bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atomic structures of the RNA end-healing 5′-OH kinase and 2′,3′-cyclic phosphodiesterase domains of fungal tRNA ligase: conformational switches in the kinase upon binding of the GTP phosphate donor
Authors: Banerjee Ankan , Goldgur Yehuda , Schwer Beate , Shuman Stewart 
Published: November 2019

AbstractFungal tRNA ligase (Trl1) rectifies RNA breaks with 2′,3′-cyclic-PO4 and 5′-OH termini. Trl1 consists of three catalytic modules: an N-terminal ligase (LIG) domain; a central polynucleotide kinase (KIN) domain; and a C-terminal cyclic phosphodiesterase (CPD) domain. Trl1 enzymes found in all human fungal pathogens are untapped targets for antifungal drug discovery. Here we report a 1.9 Å crystal structure of Trl1 KIN-CPD from the pathogenic fungus Candida albicans, which adopts an extended conformation in which separate KIN and CPD domains are connected by an unstructured linker. CPD belongs to the 2H phosphotransferase superfamily by dint of its conserved central concave β sheet and interactions of its dual HxT motif histidines and threonines with phosphate in the active site. Additional active site motifs conserved among the fungal CPD clade of 2H enzymes are identified. We present structures of the Candida Trl1 KIN domain at 1.5 to 2.0 Å resolution—as apoenzyme and in complexes with GTP•Mg2+, IDP•PO4, and dGDP•PO4—that highlight conformational switches in the G-loop (which recognizes the guanine base) and lid-loop (poised over the nucleotide phosphates) that accompany nucleotide binding.
Current status of official WeChat accounts for public health education
Authors: Sun Mingwei , Yang Liuna , Chen Wanna , Luo Hao , Zheng Kaiqiao , Zhang Yan , Lian Tingyu , Yang Yunbin , Ni Jingdong 
Published: November 2019

Abstract

Background
To investigate the current use status of official WeChat accounts for the Centers for Disease Control and Prevention in public health education and relevant factors that can impact the effectiveness of message delivery.

Methods
A retrospective survey was conducted to evaluate the effectiveness of official WeChat accounts. About 531 official WeChat accounts and 50 939 articles were analyzed using a cluster sampling survey design. The Kruskal–Wallis test and multivariate logistic regression were used to explore factors associated with the usefulness of the number of views and “Likes” of the articles.

Results
The study identified a total of 531 public WeChat accounts, including 19 province-level accounts, 179 municipal-level accounts and 333 county-level accounts. In the univariable analysis, the administrative level of the account, article order, time segment, article originality and thematic category were associated with the number of views and “Likes.” Province-level accounts, first articles, the 5:00–6:00 time segment, original articles and theme 3 (emergencies) had higher numbers of views and “Likes” than the others (P &lt; 0.05).

Conclusions
Promoting health education through Official WeChat account is an effective, sustainable and feasible strategy. Potential indicators of the impact of public health education suggest that administrators should effectively use official WeChat accounts for public health education.
Association of obstructive sleep apnea and cerebral small vessel disease: a systematic review and meta-analysis
Authors: Huang Yuhong , Yang Chunsong , Yuan Ruozhen , Liu Ming , Hao Zilong 
Published: November 2019

