bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZO-2 induces cytoplasmic retention of YAP by promoting a LATS1-ZO-2-YAP complex at tight junctions
Authors: Liu Olivia Xuan , Lin Lester Bocheng , Chew Tiweng , Motegi Fumio , Low Boon Chuan 
Published: June 2018

SummaryContact inhibition of proliferation (CIP) is a key mechanism that transduces the cell density status of tissue and organs into a unique transcriptional program by translocating YAP between the nucleus and the cytoplasm. However, the nature of the cell density-dependent cues that regulate the YAP distribution remains unclear. Here, we present evidence that tight junctions serve as a platform that controls both distribution and activity of LATS1, a kinase that phosphorylates YAP. This CIP effect is mediated by the scaffold function of junctional protein, ZO-2, by promoting LATS1 interaction with YAP in the cytoplasm, and then targeting the tripartite complex to tight junctions. There, LATS1 is activated by angiomotin and NF2, thereby stimulating YAP phosphorylation and its cytoplasmic retention. Our findings delineate novel mechanisms governing CIP, in which ZO-2 utilizes the status of cell-cell cohesion to control the phosphorylation status and therefore inactivation of YAP by LATS1 in the cytoplasm.
Why did some practices not implement new antibiotic prescribing guidelines on urinary tract infection? A cohort study and survey in NHS England primary care
Authors: Croker Richard , Walker Alex J , Goldacre Ben 
Published: June 2018

AbstractObjectivesTo describe prescribing trends and geographic variation for trimethoprim and nitrofurantoin; to describe variation in implementing guideline change; and to compare actions taken to reduce trimethoprim use in high- and low-using Clinical Commissioning Groups (CCGs).DesignA retrospective cohort study and interrupted time series analysis in English NHS primary care prescribing data; complemented by information obtained through Freedom of Information Act requests to CCGs. The main outcome measures were: variation in practice and CCG prescribing ratios geographically and over time, including an interrupted time-series; and responses to Freedom of Information requests.ResultsThe amount of trimethoprim prescribed, as a proportion of nitrofurantoin and trimethoprim combined, remained stable and high until 2014, then fell gradually to below 50% in 2017; this reduction was more rapid following the introduction of the Quality Premium. There was substantial variation in the speed of change between CCGs. As of April 2017, for the 10 worst CCGs (with the highest trimethoprim ratios): 9 still had trimethoprim as first line treatment for uncomplicated UTI (one CCG had no formulary); none had active work plans to facilitate change in prescribing behaviour away from trimethoprim; and none had implemented an incentive scheme for change in prescribing behaviour. For the 10 best CCGs: 2 still had trimethoprim as first line treatment (all CCGs had a formulary); 5 (out of 7 who answered this question) had active work plans to facilitate change in prescribing behaviour away from trimethoprim; and 5 (out of 10 responding) had implemented an incentive scheme for change in prescribing behaviour. 9 of the best 10 CCGs reported at least one of: formulary change, work plan, or incentive scheme. None of the worst 10 CCGs did so.ConclusionsMany CCGs failed to implement an important change in antibiotic prescribing guidance; and report strong evidence suggesting that CCGs with minimal prescribing change did little to implement the new guidance. We strongly recommend a national programme of training and accreditation for medicines optimisation pharmacists; and remedial action for CCGs that fail to implement guidance; with all materials and data shared publicly for both such activities.
Increased production of the extracellular polysaccharide Psl can give a growth advantage to Pseudomonas aeruginosa in low-iron conditions
Authors: Hutchison Jaime , Kaushik Karishma , Rodesney Christopher A. , Lilieholm Thomas , Bakhtiari Layla , Gordon Vernita D. 
Published: June 2018

