bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated polygenic burden for ASD is associated with the broad autism phenotype
Authors: Nayar K. , Sealock J.M. , Maltman N. , Bush L. , Cook E.H. , Davis L.K. , Losh M. 
Published: November 2019

AbstractBackgroundAutism spectrum disorder (ASD) is a multifactorial, neurodevelopmental disorder that encompasses a complex and heterogeneous set of traits. Subclinical traits that mirror the core features of ASD, referred to as the broad autism phenotype (BAP) have been documented repeatedly in unaffected relatives and are believed to reflect underlying genetic liability to ASD. The BAP may help inform the etiology of ASD by allowing the stratification of families into more phenotypically and etiologically homogeneous subgroups. This study explored polygenic scores related to the BAP.MethodsPhenotypic and genotypic information were obtained from 2,614 trios from Simons Simplex Sample. Polygenic scores of ASD (ASD-PGS) were generated across the sample to determine the shared genetic overlap between the BAP and ASD. Maternal and Paternal ASD-PGS was explored in relation to BAP traits and their child ASD symptomatology.ResultsMaternal pragmatic language was related to child’s social communicative atypicalities. In fathers, rigid personality was related to increased repetitive behaviors in children. Maternal (but not paternal) ASD-PGS was related to the pragmatic language and rigid BAP domains.ConclusionsDomain- and sex-specific associations emerged between parent and child phenotypes. ASD-PGS associations emerged with BAP in mothers only, highlighting the potential for a female protective factor, and implicating the polygenic etiology of ASD-related phenotypes in the BAP.
Pulsed electric fields create pores in the voltage sensors of voltage-gated ion channels
Authors: Rems L. , Kasimova M. A. , Testa I. , Delemotte L. 
Published: November 2019

AbstractPulsed electric fields are increasingly used in medicine to transiently increase the cell membrane permeability via electroporation, in order to deliver therapeutic molecules into the cell. One type of events that contributes to this increase in membrane permeability is the formation of pores in the membrane lipid bilayer. However, electrophysiological measurements suggest that membrane proteins are affected as well, particularly voltage-gated ion channels (VGICs). The molecular mechanisms by which the electric field could affects these molecules remain unidentified. In this study we used molecular dynamics (MD) simulations to unravel the molecular events that take place in different VGICs when exposing them to electric fields mimicking electroporation conditions. We show that electric fields induce pores in the voltage-sensor domains (VSDs) of different VGICs, and that these pores form more easily in some channels than in others. We demonstrate that poration is more likely in VSDs that are more hydrated and are electrostatically more favorable for the entry of ions. We further show that pores in VSDs can expand into so-called complex pores, which become stabilized by lipid head-groups. Our results suggest that such complex pores are considerably more stable than conventional lipid pores and their formation can lead to severe unfolding of VSDs from the channel. We anticipate that such VSDs become dysfunctional and unable to respond to changes in transmembrane voltage, which is in agreement with previous electrophyiological measurements showing a decrease in the voltage-dependent transmembrane ionic currents following pulse treatment. Finally, we discuss the possibility of activation of VGICs by submicrosecond-duration pulses. Overall our study reveals a new mechanism of electroporation through membranes containing voltage-gated ion channels.Statement of SignificancePulsed electric fields are often used for treatment of excitable cells, e.g., for gene delivery into skeletal muscles, ablation of the heart muscle or brain tumors. Voltage-gated ion channels (VGICs) underlie generation and propagation of action potentials in these cells, and consequently are essential for their proper function. Our study reveals the molecular mechanisms by which pulsed electric fields directly affect VGICs and addresses questions that have been previously opened by electrophysiologists. We analyze VGICs’ characteristics, which make them prone for electroporation, including hydration and electrostatic properties. This analysis is easily transferable to other membrane proteins thus opening directions for future investigations. Finally, we propose a mechanism for long-lived membrane permeability following pulse treatment, which to date remains poorly understood.
Local drug delivery to the entire cochlea without breaching its boundaries
Authors: Lukashkin Andrei N. , Sadreev Ildar I. , Zakharova Natalia , Russell Ian J. , Yarin Yury M. 
Published: November 2019

