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  • 1
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-08
    Description: by Yiping Zou, Michael Glenn Mason, Yuling Wang, Eugene Wee, Conny Turni, Patrick J. Blackall, Matt Trau, Jose Ramon Botella
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 2
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-08
    Description: by Milana Frenkel-Morgenstern, Lonnie Welch, Bruno Gaeta, Diane E. Kovats
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 3
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-08
    Description: by Sarah Carmona, Benjamin Lin, Tristan Chou, Katti Arroyo, Sha Sun Mammalian X chromosome dosage compensation balances X-linked gene products between sexes and is coordinated by the long noncoding RNA (lncRNA) Xist . Multiple cis and trans -acting factors modulate Xist expression; however, the primary competence factor responsible for activating Xist remains a subject of dispute. The lncRNA Jpx is a proposed competence factor, yet it remains unknown if Jpx is sufficient to activate Xist expression in mice. Here, we utilize a novel transgenic mouse system to demonstrate a dose-dependent relationship between Jpx copy number and ensuing Jpx and Xist expression. By localizing transcripts of Jpx and Xist using RNA Fluorescence in situ Hybridization (FISH) in mouse embryonic cells, we provide evidence of Jpx acting in both trans and cis to activate Xist . Our data contribute functional and mechanistic insight for lncRNA activity in mice, and argue that Jpx is a competence factor for Xist activation in vivo .
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 4
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-08
    Description: by Uta Meyer zum Büschenfelde, Laura Isabel Brandenstein, Leonie von Elsner, Kristina Flato, Tess Holling, Martin Zenker, Georg Rosenberger, Kerstin Kutsche RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1. Disease-causing RIT1 mutations enhance protein-protein interaction between RIT1 and PAK1, CDC42 or RAC1 and uncouple complex formation from serum and growth factors. We show that the RIT1-PAK1 complex regulates cytoskeletal rearrangements as expression of wild-type RIT1 and its mutant forms resulted in dissolution of stress fibers and reduction of mature paxillin-containing focal adhesions in COS7 cells. This effect was prevented by co-expression of RIT1 with dominant-negative CDC42 or RAC1 and kinase-dead PAK1. By using a transwell migration assay, we show that RIT1 wildtype and the disease-associated variants enhance cell motility. Our work demonstrates a new function for RIT1 in controlling actin dynamics via acting in a signaling module containing PAK1 and RAC1/CDC42, and highlights defects in cell adhesion and migration as possible disease mechanism underlying NS.
    Print ISSN: 1553-7390
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  • 5
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-08
    Description: by Kenneth A. Barr, John Reinitz
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 6
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-08
    Description: by Babatunde W. Odetoyin, Amy S. Labar, Adebayo Lamikanra, Aaron O. Aboderin, Iruka N. Okeke
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 7
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-08
    Description: by Tatsuya Ishii, Yasuyuki Kimura, Masanori Ichise, Keisuke Takahata, Soichiro Kitamura, Sho Moriguchi, Manabu Kubota, Ming-Rong Zhang, Makiko Yamada, Makoto Higuchi, Yoshiro Okubo, Tetsuya Suhara
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 8
    Publication Date: 2018-05-08
    Description: by Guan-Dong Yang, Paul-Michael Agapow, Gabriel Yedid
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 9
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-08
    Description: by The PLOS ONE Staff
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 10
    Publication Date: 2018-05-08
    Description: by Agnese Collino, Alberto Termanini, Paola Nicoli, Giuseppe Diaferia, Sara Polletti, Camilla Recordati, Vittoria Castiglioni, Donatella Caruso, Nico Mitro, Gioacchino Natoli, Serena Ghisletti Chronic inflammation promotes oncogenic transformation and tumor progression. Many inflammatory agents also generate a toxic microenvironment, implying that adaptive mechanisms must be deployed for cells to survive and undergo transformation in such unfavorable contexts. A paradigmatic case is represented by cancers occurring in pediatric patients with genetic defects of hepatocyte phosphatidylcholine transporters and in the corresponding mouse model ( Mdr2 -/- mice), in which impaired bile salt emulsification leads to chronic hepatocyte damage and inflammation, eventually resulting in oncogenic transformation. By combining genomics and metabolomics, we found that the transition from inflammation to cancer in Mdr2 -/- mice was linked to the sustained transcriptional activation of metabolic detoxification systems and transporters by the Constitutive Androstane Receptor (CAR), a hepatocyte-specific nuclear receptor. Activation of CAR-dependent gene expression programs coincided with reduced content of toxic bile acids in cancer nodules relative to inflamed livers. Treatment of Mdr2 -/- mice with a CAR inhibitor blocked cancer progression and caused a partial regression of existing tumors. These results indicate that the acquisition of resistance to endo- or xeno-biotic toxicity is critical for cancers that develop in toxic microenvironments.
    Print ISSN: 1553-7390
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  • 11
    Publication Date: 2018-05-08
    Description: by Han Du, Qiushi Zheng, Jian Bing, Richard J. Bennett, Guanghua Huang Sexual reproduction is a universal mechanism for generating genetic diversity in eukaryotes. Fungi exhibit diverse strategies for sexual reproduction both in nature and in the laboratory. In this study, we report the discovery of same-sex (homothallic) mating in the human fungal pathogen Candida tropicalis . We show that same-sex mating occurs between two cells carrying the same mating type ( MTL a/a or α/α) and requires the presence of pheromone from the opposite mating type as well as the receptor for this pheromone. In ménage à trois mating mixes (i.e., “a x a + α helper” or “α x α + a helper” mixes), pheromone secreted by helper strains promotes diploid C . tropicalis cells to undergo same-sex mating and form tetraploid products. Surprisingly, however, the tetraploid mating products can then efficiently mate with cells of the opposite mating type to generate hexaploid products. The unstable hexaploid progeny generated from this coupled process of same- and opposite-sex mating undergo rapid chromosome loss and generate extensive genetic variation. Phenotypic analysis demonstrated that the mating progeny-derived strains exhibit diverse morphologies and phenotypes, including differences in secreted aspartic proteinase (Sap) activity and susceptibility to the antifungal drugs. Thus, the coupling of same- and opposite-sex mating represents a novel mode to generate polyploidy and genetic diversity, which may facilitate the evolution of new traits in C . tropicalis and adaptation to changing environments.
    Print ISSN: 1553-7390
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  • 12
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-08
    Description: by Soumya Chaurasia, Christian F. Lehner Sister kinetochores are connected to the same spindle pole during meiosis I and to opposite poles during meiosis II. The molecular mechanisms controlling the distinct behavior of sister kinetochores during the two meiotic divisions are poorly understood. To study kinetochore behavior during meiosis, we have optimized time lapse imaging with Drosophila spermatocytes, enabling kinetochore tracking with high temporal and spatial resolution through both meiotic divisions. The correct bipolar orientation of chromosomes within the spindle proceeds rapidly during both divisions. Stable bi-orientation of the last chromosome is achieved within ten minutes after the onset of kinetochore-microtubule interactions. Our analyses of mnm and tef mutants, where univalents instead of bivalents are present during meiosis I, indicate that the high efficiency of normal bi-orientation depends on pronounced stabilization of kinetochore attachments to spindle microtubules by the mechanical tension generated by spindle forces upon bi-orientation. Except for occasional brief separation episodes, sister kinetochores are so closely associated that they cannot be resolved individually by light microscopy during meiosis I, interkinesis and at the start of meiosis II. Permanent evident separation of sister kinetochores during M II depends on spindle forces resulting from bi-orientation. In mnm and tef mutants, sister kinetochore separation can be observed already during meiosis I in bi-oriented univalents. Interestingly, however, this sister kinetochore separation is delayed until the metaphase to anaphase transition and depends on the Fzy/Cdc20 activator of the anaphase-promoting complex/cyclosome. We propose that univalent bi-orientation in mnm and tef mutants exposes a release of sister kinetochore conjunction that occurs also during normal meiosis I in preparation for bi-orientation of dyads during meiosis II.
    Print ISSN: 1553-7390
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  • 13
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-08
    Description: by Jiunn-Diann Lin, Chun-Hsien Hsu, Chung-Ze Wu, An-Tsz Hsieh, Chang-Hsun Hsieh, Yao-Jen Liang, Yen-Lin Chen, Dee Pei, Jin-Biou Chang
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 14
    Publication Date: 2018-05-08
    Description: by Barbara J. Meyer, Mitchell K. Byrne, Carole Collier, Natalie Parletta, Donna Crawford, Pia C. Winberg, David Webster, Karen Chapman, Gayle Thomas, Jean Dally, Marijka Batterham, Ian Farquhar, Anne-Marie Martin, Luke Grant
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 15
    Publication Date: 2018-05-08
    Description: by Joshua Amo-Adjei, Kofi Aduo-Adjei, Christiana Opoku-Nyamaah, Chimaraoke Izugbara
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 16
    Publication Date: 2018-05-10
    Description: by Zhila Esna Ashari, Nairanjana Dasgupta, Kelly A. Brayton, Shira L. Broschat Type IV secretion systems (T4SS) are multi-protein complexes in a number of bacterial pathogens that can translocate proteins and DNA to the host. Most T4SSs function in conjugation and translocate DNA; however, approximately 13% function to secrete proteins, delivering effector proteins into the cytosol of eukaryotic host cells. Upon entry, these effectors manipulate the host cell’s machinery for their own benefit, which can result in serious illness or death of the host. For this reason recognition of T4SS effectors has become an important subject. Much previous work has focused on verifying effectors experimentally, a costly endeavor in terms of money, time, and effort. Having good predictions for effectors will help to focus experimental validations and decrease testing costs. In recent years, several scoring and machine learning-based methods have been suggested for the purpose of predicting T4SS effector proteins. These methods have used different sets of features for prediction, and their predictions have been inconsistent. In this paper, an optimal set of features is presented for predicting T4SS effector proteins using a statistical approach. A thorough literature search was performed to find features that have been proposed. Feature values were calculated for datasets of known effectors and non-effectors for T4SS-containing pathogens for four genera with a sufficient number of known effectors, Legionella pneumophila , Coxiella burnetii , Brucella spp, and Bartonella spp. The features were ranked, and less important features were filtered out. Correlations between remaining features were removed, and dimensional reduction was accomplished using principal component analysis and factor analysis. Finally, the optimal features for each pathogen were chosen by building logistic regression models and evaluating each model. The results based on evaluation of our logistic regression models confirm the effectiveness of our four optimal sets of features, and based on these an optimal set of features is proposed for all T4SS effector proteins.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 17
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-10
    Description: by Anthony Fenton, Mark D. Jesky, Rachel Webster, Stephanie J. Stringer, Punit Yadav, Iain Chapple, Indranil Dasgupta, Stephen J. Harding, Charles J. Ferro, Paul Cockwell Background Patients with chronic kidney disease (CKD) are at an increased risk of developing end-stage renal disease (ESRD). We assessed for the first time whether urinary free light chains (FLC) are independently associated with risk of ESRD in patients with CKD, and whether they offer incremental value in risk stratification. Materials and methods We measured urinary FLCs in 556 patients with CKD from a prospective cohort study. The association between urinary kappa/creatinine (KCR) and lambda/creatinine (LCR) ratios and development of ESRD was assessed by competing-risks regression (to account for the competing risk of death). The change in C-statistic and integrated discrimination improvement were used to assess the incremental value of adding KCR or LCR to the Kidney Failure Risk Equation (KFRE). Results 136 participants developed ESRD during a median follow-up time of 51 months. Significant associations between KCR and LCR and risk of ESRD became non-significant after adjustment for estimated glomerular filtration rate (eGFR) and albumin/creatinine ratio (ACR), although having a KCR or LCR 〉75 th centile remained independently associated with risk of ESRD. Neither KCR nor LCR as continuous or categorical variables provided incremental value when added to the KFRE for estimating risk of ESRD at two years. Conclusions Urinary FLCs have an association with progression to ESRD in patients with CKD which appears to be explained to a degree by their correlation with eGFR and ACR. Levels above the 75 th centile do have an independent association with ESRD, but do not improve upon a current model for risk stratification.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 18
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-10