AbstractIn infections, biofilm formation is associated with a number of fitness advantages, such as resistance to antibiotics and to clearance by the immune system. Biofilm formation has also been linked to fitness advantages in environments other than in vivo infections; primarily, biofilms are thought to help constituent organisms evade predation and to promote intercellular signaling. The opportunistic human pathogen Pseudomonas aeruginosa forms biofilm infections in lungs, wounds, and on implants and medical devices. However, the tendency toward biofilm formation originated in this bacterium’s native environment, primarily plants and soil. Such environments are polymicrobial and often resource-limited. Other researchers have recently shown that the P. aeruginosa extracellular polysaccharide Psl can bind iron. For the lab strain PA01, Psl is also the dominant adhesive and cohesive “glue” holding together multicellular aggregates and biofilms. Here, we perform quantitative time-lapse confocal microscopy and image analysis of early biofilm growth by PA01. We find that aggregates of P. aeruginosa have a growth advantage over single cells of P. aeruginosa in the presence of Staphylococcus aureus in low-iron environments. Our results suggest the growth advantage of aggregates is linked to their high Psl content and to the production of an active factor by S. aureus. We posit that the ability of Psl to promote iron acquisition may have been linked to the evolutionary development of the strong biofilm-forming tendencies of P. aeruginosa.
Kinetic basis for DNA target specificity of CRISPR-Cas12a
Authors: Strohkendl Isabel , Saifuddin Fatema A. , Rybarski James R. , Finkelstein Ilya J. , Russell Rick 
Published: June 2018

SUMMARYClass II CRISPR-Cas nucleases are programmable via a single guide RNA, enabling genome editing applications in nearly all organisms. However, DNA cleavage at off-target sites that resemble the target sequence is a pervasive problem that remains poorly understood mechanistically. Here, we use quantitative kinetics to dissect the reaction steps of DNA targeting byAcidaminococcus spCas12a (also known as Cpf1). We show that Cas12a binds DNA tightly in two kinetically-separable steps. Protospacer-adjacent motif (PAM) recognition is followed by rate-limiting R-loop propagation, leading to inevitable DNA cleavage of both strands. Despite the functionally irreversible binding, Cas12a discriminates strongly against mismatches along most of the DNA target sequence, implying substantial reversibility during R-loop formation –a late transition state– and the absence of a ‘seed’ region. Our results provide a quantitative underpinning for the DNA cleavage patterns measured invivoand observations of greater reported target specificity of Cas12a than the Cas9 nuclease.
Dietary Bovine Milk Exosomes Elicit Changes in Microbial Communities in C57BL/6 Mice
Authors: Zhou Fang , Paz Henry A. , Shu Jiang , Sadri Mahrou , Cui Juan , Fernando Samodha C. , Zempleni Janos 
Published: June 2018

ABSTRACTExosomes and exosome-like vesicles participate in cell-to-cell communication in animals, plant and bacteria. Dietary exosomes in bovine milk are bioavailable in non-bovine species, but a fraction of milk exosomes reaches the large intestine. We hypothesized that milk exosomes alter the composition of the gut microbiome in mice. C57BL/6 mice were fed AIN-93G diets, defined by their content of bovine milk exosomes and RNA cargos: exosome/RNA depleted (ERD) versus exosome/RNA-sufficient (ERS) diets. Feeding was initiated at age three weeks and cecum content was collected at ages 7, 15 and 47 weeks. Microbial communities were identified by 16SrRNAgene sequencing. The dietary intake of exosomes and age had significant effects on the microbial communities in the cecum. At the phylum level, the abundance ofVerrucomicrobiawas greater in mice fed ERD compared to ERS, and the abundance of bothFirmicutesandTenericuteswas smaller in mice fed ERD compared to ERS at age 47 weeks. At the family level, the abundance ofAnaeroplasmataceaewas greater in mice fed ERD compared to ERS, and the abundance ofBifidobacteriaceae,Lachnospiraceae, andDehalobacteriaceaewas significantly greater in mice fed ERS than mice fed ERD at age 15 weeks. Exosome feeding significantly altered the abundance of 52 operational taxonomic units; diet effects were particularly strong in theLachnospiraceae,Ruminococcaceaeand theVerrucomicrobiaceaefamilies. We conclude that exosomes in bovine milk alter microbial communities in non-bovine species, suggesting that exosomes and their cargos participate in the crosstalk between bacterial and animal kingdoms.IMPORTANCEVirtually all living cells, including bacteria communicate through exosomes, which can be found in all body fluids. Exosomes and the RNA cargos have been implicated in all aspects of health and disease,e.g.,metastasis of cancer, neuronal signaling and embryonic development. Previously, we reported that exosomes and their microRNA cargos are not solely derived from endogenous synthesis, but may also be obtained from dietary sources such as bovine milk in non-bovine mammals. Here, we report for the first time that bovine milk exosomes communicate with the intestinal microbiome and alters microbial communities in mice. This is the first report suggesting that the gut microbiome facilitates the signaling by dietary exosomes across kingdoms: animal (cow) → bacteria → animal (mouse).
Heliorhodopsins are absent in diderm (Gram-negative) bacteria: Some thoughts and possible implications for activity
Authors: Flores-Uribe José , Hevroni Gur , Ghai Rohit , Pushkarev Alina , Inoue Keiichi , Kandori Hideki , Béjà Oded 
Published: June 2018