SUMMARYThe mammalian cochlea is one of the least accessible organs for drug delivery. Systemic administration of many drugs is severely limited by the blood-labyrinth barrier. Local intratympanic administration into the middle ear would be a preferable option in this case and the only option for many old and newly emerging classes of drugs but it leads to base-to-apex drug concentration gradients that are orders of magnitude and well outside the therapeutic windows. Here we present an efficient, quick, reliable and simple method of cochlear pumping, through large amplitude, low-frequency reciprocal oscillations of the stapes and round window that can consistently and uniformly deliver drugs along the entire length of the intact cochlea within minutes without disrupting cochlear boundaries. The method should facilitate novel ways of approaching the treatment of inner ear disorders since we have overcome the challenge of delivering of therapeutics along the entire length of the cochlea.GRAPHICAL ABSTRACT
Same Equilibrium. Different Kinetics. Protein Functional Consequences
Authors: Schmid Sonja , Hugel Thorsten 
Published: November 2019

AbstractIn a living cell, protein function is regulated in several ways, including post-translational modifications (PTMs), protein-protein interaction, or by the global environment (e.g. crowding or phase separation). While site-specific PTMs act very locally on the protein, specific protein interactions typically affect larger (sub-)domains, and global changes affect the whole protein in non-specific ways.Herein, we directly observe protein regulation in three different degrees of localization, and present the effects on the Hsp90 chaperone system at the levels of conformational equilibria, kinetics and protein function. Interestingly using single-molecule FRET, we find that similar functional and conformational steady-states are caused by completely different underlying kinetics. Solving the complete kinetic rate model allows us to disentangle specific and non-specific effects controlling Hsp90’s ATPase function, which has remained a puzzle up to this day. Lastly, we introduce a new mechanistic concept: functional stimulation through conformational confinement. Our results highlight how cellular protein regulation works by fine-tuning the conformational state space of proteins.SignificanceProteins are perceived more and more as dynamic systems whose function depends critically on local and global flexibility. While 3D structures of proteins are frequently available today, our models often lack the time component, namely rate constants that determine protein function and regulation.Here we used single-molecule FRET to elucidate how the chaperone protein Hsp90 is regulated on various levels, locally and globally. We find that ATPase stimulation occurs not only through specific interactions, but also non-specifically by reducing non-productive conformational flexibility; i.e. by changing kinetics rather than thermodynamics. Our work introduces ‘stimulation through conformational confinement’ as a general mechanistic concept. We anticipate that this concept plays an important role in protein regulation, phase separation, and in dynamic protein systems in general.
The accumulation of chloroplast small RNAs in unicellular algaChlamydomonas reinhardtiiis affected by nitrogen deprivation
Authors: Che-Ani Suhaimi , Azzam Ghows , Najimudin Nazalan 
Published: November 2019

ABSTRACTSmall RNAs generated from the chloroplast genome may play a role in gene regulation. Given that chloroplast function is affected by nitrogen deprivation, there is yet an attempt to link chloroplast small RNAs to this stress condition. This study aims to determine the response of chloroplast small RNAs under nitrogen deprivation and their putative mode of action. A comparative transcriptomic approach was carried out to analyze the differential accumulation of chloroplast small RNAs fromChlamydomonas reinhardtiicells grown in nitrogen-deprived versus nitrogen-based medium. A total of 101 chloroplast small RNA candidates were successfully annotated. Growth in nitrogen-deprived medium revealed 17 significantly upregulated and 12 downregulated chloroplast small RNAs. These chloroplast small RNAs originated from different genomic locations such as untranslated, intergenic or antisense regions as well as the ends of tRNA and rRNA genes. The differentially accumulated csRNAs from 3’-untranslated regions were all upregulated. In contrast, the csRNAs from the ends of tRNA and rRNA genes were all downregulated during nitrogen deprivation. Fluctuations of the chloroplast small RNA levels indicated their importance in the chloroplasts during changes in nitrogen levels. The primary sequences of three selected chloroplast small RNA were found to be conserved in the chloroplast genomes of a few microalgae, again reflecting their functional importance. The findings from this study provided new insights into the involvement of non-coding RNAs in chloroplast during metabolic stress.
Unpaired Data Empowers Association Tests
Authors: Gong Mingming , Liu Peng , Sciurba Frank C. , Stojanov Petar , Tao Dacheng , Tseng George C. , Zhang Kun , Batmanghelich Kayhan 
Published: November 2019

