bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations
Authors: Couñago Rafael M. , Allerston Charles K. , Savitsky Pavel , Azevedo Hatylas , Godoi Paulo H. , Wells Carrow I. , Mascarello Alessandra , de Souza Gama Fernando H. , Massirer Katlin B. , Zuercher William J. , Guimarães Cristiano R.W. , Gileadi Opher 
Published: March 2017

ABSTRACTThe human genome encodes two active Vaccinia-related protein kinases (VRK), VRK1 and VRK2. These proteins have been implicated in a number of cellular processes and linked to a variety of tumors. However, understanding the cellular role of VRKs and establishing their potential use as targets for therapeutic intervention has been limited by the lack of tool compounds that can specifically modulate the activity of these kinases in cells. Here we identified BI-D1870, a dihydropteridine inhibitor of RSK kinases, as a promising starting point for the development of chemical probes targeting the active VRKs. We solved co-crystal structures of both VRK1 and VRK2 bound to BI-D1870 and of VRK1 bound to two broad-spectrum inhibitors. These structures revealed that both VRKs can adopt a P-loop folded conformation, which is stabilized by different mechanisms on each protein. Based on these structures, we suggest modifications to the dihydropteridine scaffold that can be explored to produce potent and specific inhibitors towards VRK1 and VRK2.
Transcriptome profiling reveals bisphenol A alternatives activate estrogen receptor alpha in human breast cancer cells
Authors: Mesnage Robin , Phedonos Alexia , Arno Matthew , Balu Sucharitha , Corton J. Christopher , Antoniou Michael N 
Published: March 2017

AbstractBackgroundPlasticizers with estrogenic activity, such as bisphenol A (BPA), have been reported to have potential adverse health effects in humans. Due to mounting evidence of these health effects and public pressure, BPA is being phased out by the plastics manufacturing industry and replaced by other bisphenol variants in “BPA-free” products.ObjectivesWe have compared estrogenic activity of BPA to 6 bisphenol analogues (bisphenol S, BPS; bisphenol F, BPF; bisphenol AP, BPAP; bisphenol AF, BPAF; bisphenol Z, BPZ; bisphenol B, BPB) in three human breast cancer cell lines.MethodsEstrogenicity was assessed by cell growth in an estrogen receptor (ER)-mediated cell proliferation assay, and by the induction of estrogen response element (ERE)-mediated transcription in a luciferase assay. Gene expression profiles were determined in MCF-7 human breast cancer cells by microarray analysis and confirmed by Illumina-based RNA sequencing.ResultsAll bisphenols showed estrogenic activity in promoting cell growth and inducing ERE-mediated transcription. BPAF was the most potent bisphenol, followed by BPB > BPZ ~ BPA > BPF ~ BPAP > BPS. The addition of ICI 182,780 antagonized the activation of ERs by bisphenols. Data mining of ToxCast high-throughput screening assays confirms our results but also shows divergence in the sensitivities of the assays. The comparison of transcriptome profile alterations resulting from BPA alternatives with an ERα gene expression biomarker further indicates that all BPA alternatives act as ERα agonists in MCF-7 cells. These results were confirmed by RNA sequencing.ConclusionIn conclusion, BPA alternatives are not necessarily less estrogenic in a human breast cancer cell model. Three bisphenols (BPAF, BPB, and BPZ) were more estrogenic than BPA. The relevance of human exposure to BPA alternatives in hormone-dependent breast cancer risk should be investigated.
RecBlast: Cloud-Based Large Scale Orthology Detection
Authors: Rapoport Efrat , Neuhof Moran 
Published: March 2017

