bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enisamium is a small molecule inhibitor of the influenza A virus and SARS-CoV-2 RNA polymerases
Authors: Walker Alexander P , Fan Haitian , Keown Jeremy R , Margitich Victor , Grimes Jonathan M , Fodor Ervin , te Velthuis Aartjan J W 
Published: April 2020

AbstractInfluenza A virus and coronavirus strains cause a mild to severe respiratory disease that can result in death. Although vaccines exist against circulating influenza A viruses, such vaccines are ineffective against emerging pandemic influenza A viruses. Currently, no vaccine exists against coronavirus infections, including pandemic SARS-CoV-2, the causative agent of the Coronavirus Disease 2019 (COVID-19). To combat these RNA virus infections, alternative antiviral strategies are needed. A key drug target is the viral RNA polymerase, which is responsible for viral RNA synthesis. In January 2020, the World Health Organisation identified enisamium as a candidate therapeutic against SARS-CoV-2. Enisamium is an isonicotinic acid derivative that is an inhibitor of multiple influenza B and A virus strains in cell culture and clinically approved in 11 countries. Here we show usingin vitroassays that enisamium and its putative metabolite, VR17-04, inhibit the activity of the influenza virus and the SARS-CoV-2 RNA polymerase. VR17-04 displays similar efficacy against the SARS-CoV-2 RNA polymerase as the nucleotide analogue remdesivir triphosphate. These results suggest that enisamium is a broad-spectrum small molecule inhibitor of RNA virus RNA synthesis, and implicate it as a possible therapeutic option for treating SARS-CoV-2 infection. Unlike remdesivir, enisamium does not require intravenous administration which may be advantageous for the development of COVID-19 treatments outside a hospital setting.ImportanceInfluenza A virus and SARS-CoV-2 are respiratory viruses capable of causing pandemics, and the latter is responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. Both viruses encode RNA polymerases which transcribe their RNA genomes and are important targets for antiviral drugs including remdesivir. Here, we show that the antiviral drug enisamium inhibits the RNA polymerases of both influenza A virus and SARS-CoV-2. Furthermore, we show that a putative metabolite of enisamium is a more potent inhibitor, inhibiting the SARS-CoV-2 RNA polymerase with similar efficiency to remdesivir. Our data offer insight into the mechanism of action for enisamium, and implicate it as a broad-spectrum antiviral which could be used in the treatment of SARS-CoV-2 infection.
Nuclear myosin VI regulates the spatial organization of mammalian transcription initiation
Authors: Hari-Gupta Yukti , Fili Natalia , dos Santos Ália , Cook Alexander W. , Gough Rosemarie E. , Reed Hannah C. W. , Wang Lin , Aaron Jesse , Venit Tomas , Wait Eric , Grosse-Berkenbusch Andreas , Gebhardt J. Christof M. , Percipalle Piergiorgio , Chew Teng-Leong , Martin-Fernandez Marisa , Toseland Christopher P. 
Published: April 2020

SUMMARYDuring transcription, RNA Polymerase II (RNAPII) is spatially organised within the nucleus into clusters that correlate with transcription activity. While this is a hallmark of genome regulation in mammalian cells, the mechanisms concerning the assembly, organisation and stability which underpin the function these transcription factories remain unknown. Here, we have used combination of single molecule imaging and genomic approaches to explore the role of nuclear myosin VI in the nanoscale organisation of RNAPII. We reveal that myosin VI acts as the molecular anchor that holds RNAPII into transcription factories. Perturbation of myosin VI leads to the disruption of RNAPII localisation, changes in chromatin organisation and subsequently a decrease in gene expression. Overall, we uncover the fundamental role of myosin VI in the spatial regulation of gene expression during the rapid response to changes in the cellular environment.
A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5α
Authors: Saha Bhaskar , Chisholm Devon , Mandell Michael A 
Published: April 2020