    Description: by Jos Oudeman, Camiel Verhamme, Maurits P. Engbersen, Mattan W. A. Caan, Mario Maas, Martijn Froeling, Aart J. Nederveen, Gustav J. Strijkers Introduction Diffusion Tensor MRI (DT-MRI) is a promising tool for the evaluation of brachial plexus pathology. Therefore, we introduce and evaluate a fast DT-MRI protocol (8min33s scanning with 5–10 min postprocessing time) for the brachial plexus. Materials and methods Thirty healthy volunteers within three age-groups (18–35, 36–55, and 〉 56) received DT-MRI of the brachial-plexus twice. Means of fractional-anisotropy (FA), mean-diffusivity (MD), axial-diffusivity (AD), and radial-diffusivity (RD) for the individual roots and trunks were evaluated. A stepwise forward approach was applied to test for correlations with age, sex, body-mass-index (BMI), bodysurface, height, and bodyweight. Within-subject, intra-rater, and inter-rater repeatability were assessed using Bland-Altman analysis, coefficient of variation (CV), intraclass-correlation (ICC), and minimal detectable difference (MDD). Results No differences between sides and root levels were found. MD, AD, and RD correlated ( P 〈 0.05) with bodyweight. Within-subject quantification proved repeatable with CVs for FA, MD, AD, and RD of 16%, 12%, 11%, and 14%, respectively. Discussion The DT-MRI protocol was fast and repeatable. Found correlations should be considered in future studies of brachial plexus pathology.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 19
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-11
    Description: by Serafeim Perdikis, Luca Tonin, Sareh Saeedi, Christoph Schneider, José del R. Millán This work aims at corroborating the importance and efficacy of mutual learning in motor imagery (MI) brain–computer interface (BCI) by leveraging the insights obtained through our participation in the BCI race of the Cybathlon event. We hypothesized that, contrary to the popular trend of focusing mostly on the machine learning aspects of MI BCI training, a comprehensive mutual learning methodology that reinstates the three learning pillars (at the machine, subject, and application level) as equally significant could lead to a BCI–user symbiotic system able to succeed in real-world scenarios such as the Cybathlon event. Two severely impaired participants with chronic spinal cord injury (SCI), were trained following our mutual learning approach to control their avatar in a virtual BCI race game. The competition outcomes substantiate the effectiveness of this type of training. Most importantly, the present study is one among very few to provide multifaceted evidence on the efficacy of subject learning during BCI training. Learning correlates could be derived at all levels of the interface—application, BCI output, and electroencephalography (EEG) neuroimaging—with two end-users, sufficiently longitudinal evaluation, and, importantly, under real-world and even adverse conditions.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 20
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-11
    Description: by Neil Ashton
    Print ISSN: 1553-7390
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  • 21
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-11
    Description: by Tim van Mourik, Lukas Snoek, Tomas Knapen, David G. Norris The field of neuroimaging is rapidly adopting a more reproducible approach to data acquisition and analysis. Data structures and formats are being standardised and data analyses are getting more automated. However, as data analysis becomes more complicated, researchers often have to write longer analysis scripts, spanning different tools across multiple programming languages. This makes it more difficult to share or recreate code, reducing the reproducibility of the analysis. We present a tool, Porcupine, that constructs one’s analysis visually and automatically produces analysis code. The graphical representation improves understanding of the performed analysis, while retaining the flexibility of modifying the produced code manually to custom needs. Not only does Porcupine produce the analysis code, it also creates a shareable environment for running the code in the form of a Docker image. Together, this forms a reproducible way of constructing, visualising and sharing one’s analysis. Currently, Porcupine links to Nipype functionalities, which in turn accesses most standard neuroimaging analysis tools. Our goal is to release researchers from the constraints of specific implementation details, thereby freeing them to think about novel and creative ways to solve a given problem. Porcupine improves the overview researchers have of their processing pipelines, and facilitates both the development and communication of their work. This will reduce the threshold at which less expert users can generate reusable pipelines. With Porcupine, we bridge the gap between a conceptual and an implementational level of analysis and make it easier for researchers to create reproducible and shareable science. We provide a wide range of examples and documentation, as well as installer files for all platforms on our website: https://timvanmourik.github.io/Porcupine. Porcupine is free, open source, and released under the GNU General Public License v3.0.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 22
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-11
    Description: by Julia M. Kreiner, Stephen I. Wright
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  • 23
    Publication Date: 2018-05-11
    Description: by Weibing Zhang, Qiaoqiao Luo, Yan Zhu, Jiang Ma, Lei Cao, Min Yang, Pencheng Wen, Zhongmin Zhang, Xiaoling He
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 24
    Publication Date: 2018-05-11
    Description: by The PLOS ONE Staff
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 25
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-11
    Description: by Teresa Pitts, Albright G. Gayagoy, Melanie J. Rose, Ivan Poliacek, Jillian A. Condrey, M. Nicholas Musselwhite, Tabitha Y. Shen, Paul W. Davenport, Donald C. Bolser
    Electronic ISSN: 1932-6203
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  • 26
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-11
    Description: by Shanna K. Williams, Zachary P. Weiner, Robert D. Gilmore Borrelia burgdorferi , the agent of Lyme borreliosis, can elude hosts’ innate and adaptive immunity as part of the course of infection. The ability of B . burgdorferi to invade or be internalized by host cells in vitro has been proposed as a mechanism for the pathogen to evade immune responses or antimicrobials. We have previously shown that B . burgdorferi can be internalized by human neuroglial cells. In this study we demonstrate that these cells take up B . burgdorferi via coiling phagocytosis mediated by the formin, Daam1, a process similarly described for human macrophages. Following coincubation with glial cells, B . burgdorferi was enwrapped by Daam1-enriched coiling pseudopods. Coiling of B . burgdorferi was significantly reduced when neuroglial cells were pretreated with anti-Daam1 antibody indicating the requirement for Daam1 for borrelial phagocytosis. Confocal microscopy showed Daam1 colocalizing to the B . burgdorferi surface suggesting interaction with borrelial membrane protein(s). Using the yeast 2-hybrid system for identifying protein-protein binding, we found that the B . burgdorferi surface lipoprotein, BBA66, bound the FH2 subunit domain of Daam1. Recombinant proteins were used to validate binding by ELISA, pull-down, and co-immunoprecipitation. Evidence for native Daam1 and BBA66 interaction was suggested by colocalization of the proteins in the course of borrelial capture by the Daam1-enriched pseudopodia. Additionally, we found a striking reduction in coiling for a BBA66-deficient mutant strain compared to BBA66-expressing strains. These results show that coiling phagocytosis is a mechanism for borrelial internalization by neuroglial cells mediated by Daam1.
    Electronic ISSN: 1932-6203
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  • 27
    Publication Date: 2018-05-11
    Description: by Min Kyun Na, Yu Deok Won, Choong Hyun Kim, Jae Min Kim, Jin Hwan Cheong, Je Il Ryu, Myung-Hoon Han Background and purpose Osteoporosis is one of the most common chronic metabolic diseases, but detection and treatment rates are low. The aim of the current study was to evaluate the correlation between frontal skull Hounsfield unit (HU) values from brain computed tomography (CT) scans and T-scores of the lumbar spine and femoral neck from dual-energy X-ray absorptiometry (DXA) scans. Methods Patients with 〈 1 year between brain CT and DXA scans were included in the study. The average frontal skull HU value used for analysis was defined as the average of four HU values of the frontal bone. A receiver operating characteristic curve was generated, and area under the curve (AUC) was used to determine the HU values of the frontal skull for predicting osteoporosis. The frontal skull HU value with the highest sensitivity and specificity was considered the optimal cutoff value. Results In total, 899 patients who underwent both brain CT and DXA scans at a single institution were enrolled. Average skull HU values differed significantly among patients in different bone mineral density categories ( p 〈 0.001). There was a positive correlation between skull HU value and T-score (β = 105.06, p 〈 0.001, R 2 = 0.343). The mean HU value in subjects with osteoporosis was 515, and the optimal cutoff value for the prediction of osteoporosis was 610 HU (AUC = 0.775, 95% CI 0.744–0.806, p 〈 0.001). Conclusions Clinical brain CT scans can assist in the detection of osteoporosis, and patients with an HU value 〈 610 as determined via brain CT may be considered for further evaluation for possible osteoporosis.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 28
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-11
    Description: by Ruben D. Vromans, Suzanne R. Jongman The present study investigated the interplay between selective inhibition (the ability to suppress specific competing responses) and nonselective inhibition (the ability to suppress any inappropriate response) during single word production. To this end, we combined two well-established research paradigms: the picture-word interference task and the stop-signal task. Selective inhibition was assessed by instructing participants to name target pictures (e.g., dog) in the presence of semantically related (e.g., cat) or unrelated (e.g., window) distractor words. Nonselective inhibition was tested by occasionally presenting a visual stop-signal, indicating that participants should withhold their verbal response. The stop-signal was presented early (250 ms) aimed at interrupting the lexical selection stage, and late (325 ms) to influence the word-encoding stage of the speech production process. We found longer naming latencies for pictures with semantically related distractors than with unrelated distractors (semantic interference effect). The results further showed that, at both delays, stopping latencies (i.e., stop-signal RTs) were prolonged for naming pictures with semantically related distractors compared to pictures with unrelated distractors. Taken together, our findings suggest that selective and nonselective inhibition, at least partly, share a common inhibitory mechanism during different stages of the speech production process.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 29
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    Publication Date: 2018-05-11
    Description: by Louise E. Hogan, Emily Hanhauser, Kristen S. Hobbs, Christine D. Palmer, Yvonne Robles, Stephanie Jost, Anne S. LaCasce, Jeremy Abramson, Ayad Hamdan, Francisco M. Marty, Daniel R. Kuritzkes, Timothy J. Henrich Background Human Herpes Virus 8 (HHV8) can cause Kaposi’s Sarcoma (KS) in immunosuppressed individuals. However, little is known about the association between chemotherapy or hematopoietic stem cell transplantation (HSCT), circulating HHV8 DNA levels, and clinical KS in HIV-1-infected individuals with various malignancies. Therefore, we examined the associations between various malignancies, systemic cancer chemotherapy, T cell phenotypes, and circulating HHV8 DNA in 29 HIV-1-infected participants with concomitant KS or other cancer diagnoses. Methods We quantified HHV8 plasma viral loads and cell-associated HHV8 DNA and determined the relationship between circulating HHV8 DNA and lymphocyte counts, and markers of early and late lymphocyte activation, proliferation and exhaustion. Results There were no significant differences in plasma HHV8 DNA levels between baseline and post-chemotherapy time points or with the presence or absence of clinical KS. However, in two participants circulating HHV8 DNA increased following treatment for KS or HSCT for lymphoma,. We observed an approximately 2-log 10 reduction in plasma HHV8 DNA in an individual with KS and multicentric Castleman disease following rituximab monotherapy. Although individuals with clinical KS had lower mean CD4 + T cell counts and percentages as expected, there were no significant associations with these factors and plasma HHV8 levels. We identified increased proportions of CD8 + and CD4 + T cells expressing CD69 (P = 0.01 & P = 0.04 respectively), and increased CD57 expression on CD4 + T cells (P = 0.003) in participants with detectable HHV8. Conclusion These results suggest there is a complex relationship between circulating HHV8 DNA and tissue-based disease in HIV-1 and HHV8 co-infected individuals with various malignancies.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 30
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-12
    Description: by Shengjie Zhang, Hongchao Cao, Yan Li, Yanyan Jing, Shengnan Liu, Cheng Ye, Hui Wang, Shuxian Yu, Chengyuan Peng, Lijian Hui, Yu-cheng Wang, Haibing Zhang, Feifan Guo, Qiwei Zhai, Hui Wang, Ruimin Huang, Ling Zhang, Jingjing Jiang, Wei Liu, Hao Ying p38 has long been known as a central mediator of protein kinase A (PKA) signaling in brown adipocytes, which positively regulate the transcription of uncoupling protein 1 (UCP-1). However, the physiological role of p38 in adipose tissues, especially the white adipose tissue (WAT), is largely unknown. Here, we show that mice lacking p38α in adipose tissues display a lean phenotype, improved metabolism, and resistance to diet-induced obesity. Surprisingly, ablation of p38α causes minimal effects on brown adipose tissue (BAT) in adult mice, as evident from undetectable changes in UCP-1 expression, mitochondrial function, body temperature (BT), and energy expenditure. In contrast, genetic ablation of p38α in adipose tissues not only markedly facilitates the browning in WAT upon cold stress but also prevents diet-induced obesity. Consistently, pharmaceutical inhibition of p38α remarkably enhances the browning of WAT and has metabolic benefits. Furthermore, our data suggest that p38α deficiency promotes white-to-beige adipocyte reprogramming in a cell-autonomous manner. Mechanistically, inhibition of p38α stimulates the UCP-1 transcription through PKA and its downstream cAMP-response element binding protein (CREB), which form a positive feedback loop that functions to reinforce the white-to-beige phenotypic switch during cold exposure. Together, our study reveals that inhibition of p38α is able to promote WAT browning and confer metabolic benefits. Our study also indicates that p38α in WAT represents an exciting pharmacological target to combat obesity and metabolic diseases.
