bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selection and drift determine phenotypic stasis despite genetic divergence
Authors: Mallard François , Noble Luke , Guzella Thiago , Afonso Bruno , Baer Charles F. , Teotónio Henrique 
Published: September 2019

1AbstractEvolutionary theory suggests that phenotypic stasis is explained by natural selection and genetic drift, or by constraints imposed by mutation and recombination of standing genetic variation. We performed experimental evolution from standing genetic variation with the nematodeCaenorhabditis elegans, measuring individual locomotion in outcrossing populations for 240 generations. We find that, in our constant environment, locomotion bias shows no directional divergence, due to both stabilizing and disruptive selection on specific combinations of component traits. Despite phenotypic stasis, the genetic variance-covariance structure between component traits shows clear divergence from the ancestral state and extensive differentiation among replicated populations facing the same environment. Analysis of mutation accumulation experiments and genome-sequenced recombinant inbred lines from the experimental populations indicates that the evolution of the genetic variance-covariance structure is independent ofde novomutation or major effect QTL; being instead explained by the joint action of selection and drift in generating subtle linkage disequilibrium differences between small effect QTL among replicate populations. These findings indicate that phenotypic evolution is repeatable because of selection, even if the genetic structuring of component traits within lineages is mostly contingent upon drift history.
Evolution of metastases-associated fibroblasts in the lung microenvironment is driven by stage-specific transcriptional plasticity
Authors: Shani Ophir , Raz Yael , Monteran Lea , Megides Or , Shacham Hila , Cohen Noam , Silverbush Dana , Levi-Galibov Oshrat , Avivi Camilla , Sharan Roded , Madi Asaf , Scherz-Shouval Ruth , Barshack Iris , Tsarfaty Ilan , Erez Neta 
Published: September 2019

AbstractMortality from breast cancer is almost exclusively a result of tumor metastasis, and lungs are one of the main metastatic sites. Cancer-associated fibroblasts (CAFs) are prominent players in the microenvironment of breast cancer. However, their role in the metastatic niche is largely unknown. In this study, we profiled the transcriptional co-evolution of lung fibroblasts isolated from transgenic mice at defined stage-specific time points of metastases formation. Employing multiple knowledge-based platforms of data analysis provided powerful insights on functional and temporal regulation of the transcriptome of fibroblasts. We demonstrate that fibroblasts in lung metastases are transcriptionally dynamic and plastic, and reveal stage-specific gene signatures that imply functional tasks, including extracellular matrix remodeling, stress response and shaping the inflammatory microenvironment. Furthermore, we identified Myc as a central regulator of fibroblast rewiring and found that stromal upregulation of Myc transcriptional networks is associated with worse survival in human breast cancer.
Thrombospondin module 1 domain (TSP1) of the matricellular protein CCN3 shows an atypical disulfide pattern and incomplete CWR layers
Authors: Xu Emma-Ruoqi , Lafita Aleix , Bateman Alex , Hyvönen Marko 
Published: September 2019

AbstractMembers of the CCN (Cyr61/CTGF/Nov) family are a group of matricellular regulatory proteins, essential to a wide range of functional pathways in cell signalling. Through interacting with extracellular matrix components and growth factors via one of its four domains, the CCN proteins are involved in critical biological processes such as angiogenesis, cell proliferation, bone development, fibrogenesis, and tumorigenesis. We present here the crystal structure of the thrombospondin module 1 (TSP1) domain of CCN3 (previously known as Nov), which shares a similar three-stranded fold with the thrombospondin type 1 repeats of thrombospondin-1 and Spondin-1, but with variations in the disulfide connectivity. Moreover, the CCN3 TSP1 lacks the typical pi-stacked ladder of charged and aromatic residues on one side of the domain, as seen in other TSP1 domains. Using conservation analysis among orthologous domains, we show that a charged cluster in the centre of the domain is the most conserved site and predict it to be a potential functional epitope for heparan sulphate binding. This variant TSP1 domain has also been used to revise the sequence determinants of TSP1 domains and derive improved Pfam sequence profiles for identification of novel TSP1 domains in more than 10,000 proteins across diverse phyla.SynopsisThe first structure of a thrombospondin module 1 domain (TSP1) from a CCN family matricellular protein has been determined by X-ray crystallography. The structure shows a typical three-stranded fold, but with an incomplete pi-stacked structure that is usually found in these domains. The structure reveals highest conservation in the positively charged central segment, which we predict to be a binding site for heparan sulphates. The atypical features of this domain have been used to revise the definition of the TSP1 domains and identify a number of new domains in sequence databases.
A reverse chemical ecology approach to explore wood natural durability
Authors: Thomas Perrot , Guillaume Salzet , Nadine Amusant , Jacques Beauchene , Philippe Gérardin , Stéphane Dumarçay , Rodnay Sormani , Mélanie Morel-Rouhier , Eric Gelhaye 
Published: September 2019

