bluuebunny/crossref_metadata_2025_split huggingface dataset:
The gut microbiota of rural and urban individuals is shaped by geography and lifestyle
Authors: Kabwe Mubanga Hellen , Vikram Surendra , Mulaudzi Khodani , Jansson Janet K. , Makhalanyane Thulani P. 
Published: March 2020

AbstractUnderstanding the structure and drivers of gut microbiota remains a major ecological endeavour. Recent studies have shown that several factors including diet, lifestyle and geography may substantially shape the human gut microbiota. However, most of these studies have focused on the more abundant bacterial component and comparatively less is known regarding fungi in the human gut. This knowledge deficit is especially true for rural and urban African populations. Therefore, we assessed the structure and drivers of rural and urban gut mycobiota. Our participants (n=100) were balanced by geography and sex. The mycobiota of these geographically separated cohorts was characterized using amplicon analysis of the Internal Transcribed Spacer (ITS) gene. We further assessed biomarker species specific to rural and urban cohorts. In addition to phyla which have been shown to be ubiquitous constituents of gut microbiota, Pichia were key constituents of the mycobiota. We found that several factors including geographic location and lifestyle factors such as the smoking status were major drivers of gut mycobiota. Linear discriminant and the linear discriminant analysis effect size analysis revealed several distinct urban and rural biomarkers. Together, our analysis reveals distinct community structure in urban and rural South African individuals. Geography and lifestyle related factors were shown to be key drivers of rural and urban gut microbiota.ImportanceThe past decade has revealed substantial insights regarding the ecological patterns of gut microbiomes. These studies have shown clear differences between the microbiomes of individuals living in urban and rural locations. Yet, in contrast to bacteria we know substantially less regarding the fungal gut microbiota (mycobiome). Here we provide the first insights regarding the mycobiome of individuals from urban and rural locations. We show that these communities are geographically structured. Further we show that lifestyle factors, such as diet and smoking, are strong drivers explaining community variability.
Orally Bioavailable Endochin-like Quinolone Carbonate Ester Prodrug ReducesToxoplasma gondiiBrain Cysts
Authors: Doggett J. Stone , Schultz Tracey , Miller Alyssa J. , Bruzual Igor , Pou Sovitj , Winter Rolf , Dodean Rozalia , Zakharov Lev N. , Nilsen Aaron , Riscoe Michael K , Carruthers Vern B 
Published: March 2020

AbstractToxoplasmosis is a potentially fatal infection for immunocompromised people and the developing fetus. Current medicines for toxoplasmosis have high rates of adverse effects that interfere with therapeutic and prophylactic regimens. Endochin-like quinolones (ELQs) are potent inhibitors ofToxoplasma gondiiproliferationin vitroand in animal models of acute and latent infection. ELQ-316, in particular, was found to be effective orally against acute toxoplasmosis in mice and highly selective for theT. gondiicytochromebover the human cytochromeb. Despite oral efficacy, the high crystallinity of ELQ-316 limits oral absorption, plasma concentrations and therapeutic potential. A carbonate ester prodrug of ELQ-316, ELQ-334, was created to decrease crystallinity and increase oral bioavailability, which resulted in a six-fold increase in bothCmax(maximum plasma concentration) and AUC (area under the curve) of ELQ-316. The increased bioavailability of ELQ-316, when administered as ELQ-334, resulted in greater efficacy than the equivalent dose of ELQ-316 against acute toxoplasmosis and had similar efficacy against latent toxoplasmosis compared to intraperitoneal administration of ELQ-316. Carbonate ester prodrugs are a successful strategy to overcome the limited oral bioavailability of ELQs for the treatment of toxoplasmosis.
Efficacy of Guanabenz Combination Therapy Against Chronic Toxoplasmosis Across Multiple Mouse Strains
Authors: Martynowicz Jennifer , Doggett J. Stone , Sullivan William J. 
Published: March 2020

