bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of abnormal muscle forces on prenatal joint morphogenesis in mice
Authors: Sotiriou Vivien , Rolfe Rebecca A , Murphy Paula , Nowlan Niamh C 
Published: June 2019

AbstractFetal movements are essential for normal development of the human skeleton. When fetal movements are reduced or restricted, infants are at higher risk of developmental dysplasia of the hip and arthrogryposis (multiple joint contractures). Joint shape abnormalities have been reported in mouse models with abnormal or absent musculature, but the effects on joint shape in such models have not been quantified or characterised in detail. In this study, embryonic mouse forelimbs and hindlimbs at a single developmental stage (Theiler Stage 23) with normal, reduced or absent muscle were imaged in 3D. Skeletal rudiments were virtually segmented and rigid image registration was used to reliably align rudiments with each other, enabling repeatable assessment and measurement of joint shape differences between normal, reduced-muscle and absent muscle groups. We demonstrate qualitatively and quantitatively that joint shapes are differentially affected by a lack of, or reduction in, skeletal muscle, with the elbow joint being the most affected of the major limb joints. Surprisingly, the effects of reduced muscle were often more pronounced than those of absent skeletal muscle, indicating a complex relationship between muscle mass and joint morphogenesis. These findings have relevance for human developmental disorders of the skeleton in which abnormal fetal movements are implicated, particularly developmental dysplasia of the hip and arthrogryposis.
Bioactivity of curcumin on the cytochrome P450 enzymes of the steroidogenic pathway
Authors: Rodríguez Castaño Patricia , Parween Shaheena , Pandey Amit V 
Published: June 2019

AbstractTurmeric, a popular ingredient in the cuisine of many Asian countries, comes from the roots of theCurcuma longaand is known for its use in Chinese and Ayurvedic medicine. Turmeric is rich in curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcuminoids have potent wound healing, anti-inflammatory, and anti-carcinogenic activities. While curcuminoids have been studied for many years, not much is known about their effects on steroid metabolism. Since many anti-cancer drugs target enzymes from the steroidogenic pathway, we tested the effect of curcuminoids on cytochrome P450 CYP17A1, CYP21A2, and CYP19A1 enzyme activities. When using 10 µg/ml of curcuminoids, both the 17α-hydroxylase as well as 17,20 lyase activities of CYP17A1 were reduced significantly. On the other hand, only a mild reduction in CYP21A2 activity was observed. Furthermore, CYP19A1 activity was also reduced up to ~20% of control when using 1-100 µg/ml of curcuminoids in a dose-dependent manner. Molecular docking studies confirmed that curcumin could dock into the active sites of CYP17A1, CYP19A1 as well as CYP21A2. In CYP17A1 and CYP19A1, curcumin docked within 2.5 Å of central heme while in CYP21A2 the distance from heme was 3.4 Å, which is still in the same range or lower than distances of bound steroid substrates. These studies suggest that curcuminoids may cause inhibition of steroid metabolism, especially at higher dosages. Also, the recent popularity of turmeric powder as a dilatory supplement needs further evaluation for the effect of curcuminoids on steroid metabolism. Molecular structure of curcuminoids could be modified to generate better lead compounds with inhibitory effects on CYP17A1 and CYP19A1 for potential drugs against prostate cancer and breast cancer.
Effects of the estrous cycle and ovarian hormones on cue-triggered motivation and intrinsic excitability of medium spiny neurons in the Nucleus Accumbens of female rats
Authors: Alonso-Caraballo Yanaira , Ferrario Carrie R. 
Published: June 2019