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    Publication Date: 2018-05-12
    Description: by Marie Ménard, Clélia Costechareyre, Gabriel Ichim, Jonathan Blachier, David Neves, Loraine Jarrosson-Wuilleme, Reinhard Depping, Jan Koster, Pierre Saintigny, Patrick Mehlen, Servane Tauszig-Delamasure The neurotrophin-3 (NT-3) receptor tropomyosin receptor kinase C (TrkC/NTRK3) has been described as a dependence receptor and, as such, triggers apoptosis in the absence of its ligand NT-3. This proapoptotic activity has been proposed to confer a tumor suppressor activity to this classic tyrosine kinase receptor (RTK). By investigating interacting partners that might facilitate TrkC-induced cell death, we have identified the basic helix-loop-helix (bHLH) transcription factor Hey1 and importin-α3 (karyopherin alpha 4 [KPNA4]) as direct interactors of TrkC intracellular domain, and we show that Hey1 is required for TrkC-induced apoptosis. We propose here that the cleaved proapoptotic portion of TrkC intracellular domain (called TrkC killer-fragment [TrkC-KF]) is translocated to the nucleus by importins and interacts there with Hey1. We also demonstrate that Hey1 and TrkC-KF transcriptionally silence mouse double minute 2 homolog (MDM2), thus contributing to p53 stabilization. p53 transcriptionally regulates the expression of TrkC-KF cytoplasmic and mitochondrial interactors cofactor of breast cancer 1 (COBRA1) and B cell lymphoma 2–associated X (BAX), which will subsequently trigger the intrinsic pathway of apoptosis. Of interest, TrkC was proposed to constrain tumor progression in neuroblastoma (NB), and we demonstrate in an avian model that TrkC tumor suppressor activity requires Hey1 and p53.
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  • 32
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-12
    Description: by Sofia Mensurado, Margarida Rei, Telma Lança, Marianna Ioannou, Natacha Gonçalves-Sousa, Hiroshi Kubo, Marie Malissen, Venizelos Papayannopoulos, Karine Serre, Bruno Silva-Santos Interleukin 17 (IL-17)–producing γδ T cells (γδ17 T cells) have been recently found to promote tumor growth and metastasis formation. How such γδ17 T-cell responses may be regulated in the tumor microenvironment remains, however, largely unknown. Here, we report that tumor-associated neutrophils can display an overt antitumor role by strongly suppressing γδ17 T cells. Tumor-associated neutrophils inhibited the proliferation of murine CD27 − Vγ6 + γδ17 T cells via induction of oxidative stress, thereby preventing them from constituting the major source of pro-tumoral IL-17 in the tumor microenvironment. Mechanistically, we found that low expression of the antioxidant glutathione in CD27 − γδ17 T cells renders them particularly susceptible to neutrophil-derived reactive oxygen species (ROS). Consistently, superoxide deficiency, or the administration of a glutathione precursor, rescued CD27 − Vγ6 + γδ17 T-cell proliferation in vivo. Moreover, human Vδ1 + γδ T cells, which contain most γδ17 T cells found in cancer patients, also displayed low glutathione levels and were potently inhibited by ROS. This work thus identifies an unanticipated, immunosuppressive yet antitumoral, neutrophil/ROS/γδ17 T-cell axis in the tumor microenvironment.
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  • 33
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    Publication Date: 2018-05-12
    Description: by Antoine Frenoy, Sebastian Bonhoeffer The stress-induced mutagenesis hypothesis postulates that in response to stress, bacteria increase their genome-wide mutation rate, in turn increasing the chances that a descendant is able to better withstand the stress. This has implications for antibiotic treatment: exposure to subinhibitory doses of antibiotics has been reported to increase bacterial mutation rates and thus probably the rate at which resistance mutations appear and lead to treatment failure. More generally, the hypothesis posits that stress increases evolvability (the ability of a population to generate adaptive genetic diversity) and thus accelerates evolution. Measuring mutation rates under stress, however, is problematic, because existing methods assume there is no death. Yet subinhibitory stress levels may induce a substantial death rate. Death events need to be compensated by extra replication to reach a given population size, thus providing more opportunities to acquire mutations. We show that ignoring death leads to a systematic overestimation of mutation rates under stress. We developed a system based on plasmid segregation that allows us to measure death and division rates simultaneously in bacterial populations. Using this system, we found that a substantial death rate occurs at the tested subinhibitory concentrations previously reported to increase mutation rate. Taking this death rate into account lowers and sometimes removes the signal for stress-induced mutagenesis. Moreover, even when antibiotics increase mutation rate, we show that subinhibitory treatments do not increase genetic diversity and evolvability, again because of effects of the antibiotics on population dynamics. We conclude that antibiotic-induced mutagenesis is overestimated because of death and that understanding evolvability under stress requires accounting for the effects of stress on population dynamics as much as on mutation rate. Our goal here is dual: we show that population dynamics and, in particular, the numbers of cell division are crucial but neglected parameters in the evolvability of a population, and we provide experimental and computational tools and methods to study evolvability under stress, leading to a reassessment of the magnitude and significance of the stress-induced mutagenesis paradigm.
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  • 34
    Publication Date: 2018-05-12
    Description: by Mikolaj J. Sulkowski, Tae Hee Han, Carolyn Ott, Qi Wang, Esther M. Verheyen, Jennifer Lippincott-Schwartz, Mihaela Serpe
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 35
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    Publication Date: 2018-05-12
    Description: by Naveed Ahmad, M. Saleem Characterisation and thermal deterioration of desi ghee obtained from buffalo milk is presented for the first time using the potential of Fluorescence spectroscopy. The emission bands in non-heated desi ghee centred at 375 nm is labelled for vitamin D, 390 nm for vitamin K, 440–460 nm for isomers of conjugated linoleic acid (CLA), 490 nm for vitamin A and the region 620–700 nm is assigned to chlorophyll contents. Fluorescence emission spectra from all the heated and non-heated ghee samples were recorded using excitation wavelengths at 280, and 410 nm which were found best for getting maximum spectral signatures. Heating of desi ghee affects its molecular composition, however, the temperature range from 140 to 170°C may be defined safe for cooking /frying where it does not lose much of its molecular composition. Further, the rise in temperature induces prominent spectral variations which confirm the deterioration of valuable vitamins, isomers of CLA and chlorophyll contents. Fluorescence emission peak at 552 nm shows oxidation product and an increase in its intensity with the rise in temperature is observed. In order to classify heated samples at different temperatures, principal component analysis (PCA) has been applied on heated and non-heated ghee samples that further elucidated the temperature effects.
    Electronic ISSN: 1932-6203
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  • 36
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    Publication Date: 2018-05-12
    Description: by Sharukh Lokhandwala, Ned McCague, Abdullah Chahin, Braiam Escobar, Mengling Feng, Mohammad M. Ghassemi, David J. Stone, Leo Anthony Celi Rationale Factors associated with one-year mortality after recovery from critical illness are not well understood. Clinicians generally lack information regarding post-hospital discharge outcomes of patients from the intensive care unit, which may be important when counseling patients and families. Objective We sought to determine which factors among patients who survived for at least 30 days post-ICU admission are associated with one-year mortality. Methods Single-center, longitudinal retrospective cohort study of all ICU patients admitted to a tertiary-care academic medical center from 2001–2012 who survived ≥30 days from ICU admission. Cox’s proportional hazards model was used to identify the variables that are associated with one-year mortality. The primary outcome was one-year mortality. Results 32,420 patients met the inclusion criteria and were included in the study. Among patients who survived to ≥30 days, 28,583 (88.2%) survived for greater than one year, whereas 3,837 (11.8%) did not. Variables associated with decreased one-year survival include: increased age, malignancy, number of hospital admissions within the prior year, duration of mechanical ventilation and vasoactive agent use, sepsis, history of congestive heart failure, end-stage renal disease, cirrhosis, chronic obstructive pulmonary disease, and the need for renal replacement therapy. Numerous effect modifications between these factors were found. Conclusion Among survivors of critical illness, a significant number survive less than one year. More research is needed to help clinicians accurately identify those patients who, despite surviving their acute illness, are likely to suffer one-year mortality, and thereby to improve the quality of the decisions and care that impact this outcome.
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  • 37
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    Publication Date: 2018-05-12
    Description: by Zhibin Du, Akbar Ali The Wiener polarity number (which, nowadays, known as the Wiener polarity index and usually denoted by W p ) was devised by the chemist Harold Wiener, for predicting the boiling points of alkanes. The index W p of chemical trees (chemical graphs representing alkanes) is defined as the number of unordered pairs of vertices (carbon atoms) at distance 3. The inverse problems based on some well-known topological indices have already been addressed in the literature. The solution of such inverse problems may be helpful in speeding up the discovery of lead compounds having the desired properties. This paper is devoted to solving a stronger version of the inverse problem based on Wiener polarity index for chemical trees. More precisely, it is proved that for every integer t ∈ { n − 3, n − 2,…,3 n − 16, 3 n − 15}, n ≥ 6, there exists an n -vertex chemical tree T such that W p ( T ) = t .
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    Publication Date: 2018-05-12
    Description: by Fredrick Dermawan Purba, Joke A. M. Hunfeld, Aulia Iskandarsyah, Titi Sahidah Fitriana, Sawitri S. Sadarjoen, Jan Passchier, Jan J. V. Busschbach Objectives The objective of this study is to obtain population norms and to assess test-retest reliability of EQ-5D-5L and WHOQOL-BREF for the Indonesian population. Methods A representative sample of 1056 people aged 17–75 years was recruited from the Indonesian general population. We used a multistage stratified quota sampling method with respect to residence, gender, age, education level, religion and ethnicity. Respondents completed EQ-5D-5L and WHOQOL-BREF with help from an interviewer. Norms data for both instruments were reported. For the test-retest evaluations, a sub-sample of 206 respondents completed both instruments twice. Results The total sample and test-retest sub-sample were representative of the Indonesian general population. The EQ-5D-5L shows almost perfect agreement between the two tests (Gwet’s AC: 0.85–0.99 and percentage agreement: 90–99%) regarding the five dimensions. However, the agreement of EQ-VAS and index scores can be considered as poor (ICC: 0.45 and 0.37 respectively). For the WHOQOL-BREF, ICCs of the four domains were between 0.70 and 0.79, which indicates moderate to good agreement. For EQ-5D-5L, it was shown that female and older respondents had lower EQ-index scores, whilst rural, younger and higher-educated respondents had higher EQ-VAS scores. For WHOQOL-BREF: male, younger, higher-educated, high-income respondents had the highest scores in most of the domains, overall quality of life, and health satisfaction. Conclusions This study provides representative estimates of self-reported health status and quality of life for the general Indonesian population as assessed by the EQ-5D-5L and WHOQOL-BREF instruments. The descriptive system of the EQ-5D-5L and the WHOQOL-BREF have high test-retest reliability while the EQ-VAS and the index score of EQ-5D-5L show poor agreement between the two tests. Our results can be useful to researchers and clinicians who can compare their findings with respect to these concepts with those of the Indonesian general population.
