bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergent selection along elevational gradients promotes genetic and phenotypic disparities among small mammal populations
Authors: Feijó Anderson , Wen Zhixin , Cheng Jilong , Ge Deyan , Xia Lin , Yang Qisen 
Published: May 2019

AbstractSpecies distributed along mountain slopes, facing contrasting habitats in short geographic scale, are of particular interest to test how ecologically based divergent selection promotes phenotypic and genetic disparities as well as to assess isolation‐by‐environment mechanisms. Here, we conduct the first broad comparative study of phenotypic variation along elevational gradients, integrating a large array of ecological predictors and disentangling population genetic driver processes. The skull form of nine ecologically distinct species distributed over a large altitudinal range (100–4200 m) was compared to assess whether phenotypic divergence is a common phenomenon in small mammals and whether it shows parallel patterns. We also investigated the relative contribution of biotic (competition and predation) and abiotic parameters on phenotypic divergence via mixed models. Finally, we assessed the population genetic structure of a rodent species (Niviventer confucianus) via analysis of molecular variance and FST along three mountain slopes and tested the isolation‐by‐environment hypothesis using Mantel test and redundancy analysis. We found a consistent phenotypic divergence and marked genetic structure along elevational gradients; however, the species showed mixed patterns of size and skull shape trends across mountain zones. Individuals living at lower altitudes differed greatly in both phenotype and genotype from those living at high elevations, while middle‐elevation individuals showed more intermediate forms. The ecological parameters associated with phenotypic divergence along elevation gradients are partly related to species' ecological and evolutionary constraints. Fossorial and solitary animals are mainly affected by climatic factors, while terrestrial and more gregarious species are influenced by biotic and abiotic parameters. A novel finding of our study is that predator richness emerged as an important factor associated with the intraspecific diversification of the mammalian skull along elevational gradients, a previously overlooked parameter. Population genetic structure was mainly driven by environmental heterogeneity along mountain slopes, with no or a week spatial effect, fitting the isolation‐by‐environment scenario. Our study highlights the strong and multifaceted effects of heterogeneous steep habitats and ecologically based divergent selective forces in small mammal populations.
MHC‐restricted Ag85B‐specific CD8+ T cells are enhanced by recombinant BCG prime and DNA boost immunization in mice
Authors: Komine‐Aizawa Shihoko , Jiang Jiansheng , Mizuno Satoru , Hayakawa Satoshi , Matsuo Kazuhiro , Boyd Lisa F. , Margulies David H. , Honda Mitsuo 
Published: May 2019

AbstractDespite efforts to develop effective treatments and vaccines, Mycobacterium tuberculosis (Mtb), particularly pulmonary Mtb, continues to provide major health challenges worldwide. To improve immunization against the persistent health challenge of Mtb infection, we have studied the CD8+ T cell response to Bacillus Calmette‐Guérin (BCG) and recombinant BCG (rBCG) in mice. Here, we generated CD8+ T cells with an rBCG‐based vaccine encoding the Ag85B protein of M. kansasii, termed rBCG‐Mkan85B, followed by boosting with plasmid DNA expressing the Ag85B gene (DNA‐Mkan85B). We identified two MHC‐I (H2‐Kd)‐restricted epitopes that induce cross‐reactive responses to Mtb and other related mycobacteria in both BALB/c (H2d) and CB6F1 (H2b/d) mice. The H2‐Kd‐restricted peptide epitopes elicited polyfunctional CD8+ T cell responses that were also highly cross‐reactive with those of other proteins of the Ag85 complex. Tetramer staining indicated that the two H2‐Kd‐restricted epitopes elicit distinct CD8+ T cell populations, a result explained by the X‐ray structure of the two peptide/H2‐Kd complexes. These results suggest that rBCG‐Mkan85B vector‐based immunization and DNA‐Mkan85B boost may enhance CD8+ T cell response to Mtb, and might help to overcome the limited effectiveness of the current BCG in eliciting tuberculosis immunity.
A pragmatic effectiveness study of 10‐session cognitive behavioural therapy (CBT‐T) for eating disorders: Targeting barriers to treatment provision
Authors: Pellizzer Mia L. , Waller Glenn , Wade Tracey D. 
Published: May 2019