AbstractToxoplasma gondii, an obligate intracellular parasite that can cause life-threatening acute disease, differentiates into a quiescent cyst stage to establish lifelong chronic infections in animal hosts, including humans. This tissue cyst reservoir, which can reactivate into an acute infection, is currently refractory to clinically available therapeutics. Recently, we and others have discovered drugs capable of significantly reducing brain cyst burden in latently infected mice, but not to undetectable levels. In this study, we examined the use of novel combination therapies possessing multiple mechanisms of action in mouse models of latent toxoplasmosis. Our drug regimens included combinations of pyrimethamine, clindamycin, guanabenz, and endochin-like quinolones (ELQs), and were administered to two different mouse strains in an attempt to eradicate brain tissue cysts. We observed mouse strain-dependent effects with these drug treatments: pyrimethamine + guanabenz showed synergistic efficacy in C57BL/6 mice, yet did not improve upon guanabenz monotherapy in BALB/c mice. Contrary to promisingin vitroresults demonstrating toxicity to bradyzoites, we observed an antagonistic effect between guanabenz + ELQ-334in vivo. While we were unable to completely eliminate brain cyst burden, we found that a combination treatment of ELQ-334 + pyrimethamine impressively reduced brain cysts to 95% in C57BL/6 mice, which approaches the limit of detection. These analyses highlight the importance of evaluating anti-infective drugs in multiple mouse strains and will help inform further preclinical cocktail therapy studies designed to treat chronic toxoplasmosis.
Genome regulation and gene interaction networks inferred from muscle transcriptome underlying feed efficiency in Pigs
Authors: Carmelo Victor AO. , Kadarmideen Haja N. 
Published: March 2020

AbstractImprovement of feed efficiency (FE) is key for sustainability and cost reduction in pig production. Our aim was to characterize the muscle transcriptomic profiles in Danbred Duroc (Duroc) and Danbred Landrace (Landrace), in relation to FE for identifying potential biomarkers. RNA-seq data was analyzed employing differential gene expression methods, gene-gene interaction and network analysis, including pathway and functional analysis. We compared the results with genome regulation in human exercise data. In the differential expression analysis, 13 genes were differentially expressed, including:MRPS11, MTRF1, TRIM63, MGAT4A, KLH30. Based on a novel gene selection method, the divergent count, we performed pathway enrichment analysis. We found 5 significantly enriched pathways related to feed conversion ratio (FCR). These pathways were mainly mitochondrial, and summarized in the mitochondrial translation elongation (MTR) pathway. In the gene interaction analysis, highlights include the mitochondrial genes: PPIF, MRPL35, NDUFS4and the fat metabolism and obesity genes:AACS, SMPDL3B, CTNNBL1, NDUFS4andLIMD2. In the network analysis, we identified two modules significantly correlated with FCR. Pathway enrichment of modules identified MTR, electron transport chain and DNA repair as enriched pathways. In the network analysis, the mitochondrial gene groupNDUFwas a key hub group, showing potential as biomarkers. Comparing with human transcriptomic exercise studies, genes related to exercise displayed enrichment in our FCR related genes. We conclude that mitochondrial activity is a driver for FCR in muscle tissue, and mitochondrial genes could be potential biomarkers for FCR in pigs. We hypothesize that increased FE mimics processes triggered in exercised muscle.
Anti-Insulin receptor antibodies improve hyperglycaemia in a mouse model of human insulin receptoropathy
Authors: Brierley Gemma V , Webber Hannah , Rasijeff Eerika , Grocott Sarah , Siddle Kenneth , Semple Robert K 
Published: March 2020

AbstractLoss-of-function mutations in both alleles of the human insulin receptor gene (INSR) cause extreme insulin resistance (IR) and usually death in childhood, with few therapeutic options. Bivalent anti-receptor antibodies can elicit insulin-like signaling by mutant INSR in cultured cells, but whether this translates into meaningful metabolic benefitsin vivo, where dynamics of insulin signaling and receptor recycling are more complex, is unknown. To address this we adopted a strategy to model human insulin receptoropathy in mice, usingCrerecombinase delivered by adeno-associated virus to knock out endogenous hepaticInsracutely in floxedInsrmice (L- IRKO+GFP), before adenovirus-mediated ‘add-back’ of wild-type (WT) or mutant humanINSR. Two murine anti-INSR monoclonal antibodies, previously shown to be surrogate agonists for mutant INSR, were then tested by intraperitoneal injections. As expected, L-IRKO+GFP mice showed glucose intolerance and severe hyperinsulinemia, and this was fully corrected by add-back of WT but neither D734A nor S350L mutant INSR. Antibody injection improved glucose tolerance in D734A INSR-expressing mice and reduced hyperinsulinemia in both S350L and D734A INSR-expressing animals, and did not cause hypoglycemia in WT INSR-expressing mice. Antibody treatment also downregulated both wild-type and mutant INSR protein, attenuating its beneficial metabolic effects. Anti-INSR antibodies thus improve IR in an acute model of insulin receptoropathy, but these findings imply a narrow therapeutic window determined by competing effects of antibodies to stimulate receptors and induce their downregulation.One Sentence SummaryBivalent anti-insulin receptor antibodies improve glycaemic control, but downregulate receptor expression, in a novel mouse model of lethal human insulin receptoropathy.
Morphological and physiological response strategies ofVallisneria natansat different water depths and light conditions
Authors: Chou Qingchuan , Chen Jianfeng , Zhang Wei , Ren Wenjing , Yuan Changbo , Zhang Xiaolin , Cao Te , Ni Leyi , Jeppesen Erik 
Published: March 2020

