bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delineating the Genetic Component of Gene Expression in Major Depression
Authors: Dall’Aglio Lorenza , Lewis Cathryn M. , Pain Oliver 
Published: March 2020

AbstractBackgroundMajor Depression (MD) is determined by a multitude of factors including genetic risk variants which regulate gene expression (GE). Here, we examined the genetic component of GE in MD by performing a Transcriptome-Wide Association Study (TWAS), inferring GE-trait relationships from genetic, transcriptomic and phenotypic information.MethodGenes differentially expressed in depression were identified with the TWAS FUSION method, based on summary statistics from the largest genome-wide association analysis of MD (Ncases= 135,458) and GE levels from 20 tissue datasets. Follow-up analyses were performed to extensively characterize the identified associations: colocalization, conditional, and fine-mapping analyses together with functionally-enriched pathway investigations.ResultsTranscriptome-wide significant GE differences between cases and controls were found at 91 genes, 50 of which were not found in previous MD TWASs. Of the 91 significant genes, eight represented strong, colocalized, and potentially causal associations with depression, which were independent from the effect of nearby genes. Such “high-confidence associations” includeNEGR1, CTC-467M3.3, TMEM106B, CTD-2298J14.2, CCDC175, ESR2, PROX2, ZC3H7B.Lastly, TWAS-based enrichment analysis highlighted dysregulation of gene sets for long term potentiation, dendritic shaft, and memory processes in MD.ConclusionThis study has shed light on the genetic component of GE in depression by characterizing the identified associations, unravelling novel risk genes, and determining which associations are congruent with a causal model. These findings can be used as a resource for prioritizing and designing subsequent functional studies of MD.
The Synergy of Damage Repair and Retention Promotes Rejuvenation and Prolongs Healthy Lifespans in Cell Lineages
Authors: Schnitzer Barbara , Borgqvist Johannes , Cvijovic Marija 
Published: March 2020

AbstractDamaged proteins are inherited asymmetrically during cell division in the yeastSaccharomyces cerevisiae, such that most damage is retained within the mother cell. The consequence is an ageing mother and a rejuvenated daughter cell with full replicative potential. Daughters of old and damaged mothers are however born with increasing levels of damage resulting in lowered replicative lifespans. Remarkably, these prematurely old daughters can give rise to rejuvenated cells with low damage levels and recovered lifespans, called second-degree rejuvenation. We aimed to investigate how damage repair and retention together can promote rejuvenation and at the same time ensure low damage levels in mother cells, reflected in longer health spans. We developed a dynamic model for damage accumulation over successive divisions in individual cells as part of a dynamically growing cell lineage. With detailed knowledge about single-cell dynamics and relationships between all cells in the lineage we can infer how individual damage repair and retention strategies affect the propagation of damage in the population. We show that active damage retention lowers damage levels in the population by reducing the variability across the lineage, and results in larger population sizes. Repairing damage efficiently in early life, as opposed to investing in repair when damage has already accumulated, counteracts accelerated ageing caused by damage retention. It prolongs the health span of individual cells which are moreover less prone to stress. In combination, damage retention and early investment in repair are beneficial for healthy ageing in yeast cell populations.
The effect of a novel powerful ABA mimic on the improvement of color in grapes and its mechanism
Authors: Ding Shanshan , Che Chuanliang , Xu Zhihong , Du Xiaoying , Li Junkai , Li Jia-Qi , Xiao Yumei , Qin Zhaohai 
Published: March 2020