AbstractObjectiveTen‐session cognitive behavioural therapy (CBT‐T) for transdiagnostic eating disorders targets several barriers to treatment, including cost, therapist expertise, and lengthy wait lists.MethodWe used a case series design to investigate the effectiveness of CBT‐T delivered by trainee psychologists in a postgraduate training clinic. Participants were randomly allocated to commence treatment either immediately or after a 4‐week waitlist period. CBT‐T was delivered to 52 patients, by six different trainees under supervision. Measures of eating disorder cognitions and behaviours, quality of life, and general psychopathology were examined in completer and intention‐to‐treat analyses using multilevel modelling. Last observation carried forward was applied for abstinence, remission, and good outcome analyses to aid comparison with prior studies.ResultsSignificant improvements, associated with medium to large effect sizes, were found for eating disorder cognitions, behaviours quality of life, and negative affect from baseline to posttreatment, and at 1‐ and 3‐month follow‐up. Attrition (38.5%) was comparable with other treatment studies.ConclusionResults provide evidence for the effectiveness of CBT‐T delivered by trainee psychologists for transdiagnostic eating disorder patients, thus tackling some important barriers for treatment. Longer follow‐up, randomised controlled trial designs, and moderator analyses will provide more robust evidence about which patients do best with a shorter therapy.
On the incipient formation of bars and channels on alluvial fans
Authors: Tambroni Nicoletta , Seminara Giovanni , Paola Chris 
Published: May 2019

AbstractThe morphodynamics of topographic expansion has been recently investigated both experimentally, by Sittoni et al., (2014) Shaw et al., (2018), and numerically Sittoni et al., 2014. Here, we study the basic mechanism that governs the evolution of topographic and expansions and explore the instability of the bottom topography under conditions of steady but spatially expanding flow. We model the expanding flow via a by configuration where water and sediments are supplied from a central hole and flow on a cone shaped surface confined by lateral walls. The governing equations are the shallow‐water equations coupled with the Exner equation, written in cylindrical coordinates. We initially approach the problem analytically by considering the conditions required for the basic state, consisting of a pure radial flow and bottom profile, to lose stability to small amplitude perturbations. This analysis suggests that more than one mode may be unstable, encouraging us to extend the analysis to the nonlinear regime. We do this through numerical modeling of the full governing equations, which allows us to predict the establishment of a bar pattern whose features are similar to those experimentally observed. Two prominent features of the finite‐amplitude bar pattern are (1) bar apices are distributed at a radial distance from the inflow consistent with work of Shaw et al. (2018); and (2) that the flow aspect ratio of the interbar areas remain high without provoking further instability. Both features imply that in general expansion acts to reduce bar development relative to an equivalent rectilinear flow. © 2019 John Wiley & Sons, Ltd.
Context‐aware cognitive disaster management using fog‐based Internet of Things
Authors: Butt Talal Ashraf 
Published: May 2019

AbstractThe natural and man‐made disasters are inevitable in many circumstances. Thus, an effective disaster management system (DMS) is vital for any community that can use state‐of‐the‐art technologies to deal with such cataclysmic events. There is plethora of latest technologies such as Internet of Things (IoT) and cloud and fog Computing that have provided the required infrastructure and connectivity to collect and analyze data from users and physical environment for cognitive decision‐making. This article analyzes different stages of DMSs, and existing IoT solutions are also discussed that are focused on prevention, preparation, response, and recovery from disasters. It also proposes a context‐aware fog‐based IoT architecture to realize a cognitive DMS that can learn from the collected and synthesized data to reduce the impact of catastrophic events by taking immediate actions. Furthermore, the significance of the architecture is validated in different scenarios and inherent open research challenges are emphasized.
Methodology for material property determination
Authors: Yang Fengchang , Rippe Christian , Hodges Jonathan , Lattimer Brian 
Published: May 2019