AbstractBackgroundThe effective detection and comparison of orthologues is crucial for answering many questions in comparative genomics, phylogenetics and evolutionary biology. One of the most common methods for discovering orthologues is widely known as ‘Reciprocal Blast’. While this method is simple when comparing only two genomes, performing a large-scale comparison of Multiple Genes across Multiple Taxa becomes a labor-intensive and inefficient task. The low efficiency of this complicated process limits the scope and breadth of questions that would otherwise benefit from this powerful method.FindingsHere we present RecBlast, an intuitive and easy-to-use pipeline that enables fast and easy discovery of orthologues along and across the evolutionary tree. RecBlast is capable of running heavy, large-scale and complex Reciprocal Blast comparisons across multiple genes and multiple taxa, in a completely automatic way. RecBlast is available as a cloud-based web server, which includes an easy-to-use user interface, implemented using cloud computing and an elastic and scalable server architecture. RecBlast is also available as a powerful standalone software supporting multi-processing for large datasets, and a cloud image which can be easily deployed on Amazon Web Services cloud. We also include sample results spanning 448 human genes, which illustrate the potential of RecBlast in detecting orthologues and in highlighting patterns and trends across multiple taxa.ConclusionsRecBlast provides a fast, inexpensive and valuable insight into trends and phenomena across distance phyla, and provides data, visualizations and directions for downstream analysis. RecBlast's fully automatic pipeline provides a new and intuitive discovery platform for researchers from any domain in biology who are interested in evolution, comparative genomics and phylogenetics, regardless of their computational skills.
Bacterial Microtubules Exhibit Polarized Growth, Mixed-Polarity Bundling, and Destabilization by GTP Hydrolysis
Authors: Díaz-Celis César , Risca Viviana I. , Hurtado Felipe , Polka Jessica K. , Hansen Scott D. , Maturana Daniel , Lagos Rosalba , Mullins R. Dyche , Monasterio Octavio 
Published: March 2017

AbstractBacteria of the genusProsthecobacterexpress homologs of eukaryotic α-and β-tubulin, called BtubA and BtubB, that have been observed to assemble into bacterial microtubules (bMTs). ThebtubABgenes likely entered theProsthecobacterlineage via horizontal gene transfer and may derive from an early ancestor of the modern eukaryotic microtubule (MT). Previous biochemical studies revealed that BtubA/B polymerization is GTP-dependent and reversible and that BtubA/B folding does not require chaperones. To better understand bMT behavior and gain insight into the evolution of microtubule dynamics, we characterizedin vitrobMT assembly using a combination of polymerization kinetics assays, and microscopy. Like eukaryotic microtubules, bMTs exhibit polarized growth with different assembly rates at each end. GTP hydrolysis stimulated by bMT polymerization drives a stochastic mechanism of bMT disassembly that occurs via polymer breakage. We also observed treadmilling (continuous addition and loss of subunits at opposite ends) of bMT fragments. Unlike MTs, polymerization of bMTs requires KCl, which reduces the critical concentration for BtubA/B assembly and induces bMTs to form stable mixed-orientation bundles in the absence of any additional bMT-binding proteins. Our results suggest that at potassium concentrations resembling that inside the cytoplasm ofProsthecobacter, bMT stabilization through self-association may be a default behavior. The complex dynamics we observe in both stabilized and unstabilized bMTs may reflect common properties of an ancestral eukaryotic tubulin polymer.ImportanceMicrotubules are polymers within all eukaryotic cells that perform critical functions: they segregate chromosomes in cell division, organize intracellular transport by serving as tracks for molecular motors, and support the flagella that allow sperm to swim. These functions rely on microtubules remarkable range of tunable dynamic behaviors. Recently discovered bacterial microtubules composed of an evolutionarily related protein are evolved from a missing link in microtubule evolution, the ancestral eukaryotic tubulin polymer. Using microscopy and biochemical approaches to characterize bacterial microtubules, we observed that they exhibit complex and structurally polarized dynamic behavior like eukaryotic microtubules, but differ in how they self-associate into bundles and become destabilized. Our results demonstrate the diversity of mechanisms that microtubule-like filaments employ to promote filament dynamics and monomer turnover.
How to get the most bang for your buck: the evolution and physiology of nutrition-dependent resource allocation strategies
Authors: Ng’oma Enoch , Perinchery Anna M. , King Elizabeth G. 
Published: March 2017