AbstractNaturally occurring alterations in estradiol influence food intake in females. However, how motivational responses to food cues are affected by the estrous cycle or ovarian hormones is unknown. In addition, while individual susceptibility to obesity is accompanied by enhanced incentive motivational responses to food cues and increased NAc intrinsic excitability in males, studies in females are absent. Here, we examined basal differences in intrinsic NAc excitability of obesity-prone vs. obesity-resistant females and determined how conditioned approach (a measure of cue-triggered motivation), food intake, and motivation for food vary with the cycle in naturally cycling female obesity-prone, obesity-resistant, and outbred Sprague-Dawley rats. Finally, we used ovariectomy followed by hormone treatment to determine the role of ovarian hormones in cue-triggered motivation in selectively-bred and outbred female rats. We found that intrinsic excitability of NAc MSNs and conditioned approach are enhanced in female obesity-prone vs. obesity-resistant rats. These effects were driven by greater MSN excitability and conditioned approach behavior during metestrus/diestrus vs. proestrus/estrus in obesity-prone but not obesity-resistant rats, despite similar regulation of food intake and food motivation by the cycle in these groups. Furthermore, estradiol and progesterone treatment reduced conditioned approach behavior in obesity-prone and outbred Sprague-Dawley females. To our knowledge, these data are the first to demonstrate cycle- and hormone-dependent effects on the motivational response to a food cue, and the only studies to date to determine how individual susceptibility to obesity influences NAc excitability, cue-triggered food-seeking, and differences in the regulation of these neurobehavioral responses by the cycle.
Acid exposure impairs mucus secretion and disrupts mucus transport in neonatal piglet airways
Authors: Liao Yan Shin J. , Kuan Shin Ping , Guevara Maria V. , Collins Emily N. , Atanasova Kalina R. , Dadural Joshua S. , Vogt Kevin , Schurmann Veronica , Reznikov Leah R. 
Published: June 2019

ABSTRACTTenacious mucus produced by tracheal and bronchial submucosal glands is a defining feature of cystic fibrosis (CF). Although airway acidification occurs early in CF, whether transient acidification is sufficient to initiate mucus abnormalities is unknown. We studied mucus secretion and mucus transport in piglets forty-eight hours following an intra-airway acid challenge. Acid-challenged piglet airways were distinguished by increased mucin 5B (MUC5B) in the submucosal gland but decreased lung lavage fluid MUC5B, following in vivo cholinergic stimulation, suggesting a failure in submucosal gland secretion. Concomitantly, intrapulmonary airways were obstructed with glycoprotein rich material under both basal and methacholine-stimulated conditions. To mimic a CF-like environment, we also studied mucus secretion and transport under diminished bicarbonate and chloride transport conditions ex vivo. Cholinergic stimulation in acid-challenged piglet airways induced extensive mucus films, greater mucus strand formation, increased dilation of submucosal gland duct openings and decreased mucociliary transport. Finally, to elucidate potential mediators of acid-induced mucus defects, we investigated diminazene aceturate, a small molecule that inhibits the acid-sensing ion channel (ASIC). Diminazene aceturate restored surface MUC5B in acid-challenged piglet airways under basal conditions, mitigated acid-induced airway obstruction, and magnified the number of dilated submucosal gland duct openings. These findings suggest that even transient airway acidification early in life might have profound impacts on mucus secretion and transport properties. Further they highlight diminazene aceturate as an agent that might be beneficial in alleviating certain mucus defects in CF airway disease.One sentence summaryEarly life airway acidification has profound impacts on mucus secretion and transport.
Natural genetic variation screen inDrosophilaidentifies Wnt signaling, mitochondrial metabolism, and redox homeostasis genes as modifiers of apoptosis
Authors: Palu Rebecca A.S. , Ong Elaine , Stevens Kaitlyn , Chung Shani , Owings Katie G. , Goodman Alan G. , Chow Clement Y. 
Published: June 2019

