bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mouse Norovirus infection arrests host cell translation uncoupled from the stress granule-PKR-eIF2α axis
Authors: Fritzlar Svenja , Aktepe Turgut E. , Chao Yi-Wei , McAllaster Michael R. , Wilen Craig B. , White Peter A. , Mackenzie Jason M. 
Published: February 2019

AbstractThe integrated stress response (ISR) is a cellular response system activated upon different types of stresses, including viral infection, to restore cellular homeostasis. However, many viruses manipulate this response for their own advantage. In this study we investigated the association between murine norovirus (MNV) infection and the ISR and demonstrate that MNV regulates the ISR by activating and recruiting key ISR host factors. We observed that during MNV infection, there is a progressive increase in phosphorylated eukaryotic initiation factor 2 alpha (p-eIF2α) resulting in the suppression of host translation, yet MNV translation still progresses under these conditions. Interestingly, the shutoff of host translation also impacts the translation of key signalling cytokines such as IFNβ, IL-6 and TNFα. Our subsequent analyses revealed that the phosphorylation of eIF2α was mediated via Protein kinase-R (PKR), but further investigation revealed that PKR activation, phosphorylation of eIF2α and translational arrest were uncoupled during infection. We further observed that stress granules (SGs) are not induced during MNV infection, and MNV has the capacity to restrict SG nucleation and formation. We observed that MNV recruited the key SG nucleating protein G3BP1 to its replication sites and intriguingly the silencing of G3BP1 negatively impacts MNV replication. Thus, it appears, MNV utilises G3BP1 to enhance replication, but equally to prevent SG formation, intimating an anti-MNV property of SGs. Overall, thus study highlights MNV manipulation of SGs, PKR and translational control to regulate cytokine translation and to promote viral replication.ImportanceViruses hijack host machinery and regulate cellular homeostasis to actively replicate their genome, propagate and cause disease. In retaliation, cells possess various defence mechanisms to detect, destroy and clear infecting viruses as well as signal to neighbouring cells to inform them of the imminent threat. In this study, we demonstrate that the murine norovirus (MNV) infection stalls host protein translation and the production of antiviral and pro-inflammatory cytokines. However, virus replication and protein translation still ensues. We show that MNV further prevents the formation of cytoplasmic RNA granules, called stress granules (SG), by recruiting the key host protein G3BP1 to the MNV replication complex; a recruitment that is crucial to establishing and maintaining virus replication. Thus MNV promotes immune evasion of the virus by altering protein translation. Together, this evasion strategy delays innate immune responses to MNV infection and accelerates disease onset.
Water quality assessments and metagenomic analysis of the polluted river Apatlaco, Mexico
Authors: Breton-Deval Luz , Juárez Katy , Sánchez-Flores Alejandro , Vera-Estrella Rosario 
Published: February 2019

ABSTRACTThe aim of this study is to analyze the water quality parameters and bacterial diversity and thereby understand the effect of water quality on the microbial population structure in the river. The following parameters: total coliforms, chemical oxygen demand, harness, ammonium, nitrite, nitrate, total Kjeldahl nitrogen, dissolved oxygen, total phosphorus, total dissolved solids, and temperature were analyzing along 17 sampling points in the river. The worst levels of pollution were 510 mg/L chemical oxygen demand, 7 mg/L nitrite, 45 mg/L nitrate, 2 mg/L dissolved oxygen, and 756 mg/L of total dissolved solids. Whole metagenome shotgun sequencing was performed at 4 key points along the river (P1,P7,P10 and P17), the first point had clean water and the other points were polluted, as a result of this pollution, the structure of microbial communities along the river have changed. Proteobacteria and Bacteroidetes were the most representative phyla with a relative abundance of 57 and 43% respectively for P1, 82 and 15% for P7, 69 and 27% for P10 and 87 and 10% for the last point P17. P1 is rich in microorganism such as Limnohabitans a planktonic bacterium very common in freshwater ecosystems. However, in P7, P10 and P17 are rich in opportunistic pathogens such as Acinetobacter Arcobacter and Myroides that endangers the health of around 1.6 million people which live around the area. These results elucidate the influence of the pollution on the microbial community and the likely effects on the health of the people around.
Testing the exteroceptive function of nociception: the role of visual experience in shaping the spatial representations of nociceptive inputs
Authors: Vanderclausen Camille , Bourgois Marion , Volder Anne De , Legrain Valéry 
Published: February 2019