AbstractPigment content is an important quality attribute in the grape industry, and anthocyanins are the major fruit pigments. iso-PhABA is a novel and excellent ABA analog capable of the antimetabolic inactivation of ABA. In this study, we found that iso-PhABA improved the coloration of grape berries more obviously than ABA at concentrations of 2 mg/L and 5 mg/L in two grape varieties in China. iso-PhABA treatment enhanced the anthocyanin content in the two grape varieties; specifically, the anthocyanin and delphinidin contents increased in both the ‘Jufeng’ and ‘Xiahei’ varieties. An enzymatic activity test showed that iso-PhABA significantly promoted four key enzyme activities catalyzing anthocyanin biosynthesis. We also determined the affinity between iso-PhABA and ABA receptors using ABA as a control. The results indicated that iso-PhABA had significantly to moderately higher affinities for some ABA receptors, including PYR1, PYL2, PYL1, PYL3 and PYL10, which resulted in higher inhibition of the PP2C HAB1 in the presence of iso-PhABA than in the presence of ABA. iso-PhABA treatment increased the content of soluble sugars and grape yield without any apparent accompanying adverse effects on the quality of the grapes.
A reversibly induced CRISPRi system targeting Photosystem II in the cyanobacteriumSynechocystissp. PCC 6803
Authors: Liu Deng , Johnson Virginia M. , Pakrasi Himadri B. 
Published: March 2020

ABSTRACTThe cyanobacteriumSynechocystissp. PCC 6803 is used as a model organism to study photosynthesis, as it can utilize glucose as the sole carbon source to support its growth under heterotrophic conditions. CRISPR interference (CRISPRi) has been widely applied to repress the transcription of genes in a targeted manner in cyanobacteria. However, a robust and reversible induced CRISPRi system has not been explored inSynechocystis6803 to knock down and recover the expression of a targeted gene. In this study, we built a tightly controlled chimeric promoter, PrhaBAD-RSW, in which a theophylline responsive riboswitch was integrated into a rhamnose-inducible promoter system. We applied this promoter to drive the expression of ddCpf1 (DNase-dead Cpf1 nuclease) in a CRISPRi system and chose the PSII reaction center genepsbD(D2 protein) to target for repression.psbDwas specifically knocked down by over 95% of its native expression, leading to severely inhibited Photosystem II activity and growth ofSynechocystis6803 under photoautotrophic conditions. Significantly, removal of the inducers rhamnose and theophylline reversed repression by CRISPRi. Expression of PsbD recovered following release of repression, coupled with increased Photosystem II content and activity. This reversibly induced CRISPRi system inSynechocystis6803 represents a new strategy for study of the biogenesis of photosynthetic complexes in cyanobacteria.
SWI/SNF antagonizes SIR heterochromatin to promote transcription of genes expressed during mitotic exit inSaccharomyces cerevisiae
Authors: Rege Mayuri , Feldman Jessica L. , Adkins Nicholas L. , Peterson Craig L. 
Published: March 2020

ABSTRACTHeterochromatin is a repressive, specialized chromatin structure that is central to eukaryotic transcriptional regulation and genome stability. In the budding yeast,Saccharomyces cerevisiae, heterochromatin formation requires Sir2p, Sir3p, and Sir4p, and these Sir proteins create specialized chromatin structures at telomeres and silent mating type loci. Previously, we reported that the SWI/SNF chromatin remodeling enzyme can evict Sir3 from chromatin fibersin vitro, though whether this activity contributes to the role of SWI/SNF as a transcriptional activator at euchromatic loci is unknown. Here, we characterize genetic interactions between theSIRgenes (SIR2,SIR3, andSIR4) and genes encoding subunits of the chromatin remodelers SWI/SNF and INO80C, as well genes encoding the histone deacetylases Hst3 and Hst4. We find that loss ofSIRgenes partially rescues the growth defects ofswi2,ino80, andhst3/hst4mutants during replication stress conditions. Interestingly, partial suppression ofswi2,ino80, andhst3 hst4mutant phenotypes is due to the pseudo-diploid state ofsirmutants, but a significant portion is due to more direct functional interactions. Consistent with this view, transcriptional profiling of strains lacking Swi2 or Sir3 identifies a set of genes whose expression in the M/G1 phase of the cell cycle requires SWI/SNF to antagonize the repressive impact of Sir3.
Extracellular microRNA 3’ end modification across diverse body fluids
Authors: Koyano Kikuye , Bahn Jae Hoon , Xiao Xinshu 
Published: March 2020

ABSTRACTmicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in gene regulation. The presence of miRNAs in extracellular biofluids is increasingly recognized. However, most previous characterization of extracellular miRNAs focused on their overall expression levels. Alternative sequence isoforms and modifications of miRNAs were rarely considered in the extracellular space. Here, we developed a highly accurate bioinformatic method, called miNTA, to identify 3’ non-templated additions (NTAs) of miRNAs using small RNA-sequencing data. Using miNTA, we conducted an in-depth analysis of miRNA 3’ NTA profiles in 1047 extracellular RNA-sequencing data sets of 4 types of biofluids. This analysis identified abundant 3’ uridylation and adenylation of miRNAs, with an estimated false discovery rate of <5%. Strikingly, we found that 3’ uridylation levels enabled segregation of different types of biofluids, more effectively than overall miRNA expression levels. This observation suggests that 3’ NTA levels possess fluid-specific information insensitive to batch effects. In addition, we observed that extracellular miRNAs with 3’ uridylations are enriched in processes related to angiogenesis, apoptosis and inflammatory response, and this type of modification may stabilize base-pairing between miRNAs and their target genes. Together, our study provides a comprehensive landscape of miRNA NTAs in human biofluids, which paves way for further biomarker discoveries. The insights generated in our work built a foundation for future functional, mechanistic and translational discoveries.
Autophagy is responsible for the accumulation of proteogenic dipeptides in response to heat stress inArabidopsis thaliana
Authors: Thirumalaikumar Venkatesh P. , Wagner Mateusz , Balazadeh Salma , Skirycz Aleksandra 
Published: March 2020

AbstractProteogenic dipeptides are intermediates of proteolysis as well as an emerging class of small-molecule regulators with diverse and often dipeptide-specific functions. Herein, prompted by differential accumulation of dipeptides in a high-densityArabidopsis thalianatime-course stress experiment, we decided to pursue an identity of the proteolytic pathway responsible for the buildup of dipeptides under heat conditions. By querying dipeptide accumulation versus available transcript data, autophagy emerged as a top hit. To examine whether autophagy indeed contributes to the accumulation of dipeptides measured in response to heat stress, we characterized the loss-of-function mutants of crucial autophagy proteins to test whether interfering with autophagy would affect dipeptide accumulation in response to the heat treatment. This was indeed the case. This work implicates the involvement of autophagy in the accumulation of proteogenic dipeptides in response to heat stress in Arabidopsis.
Role of endothelial microRNA-150 in pulmonary arterial hypertension
Authors: Russomanno Giusy , Jo Kyeong Beom , Abdul-Salam Vahitha B. , Morgan Claire , Alzaydi Mai , Wilkins Martin R. , Wojciak-Stothard Beata 
Published: March 2020

ABSTRACTEndothelial dysfunction contributes to the vascular pathology in pulmonary arterial hypertension (PAH). Circulating levels of endothelial miR-150 are reduced in PAH and act as an independent predictor of patient survival. The role of endothelial miR-150 in vascular dysfunction in PAH is not well understood.Endothelium-targeted miR-150 delivery prevented the disease in Sugen/hypoxia mice, while endothelial knockdown of miR-150 had adverse effects. miR-150 target genes revealed significant associations with PAH pathways, including proliferation, inflammation and phospholipid signaling, with PTEN-like mitochondrial phosphatase (PTPMT1) most markedly altered. PTPMT1 reduced inflammation, apoptosis and improved mitochondrial function in human pulmonary endothelial cells and blood-derived endothelial colony forming cells (ECFCs) from idiopathic PAH. Beneficial effects of miR-150in vitroandin vivowere linked with PTPMT1-dependent biosynthesis of mitochondrial phospholipid cardiolipin and reduced expression of pro-apoptotic, pro-inflammatory and pro-fibrotic genes, includingc-MYB, NOTCH3, TGF-βandCol1a1.In conclusion, we are first to show that miR-150-PTPMT1-cardiolipin pathway attenuates pulmonary endothelial damage induced by vascular stresses and may be considered as a potential therapeutic strategy in PAH.
Exploring the complex map of insulin polymorphism: a novel crystalline form in the presence ofm-cresol
Authors: Karavassili Fotini , Valmas Alexandros , Dimarogona Maria , Giannopoulou Anastasia E. , Fili Stavroula , Norrman Mathias , Schluckebier Gerd , Beckers Detlef , Fitch Andrew N. , Margiolaki I. 
Published: March 2020