AbstractAll organisms utilize resources to grow, survive, and reproduce. The supply of these resources varies widely across landscapes and time, imposing ultimate constraints on the maximal trait values for allocation-related traits. In this review, we address three key questions fundamental to our understanding of the evolution of allocation strategies and their underlying mechanisms. First, we ask: how diverse are flexible resource allocation strategies among different organisms? We find there are many, varied, examples of flexible strategies that depend on nutrition. However, this diversity is often ignored in some of the best-known cases of resource allocation shifts, such as the commonly observed pattern of lifespan extension under nutrient limitation. A greater appreciation of the wide variety of flexible allocation strategies leads directly to our second major question: what conditions select for different plastic allocation strategies? Here, we highlight the need for additional models that explicitly consider the evolution of phenotypically plastic allocation strategies and empirical tests of the predictions of those models in natural populations. Finally, we consider the question: what are the underlying mechanisms determining resource allocation strategies? Although evolutionary biologists assume differential allocation of resources is a major factor limiting trait evolution, few proximate mechanisms are known that specifically support the model. We argue that an integrated framework can reconcile evolutionary models with proximate mechanisms that appear at first glance to be in conflict with these models. Overall, we encourage future studies to 1) mimic ecological conditions in which those patterns evolve, and 2) take advantage of the ‘omic’ opportunities to produce multi-level data and analytical models that effectively integrate across physiological and evolutionary theory.
NLR1-V, a CC-NBS-LRR encoding gene, is a potential candidate gene of the wheat powdery mildew resistance genePm21
Authors: Xing Liping , Hu Ping , Liu Jiaqian , Cui Chaofan , Wang Hui , Di Zhaocan , Zhou Shuang , Xu Jiefei , Gao Li , Huang Zhenpu , Cao Aizhong 
Published: March 2017

AbstractWheat powdery mildew caused byBlumeria graminisbf. sp.triticiis one of the most destructive diseases all over the world.Pm21,transferred from the wildHaynaldia villosato wheat, confers broad spectrum resistance throughout the whole stage, and this gene has been widely used in wheat production for more than 20 years. Cloning the candidate gene ofPm21is the prerequisite for elucidating the resistance mechanism, and is a valuable attempt to clone the target genes from the evolutionarily distant wild species. In this study, an innovative approach, which combined cytogenetic stocks development, mutagenesis, RenSeq and PacBio, was tried successfully to clone an NBS-LRR type geneNLR1-Vfrom thePm21locus. Firstly, a powdery mildew resistant cryptic alien introgression line HP33 involved very small 6VS segment was developed, and 6 independent susceptible mutants of T6VS · 6AL was identified. Then, the transcriptome ofH. villosawas obtained by NGS and the full-length NBS-LRR gene database was constructed by RenSeq-PacBio. In the following study, two expressedNLRgenes were located to thePm21locus using the HP33 as the mapping material, and onlyNLR1-Vshowed polymorphism between the wild T6VS · 6AL and its six mutants. The functional analysis indicated that silencing ofNLR1-Vcould compromise the resistance of T6VS · 6AL completely, and could also decrease the resistance of T6VS · 6DL dramatically. Moreover,NLR1-Vcould recover the resistance of the susceptible mutant and increase the resistance in the susceptible wheat. The study implied thatNLR1-V,a CC-NBS-LRR encoding gene, is a potential candidate gene of the powdery mildew resistance genePm21.
“When I am with my husband, I do not feel mosquito bite”
Authors: Quist Mary Anita , Adomah-Afari Augustine 
Published: March 2017

Purpose
The purpose of this paper is to explore how socio-cultural beliefs and practices could influence the knowledge, attitude and perception of insecticide-treated net (ITN) use in the control of malaria amongst pregnant women attending antenatal clinic.

Design/methodology/approach
Data were gathered using interviews and documentary review. Framework analysis was applied to classify emerging themes and the findings interpreted using the health belief model.

Findings
The findings showed that the pregnant women had appreciable knowledge, both the positive and negative attitudes and the perceptions of insecticide treated nets. To most of them, sleeping under an ITN would not affect pregnancy/cause abortion, but rather prevent mosquito bites and associated malaria.