AbstractAdequately localizing pain is crucial to protect the body against physical damage and react to the stimulus in external space having caused such damage. Accordingly, it is hypothesized that nociceptive inputs are remapped from a somatotopic reference frame, representing the skin surface, towards a spatiotopic frame, representing the body parts in external space. This ability is thought to be developed and shaped by early visual experience. To test this hypothesis, normally sighted and early blind participants performed temporal order judgment tasks during which they judged which of two nociceptive stimuli applied on each hand’s dorsum was perceived as first delivered. Crucially, tasks were performed with the hands either in an uncrossed posture or crossed over body midline. While early blinds were not affected by the posture, performances of the normally sighted participants decreased in the crossed condition relative to the uncrossed condition. This indicates that nociceptive stimuli were automatically remapped into a spatiotopic representation that interfered with somatotopy in normally sighted individuals, whereas early blinds seemed to mostly rely on a somatotopic representation to localize nociceptive inputs. Accordingly, the plasticity of the nociceptive system would not purely depend on bodily experiences but also on crossmodal interactions between nociception and vision during early sensory experience.
Molecular dating for phylogenies containing a mix of populations and species
Authors: Mello Beatriz , Tao Qiqing , Kumar Sudhir 
Published: February 2019

AbstractConcurrent molecular dating of population and species divergences is essential in many biological investigations, including phylogeography, phylodynamics, and species delimitation studies. Multiple sequence alignments used in these investigations frequently consist of both intra- and inter-species samples (mixed samples). As a result, the phylogenetic trees contain inter-species, inter-population, and within population divergences. To date these sequence divergences, Bayesian relaxed clock methods are often employed, but they assume the same tree prior for both inter- and intra-species branching processes and require specification of a clock model for branch rates (independent vs. autocorrelated rates models). We evaluated the impact of using the same tree prior on the Bayesian divergence time estimates by analyzing computer-simulated datasets. We also examined the effect of the assumption of independence of evolutionary rate variation among branches when the branch rates are autocorrelated. Bayesian approach with Skyline-coalescent tree priors generally produced excellent molecular dates, with some tree priors (e.g., Yule) performing the best when evolutionary rates were autocorrelated, and lineage sorting was incomplete. We compared the performance of the Bayesian approach with a non-Bayesian, the RelTime method, which does not require specification of a tree prior or selection of a clock model. We found that RelTime performed as well as the Bayesian approach, and when the clock model was mis-specified, RelTime performed slightly better. These results suggest that the computationally efficient RelTime approach is also suitable to analyze datasets containing both populations and species variation.
Free water in white matter differentiates MCI and AD from control subjects
Authors: Dumont Matthieu , Roy Maggie , Jodoin Pierre-Marc , Morency Felix C. , Houde Jean-Christophe , Xie Zhiyong , Bauer Cici , Samad Tarek A. , Van Dijk Koene R. A. , Goodman James A. , Descoteaux Maxime 
Published: February 2019