SummaryThe natural durability of wood species, defined as their inherent resistance to wood-destroying agents is a complex phenomenon depending of many biotic and abiotic factors. Besides the presence of recalcitrant polymers, the presence of compounds with antimicrobial properties is known to be important to explain wood durability. Based on the advancement in our understanding of fungal detoxification systems, a reverse chemical ecology approach was proposed to explore wood natural durability. A set of six glutathione transferases from the white-rot Trametes versicolor was used as targets to test wood extracts from seventeen French Guiana neotropical species. Fluorescent thermal shift assays allowed to quantify interactions between fungal glutathione transferases and these extracts. From these data, a model combining this approach and wood density predicts significantly wood natural durability of the tested species previously estimated by long-term soil bed tests. Overall, our findings confirm that detoxification systems could be used to explore the chemical environment encountered by wood decaying fungi and then wood natural durability.
MicroRNA and Gene Expression Analysis on Placenta Tissue: An Approach to Understanding Obstetric Antiphospholipid Syndrome at the Molecular Level
Authors: Mohamad Muhammad Aliff , Manzor Nur Fariha Mohd , Suhiman Muhammad Shazwan , Sathar Jameela , Rahman Hayati Abdul , Masri Maiza , Rahim Nur Syahrina Abdul , Hamid Nazefah Abdul , Mohamad Nor Nadeeya , Asnawi Asral Wirda Ahmad 
Published: September 2019

AbstractObstetric antiphospholipid syndrome is initiated by the action of antiphospholipid antibodies on placenta. The characteristics of APS in pregnancy include vascular thrombosis, inflammation and impairment of trophoblast implantation. MicroRNA (miRNA) expression has been suggested as one of the genetic factors that contribute to the development of this syndrome. miRNAs regulate gene expressions in a vast assortment of cellular biological mechanisms include the development of placental tissue. Hence, further investigation on the regulation of placental miRNA in APS is required. In this study, we aimed to profile miRNA expressions from placenta tissue of patients with APS. Differentially expressed miRNAs were determined for its targeted genes and pathways. Agilent microarray platform was used to measure placental microRNA expressions between normal placental tissue and those obtained from patients with APS. Differentially expressed miRNAs were detected using GeneSpring GX software 14.2 and sequences were mapped using TargetScan software to generate the predicted target genes. Pathway analysis for the genes was then performed on PANTHER and REACTOME software. Selected miRNAs and their associated genes of interest were validated using qPCR. Microarray findings revealed, 9 downregulated and 21 upregulated miRNAs expressed in placenta of patients with APS. Quantitative expressions of 3 selected miRNAs were in agreement with the microarray findings, however only miR-525-5p expression was statistically significant. Pathway analysis revealed that the targeted genes of differentially expressed miRNAs were involved in several hypothesized signalling pathways such as the vascular endothelial (VE) growth factor (VEGF) and inflammatory pathways. VE-cadherin, ras homolog member A (RHOA) and tyrosine kinase receptor (KIT) showed significant downregulation from the qPCR data while retinoblastoma gene (RET), dual specificity protein phosphatase 10 (DUSP10) and B-lymphocyte kinase (BLK) were significantly upregulated. These preliminary findings suggest the involvement of miRNAs and identified novel associated genes involvement in the mechanism of obstetric APS, particularly through the alteration of vascular-associated regulators and the inflammatory signalling cascade.
Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy
Authors: Su Xuelian , Wang Jizeng , Bao Guangjie , Zhou Haijing , Liu Lin , Zheng Qian , Guo Manli , Zhang Jinting 
Published: September 2019