AbstractMicrobial heliorhodopsins are a new type of rhodopsins with an opposite membrane topology compared to type-1 and −2 rhodopsins, currently believed to engage in light sensing. We determined their presence/absence is monoderms and diderms representatives from the Tara Oceans and freshwater 25 lakes metagenomes. Heliorhodopsins were absent in diderms, confirming our previous observations in cultured Proteobacteria. Based on these observations, we speculate on the putative role of heliorhodopsins in light-driven transport of amphiphilic molecules.
DNA methylation signature of smoking in lung cancer is enriched for exposure signatures in newborn and adult blood
Authors: Bakulski K. M. , Dou J. , Lin N. , London S. J. , Colacino J. A. 
Published: June 2018

ABSTRACTBackgroundSmoking impacts DNA methylation genome-wide in blood of both newborns from maternal smoking during pregnancy and adults from personal smoking. Smoking causes lung cancer which involves aberrant methylation. We examined whether DNA methylation smoking signatures identified in blood of newborns and adults are detectable in lung tumors.MethodsWe compared smoking-related DNA methylation in lung adenocarcinomas (61 never smokers, 91 current smokers, and 238 former smokers) quantified with the Illumina450k BeadArray in The Cancer Genome Atlas with published large consortium meta-analyses of newborn and adult blood. We assessed whether CpG sites related to smoking in blood from newborns and adults were enriched in lung adenocarcinoma.ResultsTesting CpGs differentially methylated by smoke exposure (P<10−4) we identified 296 in lung tumors, while previous meta-analyses (False Discovery Rate (FDR)<0.05) identified 6,073 in newborn blood, and for adult smoking, 18,760 in blood. The lung signals were highly enriched for those seen in newborn (32 overlapping, Penrichment=1.2×10−19) and adult blood (86 overlapping, Penrichment = 9.5×10−49). The 65 genes annotated to CpGs differentially methylated in lung tumors, but not blood, were enriched for RNA processing ontologies.ConclusionsWe found highly significant overlap between smoking-related DNA methylation signals in lung cancer and those seen in blood from newborns, from in utero exposure, or adults, from their own exposure. These results suggest that some epigenetic alterations associated with cigarette smoke exposure are tissue specific, but others are common across tissues. These findings support the value of blood-based methylation biomarkers for assessing exposure effects in target tissues.
Leader-member exchange and innovative work behavior
Authors: Saeed Bilal Bin , Afsar Bilal , Cheema Sadia , Javed Farheen 
Published: June 2018

