bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive gene expression analysis detects global reduction of proteasome subunits in schizophrenia
Authors: Hertzberg Libi , Maggio Nicola , Muler Inna , Yitzhaky Assif , Majer Michael , Haroutunian Vahram , Katsel Pavel , Domany Eytan , Weiser Mark 
Published: November 2019

ABSTRACTOBJECTIVEA main challenge in the study of schizophrenia is its high heterogeneity. While it is generally accepted that there exist several biological mechanisms that may define distinct schizophrenia subtypes, they haven’t been identified yet. We applied comprehensive gene expression analysis, searching for molecular signals that differentiate patients with schizophrenia from healthy controls, and examined whether the identified signal characterizes a particular subgroup of the patients.METHODSWe performed transcriptome sequencing of 14 superior temporal gyrus (STG) samples of relatively young (mean age: 44) subjects with schizophrenia and 15 matched controls from the Stanley Medical Research Institute. Analyses of differential expression and pathway enrichment were applied and the results were compared with those obtained from an independent cohort of elderly (mean age: 74) patients. Replicability was then tested on six additional independent datasets of various brain regions.RESULTSThe two STG cohorts of relatively young and elderly subjects showed high replicability. Pathway enrichment analysis of the down-regulated genes pointed to proteasome-related pathways. Meta-analysis of differential expression identified down-regulation of 12 of 39 proteasome subunits in schizophrenia. Down-regulation of multiple proteasome subunits was replicated in six additional datasets (overall 8 cohorts, with 267 schizophrenia and 266 control samples, from 5 brain regions, were studied). This signal was concentrated in a subgroup of the patients.CONCLUSIONSWe detect global down-regulation of proteasome subunits in a subgroup of the patients with schizophrenia. The proteasome is a major intracellular protein degradation system, where ubiquitinated proteins (proteins bound by the small protein called ubiquitin) are targeted for degradation. We hypothesize that the down-regulation we detect leads to proteasome dysfunction that causes accumulation of ubiquitinated proteins. Such accumulation has recently been identified, also in a subgroup of the studied patients with schizophrenia. Thus, down-regulation of proteasome subunits might define a biological subtype of schizophrenia.
A versatile high throughput screening platform for plant metabolic engineering highlights the major role of ABI3 in lipid metabolism regulation
Authors: Pouvreau Benjamin , Blundell Cheryl , Vohra Harpreet , Zwart Alexander B. , Arndell Taj , Singh Surinder , Vanhercke Thomas 
Published: November 2019

AbstractTraditional functional genetic studies in crops are time-consuming, complicated and cannot be readily scaled up. The reason is that mutant or transformed crops need to be generated to study the effect of gene modifications on specific traits of interest. However, many crop species have a complex genome and a long generation time. As a result, it usually takes several months to over a year to obtain desired mutants or transgenic plants, which represents a significant bottleneck in the development of new crop varieties.To overcome this major issue, we are currently establishing a versatile plant genetic screening platform, amenable to high throughput screening in almost any crop species, with a unique workflow. This platform combines protoplast transformation and fluorescence-activated cell sorting.Here we show that tobacco protoplasts can accumulate high levels of lipids if transiently transformed with genes involved in lipid biosynthesis and can be sorted based on lipid content. Hence, protoplasts can be used as a predictive tool for plant lipid engineering. Using this newly established strategy, we demonstrate the major role of ABI3 in plant lipid accumulation.We anticipate that this workflow can be applied to numerous highly valuable metabolic traits other than storage lipid accumulation. This new strategy represents a significant step towards screening complex genetic libraries, in a single experiment and in a matter of days, as opposed to years by conventional means.
BAG3 Pro209 mutants associated with myopathy and neuropathy relocate chaperones of the CASA-complex to aggresomes
Authors: Adriaenssens Elias , Tedesco Barbara , Mediani Laura , Asselbergh Bob , Crippa Valeria , Antoniani Francesco , Carra Serena , Poletti Angelo , Timmerman Vincent 
Published: November 2019

AbstractThree missense mutations targeting the same proline 209 (Pro209) codon in the co-chaperone Bcl2-associated athanogene 3 (BAG3) have been reported to cause distal myopathy, dilated cardiomyopathy or Charcot-Marie-Tooth type 2 neuropathy. Yet, it is unclear whether distinct molecular mechanisms underlie the variable clinical spectrum of the rare patients carrying these three heterozygous Pro209 mutations in BAG3. Here, we studied all three variants and compared them to the BAG3_Glu455Lys mutant, which causes dilated cardiomyopathy. We found that all BAG3_Pro209 mutants have acquired a toxic gain-of-function, which causes these variants to accumulate in the form of insoluble HDAC6- and vimentin-positive aggresomes. The aggresomes formed by mutant BAG3 led to a relocation of other chaperones such as HSPB8 and Hsp70, which, together with BAG3, promote the so-called chaperone-assisted selective autophagy (CASA). As a consequence of their increased aggregation-proneness, mutant BAG3 trapped ubiquitinylated client proteins at the aggresome, preventing their efficient clearance. Combined, these data show that all BAG3_Pro209 mutants, irrespective of their different clinical phenotypes, are characterized by a gain-of-function that contributes to the gradual loss of protein homeostasis.
Simulating isolated populations to identify emerging genetic structure in the absence of selection
Authors: Hosking C , Ogden R , Senn H 
Published: November 2019