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  • 39
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    Publication Date: 2018-05-12
    Description: by Melissa E. M. Peters, Remko Kockelkoren, Esther J. M. de Brouwer, Huiberdina L. Koek, Ronald L. A. W. Bleys, Willem P. Th. M. Mali, Jeroen Hendrikse, Annemieke M. Rozemuller, Pim A. de Jong Background Calcifications within the hippocampus were recently described for the first time on computed tomography (CT). These calcifications appeared in patients older than 50 years, the prevalence increases with age and they may be associated with cognitive decline. The aim of this study was to determine the histological basis (the presence, severity and location) of these CT-detected hippocampal calcifications of post-mortem brains. Methods CT scans of seven post-mortem brains were scored for the presence and severity (mild, moderate, severe) of hippocampal calcification. After this, samples from nine hippocampi (bilateral in two brains, unilateral in five brains) were stained with hematoxylin and eosin (HE) to indicate the cytoarchitecture, with Elastica van Gieson to analyse the elastic connective tissue of the vessel walls and with von Kossa for detection of calcium. Results In four brains (six hippocampi), calcifications were both found on CT and in corresponding histology. In three brains (three hippocampi), calcifications were absent on CT and corresponding histology. In histology, mild calcifications were located in the tail and severe calcifications involved the tail, body and sometimes the head of the hippocampus. The calcifications co-localised with precapillaries, capillaries and arteries of the molecular and granular layers of the dentate gyrus and the Cornu Ammonis 1. Conclusions In this study, calcifications of the hippocampus as seen on CT scans were histologically located in vascular structures of the tail, body and head of the hippocampus.
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  • 40
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    Publication Date: 2018-05-12
    Description: by Chelsea Virgile, Pricila Hauk, Hsuan-Chen Wu, Wu Shang, Chen-Yu Tsao, Gregory F. Payne, William E. Bentley Synthetic biologists construct innovative genetic/biological systems to treat environmental, energy, and health problems. Many systems employ rewired cells for non-native product synthesis, while a few have employed the rewired cells as ‘smart’ devices with programmable function. Building on the latter, we developed a genetic construct to control and direct bacterial motility towards hydrogen peroxide, one of the body’s immune response signaling molecules. A motivation for this work is the creation of cells that can target and autonomously treat disease, the latter signaled by hydrogen peroxide release. Bacteria naturally move towards a variety of molecular cues (e.g., nutrients) in the process of chemotaxis. In this work, we engineered bacteria to recognize and move towards hydrogen peroxide, a non-native chemoattractant and potential toxin. Our system exploits oxyRS , the native oxidative stress regulon of E . coli . We first demonstrated H 2 O 2 -mediated upregulation motility regulator, CheZ. Using transwell assays, we showed a two-fold increase in net motility towards H 2 O 2 . Then, using a 2D cell tracking system, we quantified bacterial motility descriptors including velocity, % running (of tumble/run motions), and a dynamic net directionality towards the molecular cue. In CheZ mutants, we found that increased H 2 O 2 concentration (0–200 μM) and induction time resulted in increased running speeds, ultimately reaching the native E . coli wild-type speed of ~22 μm/s with a ~45–65% ratio of running to tumbling. Finally, using a microfluidic device with stable H 2 O 2 gradients, we characterized responses and the potential for “programmed” directionality towards H 2 O 2 in quiescent fluids. Overall, the synthetic biology framework and tracking analysis in this work will provide a framework for investigating controlled motility of E . coli and other ‘smart’ probiotics for signal-directed treatment.
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    Publication Date: 2018-05-12
    Description: by Jonathan Shepherd, Geoff K. Frampton, Karen Pickett, Jeremy C. Wyatt Objective To investigate methods and processes for timely, efficient and good quality peer review of research funding proposals in health. Methods A two-stage evidence synthesis: (1) a systematic map to describe the key characteristics of the evidence base, followed by (2) a systematic review of the studies stakeholders prioritised as relevant from the map on the effectiveness and efficiency of peer review ‘innovations’. Standard processes included literature searching, duplicate inclusion criteria screening, study keyword coding, data extraction, critical appraisal and study synthesis. Results A total of 83 studies from 15 countries were included in the systematic map. The evidence base is diverse, investigating many aspects of the systems for, and processes of, peer review. The systematic review included eight studies from Australia, Canada, and the USA, evaluating a broad range of peer review innovations. These studies showed that simplifying the process by shortening proposal forms, using smaller reviewer panels, or expediting processes can speed up the review process and reduce costs, but this might come at the expense of peer review quality, a key aspect that has not been assessed. Virtual peer review using videoconferencing or teleconferencing appears promising for reducing costs by avoiding the need for reviewers to travel, but again any consequences for quality have not been adequately assessed. Conclusions There is increasing international research activity into the peer review of health research funding. The studies reviewed had methodological limitations and variable generalisability to research funders. Given these limitations it is not currently possible to recommend immediate implementation of these innovations. However, many appear promising based on existing evidence, and could be adapted as necessary by funders and evaluated. Where feasible, experimental evaluation, including randomised controlled trials, should be conducted, evaluating impact on effectiveness, efficiency and quality.
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    Publication Date: 2018-05-12
    Description: by Juan Manuel Gálvez, Daniel Castillo, Luis Javier Herrera, Belén San Román, Olga Valenzuela, Francisco Manuel Ortuño, Ignacio Rojas Most of the research studies developed applying microarray technology to the characterization of different pathological states of any disease may fail in reaching statistically significant results. This is largely due to the small repertoire of analysed samples, and to the limitation in the number of states or pathologies usually addressed. Moreover, the influence of potential deviations on the gene expression quantification is usually disregarded. In spite of the continuous changes in omic sciences, reflected for instance in the emergence of new Next-Generation Sequencing-related technologies, the existing availability of a vast amount of gene expression microarray datasets should be properly exploited. Therefore, this work proposes a novel methodological approach involving the integration of several heterogeneous skin cancer series, and a later multiclass classifier design. This approach is thus a way to provide the clinicians with an intelligent diagnosis support tool based on the use of a robust set of selected biomarkers, which simultaneously distinguishes among different cancer-related skin states. To achieve this, a multi-platform combination of microarray datasets from Affymetrix and Illumina manufacturers was carried out. This integration is expected to strengthen the statistical robustness of the study as well as the finding of highly-reliable skin cancer biomarkers. Specifically, the designed operation pipeline has allowed the identification of a small subset of 17 differentially expressed genes (DEGs) from which to distinguish among 7 involved skin states. These genes were obtained from the assessment of a number of potential batch effects on the gene expression data. The biological interpretation of these genes was inspected in the specific literature to understand their underlying information in relation to skin cancer. Finally, in order to assess their possible effectiveness in cancer diagnosis, a cross-validation Support Vector Machines (SVM)-based classification including feature ranking was performed. The accuracy attained exceeded the 92% in overall recognition of the 7 different cancer-related skin states. The proposed integration scheme is expected to allow the co-integration with other state-of-the-art technologies such as RNA-seq.
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  • 43
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    Publication Date: 2018-05-12
    Description: by Ana Caroline N. Botelho, Juliana G. Oliveira, Andreia P. Damasco, Késia T. B. Santos, Ana Flávia M. Ferreira, Gabriel T. Rocha, Penélope S. Marinho, Rita B. G. Bornia, Tatiana C. A. Pinto, Marco A. Américo, Sergio E. L. Fracalanzza, Lúcia M. Teixeira Group B Streptococcus (GBS) carriage by pregnant women is the primary risk factor for early-onset GBS neonatal sepsis. Intrapartum antibiotic prophylaxis (IAP) can prevent this transmission route, and two main approaches are recommended to base the selection of pregnant women to be submitted to IAP: the risk-based and the culture-based strategies. In Brazil, compliance to such recommendations is poor, and not much is known about GBS carriage. In the present study, 3,647 pregnant women living in Rio de Janeiro State, Brazil, were screened for GBS anogenital colonization, over a period of 8 years (2008–2015). GBS was detected in 956 (26.2%) of them, and presence of vaginal discharge was the only trait associated with a higher risk for GBS colonization. Serotypes Ia (257; 37.3%) and II (137; 19.9%) were the most frequent among 689 (72.1% of the total) GBS isolates evaluated, followed by NT isolates (84; 12.1%), serotype Ib (77; 11.1%), V (63; 9.1%), III (47; 6.8%) and IV (24; 3.5%). Estimated coverage of major serotype-based GBS vaccines currently under clinical trials would vary from 65.2% to 84.3%. All 689 isolates tested were susceptible to ampicillin and vancomycin. Resistance to chloramphenicol, clindamycin, erythromycin, levofloxacin, and tetracycline was observed in 5% (35), 2% (14), 14% (97), 5% (35) and 86% (592) of the isolates, respectively. No significant fluctuations in colonization rates, serotype distribution and antimicrobial susceptibility profiles were observed throughout the period of time investigated. The culture-based approach for IAP recommendation showed to be the best choice for the population investigated when compared to the risk-based, since the first did not increase the number of pregnant women submitted to antibiotic therapy and covered a larger number of women who were actually colonized by GBS. The fact the not all isolates were available for additional characterization, and serotype IX antiserum was not available for testing represent limitations of this study. Nevertheless, to the best of our knowledge, this is the largest investigation on GBS carriage among pregnant women in Brazil up to date, and results are useful for improving GBS prevention and treatment strategies.
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    Publication Date: 2018-05-15
    Description: by Aaditya V. Rangan, Caroline C. McGrouther, John Kelsoe, Nicholas Schork, Eli Stahl, Qian Zhu, Arjun Krishnan, Vicky Yao, Olga Troyanskaya, Seda Bilaloglu, Preeti Raghavan, Sarah Bergen, Anders Jureus, Mikael Landen, Bipolar Disorders Working Group of the Psychiatric Genomics Consortium A common goal in data-analysis is to sift through a large data-matrix and detect any significant submatrices (i.e., biclusters) that have a low numerical rank. We present a simple algorithm for tackling this biclustering problem. Our algorithm accumulates information about 2-by-2 submatrices (i.e., ‘loops’) within the data-matrix, and focuses on rows and columns of the data-matrix that participate in an abundance of low-rank loops. We demonstrate, through analysis and numerical-experiments, that this loop-counting method performs well in a variety of scenarios, outperforming simple spectral methods in many situations of interest. Another important feature of our method is that it can easily be modified to account for aspects of experimental design which commonly arise in practice. For example, our algorithm can be modified to correct for controls, categorical- and continuous-covariates, as well as sparsity within the data. We demonstrate these practical features with two examples; the first drawn from gene-expression analysis and the second drawn from a much larger genome-wide-association-study (GWAS).
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 45
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    Publication Date: 2018-05-15
    Description: by The PLOS ONE Editors
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  • 46
    Publication Date: 2018-05-15
    Description: by Thomas M. Chappell, Amanda L. P. Beaudoin, George G. Kennedy
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  • 47
    Publication Date: 2018-05-15
    Description: by Lixia Ge, Chun Wei Yap, Bee Hoon Heng Objectives The aims of the study were to identify the associations between multimorbidity and specific physical function domains among community-dwelling adults in Singapore, and to examine sex differences in the associations. Methods This study was conducted using baseline data of 1,940 participants in the Population Health Index Survey conducted in the Central Region of Singapore from November 2015 to November 2016. Physical function was assessed using the Function Component of the Late-life Function and Disability Instrument and compared between men and women. Multiple linear regressions were conducted to examine associations between multimorbidity and different physical function domains for all participants, and in men and women separately. Results The prevalence of multimorbidity in the study population was 35.0% for adults aged 21 years and above, with no differences between men and women. Multimorbidity was associated with reduced upper extremity function, basic and advanced lower extremity function, and overall function in men and women after adjusting for demographic factors. Multimorbidity had a stronger association with advanced lower extremity function and overall physical function in women than in men. Conclusions The findings of this study indicate that multimorbidity is associated with physical function domains in men and women, and in particular advanced lower extremity for women. Effective community-based interventions need to be implemented to preserve physical function in individuals with multimorbidity to keep them functionally independent and physically active in the community. Additional focus on advanced lower extremity function for women is needed.