PurposeThe purpose of this paper is to examine how leader–member exchange relates to subordinate’s innovative work behavior through core self-evaluation (CSE), domain knowledge and creative process engagement. On the basis of an interactional approach, this study hypothesized that there is an interaction between leader–member exchange, CSE and domain knowledge that affects innovative work behavior, such that leader–member exchange has the strongest positive relationship with innovative work behavior when subordinates have high levels of CSE and domain knowledge; and creative process engagement mediates the effect that this three-way interaction between leader–member exchange, CSE and domain knowledge has on innovative work behavior.Design/methodology/approachData were collected from 323 employees and their immediate supervisors (121) from automotive industry. First, subordinates completed measures of their leader–member exchange, CSE and domain knowledge. Then, the supervisors of these employees assessed their subordinates’ innovative work behavior.FindingsThe results showed that leader–member exchange, CSE and domain knowledge interacted to affect employee innovative work behavior in such a way that when CSE and domain knowledge were both high, leader–member exchange had the strongest positive relationship with innovative work behavior and creative process engagement mediated this relationship.Originality/valueThis study is the first of its kind to empirically examine the interactional perspective of leader–member exchange on innovative work behavior through domain knowledge, CSE and creative process engagement. Theoretical and practical implications and future area of research are discussed at the end.
Application of Six Sigma DMAIC methodology in plain yogurt production process
Authors: Hakimi Saeid , Zahraee Seyed Mojib , Mohd Rohani Jafri 
Published: June 2018

Purpose
This study aims to concentrate on quality improvement in plain yogurt production process at company A through adjusting the factors affecting the acidity of the yogurt and determining the optimal level of these factors.

Design/methodology/approach
Six Sigma-based framework using define-measure-analyze-improve-control (DMAIC) methodology is adopted through the application of design of experiments tool to focus on customer’s requirements to improve the quality characteristic of plain yogurt production process in dairy products manufacturing company (company A) in Iran.

Findings
The results showed that incubation time and fat percentage were significant factors on pH values of yogurt and the optimum settings for these factors were defined as 12 h for the incubation time and 1.5 per cent for the fat percentage.

Research limitations/implications
This study focused solely on the plain yogurt production process in dairy products manufacturing company.

Practical implications
Simplicity of Six Sigma plays a leading role for enabling any dairy manufacturer to determine the problem and minimize its cause through a systematic approach.

Social implications
Six Sigma has been considered to be a systematic, powerful technique to continuously improve the processes and develop the new products by using effective analytical and statistical tools and methods. This paper presents a Six Sigma-based framework using DMAIC methodology to improve the quality characteristic of plain yogurt production process in dairy products manufacturing company.

Originality/value
This study contributes to show a potential area in which Six Sigma DMAIC approach can promote to improve the quality of yogurt production process. This case can prompt managers of the company to apply Six Sigma method to address complicated problems in other processes, where causes particularly are not clear.
Relationships between employee commitment and organizational cultures: a theoretical framework
Authors: Krajcsák Zoltán 
Published: June 2018

Purpose
The purpose of this study is to describe the relationship between organizational commitment and organizational culture with self-evaluation as a mediator variable. The theoretical framework evaluates the culture–commitment relationship based on the characteristics of the individual and underpins explanations of commitment patterns assigned to certain dimensions of organizational culture.

Design/methodology/approach
The study uses a purely theoretical approach, an instrument of which is abstract model creation.

Findings
The individual factors that reinforce deliberate, affective and professional commitment are the hierarchy culture; self-esteem; and self-efficacy, respectively.

Research limitations/implications
The existence of the relationship between the four factors of self-evaluation and the dimensions of the competing values framework (CVF) can be justified by secondary data analysis, although the direction of the causality is still questionable. Practical application of the theoretical model should be supported by empirical analyses in the future.

Originality/value
Research activity in organizational psychology is still mapping the elusive relationship between organizational culture and organizational commitment. In terms of organizational culture, the model is based upon the CVF and uses the five-dimension model of employee commitment instead of the mainstream concept of organizational commitment. This theoretical framework is suitable for evaluating the relationship between organizational culture and commitment when considering the individual features of the employee and supports the explanation of commitment patterns assigned to cultural dimensions.
Do aggressive pro forma earnings-reporting firms have difficulty disclosing intellectual capital? Australian evidence
Authors: Yang Yiru 
Published: June 2018

Purpose
The purpose of this paper is to investigate whether aggressive pro forma earnings-reporting firms are difficult in relation to signalling sufficient intellectual capital (IC), and how the market reacts to aggressive pro forma earnings reporting.

Design/methodology/approach
Content analysis of 610 annual reports of Australian firms listed on the Australian Securities Exchange 200 is used to obtain IC information. Fixed-effects logistic and ordinary least squares (OLS) regressions are used to examine the hypotheses.

