bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoproteasome subunit β5i regulates diet‐induced atherosclerosis through altering MERTK‐mediated efferocytosis in Apoe knockout mice
Authors: Liao Jiawei , Xie Yunpeng , Lin Qiuyue , Yang Xiaolei , An Xiangbo , Xia Yunlong , Du Jie , Wang Feng , Li Hui‐Hua 
Published: November 2019

AbstractThe immunoproteasome contains three catalytic subunits (β1i, β2i and β5i) that are important modulators of immune cell homeostasis. A previous study showed a correlation between β5i and human atherosclerotic plaque instability; however, the causative role of β5i in atherosclerosis and the underlying mechanisms remain unknown. Here we explored this issue in apolipoprotein E (Apoe) knockout (eKO) mice with genetic deletion or pharmacological inhibition of β5i. We found that β5i expression was upregulated in lesional macrophages after an atherogenic diet (ATD). β5i/Apoe double KO (dKO) mice fed on the ATD had a significant decrease in both lesion area and necrotic core area, compared with eKO controls. Moreover, dKO mice had less caspase‐3+ apoptotic cell accumulation but enhanced efferocytosis of apoptotic cells and increased expression of Mer receptor tyrosine kinase (MERTK). Consistently, similar phenotypes were observed in eKO mice transplanted with dKO bone marrow or treated with β5i‐specific inhibitor PR‐957. Mechanistic studies in vitro revealed that β5i deletion reduced IκBα degradation and inhibited NF‐κB activation, promoting Mertk transcription and efferocytosis, thereby attenuating apoptotic cell accumulation. In conclusion, we demonstrate that β5i plays an important role in diet‐induced atherosclerosis by altering MERTK‐mediated efferocytosis. β5i might be a potential pharmaceutical target against atherosclerosis. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Oral Anticoagulant Prescription Trends, Profile Use, and Determinants of Adherence in Patients with Atrial Fibrillation
Authors: Perreault Sylvie , de Denus Simon , White‐Guay Brian , Côté Robert , Schnitzer Mireille E. , Dubé Marie‐Pierre , Dorais Marc , Tardif Jean‐Claude 
Published: November 2019

Background and PurposeData on oral anticoagulant (OAC) uptake and pattern of use are limited. Real‐life data in patients with atrial fibrillation (AF) are important for understanding patient exposure. A cohort study of new OAC users was built to assess trends of drug use from 2011 to 2017, persistence rate, switching rate, adherence level, and predictors of adherence.MethodsWe built a cohort using the Régie d’Assurance Maladie du Québec (RAMQ) and Med‐Echo administrative databases of new adult OAC users within 1 year following hospitalization with a diagnosis of AF. New users of OAC were defined as having no OAC claims in the year before cohort entry. We assessed trends of OAC use; persistence rate, defined as a gap between refills of no longer than two times the duration of the previous prescriptions; and adherence level, defined as the proportion of days covered (PDC) over a 1‐year period following initiation. Predictors of nonadherence (PDC less than 80%) were analyzed using logistic regression models.ResultsThe cohort consisted of 33,311 incident OAC users. Of total OAC claims, the proportions of warfarin claims decreased from 77.9% in 2011 to 12.7% in 2017, with direct oral anticoagulants (DOACs) accounting for 87.3% of claims, of which apixaban and rivaroxaban accounted for 60.1% and 23.4%, respectively, by the end of 2017. One year after OAC initiation, persistence rates ranged from 53% with warfarin to 77% with a high dose of apixaban. Approximately 75% of incident OAC users were considered “adherent” (PDC 80% or more), with a mean PDC of 95.6–98.1%, compared with “nonadherent,” with a mean PDC varying between 43.1% and 50.7%. Older age, female sex, higher CHA2DS2‐VASc score (to predict thromboembolic risk in AF), prior stroke, and treatment with chronic cardiovascular disease drugs were associated with high adherence levels.ConclusionThe clinical uptake of DOACs increased over time, accounting for 87.3% of prescriptions in 2017. In our study, 25% of new OAC users presented a low adherence level. Adherence to OACs remains a significant challenge in patients with AF.
Aquatic treadmill walking at three depths of water in people with traumatic brain injury
Authors: Narasaki‐Jara Mai , Wagatsuma Mayumi , Holt Jacob Lee , Acuña Stephan Manuel , Vrongistinos Konstantinos , Jung Taeyou 
Published: November 2019

