bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lysyl oxidase inhibition drives the transdifferentiation from lung adenocarcinoma to squamous cell carcinoma in mice
Authors: Yao Shun , Han Xiangkun , Tong Xinyuan , Li Fuming , Qin Zhen , Huang Hsin-Yi , Hongbin Ji 
Published: May 2018

AbstractLKB1is frequently mutated in human non-small cell lung cancer (NSCLC) andLkb1deletion in mice triggered the lung adenocarcinoma (ADC) to squamous cell carcinoma (SCC) transdifferentiation (AST) through lysyl oxidase (LOX)-dependent extracellular matrix remodeling. Here we show that pharmacological inhibition of lysyl oxidase inKrasG12D/Trp53L/Lmouse model, which is known to produce lung ADC only, triggers the ADC-to-SCC transdifferentiation independent ofLKB1status. Treatments of two different inhibitors of lysyl oxidase decrease collagen deposition and promote redox accumulation, and eventually trigger the AST. Importantly, these transited SCC show strong resistance to lysyl oxidase inhibition in stark contrast to ADC. Collectively, these findings establish a new AST mouse model independent ofLKB1inactivation status.
Choline monooxygenase transcript expression triggers glycine betaine accumulation in Suaeda maritima when subjected to a salt concentration optimal for its growth
Authors: Kuttan Sindhu , Sankararamasubramanian H.M. , Parida Ajay Kumar 
Published: May 2018

AbstractSuaeda maritima(L.) Dumort, an annual halophyte known to be a salt-accumulator is also known for the accumulation of the osmolyte, glycine betaine (GB). This study is an attempt to understand the growth and GB accumulation under optimal concentration of 200 mM NaCl in S. maritima. Salt treatment with 200 mM NaCl showed a significant increase in shoot growth after two weeks. The shoots appeared succulent and turgid after two weeks of salt treatment compared to that of the control which appeared slender and wilted. The treated seedlings also exhibited a significant increase in GB content after two weeks of salt treatment. In order to determine the molecular basis of GB accumulation, qRT PCR of three key genes involved in the pathway, choline monooxygenase, betaine aldehyde dehydrogenase and phospho-ethanolamine N-methyl transferase was performed. Transcript level expression of the three genes revealed a high up-regulation of choline monooxygeanse transcripts when compared to that of the other two transcripts at two days of salt treatment. The results indicate that S. maritima requires salt for its growth and is a natural accumulator of GB. Although all the three genes were salt inducible, the high up-regulation of choline monooxygenase greatly contributes to the accumulation of GB under optimal growth as well as NaCl concentration.AbbreviationsBADHbetaine aldehyde dehydrogenaseCMOcholine monooxygenaseGBglycine betainePEAMTphosphoethanolamine N-methyl transferase
Novel antimicrobial peptide discovery using machine learning and biophysical selection of minimal bacteriocin domains
Authors: Fields Francisco R. , Freed Stephan D. , Carothers Katelyn E. , Hamid Md Nafiz , Hammers Daniel E. , Ross Jessica N. , Kalwajtys Veronica R. , Gonzalez Alejandro J. , Hildreth Andrew D. , Friedberg Iddo , Lee Shaun W. 
Published: May 2018

AbstractBacteriocins are ribosomally produced antimicrobial peptides that represent an untapped source of promising antibiotic alternatives. However, inherent challenges in isolation and identification of natural bacteriocins in substantial yield have limited their potential use as viable antimicrobial compounds. In this study, we have developed an overall pipeline for bacteriocin-derived compound design and testing that combines sequence-free prediction of bacteriocins using a machine-learning algorithm and a simple biophysical trait filter to generate minimal 20 amino acid peptide candidates that can be readily synthesized and evaluated for activity. We generated 28,895 total 20-mer peptides and scored them for charge, α-helicity, and hydrophobic moment, allowing us to identify putative peptide sequences with the highest potential for interaction and activity against bacterial membranes. Of those, we selected sixteen sequences for synthesis and further study, and evaluated their antimicrobial, cytotoxicity, and hemolytic activities. We show that bacteriocin-based peptides with the overall highest scores for our biophysical parameters exhibited significant antimicrobial activity against E. coli and P. aeruginosa. Our combined method incorporates machine learning and biophysical-based minimal region determination, to create an original approach to rapidly discover novel bacteriocin candidates amenable to rapid synthesis and evaluation for therapeutic use.
Use of selenocysteine, the 21st amino acid, in the fungal kingdom
Authors: Mariotti Marco , Salinas Gustavo , Gabaldón Toni , Gladyshev Vadim N. 
Published: May 2018