AbstractConservation efforts are often informed by measures of genetic structure within or between isolated populations. We have established a simulation approach to investigate how isolated or captive populations can display misleading (i.e recently acquired) genetic structure as a result of genetic drift. We utilized a combination of softwares to generate isolated population genetic datasets that allow interrogation of emerging genetic structure under a range of conditions. We have developed a new statistic, S, to describe the extent of differentiation due to genetic drift between two isolated populations within the clustering software, STRUCTURE.A novel method to infer the effects of genetic drift on structure among isolated populationsGraphical AbstractSPECIFICATIONS TABLE
Transient Nodal signalling in left precursors coordinates opposed asymmetries shaping the heart loop
Authors: Desgrange Audrey , Garrec Jean-François Le , Bernheim Ségolène , Bønnelykke Tobias Holm , Meilhac Sigolène M. 
Published: November 2019

SummaryThe secreted factor Nodal has been shown to be a major left determinant. Although it is associated with severe congenital heart defects, its role in heart morphogenesis has remained poorly understood. Here, we report that Nodal is transiently active in precursors of the mouse heart tube poles, before the morphological changes of heart looping. In conditional mutants, we show that Nodal is not required to initiate asymmetric morphogenesis. We provide evidence of a heart-specific random generator of asymmetry that is independent of Nodal. Using 3D quantifications and simulations, we demonstrate that Nodal functions as a bias of this mechanism: it is required to amplify and coordinate opposed left-right asymmetries at the heart tube poles, thus generating a robust helical shape. We identify downstream effectors of Nodal signalling, regulating asymmetries in cell proliferation, cell differentiation and extra-cellular matrix composition. Our work provides novel insight into how Nodal regulates asymmetric organogenesis.
Nonlinear and complementary effects of responsive and proactive market orientation on firms’ competitive advantage
Authors: Osorio Tinoco Fabian F. , Hernández-Espallardo Miguel , Rodriguez-Orejuela Augusto 
Published: November 2019

PurposeThe purpose of this paper is to clarify how responsive market orientation (RMO) and proactive market orientation (PMO) create competitive advantage.Design/methodology/approachNonlinear and interaction effects are tested by applying hierarchical regression analysis to a sample of 272 Colombian manufacturing companies.FindingsThe results show that although market orientation promotes the competitive advantage of a business, both approaches – responsive and proactive – exhibit saturation effects and a positive interaction.Research limitations/implicationsThe main limitation of this study is the cross-sectional design and the use of a single source for data collection. It is suggested that future research includes different orientations combined with these two market orientations – responsive and proactive – for achieving competitive advantage. In addition, further studies could replicate this analysis for different environmental conditions.Originality/valueThis paper simultaneously evaluates the nonlinear and complementary effects of RMO and PMO. From a strategic standpoint, it presents an empirical confirmation of the familiarity trap, the failure trap and the positive effects of combining RMO and PMO.
Evaluating after-sales service units by developing inverse network data envelopment analysis model
Authors: Farzipoor Saen Reza , Seyedi Hosseini Nia Seyed Shahrooz 
Published: November 2019

Purpose
The purpose of this paper is to develop an inverse network data envelopment analysis (INDEA) model to solve resource allocation problems.

Design/methodology/approach
The authors estimate inputs’ variations based on outputs so that the efficiencies of decision-making unit under evaluation (DMUo) and other decision-making units (DMUs) are constant.

Findings
The new INDEA model is developed to allocate resources such that inputs are not increased while efficiency scores of all DMUs remain constant. Furthermore, the authors obtain new combinations of inputs and outputs, together with a growth in efficiency score of DMUo such that efficiency scores of other DMUs are not changed. A case study is provided.

