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  • 1
    Publication Date: 2019-07-18
    Description: Almost all animals and plants are inhabited by diverse communities of microorganisms, the microbiota, thereby forming an integrated entity, the metaorganism. Natural selection should favor hosts that shape the community composition of these microbes to promote a beneficial host-microbe symbiosis. Indeed, animal hosts often pose selective environments, which only a subset of the environmentally available microbes are able to colonize. How these microbes assemble after colonization to form the complex microbiota is less clear. Neutral models are based on the assumption that the alternatives in microbiota community composition are selectively equivalent and thus entirely shaped by random population dynamics and dispersal. Here, we use the neutral model as a null hypothesis to assess microbiata composition in host organisms, which does not rely on invoking any adaptive processes underlying microbial community assembly. We show that the overall microbiota community structure from a wide range of host organisms, in particular including previously understudied invertebrates, is in many cases consistent with neutral expectations. Our approach allows to identify individual microbes that are deviating from the neutral expectation and are therefore interesting candidates for further study. Moreover, using simulated communities, we demonstrate that transient community states may play a role in the deviations from the neutral expectation. Our findings highlight that the consideration of neutral processes and temporal changes in community composition are critical for an in-depth understanding of microbiota-host interactions.
    Type: Article , PeerReviewed
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  • 2
    Publication Date: 2019-09-23
    Description: Aquatic ecosystems worldwide continue to experience unprecedented warming and ecological change. Warming increases metabolic rates of animals, plants, and microbes, accelerating their use of energy and materials, their population growth, and interaction rates. At a much larger biological scale, warming accelerates ecosystem-level processes, elevating fluxes of carbon and oxygen between biota and the atmosphere. Although these general effects of temperature at finer and broader biological scales are widely observed, they can lead to contradictory predictions for how warming affects the structure and function of ecological communities at the intermediate scale of biological organization. We experimentally tested the hypothesis that the presence of predators and their associated species interactions modify the temperature dependence of net ecosystem oxygen production and respiration. We tracked a series of independent freshwater ecosystems (370 L) over 9 weeks, and we found that at higher temperatures, cascading effects of predators on zooplankton prey and algae were stronger than at lower temperatures. When grazing was weak or absent, standing phytoplankton biomass declined by 85%–95% (〈1-fold) over the temperature gradient (19–30 °C), and by 3-fold when grazers were present and lacked predators. These temperature-dependent species interactions and consequent community biomass shifts occurred without signs of species loss or community collapse, and only modestly affected the temperature dependence of net ecosystem oxygen fluxes. The exponential increases in net ecosystem oxygen production and consumption were relatively insensitive to differences in trophic interactions among ecosystems. Furthermore, monotonic declines in phytoplankton standing stock suggested no threshold effects of warming across systems. We conclude that local changes in community structure, including temperature-dependent trophic cascades, may be compatible with prevailing and predictable effects of temperature on ecosystem functions related to fundamental effects of temperature on metabolism.
    Type: Article , PeerReviewed
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  • 3
    Publication Date: 2019-02-01
    Description: Habitat-forming species sustain biodiversity and ecosystem functioning in harsh environments through the amelioration of physical stress. Nonetheless, their role in shaping patterns of species distribution under future climate scenarios is generally overlooked. Focusing on coastal systems, we assess how habitat-forming species can influence the ability of stress-sensitive species to exhibit plastic responses, adapt to novel environmental conditions, or track suitable climates. Here, we argue that habitat-former populations could be managed as a nature-based solution against climate-driven loss of biodiversity. Drawing from different ecological and biological disciplines, we identify a series of actions to sustain the resilience of marine habitat-forming species to climate change, as well as their effectiveness and reliability in rescuing stress-sensitive species from increasingly adverse environmental conditions.
    Type: Article , PeerReviewed
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  • 4
    Publication Date: 2018-09-05
    Description: by Jianxia Li, Xiaofei Xia, Shenjian Xu, Jiayue Wu, Linlin Peng, Liangcheng Zhao The seeds of Salix and Populus (Salicaceae) are characterized by having numerous long hairs which loosely accompanying the seeds and a small annular appendage which surrounding the base of the seed along with tufted hairs. In this study, the complete development and detailed structure of the hairs and annular appendage in Salix matsudana were investigated using standard techniques for plant anatomy and histochemistry. The results show that the hairs originate successively from the single epidermal cells of the placenta (in megaspore mother cell phase) and funiculus (in eight-nucleate phase), and that their development consists of a progressive increase in cell size and an absence of cell division. The annular appendage is initiated from four to five rows of cells at the distal end of the funiculus in octant proembryo phase and its development is characterized by reactivated meristematic activity and a size increase of these cells. The initiation and development of the hairs are irrelevant to ovule development but fertilization and a developed embryo is necessary for the annular appendage to occur. Considering the reliable fossils, we inferred that the feature of seeds surrounded by long hairs is an ancestral character, and that the detachment of hairs from the funiculus and the occurrence of an annular appendage with tufts of hairs may be the more derived states for seed dispersal in Salix and Populus .
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 5
    Publication Date: 2018-09-05
    Description: by Hong Zou, Ivan Jakovlić, Dong Zhang, Rong Chen, Shahid Mahboob, Khalid Abdullah Al-Ghanim, Fahad Al-Misned, Wen-Xiang Li, Gui-Tang Wang As a result of great diversity in life histories and a large number of described species, taxonomic and phylogenetic uncertainty permeates the entire crustacean order of Isopoda. Large molecular datasets capable of providing sufficiently high phylogenetic resolution, such as mitochondrial genomes (mitogenomes), are needed to infer their evolutionary history with confidence, but isopod mitogenomes remain remarkably poorly represented in public databases. We sequenced the complete mitogenome of Cymothoa indica , a species belonging to a family from which no mitochondrial genome was sequenced yet, Cymothoidae. The mitogenome (circular, 14484 bp, A+T = 63.8%) is highly compact, appears to be missing two tRNA genes ( trnI and trnE ), and exhibits a unique gene order with a large number of rearrangements. High compactness and the existence of palindromes indicate that the mechanism behind these rearrangements might be associated with linearization events in its evolutionary history, similar to those proposed for isopods from the Armadillidium genus (Oniscidea). Isopods might present an important model system to study the proposed discontinuity in the dynamics of mitochondrial genomic architecture evolution. Phylogenetic analyses (Bayesian Inference and Maximum Likelihood) conducted using nucleotide sequences of all mitochondrial genes resolved Oniscidea and Cymothoida suborders as paraphyletic. Cymothoa indica was resolved as a sister group (basal) to all remaining isopods, which challenges the accepted isopod phylogeny, where Cymothoida are the most derived, and Phreatoicidea the most basal isopod group. There is growing evidence that Cymothoida suborder might be split into two evolutionary distant clades, with parasitic species being the most basal split in the Isopoda clade, but a much larger amount of molecular resources carrying a high phylogenetic resolution will be needed to infer the remarkably complex evolutionary history of this group of animals with confidence.
    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: 2018-09-05
    Description: by Iara Antonia Lustosa Nogueira, Érika Joseth Sousa Nogueira da Cruz, Andréa Martins Melo Fontenele, José Albuquerque de Figueiredo Neto Background Menopause consists of a physiological process in women between 40 and 50 years of age, and it has substantial consequences for health, ranging from disturbances in lipid and glycidic metabolism to psychological stress and sleep alterations, thereby increasing women’s risk of cardiovascular diseases. Here, we attempted to identify potential lipid alterations not identified by the classic methods. Methods and results We analyzed the serum lipid profile in 40 women in pre- and post-menopause using a lipidomic approach and mass spectrometry. Lipid species presented increased concentrations, with a difference of more than 25% post-menopause and with the ceramides (N.C23:0.Cer, N.C23:0(OH).Cer and N.C24:0(OH).Cer) standing out with a fold change of 1.68, 1.59, and 1.58, respectively. It was also observed that 14 metabolites presented a significant difference in the average concentrations between pre- and post-menopause, especially the ceramide species. Strong and positive correlations were identified between various metabolites and fasting glucose, glycated hemoglobin, total cholesterol, LDL, and triglycerides. Of note were the association ceramide (N.C10:0.Cer) and lysophosphatidylethanolamine (LPE.a.C18:0) between fasting glucose and glycated hemoglobin. Conclusion This study detected lipid alterations, especially in ceramides, post-menopause, as well as correlations with glycidic and lipid markers, which may in the future be useful to investigate diseases associated with menopause.
    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: 2018-09-05
    Description: by Gillian Dale, Danielle Sampers, Stephanie Loo, C. Shawn Green The tradeoff between knowing when to seek greater rewards (exploration), and knowing when to settle (exploitation), is critical to success. One dispositional factor that may modulate this tradeoff is “grit.” Gritty individuals tend to persist in the face of difficulty and consequently experience greater life success. It is possible that they may also experience a greater tendency to explore in a reward task. However, although most exploration/exploitation tasks manipulate beliefs about the presence/magnitude of rewards in the environment, the belief of one’s ability to actually achieve a reward is also critical. As such, we investigated whether individuals higher in grit were more likely to explore, and how beliefs about the magnitude/presence of rewards, and the perceived ability to achieve a reward, modulated their exploration tendencies. Over two experiments, participants completed 4 different exploration/persistence tasks: two that tapped into participant beliefs about the presence/magnitude of rewards, and two that tapped into participant beliefs about their ability to achieve a reward. Participants also completed measures of dispositional grit (Experiment 1a and 1b), conscientiousness (Experiment 1b), and working memory (Experiment 1a and 1b). In both experiments, we found a relationship between the two “belief of rewards” tasks, as well as between the two “belief of ability” tasks, but performance was unrelated across the two types of task. We also found that dispositional grit was strongly associated with greater exploration, but only on the “belief of ability” tasks. Finally, in Experiment 1b we showed that conscientiousness better predicted exploration on the “belief of ability” tasks than grit, suggesting that it is not grittiness per se that is associated with exploration. Overall, our findings showed that individuals high in grit/conscientiousness are more likely to explore, but only when there is a known reward available that they believe they have the ability to achieve.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 8
    Publication Date: 2018-09-05
    Description: by Kazufumi Nakamura, Masakiyo Sakaguchi, Hiromi Matsubara, Satoshi Akagi, Toshihiro Sarashina, Kentaro Ejiri, Kaoru Akazawa, Megumi Kondo, Koji Nakagawa, Masashi Yoshida, Toru Miyoshi, Takeshi Ogo, Takahiro Oto, Shinichi Toyooka, Yuichiro Higashimoto, Kei Fukami, Hiroshi Ito Background Pulmonary vascular remodeling of pulmonary arterial hypertension (PAH) is characterized by an inappropriate increase of vascular cells. The receptor for advanced glycation end products (RAGE) is a type I single-pass transmembrane protein belonging to the immunoglobulin superfamily and is involved in a broad range of hyperproliferative diseases. RAGE is also implicated in the etiology of PAH and is overexpressed in pulmonary artery smooth muscle cells (PASMCs) in patients with PAH. We examined the role of RAGE in the inappropriate increase of PASMCs in patients with PAH. Methods and results PASMCs were obtained from 12 patients with PAH including 9 patients with idiopathic PAH (IPAH) and 3 patients with heritable PAH (HPAH) (2 patients with BMPR2 mutation and one patient with SMAD9 mutation) who underwent lung transplantation. Western blot analysis and immunofluorescence staining revealed that RAGE and S100A8 and A9, ligands of RAGE, were overexpressed in IPAH and HPAH-PASMCs in the absence of any external growth stimulus. PDGF-BB (10 ng/mL) up-regulated the expression of RAGE in IPAH and HPAH-PASMCs. PAH-PASMCs are hyperplastic in the absence of any external growth stimulus as assessed by 3H-thymidine incorporation. This result indicates overgrowth characterized by continued growth under a condition of no growth stimulation in PAH-PASMCs. PDGF-BB stimulation caused a higher growth rate of PAH-PASMCs than that of non-PAH-PASMCs. AS-1, an inhibitor of TIR domain-mediated RAGE signaling, significantly inhibited overgrowth characterized by continued growth under a condition of no growth stimulation in IPAH and HPAH-PASMCs (P
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 9
    Publication Date: 2018-09-05
    Description: by Clarisse Dibao-Dina, Denis Angoulvant, Jean-Pierre Lebeau, Jean-Eudes Peurois, Karim Abdallah El Hirtsi, Anne-Marie Lehr-Drylewicz Background The 20% observed mortality within 5 years among survivors of myocardial infarction may be explained in part by non-adherence to the recommended treatment over the long term. Main objective To investigate post-myocardial infarction patients’ adherence to the therapeutic, lifestyle and risk factor control recommendations of the French health authority over 6 years. Materials and methods A cohort of survivors of myocardial infarction established in Tours in 2009 was followed over 6 years. The general practitioner of the patients included in the first 1-year follow-up study was contacted to collect data on treatments, cardiovascular risk factors and lifestyle between January and June 2015. Data were described and compared with the recommendations and predictors of achieving all the recommended targets were determined. Results A total of 97 patients (52%) among the 185 patients who underwent a coronary angioplasty for MI were included at baseline. Treatment was adapted by the general practitioner on the advice on the cardiologist for 75% (73/97) patients, by both of them for 12% (12/97) and by the general practitioner alone for 7% (7/97) patients. Among the 97 initial patients, 62 were included in the final analysis at 6 years. Fatal events rate was 5% (5/97) at 1 year and 12% (11/91) at 6 years. Non-fatal events rate was 44% (43/97) at 6 months, 19% (17/91) at 1 year and 29% (18/62) at 6 years. Six years after the myocardial infarction, 6 (10%) patients achieved the recommended targets in terms of prescriptions of treatment, risk factors and lifestyle targets. Exposure to a cardiac rehabilitation program after a myocardial infarction was associated with long-term achievement of optimal therapeutic objectives (OR = 7.31 [95% CI 1.74; 44.88], p
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 10
    Publication Date: 2018-09-05
    Description: by Abdelbassat Ketfi, Merzak Gharnaout, Mohamed Bougrida, Helmi Ben Saad Background The validation of the multi-ethnic GLI-2012 spirometric norms has been debated in several countries. However, its applicability in Algeria has not been verified. Aim To ascertain how well the GLI-2012 norms fit contemporary adult Algerian spirometric data. Methods This was a cross-sectional study of a convenience sample of 300 healthy non-smoker adults (50% men, age range: 18–85 years) recruited from the Algiers region general population. All participants underwent a clinical examination and a plethysmography measurement. Z-scores for some spirometric data [FEV 1 , FVC, FEV 1 /FVC and forced expiratory flow at 25–75% of FVC (FEF 25-75% )] were calculated. If the average Z-score deviated by “ 〈 ± 0.5” from the overall mean, the GLI-2012 norms would be considered as reflective of contemporary Algerian spirometry. Results The means±SDs of age, height, weight, FVC, FEV 1 , FEV 1 /FVC and FEF 25-75% of the participants were, respectively, 48±17 years, 1.65±0.10 m, 73±14 kg, 4.04±1.04 L, 3.18±0.82 L, 0.79±0.05 and 4.09±1.09 L/s. Almost the quarter of participants were obese. The total sample means±SDs Z-scores were 0.22±0.87 for FVC, 0.04±0.88 for FEV 1 , -0.34±0.67 for FEV 1 /FVC and 0.93±0.79 for FEF 25-75% . For men and women, only the means±SDs of the FEF 25-75% Z-scores exceeded the threshold of “± 0.5”, respectively, 1.13±0.77 and 0.73±0.76. Conclusion Results of the present study, performed in an Algerian population of healthy non-smoking adults, supported the applicability of the GLI-2012 norms to interpret FEV 1 , FVC and FEV 1 /FVC but not the FEF 25-75% .