AbstractObjectiveThe purpose of this study was to analyse kinematic and spatiotemporal gait characteristics of aquatic treadmill walking among three different depths of water in individuals with traumatic brain injury.MethodsA total of 13 individuals with traumatic brain injury participated in the study and completed walking trials at three different depths as follows: waist, chest, and neck level, which was adjusted by a movable floor pool. A self‐selected comfortable walking speed at the waist level was used as a matched speed for all walking trials. Participants completed three aquatic treadmill walking trials under each of the three water depths. Each participant's gait was captured by a customized underwater motion analysis system and processed by a two‐dimensional motion analysis software.ResultsThe repeated measures analysis of variance showed significant differences in spatiotemporal and joint kinematic variables across three conditions: stance swing ratio (p = .023), peak hip flexion (p = .001), hip range of motion (p = .047), and peak ankle dorsiflexion (p = .000). Various water properties in conjunction with motor impairments might have contributed to alterations in gait kinematics.ConclusionOur findings suggest that walking in neck‐depth water may not be ideal for gait training as it appears to limit hip flexion and ankle dorsiflexion. It is recommended that waist to chest‐depth water be used to provide an accommodating environment for aquatic gait rehabilitation.
Systematic exploration of predicted destabilizing nonsynonymous single nucleotide polymorphisms (nsSNPs) of human aldehyde oxidase: A Bio‐informatics study
Authors: Coelho Catarina , Muthukumaran Jayaraman , Santos‐Silva Teresa , João Romão Maria 
Published: November 2019

AbstractAldehyde Oxidase (hAOX1) is a cytosolic enzyme involved in the metabolism of drugs and xenobiotic compounds. The enzyme belongs to the xanthine oxidase (XO) family of Mo containing enzyme and is a homo‐dimer of two 150 kDa monomers. Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) of hAOX1 have been reported as affecting the ability of the enzyme to metabolize different substrates. Some of these nsSNPs have been biochemically and structurally characterized but the lack of a systematic and comprehensive study regarding all described and validated nsSNPs is urgent, due to the increasing importance of the enzyme in drug development, personalized medicine and therapy, as well as in pharmacogenetic studies. The objective of the present work was to collect all described nsSNPs of hAOX1 and utilize a series of bioinformatics tools to predict their effect on protein structure stability with putative implications on phenotypic functional consequences. Of 526 nsSNPs reported in NCBI‐dbSNP, 119 are identified as deleterious whereas 92 are identified as nondeleterious variants. The stability analysis was performed for 119 deleterious variants and the results suggest that 104 nsSNPs may be responsible for destabilizing the protein structure, whereas five variants may increase the protein stability. Four nsSNPs do not have any impact on protein structure (neutral nsSNPs) of hAOX1. The prediction results of the remaining six nsSNPs are nonconclusive. The in silico results were compared with available experimental data. This methodology can also be used to identify and prioritize the stabilizing and destabilizing variants in other enzymes involved in drug metabolism.
Development of a Bacillus thuringiensis based dsRNA production platform to control sacbrood virus in Apis cerana
Authors: Park Min G , Kim Woo J , Choi Jae Y , Kim Jong H , Park Dong H , Kim Jun Y , Wang Minghui , Je Yeon H 
Published: November 2019

AbstractBACKGROUNDSacbrood virus (SBV) is a fatal viruses that infects the Asian honey bee, Apis cerana in Korea. Recently, RNA interference (RNAi) has been suggested as a promising strategy for the suppression of honey bee viruses. For the efficient control of SBV infection using RNAi, simple and cost‐effective methods to produce double‐stranded RNA (dsRNA) are needed.RESULTSTo develop a dsRNA production platform using Bacillus thuringiensis (Bt), pBTdsSBV‐VP1 vector was constructed in which the SBV vp1 gene was located between two oppositely oriented cyt promoters. Both strands of the vp1 gene were bidirectionally transcribed under the control of the sporulation‐dependent cyt promoter in Bt cells transformed with pBTdsSBV‐VP1, and the resulting dsRNA was easily extracted from the Bt transformant, Bt 4Q7/pBTdsSBV‐VP1, by inducing its autolysis. The replication of SBV was dramatically suppressed in A. cerana workers who ingested the dsRNA produced from the Bt 4Q7/pBTdsSBV‐VP1.CONCLUSIONIn this study, we successfully silenced SBV in its host, A. cerana, by the application of exogenous dsRNA produced from an entomopathogenic bacteria, Bt. These results suggested that Bt could be a useful dsRNA production platform to control viral pathogens in their host insects. © 2019 Society of Chemical Industry
Identification of potential candidate genes controlling pea aphid tolerance in a Pisum fulvum high‐density integrated DArTseq SNP‐based genetic map
Authors: Barilli Eleonora , Carrillo‐Perdomo Estefanía , Cobos Maria José , Kilian Andrzej , Carling Jason , Rubiales Diego 
Published: November 2019