Findings
The study finds that aggressive pro forma earnings reporting is negatively and significantly associated with sufficient IC disclosure. Moreover, this paper finds that investors react favourably to aggressive pro forma earnings reporting, and believe that pro forma earnings have greater incremental value-relevance information than statutory earnings.

Research limitations/implications
The coding framework used in this study comprises 33 IC items. Other studies have used coding frameworks comprising fewer or more varied IC items. Therefore, when comparing the results of this and other studies, the interpretation of the findings must recognise the differences in approach.

Practical implications
Sufficient IC disclosure may help investors to distinguish high-reporting-quality firms and low-reporting-quality firms. The paper demonstrates that aggressive pro forma earnings-reporting firms, which are low-reporting-quality firms, are less likely to disclose sufficient IC.

Originality/value
This paper is the first to examine the relationship between aggressive pro forma reporting and IC disclosure. Moreover, this paper built a theoretical framework based on signalling theory to develop research hypotheses, which extend the research on IC underpinned by signalling theory.
Access to gifted education among African-American and Latino males
Authors: Vega Desireé , Moore III James L. 
Published: June 2018

PurposeAcross the nation, African-American and Latino males have experienced limited access to placement in gifted education programs. This paper aims to pinpoint and describe the factors that frequently influence access to gifted education programming among African-American and Latino males.Design/methodology/approachAfrican-American and Latino males are persistently underrepresented in gifted education for reasons such as teachers’ narrow conceptions of giftedness, teachers’ bias in the nomination process and teachers’ inappropriate usage and interpretation of intelligence measures. When these students qualify for such services, they often experience feelings of isolation and loneliness due to scarce representation of other African-American and Latino male students. A review of extant literature was conducted to identify factors that influence access to gifted education programming among African-American and Latino males.FindingsAfrican-American and Latino males encounter roadblocks in being identified for gifted placement and many also experience implicit biases and stereotypical beliefs about their ability. The need for culturally competent professionals is critical to meet the academic and social-emotional needs of gifted African-American and Latino males.Practical implicationsRecommendations for school psychologists and school counselors are offered to support the needs of gifted African-American and Latino males, assist in increasing their identification and participation in gifted education, and promote academic success.Originality/valueThere is an urgent need for research on access and placement in gifted programming among African-American and Latino males. Moreover, the role of school psychologists and school counselors should be considered in facilitation of gifted identification and placement.
Etourism advertising effectiveness: banner type and engagement as moderators
Authors: Muñoz-Leiva Francisco , Liébana-Cabanillas Francisco , Hernández-Méndez Janet 
Published: June 2018

Purpose
This paper aims to analyze advertising effectiveness in terms of self-reported memory (recall) by measuring customers’ visual attention, including consumer engagement with e-tourism 2.0 tools and the banner type used as moderating variables.

Design/methodology/approach
Data were collected through a within-subject, between-groups experimental design based on eye-tracking methodology, followed by a self-administered questionnaire. Participants were instructed to visit three e-tourism tools, namely, a hotel’s blog, a social network (i.e. Facebook) page and a virtual community (i.e. TripAdvisor) page.

Findings
This research uncovers the main determinants of consumers’ self-reported recall of banner ads. The study offers empirical insight regarding the positive impact of fixation counts and visit duration on consumer recall. The findings also reveal that the impact of these measurements on consumer recall is moderated by the level of animation of the advertisement, while the number of fixations is moderated by the level of consumer engagement. Overall, the results suggest the usefulness of eye-tracking methodology in assessing the advertising effectiveness of e-tourism tools.

Research limitations/implications
The practical implications identified in this research, along with its limitations and future research opportunities, are of interest both for further theoretical development and practical applications. Scholars are therefore encouraged to further test the research propositions, including in longitudinal or mobile/smartphone-based research.

Originality/value
The authors offer a pioneering attempt in the application of eye-tracking methodology to online, e-tourism-based service innovations and examine the possible impact of visual marketing stimuli and their effects on user social network-related behavior.