AbstractPhenotypic plasticity is an important adaptation to spatial and temporal environmental variations. For submerged macrophytes, adaptation to water depth and light variation is particularly important. To determine the morphological and physiological adaptive strategies ofVallisneria natansat different water depths and light conditions, we combined field investigation, light control experiment andin situphysiological response experiment. In the field investigation and the light control experiment, both water depth and light intensity had prominent effects on the morphological ofV. natans, especially in fresh weight and leaf length. The leaf length elongated more rapidly at intermediate water depth sites with lower light intensity. In thein situexperiment, the survival boundary ofV. natansis 5.5 m in Lake Erhai. Below this depth, the chlorophyll-a content increased gradually with increasing water depth. Our results demonstrated thatV. natanscan adapt to water depth and light availability by changing morphological, physiological and resource allocation. At low light condition,V. natansinvested more resource for light acquisition, simultaneously, changing the photosynthetic pigment content to compensate for light attenuation; conversely, more resource was directed towards reproduction. These results will provide new insight for species selection when conducting aquatic plants restoration in freshwater ecosystem.HIGHLIGHTSWater depth and light availability affect the morphology, physiology, and resource allocation ofV. natans.An alternative resource allocation pattern ofV. natanscould shift between light acquisition and reproduction.
An alternative view of the millennial green product purchase: the roles of online product review and self-image congruence
Authors: Nguyen Yen Thi Hoang , Nguyen Hung Vu 
Published: March 2020

PurposeThe paper aims to provide an alternative view to green consumption behaviors of millennials. In fact, studies on green consumption have usually assumed a common attitude–behavior model for different generations. Instead, the view in this paper highlights two other constructs, online product review and self-image congruence, as the key antecedents to the behavior among the generation.Design/methodology/approachTo test our proposed model, an online survey with a sample of 305 millennials in Vietnam was conducted. The sample shares similar demographic features with the millennials in the country. The data were collected in popular social networks and then validated before being analyzed with AMOS.FindingsThe model analysis results provided supports for the key roles of online product review and self-image congruence among millennials. In particular, online product review was found to have both direct and mediational impacts on green product purchase intention. Self-image congruence was also found to be a key antecedent to the intention.Research limitations/implicationsThe model in this paper only examined the purchase intention. Moreover, only a single sample of millennials in Vietnam was investigated. Future research may incorporate the green consumption behavior to enhance the external validity and/or directly compare models for different generations or across countries to further confirm the differential generational patterns.Practical implicationsThe paper includes recommendations for managers to use the online channels and to promote green product self-matching among millennials. These recommendations are not contrary to but go beyond the frequently suggested ones for attitude-related training or communication campaigns for green consumption.Originality/valueThis paper fills an identified gap to provide an alternative view to green consumption behaviors of millennials. Different from the common attitude–behavior view in green consumption research, two key constructs of online product review and self-image congruence are highlighted for the generation in this paper.
The growth of hidden champions in China: a cognitive explanation from integrated view
Authors: Lei Linan , Wu Xiaobo , Tan Ziyan 
Published: March 2020

PurposeThere is a research gap in strategic management regarding the complement from managerial cognition literature to the behavioral theory of firm, as well as linkage between cognitive structure and cognitive process of strategy formulation in the field of managerial cognition, which also calls for further exploration. The purpose of this paper is to construct a model from an integrated view for explaining the process of cognitive reconstruction under incremental changes.Design/methodology/approachQualitative research is conducted in the form of 17 semi-structured interviews in four hidden champions operating in China. Based on the model generated from the literature review, this paper adopts the abductive logic for data analysis.FindingsThis paper draws the following conclusions. The cognitive structure is shaped by the changing environment and the performance feedback, the variance in structural attributes will affect whether the changing environment destructs the effectiveness of original cognitive structure or not, the centrality of cognitive structure will promote the efficiency of tried-and-true organizational adaptations to incremental changes, and cognitive structure reconstruction is the result of the recursive process of trial-and-error learning.Originality/valueThis paper proposes the model explaining the interaction mechanisms between cognitive structure and strategy formulation process. It also presents the iterative sense-making process for reconstructing cognitive structure in strategy formulation. Both of them extend the understanding on managerial cognition in organizational adaptations to incremental environmental changes.
Female board members: the effect of director affiliation
Authors: Arioglu Emrah 
Published: March 2020