AbstractBACKGROUNDPea (Pisum sativum) is one of the most important temperate grain legumes in the world, and its production is severely constrained by the pea aphid (Acyrthosiphon pisum). Wild relatives, such as P. fulvum, are valuable sources of allelic diversity to improve the genetic resistance of cultivated pea species against A. pisum attack. To unravel the genetic control underlying resistance to the pea aphid attack, a quantitative trait loci (QTL) analysis was performed using the previously developed high density integrated genetic linkage map originated from an intraspecific recombinant inbred line (RIL) population (P. fulvum: IFPI3260 × IFPI3251).RESULTSWe accurately evaluated specific resistance responses to pea aphid that allowed the identification, for the first time, of genomic regions that control plant damage and aphid reproduction. Eight QTLs associated with tolerance to pea aphid were identified in LGs I, II, III, IV and V, which individually explained from 17.0% to 51.2% of the phenotypic variation depending on the trait scored, and as a whole from 17.0% to 88.6%. The high density integrated genetic linkage map also allowed the identification of potential candidate genes co‐located with the QTLs identified.CONCLUSIONSOur work shows how the survival of P. fulvum after the pea aphid attack depends on the triggering of a multi‐component protection strategy that implies a quantitative tolerance. The genomic regions associated with the tolerance responses of P. fulvum during A. pisum infestation have provided six potential candidate genes that could be useful in marker‐assisted selection (MAS) and genomic assisted breeding (GAB) after functional validation in the future. © 2019 Society of Chemical Industry
Semi‐idealized simulations of wintertime flows and pollutant transport in an Alpine valley. Part II: Passive tracer tracking
Authors: Sabatier Tiphaine , Largeron Yann , Paci Alexandre , Lac Christine , Rodier Quentin , Canut Guylaine , Masson Valéry 
Published: November 2019

AbstractUnder wintertime quiescent conditions, thermally driven circulations represent one of the only sources of tracer dispersion over mountainous terrain. Those circulations can be unequally developed at a valley scale since they strongly depend on local morphological arrangement. At the same time, very heterogeneous pollutant distribution can be observed, as for instance in a French Alpine basin located in the Arve River valley. This complex basin regularly shows large variations in pollutant concentrations with certain sectors suffering from poor wintertime air quality. On the other hand, the surrounding tributary valleys appear to be less affected, suggesting that the basin local dynamics may participate in pollutant trapping. The present study intends to classify the pollutant transport mechanisms in terms of efficiency and to identify the most dynamically vulnerable atmospheric volumes regarding pollutant accumulation. This is achieved through a set of semi‐idealized high‐resolution numerical simulations reproducing a full diurnal cycle with passive tracers released continuously at a constant rate. The model is used as a laboratory in order to quantify the influence of several processes on transport mechanism efficiency. This approach underlines the high efficiency of vertical transport by anabatic winds while horizontal transport efficiency by up‐valley wind systems remains weak, leaving the surrounding tributary valleys almost unaffected by the basin pollution during daytime. At night, the efficiency of horizontal transport by the down‐valley wind systems depends on the tracer source location within the basin. In addition, the tracers emitted within the tributary valleys do not reach the basin bottom because of thermal stratification and local morphological arrangement but rather degrade the air quality of mid‐altitude villages lying along the basin sidewalls.
Laser spectroscopy steered 13C‐labelling of plant material in a walk‐in growth chamber
Authors: Slaets Johanna I. F. , Resch Christian , Mayr Leopold , Weltin Georg , Heiling Maria , Gruber Roman , Dercon Gerd 
Published: November 2019