AbstractRecent evidence show that neuroinflammation plays a role in many neurological diseases including mild cognitive impairment (MCI) and Alzheimer’s disease (AD), and that free water (FW) modeling from clinically acquired diffusion MRI (DTI-like acquisitions) can be sensitive to this phenomenon. This FW index measures the fraction of the diffusion signal explained by isotropically unconstrained water, as estimated from a bi-tensor model. In this study, we developed a simple FW processing pipeline that uses a safe white matter (WM) mask without gray matter (GM)/CSF partial volume contamination (WMsafe) near ventricles and sulci. We investigated if FW inside the WMsafe mask, including and excluding areas of white matter damage such as white matter hyperintensities (WMHs) as shown on T2 FLAIR, computed across the whole white matter could be indicative of diagnostic grouping along the AD continuum.After careful quality control, 81 cognitively normal controls (NC), 103 subjects with MCI and 42 with AD were selected from the ADNIGO and ADNI2 databases. We show that MCI and AD have significantly higher FW measures even after removing all partial volume contamination. We also show, for the first time, that when WMHs are removed from the masks, the significant results are maintained, which demonstrates that the FW measures are not just a byproduct of WMHs. Our new and simple FW measures can be used to increase our understanding of the role of inflammation-associated edema in AD and may aid in the differentiation of healthy subjects from MCI and AD patients.
“Multiple human adipocyte subtypes and mechanisms of their development”
Authors: Min So Yun , Desai Anand , Yang Zinger , Sharma Agastya , Genga Ryan M.J. , Kucukural Alper , Lifshitz Lawrence , Maehr René , Garber Manuel , Corvera Silvia 
Published: February 2019

SUMMARYHuman adipose tissue depots perform numerous diverse physiological functions, and are differentially linked to metabolic disease risk, yet only two major human adipocyte subtypes have been described, white and “brown/brite/beige.” The diversity and lineages of adipocyte classes have been studied in mice using genetic methods that cannot be applied in humans. Here we circumvent this problem by studying the fate of single mesenchymal progenitor cells obtained from human adipose tissue. We report that a minimum of four human adipocyte subtypes can be distinguished by transcriptomic analysis, specialized for functionally distinct processes such as adipokine secretion and thermogenesis. Evidence for the presence of these adipocytes subtypes in adult humans is evidenced by differential expression of key adipokines leptin and adiponectin in isolated mature adipocytes. The human adipocytes most similar to the mouse “brite/beige” adipocytes are enriched in mechanisms that promote iron accumulation and protect from oxidative stress, and are derived from progenitors that express high levels of cytokines such as IL1B, IL8, IL11 and the IL6 family cytokine LIF, and low levels of the transcriptional repressors ID1 and ID3. Our finding of this adipocyte repertoire and its developmental mechanisms provides a high-resolution framework to analyze human adipose tissue architecture and its role in systemic metabolism and metabolic disease.
Plasmodium knowlesi clinical isolates from Malaysia show extensive diversity and strong differential selection pressure at the merozoite surface protein 7D (MSP7D)
Authors: Ahmed Md Atique , Quan Fu-Shi 
Published: February 2019

AbstractBackgroundHigh proportion of human cases due to the simian malaria parasite Plasmodium knowlesi in Malaysia has been a cause of concern, as it can be severe and fatal. Merozoite surface protein 7 (MSP7) is a multigene family which forms a non-covalent complex with MSP-1 prior to receptor-ligand recognition in Plasmodium falciparum and thus an important antigen for vaccine development. However, no study has been done in any of the ortholog family members in Plasmodium knowlesi from clinical samples. Thus in this study we investigated the level of polymorphism, haplotypes, and natural selection acting at the pkmsp-7D gene in clinical samples from Malaysia.MethodsWe analyzed 36 full-length pkmsp7D gene sequences (along with the reference H-strain: PKNH_1266000) which were orthologous to pvmsp7H (PVX_082680) from clinical isolates of Malaysia available from public databases. Population genetic, evolutionary and phylogenetic analyses were performed to determine the level of genetic diversity, polymorphism, recombination and natural selection.ResultsAnalysis of 36 full-length pkmsp7D sequences identified 147 SNPs (91 non-synonymous and 56 synonymous substitutions). Nucleotide diversity across the full-length gene was higher than its ortholog in P. vivax (msp7H). Region-wise analysis of the gene indicated that the nucleotide diversity at the central region was very high (π = 0.14) compared to the 5’ and 3’ regions. Most hyper-variable SNPs were detected at the central domain. Multiple test for natural selection indicated the central region was under strong positive natural selection however, the 5’ and 3’ regions were under negative/purifying selection. Evidence of intragenic recombination were detected at the central region of the gene. Phylogenetic analysis using full-length msp7D genes indicated there was no geographical clustering of parasite population.ConclusionsHigh genetic diversity with hyper-variable SNPs and strong evidence of positive natural selection at the central region of MSP7D indicated exposure of the region to host immune pressure. Negative selection at the 5’ and the 3’ regions of MSP7D might be because of functional constraints at the unexposed regions during the merozoite invasion process of P. knowlesi. No evidence of geographical clustering among the clinical isolates from Malaysia indicated uniform selection pressure in all populations. These findings highlight the further evaluation of the regions and functional characterization of the protein as a potential blood stage vaccine candidate for P. knowlesi.
Flow characteristics of two-dimensional synthetic jets under diaphragm resonance excitation
Authors: Lin Chi-Yu , Lin Jih Lung 
Published: February 2019