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 11
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    Public Library of Science (PLoS)
    Publication Date: 2018-08-14
    Description: by Siobain Duffy The high mutation rate of RNA viruses is credited with their evolvability and virulence. This Primer, however, discusses recent evidence that this is, in part, a byproduct of selection for faster genomic replication.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 12
    Publication Date: 2018-08-14
    Description: by Rong Zhang, Zhao Ren, Wei Chen Gene co-expression network analysis is extremely useful in interpreting a complex biological process. The recent droplet-based single-cell technology is able to generate much larger gene expression data routinely with thousands of samples and tens of thousands of genes. To analyze such a large-scale gene-gene network, remarkable progress has been made in rigorous statistical inference of high-dimensional Gaussian graphical model (GGM). These approaches provide a formal confidence interval or a p-value rather than only a single point estimator for conditional dependence of a gene pair and are more desirable for identifying reliable gene networks. To promote their widespread use, we herein introduce an extensive and efficient R package named SILGGM (Statistical Inference of Large-scale Gaussian Graphical Model) that includes four main approaches in statistical inference of high-dimensional GGM. Unlike the existing tools, SILGGM provides statistically efficient inference on both individual gene pair and whole-scale gene pairs. It has a novel and consistent false discovery rate (FDR) procedure in all four methodologies. Based on the user-friendly design, it provides outputs compatible with multiple platforms for interactive network visualization. Furthermore, comparisons in simulation illustrate that SILGGM can accelerate the existing MATLAB implementation to several orders of magnitudes and further improve the speed of the already very efficient R package FastGGM. Testing results from the simulated data confirm the validity of all the approaches in SILGGM even in a very large-scale setting with the number of variables or genes to a ten thousand level. We have also applied our package to a novel single-cell RNA-seq data set with pan T cells. The results show that the approaches in SILGGM significantly outperform the conventional ones in a biological sense. The package is freely available via CRAN at https://cran.r-project.org/package=SILGGM.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 13
    Publication Date: 2018-08-14
    Description: by Simon Schäper, Hamish Yau, Elizaveta Krol, Dorota Skotnicka, Thomas Heimerl, Joe Gray, Volkhard Kaever, Lotte Søgaard-Andersen, Waldemar Vollmer, Anke Becker Members of the Rhizobiales (class of α-proteobacteria) display zonal peptidoglycan cell wall growth at one cell pole, contrasting with the dispersed mode of cell wall growth along the sidewalls of many other rod-shaped bacteria. Here, we show that the seven-transmembrane receptor (7TMR) protein RgsP (SMc00074), together with the putative membrane-anchored peptidoglycan metallopeptidase RgsM (SMc02432), have key roles in unipolar peptidoglycan formation during growth and at mid-cell during cell division in Sinorhizobium meliloti . RgsP is composed of a periplasmic globular 7TMR-DISMED2 domain, a membrane-spanning region, and cytoplasmic PAS, GGDEF and EAL domains. The EAL domain confers phosphodiesterase activity towards the second messenger cyclic di-GMP, a key regulatory player in the transition between bacterial lifestyles. RgsP and RgsM localize to sites of zonal cell wall synthesis at the new cell pole and cell divison site, suggesting a role in cell wall biogenesis. The two proteins are essential for cell wall biogenesis and cell growth. Cells depleted of RgsP or RgsM had an altered muropeptide composition and RgsM binds to peptidoglycan. RgsP and RgsM orthologs are functional when interchanged between α-rhizobial species pointing to a conserved mechanism for cell wall biogenesis/remodeling within the Rhizobiales. Overall, our findings suggest that RgsP and RgsM contribute to the regulation of unipolar cell wall biogenesis in α-rhizobia.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 14
    Publication Date: 2018-08-14
    Description: by Kyubum Lee, Maria Livia Famiglietti, Aoife McMahon, Chih-Hsuan Wei, Jacqueline Ann Langdon MacArthur, Sylvain Poux, Lionel Breuza, Alan Bridge, Fiona Cunningham, Ioannis Xenarios, Zhiyong Lu Manually curating biomedical knowledge from publications is necessary to build a knowledge based service that provides highly precise and organized information to users. The process of retrieving relevant publications for curation, which is also known as document triage, is usually carried out by querying and reading articles in PubMed. However, this query-based method often obtains unsatisfactory precision and recall on the retrieved results, and it is difficult to manually generate optimal queries. To address this, we propose a machine-learning assisted triage method. We collect previously curated publications from two databases UniProtKB/Swiss-Prot and the NHGRI-EBI GWAS Catalog, and used them as a gold-standard dataset for training deep learning models based on convolutional neural networks. We then use the trained models to classify and rank new publications for curation. For evaluation, we apply our method to the real-world manual curation process of UniProtKB/Swiss-Prot and the GWAS Catalog. We demonstrate that our machine-assisted triage method outperforms the current query-based triage methods, improves efficiency, and enriches curated content. Our method achieves a precision 1.81 and 2.99 times higher than that obtained by the current query-based triage methods of UniProtKB/Swiss-Prot and the GWAS Catalog, respectively, without compromising recall. In fact, our method retrieves many additional relevant publications that the query-based method of UniProtKB/Swiss-Prot could not find. As these results show, our machine learning-based method can make the triage process more efficient and is being implemented in production so that human curators can focus on more challenging tasks to improve the quality of knowledge bases.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 15
    Publication Date: 2018-08-14
    Description: by Massimo Ralli, Antonio Greco, Armando Boccassini, Giancarlo Altissimi, Carlo Di Paolo, Vincenzo Falasca, Armando De Virgilio, Antonella Polimeni, Giancarlo Cianfrone, Marco de Vincentiis Objective Determine in a cohort of patients with normal hearing and chronic tinnitus if self-reported history for temporomandibular joint (TMJ) dysfunction and a positive modulation of tinnitus in the TMJ region could be suggestive of an underlying TMJ disorder. Patients and methods The study included 226 patients presenting to the Head and Neck Service of our University Hospital. Following audiological and somatic tinnitus evaluation, patients were divided into two groups. The study group (n = 134) included subjects that met both the following criteria: A) a self-reported history for TMJ dysfunction and B) a positive modulation of tinnitus following somatic maneuvers in the TMJ region. The control group (n = 92) included patients with similar demographic and tinnitus characteristics that did not meet the proposed criteria for somatic tinnitus. Afterwards, patients underwent clinical TMJ evaluation in the Service of Clinical Gnathology of our University. Results One hundred thirty-one patients (57.9%) received a clinical diagnosis of TMJ disorder according to DC/TMD Axis I; 79.1% in the study group and 27.2% in the control group. Ninety-five (42.1%) patients were negative for TMJ disorders; 20.9% in the study group and 72.8% in the control group. A significantly higher number of TMJ disorders was found in patients in the study group compared to the control group (p
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 16
    Publication Date: 2018-08-14
    Description: by Péter L. Erdős, Tamás Róbert Mezei, István Miklós, Dániel Soltész Since 1997 a considerable effort has been spent on the study of the swap (switch) Markov chains on graphic degree sequences. All of these results assume some kind of regularity in the corresponding degree sequences. Recently, Greenhill and Sfragara published a breakthrough paper about irregular normal and directed degree sequences for which rapid mixing of the swap Markov chain is proved. In this paper we present two groups of results. An example from the first group is the following theorem: let d → be a directed degree sequence on n vertices. Denote by Δ the maximum value among all in- and out-degrees and denote by | E → | the number of edges in the realization. Assume furthermore that Δ 〈 1 2 | E → | - 4. Then the swap Markov chain on the realizations of d → is rapidly mixing. This result is a slight improvement on one of the results of Greenhill and Sfragara. An example from the second group is the following: let d be a bipartite degree sequence on the vertex set U ⊎ V , and let 0 〈 c 1 ≤ c 2 〈 | U | and 0 〈 d 1 ≤ d 2 〈 | V | be integers, where c 1 ≤ d( v ) ≤ c 2 : ∀ v ∈ V and d 1 ≤ d( u ) ≤ d 2 : ∀ u ∈ U . Furthermore assume that ( c 2 − c 1 − 1)( d 2 − d 1 − 1) 〈 max{ c 1 (| V | − d 2 ), d 1 (| U | − c 2 )}. Then the swap Markov chain on the realizations of d is rapidly mixing. A straightforward application of this latter result shows that when a random bipartite or directed graph is generated under the Erdős—Rényi G ( n , p ) model with mild assumptions on n and p then the degree sequence of the generated graph has, with high probability, a rapidly mixing swap Markov chain on its realizations.
    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: 2018-08-14
    Description: by Remo M. A. van der Heiden, Christian P. Janssen, Stella F. Donker, Lotte E. S. Hardeman, Keri Mans, J. Leon Kenemans We investigate how susceptible human drivers are to auditory signals in three situations: when stationary, when driving, or when being driven by an autonomous vehicle. Previous research has shown that human susceptibility is reduced when driving compared to when being stationary. However, it is not known how susceptible humans are under autonomous driving conditions. At the same time, good susceptibility is crucial under autonomous driving conditions, as such systems might use auditory signals to communicate a transition of control from the automated vehicle to the human driver. We measured susceptibility using a three-stimulus auditory oddball paradigm while participants experienced three driving conditions: stationary, autonomous, or driving. We studied susceptibility through the frontal P3 (fP3) Electroencephalography Event-Related Potential response (EEG ERP response). Results show that the fP3 component is reduced in autonomous compared to stationary conditions, but not as strongly as when participants drove themselves. In addition, the fP3 component is further reduced when the oddball task does not require a response (i.e., in a passive condition, versus active). The implication is that, even in a relatively simple autonomous driving scenario, people’s susceptibility of auditory signals is not as high as would be beneficial for responding to auditory stimuli.
    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: 2018-08-14
    Description: by Momina Hussain, Muhammad Atif Iqbal, Bradley J. Till, Mehboob-ur- Rahman Wheat is a staple food crop of many countries. Improving resilience to biotic and abiotic stresses remain key breeding targets. Among these, rust diseases are the most detrimental in terms of depressing wheat production. In the present study, chemical mutagenesis was used to induce mutations in the wheat variety NN-Gandum-1. This cultivar is moderately resistant to leaf and yellow rust. The aim of mutagenesis was to improve resistance to the disease as well as to study function of genes conferring resistance to the disease. In the present investigation, a 0.8% EMS dose was found optimum for supporting 45–55% germination of NN-Gandum-1. A total of 3,634 M 2 fertile plants were produced from each of the M 1 plant. Out of these, 33 (0.91%) and 20 plants (0.55%) showed absolute resistance to leaf and yellow rust, respectively. While 126 (3.46%) and 127 plants (3.49%) exhibited high susceptibility to the leaf and yellow rust, respectively. In the M 4 generation, a total of 11 M 4 lines (nine absolute resistant and two highly susceptible) and one wild type were selected for NGS-based exome capture assay. A total of 104,779 SNPs were identified that were randomly distributed throughout the wheat sub genomes (A, B and D). Induced mutations in intronic sequences predominated. The highest total number of SNPs detected in this assay were mapped to chr.2B (14,273 SNPs), which contains the highest number of targeted base pairs in the assay. The average mutation density across all regions interrogated was estimated to be one mutation per 20.91 Mb. The highest mutation frequency was found in chr.2D (1/11.7 kb) and the lowest in chr.7D (1/353.4 kb). Out of the detected mutations, 101 SNPs were filtered using analysis criteria aimed to enrich for mutations that may affect gene function. Out of these, one putative SNP detected in Lr21 were selected for further analysis. The SNP identified in chimeric allele ( Lr21 ) of a resistant mutant (N1-252) was located in a NBS domain of chr.1BS at 3.4 Mb position. Through computational analysis, it was demonstrated that this identified SNP causes a substitution of glutamic acid with alanine, resulting in a predicted altered protein structure. This mutation, therefore, is a candidate for contributing to the resistance phenotype in the mutant line. Based on this work, we conclude that the wheat mutant resource developed is useful as a source of novel genetic variation for forward-genetic screens and also as a useful tool for gaining insights into the important biological circuits of different traits of complex genomes like wheat.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 19
    Publication Date: 2018-08-14
    Description: by Fernanda Almeida, Amanda Aparecida Seribelli, Marta Inês Cazentini Medeiros, Dália dos Prazeres Rodrigues, Alessandro de MelloVarani, Yan Luo, Marc W. Allard, Juliana Pfrimer Falcão Whole genome sequencing (WGS) has been used as a powerful technology for molecular epidemiology, surveillance, identification of species and serotype, identification of the sources of outbreaks, among other purposes. In Brazil, there is relatively few epidemiological data on Salmonella . In this study, 90 Salmonella Typhimurium strains had their genome sequenced to uncover the diversity of Salmonella Typhimurium isolated from humans and food, between 1983 and 2013, from different geographic regions in Brazil based on single nucleotide polymorphism (SNP) analysis. A total of 39 resistance genes were identified, such as aminoglycoside, tetracycline, sulfonamide, trimethoprim, beta-lactam, fluoroquinolone, phenicol and macrolide, as well as the occurrence of point mutations in some of the genes such as gyrA , gyrB , parC and parE . A total of 65 (72.2%) out of 90 S . Typhimurium strains studied were phenotypically resistant to sulfonamides, 44 (48.9%) strains were streptomycin resistant, 27 (30%) strains were resistant to tetracycline, 21 (23.3%) strains were gentamicin resistant, and seven (7.8%) strains were resistant to ceftriaxone. In the gyrA gene, it was observed the following amino acid substitutions: Asp(87)→Gly, Asp(87)→Asn, Ser(83)→Phe, Ser(83)→Tyr. Phylogenetic results placed the 90 S . Typhimurium strains into two major clades suggesting the existence of a prevalent subtype, likely more adapted, among strains isolated from humans, with some diversity in subtypes in foods. The variety and prevalence of resistant genes found in these Salmonella Typhimurium strains reinforces their potential hazard for humans and the risk in foods in Brazil.
    Electronic ISSN: 1932-6203
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  • 20
    Publication Date: 2018-08-14
    Description: by D. Ntirampeba, I. Neema, L. Kazembe Background Making inferences about measles distribution patterns at small area level is vital for more focal targeted intervention. However, in statistical literature, the analysis of originally collected data on one resolution with the purpose to make inferences on a different level of spatial resolution is referred to as the misalignment problem. In Namibia the measles data were available in aggregated format at regional level for the period 2005 to 2014. This leads to a spatial misalignment problem if the purpose is to make decisions at constituency level. Moreover, although data on risk covariates of measles could be obtained at constituency level, they were not available each year between 2005 and 2014. Thus, assuming that covariates were constant through the study period would induce measurement errors which might have effects on the analysis results. This paper presents a spatio-temporal model through a multi-step approach in order to deal with misalignment and measurement error. Methods For the period 2005–2014, measles data from the Ministry of Health and Social Services (MoHSS) were analysed in two steps. First, a multi-step approach was applied to correct spatial misalignment in the data. Second, a classical measurement error model was fitted to account for measurement errors. The time effects were specified using a nonparametric formulation for the linear trend through first order random walk. An interaction between area and time was modelled through type I and type II interaction structures. Results The study showed that there was high variation in measles risk across constituencies and as well as over the study period (2005–2014). Furthermore, the risk of measles was found to be associated with (i) the number of people aged between 0 and 24 years, (ii) the percentages of women aged 15–49 with an educational level more than secondary, (iii) the percentages of children age 12–23 months who received measles vaccine, (iv) the percentages of malnourished children under 5 years, and (vi) the measles cases for each previous year. Conclusion The study showed some of the determinants of measles risk and revealed areas at high risk through disease mapping. Additionally, the study showed a non-linear temporal distribution of measles risk over the study period. Finally, it was shown that ignoring the measurement errors may yield misleading results. It was recommended that group and geographically targeted intervention, prevention and control strategies can be tailored on the basis these findings.