PurposeThis study aims to investigate whether female directors have an effect on company financial performance in a patriarchal emerging country that has a collectivistic culture with a substantial gender equality gap and is characterized with a paternalistic management culture. In addition, it aims to investigate whether the affiliations of female directors matter performance-wise in a setting where the majority of the companies are ultimately controlled by large business groups including families.Design/methodology/approachThe current study uses a unique hand-collected data set that covers all non-financial public companies quoted at the Borsa Istanbul between the years 2009 and 2017. To investigate the relationships between the presence and ratio of female directors and company financial performance, the current study uses the pooled ordinary least squares method, as well as the firm-fixed effects method to overcome potential omitted variables problems and various generalized method of moments methods to overcome potential reverse causality problems.FindingsThe findings of the current study demonstrate that the presence and percentage of female directors both have a positive effect on company financial performance in a cultural setting where the opposite might be expected. They also present evidence suggesting that the effect becomes larger as the level of the independence of female directors becomes greater.Originality/valueThe current study demonstrates that the presence of female directors on boards has a positive effect on company financial performance, even in a cultural setting that is very different from those of countries where the majority of previous studies on female directors are conducted on. In addition, it demonstrates how company financial performance varies with the level of the affiliation of female directors.
Housing sales of real estate developers in Turkey
Authors: Selvi Murat Selim , Pajo Aykut , Çakir Ceyda , Demir Emre 
Published: March 2020

Purpose
Because of competition, residential property developers use a variety of promotional tools to gain recognition and increase their market share and the demand for housing, and to manage their customer relations. This study aims to examine what real estate developers did to detect the need for types of housing, and pricing and promoting housing. It also sought clues about how they manage customer relations in residential sales.

Design/methodology/approach
In this study, semi-structured interviews were conducted with real estate developers. This study has heuristic characteristics based on qualitative data. Document reviews, descriptive analysis and discourse analysis were carried out on the interview data and other sources. As purposeful sampling is generally used in qualitative studies; intensity sampling, homogeneous sampling, criterion sampling and snowball sampling were used together in this study.

Findings
The study found that real estate developers were inadequate at advertising and promoting, allocated little budget for promotion and did not use technology sufficiently. The real estate developers gave discounts at rates that did not actually desire, had to create payment plans, and as a result, they lost customers because they could not manage customer relations well.

Research limitations/implications
Interviews were conducted with 15 real estate developers who have been selling residential properties for more than 10 years in Süleymanpasa and Çorlu districts of Tekirdag. Data obtained are mostly qualitative.

Originality/value
This study aimed to determine real estate developers’ ability to implement a variety of promotional strategies and manage customer relations. Results and conclusions can offer significant clues about real estate developers with similar characteristics. Its conclusions of this study can be compared to similar studies of real estate developers in many regions of Turkey.
False self-employment: the role of occupations
Authors: Kösters Lian , Smits Wendy 
Published: March 2020

PurposeThis paper analyses the relation between occupational characteristics and the probability that a worker in the Netherlands has a false self-employed arrangement instead of an employee arrangement. These are arrangements in which self-employed workers perform tasks in the hierarchy of the firm as if they were employees.Design/methodology/approachData from the Dutch Labour Force Survey is used to analyse the relationship between occupational skill, routine and wage level and the probability to be a false self-employed or a standard or non-standard employee.FindingsThe results show that the probability to be false self-employed decreases slightly with the skill level of the occupation, but there is no evidence that false self-employment is more likely in low paid, routine occupations. Workers in the lowest paid occupations are more likely to have a non-standard contract as an employee. False self-employment arrangements are more likely in the (lower) middle paid occupations. Finally, the results show that working in the highest paid occupations increases the probability of being in a false self-employed arrangement, but only in arrangements that are characterised by economic and organizational dependency. These are arrangements with financial dependency on one client for income combined with dependency on this client on when and where to work.Originality/valueThis study makes an important contribution to the literature on identifying vulnerable self-employed workers as well as to the literature on mechanisms behind the growth of solo self-employment.