Purpose
This paper aims to experimentally study the external flow characteristic of an isolated two-dimensional synthetic jet actuator undergoing diaphragm resonance.

Design/methodology/approach
The resonance frequency of the diaphragm (40 Hz) depends on the excitation mechanism in the actuator, whereas it is independent of cavity geometry, excitation waveform and excitation voltage. The velocity response of the synthetic jet is influenced by excitation voltage rather than excitation waveform. Thus, this investigation selected four different voltages (5, 10, 15 and 20 V) under the same sine waveform as experiment parameters.

Findings
The velocity field along the downstream direction is classified into five regions, which can be obtained by hot-wire measurement. The first region refers to an area in which flow moves from within the cavity to the exit of orifice through the oscillation of the diaphragm, but prior to the formation of the vortex of a synthetic jet. In this region, two characteristic frequencies exist at 20 and 40 Hz in the flow field. The second region refers to the area in which the vortices of a synthetic jet fully develop following their initial formation. In this region, the characteristic frequencies at 20 and 40 Hz still occur in the flow field. The third region refers to the area in which both fully developed vortices continue traveling downstream. It is difficult to obtain the characteristic frequency in this flow field, because the mean center velocities (ū) decay downstream and are proportional to (x/w)−1/2 for the four excitation voltages. The fourth region reveals variations in both vortices as they merge into a single vortex. The mean center velocities (ū) are approximately proportional to (x/w)0 in this region for the four excitation voltages. A fifth region deals with variations in the vortex of a synthetic jet after both vortices merge into one, in which the mean center velocities (ū) are approximately proportional to (x/w)−1 in this region for the four excitation voltages (x/w is the dimensionless streamwise distance).

Originality/value
Although the flow characteristics of synthetic jets had reported for flow control in some literatures, variations of flow structure for synthetic jets are still not studied under the excitation of diaphragm resonance. This paper showed some novel results that our velocity response results obtained by hot-wire measurement along the downstream direction compared with flow visualization resulted in the classification of five regions under the excitation of diaphragm resonance. In the future, it makes valuable contributions for experimental findings to provide researchers with further development of flow control.
Further Development of a Specific Conductivity Approach to Measure Groundwater Discharge Area within Lakes
Authors: Bischof Stefan M. , Herwig Brian R. , Sebestyen Stephen D. , Hanson Mark A. , Zimmer Kyle D. , Cotner James B. , Kroeger Timothy J. 
Published: February 2019