ABSTRACTApoptosis is the primary cause of degeneration in a number of neuronal, muscular, and metabolic disorders. These diseases are subject to a great deal of phenotypic heterogeneity in patient populations, primarily due to differences in genetic variation between individuals. This creates a barrier to effective diagnosis and treatment. Understanding how genetic variation influences apoptosis could lead to the development of new therapeutics and better personalized treatment approaches. In this study, we examine the impact of the natural genetic variation in theDrosophilaGenetic Reference Panel (DGRP) on two models of apoptosis-induced retinal degeneration: overexpression ofp53orreaper(rpr). We identify a number of known apoptotic, neural, and developmental genes as candidate modifiers of degeneration. We also use Gene Set Enrichment Analysis (GSEA) to identify pathways that harbor genetic variation that impact these apoptosis models, including Wnt signaling, mitochondrial metabolism, and redox homeostasis. Finally, we demonstrate that many of these candidates have a functional effect on apoptosis and degeneration. These studies provide a number of avenues for modifying genes and pathways of apoptosis-related disease.
ASFVdb: An integrative resource for genomics and proteomics analyses of African swine fever
Authors: Zhu Zhenglin , Meng Geng 
Published: June 2019

AbstractThe recent outbreaks of African swine fever (ASF) in China and Europe have threatened the swine industry globally. To control the transmission of the African swine fever virus (ASFV), we developed ASFVdb, the African swine fever virus database, an online data visualization and analysis platform for comparative genomics and proteomics. On the basis of known ASFV genes, ASFVdb reannotates the genomes of every strain and annotates 4833 possible ORFs. Moreover, ASFVdb performs a thorough analysis of the population genetics of all the published genomes of ASFV strains and performs functional and structural predictions for all genes. For each ASFV gene, visitors can obtain not only basic information of the gene but also the distribution of the gene in strains, conserved or high mutation regions, possible subcellular location of the gene and topology of the gene. In the genome browser, ASFVdb provides sliding window population genetics analysis results, which facilitate genetics and evolutional analyses at the genomic level. The web interface is constructed based on SWAV 1.0. ASFVdb is freely accessible athttp://asfvdb.popgenetics.net.
Using Machine Learning to Identify True Somatic Variants from Next-Generation Sequencing
Authors: Wu Chao , Zhao Xiaonan , Welsh Mark , Costello Kellianne , Cao Kajia , Tayoun Ahmad Abou , Li Marilyn , Sarmady Mahdi 
Published: June 2019

AbstractBackgroundMolecular profiling has become essential for tumor risk stratification and treatment selection. However, cancer genome complexity and technical artifacts make identification of real variants a challenge. Currently, clinical laboratories rely on manual screening, which is costly, subjective, and not scalable. Here we present a machine learning-based method to distinguish artifacts from bona fide Single Nucleotide Variants (SNVs) detected by NGS from tumor specimens.MethodsA cohort of 11,278 SNVs identified through clinical sequencing of tumor specimens were collected and divided into training, validation, and test sets. Each SNV was manually inspected and labeled as either real or artifact as part of clinical laboratory workflow. A three-class (real, artifact and uncertain) model was developed on the training set, fine-tuned using the validation set, and then evaluated on the test set. Prediction intervals reflecting the certainty of the classifications were derived during the process to label “uncertain” variants.ResultsThe optimized classifier demonstrated 100% specificity and 97% sensitivity over 5,587 SNVs of the test set. 1,252 out of 1,341 true positive variants were identified as real, 4,143 out of 4,246 false positive calls were deemed artifacts, while only 192(3.4%) SNVs were labeled as “uncertain” with zero misclassification between the true positives and artifacts in the test set.ConclusionsWe presented a computational classifier to identify variant artifacts detected from tumor sequencing. Overall, 96.6% of the SNVs received a definitive label and thus were exempt from manual review. This framework could improve quality and efficiency of variant review process in clinical labs.
Phosphorylation of Ser111 in Rab8a modulates Rabin8 dependent activation by perturbation of side chain interaction networks
Authors: Pourjafar-Dehkordi Danial , Vieweg Sophie , Itzen Aymelt , Zacharias Martin 
Published: June 2019