    Electronic ISSN: 1932-6203
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  • 21
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    Publication Date: 2018-08-14
    Description: by Elena Deligianni, Natalie C. Silmon de Monerri, Paul J. McMillan, Lucia Bertuccini, Fabiana Superti, Maria Manola, Lefteris Spanos, Christos Louis, Michael J. Blackman, Leann Tilley, Inga Siden-Kiamos Pore forming proteins such as those belonging to the membrane attack/perforin (MACPF) family have important functions in many organisms. Of the five MACPF proteins found in Plasmodium parasites, three have functions in cell passage and one in host cell egress. Here we report an analysis of the perforin-like protein 4, PPLP4, in the rodent parasite Plasmodium berghei . We found that the protein is expressed only in the ookinete, the invasive stage of the parasite formed in the mosquito midgut. Transcriptional analysis revealed that expression of the pplp4 gene commences during ookinete development. The protein was detected in retorts and mature ookinetes. Using two antibodies, the protein was found localized in a dotted pattern, and 3-D SIM super-resolution microcopy revealed the protein in the periphery of the cell. Analysis of a C-terminal mCherry fusion of the protein however showed mainly cytoplasmic label. A pplp4 null mutant formed motile ookinetes, but these were unable to invade and traverse the midgut epithelium resulting in severely impaired oocyst formation and no transmission to naïve mice. However, when in vitro cultured ookinetes were injected into the thorax of the mosquito, thus by-passing midgut passage, sporozoites were formed and the mutant parasites were able to infect naïve mice. Taken together, our data show that PPLP4 is required only for ookinete invasion of the mosquito midgut. Thus PPLP4 has a similar role to the previously studied PPLP3 and PPLP5, raising the question why three proteins with MACPF domains are needed for invasion by the ookinete of the mosquito midgut epithelium.
    Electronic ISSN: 1932-6203
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  • 22
    Publication Date: 2018-08-14
    Description: by Lincoln S. C. Wong, Tim P. Lynch, Neville S. Barrett, Jeffrey T. Wright, Mark A. Green, David J. H. Flynn The critically endangered spotted handfish ( Brachionichthys hirsutus ) is restricted to a limited number of locations in south-eastern Tasmania, Australia. As is often the case for rare species, conducting statistically adequate surveys for B . hirsutus can be costly and time consuming due to the low probability of encountering individuals. For the first time we used a highly efficient and rigorous Global Positioning System (GPS) parameterised underwater visual census (GUVC) to survey B . hirsutus abundance within all nine known local populations in the Derwent Estuary within one season. In addition, a benthic microhabitat assessment was conducted simultaneously using a GoPro ® camera attached to diver to determine B . hirsutus microhabitat preferences. B . hirsutus local populations varied between sites, with densities ranging from 1.58 to 43.0 fishes per hectare. B . hirsutus demonstrates a strong preference for complex microhabitat features, such as depressions and ripple formations filled with biogenic substrates (e.g. shells) but avoids simple, low relief microhabitats (e.g. sand flats) and areas dominated by ephemeral, filamentous algae. Complex microhabitats may enable B . hirsutus to avoid predators, increase forage opportunities or provide higher quality spawning sites. This first wide-scale application of GUVC for B . hirsutus allowed us to survey a larger number of sites than previously possible to provide a robust reference point for future long-term monitoring.
    Electronic ISSN: 1932-6203
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  • 23
    Publication Date: 2018-08-14
    Description: by Anny H. Xiang, Mary Helen Black, Yu-Hsiang Shu, Jun Wu, Adrienne MacKay, Corinna Koebnick, Richard M. Watanabe, Thomas A. Buchanan Obesity and adipokines are associated with development of type 2 diabetes. However, limited longitudinal studies have examined their roles on declining β-cell function over time. This report assessed three adiposity measures (BMI, percent body fat, trunk fat), insulin resistance, and fifteen adipokines in relationship to longitudinal change in β-cell function measured by disposition index (DI) from frequently-sampled-intravenous-glucose-tolerance testing. The results showed that three factors were significantly and independently associated with rate of change in DI over time: rate of change in BMI (negative), rate of change in IL-6 (negative), and baseline adiponectin (positive). The association was the strongest for changing BMI and was largely explained by changing insulin resistance; the association with changing IL-6 was also largely explained by changing insulin resistance. Baseline adiponectin remained positively associated after adjustment for changing insulin resistance, suggesting an independent effect of adiponectin to preserve or improve β-cell function. These findings provide evidence and potential mechanisms for the role of obesity in promoting β-cell dysfunction, highlighting the potential importance of mitigating obesity and its metabolic effects in preventing and treating type 2 diabetes.
    Electronic ISSN: 1932-6203
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  • 24
    Publication Date: 2018-08-14
    Description: by Mareen Matz, Frederik Heinrich, Christine Lorkowski, Kaiyin Wu, Jens Klotsche, Qiang Zhang, Nils Lachmann, Pawel Durek, Klemens Budde, Mir-Farzin Mashreghi Interstitial fibrosis/tubular atrophy (IFTA) is associated with reduced allograft survival, whereas antibody-mediated rejection (ABMR) is the major cause for renal allograft failure. To identify specific microRNAs and their regulation involved in these processes, total RNA from blood cells of 16 kidney transplanted (KTx) patients with ABMR, stable graft function (SGF) and with T-cell mediated rejection (TCMR) was isolated. MicroRNA expression was determined by high-throughput sequencing. Differentially expressed candidate microRNAs were analyzed with RT-PCR in patients with SGF (n = 53), urinary tract infection (UTI) (n = 17), borderline rejection (BL) (n = 19), TCMR (n = 40), ABMR (n = 22) and IFTA (n = 30). From the 301 detected microRNAs, 64 were significantly regulated between the three cohorts. Selected candidate microRNAs miR-223-3p, miR-424-3p and miR-145-5p distinguished TCMR and ABMR from SGF, but not from other pathologies. Most importantly, miR-145-5p expression in IFTA patients was significantly downregulated and displayed a high diagnostic accuracy compared to SGF alone (AUC = 0.891) and compared to SGF, UTI, BL, TCMR and ABMR patients combined (AUC = 0.835), which was verified by cross-validation. The identification of miR-145-5p as IFTA specific marker in blood constitutes the basis for evaluating this potentially diagnostic microRNA as biomarker in studies including high numbers of patients and different pathologies and also the further analysis of fibrosis causing etiologies after kidney transplantation.
    Electronic ISSN: 1932-6203
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  • 25
    Publication Date: 2018-08-14
    Description: by Jean-Noël Hubert, Tatiana Zerjal, Frédéric Hospital Devil Facial Tumor Disease (DFTD) is an aggressive cancer notorious for its rare etiology and its impact on Tasmanian devil populations. Two regions underlying an evolutionary response to this cancer were recently identified using genomic time-series pre- and post-DTFD arrival. Here, we support that DFTD shaped the genome of the Tasmanian devil in an even more extensive way than previously reported. We detected 97 signatures of selection, including 148 protein coding genes having a human orthologue, linked to DFTD. Most candidate genes are associated with cancer progression, and an important subset of candidate genes has additional influence on social behavior. This confirms the influence of cancer on the ecology and evolution of the Tasmanian devil. Our work also demonstrates the possibility to detect highly polygenic footprints of short-term selection in very small populations.
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  • 26
    Publication Date: 2018-08-14
    Description: by Francesco Bisognin, Giulia Lombardi, Donatella Lombardo, Maria Carla Re, Paola Dal Monte Background The new Xpert MTB/RIF Ultra assay (Ultra, Cepheid, Sunnyvale, USA) is a cartridge-based automated diagnostic test that can simultaneously identify Mycobacterium tuberculosis complex (MTB) and resistance to Rifampicin (RIF). With respect to the previous version Xpert MTB/RIF assay (Xpert), IS6110/IS1081 repetitive elements probes have been added allowing the detection of lower MTB load, defined by the new semi-quantitative category “trace” with indeterminate RIF resistance. The aim of this study was to evaluate performance of the new version Ultra on Xpert-negative, but TB culture-positive clinical samples. Methods The de-identified frozen samples (-20 °C) collected over a 4-year period (February 2014-October 2017), which had previously resulted smear-negative, Xpert-negative but MTB culture-positive, were analyzed with Ultra. The de-frosted samples were loaded into the cartridge using the same process as the previous version, according to manufacturer’s instruction. Results During the study period 382 MTB culture-positive samples were archived: 314 resulted Xpert-positive and 68 Xpert-negative. Thirty-one of the 68 Xpert-negative samples resulted positive with Ultra, with an overall improvement in MTB detection of 45.6%. Out of 36 Xpert-negative respiratory samples, 18 resulted Ultra-positive with the following semi-quantitative loads: “low”(n = 1), “very low”(n = 11), “trace”(n = 6), with an improvement in MTB detection of 50%. The best performance was achieved on bronchoalveolar lavage specimens (53.8%). Out of 32 Xpert-negative non-respiratory samples, 13 resulted Ultra-positive with the following semi-quantitative loads: “very low”(n = 7), “trace”(n = 6), with an improvement in MTB detection of 40.6%. The best performance was achieved on biopsies (55.6%) and lymph nodes (50%). The new category “trace” detected 12 out of the 31 Ultra-positive MTB samples; in the remaining 19 samples RIF susceptibility was determined with 100% concordance with the phenotypic susceptibility test. The mean time to positivity of samples found negative by Ultra was significantly longer in comparison to positive samples in liquid culture. Conclusions Our results are consistent with the few studies published so far and confirm the better performance of Ultra compared to the previous version in both respiratory and non-respiratory smear-negative samples, with an overall improvement of 45.6%.
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  • 27
    Publication Date: 2018-08-14
    Description: by Noriko Otsuki, Reiko Arakawa, Kaori Kaneko, Ryoko Aoki, Masayuki Arakawa, Kayoko Saito Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disorder caused by insufficiency of functional survival motor neuron (SMN) protein. Several clinical trials have been conducted with the aim of upregulating the expression of the SMN protein in SMA patients. In order to evaluate the efficiency of these SMN-targeted approaches, it has become necessary to verify SMN protein levels in the cells of SMA patients. Accordingly, we have developed a method allowing the evaluation of the functional SMN protein with 〈 1.5 mL of peripheral blood using imaging flow cytometry. The expression of SMN protein in CD3 + , CD19 + , and CD33 ++ cells obtained from SMA patients, was significantly reduced compared with that in cells from control subjects. In spot analysis of CD33 ++ cells, the intensities of SMN spots were significantly reduced in SMA subjects, when compared with that in controls. Therefore, SMN spots implied the presence of functional SMN protein in the cell nucleus. To our knowledge, our results are the first to demonstrate the presence of functional SMN protein in freshly isolated peripheral blood cells. We anticipate that SMN spot analysis will become the primary endpoint assay for the evaluation and monitoring of therapeutic intervention, with SMN serving as a reliable biomarker of therapeutic efficacy in SMA patients.
    Electronic ISSN: 1932-6203
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  • 28
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    Publication Date: 2018-09-06
    Description: by Merel Maslowski, Antje S. Meyer, Hans Rutger Bosker Listeners are known to use adjacent contextual speech rate in processing temporally ambiguous speech sounds. For instance, an ambiguous vowel between short /α/ and long /a:/ in Dutch sounds relatively long (i.e., as /a:/) embedded in a fast precursor sentence, but short in a slow sentence. Besides the local speech rate, listeners also track talker-specific global speech rates. However, it is yet unclear whether other talkers’ global rates are encoded with reference to a listener’s self-produced rate. Three experiments addressed this question. In Experiment 1, one group of participants was instructed to speak fast, whereas another group had to speak slowly. The groups were compared on their perception of ambiguous /α/-/a:/ vowels embedded in neutral rate speech from another talker. In Experiment 2, the same participants listened to playback of their own speech and again evaluated target vowels in neutral rate speech. Neither of these experiments provided support for the involvement of self-produced speech in perception of another talker’s speech rate. Experiment 3 repeated Experiment 2 but with a new participant sample that was unfamiliar with the participants from Experiment 2. This experiment revealed fewer /a:/ responses in neutral speech in the group also listening to a fast rate, suggesting that neutral speech sounds slow in the presence of a fast talker and vice versa. Taken together, the findings show that self-produced speech is processed differently from speech produced by others. They carry implications for our understanding of rate-dependent speech perception in dialogue settings, suggesting that both perceptual and cognitive mechanisms are involved.
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  • 29
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    Publication Date: 2018-09-06
    Description: by Jill A. McDonald, Anup Amatya, Charlotte C. Gard, Jesus Sigala Background Cesarean delivery occurs in one in three US births and poses risks for mothers and infants. Hispanic cesarean rates were higher than non-Hispanic white rates in the US in 2016. In 2009, cesarean rates among Hispanics on the US-Mexico border exceeded rates among US Hispanics. Since 2009, rates have declined nationwide, but border Hispanic rates have not been studied. Objective To compare cesarean delivery rates and trends in Hispanics and non-Hispanic whites in border and nonborder counties of the four US border states before and after 2009. Study Design We used data from birth certificates to calculate percentages of cesarean deliveries among all births and births to low-risk nulliparous women during 2000–2015, and among births to low-risk women with and without a previous cesarean during 2009–2015. We calculated 95% confidence intervals around rates and used regular and piecewise linear regression to estimate trends for four ethnic-geographic subpopulations defined by combinations of Hispanic ethnicity and border-nonborder status. Results Of the four subpopulations, border Hispanic rates were highest every year for all cesarean outcomes. In 2015 they were 38.3% overall, 31.4% among low-risk nulliparous women, and 21.1% and 94.6% among low-risk women without and with a previous cesarean, respectively. Nonborder Hispanic rates in 2015 were lowest for all outcomes but repeat cesarean. Rates for all four subpopulations rose steadily during 2000–2009. Unlike rates for non-Hispanic whites, border and nonborder Hispanic rates did not decline post-2009. Most of the border Hispanic excess can be attributed to higher cesarean rates in Texas. Discussion Border Hispanic cesarean rates remain higher than those among other Hispanics and non-Hispanic whites in border states and show no signs of declining. This continuing disparity warrants further analysis using individual as well as hospital, environmental and other contextual factors to help target prevention measures.