AbstractStem cell apoptosis exists widely in embryonic development, tissue regeneration, repair, aging and pathophysiology of disease. The molecular mechanism of stem cell apoptosis has been extensively investigated. However, alterations in biomechanics and nanomorphology have rarely been studied. Therefore, an apoptosis model was established for bone marrow mesenchymal stem cells (BMSCs) and the reconstruction of the mechanical properties and nanomorphology of the cells were investigated in detail. Atomic force microscopy (AFM), scanning electron microscopy (SEM), laser scanning confocal microscopy (LSCM), flow cytometry and Cell Counting Kit-8 analysis were applied to assess the cellular elasticity modulus, geometry, nanomorphology, cell surface ultrastructure, biological viability and early apoptotic signal (phosphatidylserine, PS). The results indicated that the cellular elastic modulus and volume significantly decreased, whereas the cell surface roughness obviously increased during the first 3 h of cytochalasin B (CB) treatment. Moreover, these alterations preceded the exposure of biological apoptotic signal PS. These findings suggested that cellular mechanical damage is connected with the apoptosis of BMSCs, and the alterations in mechanics and nanomorphology may be a sensitive index to detect alterations in cell viability during apoptosis. The results contribute to a further understanding of the apoptosis from the perspective of cell mechanics.
Effect of dining experience on future intention in quick service restaurants
Authors: Richardson Scott , Lefrid Mohammed , Jahani Shiva , Munyon Matthew D. , Rasoolimanesh S. Mostafa 
Published: September 2019

Purpose
The purpose of this paper is to examine the effect of the dining experience including food quality, service quality, convenience and ambiance on overall satisfaction and customers’ intention to revisit in quick service restaurants (QSRs). In addition, the mediating effects of overall satisfaction between dining experience dimensions and customer intention to revisit have been investigated in this study.

Design/methodology/approach
Data were collected online from 278 participants in the USA and analyzed using partial least square structure equation modeling (SmartPLS).

Findings
Food quality, service quality and convenience are strong predictors of both overall satisfaction and intention to revisit and recommend QSRs. However, ambiance did not directly influence the customer overall satisfaction in a QSR setting, Also, overall satisfaction did not mediate the relationship between the dining experience attributes and future intention to revisit and recommend QSRs.

Research limitations/implications
This study makes a significant contribution to the QSRs literature by examining the effects of dining experience on satisfaction and intention to revisit, as well as the meditation role of satisfaction. Moreover, this study has several practical implications for QSRs practitioners and foodservice marketers. Self-selection to take the online questionnaire is considered one of this study’s limitations.

Practical implications
Restaurant managers, especially in the QSR segment, could benefit from the outcome of this study by utilizing their limited resources on improving their customers’ satisfaction and restaurants profitability.

Social implications
By understanding which attributes of the dining experience value most during their visit to QSRs, this study aims to provide some insight on how to improve QSR customers overall satisfaction and future intention.

Originality/value
This study is unique as it applies attributes from fine dining and casual dining attributed to QSRs in the USA. In addition, this study is the first on QSRs to use SmartPLS as statistical tool for analyzing the collected data and simultaneously accounting the relationships between the constructs introduced in this study.
Corporate social responsibility and business ethics: conceptualization, scale development and validation
Authors: Harrison Dana E. , Ferrell O.C. , Ferrell Linda , Hair, Jr Joe F. 
Published: September 2019

Purpose
The purpose of this paper is to theoretically develop and empirically validate separate scales that represent a consumer’s expectations of business ethics (BE) and corporate social responsibility (CSR).