AbstractStudy ObjectivesThe objective of the present study was to investigate the association between obstructive sleep apnea (OSA) and the presence of various neuroimaging marker of cerebral small vessel disease (CSVD).MethodsWe systematically searched PubMed, Embase, Web of Science, Scopus, and Cochrane library (from inception to May 2019) for studies evaluating the association between OSA and CSVD, which included white matter hyperintensities (WMH), silent brain infarction (SBI), cerebral microbleeds (CMBs), and perivascular spaces (PVS). Pooled odds ratios (ORs) with 95% confidence interval (CIs) were estimated using random-effects meta-analysis.ResultsAfter screening 7290 publications, 20 studies were finally included involving 6036 subjects. The sample size ranged from 27 to 1763 (median 158, interquartile range: 67–393). The meta-analysis showed that moderate to severe OSA was positively associated with WMH (13 studies, n = 4412, OR = 2.23, 95% CI = 1.53 to 3.25, I2 = 80.3%) and SBI (12 studies, n = 3353, OR 1.54, 95% CI = 1.06 to 2.23, I2 = 52%). There was no association with CMBs (three studies, n = 342, OR = 2.17, 95% CI = 0.61 to 7.73, I2 = 60.2%) or PVS (two studies, n = 267, OR = 1.56, 95% CI = 0.28 to 8.57, I2 = 69.5%). There was no relationship between mild OSA and CSVD.ConclusionCurrent evidence suggests that moderate to severe sleep apnea is positively related to WMH and SBI, but not CMBs or PVS, which suggests that OSA may contribute to the pathogenesis of CSVD. Further large cohort studies should be prioritized to confirm the findings.
Passive Smoking and Disease Severity in Childhood Pneumonia Under 5 Years of Age
Authors: Sismanlar Eyuboglu Tugba , Aslan Ayse Tana , Kose Mehmet , Pekcan Sevgi , Hangul Melih , Gulbahar Ozlem , Cingirt Mehmet , Bedir Demirdag Tuga , Tezer Hasan , Budakoglu Isıl Irem 
Published: November 2019

Abstract

Objective
To objectively investigate the effect of passive smoking on pneumonia and disease severity in children aged less than 5 years by using cotinine as an indicator of passive smoking.

Methods
Between December 2015 and April 2016, children aged less than 5 years with pneumonia and age-matched healthy controls were included in this study, which was conducted at three tertiary pediatric pulmonology centers. A questionnaire was given to the parents regarding demographic data and smoking status at home. Urinary cotinine/creatinine ratio (CCR) was measured. The data from the pneumonia and control groups, as well as children with mild and severe pneumonia within the pneumonia group, were compared.

Results
A total of 227 subjects were included in the study; there were 74 children in the pneumonia group and 153 in the control group. The mean age of all the children was 33.4 ± 1.28 months. Of all subjects, 140 were male and 102 were exposed to passive smoking by their parents at home. There were statistically significant differences in age, number of people in the home, and mother’s and father’s age between the control and pneumonia groups (p &lt; 0.05). No difference was found in the CCR in the control and pneumonia group (p &gt; 0.05). Age and urinary CCR were significantly different between children with mild and severe pneumonia (p &lt; 0.05).

Conclusion
We showed that passive smoking exposure was associated with the development of severe pneumonia in children. Further studies are needed to examine the underlying cause in detail.
Chloroplast cold-resistance is mediated by the acidic domain of the RNA binding protein CP31A
Authors: Okuzaki Ayako , Lehniger Marie-Kristin , Muino Jose M , Lenzen Benjamin , Rühe Thilo , Leister Dario , Ohler Uwe , Schmitz-Linneweber Christian 
Published: November 2019

AbstractChloroplast RNA metabolism is characterized by long-lived mRNAs that undergo a multitude of post-transcriptional processing events. Chloroplast RNA accumulation responds to environmental cues, foremost light and temperature. A large number of nuclear-encoded RNA-binding proteins (RBPs) are required for chloroplast RNA metabolism, but we do not yet know how chloroplast RBPs convert abiotic signals into gene expression changes. Previous studies showed that the chloroplast ribonucleoprotein 31A (CP31A) is required for the stabilization of multiple chloroplast mRNAs in the cold, and that the phosphorylation of CP31A at various residues within its N-terminal acidic domain (AD) can alter its affinity for RNAin vitro. Loss of CP31A leads to cold sensitive plants that exhibit bleached tissue at the center of the vegetative rosette. Here, by applying RIP-Seq, we demonstrated that CP31A shows increased affinity for a large number of chloroplast RNAsin vivoin the cold. Among the main targets of CP31A were RNAs encoding subunits of the NDH complex and loss of CP31A lead to reduced accumulation ofndhtranscripts. Deletion analyses revealed that cold-dependent RNA binding and cold resistance of chloroplast development both depend on the AD of CP31A. Together, our analysis established the AD of CP31A as a key mediator of cold acclimation of the chloroplast transcriptome.One sentence summaryCold exposure induces increased RNA association of the RRM protein CP31A, which mediates cold-resistance ofArabidopsis thalianavia its acidic domain
Stathmin-2 Mediates Glucagon Secretion from Pancreatic α-Cells
Authors: Asadi Farzad , Dhanvantari Savita 
Published: November 2019