    Electronic ISSN: 1932-6203
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  • 30
    Publication Date: 2018-09-06
    Description: by Tenglong Xie, Wanrong Gu, Liguo Zhang, Lijie Li, Danyang Qu, Caifeng Li, Yao Meng, Jing Li, Shi Wei, Wenhua Li Maize ( Zea mays L.), an important agricultural crop, suffers from drought stress frequently during its growth period, thus leading to a decline in yield. 2-(3,4-Dichlorophenoxy) triethylamine (DCPTA) regulates many aspects of plant development; however, its effects on crop stress tolerance are poorly understood. We pre-treated maize seedlings by adding DCPTA to a hydroponic solution and then subjected the seedlings to a drought condition [15% polyethylene glycol (PEG)-6000 treatment]. The activities of superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX), and glutathione reductase (GR) were enhanced under drought stress and further enhanced by the DCPTA application. The activities of monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and catalase (CAT) declined continuously under drought stress; however, the activities partially recovered with DCPTA application. Up-regulation of the activities and transcript levels of APX, GR, MDHAR and DHAR in the DCPTA treatments contributed to the increases in ascorbate (AsA) and glutathione (GSH) levels and inhibited the increased generation rate of superoxide anion radicals (O 2 · − ), the contents of hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA), and the electrolyte leakage (EL) induced by drought. These results suggest that the enhanced antioxidant capacity induced by DCPTA application may represent an efficient mechanism for increasing the drought stress tolerance of maize seedlings.
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  • 31
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    Publication Date: 2018-09-06
    Description: by Sebbi L. Kankondi, Christopher D. McQuaid, Morgana Tagliarolo Predicting ecological responses to climate change requires an understanding of the mechanisms that influence species’ tolerances to temperature. Based on the idea that air and water breathing animals are differentially suited to life in either medium due to differences in their respiratory morphology, we examined the possibility that the thermal tolerances of co-existing intertidal pulmonate and patellogastropod limpets may differ in different breathing media. We tested this by determining each species’ median lethal temperature (LT 50 ) and cardiac Arrhenius breakpoint temperature (ABT) as measures of upper thermal tolerance limits, in air and water. Although all these species can survive in air and water, we hypothesised that the pulmonate limpets, Siphonaria capensis and S . serrata , would have higher thermal limits than the patellogastropod limpets, Cellana capensis and Scutellastra granularis , in air and vice versa in water. The results did not support our hypotheses, since C . capensis had similar thermal tolerance limits to the pulmonate limpets in air and the pulmonate limpets had thermal tolerance limits similar to or higher than S . granularis in water. Thus, considering pulmonate and patellid limpets as groups, we found no differences in their collective upper thermal tolerance limits in either medium. We conclude that differences between these two limpet groups in their respiratory morphology do not influence thermal tolerance, but that tolerances are species-specific.
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  • 32
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    Publication Date: 2018-09-06
    Description: by Xiuxia Mu, Chongliang Zhang, Chi Zhang, Binduo Xu, Ying Xue, Yiping Ren It is difficult to determine ages of eels via otoliths, because multiple alternating translucent and opaque zones in the otoliths are hard to identify. In this study, we developed an efficient age determination method for whitespotted conger ( Conger myriaster ), using random forest models with otolith weight and length, total body length, capture location and season as predictors. 409 specimens were collected from six locations in Yellow and East China Sea between October 2016 and December 2017. Overall OOB error rate was 17.36% compared with 16.26% for the external cross-validation dataset, and the error of age was within one year. Otolith weight and total length were the most important predictors, followed by otolith length, capture locations and seasons. There were no significant differences between the results derived from otolith/somatic morphometrics and otoliths annuli in the estimation of age composition and von Betalanffy Growth Functions growth curve. Our results demonstrated that random forest model with otolith and somatic morphometrics is an efficient and reliable approach for age determination of C . myriaster , which may also be applied to other eel species.
    Electronic ISSN: 1932-6203
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  • 33
    Publication Date: 2018-09-06
    Description: by Ute Lina Fahlenkamp, Lisa Christine Adams, Sarah Maria Böker, Günther Engel, Minh Huynh Anh, Moritz Wagner, Bernd Hamm, Marcus Richard Makowski Aim To compare the potential of a gadoxetate disodium enhanced navigator-triggered 3D T1 magnetic-resonance cholangiography (MRC) sequence with a specific inversion recovery prepulse to T2-weighted MRCP for assessment of the hepatobiliary system. Materials and methods 30 patients (12 male, 18 female) prospectively underwent conventional navigator-triggered 3D turbo spin-echo T2-weighted MRCP and 3D T1 MRC with a specific inversion pulse to minimise signal from the liver 30 minutes after administration of gadoxetate disodium on a 1.5 T MRI system. For qualitative evaluation, biliary duct depiction was assessed segmentally following a 5-point Likert scale. Visualisation of hilar structures as well as image quality was recorded. Additionally, the extrahepatic bile ducts were assessed quantitatively by calculation of signal-to-noise ratios (SNR). Results The advantages of T1 3D MRC include reduced affection of image quality by bowel movement and robust depiction of the relative position of the extrahepatic bile ducts in relation to the portal vein and the duodenum compared to T2 MRCP. However, overall T1 3D MRC did not significantly (p 〉 0.05) improve the biliary duct depiction compared to T2 MRCP in all segments: Common bile duct 4.1 vs. 4.4, right hepatic duct 3.6 vs. 4.2, left hepatic duct 3.5 vs. 4.1. Image quality did not differ significantly (p 〉 0.05) between both sequences (3.6 vs. 3.5). SNR measurements for the hepatobiliary system did not differ significantly (p 〉 0.05) between navigator-triggered T1 3D MRC and T2 MRCP. Conclusions This preliminary study demonstrates that T1 3D MRC of a specific inversion recovery prepulse has potential to complement T2 MRCP, especially for the evaluation of liver structures close to the hilum in the diagnostic work-up of the biliary system in patients receiving gadoxetate disodium.
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  • 34
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    Publication Date: 2018-09-06
    Description: by Xianlei Gao, Songgang Wang, Yeyang Xu, Hao Li, Hua Zhao, Xin Pan Medical carbon material has been extensively studied due to their excellent biological and mechanical properties. However, the dissociation of the surface carbon particles greatly limited the application of medical carbon material (MCM). To overcome this defect, we introduced the polydimethylsiloxane, a polymer-coating material (PCM) that possesses acceptable biocompatibility, into medical carbon material to prevent the shedding of carbon debris. Additionally, to reduce inflammatory reactions and increase surface hydrophilicity, ferulic acid, also called Chinese medicine coating material (CCM), was used to modify the surface of polymer-coating material. We investigated the proliferation and adhesion of NIH-3T3 cells onto MCM, PCM and CCM in vitro . We showed that CCM exhibited excellent biological activity to promote cell growth. Twelve weeks after CCM implantation, bone defects were repaired, and the material showed acceptable chemical stability. The results indicated that the CCM composite possesses excellent mechanical property and favorable biocompatibility, which can be used for clinical bone repair.
    Electronic ISSN: 1932-6203
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  • 35
    Publication Date: 2018-09-06
    Description: by Hon-Yen Wu, Jenq-Wen Huang, Wan-Chuan Tsai, Yu-Sen Peng, Hung-Yuan Chen, Ju-Yeh Yang, Shih-Ping Hsu, Mei-Fen Pai, Mei-Ju Ko, Kuan-Yu Hung, Hsien-Ching Chiu Background Uremic pruritus is a common and frustrating symptom among patients receiving peritoneal dialysis (PD). This study aimed to examine the prognostic importance of uremic pruritus and to identify the determinants for higher pruritus intensity in PD patients. Methods We conducted a prospective cohort study of patients receiving maintenance PD. A visual analogue scale (VAS) score was used to measure the intensity of uremic pruritus. The composite endpoint of PD technique failure or all-cause death was assessed using a multivariable Cox proportional hazards model. The determinants for the VAS score of uremic pruritus was assessed using a multivariable linear regression model. Results Among the 85 PD patients, 24 (28%) had uremic pruritus. During a median follow-up of 28.0 months, 12 patients experienced technique failure, and 7 died. We found that a higher VAS score of pruritus intensity was an independent risk factor for technique failure or death (hazard ratio, 1.64; 95% confidence interval, 1.18 to 2.28; P = 0.003) after adjusting for a variety of confounding factors. We also found that a weekly total Kt/V of less than 1.88, a longer duration of dialysis, a higher dietary protein intake, and higher blood levels of intact parathyroid hormone and high-sensitivity C-reactive protein were independent determinants of higher VAS scores of pruritus intensity. Conclusions Our results show that uremic pruritus is an independent risk factor of technique failure and death in patients receiving PD. We also found that a weekly total Kt/V 〈 1.88 is associated with higher intensity of uremic pruritus in PD patients.
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  • 36
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    Publication Date: 2018-09-06
    Description: by Anselme Simeon Sanou, Abdoulaye Hama Diallo, Penny Holding, Victoria Nankabirwa, Ingunn Marie S. Engebretsen, Grace Ndeezi, James K. Tumwine, Nicolas Meda, Thorkild Tylleskar, Esperance Kashala-Abotnes Background We aimed to study the effects of schooling on aspects of attention using the Test of Variables of Attention (TOVA) among children in rural Burkina Faso. Methods We re-enrolled children of a previously community-based cluster randomized exclusive breastfeeding trial in rural Burkina Faso. A total of 534 children (280 boys and 254 girls) aged 6 to 8 years were assessed using the TOVA. We examined the effect size difference using Cohen’s d, ANOVA and conducted regression analyses. Results Forty nine percent of the children were in school. Children not in school performed poorly with a small effect size difference for ‘Response Time’, ‘Errors of omission’, and ‘Errors of commission’ compared to children in school. The effect size difference was moderate for ‘Response Time Variability’, and ‘D prime score’. Conclusion Schooling affects different aspects of attention in rural Burkina Faso. In settings where literacy and schooling rate is low, public sensitizations of the benefits of schooling need to be reinforced and advice on sending children to school need to be provided continuously.
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  • 37
    Publication Date: 2018-09-05
    Description: by Marc Schiltz In this Perspective, a group of national funders, joined by the European Commission and the European Research Council, announce plans to make Open Access publishing mandatory for recipients of their agencies’ research funding.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 38
    Publication Date: 2018-09-05
    Description: by Konstantin Knoblich, Sara Cruz Migoni, Susan M. Siew, Elizabeth Jinks, Baksho Kaul, Hannah C. Jeffery, Alfie T. Baker, Muath Suliman, Katerina Vrzalikova, Hisham Mehenna, Paul G. Murray, Francesca Barone, Ye H. Oo, Philip N. Newsome, Gideon Hirschfield, Deirdre Kelly, Steven P. Lee, Biju Parekkadan, Shannon J. Turley, Anne L. Fletcher The microenvironment of lymphoid organs can aid healthy immune function through provision of both structural and molecular support. In mice, fibroblastic reticular cells (FRCs) create an essential T-cell support structure within lymph nodes, while human FRCs are largely unstudied. Here, we show that FRCs create a regulatory checkpoint in human peripheral T-cell activation through 4 mechanisms simultaneously utilised. Human tonsil and lymph node–derived FRCs constrained the proliferation of both naïve and pre-activated T cells, skewing their differentiation away from a central memory T-cell phenotype. FRCs acted unilaterally without requiring T-cell feedback, imposing suppression via indoleamine-2,3-dioxygenase, adenosine 2A Receptor, prostaglandin E2, and transforming growth factor beta receptor (TGFβR). Each mechanistic pathway was druggable, and a cocktail of inhibitors, targeting all 4 mechanisms, entirely reversed the suppressive effect of FRCs. T cells were not permanently anergised by FRCs, and studies using chimeric antigen receptor (CAR) T cells showed that immunotherapeutic T cells retained effector functions in the presence of FRCs. Since mice were not suitable as a proof-of-concept model, we instead developed a novel human tissue–based in situ assay. Human T cells stimulated using standard methods within fresh tonsil slices did not proliferate except in the presence of inhibitors described above. Collectively, we define a 4-part molecular mechanism by which FRCs regulate the T-cell response to strongly activating events in secondary lymphoid organs while permitting activated and CAR T cells to utilise effector functions. Our results define 4 feasible strategies, used alone or in combinations, to boost primary T-cell responses to infection or cancer by pharmacologically targeting FRCs.
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  • 39
    Publication Date: 2018-09-05
    Description: by Alexander J. Titus, Audrey Flower, Patrick Hagerty, Paul Gamble, Charlie Lewis, Todd Stavish, Kevin P. O’Connell, Greg Shipley, Stephanie M. Rogers Genomic data are becoming increasingly valuable as we develop methods to utilize the information at scale and gain a greater understanding of how genetic information relates to biological function. Advances in synthetic biology and the decreased cost of sequencing are increasing the amount of privately held genomic data. As the quantity and value of private genomic data grows, so does the incentive to acquire and protect such data, which creates a need to store and process these data securely. We present an algorithm for the Secure Interrogation of Genomic DataBases (SIG-DB). The SIG-DB algorithm enables databases of genomic sequences to be searched with an encrypted query sequence without revealing the query sequence to the Database Owner or any of the database sequences to the Querier. SIG-DB is the first application of its kind to take advantage of locality-sensitive hashing and homomorphic encryption to allow generalized sequence-to-sequence comparisons of genomic data.
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  • 40
    Publication Date: 2018-09-05
    Description: by Davide Risso, Liam Purvis, Russell B. Fletcher, Diya Das, John Ngai, Sandrine Dudoit, Elizabeth Purdom Clustering of genes and/or samples is a common task in gene expression analysis. The goals in clustering can vary, but an important scenario is that of finding biologically meaningful subtypes within the samples. This is an application that is particularly appropriate when there are large numbers of samples, as in many human disease studies. With the increasing popularity of single-cell transcriptome sequencing (RNA-Seq), many more controlled experiments on model organisms are similarly creating large gene expression datasets with the goal of detecting previously unknown heterogeneity within cells. It is common in the detection of novel subtypes to run many clustering algorithms, as well as rely on subsampling and ensemble methods to improve robustness. We introduce a Bioconductor R package, clusterExperiment, that implements a general and flexible strategy we entitle Resampling-based Sequential Ensemble Clustering (RSEC). RSEC enables the user to easily create multiple, competing clusterings of the data based on different techniques and associated tuning parameters, including easy integration of resampling and sequential clustering, and then provides methods for consolidating the multiple clusterings into a final consensus clustering. The package is modular and allows the user to separately apply the individual components of the RSEC procedure, i.e., apply multiple clustering algorithms, create a consensus clustering or choose tuning parameters, and merge clusters. Additionally, clusterExperiment provides a variety of visualization tools for the clustering process, as well as methods for the identification of possible cluster signatures or biomarkers. The R package clusterExperiment is publicly available through the Bioconductor Project, with a detailed manual (vignette) as well as well documented help pages for each function.