AbstractTo achieve a holistic view of the underlying mechanisms of human diseases, the biomedical research community is moving toward harvesting retrospective data available in Electronic Healthcare Records (EHRs). The first step for causal understanding is to perform association tests between types of potentially high-dimensional biomedical data, such as genetic, blood biomarkers, and imaging data. To obtain a reasonable power, current methods require a substantial sample size of individuals with both data modalities. This prevents researchers from using much larger EHR samples that include individuals with at least one data type, limits the power of the association test, and may result in higher false discovery rate. We present a new method called the Semi-paired Association Test (SAT) that makes use of both paired and unpaired data. In contrast to classical approaches, incorporating unpaired data allows SAT to produce better control of false discovery and, under some conditions, improve the association test power. We study the properties of SAT theoretically and empirically, through simulations and application to real studies in the context of Chronic Obstructive Pulmonary Disease. Our method identifies an association between the high-dimensional characterization of Computed Tomography (CT) chest images and blood biomarkers as well as the expression of dozens of genes involved in the immune system.
An rpw8 quadruple mutant of Arabidopsis Col-0 is partially compromised in bacterial and fungal resistance
Authors: Castel Baptiste , Wu Yan , Xiao Shunyuan , Jones Jonathan D G 
Published: November 2019

AbstractThe plant immune system relies on both cell-surface and intracellular NLR (nucleotide-binding, leucine-rich repeat) receptors. NLRs respond to pathogen effectors and activate effector-triggered immunity: a cocktail of responses, often accompanied by cell death, resulting in resistance.RPW8 encodes an unusual non-NLR Resistance (R) protein and confers broad-spectrum powdery mildew resistance. It requires genetic components also required by some NLRs, resembles the HeLo-containing protein MLKL (necroptosis executor in animals) and HET-S (cell death executor in fungi) and is targeted to the extra-haustorial membrane during powdery mildew infection by its N-terminal non-cleaved signal anchor domain. RPW8 displays extensive recent duplication events in Arabidopsis and certain alleles can induce oligomerisation-dependent activation of the NLR RPP7.All these features enabled us to formulate hypotheses for RPW8 function: (1) RPW8 could be a cell death executor for defence against pathogens. (2) RPW8 could be a decoy for effector targets.To test these hypotheses, we generated a quadruple knock-out mutant of the four RPW8-homologous copies in Arabidopsis Col-0, using CRISPR. The mutant still displays cell death upon activation of four well-characterised NLRs. However, it is partially impaired in powdery mildew resistance and also in bacterial resistance. Interestingly Col-0_rpw8 is delayed in flowering transition. In conclusion, RPW8 plays a broad role in immunity and plant development, beyond resistance to powdery mildew. There is no evidence that it is involved in executing ETI-associated cell death.
CEO age and analysts forecast properties
Authors: Haider Imran , Sultana Nigar , Singh Harjinder , Tham Yeut Hong 
Published: November 2019

Purpose
The purpose of this paper is to assess whether there is an association between CEO age and analysts forecast properties (particularly forecast accuracy and bias/optimism). CEOs, having the central role in managing firms, can significantly influence the financial and non-financial decisions in an organisation. Furthermore, having been identified as key culprits in past major accounting scandals, it is also important to identify the CEO characteristics that affect financial reporting decisions.