Design/methodology/approach
A literature review and qualitative research were conducted to generate items for the scales. Initial item reduction was performed qualitatively based on a panel of experts. A follow-up quantitative assessment using an exploratory factor analysis further reduced the items. The scales were then validated using confirmatory composite analysis with partial least squares-structural equation modeling.

Findings
Separate scales representing consumers’ expectations of BE and CSR behaviors were developed. The scales exhibited reliability, convergent validity, discriminant validity and external validity.

Practical implications
The separation of these scales into two components will facilitate more precise examination of consumer perceptions of these two components of product and brand images, and how they may impact brand attitudes and brand trust.

Originality/value
This is the first effort to develop separate scales for consumer expectations of ethics and CSR, and assess their impact on brand outcomes.
Association between dietary diversity and obesity in Ardebil adults: a case-control study
Authors: Mohajeri Mahsa , Hoojeghani Shiva , Pourfarzi Farhad , Ghahremanzadeh Mohammad , Barzegar Ali 
Published: September 2019

PurposeObesity is a multi-factorial problem that develops from an interaction between diet, genetics, physical activity, medication, and other factors. This paper aims to examine the association between dietary diversity score (DDS) and obesity among adults of Ardebil.Design/methodology/approachThis case-control study was conducted on 204 cases (obese and overweight participants) and 204 controls (healthy weight individuals) matched by socioeconomic status (SES), age (older than 30 years) and sex. Dietary intake was assessed using a 24 h food recall questionnaire. Data on physical activity and socio-demographic variables were gathered. DDS was computed based on the scoring of the 14 food groups recommended by the Food and Agriculture organization guideline.FindingsThe DDS of the obese group was higher (5.02 ± 1.02) than that of the healthy weight group (4.23 ± 1.18) (p < 0.001). There was a significant association between DDS and body mass index (BMI) in both groups of study, but this association was more significant in the obese group (β= 0.501,p = 0.021) than that of healthy weight group (β= 0.413,p= 0.042). Vegetable food group score in both groups of the study was associated with obesity inversely (p < 0.05).Originality/valueThis study was conducted for the first time in Ardabil city and the results showed for the first time that there is a relationship between dietary diversity and obesity. People with a higher dietary diversity score are more likely to be obese. In fact, this study for the first time proved that people who are obese have a more varied diet but less vegetables and fruits.
Breast cancer drugs perturb fundamental vascular functions of endothelial cells by attenuating protein S‐nitrosylation
Authors: Giri Suvendu , Katakia Yash Tushar , Chatterjee Suvro , Gajalakshmi Palanivel 
Published: September 2019

AbstractCardiovascular side effects of broadly used chemotherapeutic drugs such as Tamoxifen citrate (TC), Capecitabine (CP) and Epirubicin (EP) among cancer survivors are well established. Nitric oxide (NO) is known to protect cardiovascular tissues under conditions of stress. NO can act through cyclic guanosine monophosphate (cGMP)‐dependent and ‐independent pathways. Particularly, the S‐nitrosylation of SH‐groups in a protein by NO falls under cGMP‐independent effects of NO. TC, CP, and EP are hypothesized as interfering with cellular protein S‐nitrosylation, which, in turn, may lead to endothelial dysfunctions. The results show that all three drugs attenuate nitrosylated proteins in endothelial cells. A significant reduction in endogenous S‐nitrosylated proteins was revealed by Saville–Griess assay, immunofluorescence and western blot. Incubation with the drugs causes a reduction in endothelial migration, vasodilation and tube formation, while the addition of S‐nitrosoglutathione (GSNO) has a reversal of this effect. In conclusion, results indicate the possibility of decreased cellular nitrosothiols as being one of the reasons for endothelial dysfunctions under TC, CP and EP treatment. Identification of the down‐regulated S‐nitrosylated proteins so as to correlate their implications on fundamental vascular functions could be an interesting phenomenon.
Chronic sleep fragmentation shares similar pathogenesis with neurodegenerative diseases: Endosome‐autophagosome‐lysosome pathway dysfunction and microglia‐mediated neuroinflammation
Authors: Xie Yi , Ba Li , Wang Min , Deng Sai‐Yue , Chen Si‐Miao , Huang Li‐Fang , Zhang Min , Wang Wei , Ding Feng‐Fei 
Published: September 2019