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  • 48
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    Publication Date: 2018-05-15
    Description: by Ahmad Abu Turab Naqvi, Mohd Shahbaaz, Faizan Ahmad, Md. Imtaiyaz Hassan
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    Publication Date: 2018-05-15
    Description: by Barbara Scotti, Giulio Disanto, Rosaria Sacco, Marilu’ Guigli, Chiara Zecca, Claudio Gobbi Background Despite positive results from phase II and observational studies, Rituximab (RTX) is not currently approved for multiple sclerosis (MS) treatment and can only be used off-label. Objective To characterize MS patients treated with RTX and investigate its effectiveness and safety in a clinical practice setting. Methods Observational analysis of data collected from MS patients at the Neurocenter of Southern Switzerland. Relapses, EDSS worsening, MRI lesion accrual and "evidence of disease activity” (EDA) status were described by Cox regression. RTX and natalizumab treated patients were matched by propensity scores. Results Out of 453 MS patients, 82 were treated with RTX, 43 (52.4%) relapsing-remitting (RRMS) and 39 (47.6%) progressive MS (median age = 48 [40–54] years, females n = 60 [73.2%], EDSS = 4.0 [2.5–6.0], median follow-up = 1.5 [1.0–2.5] years). Three relapses occurred and 59 (75.6%) patients had not EDA at follow-up end. Time to EDA was similar in RTX and natalizumab treated RRMS patients (HR = 1.64, 95%CI = 0.46–5.85, p = 0.44). Twenty-four patients presented non infusion related adverse events (infections), requiring RTX discontinuation in 6 individuals. Conclusion These results provide further evidence for RTX being effective in MS treatment, to a similar extent to natalizumab in RRMS. Clinicians must be vigilant for the potential occurrence of infections.
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    Publication Date: 2018-05-15
    Description: by Michelle L. Gatton, Sadmir Ciketic, John W. Barnwell, Qin Cheng, Peter L. Chiodini, Sandra Incardona, David Bell, Jane Cunningham, Iveth J. González Background Malaria rapid diagnostic tests (RDTs) can produce false positive (FP) results in patients with human African trypanosomiasis and rheumatoid factor (RF), but specificity against other infectious agents and immunological factors is largely unknown. Low diagnostic specificity caused by cross-reactivity may lead to over-estimates of the number of malaria cases and over-use of antimalarial drugs, at the cost of not diagnosing and treating the true underlying condition. Methods Data from the WHO Malaria RDT Product Testing Programme was analysed to assess FP rates of 221 RDTs against four infectious agents (Chagas, dengue, Leishmaniasis and Schistosomiasis) and four immunological factors (anti-nuclear antibody, human anti-mouse antibody (HAMA), RF and rapid plasma regain). Only RDTs with a FP rate against clean negative samples less than 10% were included. Paired t-tests were used to compare product-specific FP rates on clean negative samples and samples containing non- Plasmodium infectious agents and immunological factors. Results Forty (18%) RDTs showed no FP results against any tested infectious agent or immunological factor. In the remaining RDTs significant and clinically relevant increases in FP rates were observed for samples containing HAMA and RF ( P
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  • 51
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    Publication Date: 2018-05-15
    Description: by Vinoth K. Manoharan, Berin P. Varghese, Anandan Paldurai, Siba K. Samal Newcastle disease (ND) causes severe economic loss to poultry industry worldwide. Frequent outbreaks of ND in commercial chickens vaccinated with live vaccines suggest a need to develop improved vaccines that are genetically matched against circulating Newcastle disease virus (NDV) strains. In this study, the fusion protein cleavage site (FPCS) sequence of NDV strain Banjarmasin/010 (Banj), a genotype VII NDV, was individually modified using primer mutagenesis to those of avian paramyxovirus (APMV) serotypes 2, 7 and 8 and compared with the recombinant Banjarmasin (rBanj) with avirulent NDV LaSota cleavage site (rBanj-LaSota). These FPCS mutations changed the in vitro cell-to-cell fusion activity and made rBanj FPCS mutant viruses highly attenuated in chickens. When chickens immunized with the rBanj FPCS mutant viruses and challenged with the virulent Banj, there was reduced challenge virus shedding observed compared to chickens immunized with the heterologous vaccine strain LaSota. Among the genotype VII NDV Banj vaccine candidates, rBanj-LaSota and rBanj containing FPCS of APMV-8 induced highest neutralizing antibody titers and protected chickens with reduced challenge virus shedding. These results show the effect of the F protein cleavage site sequence in generating genotype VII matched NDV vaccines.
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  • 52
    Publication Date: 2018-05-15
    Description: by Hikaru Ihira, Norie Sawada, Motoki Iwasaki, Taiki Yamaji, Atsushi Goto, Mitsuhiko Noda, Hiroyasu Iso, Shoichiro Tsugane, the JPHC Study Group Adult height is determined by both genetic characteristics and environmental factors in early life. Although previous studies have suggested that adult height is associated with risk of mortality, comprehensive associations between height and all-cause and cause-specific mortality in the Japanese population are unclear. We aimed to evaluate the associations between adult height and all-cause and cause-specific mortality among Japanese men and women in a prospective cohort study. We investigated 107,794 participants (50,755 men and 57,039 women) aged 40 to 69 years who responded to the baseline questionnaire in the Japan Public Health Center-based Prospective Study. Participants were classified by quartile of adult height obtained from a self-reported questionnaire in men (
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  • 53
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    Publication Date: 2018-05-15
    Description: by Hiromi Kitazume, Mehmet Dayi, Ryusei Tanaka, Taisei Kikuchi Oxygen is required for the completion of almost all known metazoan lifecycles, but many metazoans harbour abilities to withstand varying degrees and periods of hypoxia. Caenorhabditis elegans , one of the most popular model organism is extensively used as a model for the study of hypoxia and anoxia biology and it has been found that this nematode is capable of tolerance to varying degrees of hypoxia. Considering the extremely high diversity of nematodes, the effects of low oxygen concentration and mechanisms of adaptation to oxygen depletion differ among species. In this study, we used a simple assay to examine anoxia tolerance in four nematode species, including three free-living and one plant parasitic nematode. We found that the plant parasitic nematode Bursaphelenchus xylophilus can survive more than 14 days under anoxic conditions. Comparisons of behaviour during anoxia induction and the repertoire of oxygen sensation genes among the tested species suggested the existence of different oxygen sensation systems between B . xylophilus and C . elegans , which quickly introduce suspended animation in response to oxygen depletion to survive long-term anoxia.
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  • 54
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    Publication Date: 2018-05-15
    Description: by Louis-Solal Giboin, Ehsan Amiri, Raphael Bertschinger, Markus Gruber Purpose Active recovery is often used by athletes after strenuous exercise or competition but its underlying mechanisms are not well understood. We hypothesized that active recovery speeds-up recovery processes within the muscle and the central nervous system (CNS). Methods We assessed muscular and CNS recovery by measuring the voluntary activation (VA) in the vastus lateralis muscle with transcranial magnetic stimulation (VA TMS ) and peripheral nerve stimulation (VA PNS ) during maximal voluntary contractions (MVC) of the knee extensors in 11 subjects. Measurements were performed before and after a fatiguing cycling time-trial, after an active and a passive recovery treatment and after another fatiguing task (1 min MVC). The measurements were performed a second time 24 h after the time-trial. Results We observed a time × group interaction effect for VA TMS (p = 0.013). Post-hoc corrected T-tests demonstrated an increased VA TMS after active recovery when measured after the 1 min MVC performed 24 h after the time-trial (mean ± SD; 95.2 ± 4.1% vs. 89.2 ± 6.6%, p = 0.026). No significant effects were observed for all other variables. Conclusions Active recovery increased aspects of central, rather than muscle recovery. However, no effect on MVC was seen, implying that even if active recovery speeds up CNS recovery, without affecting the recovery of muscle contractile properties, this doesn´t translate into increases in overall performance.
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  • 55
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    Publication Date: 2018-05-15
    Description: by Estrella Rubio-Solsona, Salvador Martí, Juan J. Vílchez, Francesc Palau, Janet Hoenicka Ankyrin repeat and kinase domain containing 1 ( ANKK1 ) gene has been widely related to neuropsychiatry disorders. The localization of ANKK1 in neural progenitors and its correlation with the cell cycle has suggested its participation in development. However, ANKK1 functions still need to be identified. Here, we have further characterized the ANKK1 localization in vivo and in vitro , by using immunolabeling, quantitative real-time PCR and Western blot in the myogenic lineage. Histologic investigations in mice and humans revealed that ANKK1 is expressed in precursors of embryonic and adult muscles. In mice embryos, ANKK1 was found in migrating myotubes where it shows a polarized cytoplasmic distribution, while proliferative myoblasts and satellite cells show different isoforms in their nuclei and cytoplasm. In vitro studies of ANKK1 protein isoforms along the myogenic progression showed the decline of nuclear ANKK1-kinase until its total exclusion in myotubes. In adult mice, ANKK1 was expressed exclusively in the Fast-Twitch muscles fibers subtype. The induction of glycolytic metabolism in C2C12 cells with high glucose concentration or treatment with berberine caused a significant increase in the ANKK1 mRNA. Similarly, C2C12 cells under hypoxic conditions caused the increase of nuclear ANKK1. These results altogether show a relationship between ANKK1 gene regulation and the metabolism of muscles during development and in adulthood. Finally, we found ANKK1 expression in regenerative fibers of muscles from dystrophic patients. Future studies in ANKK1 biology and the pathological response of muscles will reveal whether this protein is a novel muscle disease biomarker.
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  • 56
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    Publication Date: 2018-05-15
    Description: by Kara B. Marley, Larry A. Kuehn, John W. Keele, Benjamin W. Wileman, Michael G. Gonda Individuals often respond differently to the same vaccine; some of this variation may be caused by genetic differences among animals. Our objective was to estimate heritability and identify genomic regions associated with humoral response to an Escherichia coli O157:H7 vaccine in beef cattle. Crossbred beef cattle (n = 651) were vaccinated with a commercially available E . coli O157:H7 vaccine. Serum was collected at time of initial vaccination (d 0), booster (d 21), and d 56 after initial vaccination. Total antibodies specific to siderophore receptor and porin proteins in the vaccine were quantified by enzyme-linked immunosorbent assay. Genomic DNA was isolated from whole blood and genotyped with the bovine GeneSeek Genomic Profiler-High Density 78K or 26K Single Nucleotide Polymorphism BeadChip and imputed to 777,000 SNP genotypes. Heritability was estimated by restricted maximum likelihood (REML) using both 1) pedigree and 2) genomic relationships among individuals. Fixed effects were contemporary group, calf age, sex, principal components from SNP genotype data, and pedigree-derived heterozygosity effects. Additive and dominance effects of SNPs were estimated individually while accounting for contemporary group, sex, and the top 20 principal components calculated from the genomic relationship matrix. Heritability of initial response to vaccination (d 21 –d 0) was 0.10 ± 0.175 using pedigree relationships and 0.14 ± 0.149 using genomic relationships, but neither estimate was statistically different from zero. Heritability of booster (d 56 –d 21) and overall (d 56 –d 0) responses were low and not statistically significant from zero. There were no clusters of linked SNP associated with vaccine response, but eight regionally isolated SNPs were significantly associated with initial or overall response to vaccination. Regional genetic variation for initial response to an E . coli O157:H7 vaccine was observed, although overall heritability of this response was not statistically significant from zero.
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  • 57
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    Publication Date: 2018-05-15
    Description: by Claudia Agabiti-Rosei, Valentina Trapletti, Silvia Piantoni, Paolo Airò, Angela Tincani, Carolina De Ciuceis, Claudia Rossini, Francesco Mittempergher, Amin Titi, Nazario Portolani, Stefano Caletti, Maria Antonietta Coschignano, Enzo Porteri, Guido A. M. Tiberio, Paola Pileri, Leonardo Solaini, Rajesh Kumar, Silvia Ministrini, Enrico Agabiti Rosei, Damiano Rizzoni Objective It has been previously demonstrated that T lymphocytes may be involved in the development of hypertension and microvascular remodeling, and that circulating T effector lymphocytes may be increased in hypertension. In particular, Th1 and Th 17 lymphocytes may contribute to the progression of hypertension and microvascular damage while T-regulatory (Treg) lymphocytes seem to be protective in this regard. However, no data is available about patients with severe obesity, in which pronounced microvascular alterations were observed. Design and methods We have investigated 32 severely obese patients undergoing bariatric surgery, as well as 24 normotensive lean subjects and 12 hypertensive lean subjects undergoing an elective surgical intervention. A peripheral blood sample was obtained before surgery for assessment of CD4+ T lymphocyte subpopulations. Lymphocyte phenotype was evaluated by flow cytometry in order to assess T-effector and Treg lymphocytes. Results A marked reduction of several Treg subpopulations was observed in obese patients compared with controls, together with an increased in CD4+ effector memory T-effector cells. Conclusion In severely obese patients, Treg lymphocytes are clearly reduced and CD4+ effector memory cells are increased. It may be hypothesized that they might contribute to the development of marked microvascular alterations previously observed in these patients.