In this study, the first crystal structure of a novel crystal form of human insulin bound tometa-cresol in an acidic environment is reported. The combination of single-crystal and powder X-ray diffraction crystallography led to the detection of a previously unknown monoclinic phase (P21). The structure was identified from the powder patterns and was solved using single-crystal diffraction data at 2.2 Å resolution. The unit-cell parameters at pH 6.1 area= 47.66,b = 70.36,c = 84.75 Å, β = 105.21°. The structure consists of two insulin hexamers per asymmetric unit. The potential use of this insulin form in microcrystalline drugs is discussed.
Flori Pharma: maintaining ethics in an unethical sales environment
Authors: Sattar Muhammad Muzamil , Qazi Asad Ali , Shahzad Farhan , Shaikh Abdul Rehman 
Published: March 2020

Learning outcomes
The learning outcomes are as follows: what tasks are to be done by medical representatives in pharmaceutical industry? This study also highlights various competencies required to do effective selling in this industry; analyzes and discusses different unethical practices going on in the market; explains why ethical norms are necessary in sales context when sales targets are already achievable with unethical means; and develops and comments on strategies Flori Pharmaceutical can make to overcome on these unethical issues. What should be the response of Dahar to the email of Naveed khan? What course of action should be taken by Dahar in the deceitful reporting case of Mohsin Ali?

Case overview/synopsis
Flori is considered a leading and growing multinational organization in the highly competitive environment of Pakistan pharmaceutical industry with over 40 years of experience. The company aims to command a leading position in developing new health-care products as it offers a wide range of diabetic, cardiovascular, respiratory and vitamin products based on quality as a result of high research and examination. Recently, an email to Bilal Dahar on March 2017 from Flori’s star sales person Naveed Khan has forced management to take some strong decisions regarding ethical norms and values to be adopted by medical representatives of Flori pharmaceuticals. The email highlighted the issues related to sales pressure which are leading toward unethical sales practices. Dahar just not have to maintain Flori’s ethical code of conduct but he and his team also has to work hard to achieve more than 26% growth rate in sales revenue as compared to last year. Dahar knew that the highly competitive environment of pharmaceutical industry has led most of the stake holders to indulge in unethical behavior to achieve their individual targets. He knew that this is dangerous in long term for the multinational organizations such as Flori pharmaceuticals as if the similar behavior continues, the sales culture and values of the organization would be on stake. He also has to decide what decision to be taken against deceitful reporting issue of one of the top-performer territory managers, who was key person in helping Flori to close the sales year 2016 with the revenue of Rs. 6.4bn, a 26% growth over the last year. The case is rich enough to provide a platform regarding management of several ethical challenges in pharmaceutical selling and developing strategies based on them.

Complexity academic level
BBA, MBA final year.

Supplementary materials
Teaching Notes are available for educators only.

Subject code
CSS 8: Marketing.
Impact of policy initiatives and collaborative synergy on sustainability and business growth of Indian SMEs
Authors: Das Maitreyee , Rangarajan Krishnamachari 
Published: March 2020

PurposeThe influence of sustainability practices, especially those related to the environment and society in driving business growth is evident from the annual sustainability reports of big corporations. Also, there has been a plethora of research relating sustainability performance to the financial performance of these companies. However, in the case of small and medium-sized enterprises, a very limited research study has been done so far considering the societal and environmental aspects of their business operations. Small and medium enterprises (SMEs), especially those in the emerging economy have grossly neglected their responsibilities and obligations towards the environment and society. SMEs are considered as growth engines for any nation. However, literature has shown that a large percentage of SMEs across the world fail within a few years of their incorporation. This paper aims to verify the relationship between sustainability performance and business growth for SMEs in the developing economy.Design/methodology/approachIn the paper, the authors have tried to develop a model taking a sample of 200 SMEs from Indian leather and chemical sectors and find out how the factors like collaborative synergy and government policy initiatives impact the sustainability performance of small and medium firms and how in turn, their improved sustainability performance helps them to drive sustainable business growth. Data were mainly collected through primary survey and also from the company websites.FindingsEmpirical results of the study reveal that both policy initiatives and collaborative synergy positively influence the firm’s sustainability performance and, in turn, the company’s business growth is positively impacted by their enhanced sustainability performance. Company size was found to have a moderating effect on this relationship.Originality/valueThere are theoretical and conceptual papers elaborating on the importance of adoption of sustainability practices in SME business operations but no empirical study has been conducted to mathematically relate the factors of sustainability and business growth. The authors have tried to build a model relating the factors of sustainability improvement with those of the business growth of the firm and also verified the influence of control variables like company size on the proposed relationship.
Organisational culture, leadership behaviour and job satisfaction in the Vietnam context
Authors: Tran Quan H.N. 
Published: March 2020