Research limitations/implications
The limitations include the sample size of participants and health facilities used. Lack of application of a quantitative research method meant that the authors could not quantify the findings to ensure generalisation to the entire population.

Practical implications
The findings suggest that health policy makers, implementers and health professionals need to appreciate the perception and the attitude of pregnant women when designing policy guidelines for the malaria control programme.

Social implications
This paper helps to elucidate on how socio-cultural beliefs and practices could influence the knowledge, attitude and perception of ITN usage amongst both pregnant women and people in malaria endemic communities.

Originality/value
This paper suggests that health policy makers, implementers and health professionals have to devise strategies to address socio-cultural beliefs and practices in the scaling up of malaria control programmes.
Exploring risks, advantages and interpersonal trust in buyer-salesperson relationships in direct selling in a non-western country
Authors: Poon Patrick , Albaum Gerald , Yin Cheng-Yue 
Published: March 2017

Purpose
The purpose of this paper is to examine the dimensions of interpersonal trust which would affect the buyer-salesperson relationship in a direct selling situation. It also investigates consumers’ perceived risk and advantages of direct selling.

Design/methodology/approach
A questionnaire survey of consumers (and also non-consumers) of direct selling companies in Hong Kong was performed by means of mall-intercept interview. The major measurements were perceived risk, perceived advantages, trust dimensions, and repurchase intention.

Findings
The results show that there are six dimensions of interpersonal trust in the buyer-seller relationship in direct selling, but only one dimension (i.e. honesty) has a significant relationship with repurchase intention. The ability to shop at home is found to have the highest advantage rating of direct selling. In addition, direct selling is perceived to have a lower level of risk than unsolicited telephone call such as telemarketing.

Originality/value
This is the first study to investigate the effects of different dimensions of interpersonal trust on consumer buying behavior under a direct selling situation in Asia. The study also serves as a foundation for studying the applicability and usefulness of all trust measures in other western or non-western cultures/nations.
Dominant logics and the manager’s role in university business incubators
Authors: Redondo María , Camarero Carmen 
Published: March 2017

PurposeThis paper aims to investigate the role of university business incubator managers as drivers of the training and advice given to academic incubatees. Based on the institutional logics approach, the current paper proposes that the dominant logic, academic versus commercial, determines the degree of emphasis on personal assistance, business assistance and networking training.Design/methodology/approachTo test the proposed hypotheses, data were collected from 93 incubation programmes from Spanish and Dutch universities through questionnaires addressed to their respective managers, as well as clients.FindingsThe results indicate that the greater the managers’ experience in the business and entrepreneurial world, the greater the fostering of personal and business assistance and networking activities in the incubator. Managers lacking an entrepreneurial profile weaken incubatee access to other business networks and prove less efficient in business training.Originality/valueThis research makes a contribution to the study of university incubatees, showing that managers can be involved in different institutional logics, whether they be academic or commercial, and that the dominant logic determines the activities promoted and, consequently, the success of the incubation process. Business and entrepreneurial experience is key to instilling business logic in incubatees together with the training and assistance they require.
Exploring the dark side of cooperative buyer-seller relationships
Authors: Grandinetti Roberto 
Published: March 2017

PurposeThis paper aims to study the dark side of cooperative buyer-seller relationships to improve our knowledge of this phenomenon.Design/methodology/approachA selective definition of dark side has been adopted, linking it to relationships of a cooperative nature within which one of the two partners assumes an opportunistic behavior. Taking into account this definition, the first part of the paper critically reviews those studies which have analyzed cooperative relations along the supply chain, drawing attention to the formation of a dark side. The second part of the paper re-examines the association between cooperation and opportunism, taking the point of view of the disadvantaged partner and adopting the networking perspective developed by the Industrial Marketing and Purchasing (IMP) Group.FindingsThe literature review enables one to identify two types of dark side. In the first case, the partner at a disadvantage is aware of what is going on, but remains trapped in the relationship because of a power imbalance and a strong dependence. In the second case, the relationship is spoilt by one partner keeping a secret from the other, exploiting an information asymmetry. The main constructs of the IMP approach have made possible to shed light on the two different types of dark side – trap and secret – that were examined from the perspective of the disadvantaged partner.Practical implicationsThe analysis of the disadvantaged partner has made it possible to understand what strategies he can use to prevent or mitigate such a disadvantaged position.Originality/valueThe paper develops an original view of the phenomenon of dark side in cooperative relationships.
Organizational buying decision approaches in manufacturing industry: developing measures and typology
Authors: Sinčić Ćorić Dubravka , Anić Ivan-Damir , Piri Rajh Sunčana , Rajh Edo , Kurnoga Nataša 
Published: March 2017