ABSTRACTTRIM5α is a key cross-species barrier to retroviral infection, with certain TRIM5 alleles conferring increased risk of HIV-1 infection in humans. TRIM5α is best known as a species-specific restriction factor that directly inhibits the viral life cycle. Additionally, it is also a pattern-recognition receptor (PRR) that activates inflammatory signaling. How TRIM5α carries out its multi-faceted actions in antiviral defense remains incompletely understood. Here, we show that proteins required for autophagy, a cellular self-digestion pathway, play an important role in TRIM5α’s function as a PRR. Genetic depletion of proteins involved in all stages of the autophagy pathway prevented TRIM5α-driven expression of NF-κB and AP1 responsive genes. One of these genes is the preeminent antiviral cytokine interferon β (IFN-β), whose TRIM5-dependent expression was lost in cells lacking the autophagy proteins ATG7, BECN1, and ULK1. Moreover, we found that the ability of TRIM5α to stimulate IFN-β expression in response to recognition of a TRIM5α-restricted HIV-1 capsid mutant (P90A) was abrogated in cells lacking autophagy factors. Stimulation of human macrophage-like cells with the P90A virus protected them against subsequent infection with an otherwise resistant wild type HIV-1 in a manner requiring TRIM5α, BECN1, and ULK1. Mechanistically, TRIM5α was attenuated in its ability to activate the kinase TAK1 in autophagy deficient cells, and both BECN1 and ATG7 contributed to the assembly of TRIM5α-TAK1 complexes. These data demonstrate a non-canonical role for the autophagy machinery in assembling antiviral signaling complexes and demonstrate a role for autophagy in the establishment of a TRIM5α-dependent antiviral state.SIGNIFICANCE STATEMENTTRIM5α is an antiretroviral protein that employs multiple mechanisms to protect cells against infection. Previous studies have linked TRIM5α to autophagy, a cytoplasmic quality control pathway with numerous roles in immunity, raising the possibility that TRIM5α engages autophagy in antiviral defense. This concept has been controversial, since TRIM5α’s best-known role as a directly acting antiretroviral effector is autophagy independent. However, retroviral restriction is only one aspect of TRIM5α function. We demonstrate that autophagy is crucial to another TRIM5α action: its role as a pattern-recognition receptor. We show that autophagy machinery is required for TRIM5α to transduce antiviral signaling and to establish an antiretroviral state. Our data indicate that autophagy provides TRIM5α with a platform upon which to activate antiviral responses.
Atypical employment over the life cycle
Authors: Bachmann Ronald , Felder Rahel , Tamm Marcus 
Published: April 2020

PurposeThis paper analyses how the employment histories of cohorts born after World War II in Germany have changed. A specific focus is on the role of atypical employment in this context.Design/methodology/approachThis paper uses data from the adult cohort of the National Educational Panel Study and presents descriptive evidence on employment patterns for different cohorts. In addition, a sequence analysis of employment trajectories illustrates key aspects related to the opportunities and risks of atypical employment.FindingsYounger cohorts are characterised by acquiring more education, by entering into employment at a higher age and by experiencing atypical employment more often. The latter is associated with much higher employment of women for younger cohorts. The sequence analysis reveals that the proportion of individuals whose entry into the labour market is almost exclusively characterised by atypical employment rises significantly across the cohorts. Moreover, a substantial part of the increase in atypical employment is due to the increased participation of women, with part-time jobs or mini-jobs playing an important role in re-entering the labour market after career breaks.Originality/valueThe most important contribution of this article to the existing literature lies in the life course perspective taken for different birth cohorts. The findings are of great interest to the general debate about the success of the German labour market in recent decades and its implications for individual labour-market histories, but also about rising income inequality at about the same time.
How gender biases drive venture capital decision-making: exploring the gender funding gap
Authors: Balachandra Lakshmi 
Published: April 2020

Purpose
Men founders raise almost 50× more venture capital (VC) than women. As 93 per cent of VCs are men, because of the significant gender imbalance in gatekeepers and investment decision-makers for early-stage capital, there may be critical outcomes for women entrepreneurs who are being caused from men having overweighed in decision-making roles. Outcomes include biases against women by VCs that prevent their ventures from being considered for funding from the pitch as well as obtaining opportunities to pitch VCs in consideration for funding from biases in the evaluations of the businesses themselves.