ABSTRACTSelenoproteins are a diverse class of proteins containing selenocysteine (Sec), the 21st amino acid, incorporated into proteins during translation through a unique recoding mechanism. Selenoproteins fulfil essential roles in several lineages, including vertebrates; yet, they are not ubiquitous across the tree of life. In particular, the fungal kingdom was thought to lack selenoproteins, a paradigm that we defy here. We show that the genetic machinery for Sec utilization is present in the genomes of five species belonging to diverse early-branching fungal phyla (Chytridiomycota, Zoopagomycota, and Mucoromycota). We identified several selenoprotein genes in each of these genomes, and we detected canonical Sec insertion RNA structures (SECIS elements) for some of them. The identified selenoproteins are known or predicted oxidoreductases, some of which are conserved in mammals. Phylogenetic analyses support a scenario of vertical inheritance of the Sec trait within eukaryotes and fungi. Sec was then lost in numerous independent events in various fungal lineages, even within Sec-containing phyla. Notably, Sec was lost at the base of Dikarya, resulting in the absence of this trait in Saccharomyces cerevisiae and other well studied fungi. Our results indicate that, despite scattered occurrence, selenoproteins are found in all kingdoms of life.
ATTENTION! The following preprint should no longer be cited as the manuscript and data in their present form are no longer valid!
Authors: Brunner Nikolaus , Groeger Stephan , Canelas Raposo Joao , Bruckmaier Rupert M. , Gross Josef J. 
Published: May 2018

AbstractSubclinical ketosis (SCK) and periparturient diseases considerably account for economic and welfare losses in dairy cows. The majority of scientific reports investigating the prevalence of SCK and production diseases are based on empirical studies conducted in Western Europe and North America. The present study surveyed the prevalence of SCK and production-related clinical diseases in early lactating cows in various countries across the world other than those in North America and Western Europe. Twelve countries of South and Central America (Argentina, Brazil, Chile, Colombia, Mexico), Africa (South Africa), Asia (Thailand, China), Eastern Europe (Russia, Ukraine), Australia and New Zealand were assessed, and data from a total of 8,902 cows kept at 541 commercial dairy farms were obtained. A minimum of 5 cows per farm were blood sampled and examined once after parturition up to day 21 of lactation. Blood concentration of β-hydroxybutyrate (BHBA) was measured (threshold for SCK: 1.2 mmol/l) and the presence of production-related diseases such as milk fever, retained placenta, mastitis, metritis, displaced abomasum, claw disease and clinical ketosis was recorded. More than 95% of all cows were examined in their second week of lactation. Across all investigated countries, the SCK prevalence was 24.1%, ranging from 8.3% up to 40.1%. The prevalence of production-related diseases detected during the first 21 days of lactation was relatively low (< 5%). Calculated odds ratios did not indicate an elevated risk for production diseases in cows with SCK. Despite differences in production systems across countries and variation between individual farms within a region, the present study data on SCK prevalence align with observations in Western European and North American dairy herds. At the very early stage of sampling and clinical examination for detection of SCK, it cannot be excluded that certain production diseases such as DA, lameness and mastitis have developed later.
First person experience of threat modulates cortical network encoding human peripersonal space
Authors: de Borst A.W. , Sanchez-Vives M.V. , Slater M. , de Gelder B. 
Published: May 2018

AbstractPeripersonal space is the area directly surrounding the body, which supports object manipulation and social interaction, but is also critical for threat detection. In the monkey, ventral premotor and intraparietal cortex support initiation of defensive behavior. However, the brain network that underlies threat detection in human peripersonal space still awaits investigation. We combined fMRI measurements with a preceding virtual reality training from either first or third person perspective to manipulate whether approaching human threat was perceived as directed to oneself or another. We found that first person perspective increased body ownership and identification with the virtual victim. When threat was perceived as directed towards oneself, synchronization of brain activity in the human peripersonal brain network was enhanced and connectivity increased from premotor and intraparietal cortex towards superior parietal lobe. When this threat was nearby, synchronization also occurred in emotion-processing regions. Priming with third person perspective reduced synchronization of brain activity in the peripersonal space network and increased top-down modulation of visual areas. In conclusion, our results showed that after first person perspective training peripersonal space is remapped to the virtual victim, thereby causing the fronto-parietal network to predict intrusive actions towards the body and emotion-processing regions to signal nearby threat.
The metabolic redox regime ofPseudomonas putidatunes its evolvability towards novel xenobiotic substrates
Authors: Akkaya Özlem , Pérez-Pantoja Danilo R. , Calles Belén , Nikel Pablo I. , de Lorenzo Victor 
Published: May 2018