Purpose
This paper aims to explore buying decision factors and approaches of companies operating in manufacturing industry in Croatia.

Design/methodology/approach
The data collected by company survey were analysed using exploratory and confirmatory factor analyses, cluster analysis and cross-tabulation analysis.

Findings
Results show that manufacturers are influenced by six distinctive factors when making purchasing decisions. These are supplier’s flexibility, supplier’s reliability, interdepartmental communication, top management support, routine purchases and buyer’s price sensitivity. Manufacturers can be classified in four different groups according to their buying decision-making patterns.

Practical implications
This paper provides a set of factors and approaches which might help selling companies and sales representatives understand the purchasing practices of buying company better, and develop adaptive selling approaches accordingly.

Originality/value
Based on a literature review and field research, an instrument of organizational buying behaviour was developed and tested in the Croatian manufacturing industry. The factors of organizational buying behaviour patterns were identified, and the typology of buying decision approaches applicable for manufacturing industry was developed.
The work is never ending: uncovering teamwork sustainability using realistic evaluation
Authors: Frykman Mandus , von Thiele Schwarz Ulrica , Muntlin Athlin Åsa , Hasson Henna , Mazzocato Pamela 
Published: March 2017

PurposeThe purpose of this paper is to uncover the mechanisms influencing the sustainability of behavior changes following the implementation of teamwork.Design/methodology/approachRealistic evaluation was combined with a framework (DCOM®) based on applied behavior analysis to study the sustainability of behavior changes two and a half years after the initial implementation of teamwork at an emergency department. The DCOM® framework was used to categorize the mechanisms of behavior change interventions (BCIs) into the four categories of direction, competence, opportunity, and motivation. Non-participant observation and interview data were used.FindingsThe teamwork behaviors were not sustained. A substantial fallback in managerial activities in combination with a complex context contributed to reduced direction, opportunity, and motivation. Reduced direction made staff members unclear about how and why they should work in teams. Deterioration of opportunity was evident from the lack of problem-solving resources resulting in accumulated barriers to teamwork. Motivation in terms of management support and feedback was reduced.Practical implicationsThe implementation of complex organizational changes in complex healthcare contexts requires continuous adaption and managerial activities well beyond the initial implementation period.Originality/valueBy integrating the DCOM® framework with realistic evaluation, this study responds to the call for theoretically based research on behavioral mechanisms that can explain how BCIs interact with context and how this interaction influences sustainability.
Workplace spirituality, perceived organizational support and innovative work behavior
Authors: Afsar Bilal , Badir Yuosre 
Published: March 2017

Purpose
Synthesizing theories of innovative work behavior, workplace spirituality and person-organization (P-O) fit, this paper aims to build and test a theoretical model linking workplace spirituality, perceived organizational support (POS) and innovative work behavior via P-O fit. This study examined the mediating effect of P-O fit on the relationship of workplace spirituality and POS with innovative work behavior (IWB).

Design/methodology/approach
A sample of 434 employees and 59 supervisors from five leading hotels of China was used for this study.

Findings
This study found that workplace spirituality and POS both positively affected P-O fit. Workplace spirituality, P-O fit and POS positively influenced innovative work behavior. P-O fit acted as a partial mediator between workplace spirituality and IWB and between POS and IWB.

Originality/value
This study has tested the effect of workplace spirituality as an antecedent of innovative work behavior for the first time.