PurposeThe purpose of this paper is to challenge the influence of organisational culture types on leadership behaviour and job satisfaction. The theory of culture was divided into four characteristics, namely, clan, hierarchy, adhocracy and market.Design/methodology/approachA purposive questionnaire was adapted to collect surveys from 294 working people in several sector organisations in Vietnam. The questionnaire included two main parts. The first part comprising demographic questions. The second part included three constituted scales to evaluate organisational culture types, leadership behaviour and job satisfaction. Correlation and linear regression analysis were adapted to use to challenge connections among variables.FindingsHierarchy culture negatively connected to relationship-oriented leadership behaviour. Adhocracy culture positively affected job satisfaction. Clan and market cultures insignificantly predicted leadership style and job satisfaction.Research limitations/implicationsThe research is structured in 294 working people in various Vietnamese sector organisations. This small sample is unlikely to represent the popularity of the findings. Further research should collect samples in more organisations and industries in Vietnam to improve the efficiency of the results. The research findings may support leaders and superiors to choose a proper organisational culture that will reduce employee dissatisfaction.Originality/valueThe research is conducive to the studies on organisational culture, especially the association between leadership behaviour and job satisfaction in Vietnamese sector organisations
How to balance interfirm relationships? A case from high-speed railway industry
Authors: Zhang Na , Deng Xiaopeng , Hwang Bon-Gang , Niu Yanliang 
Published: March 2020

Purpose
Balancing interfirm relationships is important for firms’ long-term superior performance. However, prior studies mainly focus on interfirm competition or interfirm cooperation separately, ignoring the balance of interfirm relationships. To bridge this gap in knowledge, this study aims to develop a framework to evaluate the balance of interfirm competition and interfirm cooperation and propose strategies to optimize a firm’s interfirm relationships.

Design/methodology/approach
After an in-depth literature review, a framework was developed for evaluating and optimizing the interfirm relationships. Taking the high-speed railway industry as an example, the proposed framework was implemented.

Findings
The results of the case confirm that the balancing of interfirm relationships can lead to more superior firm performance. Also, rather than mutual suppression, the interfirm competition and interfirm cooperation present a roughly positive relationship.

Originality/value
This study would contribute to the existing knowledge body by developing a framework for balancing interfirm relationships. Also, this study can aid practitioners in evaluating and optimizing their interfirm relationship structures.
A system proposal for rapid detecting of anthropometric data and affecting design strategies
Authors: Erkan Ilker 
Published: March 2020

PurposeThe purpose of this study on architecture, design, ergonomics and anthropometry was to ensure compliance with the human-machine-work environment, minimize human error and obtain anthropometric measurements accurately, safely and rapidly.Design/methodology/approachThe developed system efficiently extracted anthropometric data for 15,243 individuals with an accuracy rate of 98.8 per cent, focusing on the values for “shoulder breath” and “body depth.” In this study, a new anthropometric measurement system was developed and subsequently applied to obtain anthropometric measurements easily and quickly. The effect of the newly collected anthropometric data on the design discipline was evaluated.FindingsThe findings highlighted the need to update the anthropometric data used in other design studies. In addition to contributing to designing discipline, the updated anthropometric data are considered suitable for use in many different fields.Research limitations/implicationsThe design discipline and related disciplines are expected to take advantage of these measurements. Updating the aforementioned data will also be easier and faster because of the simplicity and affordability of the system.Originality/valueThis is the first and only such study in Turkey with regard to the up-to-date anthropometric measurements obtained and the size of the database created.