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  • 58
    Publication Date: 2018-05-15
    Description: by Jagamya Vijayaraghavan, Vijay Kumar, Nikhil P. Krishnan, Ross T. Kaufhold, Ximin Zeng, Jun Lin, Focco van den Akker The bacterial soluble lytic transglycosylase (LT) breaks down the peptidoglycan (PG) layer during processes such as cell division. We present here crystal structures of the soluble LT Cj0843 from Campylobacter jejuni with and without bulgecin A inhibitor in the active site. Cj0843 has a doughnut shape similar but not identical to that of E . coli SLT70. The C-terminal catalytic domain is preceded by an L-domain, a large helical U-domain, a flexible linker, and a small N-terminal NU-domain. The flexible linker allows the NU-domain to reach over and complete the circular shape, using residues conserved in the Epsilonproteobacteria LT family. The inner surface of the Cj0843 doughnut is mostly positively charged including a pocket that has 8 Arg/Lys residues. Molecular dynamics simulations with PG strands revealed a potential functional role for this pocket in anchoring the negatively charged terminal tetrapeptide of the PG during several steps in the reaction including homing and aligning the PG strand for exolytic cleavage, and subsequent ratcheting of the PG strand to enhance processivity in degrading PG strands.
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  • 59
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    Publication Date: 2018-05-15
    Description: by Mathias F. Rockenbach, Caio C. G. Corrêa, Angelo S. Heringer, Ismael L. J. Freitas, Claudete Santa-Catarina, Antônio T. do Amaral-Júnior, Vanildo Silveira Although heterosis has significantly contributed to increases in worldwide crop production, the molecular mechanisms regulating this phenomenon are still unknown. In the present study, we used a comparative proteomic approach to explore hybrid vigor via the proteome of both the popcorn L54 ♀ and P8 ♂ genotypes and the resultant UENF/UEM01 hybrid cross. To analyze the differentially abundant proteins involved in heterosis, we used the primary roots of these genotypes to analyze growth parameters and extract proteins. The results of the growth parameter analysis showed that the mid- and best-parent heterosis were positive for root length and root dry matter but negative for root fresh matter, seedling fresh matter, and protein content. The comparative proteomic analysis identified 1343 proteins in the primary roots of hybrid UENF/UEM01 and its parental lines; 220 proteins were differentially regulated in terms of protein abundance. The mass spectrometry proteomic data are available via ProteomeXchange with identifier “PXD009436”. A total of 62 regulated proteins were classified as nonadditive, of which 53.2% were classified as high parent abundance (+), 17.8% as above-high parent abundance (+ +), 16.1% as below-low parent abundance (− −), and 12.9% as low parent abundance (-). A total of 22 biological processes were associated with nonadditive proteins; processes involving translation, ribosome biogenesis, and energy-related metabolism represented 45.2% of the nonadditive proteins. Our results suggest that heterosis in the popcorn hybrid UENF/UEM01 at an early stage of plant development is associated with an up-regulation of proteins related to synthesis and energy metabolism.
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  • 60
    Publication Date: 2018-05-15
    Description: by Dvora Joseph Davey, Elise Farley, Catriona Towriss, Yolanda Gomba, Linda-Gail Bekker, Pamina Gorbach, Steven Shoptaw, Thomas Coates, Landon Myer HIV acquisition during pregnancy and breastfeeding significantly contributes toward paediatric HIV infection; however, little is known about risk behaviours in HIV-uninfected pregnant and postpartum women. We conducted twenty-six in-depth-interviews between July and December 2016 using a semi-structured interview guide among HIV-uninfected pregnant and recently postpartum women at-risk of HIV acquisition (defined as reporting ≥1 of the following: partner’s serostatus unknown or HIV-infected, recent condomless sex in pregnancy, and/or alcohol use during pregnancy) who attended primary healthcare services. Our study contextualizes factors related to risky sexual behaviours during pregnancy and postpartum periods and assesses knowledge and hypothetical acceptability of pre-exposure prophylaxis (PrEP) in pregnancy. Translated and transcribed data were coded and analysed by three researchers using a thematic analysis approach. In interviews with HIV-uninfected pregnant/postpartum women at-risk of HIV acquisition, we identified common themes associated with sexual risk behaviours during pregnancy, including: lack of control over decisions in sex and condom use in pregnancy, low perceived risk (e.g. beliefs that their partner has the same HIV-negative serostatus), and socio-cultural beliefs around condom use during pregnancy (e.g. contact with sperm is essential for baby’s development). PrEP knowledge was low among HIV-uninfected pregnant and breastfeeding women, and potential acceptability was good, though primary concerns were around the potential impact on the infant. While mothers presented a clear desire to protect themselves from HIV acquisition once pregnant, they also reported lack of control, and socio-cultural beliefs, like sex is good for the baby, that increased their risk of seroconversion. Mothers had limited PrEP awareness but reported hypothetical willingness to use PrEP because of concerns over HIV acquisition and onward mother to child transmission.
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  • 61
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    Publication Date: 2018-05-16
    Description: by Franziska Zeyer, Benedikt Mothes, Clara Will, Melanie Carevic, Jennifer Rottenberger, Bernd Nürnberg, Dominik Hartl, Rupert Handgretinger, Sandra Beer-Hammer, Michael S. D. Kormann
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  • 62
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    Publication Date: 2018-05-16
    Description: by Miklós Lengyel, Gábor Czirják, Péter Enyedi Two-pore domain K + channels (K 2P ) are responsible for background K + currents and regulate the resting membrane potential and cellular excitability. Their activity is controlled by a large variety of physicochemical factors and intracellular signaling pathways. The majority of these effects converge on the intracellular C-terminus of the channels, resulting in the modification of the gating at the selectivity filter. Another gating mechanism, the activation gate at the helix bundle crossing is also well documented in other K + channel families, however, it remains uncertain whether this type of gating is functional in K 2P channels. The regulation of TWIK-related spinal cord K + channel (TRESK) is different from the other K 2P channels. Regulatory factors acting via the C-terminus are not known, instead channel activity is modified by the phosphorylation/dephosphorylation of the unusually long intracellular loop between the 2 nd and 3 rd transmembrane segments. These unique structural elements of the regulation lead us to examine channel gating at the bundle crossing region. Ba 2+ was applied to the intracellular side of excised membrane patches and the characteristics of the channel block were determined. We compared the kinetics of the development of Ba 2+ block when the channels were phosphorylated (inhibited) or dephosphorylated (activated) and also in different mutants mimicking the two functional states. Neither the phosphorylation/dephosphorylation nor the point mutations influenced the development of Ba 2+ block, suggesting that the conformational changes of the bundle crossing region do not contribute to the phosphorylation-dependent gating of TRESK.
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  • 63
    Publication Date: 2018-05-16
    Description: by Youjia Du, Carla G. Taylor, Harold M. Aukema, Peter Zahradka Consumption of different PUFAs (polyunsaturated fatty acids) can induce functional changes in blood vessels via endothelial cells, which interact with dietary factors in the circulation. The basement membrane that separates the endothelium from the smooth muscle cells of the medial layer can also influence the functional state of endothelial cells. However, the effect of basement membrane on the endothelial response to dietary PUFAs in relation to growth state (e.g. proliferation versus quiescence) has never been investigated. We therefore compared the viability (CCK kit) and proliferation (bromodeoxyuridine incorporation) of EA.hy926 endothelial cells grown on Matrigel or collagen versus non-coated plates. EA.hy926 viability and proliferation were also assessed after treatment with 0–150 μM of PUFAs [linoleic acid (LA), arachidonic acid (AA), α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. Our study showed that only cells grown on Matrigel-coated plates reached quiescence after becoming confluent with a decreased level of MCM2 and p-cyclin D1 (T286), increased levels of p27kip1 and a low level of apoptosis and senescence. AA, EPA and DHA decreased the viability and proliferation of subconfluent cells grown on plastic dishes in a dose-dependent manner, while the presence of Matrigel made the cells resistant to these adverse effects. Confluent cell viability was less sensitive to higher concentrations of AA, EPA and DHA than subconfluent cells, and a significant increase in caspase-3 cleavage was only observed in confluent cells treated with DHA. Higher concentrations of AA, EPA and DHA suppressed DNA synthesis by both subconfluent and confluent cells, while precursor C18 PUFAs (LA and ALA) had no negative effects on viability and proliferation. Our study is the first to show that extracellular matrix and growth state are important factors in the EA.hy926 cell response to PUFAs, and that the mechanisms by which individual PUFAs operate may be growth state-dependent.
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    Publication Date: 2018-05-16
    Description: by Nobuo Imai, Takuya Furukawa, Riyou Tsujino, Shumpei Kitamura, Takakazu Yumoto While many tropical countries are experiencing rapid deforestation, some have experienced forest transition (FT) from net deforestation to net reforestation. Numerous studies have identified causative factors of FT, among which forest scarcity has been considered as a prerequisite for FT. In fact, in SE Asia, the Philippines, Thailand and Viet Nam, which experienced FT since 1990, exhibited a lower remaining forest area (30±8%) than the other five countries (68±6%, Cambodia, Indonesia, Laos, Malaysia, and Myanmar) where forest loss continues. In this study, we examined 1) the factors associated with forest scarcity, 2) the proximate and/or underlying factors that have driven forest area change, and 3) whether causative factors changed across FT phases (from deforestation to net forest gain) during 1980–2010 in the eight SE Asian countries. We used production of wood, food, and export-oriented food commodities as proximate causes and demographic, social, economic and environmental factors, as well as land-use efficiency, and wood and food trade as underlying causes that affect forest area change. Remaining forest area in 1990 was negatively correlated with population density and potential land area of lowland forests, while positively correlated with per capita wood production. This implies that countries rich in accessible and productive forests, and higher population pressures are the ones that have experienced forest scarcity, and eventually FT. Food production and agricultural input were negatively and positively correlated, respectively, with forest area change during 1980–2009. This indicates that more food production drives deforestation, but higher efficiency of agriculture is correlated with forest gain. We also found a U-shaped response of forest area change to social openness, suggesting that forest gain can be achieved in both open and closed countries, but deforestation might be accelerated in countries undergoing societal transition. These results indicate the importance of environmental, agricultural and social variables on forest area dynamics, and have important implications for predicting future tropical forest change.
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    Publication Date: 2018-05-16
    Description: by Zihao Yuan, Tao Zhou, Lisui Bao, Shikai Liu, Huitong Shi, Yujia Yang, Dongya Gao, Rex Dunham, Geoff Waldbieser, Zhanjiang Liu Channel catfish ( Ictalurus punctatus ) is a highly adaptive species and has been used as a research model for comparative immunology, physiology, and toxicology among ectothermic vertebrates. It is also economically important for aquaculture. As such, its reference genome was generated and annotated with protein coding genes. However, the repetitive elements in the catfish genome are less well understood. In this study, over 417.8 Megabase (MB) of repetitive elements were identified and characterized in the channel catfish genome. Among them, the DNA/TcMar-Tc1 transposons are the most abundant type, making up ~20% of the total repetitive elements, followed by the microsatellites (14%). The prevalence of repetitive elements, especially the mobile elements, may have provided a driving force for the evolution of the catfish genome. A number of catfish-specific repetitive elements were identified including the previously reported Xba elements whose divergence rate was relatively low, slower than that in untranslated regions of genes but faster than the protein coding sequences, suggesting its evolutionary restrictions.
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  • 66
    Publication Date: 2018-05-16
    Description: by Mei Dai, Yi Lin, Salim S. El-Amouri, Mara Kohls, Dao Pan Primary brain microvessels (BrMV) maintain the cellular characters and molecular signatures as displayed in vivo, and serve as a vital tool for biomedical research of the blood-brain barrier (BBB) and the development/optimization of brain drug delivery. The variations of relative purities or cellular composition among different BrMV samples may have significant consequences in data interpretation and research outcome, especially for experiments with high-throughput genomics and proteomics technologies. In this study, we aimed to identify suitable reference gene (RG) for accurate normalization of real-time RT-qPCR analysis, and determine the proper marker genes (MG) for relative purity assessment in BrMV samples. Out of five housekeeping genes, β-actin was selected as the most suitable RG that was validated by quantifying mRNA levels of alpha-L-iduronidase in BrMV isolated from mice with one or two expressing alleles. Four marker genes highly/selectively expressed in BBB-forming capillary endothelial cells were evaluated by RT-qPCR for purity assessment, resulting in Cldn 5 and Pecam1 as most suitable MGs that were further confirmed by immunofluorescent analysis of cellular components. Plvap proved to be an indicator gene for the presence of fenestrated vessels in BrMV samples. This study may contribute to the building blocks toward overarching research needs on the blood-brain barrier.