Design/methodology/approach
This paper is a consolidation of several studies the author has conducted in VC decision-making and gender bias to understand the drivers of the enormous gender gap in VC funding. The author presented it as a talk at the University of Regina and was asked to submit a paper about it here.

Findings
The findings reveal how the 93 per cent male context of the VC industry is in itself a significant cause of the gender gap in funding. If there were more women VCs, more women entrepreneurs would be funded.

Originality/value
The author showcases how the gender gap in decision-making roles in VC has important implications for women entrepreneurs to obtain funding.
Determinants of variation in public investment in emerging Europe
Authors: Randjelovic Sasa 
Published: April 2020

PurposeThis paper evaluates the economic, political and institutional determinants of variation in public investment in emerging Europe.Design/methodology/approachPanel econometrics (panel-corrected standard error, generalized least squares and the two-stage least squares) methods have been applied using annual data from 2000 to 2017 for 16 countries from Central and Eastern Europe (CEE).FindingsPublic investment was procyclical in relation to output and negatively associated with the level of public debt. Austerity episodes triggered a significant drop in public investment. Positive drifts in public investment during election periods and the negative impact of the number of cabinet seats held by left-wing parties have been captured. While no firm evidence on the impact of EU membership was found, the results show that arrangements with the IMF were strongly associated with lower public investment. Political factors were of greater importance in Central Europe and the Baltics, while institutional factors had a more significant impact in South Eastern Europe.Practical implicationsTo foster public capital formation, it is necessary to: 1) strengthen the countercyclicality of public investment policy and to keep public debt at a low level; 2) adjust the fiscal criteria for EU membership in a manner that would enable countries to use the EU structural fund more effectively, while maintaining fiscal sustainability; 3) put a stronger emphasis on structural features of fiscal policy when designing country-level arrangements with the IMF.Originality/valueThe paper contributes to the literature on determinants of public investment policy by adding empirical evidence for emerging Europe countries.
Lean thinking and higher education management: revaluing the business school programme management
Authors: Zighan Saad , EL-Qasem Ahmed 
Published: April 2020

PurposeThis paper explores the applications of lean thinking in re-evaluating the business school curriculum, syllabus and intended learning objectives to enhance the employability of graduates through identifying and eliminating non–value-added activities.Design/methodology/approachThe research employed multilevel qualitative methodology, where 55 semi-structured interviews were conducted to collect data from academics, students and graduates from several private and public universities in Jordan.FindingsThe study finds that the application of lean thinking in the business school is twofold – it helps the developer of the school curriculum to get rid of many superfluous and non–value-added activities and also emphasises and reinforces the value-added activities. Value stream mapping, with a consideration for internal and external outputs, has been found to be a useful tool for developing an employability-focussed curriculum that equips business school students with the required competences and skills in the labour market.Research limitations/implicationsThe study is based on a qualitative research approach. The generalisability of the findings is difficult to assess, and future research would benefit from the insights obtained from the quantitative dataPractical implicationsIn practice, this study has identified different types of non–value-added and unnecessary activities in business school curriculum and has made suggestions for the development of a more employability-focussed curriculum.Originality/valueThis paper investigates the non–value-added activities of the business school curriculum, syllabus and the intended learning objectives to enhance the employability of graduates in Jordan.
Doctoral student persistence and progression: a program assessment
Authors: Boone Shawn C. , De Charon Linda , Hill Marcia (Marty) , Preiss Amy , Ritter-Williams Debbie , Young Elizabeth 
Published: April 2020