SummaryPredicting solid material pyrolysis requires numerous parameters/properties that are time consuming and difficult to measure. Multiobjective optimization techniques have been used to determine these parameters; however, a methodology for the types of tests needed for the optimization and parameters that should be optimized versus measured has not been fully established. This study investigated combinations of testing protocols and parameters for optimization to determine a testing and optimization methodology that results in the accurate parameters. A Shuffled Complex Evolution (SCE) optimization routine was used to determine parameters based on some parameters being known (ie, measured) and others being determined through optimization and different combinations of types of input data. The results indicate that material testing should be done at three different heating rates in a thermogravimetric analyzer (TGA) and at three different heat fluxes in the cone calorimeter. The TGA tests and two cone calorimeter tests are input into the SCE optimization routine to determine the remaining parameters. The third cone calorimeter test is used to validate the parameters determined using the methodology. The method provides parameters within 20% of the actual parameters input into the Fire Dynamics Simulator (FDS) virtual experiment models. This method is applied to Polymethyl methacrylate (PMMA) experimental data to prove effectiveness.
Variable spaced particle in mesh‐free method to handle wave‐floating body interactions
Authors: Rijas A.S. , Sriram V. , Yan S. 
Published: May 2019

SummaryIn this work, the motion of a two‐dimensional rectangular freely floating body under waves is simulated using Improved Meshless Local Petrov‐Galerkin method with Rankine Source function (IMLPG_R) with variable spacing resolutions. The IMLPG_R method is a particle method that solves Navier–Stokes equations using the fractional step method to capture the wave properties. However, many existing particle methods are computationally intensive to model the wave‐floating body due to the requirement of fine particles, needing uniform distribution throughout the domain. To improve the computational efficiency and capture the body response properly, variable spaced particle distribution with fine resolution near the floating body and coarse resolution far from the body is implemented. Numerical schemes to handle variable resolutions are reported. An iterative scheme to handle the wave‐floating body is implemented in the particle method. Two test cases, one with small wave and another with steep waves, are simulated for uniform particle distribution and the result shows good agreement with literature. Based on this, the performance of the variable spaced particle distribution is tested in coupling with floating body solver. The application of the method for wave impact load from the green water loading of the floating structure is also simulated.
Liver safety evaluation of endothelin receptor antagonists using HepatoPac®: A single model impact assessment on hepatocellular health, function and bile acid disposition
Authors: Aleo Michael D. , Ukairo Okechukwu , Moore Amanda , Irrechukwu Onyi , Potter David M. , Schneider Richard P. 
Published: May 2019

AbstractMarketed (bosentan, ambrisentan) and discontinued (sitaxsentan, CI‐1034) endothelin receptor antagonists were examined in the human micropatterned hepatocyte co‐culture (MPCC) model HepatoPac®. Differences across hepatocellular health (cellular adenosine triphosphate/glutathione content), function (urea production/albumin secretion) and taurocholic acid transport (biliary clearance/excretion index) were compared using amiodarone and ciclosporin A as positive controls. Ambrisentan had the weakest potency in all six endpoints, while sitaxsentan, bosentan and CI‐1034 had more potent effects on hepatobiliary transport than health/function endpoints. Normalization to clinical Cmax gave the following relative rank order of safety based on margins for each endpoint: ambrisentan ≥ CI‐1034 ~ bosentan > sitaxsentan. These data suggested impaired hepatobiliary disposition might contribute to a more prominent role in liver injury associated within sensitive human populations exposed to these compounds than direct hepatocellular toxicity. Rat, dog and monkey MPCCs also showed greater sensitivity potential to disrupted hepatobiliary disposition compared with hepatocellular health/functional endpoints. Drug metabolism competency was exhibited across all species. In vivo, rats and dogs appear more resistant to transaminase elevations and/or histological evidence of liver injury caused by these mechanisms even at exceedingly high systemic exposures relative to sensitive humans. Rats and dogs are resistant to hepatobiliary toxicants due to physiological differences in bile composition/handling. Although traditional animal testing provides adequate safety coverage for advancement of novel pharmaceuticals into clinical trials, supplemental assays employing human MPCCs may strengthen weight‐of‐evidence predictions for sensitive human populations. Proving the predictive value of this single impact assessment model in advance of clinical trial information for human liver injury risk is needed across more pharmaceuticals.
MicroRNA‐326 suppresses iNOS expression and promotes autophagy of dopaminergic neurons through the JNK signaling by targeting XBP1 in a mouse model of Parkinson's disease
Authors: Zhao Xiao‐Hui , Wang Yong‐Bing , Yang Juan , Liu Hui‐Qin , Wang Ling‐Ling 
Published: May 2019

AbstractParkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, and substantia nigra is primarily one of the damaged brain regions. Evidence indicates that microRNAs (miRNAs) is involved in the pathophysiology of this disease. The present study aimed to investigate the biological function of miR‐326 in PD through the JNK signaling pathway by targeting X‐box binding protein 1 (XBP1). After liposome complexes were prepared, healthy male C57BL/6 mice were selected to construct a mouse model of PD. The targeting relationship between miR‐326 and XBP1 was confirmed. The expression of miR‐326 and XBP1 was measured in PD mice, and gain‐ and loss‐function assay was conducted to examine the regulatory effect of miR‐326 and XBP1 on inducible nitric oxide synthase (iNOS) expression and autophagy of dopaminergic neurons of PD mice. Mice treated with miR‐326 mimic and siRNA‐XBP1 showed increased traction test scores, activation of autophagy, expression of LC3‐II, c‐Jun, and p‐α‐Syn, but diminished climbing time and expressions of iNOS, α‐Syn, and p‐c‐Jun. The siRNA‐XBP1 treatment could reverse the effect of miR‐326 inhibitor on PD mice. Overexpression of miR‐326 inhibits iNOS expression and promotes autophagy of dopaminergic neurons through JNK signaling by targeting XBP1.
Overexpression of miR‐224‐3p alleviates apoptosis from cerebral ischemia reperfusion injury by targeting FIP200
Authors: Deng Yiming , Ma Gaoting , Dong Qihao , Sun Xuan , Liu Lian , Miao Zhongrong , Gao Feng 
Published: May 2019

AbstractAimsIn previous studies, numerous differential microRNAs (miRNAs) in cerebral ischemic/reperfusion (I/R) injury were identified using the miRNA microarray analysis. However, the relationship between miRNA and cerebral I/R injury remains largely unknown. In this study, we investigated the function and explored the possible mechanism of miR‐224‐3p in cerebral I/R injury.MethodsOxygen glucose deprivation model in N2a cells were used to perform the cerebral I/R injury in vitro. Trypan blue staining, reactive oxygen species (ROS) production, and caspase‐3 were measured to evaluate the function of miR‐224‐3p.ResultsOverexpression of miR‐224‐3p alleviated the apoptosis induced by oxygen glucose deprivation (OGD) and cleaved caspase‐3 was significantly reduced. We further provided the possible mechanism that miR‐224‐3p may protect cells from cerebral I/R injury by targeting FAK family‐interacting protein (FIP200). Further rescue experiment proved that overexpression of FIP200 partially blocked the effect of miR‐224‐3p.ConclusionsWe evaluated the function and mechanism of miR‐224‐3p in ischemic brain injury. miR‐224‐3p may serve as a potential target for new therapeutic intervention.
Transcriptomic analysis reveals the molecular mechanism of Alzheimer‐related neuropathology induced by sevoflurane in mice
Authors: Ge Xing , Zhang Ying , Zuo Yong , Israr Muhammad , Li Bowen , Yu Peng , Gao Guofen , Chang Yan‐Zhong , Shi Zhenhua 
Published: May 2019