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  • 67
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    Publication Date: 2018-05-16
    Description: by Yong Si, Lihong Wang, Qing Zhou, Xiaohua Huang REEs in the environment can be absorbed by plants and sequestered by plant phytoliths. Acid rain can directly or indirectly affect plant physiological functions. Currently, the effects of REEs and acid rain on phytolith-REEs complex in plants are not yet fully understood. In this study, a high-silicon accumulation crop, rice ( Oryza sativa L.), was selected as a representative of plants, and orthogonal experiments were conducted under various levels of lanthanum [La(III)] and pH. The results showed that various La(III) concentrations could significantly improve the efficiency and sequestration of phytolith La(III) in germinated rice seeds. A pH of 4.5 promoted phytolith La(III) sequestration, while a pH of 3.5 inhibited sequestration. Compared with the single treatment with La(III), the combination of La(III) and acid rain inhibited the efficiency and sequestration of phytolith La(III). Correlation analysis showed that the efficiency of phytolith La(III) sequestration had no correlation with the production of phytolith but was closely correlated with the sequestration of phytolith La(III) and the physiological changes of germinated rice seeds. Phytolith morphology was an important factor affecting phytolith La(III) sequestration in germinated rice seeds, and the effect of tubes on sequestration was more significant than that of dumbbells. This study demonstrated that the formation of the phytolith and La(III) complex could be affected by exogenous La(III) and acid rain in germinated rice seeds.
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    Publication Date: 2018-05-16
    Description: by Sung-Sahn Lee, Yong-In Lee, Dong-Uk Kim, Dae-Hee Lee, Young-Wan Moon Background Achieving proper rotational alignment of the femoral component in total knee arthroplasty (TKA) for valgus knee is challenging because of lateral condylar hypoplasia and lateral cartilage erosion. Gap-based navigation-assisted TKA enables surgeons to determine the angle of femoral component rotation (FCR) based on the posterior condylar axis. This study evaluated the possible factors that affect the rotational alignment of the femoral component based on the posterior condylar axis. Materials and methods Between 2008 and 2016, 28 knees were enrolled. The dependent variable for this study was FCR based on the posterior condylar axis, which was obtained from the navigation system archives. Multiple regression analysis was conducted to identify factors that might predict FCR, including body mass index (BMI), Kellgren-Lawrence grade (K-L grade), lateral distal femoral angles obtained from the navigation system and radiographs (NaviLDFA, XrayLDFA), hip-knee-ankle (HKA) axis, lateral gap under varus stress (LGVS), medial gap under valgus stress (MGVS), and side-to-side difference (STSD, MGVS − LGVS). Results The mean FCR was 6.1° ± 2.0°. Of all the potentially predictive factors evaluated in this study, only NaviLDFA ( β = −0.668) and XrayLDFA ( β = −0.714) predicted significantly FCR. Conclusions The LDFAs, as determined using radiographs and the navigation system, were both predictive of the rotational alignment of the femoral component based on the posterior condylar axis in gap-based TKA for valgus knee. A 1° increment with NaviLDFA led to a 0.668° decrement in FCR, and a 1° increment with XrayLDFA led to a 0.714° decrement. This suggests that symmetrical lateral condylar hypoplasia of the posterior and distal side occurs in lateral compartment end-stage osteoarthritis with valgus deformity.
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    Publication Date: 2018-05-16
    Description: by Pavel Dietz, Anne Quermann, Mireille Nicoline Maria van Poppel, Heiko Striegel, Hannes Schröter, Rolf Ulrich, Perikles Simon Study objectives In order to increase the value of randomized response techniques (RRTs) as tools for studying sensitive issues, the present study investigated whether the prevalence estimate for a sensitive item π^s assessed with the unrelated questionnaire method (UQM) is influenced by changing the probability of receiving the sensitive question p . Material and methods A short paper-and-pencil questionnaire was distributed to 1.243 university students assessing the 12-month prevalence of physical and cognitive doping using two versions of the UQM with different probabilities for receiving the sensitive question ( p ≈ 1/3 and p ≈ 2/3). Likelihood ratio tests were used to assess whether the prevalence estimates for physical and cognitive doping differed significantly between p ≈ 1/3 and p ≈ 2/3. The order of questions (physical doping and cognitive doping) as well as the probability of receiving the sensitive question ( p ≈ 1/3 or p ≈ 2/3) were counterbalanced across participants. Statistical power analyses were performed to determine sample size. Results The prevalence estimate for physical doping with p ≈ 1/3 was 22.5% (95% CI: 10.8–34.1), and 12.8% (95% CI: 7.6–18.0) with p ≈ 2/3. For cognitive doping with p ≈ 1/3, the estimated prevalence was 22.5% (95% CI: 11.0–34.1), whereas it was 18.0% (95% CI: 12.5–23.5) with p ≈ 2/3. Likelihood-ratio tests revealed that prevalence estimates for both physical and cognitive doping, respectively, did not differ significantly under p ≈ 1/3 and p ≈ 2/3 (physical doping: χ 2 = 2.25, df = 1, p = 0.13; cognitive doping: χ 2 = 0.49, df = 1, p = 0.48). Bayes factors computed with the Savage-Dickey method favored the null (“the prevalence estimates are identical under p ≈ 1/3 and p ≈ 2/3”) over the alternative (“the prevalence estimates differ under p ≈ 1/3 and p ≈ 2/3”) hypothesis for both physical doping (BF = 2.3) and cognitive doping (BF = 5.3). Conclusion The present results suggest that prevalence estimates for physical and cognitive doping assessed by the UQM are largely unaffected by the probability for receiving the sensitive question p .
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 70
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-16
    Description: by Jinju Ma, Liyi Ma, Hong Zhang, Zhongquan Zhang, Youqiong Wang, Kai Li, Xiaoming Chen Background Insect wax is a famous biological resource for the role in economic production in China. Insect wax is a good source of policosanol, which may is a candidate supplement in foodstuff and pharmaceuticals that has important physiological activities. Therefore, this work aims to investigate a high-yield and rapid method for policosanol fabrication from insect wax. Results The conditions for policosanol fabrication were optimized as follows: an oil bath temperature of 112.7°C and reductant dosage of 0.97 g (used for the reduction of 10.00 g of insect wax). The yield of policosanol reached 83.20%, which was 4 times greater than that of existing methods, such as saponification. The total content of policosanol obtained under the optimal conditions reached 87%. In other words, a high yield of policosanol was obtained from insect wax (723.84 mg/g), that was 55 times higher than that generated from beeswax-brown via saponification. The concentrations of metal residues in policosanol were within the limits of the European Union regulations and EFSA stipulation. The LD50 values for oral doses of insect wax and policosanol were both 〉 5 g/kg. Conclusion Policosanol was fabricated via solvent-free reduction from insect wax using LiAlH 4 at a high yield. The fabrication conditions were optimized. Policosanol and insect wax showed high security, which made them potential candidates as supplements in foods, pharmaceuticals and cosmetics. The rapid and high-yield method has great potential for commercial manufacturing of policosanol.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 71
    Publication Date: 2018-05-16
    Description: by Eli Skeie, Anne Mette Koch, Stig Harthug, Unni Fosse, Kari Sygnestveit, Roy Miodini Nilsen, Randi J. Tangvik Surgical site infections (SSI) are amongst the most common health care-associated infections and have adverse effects for patient health and for hospital resources. Although surgery guidelines recognize poor nutritional status to be a risk factor for SSI, they do not tell how to identify this condition. The screening tool Nutritional Risk Screening 2002 is commonly used at hospitals to identify patients at nutritional risk. We investigated the association between nutritional risk and the incidence of SSI among 1194 surgical patients at Haukeland University Hospital (Bergen, Norway). This current study combines data from two mandatory hospital-based registers: a) the incidence of SSI within 30 days after surgery, and b) the point-prevalence of patients at nutritional risk. Patients with more than 30 days between surgery and nutritional risk screening were excluded. Associations were assessed using logistic regression, and the adjusted odds ratio included age (continuous), gender (male/female), type of surgery (acute/elective) and score from The American Society of Anesthesiologists Physical Status Classification System. There was a significant higher incidence of SSI among patients at nutritional risk (11.8%), as compared to those who were not (7.0%) (p = 0.047). Moreover, the incidence of SSI was positively associated with the prevalence of nutritional risk in both simple (OR 1.76 (95% CI: 1.04, 2.98)) and adjusted (OR 1.81 (95% CI: 1.04, 3.16)) models. Answering “yes” to the screening questions regarding reduced dietary intake and weight loss was significantly associated with the incidence of SSI (respectively OR 2.66 (95% CI: 1.59, 4.45) and OR 2.15 (95% CI: 1.23, 3.76)). In conclusion, we demonstrate SSI to occur more often among patients at nutritional risk as compared to those who are not at nutritional risk. Future studies should investigate interventions to prevent both SSI and nutritional risk among surgical patients.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 72
    Publication Date: 2018-05-16
    Description: by Adam Yasgar, Steven A. Titus, Yuhong Wang, Carina Danchik, Shyh-Ming Yang, Vasilis Vasiliou, Ajit Jadhav, David J. Maloney, Anton Simeonov, Natalia J. Martinez
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 73
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-16
    Description: by Tatsuyuki Sato, Masaru Hatano, Yukiko Iwasaki, Hisataka Maki, Akihito Saito, Shun Minatsuki, Toshiro Inaba, Eisuke Amiya, Keishi Fujio, Masafumi Watanabe, Kazuhiko Yamamoto, Issei Komuro Background The prevalence of pulmonary arterial hypertension (PAH) in primary Sjögren’s syndrome (SS) had been reported to be rare. However, recent studies using echocardiography as a screening method showed conflicting results, and the true prevalence is still unclear. Since diagnosing primary SS is difficult because of its heterogeneous nature, a number of patients with primary-SS-associated PAH may be misdiagnosed with idiopathic PAH, losing their chance to undergo immunosuppressive therapy. Therefore, we sought to elucidate the prevalence of primary SS among patients who initially present with PAH. Methods From our prospective institutional PAH database, 40 consecutive patients without any obvious cause of PAH at the time of PAH diagnosis were identified. We retrospectively evaluated the prevalence of primary SS diagnosed during or after the initial assessment of PAH. Results During the initial assessment, one patient was diagnosed with primary-SS-associated PAH. Among the 25 patients who were initially diagnosed with idiopathic PAH, five were diagnosed with primary SS during their course of the disease. Of the five patients, three had key signs suggesting primary SS and were probably underdiagnosed at the time of initial evaluation. The remaining two patients, who were finally diagnosed with primary SS, did not have any specific signs suggesting primary SS at the time of initial evaluation but showed positive conversion of their autoantibodies during the course of PAH. Conclusion The prevalence of primary-SS-associated PAH may be relatively high among patients who undergo initial evaluation for PAH. Furthermore, primary-SS-associated PAH may be underdiagnosed with routine evaluation for the primary cause of PAH. Clinicians should pay specific attention and carefully evaluate the possibility of primary SS in patients with PAH.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 74
    Publication Date: 2018-05-16
    Description: by Gitta Kleijn, Birgit I. Lissenberg-Witte, Ernst T. Bohlmeijer, Bas Steunenberg, Kitty Knipscheer-Kuijpers, Vincent Willemsen, Annemarie Becker, Egbert F. Smit, Corien M. Eeltink, Anna M. E. Bruynzeel, Maurice van der Vorst, Remco de Bree, C. René Leemans, Michiel W. M. van den Brekel, Pim Cuijpers, Irma M. Verdonck-de Leeuw Background The aim of this study was to evaluate the efficacy of an intervention combining Life Review Therapy (LRT) and Memory Specificity Training (MST) (LRT-MST) to improve ego-integrity and despair among cancer patients in palliative care. Methods In this multicentre randomized controlled trial, cancer patients in palliative care were randomized to the intervention group (LRT-MST; n = 55) or waiting-list control group (n = 52). LRT-MST is a 4-session home-based psychological intervention that aims to retrieve specific positive memories, to re-evaluate life events and to reconstruct the story of a patient’s life, including the diagnosis of incurable cancer. Outcome measures were ego-integrity and despair (NEIS), psychological distress, anxiety and depression (HADS), quality of life (EORTC QLQ-C15-PAL), and specificity of the autobiographical memory (AMT). NEIS, HADS and EORTC QLQ-C15-PAL were assessed at baseline (T0), 1 month later (post-treatment; T1), and at 1 month follow-up (T2). AMT was assessed at T0 and T1. Linear mixed models (intention to treat) were used to assess group differences in changes over time. Independent samples t-tests were used to assess group differences at T0, T1, and T2, and effect sizes (ES) were calculated at T1 and T2. Results The course of ego-integrity (not despair) improved significantly over time ( p = .007) in the intervention group compared to the waiting-list control group, with moderate, but insignificant, effect sizes at T1 (ES = .42) and T2 (ES = .48). Compliance rate was 69% and total dropout rate was 28%, both primarily related to disease progression and death. Conclusions LRT-MST seems effective among cancer patients in palliative care to improve the course of ego-integrity.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 75
    Publication Date: 2018-05-16
    Description: by Bo-jian Chen, Kai Liu, Lin-jun Zhou, Guilherme Gomes-Silva, Carolin Sommer-Trembo, Martin Plath Consistent individual differences in behavioral tendencies (animal personality) can affect individual mate choice decisions. We asked whether personality traits affect male and female mate choice decisions similarly and whether potential personality effects are consistent across different mate choice situations. Using western mosquitofish ( Gambusia affinis ) as our study organism, we characterized focal individuals (males and females) twice for boldness, activity, and sociability/shoaling and found high and significant behavioral repeatability. Additionally, each focal individual was tested in two different dichotomous mate choice tests in which it could choose between computer-animated stimulus fish of the opposite sex that differed in body size and activity levels, respectively. Personality had different effects on female and male mate choice: females that were larger than average showed stronger preferences for large-bodied males with increasing levels of boldness/activity (i.e., towards more proactive personality types). Males that were larger than average and had higher shoaling tendencies showed stronger preferences for actively swimming females. Size-dependent effects of personality on the strength of preferences for distinct phenotypes of potential mating partners may reflect effects of age/experience (especially in females) and social dominance (especially in males). Previous studies found evidence for assortative mate choice based on personality types or hypothesized the existence of behavioral syndromes of individuals’ choosiness across mate choice criteria, possibly including other personality traits. Our present study exemplifies that far more complex patterns of personality-dependent mate choice can emerge in natural systems.