Originality/value
This paper proposes INDEA model to estimate inputs (outputs) without changing efficiency scores of DMUs.
A framework for addressing the challenges of business process change during enterprise systems integration
Authors: Javidroozi Vahid , Shah Hanifa , Feldman Gerald 
Published: November 2019

Purpose
Enterprise systems integration (ESI) is necessary for today’s business environment to access real-time data and quickly respond to fluctuating market demand. business process change (BPC) as a significant prerequisite of ESI encompasses various challenges that must be tackled by employing success factors, techniques and approaches. The purpose of this paper is to focus on BPC challenges and develop a conceptual framework for addressing BPC challenges in ESI.

Design/methodology/approach
BPC challenges and their success factors were first identified through a literature analysis. Then, the findings from the literature were thematically analysed and qualitatively validated through 35 unstructured interviews for developing the conceptual framework.

Findings
The findings from the literature suggested 17 BPC challenge along with their success factors. During the validation process, 15 BPC challenges were accepted by all interviewees, while most of the respondents disagreed with the two challenges of “consolidation of information system re-engineering with BPR”, and “customization”. Moreover, “risk” was suggested as a BPC challenge by several interviewees. Thus, the study offered a modified list of BPC challenges, which was empirically validated.

Originality/value
The study proposes a conceptual framework for addressing BPC challenges in ESI that enables enterprises to design their systems integration roadmap, based on an understanding of BPC challenges and their success factors, as well as supporting solution providers to develop solutions for effective and efficient BPC. Furthermore, the framework will act as a basis for BPC and developing a similar framework for other related contexts, such as smart cities.
Reengineering of the software development process in a technology services company
Authors: Lopez-Arredondo Laura P. , Perez Cynthia B. , Villavicencio-Navarro Jesus , Mercado Kathya E. , Encinas Martin , Inzunza-Mejia Patricia 
Published: November 2019

Purpose
The purpose of this paper is to address the need of a reengineering of the software development process in a Mexican technology services company. In general, the main risk faced by small- and medium-sized software developers (SMEs) is the inability to meet delivery times or to adjust to project requirements, whether through lack of follow-up on the critical activities of the development process or through an inadequate distribution of workloads among members of the project team.

Design/methodology/approach
The methodology used to carry out the reengineering of the software development process is Hammer and Champy, which consists of six stages: introduction to the current situation of the company and the need for change; identification of the business processes; selection of the business process to be redesigned; understanding of the process selected; proposal for reengineering the business process selected; and the results of the comparison between the current situation of the process and the proposed reengineering of the process through the use of Business Process Model and Notation (BPMN 2.0).

Findings
Based on the results, the paper shows the importance of the analysis and implementation of the reengineering in a software development company. It describes step-by-step how to apply the methodology of Hammer and Champy in a business process through simulated scenarios, using BPMN 2.0. By carrying out the implementation of the proposed reengineering, the company would therefore save 45.12 percent of costs, 41.17 percent of time, and a better distribution of resources, at the same time guaranteeing the satisfaction of its clients.

Originality/value
The study addresses the current needs of small- and medium-sized software developers, providing a step-by-step guide to the implementation of a process reengineering methodology, performing an analysis and modeling of processes in BPMN 2.0 and providing results through a simulation of the critical process, with the aim to observe the flow of activities and the significant improvements that would be achieved by implementing the reengineering proposal. This simulation schema allows business owners to observe the potential of the changes and to verify the positive impact they would have on the company before beginning to make operational changes in the organization.
How communication climate and organizational identification impact change
Authors: Neill Marlene S. , Men Linjuan Rita , Yue Cen April 
Published: November 2019

PurposeThe purpose of this paper is to examine why and how an open and participative communication climate matters for employee organizational identification and their change-specific responses, specifically employees’ attitudinal and behavioral reactions.Design/methodology/approachTo test the hypothesized model, the authors conducted an online survey using a stratified and quota random sample of 1,034 US employees working in diverse industry sectors in June of 2018, with the assistance of a premier global provider of survey services, Survey Sampling International. To test the hypothesized model, structural equation modeling analysis was employed using AMOS 24.0 software.FindingsAn open and participative communication climate directly contributes to employee affective commitment to change and behavioral support. Communication climate featured by openness and participation boosts employee identification with the organization, which leads to positive employee reaction to change. When employees identify with the organization, they tend to believe in the inherent value of the change and are more likely to support the change initiative in action through cooperation and championship.Originality/valueTheoretically, the study contributes to the change management and communication literature by focusing on the role of communication climate in inducing employee reaction to organizational change. Practically, the study offers insights for change managers, internal communication professionals and organizational leaders. Organizational leaders need to be open, create a trusting atmosphere and actively involve employees in the decision-making process. Organizational leaders and communicators should also strive to boost employee identification with the organization, especially during change.
Corporate governance andShariahnon-compliant risk in Islamic banks: evidence from Southeast Asia
Authors: Basiruddin Rohaida , Ahmed Habib 
Published: November 2019