AbstractInhibition of glucagon hypersecretion from pancreatic α-cells is an appealing strategy for the treatment of diabetes. Our hypothesis is that proteins that associate with glucagon within alpha cell secretory granules will regulate glucagon secretion, and may provide druggable targets for controlling abnormal glucagon secretion in diabetes. Recently, we identified a dynamic glucagon interactome within the secretory granules of the α cell line, αTC1-6, and showed that select proteins within the interactome could modulate glucagon secretion. In the present study, we show that one of these interactome proteins, the neuronal protein stathmin-2, is expressed in aTC1-6 cells and in mouse pancreatic alpha cells, and is a novel regulator of glucagon secretion. Stathmin-2 was co-secreted with glucagon in response to 55 mM K+, and immunofluorescence confocal microscopy showed co-localization of stathmin-2 with glucagon and the secretory granule markers chromogranin A and VAMP-2 in αTC1-6 cells. In mouse pancreatic islets, Stathmin-2 co-localized with glucagon, but not with insulin, indicating that it is an alpha cell protein. To show a function for stathmin-2 in regulating glucagon secretion, we showed that siRNA - mediated depletion of stathmin-2 in aTC1-6 cells caused glucagon secretion to become constitutive without any effect on proglucagon mRNA levels, while overexpression of stathmin-2 completely abolished both basal and K+-stimulated glucagon secretion. Overexpression of stathmin-2 increased the localization of glucagon into the endosomal-lysosomal compartment, while depletion of stathmin-2 reduced the endosomal localization of glucagon. Therefore, we describe stathmin-2 as having a novel role as an alpha cell secretory granule protein that modulates glucagon secretion via trafficking through the endosomal-lysosomal system. These findings describe a potential new pathway for the regulation of glucagon secretion, and may have implications for controlling glucagon hypersecretion in diabetes.
Background radiation impacts human longevity and cancer mortality: Reconsidering the linear no-threshold paradigm
Authors: David Elroei , Wolfson Marina , Fraifeld Vadim E. 
Published: November 2019

AbstractBACKGROUNDThe current linear-no-threshold paradigm assumes that any exposure to ionizing radiation carries some risk, thus every effort should be made to maintain the exposures as low as possible. Here, we examined whether background radiation impacts human longevity and cancer mortality.METHODSOur data covered the entire US population of the 3139 US counties, encompassing over 320 million people. The data on background radiation levels, the average of 5-year age-adjusted cancer mortality rates, and life expectancy for both males and females in each county, was extracted using publicly available tools from official sources, and analyzed with JMP®™ software.RESULTSWe found for the first time that life expectancy, the most integrative index of population health, was approximately 2.5 years longer in people living in areas with a relatively high vs. low background radiation (≥ 180 mrem/year and ≤ 100 mrem/year, respectively; p < 0.005; 95% confidence interval [CI]). This radiation-induced lifespan extension could to a great extent be associated with the decrease in cancer mortality rate observed for several common cancers (lung, pancreas and colon cancers for both genders, and brain and bladder cancers for males only; p < 0.05; 95% CI).CONCLUSIONSExposure to a high background radiation displays clear beneficial health effects in humans. These hormetic effects provide strong evidence for re-considering the linear no-threshold paradigm, at least within the natural range of low-dose radiation.
Varstation: a complete and efficient tool to support NGS data analysis
Authors: Faria ACO , Caraciolo MP , Minillo RM , Almeida TF , Pereira SM , Cervato MC , Filho JBO 
Published: November 2019