    Electronic ISSN: 1932-6203
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  • 76
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-17
    Description: by Michael C. Saul, Sharon A. Stevenson, Changjiu Zhao, Terri M. Driessen, Brian E. Eisinger, Stephen C. Gammie Contemporary rodent models for bipolar disorders split the bipolar spectrum into complimentary behavioral endophenotypes representing mania and depression. Widely accepted mania models typically utilize single gene transgenics or pharmacological manipulations, but inbred rodent strains show great potential as mania models. Their acceptance is often limited by the lack of genotypic data needed to establish construct validity. In this study, we used a unique strategy to inexpensively explore and confirm population allele differences in naturally occurring candidate variants in a manic rodent strain, the Madison (MSN) mouse strain. Variants were identified using whole exome resequencing on a small population of animals. Interesting candidate variants were confirmed in a larger population with genotyping. We enriched these results with observations of locomotor behavior from a previous study. Resequencing identified 447 structural variants that are mostly fixed in the MSN strain relative to control strains. After filtering and annotation, we found 11 non-synonymous MSN variants that we believe alter protein function. The allele frequencies for 6 of these variants were consistent with explanatory variants for the Madison strain’s phenotype. The variants are in the Npas2 , Cp , Polr3c , Smarca4 , Trpv1 , and Slc5a7 genes, and many of these genes’ products are in pathways implicated in human bipolar disorders. Variants in Smarca4 and Polr3c together explained over 40% of the variance in locomotor behavior in the Hsd:ICR founder strain. These results enhance the MSN strain’s construct validity and implicate altered nucleosome structure and transcriptional regulation as a chief molecular system underpinning behavior.
    Electronic ISSN: 1932-6203
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  • 77
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-17
    Description: by Damiano Pasetto, Flavio Finger, Anton Camacho, Francesco Grandesso, Sandra Cohuet, Joseph C. Lemaitre, Andrew S. Azman, Francisco J. Luquero, Enrico Bertuzzo, Andrea Rinaldo Computational models of cholera transmission can provide objective insights into the course of an ongoing epidemic and aid decision making on allocation of health care resources. However, models are typically designed, calibrated and interpreted post-hoc . Here, we report the efforts of a team from academia, field research and humanitarian organizations to model in near real-time the Haitian cholera outbreak after Hurricane Matthew in October 2016, to assess risk and to quantitatively estimate the efficacy of a then ongoing vaccination campaign. A rainfall-driven, spatially-explicit meta-community model of cholera transmission was coupled to a data assimilation scheme for computing short-term projections of the epidemic in near real-time. The model was used to forecast cholera incidence for the months after the passage of the hurricane (October-December 2016) and to predict the impact of a planned oral cholera vaccination campaign. Our first projection, from October 29 to December 31, predicted the highest incidence in the departments of Grande Anse and Sud, accounting for about 45% of the total cases in Haiti. The projection included a second peak in cholera incidence in early December largely driven by heavy rainfall forecasts, confirming the urgency for rapid intervention. A second projection (from November 12 to December 31) used updated rainfall forecasts to estimate that 835 cases would be averted by vaccinations in Grande Anse (90% Prediction Interval [PI] 476-1284) and 995 in Sud (90% PI 508-2043). The experience gained by this modeling effort shows that state-of-the-art computational modeling and data-assimilation methods can produce informative near real-time projections of cholera incidence. Collaboration among modelers and field epidemiologists is indispensable to gain fast access to field data and to translate model results into operational recommendations for emergency management during an outbreak. Future efforts should thus draw together multi-disciplinary teams to ensure model outputs are appropriately based, interpreted and communicated.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 78
    Publication Date: 2018-05-17
    Description: by Entcho Klenske, Steffen Zopf, Clemens Neufert, Andreas Nägel, Jürgen Siebler, Jürgen Gschossmann, Steffen Mühldorfer, Lukas Pfeifer, Sarah Fischer, Francesco Vitali, Marietta Iacucci, Subrata Ghosh, Michelle G. Rath, Peter Klare, Gian E. Tontini, Markus F. Neurath, Timo Rath Background and aims Dye-less chromoendoscopy is an emerging technology for colorectal polyp characterization. Herein, we investigated whether the newly introduced I-scan optical enhancement (OE) can accurately predict polyp histology in vivo in real-time. Methods In this prospective three-phased study, 84 patients with 230 diminutive colorectal polyps were included. During the first two study phases, five endoscopists assessed whether analysis of polyp colour, surface and vascular pattern under i-scan OE can differentiate in vivo between adenomatous and hyperplastic polyps. Finally, junior and experienced endoscopists (JE, EE, each n = 4) not involved in the prior study phases made a post hoc diagnosis of polyp histology using a static i-scan OE image database. Histopathology was used as a gold-standard in all study phases. Results The overall accuracy of i-scan OE for histology prediction was 90% with a sensitivity, specificity, positive (PPV) and negative prediction value (NPV) of 91%, 90%, 86% and 94%, respectively. In high confidence predictions, the diagnostic accuracy increased to 93% with sensitivity, specificity, PPV and NPV of 94%, 91%, 89% and 96%. Colonoscopy surveillance intervals were predicted correctly in ≥ 90% of patients. In the post hoc analysis EE predicted polyp histology under i-scan OE with an overall accuracy of 91%. After a single training session, JE achieved a comparable diagnostic performance for predicting polyp histology with i-scan OE. Conclusion The histology of diminutive colorectal polyps can be accurately predicted with i-scan OE in vivo in real-time. Furthermore, polyp differentiation with i-scan OE appears to require only a short learning curve.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 79
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-17
    Description: by Zeeshan Akhtar, Pukhraj Rishi, Ramasubramanian Srikanth, Ekta Rishi, Muna Bhende, Rajiv Raman Aim To determine choroidal thickness in healthy Indian subjects using Swept source optical coherence tomography (SS-OCT). Methods In this prospective, observational, cross-sectional study; healthy Indian subjects (n = 230) with no history of ocular and/or systemic disorders were enrolled in the study. Choroidal thickness was measured for 230 eyes using SS-OCT. Subjects were divided into six age groups. Main outcome measures were subfoveal choroidal thickness (SFCT) and macular choroidal thickness (MCT) up to 3 mm at 500-micron interval from the fovea was measured in eight different quadrants. Results The mean SFCT was 307±79 μm and mean MCT was 285±75 μm. No difference in the choroidal thickness was found among genders. Mean SFCT of the different age groups was 327±68 μm (12–18 years), 364±70 μm (18.1–30 years), 321±78 μm (30.1–40 years), 304±79 μm (40.1–50 years), 283±69 μm (50.1–60 years) and 262±72μm (above 60 years; p
    Electronic ISSN: 1932-6203
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  • 80
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-17
    Description: by Jukka M. Leppänen, Julia K. Cataldo, Michelle Bosquet Enlow, Charles A. Nelson Infants from an early age have a bias to attend more to faces than non-faces and after 5 months are particularly attentive to fearful faces. We examined the specificity of this “fear bias” in 5-, 7-, and 12-month-old infants ( N = 269) and 36-month-old children ( N = 191) and whether its development is associated with features of the early rearing environment, specifically maternal anxiety and depression symptoms. Attention dwell times were assessed by measuring the latencies of gaze shifts from a stimulus at fixation to a new stimulus in the visual periphery. In infancy, dwell times were shorter for non-face control stimuli vs. happy faces at all ages, and happy vs. fearful, but not angry, faces at 7 and 12 months. At 36 months, dwell times were shorter for non-faces and happy faces compared to fearful and angry faces. Individual variations in attention dwell times were not associated with mothers’ self-reported depression or anxiety symptoms at either age. The results suggest that sensitivity to fearful faces precedes a more general bias for threat-alerting stimuli in early development. We did not find evidence that the initial manifestation of these biases is related to moderate variations in maternal depression or anxiety symptoms.
    Electronic ISSN: 1932-6203
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  • 81
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-17
    Description: by Emine Yaylali, Paul G. Farnham, Stacy Cohen, David W. Purcell, Heather Hauck, Stephanie L. Sansom Objective To estimate the optimal allocation of Centers for Disease Control and Prevention (CDC) HIV prevention funds for health departments in 52 jurisdictions, incorporating Health Resources and Services Administration (HRSA) Ryan White HIV/AIDS Program funds, to improve outcomes along the HIV care continuum and prevent infections. Methods Using surveillance data from 2010 to 2012 and budgetary data from 2012, we divided the 52 health departments into 5 groups varying by number of persons living with diagnosed HIV (PLWDH), median annual CDC HIV prevention budget, and median annual HRSA expenditures supporting linkage to care, retention in care, and adherence to antiretroviral therapy. Using an optimization and a Bernoulli process model, we solved for the optimal CDC prevention budget allocation for each health department group. The optimal allocation distributed the funds across prevention interventions and populations at risk for HIV to prevent the greatest number of new HIV cases annually. Results Both the HIV prevention interventions funded by the optimal allocation of CDC HIV prevention funds and the proportions of the budget allocated were similar across health department groups, particularly those representing the large majority of PLWDH. Consistently funded interventions included testing, partner services and linkage to care and interventions for men who have sex with men (MSM). Sensitivity analyses showed that the optimal allocation shifted when there were differences in transmission category proportions and progress along the HIV care continuum. Conclusion The robustness of the results suggests that most health departments can use these analyses to guide the investment of CDC HIV prevention funds into strategies to prevent the most new cases of HIV.
    Electronic ISSN: 1932-6203
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