RationaleCarbon‐13 (13C)‐labelled plant material forms the basis for experiments elucidating soil organic carbon dynamics and greenhouse gas emissions. Quantitative field‐scale tracing is only possible if plants are labelled homogeneously in large quantities. By using a laser spectrometer to automatically steer the isotopic ratio in the chamber, it is possible to obtain large amounts of homogeneously labelled plant material.MethodsNinety‐six maize plants were labelled for 25 days until tassel formation in a 15 m3 walk‐in growth chamber with a continuous air δ13C‐CO2 value of 400‰. A Los Gatos Research laser absorption spectrometer controlled the ambient δ13C‐CO2 value in the chamber through steering of the mass flow controllers with 13C‐enriched and natural abundance CO2 gas.ResultsLaser absorption spectroscopy steering kept the δ13C value of chamber air between 368 and 426‰. The resulting 1 kg dry matter of 13C‐labelled shoots showed an average δ13C value of 384‰ and accuracy of 8‰ (half width of the 95% confidence interval). Only the oldest leaves showed larger heterogeneity. The growth chamber eliminated variability between plants. The δ13C value of the stabile material did not differ significantly from that of bulk material.ConclusionsLaser spectroscopy controlled 13C labelling of plants in a walk‐in growth chamber successfully kept the isotopic ratio of the CO2 in the chamber air constant. Therefore, large quantities of material were labelled homogeneously at the inter‐ and intra‐plant level, thus establishing a method to provide high‐quality input for quantitative isotopic tracer studies.
Single-cell high-content imaging parameters predict functional phenotype of cultured human bone marrow stromal stem cells
Authors: Kowal Justyna M. , Schmal Hagen , Halekoh Ulrich , Hjelmborg Jacob B. , Kassem Moustapha 
Published: November 2019

AbstractCultured human bone marrow stromal (mesenchymal) stem cells (hBM-MSCs) are heterogenous cell populations exhibiting variable biological properties. Quantitative high-content imaging technology allows identification of morphological markers at a single cell resolution that are determinant for cellular functions. We determined the morphological characteristics of cultured primary hBM-MSCs and examined their predictive value for hBM-MSC functionality. BM-MSCs were isolated from 56 donors and characterized for their proliferative and differentiation potential. We correlated these data with cellular and nuclear morphological features determined by Operetta; a high-content imaging system. Cell area, cell geometry, and nucleus geometry of cultured hBM-MSCs exhibited significant correlation with expression of hBM-MSC membrane markers: ALP, CD146, and CD271. Proliferation capacity correlated negatively with cell and nucleus area and positively with cytoskeleton texture features. In addition, in vitro differentiation to osteoblasts as well as in vivo heterotopic bone formation was associated with decreased ratio of nucleus width to length. Multivariable analysis applying a stability selection procedure identified nuclear geometry and texture as predictors for hBM-MSCs differentiation potential to osteoblasts or adipocytes. Our data demonstrate that by employing a limited number of cell morphological characteristics, it is possible to predict the functional phenotype of cultured hBM-MSCs and thus can be used as a screening test for “quality” of hBM-MSCs prior their use in clinical protocols.Significance statement Clinical trials employing cultured human bone marrow mesenchymal stem cells (hBM-MSCs) demonstrate the presence of a large inter-donor variability in biological functions and clinical efficacy. By applying high-content imaging methodology to cultured BM-MSCs obtained from a large cohort of donors, morphological features including cell area and nucleus geometry as predictors for cell differentiation and proliferation were identified. These parameters can serve as selection criteria for BM-MSC populations to be used in clinical trials of enhancing bone regeneration.
Introducing LIVA to measure long‐term firm performance
Authors: Wibbens Phebo D. , Siggelkow Nicolaj 
Published: November 2019

ABSTRACTResearch summaryThis article introduces a new measure of long‐term firm performance: long‐term investor value appropriation (LIVA). This measure helps to address a disconnect between the common theoretical assumption that managers optimize firm value, and the widespread empirical practice of measuring performance using short‐term ratios such as return on assets (ROA). LIVA can lead to markedly different strategic insights compared to commonly used measures such as ROA and cumulative abnormal returns. For instance, the widely cited finding of a U‐shaped relation between acquisition experience and performance turns out to be largely driven by short‐term stock price movements and vanishes when using 10‐year LIVA.Managerial summaryManagers have a large number of performance measures at their disposal, such as return on assets, total shareholder returns, and earnings before interest and taxes. However, these short‐term measures do not capture well whether a firm creates long‐term shareholder value, which is one of the primary objectives for most firms. Addressing that gap, this article introduces a new measure called long‐term investor value appropriation (LIVA). LIVA can be constructed using publicly available stock market data and it can help managers to better analyze historical long‐term performance.
The noncanonical BMP signaling pathway plays an important role in club cell regeneration
Authors: Shafiquzzaman Md , Biswas Soma , Li Ping , Mishina Yuji , Li Baojie , Liu Huijuan 
Published: November 2019

