isoform is the most up regulated isoform in activated T cells and in this report the relevance of this finding is evaluated in an infectious disease model. Genetic ablation of HK2 was achieved in only T cells and the outcome was evaluated by measures of T cell function. Our results show that CD4 T cells from both HK2 depleted and WT animals displayed similar responses to in vitro stimulation and yielded similar levels of Th1, Treg or Th17 subsets when differentiated in vitro. A modest increase in the levels of proliferation was observed in CD4 T cells lacking HK2. Deletion of HK2 led to enhanced levels of HK1 indicative of a compensatory mechanism. Finally, CD4 T cell mediated immuno-inflammatory responses to a virus infection were similar between WT and HK2 KO animals. The observations that the expression of HK2 appears non-essential for CD4 T cell responses against virus infections is of interest since it suggests that targeting HK2 for cancer therapy may not have untoward effects on CD4 T cell mediated immune response against virus infections.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191533
  • Sensitive detection of fluorescence in western blotting by merging images

    • Authors: Yukari Kondo Shinichiro Higa Takeshi Iwasaki Tomoya Matsumoto Kazumitsu Maehara Akihito Harada Yoshihiro Baba Masatoshi Fujita Yasuyuki Ohkawa
      Abstract: by Yukari Kondo, Shinichiro Higa, Takeshi Iwasaki, Tomoya Matsumoto, Kazumitsu Maehara, Akihito Harada, Yoshihiro Baba, Masatoshi Fujita, Yasuyuki OhkawaThe western blotting technique is widely used to analyze protein expression levels and protein molecular weight. The chemiluminescence method is mainly used for detection due to its high sensitivity and ease of manipulation, but it is unsuitable for detailed analyses because it cannot be used to detect multiple proteins simultaneously. Recently, more attention has been paid to the fluorescence detection method because it is more quantitative and is suitable for the detection of multiple proteins simultaneously. However, fluorescence detection can be limited by poor image resolution and low detection sensitivity. Here, we describe a method to detect fluorescence in western blots using fluorescence microscopy to obtain high-resolution images. In this method, filters and fluorescent dyes are optimized to enhance detection sensitivity to a level similar to that of the chemiluminescence method.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191532
  • Decreased α-cell mass and early structural alterations of the exocrine
           pancreas in patients with type 1 diabetes: An analysis based on the nPOD

    • Authors: Fidéline Bonnet-Serrano Marc Diedisheim Roberto Mallone Etienne Larger
      Abstract: by Fidéline Bonnet-Serrano, Marc Diedisheim, Roberto Mallone, Etienne LargerBackground and aims Abnormal glucagon secretion and functional alterations of the exocrine pancreas have been described in patients with type 1 diabetes (T1D), but their respective anatomical substrata have seldom been investigated. Our aim was to develop an automated morphometric analysis process to characterize the anatomy of α-cell and exocrine pancreas in patients with T1D, using the publicly available slides of the Network for Pancreatic Organ Donors (nPOD). Materials and methods The ratio of β- and α-cell area to total tissue area were quantified in 75 patients with T1D (thereafter patients) and 66 control subjects (thereafter controls), on 2 insulin-stained and 4 glucagon-stained slides from both the head and the tail of the pancreas. The β- and α-cell masses were calculated in the 66 patients and the 50 controls for which the pancreas weight was available. Non-exocrine-non-endocrine tissue area (i.e. non-acinar, non-insular tissue) to total tissue area ratio was evaluated on both insulin- and glucagon-stained slides. Results were expressed as mean ±SD. Results An automated quantification method was set up using the R software and was validated by quantification of β-cell mass, a well characterized parameter. β-cell mass was 29.6±112 mg in patients and 628 ±717 mg in controls (p
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191528
  • Arrhythmogenic drugs can amplify spatial heterogeneities in the electrical
           restitution in perfused guinea-pig heart: An evidence from assessments of
           monophasic action potential durations and JT intervals

    • Authors: Oleg E. Osadchii
      Abstract: by Oleg E. OsadchiiNon-uniform shortening of the action potential duration (APD90) in different myocardial regions upon heart rate acceleration can set abnormal repolarization gradients and promote arrhythmia. This study examined whether spatial heterogeneities in APD90 restitution can be amplified by drugs with clinically proved proarrhythmic potential (dofetilide, quinidine, procainamide, and flecainide) and, if so, whether these effects can translate to the appropriate changes of the ECG metrics of ventricular repolarization, such as JT intervals. In isolated, perfused guinea-pig heart preparations, monophasic action potentials and volume-conducted ECG were recorded at progressively increased pacing rates. The APD90 measured at distinct ventricular sites, as well as the JTpeak and JTend values were plotted as a function of preceding diastolic interval, and the maximum slopes of the restitution curves were determined at baseline and upon drug administration. Dofetilide, quinidine, and procainamide reverse rate-dependently prolonged APD90 and steepened the restitution curve, with effects being greater at the endocardium than epicardium, and in the right ventricular (RV) vs. the left ventricular (LV) chamber. The restitution slope was increased to a greater extent for the JTend vs. the JTpeak interval. In contrast, flecainide reduced the APD90 restitution slope at LV epicardium without producing effect at LV endocardium and RV epicardium, and reduced the JTpeak restitution slope without changing the JTend restitution. Nevertheless, with all agents, these effects translated to the amplified epicardial-to-endocardial and the LV-to-RV non-uniformities in APD90 restitution, paralleled by the increased JTend vs. JTpeak difference in the restitution slope. In summary, these findings suggest that arrhythmic drug profiles are partly attributable to the accentuated regional heterogeneities in APD90 restitution, which can be indirectly determined through ECG assessments of the JTend vs. JTpeak dynamics at variable pacing rates.
      PubDate: 2018-01-19T22:00:00Z
      DOI: 10.1371/journal.pone.0191514
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