AbstractGroundwater exchanges with most lakes are rarely quantified because there are many technical challenges to quantification. We investigated a lakebed mapping approach to infer the relative areas of groundwater exchange in 12 prairie shallow lakes and five Laurentian mixed forest shallow lakes in Minnesota, USA in 2011. We used a relatively common approach (seepage meters) to provide baseline information on the magnitude and direction of flow at four locations in each lake. To expand from point measurements to the whole‐lake scale, we explored use of specific conductivity as a cheaper and more time efficient proxy for groundwater discharge to lakes. We validated the approach at near shore stations in each lake where seepage meter measurements and specific conductivity surveys overlapped. Specific conductivity surveys provided a similar assessment of groundwater discharge compared to seepage meters for 50% of the lake‐sampling period combinations. The lakebed mapping approach, when validated for a lake with a limited number of seepage meter (or alternative methods) measurements, offers the advantages of being more time and labor efficient over the use of a similar number of seepage meter monitoring locations; seepage meters (or piezometers, for example) are costlier in terms of equipment and labor, even for single‐lake studies. We show the combined approach could provide useful baselines for understanding and mapping groundwater exchange in shallow lakes.
Career caseload predicts interobserver agreement on the final classification of a mammogram
Authors: Abdelrahman Mostafa A , Rawashdeh Mohammad A , McEntee Mark , Abu Tahoun Laila , Brennan Patrick 
Published: February 2019

AbstractIntroductionDifferences in radiologists’ experience can potentially introduce interobserver variability in reading mammograms. This work investigated the effect of radiologists’ experience on agreement on mammographic final classification.MethodsThis was a cross‐sectional study. Seventeen radiologists were asked to provide their final impression on 60 mammogram cases. Experience parameters included breast subspecialty, years reading mammograms, cases read per year and career caseload. Career caseload was calculated by multiplying years reading mammograms by the average number of cases read per year. The interobserver agreement was calculated using Cohen kappa (κ). The difference in κ between radiologists’ groups was compared using the independent‐sample t‐test and analysis of variance.ResultsThe average interobserver agreement was 0.25 (fair). A small difference was found in favour of breast radiologists against general radiologists (κ = 0.21 and 0.29, respectively, P = 0.019). Years reading mammograms and cases read per year did not seem to significantly affect the interobserver agreement (P = 0.056 and 0.273 respectively). Radiologist who had career caseload of at least 2500 cases showed significantly higher consistency than those who read less. κ for radiologists who had career caseload of 2500–4000 cases and >4000 cases was 0.33 and 0.28, respectively, whereas for <2500 κ was 0.17 (P = 0.001).ConclusionA fair level of interobserver agreement on the final classification of a mammogram was demonstrated. Career caseload was the most important experience parameter to associate with the interobserver agreement. Training strategies aiming to increase radiologists’ career caseload may be beneficial.
Diabetes mellitus and survival of non‐small cell lung cancer patients after surgery: A comprehensive systematic review and meta‐analysis
Authors: Deng Han‐Yu , Zheng Xi , Zha Panpan , Peng Lei , Huang Kai‐Li , Qiu Xiao‐Ming 
Published: February 2019

BackgroundDiabetes mellitus (DM) is one of the most common comorbidities in surgically treated non‐small cell lung cancer (NSCLC) patients and has a negative impact on short‐term outcomes. However, the impact of DM on long‐term survival of such patients remains controversial; therefore, we conducted a comprehensive updated meta‐analysis.MethodsWe systematically searched relevant studies in PubMed, Embase, Cochrane Library, and Web of Science up to 6 September 2018. Hazard ratios (HRs) for the impact of DM on overall survival (OS) and recurrence‐free survival (RFS) of patients with surgically treated NSCLC were extracted and analyzed using the STATA 12.0 package.ResultsWe included 13 cohort studies consisting of 4343 patients (730 patients with DM and 3613 patients without) with surgically treated NSCLC. Meta‐analysis showed that patients with DM had significantly poorer OS (random effects: HR 1.30, 95% confidence interval 1.05–1.60; P = 0.016) than those without. However, with a limited sample size, there was no significant difference in RFS (random effects: HR 1.06, 95% confidence interval 0.71–1.58; P = 0.786) between patients with and without DM after surgical resection of NSCLC.ConclusionDM is an independent unfavorable prognostic factor for patients with surgically treated NSCLC. High‐quality studies with appropriate adjustment for confounding factors are needed to confirm our conclusions.