AbstractSummaryVarstation is a cloud-based NGS data processor and analyzer for human genetic variation. This resource provides a customizable, centralized, safe and clinically validated environment aiming to improve and optimize the flow of NGS analyses and reports related with clinical and research genetics.Availability and implementationVarstation is freely available at http://varstation.com, for academic use.Contactcontact@varstation.comSupplementary informationSupplementary data are available at Bioinformatics online.
Fibrotic human lung extracellular matrix as a disease-specific substrate for 3D in-vitro models of pulmonary fibrosis
Authors: Germanguz Igal , Aranda Evelyn , Xiong Jennifer C. , Kissel Natalia , Nichols Alexandra , Gadee Eddie , O’Neill John D. 
Published: November 2019

ABSTRACTIdiopathic pulmonary fibrosis (IPF) is an irreversible and uniformly fatal lung disease marked by destruction and scarring of the lung parenchyma and progressive loss of respiratory function. IPF affects nearly 3 million people worldwide, and annual mortality in the US alone exceeds 40,000. Nintedanib and pirfenidone, the only drugs approved for the treatment of IPF, slow progression but do not cure the disease. Consequently, there is a pressing need for effective treatments beside lung transplantation. Unfortunately, predictive models of IPF are not available, underscoring the critical need for physiologically relevant in-vitro substrates that enable quantitative and mechanistic studies of human IPF. Here we report the development and characterization of a human pulmonary fibrosis-specific cell culture substrate comprised of intact fibrotic lung extracellular matrix that recapitulates the human IPF disease environment in vitro. We document the activation and disease-specific phenotype of human lung fibroblasts cultured in the IPF disease-specific substrate, and establish feasibility of testing antifibrotic agents using this substrate. Altogether, our results demonstrate the applicability of this fibrosis-specific substrate for 3D in-vitro models of IPF and cell-based assays in early-stage drug discovery.
A minimal synaptic model for direction selective neurons inDrosophila
Authors: Zavatone-Veth Jacob A. , Badwan Bara A. , Clark Damon A. 
Published: November 2019

AbstractVisual motion estimation is a canonical neural computation. InDrosophila, recent advances have identified anatomical and functional circuitry underlying direction-selective computations. Models with varying levels of abstraction have been proposed to explain specific experimental results, but have rarely been compared across experiments. Here we construct a minimal, biophysically inspired synaptic model forDrosophila’s first-order direction-selective T4 cells using the wealth of available anatomical and physiological data. We show how this model relates mathematically to classical models of motion detection, including the Hassenstein-Reichardt correlator model. We used numerical simulation to test how well this synaptic model could reproduce measurements of T4 cells across many datasets and stimulus modalities. These comparisons include responses to sinusoid gratings, to apparent motion stimuli, to stochastic stimuli, and to natural scenes. Without fine-tuning this model, it sufficed to reproduce many, but not all, response properties of T4 cells. Since this model is flexible and based on straightforward biophysical properties, it provides an extensible framework for developing a mechanistic understanding of T4 neural response properties. Moreover, it can be used to assess the sufficiency of simple biophysical mechanisms to describe features of the direction-selective computation and identify where our understanding must be improved.
Suppression of Docetaxel induced apoptosis in Survivin-depleted cells due to failure of sustained mitotic block
Authors: Han Teng-Long , Sha Hang , Jiang Zhi-Xin 
Published: November 2019