AbstractGTPases are key-players in cellular signaling processes. Phosphorylation of Rab proteins, which belong to the Ras superfamily of small GTPases regulating intracellular transport, has recently been implicated in the pathogenesis of Parkinson Disease (PD). For Rab8a, it was shown that serine 111 phosphorylation (pS111) is dependent on the protein kinase PINK1, and that mimicking the phosphorylation at S111 by a serine/glutamate substitution (S111E) impaired Rab8a activation by its cognate nucleotide exchange factor (GEF) Rabin8. Here, we performed comparative Molecular Dynamics and free energy simulations on Rab8a and Rab8a:Rabin8 complexes to elucidate the molecular details on how pS111 and S111E may influence the interaction with Rabin8. The simulations indicate that S111E and pS111 establish an intramolecular interaction with arginine 79 (R79). In the complex, this interaction persists, and therefore perturbs a favorable intermolecular salt-bridge contact between R79 in Rab8a and the acidic aspartate 187 (D187) in Rabin8. Binding free analysis reveals that S111E and pS111, as well as the mutation R79A, in Rab8a drastically reduce the binding affinity to Rabin8. Combining the R79A mutation with S111E or pS111, respectively, nearly diminishes Rab8a-Rabin8 binding. In vitro experiments confirm our computational results showing that the nucleotide exchange rates of the respective Rab8a mutants are decreased by >80% in the presence of Rabin8 compared to wild type. In addition to specific insights into how S111 phosphorylation of Rab8a can influence GEF-mediated activation, the simulations demonstrate how side chain modifications in general can allosterically influence the network of surface side chain interactions between binding partners.
Meta-analysis of Gene Expression Microarray Datasets in Chronic Obstructive Pulmonary Disease
Authors: Rogers Lavida R. K. , Verlinde Madison , Mias George I. 
Published: June 2019

AbstractChronic obstructive pulmonary disease (COPD) was classified by the Centers for Disease Control and Prevention in 2014 as the 3rd leading cause of death in the United States (US). The main cause of COPD is exposure to tobacco smoke and air pollutants. Problems associated with COPD include under-diagnosis of the disease and an increase in the number of smokers worldwide. The goal of our study is to identify disease variability in the gene expression profiles of COPD subjects compared to controls. We used pre-existing, publicly available microarray expression datasets to conduct a meta-analysis. Our inclusion criteria for microarray datasets selected for smoking status, age and sex of blood donors reported. Our datasets used Affymetrix, Agilent microarray platforms (7 datasets, 1,262 samples). We re-analyzed the curated raw microarray expression data using R packages, and used Box-Cox power transformations to normalize datasets. To identify significant differentially expressed genes we ran an analysis of variance with a linear model with disease state, age, sex, smoking status and study as effects that also included binary interactions. We found 1,513 statistically significant (Benjamini-Hochberg-adjusted p-value <0.05) differentially expressed genes with respect to disease state (COPD or control). We further filtered these genes for biological effect using results from a Tukey test post-hoc analysis (Benjamini-Hochberg-adjusted p-value <0.05 and 10% two-tailed quantiles of mean differences between COPD and control), to identify 304 genes. Through analysis of disease, sex, age, and also smoking status and disease interactions we identified differentially expressed genes involved in a variety of immune responses and cell processes in COPD. We also trained a logistic regression model using the 304 genes as features, which enabled prediction of disease status with 84% accuracy. Our results give potential for improving the diagnosis of COPD through blood and highlight novel gene expression disease signatures.
Examining the shared development of socialist political economics with Chinese characteristics
Authors: Liu Can 
Published: June 2019

Purpose
The shared development concept is crucial for the construction of a socialist political economy with Chinese characteristics. The paper aims to discuss this issue.

Design/methodology/approach
This is because shared development constitutes the logic thread of the socialist political economy with Chinese characteristics and the core for the formation and development of its whole system.

Findings
China’s modernization is well underway and is following a unique path with its own characteristics, whereby shared development is undoubtedly one of its core values.

Originality/value
In the new era, the development path under the concept of shared development of socialism with Chinese characteristics must adhere to the all-round development of human beings, promote social equity and justice via development, and embrace inclusive growth, specifically, pro-poor growth.
Recapitulation of the relationship between economic thoughts and realities
Authors: Liang Hua 
Published: June 2019

Purpose
It is rather common for China’s current academic circles to use western doctrines that originated in situ to explain China’s economic problems, a suspicion of scenario misplacement may thus arise. The root cause lies in the lack of reflection about the current relationship between economic thoughts and realities. The paper aims to discuss these issues.