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  • 41
    Publication Date: 2018-09-05
    Description: by Yong Yang, Isaac Edery Similar to many diurnal animals, Drosophila melanogaster exhibits a mid-day siesta that is more robust as ambient temperature rises, an adaptive response aimed at minimizing exposure to heat. Mid-day siesta levels are partly regulated by the thermosensitive splicing of a small intron (termed dmpi8) found in the 3’ untranslated region (UTR) of the circadian clock gene period ( per ). Using the well-studied D . melanogaster latitudinal cline along the eastern coast of Australia, we show that flies from temperate populations sleep less during the day compared to those from tropical regions. We identified combinations of four single nucleotide polymorphisms (SNPs) in the 3’ UTR of per that yield several different haplotypes. The two most abundant of these haplotypes exhibit a reciprocal tropical-temperate distribution in relative frequency. Intriguingly, transgenic flies with the major tropical isoform manifest increased daytime sleep and reduced dmpi8 splicing compared to those carrying the temperate variant. Our results strongly suggest that for a major portion of D . melanogaster in Australia, thermal adaptation of daily sleep behavior included spatially varying selection on ancestrally derived polymorphisms in the per 3’ UTR that differentially control dmpi8 splicing efficiency. Prior work showed that African flies from high altitudes manifest reduced mid-day siesta levels, indicative of parallel latitudinal and altitudinal adaptation across continents. However, geographical variation in per 3’ UTR haplotypes was not observed for African flies, providing a compelling case for inter-continental variation in factors targeted by natural selection in attaining a parallel adaptation. We propose that the ability to calibrate mid-day siesta levels to better match local temperature ranges is a key adaptation contributing to the successful colonization of D . melanogaster beyond its ancestral range in the lowlands of Sub-Saharan Africa.
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  • 42
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    Publication Date: 2018-09-05
    Description: by Mariela Scortti, Lei Han, Sonsiray Alvarez, Alexandre Leclercq, Alexandra Moura, Marc Lecuit, Jose Vazquez-Boland Elucidating the relationships between antimicrobial resistance and virulence is key to understanding the evolution and population dynamics of resistant pathogens. Here, we show that the susceptibility of the gram-positive bacterium Listeria monocytogenes to the antibiotic fosfomycin is a complex trait involving interactions between resistance and virulence genes and the environment. We found that a FosX enzyme encoded in the listerial core genome confers intrinsic fosfomycin resistance to both pathogenic and non-pathogenic Listeria spp. However, in the genomic context of the pathogenic L . monocytogenes , FosX-mediated resistance is epistatically suppressed by two members of the PrfA virulence regulon, hpt and prfA , which upon activation by host signals induce increased fosfomycin influx into the bacterial cell. Consequently, in infection conditions, most L . monocytogenes isolates become susceptible to fosfomycin despite possessing a gene that confers high-level resistance to the drug. Our study establishes the molecular basis of an epistatic interaction between virulence and resistance genes controlling bacterial susceptibility to an antibiotic. The reported findings provide the rationale for the introduction of fosfomycin in the treatment of Listeria infections even though these bacteria are intrinsically resistant to the antibiotic in vitro .
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  • 43
    Publication Date: 2018-09-05
    Description: by Amanda C. Davis-Roca, Nikita S. Divekar, Rachel K. Ng, Sarah M. Wignall Chromosome congression and segregation in C . elegans oocytes depend on a complex of conserved proteins that forms a ring around the center of each bivalent during prometaphase; these complexes are then removed from chromosomes at anaphase onset and disassemble as anaphase proceeds. Here, we uncover mechanisms underlying the dynamic regulation of these ring complexes (RCs), revealing a strategy by which protein complexes can be progressively remodeled during cellular processes. We find that the assembly, maintenance, and stability of RCs is regulated by a balance between SUMO conjugating and deconjugating activity. During prometaphase, the SUMO protease ULP-1 is targeted to the RCs but is counteracted by SUMO E2/E3 enzymes; then in early anaphase the E2/E3 enzymes are removed, enabling ULP-1 to trigger RC disassembly and completion of the meiotic divisions. Moreover, we found that SUMO regulation is essential to properly connect the RCs to the chromosomes and then also to fully release them in anaphase. Altogether, our work demonstrates that dynamic remodeling of SUMO modifications facilitates key meiotic events and highlights how competition between conjugation and deconjugation activity can modulate SUMO homeostasis, protein complex stability, and ultimately, progressive processes such as cell division.
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  • 44
    Publication Date: 2018-09-05
    Description: by Fabio Bulleri, Britas Klemens Eriksson, Ana Queirós, Laura Airoldi, Francisco Arenas, Christos Arvanitidis, Tjeerd J. Bouma, Tasman P. Crowe, Dominique Davoult, Katell Guizien, Ljiljana Iveša, Stuart R. Jenkins, Richard Michalet, Celia Olabarria, Gabriele Procaccini, Ester A. Serrão, Martin Wahl, Lisandro Benedetti-Cecchi Habitat-forming species sustain biodiversity and ecosystem functioning in harsh environments through the amelioration of physical stress. Nonetheless, their role in shaping patterns of species distribution under future climate scenarios is generally overlooked. Focusing on coastal systems, we assess how habitat-forming species can influence the ability of stress-sensitive species to exhibit plastic responses, adapt to novel environmental conditions, or track suitable climates. Here, we argue that habitat-former populations could be managed as a nature-based solution against climate-driven loss of biodiversity. Drawing from different ecological and biological disciplines, we identify a series of actions to sustain the resilience of marine habitat-forming species to climate change, as well as their effectiveness and reliability in rescuing stress-sensitive species from increasingly adverse environmental conditions.
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  • 45
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    Publication Date: 2018-09-05
    Description: by Florian Kamm, Ulrike Strauch, Frauke Degenhardt, Rocio Lopez, Claudia Kunst, Gerhard Rogler, Andre Franke, Frank Klebl, Florian Rieder
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 46
    Publication Date: 2018-09-05
    Description: by Sangwoo Lee, Hang-Suk Chun, Jieon Lee, Han-Jin Park, Ki-Tae Kim, Cheol-Hee Kim, Seokjoo Yoon, Woo-Keun Kim Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder characterized by impaired or abnormal social interaction and communication and by restricted and repetitive behaviour. ASD is highly prevalent in Asia, Europe, and the United States, and the frequency of ASD is growing each year. Recent epidemiological studies have indicated that ASD may be caused or triggered by exposure to chemicals in the environment, such as those in the air or water. Thus, toxicological studies are needed to examine chemicals that might be implicated. However, the experimental efficiency of existing experimental models is limited, and many models represent challenges in terms of animal welfare. Thus, alternative ASD animal models are necessary. To address this, we examined the efficacy of the zebrafish embryo/larva as an alternative model of ASD. Specifically, we exposed zebrafish to valproic acid (0, 12.5, 25, 50, or 100 μM), which is a chemical known to induce autism-like effects. We then analysed subsequent developmental, behavioural, and transcriptomic changes. We found that 100 μM and 50 μM valproic acid decreased the hatching rate and locomotor activity of zebrafish embryos/larvae. Transcriptomic analysis revealed significant alterations in a number of genes associated with autism, such as adsl , mbd5 , shank3 , and tsc1b . Additionally, we found changes in gene ontology that were also reported in previous studies. Our findings indicate that zebrafish embryos/larvae and humans with ASD might have common physiological pathways, indicating that this animal model may represent an alternative tool for examining the causes of and potential treatments for this illness.
    Electronic ISSN: 1932-6203
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  • 47
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    Publication Date: 2018-09-05
    Description: by Zeynep Ertem, Dorrie Raymond, Lauren Ancel Meyers Forecasting the emergence and spread of influenza viruses is an important public health challenge. Timely and accurate estimates of influenza prevalence, particularly of severe cases requiring hospitalization, can improve control measures to reduce transmission and mortality. Here, we extend a previously published machine learning method for influenza forecasting to integrate multiple diverse data sources, including traditional surveillance data, electronic health records, internet search traffic, and social media activity. Our hierarchical framework uses multi-linear regression to combine forecasts from multiple data sources and greedy optimization with forward selection to sequentially choose the most predictive combinations of data sources. We show that the systematic integration of complementary data sources can substantially improve forecast accuracy over single data sources. When forecasting the Center for Disease Control and Prevention (CDC) influenza-like-illness reports (ILINet) from week 48 through week 20, the optimal combination of predictors includes public health surveillance data and commercially available electronic medical records, but neither search engine nor social media data.
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  • 48
    Publication Date: 2018-09-05
    Description: by Jessica Potts, Alex Sirker, Sara C. Martinez, Martha Gulati, Mirvat Alasnag, Muhammad Rashid, Chun Shing Kwok, Joie Ensor, Danielle L. Burke, Richard D. Riley, Lene Holmvang, Mamas A. Mamas Background Prior studies have reported inconsistencies in the baseline risk profile, comorbidity burden and their association with clinical outcomes in women compared to men. More importantly, there is limited data around the sex differences and how these have changed over time in contemporary percutaneous coronary intervention (PCI) practice. Methods and results We used the Nationwide Inpatient Sample to identify all PCI procedures based on ICD-9 procedure codes in the United States between 2004–2014 in adult patients. Descriptive statistics were used to describe sex-based differences in baseline characteristics and comorbidity burden of patients. Multivariable logistic regressions were used to investigate the association between these differences and in-hospital mortality, complications, length of stay and total hospital charges. Among 6,601,526 patients, 66% were men and 33% were women. Women were more likely to be admitted with diagnosis of NSTEMI (non-ST elevation acute myocardial infarction), were on average 5 years older (median age 68 compared to 63) and had higher burden of comorbidity defined by Charlson score ≥3. Women also had higher in-hospital crude mortality (2.0% vs 1.4%) and any complications compared to men (11.1% vs 7.0%). These trends persisted in our adjusted analyses where women had a significant increase in the odds of in-hospital mortality men (OR 1.20 (95% CI 1.16,1.23) and major bleeding (OR 1.81 (95% CI 1.77,1.86). Conclusion In this national unselected contemporary PCI cohort, there are significant sex-based differences in presentation, baseline characteristics and comorbidity burden. These differences do not fully account for the higher in-hospital mortality and procedural complications observed in women.
    Electronic ISSN: 1932-6203
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  • 49
    Publication Date: 2018-09-05
    Description: by Shilu Mathew, Asmaa A. Al Thani, Hadi M. Yassine Background With the emergence of new influenza virus strains that are resistant to current inhibitors such as oseltamivir (anti-neuraminidase (NA)) and amantadine (anti-M2 proton channel), influenza A viruses continue to be a serious threat to the public health worldwide. With this in view, there is a persistent need for the development of broader and more effective vaccines and therapeutics. Identification of broadly neutralizing antibodies (bNAbs) that recognize relatively invariant structures ‎on influenza haemagglutinin (HA) stem has invigorated efforts to develop universal influenza vaccines. Aim The current computational study is designed to identify potential flavonoid inhibitors that bind to the contact epitopes of HA stem that are targeted by broadly neutralizing antibodies (bNAb). Method In this study, we utilized the three-dimensional crystallographic structure of different HA subtypes (H1, H2, H5, H3, and H7) in complex with bNAb to screen for potential broadly reactive influenza inhibitors. We performed Quantitative Structure-Activity and Relationship (QSAR) for 100 natural compounds known for their antiviral activity and performed molecular docking using AutoDock 4.2 suite. Furthermore, we conducted virtual screening of 1413 bioassay hit compounds by using virtual lab bench CLC Drug Discovery. Results The results showed 18 lead flavonoids with strong binding abilities to bNAb epitopes of various HA subtypes. These 18 broadly reactive compounds exhibited significant interactions with an average of seven Hbonds, docking energy of -22.43 kcal·mol −1 , and minimum interaction ‎ energy of -4.65 kcal·mol −1 , with functional contact residues. Procyanidin depicted strong interactions with group 1 HAs, whereas both sorbitol and procyanidin exhibited significant interactions with group 2 HAs. Conclusion Using in silico docking analysis, we identified 18 bioactive flavonoids with potential strong binding cababilities to influenza HA-stems of various subtypes, which are the target for bNAb. The virtual screened bioassay hit compounds depicted a high number of Hbonds but low interaction and docking values compared to antiviral flavonoids. Using structure-based design and nanotechnology-based approaches, identified molecules could be modified to generate next generation anti-influenza drugs.
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  • 50
    Publication Date: 2018-09-05
    Description: by María del Mar Sánchez-Fernández, Gustavo A. Reyes del Paso, José Manuel Gil-Cunquero, María José Fernández-Serrano Objective There is evidence of cognitive impairment in patients with end-stage renal disease in hemodialysis (ESRD-HD). However, few studies have exhaustively analyzed executive functions (EFs) in this population, especially considering the influence of a wide range of clinical variables. This study analyzes performance in different EF components in ESRD-HD patients compared to a group of healthy controls (HCs), in addition to the acute effects of HD and the associations of cognitive performance with clinical variables. Method EFs were evaluated pre- and post-HD in 43 ESRD-HD patients and 42 HCs, using a battery of tests designed to assess EF domains. Age, schooling, mood and blood pressure were statistically controlled. Associations between performance and clinical factors were computed by correlations and hierarchical multiple regression analyses. Results The performance of the ESRD-HD patients was significantly lower than that of HCs in all the EF domains except for planning. Group differences were marginally significant for reasoning. HD produced no acute changes in global performance, with improvements see only in inhibition and working memory. EF scores were positively associated with total number of months previously transplanted, body mass index (BMI), dry weight, and levels of hemoglobin, albumin, ferritin, calcium, phosphorus, sodium, urea, and creatinine. Conclusions Global EF functioning was lower in ESRD-HD patients than in HCs. No major acute HD-related EF changes were detected. These findings underline the importance of an adequate nutritional status for maintaining executive functioning in ESRD-HD patients.
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  • 51
    Publication Date: 2018-09-05
    Description: by Louis Clark, Danielle Leatherby, Elizabeth Krilich, Alexander J. Ropelewski, John Perozich Luciferases, aryl- and fatty-acyl CoA synthetases, and non-ribosomal peptide synthetase proteins belong to the class I adenylate-forming enzyme superfamily. The reaction catalyzed by the adenylate-forming enzymes is categorized by a two-step process of adenylation and thioesterification. Although all of these proteins perform a similar two-step process, each family may perform the process to yield completely different results. For example, luciferase proteins perform adenylation and oxidation to produce the green fluorescent light found in fireflies, while fatty-acyl CoA synthetases perform adenylation and thioesterification with coenzyme A to assist in metabolic processes involving fatty acids. This study aligned a total of 374 sequences belonging to the adenylate-forming superfamily. Analysis of the sequences revealed five fully conserved residues throughout all sequences, as well as 78 more residues conserved in at least 60% of sequences aligned. Conserved positions are involved in magnesium and AMP binding and maintaining enzyme structure. Also, ten conserved sequence motifs that included most of the conserved residues were identified. A phylogenetic tree was used to assign sequences into nine different groups. Finally, group entropy analysis identified novel conservations unique to each enzyme group. Common group-specific positions identified in multiple groups include positions critical to coordinating AMP and the CoA-bound product, a position that governs active site shape, and positions that help to maintain enzyme structure through hydrogen bonds and hydrophobic interactions. These positions could serve as excellent targets for future research.