Abstract
The bronchiole is a major site for the development of several life-threatening disorders, including chronic obstructive pulmonary disease and lung adenocarcinomas. The bronchiolar epithelium is composed of club cells and ciliated epithelial cells, with club cells serving as progenitor cells. Presently, the identity of the cells involved in regeneration of bronchiolar epithelium and the underlying mechanisms remain incompletely understood. Here, we show that Prrx1, a homeobox transcription factor, can mark club cells in adult mice during homeostasis and regeneration. We further show that the noncanonical signaling pathway of BMPs, BMPR1A-Tak1-p38MAPK, plays a critical role in club cell regeneration. Ablation of Bmpr1a, Tak1, or Mapk14 (encoding p38α) in Prrx1+ club cells caused minimal effect on bronchiolar epithelium homeostasis, yet it resulted in severe defects in club cell regeneration and bronchiole repair in adult mice. We further show that this pathway supports proliferation and expansion of the regenerating club cells. Our findings thus identify a marker for club cells and reveal a critical role for the BMP noncanonical pathway in club cell regeneration.
Photographic validation of target versus nontarget take of brown treesnake baits
Authors: Siers Shane R. , Shiels Aaron B. , Payne Cynthia G. , Chlarson Francine M. , Clark Craig S. , Mosher Stephen M. 
Published: November 2019

ABSTRACTUse of toxic baits or other tools for managing nuisance species must ensure that the species of interest is adequately targeted while exposure to nontarget species is minimized. Nontarget takes of acetaminophen‐laced baits for control of invasive brown treesnakes (Boiga irregularis) on Guam may put those animals at risk of lethal intoxication and render the bait unavailable to the intended target species. We used wildlife cameras to identify species removing toxic and nontoxic baits from brown treesnake bait stations designed to exclude nontarget taxa in 2015 and 2016. Throughout various sites and habitat types, and balanced by season (wet vs. dry), we monitored 512 bait stations. From those, 140 of the baits were taken and the species taking the bait was successfully identified. Brown treesnakes took 124 (88.6%) of the baits, 13 (9.3%) were taken by small coconut crabs (Birgus latro), and 3 (2.1%) were taken by monitor lizards (Varanus indicus). The greatest incidence of nontarget bait takes was by small coconut crabs at 2 adjacent sites atop the same cliff line during a single season; 96.9% of bait takes at all other sites were by brown treesnakes. Bait takes by brown treesnakes were particularly infrequent (2.3%) at sites associated with endangered swiftlet (Aerodramus bartschi) caves where intensive snake control was employed. Although the majority of baits in bait stations are taken by brown treesnakes, local and temporal pulses in nontarget species activity, particularly by crabs, may bias results, which would not be accounted for without supplemental validation by cameras. © 2019 The Authors. Wildlife Society Bulletin published by Wiley Periodicals, Inc. on behalf of The Wildlife Society. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
Evaluating a mustard extraction technique for sampling earthworms
Authors: Starking Melissa D. , Roloff Gary J. 
Published: November 2019

ABSTRACTWe examined efficacy of a mustard extraction technique for quantifying earthworm occupancy and density using a mesocosm experiment. In May 2017, we placed 12 earthworms from 2 ecological groups (6 surface dwelling [epigeic] and 6 deep dwelling [anecic]) into mesocosms (0.144 m2 surface area) constructed from soils typically found in northern hardwood forests of Michigan, USA. We evaluated 2 soil depths (15 and 30 cm) and a soil moisture gradient (dry to wet). We found occupancy of epigeic earthworms was accurately portrayed 92% of the time through leaf searches, and subsequent mustard phase did not improve accuracy. For anecic earthworms, we found that occupancy was accurately portrayed 50% of the time through leaf searches and mustard phase increased accuracy to 92%. We found that mustard extraction produced 0–83% (median = 50%) of epigeic earthworms available for capture, with most recovered through leaf searches (median = 42%). We found that mustard extraction produced 0–67% (median = 33%) of anecic earthworms available for capture, with most (median = 20%) recovered during the mustard phase. Our results lend support for using mustard extraction as a technique for quantifying occupancy of epigeic and anecic earthworms, but caution that density estimates are likely low. © 2019 The Wildlife Society.