Design/methodology/approach
Correctly understanding economic thoughts associated with the brand of “that era” and effectively deducing its characteristics is of great significance to finding new features of this era and constructing new ideas with the characteristics of “this era.”

Findings
This motif is exactly the keynote on which to base the study of economic history and economic thought.

Originality/value
In a period of major historical turning points, the economic realities on which the economic thinking about that era (the era of economists) relied was undergoing major changes, and re-emphasizing the ancient topic of the relationship between economic thoughts and economic realities became particularly urgent.
Converging HRM practices? A comparison of high performance work system practices in MNC subsidiaries and domestic firms in Pakistan
Authors: Ahmad Mansoor , Allen Matthew M.C. , Raziq Muhammad Mustafa , ur Rehman Wali 
Published: June 2019

PurposeExisting work on convergence/divergence among HRM practices in MNCs and local firms mainly focuses on Europe and the USA. Limited research examines these organizations in Pakistan, hindering our understanding of what policies MNCs are likely to adopt there as well as the extent of any differences between HRM in MNC subsidiaries and local firms. The purpose of this paper is to examine the similarities and differences between the HRM practices of MNC subsidiaries and domestic firms to assess if there is evidence for convergence or divergence.Design/methodology/approachThe authors targeted MNC subsidiaries and domestically owned firms working in the banking, information technology and pharmaceutical sectors in Pakistan. These sectors have enjoyed a steady inflow of foreign direct investment and have a sizeable number of MNC subsidiaries. Out of 1,081 companies, some 392 participated in a face-to-face survey (response rate of 36.4 percent). The authors ran a series of binary logistic regression models to test the hypothesized relationships between HR practices and nationality of ownership.FindingsThe authors reveal that a small minority of both types of firm use some practices, such as high compensation contingent on performance and performance review, appraisal and career development. However, domestic firms use some practices, such as extensive training, performance appraisals and performance-related pay significantly less than their multinational counterparts. The authors argue that these differences reflect institutional influences in Pakistan as well as a potential opportunity for local firms to change their HRM practices. In other areas, such as recruitment and employee involvement, there are no differences between the two groups.Originality/valueThe authors deepen our understanding of the types of HR practices that local companies in an emerging economy are likely to adopt as well as those that they are unlikely to adopt. Existing research has tended to downplay HRM in Pakistan and the different use of individual HRM practices among MNC subsidiaries and local firms. This research reveals that some companies in Pakistan have sophisticated HRM practices in place in some areas; however, MNC subsidiaries make greater use of some HR practices, reflecting different cultural norms between the two groups.
Support for supervisors: HR enabling flexible work
Authors: Williams Penelope 
Published: June 2019

PurposeFlexible work arrangements (FWAs) are routinely offered in organizational policy, yet employee access to FWAs is highly dependent upon support from their immediate supervisor. There is little empirical research that specifically investigates the role of the human resource function (HR) in supporting managers to implement FWA policy. Through the lens of HR systems theory, the purpose of this paper is to examine how HR supports managers to implement FWAs.Design/methodology/approachUsing a case study in the Australian Insurance industry, this paper analyzes corporate documents and interviews with 47 managers, supervisors and HR staff across four diverse business units.FindingsThis study identifies supervisors’ perceived ability to implement FWAs as a potential barrier to utilization. Five mechanisms of HR support to overcome perceived barriers are identified in the data. An HR system that enables managers to support FWAs requires alignment of HR policies; the provision of supportive technology; an HR structure that facilitates proactive advice and support; HR business partners with influence; and managerial training on FWAs.Practical implicationsThis paper provides HR practitioners with insights into the mechanisms that can support managers to implement FWAs or other devolved HR policies.Originality/valueApplying HR systems theory, this case study utilizes the perspectives of senior managers, supervisors and HR staff to explain how the HR function supports or constrains managers in the effective implementation of FWAs.