    Electronic ISSN: 1932-6203
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  • 52
    Publication Date: 2018-09-05
    Description: by Yu-Feng Xing, Da-Qiao Zhou, Jing-Song He, Chun-Shan Wei, Wei-Chao Zhong, Zhi-Yi Han, De-Ti Peng, Mu-Min Shao, Tung-Ting Sham, Daniel Kam-Wah Mok, Chi-On Chan, Guang-Dong Tong Background The aim of this study is to reveal the clinical and histopathological features of HBsAg-positive and HBeAg-positive chronic hepatitis B infected patients with high level of HBV DNA, from 17 hospitals and medical centres in China, with alanine aminotransferase levels within the lower region of normal range versus those with levels within the upper region of normal range and to investigate the clinical risk factors for the requirement of treatment through the examination of liver biopsy. Methods Liver biopsy was performed on high level of HBV DNA of 455 patients with HBsAg-positive and HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase level. Liver necroinflammation and fibrosis were graded per the Knodell histological activity index and Ishak’s fibrosis score, respectively. Univariate analysis of the clinical parameters versus necroinflammation and fibrosis was carried out. Results Of the subjects in this multicentre-based study, 5.49% and 10.11% had significant necroinflammation with Knodell histological activity index ≥ 9 and hepatic fibrosis stages with Ishak scores ≥ 3, respectively. The subjects were stratified into three age groups (30–39, 40–49 and ≥ 50 years), and our data clearly suggested that age, particularly in the age group over 50, was an independent predictor of liver necroinflammation and fibrosis. Lower HBV-DNA viral levels were found in patients with Knodell histological activity index ≥ 9 or advanced fibrosis (Ishak scores ≥ 3). Conclusion Our results showed that histological changes in liver tissues were observed in a significant proportion of patients with persistently normal alanine aminotransferase level. According to the data evaluation results, liver biopsy is advisable for HBeAg-positive chronic hepatitis B infected patients aged older than 40 and high HBV-DNA viral load in China.
    Electronic ISSN: 1932-6203
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  • 53
    Publication Date: 2018-09-05
    Description: by Shunsuke Tomomori, Yukiko Nakano, Hidenori Ochi, Yuko Onohara, Akinori Sairaku, Takehito Tokuyama, Chikaaki Motoda, Hiroya Matsumura, Michitaka Amioka, Naoya Hironobe, Yousaku Ookubo, Shou Okamura, Hiroshi Kawazoe, Kazuaki Chayama, Yasuki Kihara Introduction The single nucleotide polymorphism (SNP) rs2106261 in the transcription factor gene ZFHX3 (16q22), a major regulator of inflammation, has been reported linking to atrial fibrillation (AF) by genome-wide association studies. Inflammation is known to be a strong predictor of atrial fibrillation recurrence after ablation, so we examined the association of the ZFHX3 SNP rs2106261 to inflammation marker expression and recurrence after AF ablation. Methods We genotyped ZFHX3 SNP rs2106261 and compared the minor (T) allele frequency between 362 paroxysmal AF (PAF) patients underwent pulmonary vein isolation (PVI) and 627 non-AF controls. We also analyzed associations between ZFHX3 SNP rs2106261 genotype and recurrence rate after pulmonary vein isolation and the inflammation markers. Results The minor (T) allele frequency of the ZFHX3 SNP rs2106261 was significantly higher in AF patients than non-AF controls (odds ratio 1.52, p = 2.2×10 −5 ). Multivariable analysis revealed that the minor allele (T) decreased AF recurrence rate after pulmonary vein isolation (hazard ratio 0.53, p = 0.04). Further, neutrophil/lymphocyte (N/L) ratio, C-reactive protein (CRP), and interleukin-6 (IL-6) expression levels were lower in PAF patients with the ZFHX3 SNP rs2106261 minor allele (TT+TC) than in CC patients (N/L ratio: CC 2.22 ± 0.08, TT+TC 1.98 ± 0.06, p = 0.018; CRP: CC 0.103 ± 0.009 mg/dl, TT+TC 0.076 ±0.007 mg/dl, p = 0.016; IL-6: CC 60.3 ± 3.0 pg/ml, TT+TC 52.8 ± 2.3 pg/ml, p = 0.04). Conclusions The ZFHX3 SNP rs2106261 minor allele is associated with lower AF recurrence rate after pulmonary vein isolation. Low baseline inflammation conferred by this allele may reduce AF recurrence risk.
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  • 54
    Publication Date: 2018-09-05
    Description: by Carol Kingdon, Soo Downe, Ana Pilar Betran Objective When medically indicated, caesarean section can prevent deaths and other serious complications in mothers and babies. Lack of access to caesarean section may result in increased maternal and perinatal mortality and morbidity. However, rising caesarean section rates globally suggest overuse in healthy women and babies, with consequent iatrogenic damage for women and babies, and adverse impacts on the sustainability of maternity care provision. To date, interventions to ensure that caesarean section is appropriately used have not reversed the upward trend in rates. Qualitative evidence has the potential to explain why and how interventions may or may not work in specific contexts. We aimed to establish stakeholders’ views on the barriers and facilitators to non-clinical interventions targeted at organizations, facilities and systems, to reduce unnecessary caesarean section. Methods We undertook a systematic qualitative evidence synthesis using a five-stage modified, meta-ethnography approach. We searched MEDLINE, CINAHL, PsychINFO, EMBASE and grey literature databases (Global Index Medicus, POPLINE, AJOL) using pre-defined terms. Inclusion criteria were qualitative and mixed-method studies, investigating any non-clinical intervention to reduce caesarean section, in any setting and language, published after 1984. Study quality was assessed prior to data extraction. Interpretive thematic synthesis was undertaken using a barriers and facilitators lens. Confidence in the resulting Summaries of Findings was assessed using GRADE-CERQual. Results 8,219 studies were identified. 25 studies were included, from 17 countries, published between 1993–2016, encompassing the views of over 1,565 stakeholders. Nineteen Summary of Findings statements were derived. They mapped onto three distinct themes:Health system, organizational and structural factors (6 SoFs); Human and cultural factors (7 SoFs); and Mechanisms of effect to achieve change factors (6 SoFs). The synthesis showed how inter- and intra-system power differentials, and stakeholder commitment, exert strong mechanisms of effect on caesarean section rates, independent of the theoretical efficacy of specific interventions to reduce them. Conclusions Non-clinical interventions to reduce caesarean section are strongly mediated by organisational power differentials and stakeholder commitment. Barriers may be greatest where implementation plans contradict system and cultural norms. Protocol registration PROSPERO: CRD42017059456
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  • 55
    Publication Date: 2018-09-08
    Description: by Ashish Goyal, Ethan Obie Romero-Severson Background Hepatitis D virus (HDV), which requires the presence of hepatitis B virus (HBV), is a deadly yet neglected disease that rapidly leads to liver cancer and disease-induced mortality. This co-dependence creates complex transmission dynamics that make it difficult to predict the efficacy of interventions aimed at HBV and/or HDV control in endemic regions, such as certain municipalities of Brazil, where up to 65% of HBV-infected persons are co-infected. Methodology We created a mathematical model that captures the joint transmission dynamics of HBV and HDV, incorporating mother-to-child, sexual and household transmission. With an aim to minimize the number of total infections and disease-induced mortality in 2027, we then determined optimal strategies for Brazil and its sub-regions under a constrained budget, which was dynamically allocated among HBV and HDV screening, HBV and HDV treatment, HBV newborn and adult vaccination, and awareness programs. Three treatment options were considered, namely: Tenofovir, PEGylated-Interferon, and nucleic acid polymers (NAP). Results The additional cost of HDV screening and the use of a more expensive PEGylated-Interferon are offset by not wasting resources on treating co-infected persons with Tenofovir. The introductory price of NAP treatment must be less than $16,000 per course to become competitive with Tenofovir and PEGylated-Interferon in Brazil. Conclusion Additional screening for HDV is beneficial, even in a low HBV and HDV endemic regions of Brazil. We recommend PEGylated-Interferon, wherever possible, for both HBV and HDV. If PEGylated-Interferon is not available in abundance, PEGylated-Interferon for co-infections and 4-year Tenofovir treatment for mono-infections is recommended.
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  • 56
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    Publication Date: 2018-09-08
    Description: by T. E. Arnold, W. F. Kenney, J. H. Curtis, T. S. Bianchi, M. Brenner
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  • 57
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    Publication Date: 2018-09-08
    Description: by Andrea M. Zimmerman The number of biomedical PhD scientists undergoing training and graduating far exceeds the number of academic faculty positions and academic research jobs. This trend compels biomedical PhD scientists to increasingly seek career paths outside of academia. Prior studies have used quantitative methodology to determine trends and outcomes of single factors contributing to this shift, but there is a literature gap in studies considering multiple factors and in qualitative work focusing on biomedical PhD scientists’ experiences and their processes of career navigation. This paper draws on a social cognitive career theory (SCCT) framework and incorporates case study data from a southeastern Tier 1 research university to explore a nexus of factors influencing PhD scientists’ employment sector preferences and job search processes. It simultaneously concludes that relationships with faculty, particularly the mentor advisor, are essential to the opportunities available to these professionals and to the career paths they choose.
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  • 58
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    Publication Date: 2018-09-08
    Description: by Lisa Kawatsu, Kazuhiro Uchimura, Akihiro Ohkado Background The World Health Organization recommends that systematic testing and screening of latent tuberculosis infection (LTBI) among the incarcerated population “should be considered”, though based on evidence of either low or very low quality. However, in Japan, a TB middle-burden country, systematic screening for LTBI in correctional facilities is currently not conducted. As part of a larger study to determine the cost-effectiveness of LTBI screening in correctional facilities in Japan, this study was conducted to determine the situation of LTBI, including treatment outcome, among the incarcerated population in Japan, and provide the essential data for cost-effectiveness analysis. Method A cross-sectional study was conducted between 2017 and 2018 with public health centers which have one or more correctional facilities under their jurisdiction. Questionnaire surveys were sent to collect information on their policy of managing LTBI patients notified from correctional facilities, including whether or not there was a standardized procedure for initiating LTBI treatment, and also to collect sociodemographic information and treatment outcome of LTBI patients who were notified from the respective correctional facilities in 2015 and 2016. Results The survey was sent to a total of 163 public health centers, out of which 133 (81.6%) responded. 8 of the 133 public health centers actively guided the correctional facilities regarding LTBI treatment initiation through a standardized procedure, while 115 either had not established such procedure or were unaware of how LTBI treatment was being initiated in the correctional facilities. A total of 91 LTBI patients were notified from the correctional facilities in 2015 and 2016, and the information of 89 were available for analysis. 82 were males, and 83 were Japan-born. Treatment outcome was known for 88 patients, of which 70 had completed treatment. Of the 18 who did not complete the treatment, 15 had been lost to follow-up upon release from the facilities. Among those who had been released whilst on treatment, the proportion of those who completed the treatment was higher in those patients who received pre-release visit by a public health nurse, than those who did not. Conclusions LTBI treatment was often being initiated without consideration for the patients’ prison term. The treatment completion rate within jail was high, indicating the possibility that incarcerated population can benefit for LTBI treatment. On the other hand, the completion rate decreased significantly among those who had been released while still on treatment. In order to optimize the benefit, initiation of LTBI must carefully be considered upon the patient’s prison term, as well as coordination among the relevant organizations to ensure continuity of care after release.
    Electronic ISSN: 1932-6203
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  • 59
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    Publication Date: 2018-09-07
    Description: by Elliot A. Layden, John T. Cacioppo, Stephanie Cacioppo Loneliness is thought to serve as an adaptive signal indicating the need to repair or replace salutary social connections. Accordingly, loneliness may influence preferences for interpersonal distance. If loneliness simply motivates a desire to socially reconnect, then loneliness may be associated with a preference for smaller interpersonal distances. According to the evolutionary model of loneliness, however, loneliness also signals an inadequacy of mutual aid and protection, augmenting self-preservation motives. If loneliness both increases the motivation to reconnect and increases the motivation for self-protection, then the resulting approach-avoidance conflict should produce a preference for larger interpersonal distance, at least within intimate (i.e., proximal) space. Here, we report two survey-based studies of participants’ preferences for interpersonal distance to distinguish between these competing hypotheses. In Study 1 ( N = 175), loneliness predicted preferences for larger interpersonal distance within intimate space net gender, objective social isolation, anxiety, depressive symptomatology, and marital status. In Study 2 ( N = 405), we replicated these results, and mediation analyses indicated that measures of social closeness could not adequately explain our findings. These studies provide compelling evidence that loneliness predicts preferences for larger interpersonal distance within intimate space, consistent with predictions from the evolutionary model of loneliness.
    Electronic ISSN: 1932-6203
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  • 60
    Publication Date: 2018-09-07
    Description: by Chungwon J. Chung, Sang-Ho Cha, Amanda L. Grimm, Dharani Ajithdoss, Joanna Rzepka, Grace Chung, Jieun Yu, William C. Davis, Chak-Sum Ho Porcine reproductive and respiratory syndrome virus (PRRSV) infection is difficult to control because the virus undergoes antigenic variation during infection and also modulates the protective host immune response. Although current vaccines do not provide full protection, they have provided insight into the mechanisms of protection. Live PRRSV vaccines induce partial protection before the appearance of neutralizing antibody, suggesting cell-mediated immunity or other mechanisms may be involved. Herein, we demonstrate recovery from infection is associated with development of cytotoxic T-lymphocytes (CTL) that can kill PRRSV-infected target cells. Initial experiments showed survival of PRRSV-infected monocyte derived macrophage (MDM) targets is reduced when overlaid with peripheral blood mononuclear cells (PBMC) from gilts that had recovered from PRRSV infection. Further studies with PBMC depleted of either CD4 + or CD8 + T-cells and positively selected subpopulations of CD4 + and CD8 + T-cells showed that both CD4 + and CD8 + T-cells were involved in killing. Examination of killing at different time points revealed killing was biphasic and mediated by CTL of different phenotypes. CD4 + CD8 +high were associated with killing target cells infected for 3–6 hours. CD4 + CD8 - CTL were associated with killing at 16–24 hours. Thus, all the anti-PRRSV CTL activity in pigs was attributed to two phenotypes of CD4 + cells which is different from the anti-viral CD4 - CD8 + CTL phenotype found in most other animals. These findings will be useful for evaluating CTL responses induced by current and future vaccines, guiding to a novel direction for future vaccine development.
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  • 61
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    Publication Date: 2018-09-07
    Description: by Tsubasa S. Matsui, Hugejile Wu, Shinji Deguchi Adherent cells such as endothelial cells sense applied mechanical stretch to adapt to changes in their surrounding mechanical environment. Despite numerous studies, signaling pathways underlying the cellular mechanosensing and adaptation remain to be fully elucidated partly because of the lack of tools that allow for a comprehensive screening approach. Conventionally, multi-well cell culture plates of standard configurations are used for comprehensive analyses in cell biology study to identify key molecules in a high-throughput manner. Given that situation, here we design a 96-well cell culture plate made of elastic silicone and mechanically stretchable using a motorized device. Computational analysis suggested that highly uniform stretch can be applied to each of the wells other than the peripheral wells. Elastic image registration-based experimental evaluation on stretch distributions within individual wells revealed the presence of larger variations among wells compared to those in the computational analysis, but a stretch level of 10%–that has been employed in conventional studies on cellular response to stretch—was almost achieved with our setup. We exposed vascular smooth muscle cells to cyclic stretch using the device to demonstrate morphological repolarization of the cells, i.e. typical cellular response to cyclic stretch. Because the deformable multi-well plate validated here is compatible with other high-throughput screening-oriented technologies, we expect this novel system to be utilized for future comprehensive analyses of stretch-related signaling pathways.