PurposeGlobally, traditional and online doctoral programs face difficulties with student persistence and progression. An online doctoral school implemented a first-year program sequence taught by a cadre of 20 specialized faculty members who engage in best practices to assist students in persisting and progressing toward program completion.Design/methodology/approachThis qualitative program assessment using content analysis examined the program effectiveness of one online doctoral program's first-year program sequence. Two research questions guided this program assessment, they were: RQ1. Based on online doctoral students' perspectives, what motivators contribute to online doctoral student persistence and progression in an online doctoral program? RQ2. How do online faculty contribute to online doctoral student persistence and progression? Data collection included myriad of program metrics: content area meetings (CAMs); closing the loop assessment data; faculty and student end of course survey data; and faculty and student semistructured interviews.FindingsThe resultant themes indicated that students are motivated by support from family, friends and religious beliefs; and students persist based on support from fellow doctoral students and faculty members. Additional themes revealed that faculty members motivate students through building faculty–student relationships, individual coaching, providing university resources and through clarification of program requirements; and faculty members perceive that face-to-face doctoral residencies greatly contribute to student persistence and progression through interpersonal interaction and through improved clarity.Originality/valueImplications of this program assessment have far-reaching impact on how doctoral granting institutions can structure small cadres of faculty to develop interpersonal relationships with doctoral students with focus on support and development.
Institutions and organisational work-life balance (WLB) policies and practices
Authors: Nwagbara Uzoechi 
Published: April 2020

PurposeThis paper examines the relationship between the institution’s organizational work-life-balance (WLB) policies and practices and subsequent challenges faced by Nigerian workers. The paper argues that institutions shape WLB practices (and policies), and thus, constitute WLB challenges.Design/methodology/approachRelying on qualitative, interpretive approach, and the institution-based view of organizational practice, the study investigates the relationship between institutions, WLB practices/policies, and subsequent challenges that female workers undergo, using 25 semi-structured interviews.FindingsThe findings reveal Nigeria’s unique institutional context frames and foster challenges for female workers. Also, it was identified that institutional and sociocultural pressures on female employees demonstrate that consequent challenges, while common to female workers in other countries, are more intense and challenging in Nigeria because of its peculiar institutions and context.Research limitations/implicationsThis study offers an opportunity to unpick how institutions are important in understanding organizational practices as part of wider social structures, which influence organizational realities, including WLB. The qualitative, exploratory approach undertaken can limit generalizing the findings.Originality/valueThis study contributes to the emerging concept of WLB discourse from the developing countries’ perspective. It also reveals how WLB discourse differs from nonwestern context and emphasizes previously identified challenges that female workers experience based on WLB practice. The study also sheds light on how institutions shape organizational practice.
Knowledge sharing to support climate change adaptation in Zimbabwe
Authors: Chisita Collence Takaingenhamo , Fombad Madelien C. 
Published: April 2020

PurposeKnowledge sharing for evidence-based climate change adaptation is key to reducing vulnerabilities. The disastrous effects of the recent tropical cyclone Idai in Zimbabwe’s eastern highlands, whereby lives and livelihoods were destroyed, calls for fundamental rethinking on how knowledge sharing can be useful in reducing vulnerabilities. This study aims to examine how knowledge sharing practices among selected climate action organisations can support positive results in evidence-based climate change adaptation in Zimbabwe and recommends a strategy to enhance knowledge sharing for evidence-based climate change adaptation.Design/methodology/approachThe researcher opted for a qualitative research methodology, and interviews were conducted with research participants to get in-depth information. The target population for the research is drawn from three climate change organisations in Zimbabwe. These participants were chosen because of their direct involvement in climate change adaptation and mitigation. Purposive sampling was used because it was considered an easy and informal method to reach the target population. The responses were coded and readied for analysis. Categories for analysis were also determined and described. The next section focuses on the presentation and interpretation of the responses.FindingsThe study found out that even though there is evidence of knowledge sharing in the selected organisations, there was a need for a strategy that integrates the efforts of all climate action organisation to realise successful climate change adaptation. Successful climate change adaptation requires an integrative force in the form of a strategy that supports knowledge sharing. The strategy breaks the silo mode of operation by bringing together all stakeholders through knowledge sharing.Research limitations/implicationsThe research study was unique to the Zimbabwean climate change and adaptation context and only a purposive sampling of participants representing three climate change action was feasible.Social implicationsThe proposed model will enhance knowledge sharing among climate change and adaptation organisations in Zimbabwe. It will transform knowledge management practices among climate change organisations in Zimbabwe.Originality/valueThe study recommends a knowledge sharing strategy that can be useful in supporting climate change adaptation. The model will support decision-making by providing access to shareable information on climate change. The proposed knowledge sharing strategy integrates the efforts of all stakeholders, including communities, government and academia, among many. The study proposes an original model for climate change adaptation for Zimbabwe.
Quorum sensing regulation confronts the development of a viable but non‐culturable state in Vibrio cholerae
Authors: Wu Bin , Liang Weili , Yan Meiying , Li Jie , Zhao Hongqun , Cui Lunbiao , Zhu Fengcai , Zhu Jun , Kan Biao 
Published: April 2020