AbstractThe antitumor effect of taxanes have been attributed to their ability to induce mitotic arrest through activation of the spindle assembly checkpoint. Cell death following prolonged mitotic arrest is mediated by the intrinsic apoptosis pathway. Accordingly, factors that influence the robustness of mitotic arrest or disrupt the apoptotic machinery might confer drug resistance. Survivin is an inhibitor of apoptosis protein. Its overexpression has been associated with resistance to multiple anticancer agents including taxanes, and its targeting led to drug sensitization. On the other hand, Survivin is a key regulator of mitosis, which is shown to be required for stable activation of the spindle assembly checkpoint. Since the sensitivity of taxanes depends on a functional spindle checkpoint, inhibition of Survivin may lead to drug resistance, which is the opposite effect of its anti-apoptotic function. Here we show that Survivin-depleted cells escape the mitotic block following Docetaxel treatment, thereby evading drug induced apoptosis. Moreover, Survivin depletion increases the level of mitotic catastrophe and cellular senescence induced by Docetaxel and enhanced its efficacy against clonogenic survival of tumor cells. Our finding suggests that inhibition of Survivin promotes non-apoptotic mechanisms following Docetaxel treatment rather than increases the sensitivity of apoptosis.
Working capital management and firm performance in China
Authors: Ren Ting , Liu Nan , Yang Hongyan , Xiao Youzhi , Hu Yijun 
Published: November 2019

Purpose
The purpose of this paper is to examine the relationship between working capital management (WCM) and firm performance in the context of the Chinese economy. Specifically, it investigates the effects of ownership structures as an internal factor and of institutional environments (IE) as an external factor shaping this relationship.

Design/methodology/approach
The study applies two-way fixed effect regression models to a sample of Chinese listed manufacturing firms for the period of 2010 to 2017. WCM is measured by cash conversion cycles (CCC); profitability is measured by core profit ratios; ownership structures are classified based on state-owned enterprises (SOEs) and non-SOEs; and IEs are measured from dimensions of factor markets (FM) and legal systems (LS).

Findings
First, the results show a negative relationship between CCC and firm performance. Second, the negative relationship between CCC and profitability is significant for non-SOEs but not for SOEs. Third, both the FM and LS strengthen the negative association between CCC and profitability. Fourth, the moderating effect of FMs and LSs is evident for non-SOEs only. The results hold when using alternative measures of WCM and profitability and while controlling for additional variables.

Originality/value
The current study shows that while WCM has a significant effect on the profitability of Chinese firms, such an effect greatly depends on the ownership structures and IE involved. The results thus offer important implications in helping the Chinese government create better IEs and in allowing manufacturing firms to improve upon their WCM practices.
Consumer acceptance of food obtained from olive by-products
Authors: Perito Maria Angela , Di Fonzo Antonella , Sansone Marcello , Russo Carlo 
Published: November 2019

Purpose
The purpose of this paper is to evaluate the market potential of food obtained from olive by-products. The marketing of such by-products (e.g. olive leaves and pulp) is a challenging opportunity for the sustainable development of the sector. Yet, consumer demand is still poorly understood. The paper contributes to filling the knowledge gap with an empirical survey of a sample of Italian consumers.

Design/methodology/approach
The authors provide an assessment of consumers’ willingness to accept (WTA) food from olive by-products. The authors collected structured questionnaire from a sample of 289 Italian consumers. The authors asked to consumers their willingness to try a variety of food products containing olive by-products, as a proxy for their WTA the products. In order to investigate the drivers of the average WTA, the authors used the information in the questionnaire to build four constructs of interest: technophobia, neophobia, perception of benefits and awareness about sustainable consumption. The choice of the constructs and the variables was driven by the existing literature.

Findings
The paper shows how the WTA food with olive by-products is a general attitude of the consumer, rather than product-specific choice. The results suggest that consumers perceive the use of olive by-products as a new technology for preparing well-known food products. The authors did not find statistical evidence of the wariness of olive by-products as new food products. Technophobia is the most important factor hampering the marketing of olive by-products.

Originality/value
The paper is a first attempt of exploring the topic of WTA food with olive by-products.