    Electronic ISSN: 1932-6203
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  • 62
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    Publication Date: 2018-09-07
    Description: by Amy Tasca, Kristina Astleford, Nicholas C. Blixt, Eric D. Jensen, Rajaram Gopalakrishnan, Kim C. Mansky Bone remodeling occurs via coupling between bone resorption by osteoclasts and bone formation by osteoblasts. The mechanisms that regulate osteoclast signals to osteoblasts are not well understood. Published studies have reported that BMP signaling in osteoclasts regulate osteoclast coupling targets. To investigate the necessity of canonical BMP signaling on osteoclast differentiation and coupling, we mated Smad1 fl/fl ; Smad5 fl/fl mice to c-Fms-Cre mice. We analyzed male mice at 3 months of age to determine the skeletal phenotype of the Smad1 fl/fl ; Smad5 fl/fl ;c-Fms-Cre (SMAD1/5 cKO) mice. There was a 1.2-fold decrease in trabecular BV/TV in SMAD1/5 cKO. Analyses of osteoclast serum markers in SMAD1/5 cKO mice, showed a significant increase in CTX-1 (1.5 fold) and TRAP ELISA (3 fold) compared to control mice. In these same mice, there was a 1.3-fold increase in cortical thickness. Consistent with the increase in cortical thickness, we found a 3-fold increase in osteoblast activity as measured by P1NIP ELISA assay from SMAD1/5 cKO mice. To explain the changes in cortical thickness and P1NP activity, we determined conditioned media from SMAD1/5 cKO osteoclast cultures enhanced mineralization of an osteoblast cell line and coupling factors expressed by osteoclasts that regulate osteoblast activity Wnt1 (4.5-fold increase), Gja1 (3-fold increase) and Sphk1 (1.5-fold increase) were all upregulated in osteoclasts from SMAD1/5 cKO compared to control osteoclasts. Lastly osteoclasts treated with dorsomorphin, a chemical inhibitor of SMAD1/5 signaling, demonstrates an increase in Wnt1 and Gja1 expression similar to the SMAD1/5 cKO mice. Previous studies demonstrated that TGF-β signaling in osteoclasts leads to increases in WNT1 expression by osteoclasts. Therefore, our data suggest that TGF-β and BMP signaling pathways in osteoclasts could act in an antagonistic fashion to regulate osteoblast activity through WNT1 and other coupling factors.
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  • 63
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    Publication Date: 2018-09-07
    Description: by Chi-syuan Pan, Teressa Reanne Ju, Chi Chan Lee, Yu-Pei Chen, Chung-Y. Hsu, Dong-Zong Hung, Wei-Kung Chen, I-Kuan Wang Introduction Alcohol use disorder (AUD) is a spectrum of high risk behaviors including alcohol abuse and dependence. Chronic kidney disease (CKD) is progressive loss of renal function for more or equal to 3 months or presence of any irreversible kidney damage. Common risk factors of CKD have been identified, but the impact of alcohol consumption on kidney function is controversial. The study aims to investigate the relationship between alcohol use disorder and CKD on a national scale. Methods This retrospective cohort study was conducted using Taiwan’s National Health Insurance research database. Patients aged 20 years or older, without CKD and with the diagnosis of AUD (ICD-9-CM codes 303.X; 305.0, V113) from years 2000 to 2013 were enrolled. Control cohort was selected to match the demographics of the target population. Patients were followed until the end of 2013 or earlier if they developed CKD, died, or lost follow up. Baseline characteristics and comorbidities were identified for risk stratification. Results We identified 11639 patients in the AUD cohort and 46556 patients in the control cohort. Compared to patients in the control cohort, those in the AUD group were more likely to have multiple comorbidities (p 〈 0.001 for all comorbidities). After adjustment of age, gender, baseline comorbidities, and nonsteroidal anti-inflammatory drug use, the diagnosis of AUD was associated with an increased risk of CKD development (aHR = 1.62, 95% CI, 1.46–1.81).During the mean follow up periods of 6.47 (standard deviation (SD) = 3.80) years for the AUD cohort and 7.23 (SD = 3.75) years for the control cohort, the overall incidence density of CKD was significantly higher in patients with AUD than those in the control cohort (3.48 vs 6.51 per 1000 person-years, aHR = 1.68, 95% CI, 1.50–1.87). Kaplan-Meier analysis showed that the AUD cohort had a higher cumulative incidence of CKD than the control cohort (log-rank test, p value 〈 0.001). Patients with AUD had higher risks of CKD in all the stratified groups, except for the subgroup with age over 65 years old. Conclusion Our study suggested that AUD was associated with an increased incidence of newly diagnosed CKD by nearly two folds. Young age, in particular, had a higher association between AUD and CKD. Considering the preventable nature of AUD, establishing effective health policies is imperative to reduce high-risk alcohol behaviors and thereby prevent alcohol-related kidney disease. Further prospective studies are warranted to further elucidate the causation of AUD on kidney function.
    Electronic ISSN: 1932-6203
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  • 64
    Publication Date: 2018-09-08
    Description: by Tao Han Lee, Cheng-Chia Lee, Chau-Yee Ng, Ming-Yang Chang, Su-Wei Chang, Pei-Chun Fan, Wen-Hung Chung, Ya-Chung Tian, Yung-Chang Chen, Chih-Hsiang Chang Background Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are severe drug-induced cutaneous adverse reactions with high mortality. Acute kidney injury (AKI) was a common complication in an SJS/TEN group and noted as an independent risk factor for mortality in patients with SJS/TEN. To determine whether AKI staging can predict the outcome of patients with SJS/TEN, we compared the discriminative power of an AKI KDIGO staging system with that of SCROTEN, APACHE II, APACHE III, and SOFA. Materials and methods We retrospectively analyzed the data of 75 patients who were diagnosed with SJS, TEN, or SJS/TEN overlap syndrome at a tertiary care university hospital between January 1, 2011 and December 31, 2014. The baseline characteristics, biochemical analysis data, medication use, and outcomes of the patients were assessed, and the discriminative ability for predicting mortality was determined for each prognostic model. Results Of the 75 patients, 23 (30.7%) had AKI, of whom 13 (56.5%) died during the index admission. Of the prognostic risk models analyzed, the KDIGO staging system showed similar discriminative ability in predicting in-hospital mortality as did the other models. In addition, combining KDIGO with other scoring systems yielded significantly more accurate risk prediction for in-hospital mortality compared with the other individual scores alone, as measured by net reclassification index. The patients with KDIGO stages 2 and 3 exhibited a significantly lower 1-year survival rate than did those with KDIGO stages 0 and 1. Conclusion AKI KDIGO staging has good discriminative ability and is easy to utilize for predicting mortality.
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  • 65
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    Publication Date: 2018-09-08
    Description: by Hosung Shin, Eunsuk Ahn The aim of the present study was to assess the regional deprivation and individual factors that influence how far a person will travel to access dental care. Using data from the Korea Health Panel (2008 to 2011), we selected a group of 4,256 subjects and geocoded their homes and dental hospitals/clinics. Using the road network analysis, we calculated the distance traveled by the subjects for dental care. We used the generalized estimating equation (GEE) for repeated data analysis and included an interaction term between regional deprivation and individual income to determine the effects of the two factors on the choice of a dental hospital/clinic. When the regional deprivation index was divided into three quarters (high, middle, and low), urban areas had higher”high” and “low" levels of deprivation, and rural areas had relatively higher middle level of deprivation. GEE regression showed that the level of education, regional deprivation level, and income all affected the distance traveled to dental clinics. The regional deprivation level had a higher association than income with the travel distance. At the same income level, subjects who lived in the least deprived areas were more likely to travel longer distances than subjects living in the most deprived areas. Regarding the distribution of dental hospitals/clinics, incentive based dental polices for either dental providers or patients are needed that will assure the delivery of dental care despite spatial inequality.
    Electronic ISSN: 1932-6203
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  • 66
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    Publication Date: 2018-09-08
    Description: by Akanksha Choudhary, Ashish Singh This study aims to analyse the relationship between intergenerational educational mobility and the overall health of the Indian women. It uses a nationally representative survey, India Human Development Survey (IHDS) 2011–12, and logistic regressions to study this relationship. The sample comprises of women aged 45 years and older. We find that the women experiencing upward intergenerational educational mobility (vis-a-vis their mothers) have significantly higher chances of experiencing good overall health compared to the women who are having same or lesser level of education as that of their mothers. Besides, women suffering from short term or major morbidity have remarkably lower chances of having overall good health. Also, women from rural India have significantly lesser chances of having overall good health as compared to that of urban areas. Further, Muslim women have lesser chances of having overall good health as that of women from other religious categories. Moreover, there is a significant variation in the overall health of women as we move from the eastern region to the western region of India.
    Electronic ISSN: 1932-6203
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  • 67
    Publication Date: 2018-09-07
    Description: by José Biurrun Manresa, Ole Kæseler Andersen, André Mouraux, Emanuel N. van den Broeke High frequency electrical stimulation (HFS) of the skin induces increased pinprick sensitivity in the surrounding unconditioned skin. The aim of the present study was to investigate the contribution of A-fiber nociceptors to this increased pinprick sensitivity. For this we assessed if the perception and brain responses elicited by low-intensity intra-epidermal electrical stimulation (IES), a method preferentially activating Aδ-fiber nociceptors, are increased in the area of HFS-induced increased pinprick sensitivity. HFS was delivered to one of the two forearms of seventeen healthy volunteers. Mechanical pinprick stimulation and IES were delivered at both arms before HFS (T0), 20 minutes after HFS (T1) and 45 minutes after HFS (T2). In all participants, HFS induced an increase in pinprick perception at the HFS-treated arm, adjacent to the site of HFS. This increase was significant at both T1 and T2. HFS did not affect the percept elicited by IES, but did enhance the magnitude of the N2 wave of IES-evoked brain potentials, both at T1 and at T2. Our results show that HFS induces a long-lasting enhancement of the N2 wave elicited by IES in the area of secondary hyperalgesia, indicating that HFS enhances the responsiveness of the central nervous system to nociceptive A-fiber input. However, we found no evidence that HFS affects the perception elicited by IES, which may suggest that the population of nociceptors that mediate the perception elicited by IES do not contribute to HFS-induced increased pinprick sensitivity.
    Electronic ISSN: 1932-6203
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  • 68
    Publication Date: 2018-09-07
    Description: by Hui-Wen Lin, Li-Fong Lin, Hung-Chou Chen, Tsan-Hon Liou, Shih-Wei Huang Background Patients with chronic obstructive pulmonary disease (COPD) are at a higher risk of many types of cancer. However, specific investigation of the risk of prostate cancer and the influence of COPD pharmacotherapy in patients with COPD is lacking. This study investigated the risk and influence of COPD pharmacotherapy on risk of prostate cancer in patients with COPD. Methods This retrospective cohort study used data from Taiwan’s Longitudinal Health Insurance Database 2005 (LHID2005). The study cohort comprised COPD patients who received treatment between 2004 and 2008, and who were identified from the LHID2005. The control cohort comprised patients without COPD and was matched to the study cohort by age and sex. Two-stage propensity score calibration with the National Health Interview Survey 2005 was performed to obtain the missing confounders of smoking, alcohol drinking, and body mass index in the LHID. The hazard ratio (HR) and adjusted HR were estimated. Moreover, the influence of inhaled medications and other related medication on the risk of prostate cancer was analyzed by Cox proportional hazard regression. Results The COPD cohort comprised 12,774 patients, and the control cohort comprised 38,322 patients (1:3). The incidence of prostate cancer was 633 per 100,000 person-years in the COPD cohort and 361 per 100,000 person-years in the control cohort. The propensity score calibration-adjusted HR was 1.62 (95% CI, 1.40–1.87, p 〈 0.001) in the COPD cohort. Further analysis revealed that the adjusted HR for the risk of prostate cancer was 1.61 (95% CI, 1.19–2.16, p = 0.002) in patients with COPD who used short-acting muscarinic antagonists (SAMAs) and 1.89 (95% CI, 1.40–2.54, p 〈 0.001) in patients with COPD who used short-acting beta-agonists (SABAs). COPD patients had lower risk of prostate cancer when using statin (HR = 0.63, 95% CI, 0.45–0.89, p = 0.010) or aspirin (HR = 0.55, 95% CI, 0.35–0.85, p = 0.008). Conclusion Patients with COPD are at a higher risk of prostate cancer, particularly those using SAMAs or SABAs. This finding suggests that inflammation control may be an effective strategy for decreasing the risk of prostate cancer.
    Electronic ISSN: 1932-6203
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  • 69
    Publication Date: 2018-09-07
    Description: by Nicolas Hegerle, Myeongjin Choi, James Sinclair, Mohammed N. Amin, Morgane Ollivault-Shiflett, Brittany Curtis, Rachel S. Laufer, Surekha Shridhar, Jerod Brammer, Franklin R. Toapanta, Ian Alan Holder, Marcela F. Pasetti, Andrew Lees, Sharon M. Tennant, Alan S. Cross, Raphael Simon Klebsiella pneumoniae (KP) and Pseudomonas aeruginosa (PA) are important human pathogens that are associated with a range of infection types, including wound and disseminated infections. Treatment has been complicated by rising rates of antimicrobial resistance. Immunoprophylactic strategies are not constrained by antimicrobial resistance mechanisms. Vaccines against these organisms would be important public health tools, yet they are not available. KP surface O polysaccharides (OPS) are protective antigens in animal models of infection. Similarly, PA flagellin (Fla), the major subunit of the flagellar filament, is required for virulence and is a target of protective antibodies in animal models. We report herein the development of a combined KP and PA glycoconjugate vaccine comprised of the four most common KP OPS types associated with human infections (O1, O2, O3, O5), chemically linked to the two Fla types of PA (FlaA, FlaB). Conjugation of KP OPS to PA Fla enhanced anti-polysaccharide immune responses and produced a formulation that generated antibody titers to the four KP OPS types and both PA Fla antigens in rabbits. Passive transfer of vaccine-induced rabbit antisera reduced the bacterial burden and protected mice against fatal intravenous KP infection. Mice passively transferred with conjugate-induced antisera were also protected against PA infection after thermal injury with a FlaB-expressing isolate, but not a FlaA isolate. Taken together, these promising preclinical results provide important proof-of-concept for a broad spectrum human vaccine to prevent KP and PA infections.
    Electronic ISSN: 1932-6203
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  • 70
    Publication Date: 2018-09-07
    Description: by Cintia Lepesqueur, Scheila Scherrer, Marcos C. Vieira, Mário Almeida-Neto, Danielle M. Salcido, Lee A. Dyer, Ivone R. Diniz β diversity of herbivorous insects in the tropics is usually very high, and there is often strong dissimilarity in herbivore species composition across different spatial scales and different abiotic gradients. Similarly, turnover is high for trophic interactions between herbivorous insects and their host plants. Two factors have been proposed to explain temporal or spatial differences in trophic interactions: changes in species composition and temporal changes in the behavior of shared species. The goal of this study was to evaluate determinants of high β diversity of trophic interactions between lepidopteran caterpillars and their host plants across dry and rainy seasons and their transitions. Over the course of a year, interaction diversity data were collected from 275 temporary plots in Cerrado vegetation, comprising 257 species of caterpillars, 137 species of host plants and 503 different trophic interactions. All these diversity parameters varied across seasons. Species assemblages of caterpillars and plants were different among the four seasons, and there was a high turnover of interactions between the seasons. The high temporal β diversity of trophic interactions was mostly due to interaction rewiring between co-occurring species, as opposed to changes in species composition over time.