Design/methodology/approach
This study adopts the upper echelon theory on the relationship between CEO age and analysts forecast properties. The authors use a sample of 2,730 Australian firm-year observations for the period 2004–2013 drawn from IBES, Connect 4 and SIRCA databases.

Findings
The authors find that analyst forecast accuracy increases and bias (optimism) reduces with the CEO age. The authors conclude that earnings and related information provided to analysts improves with the CEO age, which increases the forecast accuracy and reduces bias (optimism). Additional results suggest that the positive (negative) effect of CEO age on forecast accuracy (bias) remains until the CEOs reach the age of their retirement age (65 years). The results remain consistent with a number of sensitivity tests and provide implication for stakeholders such as firms, analysts, auditors, financial statements users and regulators.

Practical implications
The authors demonstrate that the relationship between CEO age and analyst forecast properties is not linear but is, in fact, curvilinear substantiating concerns that CEOs that are much younger or much older do not help increase the quality of the information environment. Consequently, firms hiring CEOs in the right age bracket also benefit by having higher-quality information environment leading possibly to reduce costs such as those relating to debt and/or equity ultimately increasing firm value.

Originality/value
Empirical studies on the association between CEO age and analysts earnings properties in Australia are scarce and this paper contributes to the determinants of the analysts forecast accuracy and bias (optimism) and the CEO age literature.
Explaining university student loyalty: theory, method, and empirical research in Chile
Authors: Gallegos Juan Alejandro , Vasquez Arturo 
Published: November 2019

PurposeThe purpose of this paper is to explain student loyalty beyond its customary relationship with student satisfaction by including two relational variables, trust and commitment, two cognitive traits (service familiarity and communication) and one affective trait (opportunism) as moderators of the impact of trust and commitment on loyalty.Design/methodology/approachTwo relational constructs (trust and commitment) are employed to improve the loyalty model and key comparisons are performed to know if career, cohort and sourcing school generate differences in the explanation of student loyalty.FindingsResults show that the explanation chain that starts with student satisfaction but continues with the development of student trust and the reaching of student commitment culminates with student loyalty. The moderators (student opportunism, service familiarity, communication, age and available income for education) significantly contribute to the explanatory power of the model. Career is a meaningful differentiator in reaching student loyalty as are student cohort and the type of high school from which the student came.Research limitations/implicationsThis is one of first empirical studies on university student loyalty. Future research could test the same or new hypotheses using different samples and contexts.Practical implicationsUniversity policies may benefit from the inclusion of norms regarding relational processes and outcomes such as the value of trust in the interactions and systematic recognition and awards assigned to student commitment achievements.Originality/valueThe explanation chain of customer loyalty was successfully applied to student loyalty, and strengthened with the addition of meaningful moderating variables.
Web scraping for food price research
Authors: Hillen Judith 
Published: November 2019

Purpose
The purpose of this paper is to discuss web scraping as a method for extracting large amounts of data from online sources. The author wants to raise awareness of the method’s potential in the field of food price research, hoping to enable fellow researchers to apply this method.

Design/methodology/approach
The author explains the technical procedure of web scraping, reviews the existing literature, and identifies areas of application and limitations for food price research.

Findings
The author finds that web scraping is a promising method to collect customised, high-frequency data in real time, overcoming several limitations of currently used food price data sources. With today’s applications mostly focussing on (online) consumer prices, the scope of applications for web scraping broadens as more and more price data are published online.

Research limitations/implications
To better deal with the technical and legal challenges of web scraping and to exploit its scalability, joint data collection projects in the field of agricultural and food economics should be considered.