SummaryVibrio cholerae can enter a viable but non‐culturable (VBNC) state when it encounters unfavourable environments; VBNC cells serve as important reservoirs and still pose threats to public health. The genetic regulation of V. cholerae entering its VBNC state is not well understood. Here, we show a confrontation strategy adapted by V. cholerae O1 in which it utilizes a quorum sensing (QS) system to prevent transition into a VBNC state under low nutrition and temperature conditions. The upregulation of hapR resulted in a prolonged culturable state of V. cholerae in artificial sea water at 4°C, whereas the mutation of hapR led to fast entry into the VBNC state. We also observed that different V. cholerae O1 natural isolates with distinct QS functions present a variety of abilities to maintain culturability during the transition to a VBNC state. The strain groups with higher or constitutive expression of QS genes exhibit a greater tendency to maintain the culturable state during VBNC induction than those lacking QS functional groups. In summary, HapR‐mediated QS regulation is associated with the transition to the VBNC state in V. cholerae. HapR expression causes V. cholerae to resist VBNC induction and become dominant over competitors in changing environments.
Effects of cross‐border capital flows on stock returns of dual‐listed firms in mainland China and Hong Kong: Evidence from a natural experiment
Authors: Wu Jia , Lin Jiada , Yang Zhenyu , Dong Luo 
Published: April 2020

AbstractThis study analyses the effects of the Shanghai–Hong Kong Stock Market Connect policy on the price disparity between A‐shares and H‐shares of dual‐listed companies (DLC). Using a difference‐in‐difference estimation method, we show that the policy decreases the relative twin cumulative abnormal returns of treated DLC by 3% and narrows the price gaps between A‐shares and H‐shares. We determine that the rising demand for H‐shares, which are newly accessible by mainland investors, drives the price of H‐shares up. By contrast, the price of A‐shares remains unchanged. Further analysis reveals that cross‐border capital flow is the main force of the policy.
Cardiogenesis with a focus on vasculogenesis and angiogenesis
Authors: Borasch Katrin , Richardson Kenneth , Plendl Johanna 
Published: April 2020

AbstractThe initial intraembryonic vasculogenesis occurs in the cardiogenic mesoderm. Here, a cell population of proendocardial cells detaches from the mesoderm that subsequently generates the single endocardial tube by forming vascular plexuses. In the course of embryogenesis, the endocardium retains vasculogenic, angiogenic and haematopoietic potential. The coronary blood vessels that sustain the rapidly expanding myocardium develop in the course of the formation of the cardiac loop by vasculogenesis and angiogenesis from progenitor cells of the proepicardial serosa at the venous pole of the heart as well as from the endocardium and endothelial cells of the sinus venosus. Prospective coronary endothelial cells and progenitor cells of the coronary blood vessel walls (smooth muscle cells, perivascular cells) originate from different cell populations that are in close spatial as well as regulatory connection with each other. Vasculo‐ and angiogenesis of the coronary blood vessels are for a large part regulated by the epicardium and epicardium‐derived cells. Vasculogenic and angiogenic signalling pathways include the vascular endothelial growth factors, the angiopoietins and the fibroblast growth factors and their receptors.