ABSTRACTDuring evolution of biodegradation pathways for xenobiotic compounds, the transition towards novel substrates of Rieske non-heme iron oxygenases borne by environmental bacteria is frequently associated with faulty reactions. Such reactions release reactive oxygen species (ROS), endowed with high mutagenic potential. The present work studies how the operation of a given metabolic network by a bacterial host may either foster or curtail the still-evolving biochemical pathway for catabolism of 2,4-dinitrotoluene (2,4-DNT). To this end, the genetically tractable strainPseudomonas putidaEM173 was chromosomally implanted with a Tn7 construct carrying the whole genetic complement (recruited from the environmental isolateBurkholderiasp. R34) necessary for complete biodegradation of 2,4-DNT. By using reporter technology and direct measurements of ROS formation, we observed that the engineeredP. putidastrain experienced oxidative stress when catabolizing the nitroaromatic substrate. However, ROS was neither translated into significant activation of the SOS response to DNA damage nor resulted in a mutagenic regime (unlikeBurkholderiasp. R34, the original host of the pathway). To inspect whether the tolerance ofP. putidato oxidative insults could be traced to its characteristic reductive redox regime, we artificially lowered the pool of NAD(P)H by conditional expression of a water forming, NADH-specific oxidase. Under the resulting low-NAD(P)H status, 2,4-DNT triggered a conspicuous mutagenic and genomic diversification scenario. These results indicate that the background biochemical network of environmental bacteria ultimately determines the evolvability of metabolic pathways. Moreover, the data explains the efficacy of some bacteria such as Pseudomonads to host and evolve new catabolic routes.IMPORTANCESome environmental bacteria evolve new capacities for aerobic biodegradation of chemical pollutants by adapting pre-existing redox reactions to recently faced compounds. The process typically starts by co-option of enzymes of an available route to act on the chemical structure of the substrates-to-be. The critical bottleneck is generally the first biochemical step and most of the selective pressure operates on reshaping the initial reaction. In Rieske non-heme iron oxygenases, the interim uncoupling of the novel substrate to the old enzymes results in production of highly mutagenic ROS. In this work, we demonstrate that the background metabolic regime of the bacterium that hosts an evolving catabolic pathway (e.g. biodegradation of the xenobiotic 2,4-DNT) determines whether the cells would either adopt a genetic diversification regime or a robust ROS-tolerant state. These results expose new perspectives to contemporary attempts for rational assembly of whole-cell biocatalysts, as pursued by present-day metabolic engineering.
The effect of supervised work experience on the acquisition of employability skills among Malaysian students
Authors: Kamaliah Sharifah , Roslan Samsilah , Bakar Ab Rahim , Ghiami Zeinab 
Published: May 2018

Purpose
The vocational education and training (VET) system needs a future change in order to be more accountable to employers (and their associations) for training outcomes that match employer expectations. As part of this, an important focus is employability skills that go beyond work-related technical and interpersonal skills to include employer-preferred values, attitudes and personality dimensions. The purpose of this paper is to determine the effect of supervised work experiences (SWEs), among other factors, on undergraduate vocational trainees’ acquisition of employability skills.

Design/methodology/approach
A total of 138 respondents ranging in age from 17 to 24 years who successfully completed their two years program awarded with Malaysian Skill Certificate were included. They were divided into two sub-populations, trainees participating and trainees not participating in the SWE. Descriptive analysis, Correlation and ANCOVA were applied for data analysis.

Findings
The results showed that participating students achieved a moderately higher level of employability skills compared to students not participating in the SWE. The findings also revealed other factors contributing to the acquisition of employability skills, including gender, age, work experience, self-concept and achievement motivation. However, achievement motivation was found to be significantly related to the acquisition of employability skills. Therefore, participation of vocational trainees in the SWE influences the acquisition of employability skills which are identified as career success skills and could facilitate youth in transition from school to work.

Research limitations/implications
Although the research has reached the aims, there were a few limitations which may effect on generalization of the findings. Because of the limit access to students from all majors in vocational training, this study focused on six types of skills. In addition, the number of participants from different courses was not equal.

Practical implications
The research findings also imply several practical implications. First, based on the finding, it can be suggested that industries provide students’ vocational training under supervision of expert in their course area in order to enrich the level of trainees’ acquisition of employability skills. Second, referring to the finding, focusing on the key aspects of employability skills, industries can improve the trainees learning process and producing workers with abilities to allow them to interact with job duties in the organization of workplace.

Originality/value
This study can serve as a model for evaluation when implementing school to work programs.
Human capital and labor: the effect of entrepreneur characteristics on venture success
Authors: Lee Byungku 
Published: May 2018