AbstractAnesthetics could induce cognitive dysfunctions, such as Alzheimer's disease in humans or mice. However, the precise molecular mechanism is unclear. Sevoflurane is a common anesthetic widely used in clinical practice. Here, we demonstrated the induction of cognitive dysfunction induced by Sev in mice to corroborate the signaling pathway and the differentially expressed genes (DEGs) followed by analyzing their functions. The cognitive function of mice was measured by the Morris water maze test. Transcriptomic data were annotated with Illumina HiSeq. 2000. Further, the changes in related proteins or genes were analyzed by western blotting and real‐time quantitative polymerase chain reaction. Our results showed that Sev could cause a decline in cognitive competence in mice. The transcriptomic data indicated that adding up to 566 genes were upregulated and 1073 genes were downregulated. The genes of Plin4, Lcn2, Lrg1, Foxf1, and Ctla2a were significantly upregulated, while the genes of Arc, Npas4, Egr2, Hes5, and Cdh9 were downregulated dramatically. The Gene Ontology term with the highest enrichment of DEGs are involved in the regulation of cellular and macromolecule metabolism and cation and nucleic acid binding, respectively. The Kyoto encyclopedia of genes and genomes analysis indicated that the mitogen‐activated protein kinases (MAPK) pathway was one of the most important metabolic pathways. In addition, the metabolic pathways related to cognitive function, such as the nervous system and neurodegenerative disease showed significant changes. Furthermore, we found that p38, c‐Jun N‐terminal kinase, and extracellular signal‐regulated kinase of the MAPK signaling pathway played important roles in this process. In conclusion, these results provide the first important clues for identifying the DEGs and signaling pathways in the hippocampus due to a Sev‐induced cognitive deficiency in mice.
SOD1 in amyotrophic lateral sclerosis development – in silico analysis and molecular dynamics of A4F and A4V variants
Authors: Da Silva Aloma Nogueira Rebello , Pereira Gabriel Rodrigues Coutinho , Moreira Lorena Giannini Alves , Rocha Catielly Ferreira , De Mesquita Joelma Freire 
Published: May 2019

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized by the selective loss of motor neurons. Approximately 5% to 10% of patients with ALS have a family history of the disease, and approximately 20% of familial amyotrophic lateral sclerosis (fALS) cases are associated with mutations in Cu/Zn superoxide dismutase (SOD1). In this study, we evaluated the structural and functional effects of human A4F and A4V SOD1 protein mutations. We performed an in silico analysis using prediction algorithms of nonsynonymous single‐nucleotide polymorphisms (nsSNPs) associated with the fALS development. Our structural conservation results show that the mutations analyzed (A4V and A4F) were in a highly conserved region. Molecular dynamics simulations using the Linux GROMACS package revealed how these mutations affect protein structure, protein stability, and aggregation. These results suggest that there might be an effect on the SOD1 function. Understanding the molecular basis of disease provides new insights useful for rational drug design and advancing our understanding of the ALS development.
Effects of Pro1266Leu mutation on structure and function of glycoprotein Ib binding domain of von Willebrand factor
Authors: Naqvi Ahmad Abu Turab , Alajmi Mohamed F. , Rehman Tabish , Hussain Afzal , Hassan Imtaiyaz 
Published: May 2019

AbstractGlycoprotein Ibα (GpIbα) binding ability of A1 domain of von Willebrand factor (vWF) facilitates platelet adhesion that plays a crucial role in maintaining hemostasis and thrombosis at the site of vascular damage. There are both “loss as well as gain of function” mutations observed in this domain. Naturally occurring “gain of function” mutations leave self‐activating impacts on the A1 domain which turns the normal binding to characteristic constitutive binding with GPIbα. These “gain of function” mutations are associated with the von Willebrand disease type 2B. In recent years, studies focused on understanding the mechanism and conformational patterns attached to these phenomena have been conducted, but the conformational pathways leading to such binding patterns are poorly understood as of now. To obtain a microscopic picture of such events for the better understanding of pathways, we used molecular dynamics (MD) simulations along with principal component analysis and normal mode analysis to study the effects of Pro1266Leu (Pro503Leu in structural context) mutation on the structure and function of A1 domain of vWF. MD simulations have provided atomic‐level details of intermolecular motions as a function of time to understand the dynamic behavior of A1 domain of vWF. Comparative analysis of the trajectories obtained from MD simulations of both the wild type and Pro503Leu mutant suggesting appreciable conformational changes in the structure of mutant which might provide a basis for assuming the “gain of function” effects of these mutations on the A1 domain of vWF, resulting in the constitutive binding with GpIbα.