Originality/value
In agricultural and food economics, web scraping as a data collection technique has received little attention. This is one of the first articles to address this topic with particular focus on food price analysis.
The effects of relationship bonds on bank employees’ psychological responses and boundary-spanning behaviors
Authors: Lee Myoung-Soung , Han Sang-Lin 
Published: November 2019

PurposeThe purpose of this paper is to examine the effects of relationship bonds on the psychological response and behavior of bank employees based on the job demands–resources theory. Specifically, it examines the effects of relationship bonds in terms of person–job (P–J) fit, emotional exhaustion, job satisfaction and boundary-spanning behaviors, all of which comprise the behavioral dimensions of bank employees. In addition, the study examines how the resiliency of bank employees influences their emotional exhaustion and determines whether a moderating effect related to emotional exhaustion exists.Design/methodology/approachTo achieve this aim, data were collected from 365 customer-facing banking employees in South Korea. Reliability, validity and the hypotheses were verified through structural equation modeling; any moderating effects were identified using the bootstrap method and the process model.FindingsStudy results showed that financial, structural, internal social and external social bonds – the bonds pertaining to relationship elements – have positive effects on P–J fit. P–J fit influenced emotional exhaustion negatively and job satisfaction positively. Furthermore, emotional exhaustion negatively influenced job satisfaction. Job satisfaction had positive effects on service delivery, external representation and internal influence, the elements comprising boundary-spanning behavior. Finally, resiliency was shown to lower emotional exhaustion but revealed no moderating effect.Originality/valueFirst, this study examined relationship bonds, which reference relationship marketing when introducing organizational resources that influence the psychological and behavioral responses of bank employees. Second, this study introduced resiliency as a personal resource and clarified the way it applies to an individual’s psychological response. Third, existing literature has been limited to conducting fragmented research of the psychological factors that intervene in predisposing factors and job outcomes. This study makes a unique contribution by establishing a psychological response process.
Evolutionary awareness: Darwin among the organizational sciences
Authors: Duening Thomas , Nicholson Nigel , Bradley-Geist Jill 
Published: November 2019

PurposeRecent criticisms of organizational science theory have lamented a lack of depth and a growing “maturity” that is impeding empirical advances. The purpose of this paper is to propose that organizational scientists can address this problem by embracing “evolutionary awareness” (EA). EA builds on theories and constructs developed in the evolutionary sciences that serve to add depth to theory building.Design/methodology/approachThe design of the paper is first to introduce the concept of EA and identify its four key constructs. Next, the authors apply EA to three areas of research within organizational science: human motivation, interpersonal communication and leadership. The authors’ intent is to show that EA constructs extend and deepen traditional organizational science theorizing. Thereby, the authors show that the problems noted above, i.e., lack of depth and maturing theories, can be addressed by embracing EA.FindingsThe findings are that EA substantially enhances and freshens theorizing in the organizational sciences in the areas of human motivation, communication and leadership. By extension, other areas of interest will also benefit by embracing the EA perspective.Research limitations/implicationsThe implications of the research are many. Organizational scientists can advance theory building, research and practical prescriptions by embracing EA. They can also engage in interdisciplinary research programs with scholars in the evolutionary sciences eager to see their work having practical implications. The limitation of this work is that the authors were only able to show a limited application of EA to three areas of interest to organizational science scholars.Practical implicationsThe practical implications of this research are potentially far reaching. At this very moment, scholars in a wide array of disciplines are re-casting their views of humanity, cognition, values and other constructs based on the acceptance of evolution and its primary mechanism, variation and selection based on consequences. These changes will usher in new ideas about leadership, work-life balance, organizational purpose and many others.Social implicationsA much-needed “consilience” across the human sciences through embracement of the EA perspective may provide insights that will advance human flourishing in organizations and beyond. The authors believe that an increasingly veridical understanding of humanity will produce substantial social impact.Originality/valueThis work will provide an encompassing perspective that will assist organizational scholars in advancing their theory building and research questions. A much-needed “consilience” across the human sciences may provide insights that will advance human flourishing in organizations and beyond.