PurposeThis study aims to investigate the relationship between corporate governance andShariahnon-compliant risk (SNCR) that is unique for Islamic banks. The study examines the roles ofShariahcommittee along with the board of directors in mitigating SNCR.Design/methodology/approachThe paper empirically investigates the implications of characteristics of board of directors andShariahcommittee on the SNCR by using a sample of 29 full-fledge Islamic banks from Malaysia and Indonesia over the period 2007-2017. All data is hand collected from the Islamic banks' annual reports with the exception of country-level data collected from the World Bank database.FindingsThe results show that banks with a smaller board size and higher proportion of independent board members are likely to have lower SNCR. The findings also indicate that the financial expertise and higher frequency ofShariahcommittee meetings reduces the SNCR. Collectively, the analysis shows that banks with strong corporate governance environments reduce SNCR.Practical implicationsThe findings of the study shed light on the relationship between corporate governance practice,Shariahcommittee characteristics and SNCR. The results can be used by different stakeholders such as policymakers, boards of directors and senior management of Islamic banks to mitigate SNCR.Originality/valueThis study extends the literature on corporate governance and risk-taking by including additional dimensions of governance and risk type. The corporate governance mechanism at the board level is complemented by including theShariahcommittee characteristics and SNCR which is relevant to Islamic financial institutions is examined.
A rejoinder on managerial discretion: Andersen (2017) vs Haj Youssef and Teng (2019)
Authors: Andersen Jon Aarum 
Published: November 2019

PurposeThis paper aims to demonstrate the efforts of Hay Youssef and Tang (2019) to reaffirm the importance of managerial discretion is unsuccessful.Design/methodology/approachTheoretical frameworks from traditional and recent literature on the concept of managerial discretion are related to corporate governance scholarship.FindingsThere are in fact no studies on managerial discretion based on explicit theoretical and empirical definitions and thus no studies published which have measured the degrees of managers’ discretion. The conclusion is that the inability to define the notion of managerial discretion is tantamount to the inability to research it.Practical implicationsResearch on managerial discretion does not provide any advice to owners and directors of boards on granting top executives a high or a low degree of discretion.Originality/valueThis paper reaffirms the conclusion of Andersen (2017) that corporate governance scholarship will improve if it abandons the concept of managerial discretion.
Optimal design of RAM cell using novel 2:1 multiplexer in QCA technology
Authors: Majeed Ali H. , Alkaldy Esam , Zainal Mohd Shamian , Navi Keivan , Nor Danial 
Published: November 2019

PurposeQuantum-dot cellular automata (QCA) has attracted computer scientists as new emerging nanotechnology for replacement the current CMOS technology because it has unique characteristics such as high frequency, extremely small feature size and low power consumption. The main building blocks in QCA are the majority gate and inverter so any Boolean function can be represented using these gates. Many important circuits were the target for implemented in this technology in an optimal form, such as random-access memory (RAM) cell. QCA-RAM cells were introduced in literature with different forms but most of them are not optimized enough. This paper aims to demonstrate QCA inherent capabilities that can facilitate the design of many important gates such as the XOR gate and multiplexer (MUX) without following any Boolean function to get an optimum design in terms of complexity and delay.Design/methodology/approachIn this paper, a novel structure of QCA-MUX in an optimal form will be used to design two unique structures of a RAM cell. The proposed RAM cells are the lowest cost required compared with different counterparts. The presented RAM cells used a new approach that follows the new suggested block diagram. The presented circuits are simulated and tested with QCADesigner and QCAPro tools.FindingsThe comparison of the proposed circuits with the previously reported in the literature show noticeable improvements in speed, area, and the number of cells. The cost function analysis results for the proposed RAM cells show significant improvement compared to older circuits.Originality/valueA novel structure of QCA-MUX in an optimal form will be used to design two unique structures of a RAM cell.
Stability and development of user innovation strategies for video game producers
Authors: Koch Stefan , Artmayr Philipp 
Published: November 2019

Purpose
The purpose of this paper is to focus on user innovation strategies and their stability in the video game industry. The main research questions addressed are whether a significant portion of video game companies employ user innovation, and how these strategies are showing signs of success and evolve over time.

Design/methodology/approach
From various online data sources, information was extracted for 2,003 video game companies and 3,923 video games and analyzed using quantitative statistical approaches.

Findings
The analysed data show that a significant proportion of video game companies rely on user innovation-related strategies. If user innovation possibilities are provided, user ratings also tend to be higher. Over time, this strategy of enabling user innovation becomes more prevalent, but companies do also abandon such strategies or use them selectively. Especially, never employing them is associated with decreased company lifespan.

Originality/value
This is the first paper providing a large-scale insight into the evolution of user innovation strategies in an industry.