PurposeThe purpose of this paper is to offer a unique perspective on the role of entrepreneurs’ hard work for the relationship between entrepreneur human capital and venture success. To this end, this study examined whether entrepreneurs with high human capital work harder than entrepreneurs with low human capital, the effect of entrepreneurs’ hard work on venture performance, and whether entrepreneurs’ hard work mediates the relationship between entrepreneur human capital and venture performance.Design/methodology/approachIn this explorative study, the role of entrepreneurs’ hard work as a mediator that transfers entrepreneur human capital into venture success was examined in a sample of 2,648 single-founder startups in the USA and 21,184 observations during the period of 2004-2011.FindingsThe effect of entrepreneurs’ industry experience on entrepreneurs’ hard work was significantly positive, while the effect of entrepreneurs’ general education on entrepreneurs’ hard work was significantly negative. Moreover, entrepreneurs’ hard work was a significant predictor of venture success. Finally, the results showed that entrepreneurs’ hard work partially mediates the positive relationship between entrepreneurs’ industry experience and venture success.Originality/valueOn one hand, the link between human capital and firm performance has been studied thoroughly and findings so far support the positive link between them. On the other hand, there has been continuous criticism that human capital gained much of its attention at the expense of human labor. There is a paucity of research, however, that investigating the dynamics of the relationships between human capital and human labor. This study provides an empirical explanation of such dynamics of the relationships of human characteristics in the context of entrepreneurship.
Site specific assessment of wind characteristics and determination of wind loads effects on wind turbine components and energy generation
Authors: Wei Jiang , Hulio Zahid Hussain , Rashid Haroon 
Published: May 2018

PurposeThe purpose of this paper is to analyze wind characteristics and their effects on wind turbine components and energy generation at the candidate site.Design/methodology/approachThe methodology covered the detailed investigation of wind characteristics using Weibullkandcparameters and standard deviation at 30 m above the ground level (AGL). The wind shear coefficient and air density were also studied. The weight model was developed to determine the effects on wind turbine components and energy generation. At last, an economic assessment was carried out to determine the pre- and post-effects of the weight model on the cost of energy per kilowatt-hour.FindingsThe mean standard deviation, Weibullkparameter and Weibullcparameter were found to be 2.157, 2.617 and 6.087 m/s, respectively, at 30 m for a period of a year. The mean wind shear coefficient was found to be 0.176 for a year. The calculated results showed that site-specific midrange and amplitude force were 40.95 per cent and 37.75 per cent on wind turbine mechanical components, respectively. The average rise in force and drop in energy was found to be 35.50 per cent and 47.55 per cent, respectively. The lift coefficient, drag coefficient and pitching moment considering values (a, 0.1 and 0.2) showed an increase in force on wind turbine components that resulted in a drop in energy. The cost assessment results showed that the cost of energy was increased from US$0.032/kWh to 0.0466/kWh for wind turbineA.Practical implicationsAn accurate determination of the weight factor is necessary for near-reality assessment of wind energy yield and rise of force on the wind turbine. The results paved the way for site-specific design optimization of wind turbines.Originality/valueThe study contributes to the site-specific wind characteristic-based weight model to determine the effects of wind loads on wind turbine components and energy generation and compared with the specified design standard. The lift coefficient, drag coefficient and pitching moment coefficient show a rise in the force while considering the weight factor values. The results show that the site has the potential to generate energy at the lowest cost per kilowatt-hour, but it needs wind turbine design adjustments according to site-specific wind characteristics. If site-specific wind characteristics are considered, it would lead to maximum energy generation and high reliability of wind turbine components.
Winery website loyalty: the role of sales promotion and service attributes
Authors: Pelet Jean-Eric , Lecat Benoît , Khan Jashim , Rundle-Thiele Sharyn , Lee Linda W. , Ellis Debbie , Wolf Marianne McGarry , Kavoura Androniki , Katsoni Vicky , Wegmann Anne Lena 
Published: May 2018

Purpose
This paper aims to examine the relationship between feelings toward buying wine on mobile phones and m-commerce website loyalty by examining the mediating role of sales promotion and the moderating role of service attributes of the m-commerce websites in influencing the mediation.

Design/methodology/approach
A total of 3,318 completed surveys were collected. Drawing on a large non-probability criterion-based purposive sample across six countries (France, Germany, Greece, South Africa, USA and Canada), mediation analysis was performed to examine the hypothesized relationships.

Findings
Results show that sales promotion mediates the relationship between feelings toward buying wine on mobile phones and m-commerce website loyalty. Moderated mediation reveals that the indirect pathways (sales promotion) through which feelings toward buying wine over mobile exert its effect on m-commerce website loyalty are dependent on the value of service (wine delivery) attributes of the website. The results demonstrate that sales promotion and service are of paramount importance to wineries and wine marketers.

Research limitations/implications
Wine producers and retailers should consider the use of sales promotion to enhance sales and loyalty to m-commerce websites.

Practical implications
Wine producers and retailers should consider use sales promotion (such as SMS or push notifications) to enhance sales and influence consumer feelings and hence their loyalty.

Originality/value
Wine m-commerce studies are limited, especially with an international perspective comparing six different countries: three from the old world (France, Germany and Greece) and three from the new world (North America with USA and Canada; and South Africa). Altogether, these six countries represent around 40 per cent of the world’s wine consumption.