    Electronic ISSN: 1932-6203
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  • 71
    Publication Date: 2018-09-07
    Description: by Ewa Strauss, Jolanta Tomczak, Ryszard Staniszewski, Grzegorz Oszkinis Background Little is known on the role of selenoprotein genes in cardiovascular disease. This study examines the associations of the SEPP1 , SELENOS , TXNRD1 , TXNRD2 , GPX4 , and SOD2 polymorphisms and selenoprotein P (SeP) and thioredoxin concentrations with the development of abdominal aortic aneurysm (AAA) and aortoiliac occlusive disease (AOID), as well as their influence on cardiac phenotype. Methods 564 patients with AAA, 400 patients with AIOD, and 543 controls were enrolled and characterized for coronary artery disease, myocardial infarction, and systolic heart failure (HF) occurrence. In AAA, the coexistence of peripheral arterial disease (PAD) was examined. Genotypes were determined using TaqMan-based assays. Selenoprotein concentration was assessed using the ELISA method. Results The SELENOS rs34713741T , SEPP1 rs3877899A , and GPX4 rs713041T alleles were related to a 30–60% increase in the AIOD/PAD risk in the recessive or dominant model (all associations at P 〈 .05). The SEPP1 rs3877899A allele was a protective factor for the development of AAA without concomitant PAD (OR = 0.68 for the dominant model, P = .014), but not AAA with concomitant PAD. The cumulative two-locus effects of selenoprotein genes on the AAA/AIOD risk were observed, including the multiplicative interaction between the SELENOS rs34713741T and GPX4 rs713041T alleles (both in the recessive model) affecting the AIOD risk (OR = 5.27, P = .001) and its clinical phenotype. Coexistence of HF in aortic diseases was related to both the SEPP1 rs7579A allele (OR = 1.83 for carriers, P = .013) and increased SeP concentrations; SeP level ≥8.5 mg/mL caused a 3.5-fold increase in the risk of HF. In AAA, SeP levels were correlated with BMI ( r = -0.575, P 〈 .0001). Conclusions Our results provide evidence that selenoprotein polymorphisms constitute a risk factor for HF and peripheral atherosclerosis, but prevent the development of AAA. Excessive weight might result in reduced antioxidant reserve efficiency in AAA. Validation studies are required to establish whether SeP concentration may be a marker for HF.
    Electronic ISSN: 1932-6203
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  • 72
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    Publication Date: 2018-09-07
    Description: by John M. Halley, Kyle S. Van Houtan, Nate Mantua Human activities are exposing organisms not only to direct threats (e.g. habitat loss) but also to indirect environmental pressures such as climate change, which involves not just directional global warming but also increasing climatic variability. Such changes will impact whole communities of organisms and the possible effects on population dynamics have raised concerns about increased extinction rates. Conservation-minded approaches to extinction risk vary from range shifts predicted by climate envelope models with no population dynamics to population viability analyses that ignore environmental variability altogether. Our modelling study shows that these extremes are modelling responses to a spectrum of environmental sensitivity that organisms may exhibit. We show how the survival curve plays a major role in how environmental variability leads to population fluctuations. While it is often supposed that low-fecundity organisms (those with high parental investment) will be the most vulnerable to climate change, it is those with high fecundity (low parental investment) that are likely to be more sensitive to such changes. We also find that abundance variations in high fecundity populations is driven primarily by fluctuations in the survival of early life stages, the more so if those environmental changes are autocorrelated in time. We show which types of conservation actions are most appropriate for a number of real populations. While the most effective conservation actions for organisms of low fecundity is to avoid killing them, for populations with high fecundity (and low parental investment), our study suggests conservation should focus more on protecting early life stages from hostile environments.
    Electronic ISSN: 1932-6203
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  • 73
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    Publication Date: 2018-09-11
    Description: by Nicole Marquardt, Malte Feja, Hana Hünigen, Johanna Plendl, Lena Menken, Heidrun Fink, Bettina Bert In the European Union (EU) millions of laboratory mice are used and killed for experimental and other scientific purposes each year. Although controversially discussed, the use of carbon dioxide (CO 2 ) is still permitted for killing rodents according to the Directive 2010/63/EU. Within the scope of refinement, our aim was to investigate if isoflurane and sevoflurane are an appropriate alternative killing method to CO 2 in mice. Different concentrations of CO 2 (filling rates of 20%, 60%, 100%; CO 2 20, 60, 100), isoflurane (Iso 2%, 5%) and sevoflurane (Sevo 4.8%, 8%) were compared in two mouse strains (NMRI, C57Bl/6J) using a broad spectrum of behavioral parameters, including the approach-avoidance test, and analyzing blood for stress parameters (glucose, adrenaline, noradrenaline). We focused in our study on the period from the beginning of the gas inlet to loss of consciousness, as during this period animals are able to perceive pain and distress. Our results show that only higher concentrations of CO 2 (CO 2 60, 100) and isoflurane (5%) induced surgical tolerance within 300 s in both strains, with CO 2 100 being the fastest acting inhalant anesthetic. The potency of halogenated ethers depended on the mouse strain, with C57Bl/6J being more susceptible than NMRI mice. Behavioral analysis revealed no specific signs of distress, e. g. stress-induced grooming, and pain, i. e. audible vocalizations, for all inhalant gases. However, adrenaline and noradrenaline plasma concentrations were increased, especially in NMRI mice exposed to CO 2 in high concentrations, whereas we did not observe such increase in animals exposed to isoflurane or sevoflurane. Escape latencies in the approach-avoidance test using C57Bl/6J mice did not differ between the three inhalant gases, however, some animals became recumbent during isoflurane and sevoflurane but not during CO 2 exposure. The rise in catecholamine concentrations suggests that CO 2 exposure might be linked to a higher stress response compared to isoflurane and sevoflurane exposure, although we did not observe a behavioral correlate for that. Follow-up studies investigating other fast-acting stress hormones and central anxiety circuits are needed to confirm our findings.
    Electronic ISSN: 1932-6203
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  • 74
    Publication Date: 2018-09-11
    Description: by Arianne C. Richard, James E. Peters, Natalia Savinykh, James C. Lee, Eric T. Hawley, Françoise Meylan, Richard M. Siegel, Paul A. Lyons, Kenneth G. C. Smith Chronic inflammation in inflammatory bowel disease (IBD) results from a breakdown of intestinal immune homeostasis and compromise of the intestinal barrier. Genome-wide association studies have identified over 200 genetic loci associated with risk for IBD, but the functional mechanisms of most of these genetic variants remain unknown. Polymorphisms at the TNFSF15 locus, which encodes the TNF superfamily cytokine commonly known as TL1A, are associated with susceptibility to IBD in multiple ethnic groups. In a wide variety of murine models of inflammation including models of IBD, TNFSF15 promotes immunopathology by signaling through its receptor DR3. Such evidence has led to the hypothesis that expression of this lymphocyte costimulatory cytokine increases risk for IBD. In contrast, here we show that the IBD-risk haplotype at TNFSF15 is associated with decreased expression of the gene by peripheral blood monocytes in both healthy volunteers and IBD patients. This association persists under various stimulation conditions at both the RNA and protein levels and is maintained after macrophage differentiation. Utilizing a “recall-by-genotype” bioresource for allele-specific expression measurements in a functional fine-mapping assay, we localize the polymorphism controlling TNFSF15 expression to the regulatory region upstream of the gene. Through a T cell costimulation assay, we demonstrate that genetically regulated TNFSF15 has functional relevance. These findings indicate that genetically enhanced expression of TNFSF15 in specific cell types may confer protection against the development of IBD.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 75
    Publication Date: 2018-09-11
    Description: by Matthias Zielonka, Maximilian Breuer, Jürgen Günther Okun, Matthias Carl, Georg Friedrich Hoffmann, Stefan Kölker Hyperammonemia is the common biochemical hallmark of urea cycle disorders, activating neurotoxic pathways. If untreated, affected individuals have a high risk of irreversible brain damage and mortality. Here we show that acute hyperammonemia strongly enhances transamination-dependent formation of osmolytic glutamine and excitatory glutamate, thereby inducing neurotoxicity and death in ammoniotelic zebrafish larvae via synergistically acting overactivation of NMDA receptors and bioenergetic impairment induced by depletion of 2-oxoglutarate. Intriguingly, specific and irreversible inhibition of ornithine aminotransferase (OAT) by 5-fluoromethylornithine rescues zebrafish from lethal concentrations of ammonium acetate and corrects hyperammonemia-induced biochemical alterations. Thus, OAT inhibition is a promising and effective therapeutic approach for preventing neurotoxicity and mortality in acute hyperammonemia.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 76
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    Publication Date: 2018-09-11
    Description: by Sunyoung Park, Myung-Sun Kim This study used event-related potentials (ERPs) and a modified spatial 2 -back task to investigate spatial working memory in binge drinking (BD) college students. Based on the Korean version of the Alcohol Use Disorder Identification Test (AUDIT-K) and Alcohol Use Questionnaire (AUQ) scores, participants were assigned into BD ( n = 25) and non-BD ( n = 25) groups. The modified spatial 2 -back task includes congruent, incongruent, and lure conditions and participants are required to respond as rapidly and accurately as possible to the congruent stimuli but not to the incongruent and lure stimuli. The BD and non-BD groups exhibited comparable performances on the spatial 2 -back task but the BD group showed significantly larger P3 amplitudes than the non-BD group. Additionally, the non-BD group showed larger P3 amplitudes in response to the congruent stimuli compared to the incongruent and lure stimuli whereas the P3 amplitudes in the BD group did not differ significantly among the three conditions. These results indicate that the BD individuals exerted greater effort to maintain performance levels comparable to non-BD individuals and that they were less efficient in differentiating or allocating attentional resources between relevant and irrelevant information.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 77
    Publication Date: 2018-09-11
    Description: by Rafael Campos, Alberto Fernando Oliveira Justo, Fabíola Z. Mónica, José Carlos Cogo, Ronilson Agnaldo Moreno, Valéria Barbosa de Souza, Andre Almeida Schenka, Gilberto De Nucci Endothelium is the main source of catecholamine release in the electrical-field stimulation (EFS)–induced aortic contractions of the non- venomous snake Panterophis guttatus . However, adrenergic vasomotor control in venomous snakes such as Crotalus durissus terrificus and Bothrops jararaca has not yet been investigated. Crotalus and Bothrops aortic rings were mounted in an organ bath system. EFS-induced aortae contractions were performed in the presence and absence of guanethidine (30 μM), phentolamine (10 μM) or tetrodotoxin (1 μM). Frequency-induced contractions were also performed in aortae with endothelium removed. Immunohistochemical localization of both tyrosine hydroxylase (TH) and S-100 protein in snake aortic rings and brains, as well as in human tissue (paraganglioma tumour) were carried out. EFS (4 to 16 Hz) induced frequency-dependent aortic contractions in both Crotalus and Bothrops . The EFS-induced contractions were significantly reduced in the presence of either guanethidine or phentolamine in both snakes (p
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 78
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    Publication Date: 2018-09-11
    Description: by Sumit Kumar Das, Laishram Ladusingh Introduction There is an evidence of increasing inpatient expenditure for decedents. Estimates used to assess the economic burden of out-of-pocket (OOP) healthcare expenditure provide an underestimation for inpatient decedent cases. The aims of this paper are to study the trend and pattern of inpatient decedent expenditure and decipher the reasons behind the increasing cost in India. Methods Using three rounds of national level National Sample Survey (NSS) data on morbidity & healthcare conducted during 1995–2015 in India, total and component-wise cost of dying was estimated by the socio-demographic characteristics and types of diseases. Generalised linear model was employed to find the changing effect of inpatient decedents on inpatient expenditure on three-time points. Results More than half among inpatient decedents were elderly. Mean inpatient expenditure for neoplasm, circulatory system-related diseases and external causes of mortality and morbidity increased substantially during these two decades. Mean decedent inpatient expenditure become double, diagnostic and bed charges increased by 243%, 323% respectively during 2004–05 to 2014–15. During 2014–15 average decedents aged 15–59 years spent ₹53599 in last twelve month of their life. Controlling all other potential factors, the inpatient expenditure among decedents increased substantially between 1995–96 and 2014–15. Discussion Out-of-pocket inpatient health expenditure widened between survivor and decedents in between 1995–2014. Increase in the proportion of elderly, proportion of non-communicable and lifestyle-related diseases, expenses on drugs, diagnostics, bed charges largely private sector expenses were the leading reasons for increasing inpatient decedent expenditure. Age-based risk adjustment and modification of end-of-life care are strongly required, future social insurance based on the health-based value of out-of-pocket expenditure rather than their pure consumption value need to be designed to tackle the burden.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 79
    Publication Date: 2018-09-11
    Description: by Yun Wang, Li Wen, Shi Zhou, Yong Zhang, Xin-Hao Wang, You-Yu He, Allan Davie, Suzanne Broadbent Aims The aims of this study were to determine the effects of four weeks of intermittent exposure to a moderate hypoxia environment (15% oxygen), and compare with the effects of exercise in normoxia or hypoxia, on glucose homeostasis, insulin sensitivity, GLUT4 translocation, insulin receptor phosphorylation, Akt-dependent GSK3 phosphorylation and Akt activity in skeletal muscle of obese mice with type 2 diabetes. Methods C57BL/6J mice that developed type 2 diabetes with a high-fat-diet (55% fat) (fasting blood glucose, FBG = 13.9 ± 0.69 (SD) mmol/L) were randomly allocated into diabetic control (DC), rest in hypoxia (DH), exercise in normoxia (DE), and exercise in hypoxia (DHE) groups (n = 7, each), together with a normal-diet (4% fat) control group (NC, FBG = 9.1 ± 1.11 (SD) mmol/L). The exercise groups ran on a treadmill at intensities of 75–90% VO 2 max. The interventions were applied one hour per day, six days per week for four weeks. Venous blood samples were analysed for FBG, insulin (FBI) and insulin sensitivity (QUICKI) pre and post the intervention period. The quadriceps muscle samples were collected 72 hours post the last intervention session for analysis of GLUT4 translocation, insulin receptor phosphorylation, Akt expression and phosphorylated GSK3 fusion protein by western blot. Akt activity was determined by the ratio of the phosphorylated GSK3 fusion protein to the total Akt protein. Results The FBG of the DH, DE and DHE groups returned to normal level (FBG = 9.4 ± 1.50, 8.86 ± 0.94 and 9.0 ± 1.13 (SD) mmol/L for DH, DE and DHE respectively, P 〈 0.05), with improved insulin sensitivity compared to DC (P 〈 0.05), after the four weeks treatment, while the NC and DC showed no significant changes, as analysed by general linear model with repeated measures. All three interventions resulted in a significant increase of GLUT4 translocation to cell membrane compared to the DC group (P 〈 0.05). The DE and DH showed a similar level of insulin receptor phosphorylation compared with NC that was significantly lower than the DC (P 〈 0.05) post intervention. The DH and DHE groups showed a significantly higher Akt activity compared to the DE, DC and NC (P 〈 0.05) post intervention, as analysed by one-way ANOVA. Conclusions This study produced new evidence that intermittent exposure to mild hypoxia (0.15 FiO 2 ) for four weeks resulted in normalisation of FBG, improvement in whole body insulin sensitivity, and a significant increase of GLUT4 translocation in the skeletal muscle, that were similar to the effects of exercise intervention during the same time period, in mice with diet-induced type 2 diabetes. However, exercise in hypoxia for four weeks did not have additive effects on these responses. The outcomes of the research may contribute to the development of effective, alternative and complementary interventions for management of hyperglycaemia and type 2 diabetes, particularly for individuals with limitations in participation of physical activity.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 80
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