AbstractAimsInsufficient sleep has been found to result in varying degrees of cognitive impairment and emotional changes. Sleep was reported probably responsible for cleaning metabolic wastes in brain by increasing extracellular bulk flow. Herein, we propose that chronic sleep insufficiency in young adult wild‐type mice is also linked with dysfunction of intracellular protein degradation pathways and microglia‐mediated neuroinflammation, which are potentially important mechanisms in the initiation of neurodegeneration.MethodsWe applied the chronic sleep fragmentation (CSF) model to induce chronic sleep insufficiency in wild‐type mice. After 2 months of CSF, cognitive function, amyloid‐β accumulation, dysfunction of endosome‐autophagosome‐lysosome pathway, and microglia activation were evaluated.ResultsFollowing CSF, impairment of spatial learning and memory, and aggravated anxiety‐like behavior in mice were identified by behavioral experiments. Increased intracellular amyloid‐β accumulation was observed in cortex and hippocampus. Mechanistically, CSF could significantly enhance the expression of Rab5 (early endosome marker), Rab7 (late endosome marker), as well as LC3B (autophagosome marker), and autophagy‐positive regulatory factors in brain detected by immunofluorescent staining and Western blot. In addition, activation of microglia was evident by enhanced CD68, CD16/32, and CD206 levels after CSF treatment.ConclusionsChronic sleep fragmentation could initiate pathogenetic processes similar to the early stage of neurodegeneration, including dysfunction of endosome‐autophagosome‐lysosome pathway and microglia‐mediated neuroinflammation. Our findings further strengthen the link between chronic sleep insufficiency and the initiation of neurodegeneration even if lack of genetic predisposition.
Intratumour heterogeneity in endometrial serous carcinoma assessed by targeted sequencing and multiplex ligation‐dependent probe amplification: a descriptive study
Authors: Cuevas Dolors , Velasco Ana , Vaquero Marta , Santacana Maria , Gatius Sònia , Eritja Núria , Estaran Elena , Matias‐Guiu Xavier 
Published: September 2019

AimsEndometrial serous carcinoma (ESC) represents the most aggressive subtype of endometrial carcinoma (EC). According to The Cancer Genome Atlas (TCGA), ESC exhibits a genomic profile characterised by frequent TP53 mutations and somatic copy‐number alterations (SCNA). Several studies have suggested the role of intratumour heterogeneity (ITH) in tumour progression and therapy resistance, highlighting ITH as a challenge for personalised medicine. ITH is described as the co‐existence of clonal and subclonal cellular populations within a single tumour. To date, the extent and prevalence of ITH in ESC have not been fully evaluated. The aim of this study was to address ITH analysis in ESC. We performed a descriptive integrated molecular approach using targeted sequencing and multiplex ligation‐dependent probe amplification (MLPA) to identify mutations and SCNA patterns, respectively.Methods and resultsEight ESC were examined, selecting three tumour regions per case and their corresponding normal tissue. For targeted sequencing a gene panel of 40 genes based on TCGA and other survey data was performed. For MLPA different probe mixes were used to detect SCNA in 106 genes. Analysis of mutations and SCNA were performed in each sample and comparative analysis of the three tumour regions was also conducted. Targeted sequencing showed that mutations in TP53, PIK3CA and PPP2R1A were ubiquitous in all tumour regions. Moreover, MLPA results demonstrated a high frequency of SCNA, according to the already known presence of genomic instability in ESC. Unlike the homogeneous distribution of somatic mutations, SCNA exhibited ITH affecting targetable genes such as ERBB2.ConclusionsOur study suggests that somatic gene copy‐number alterations are the main source of ITH in ESC.