bluuebunny/crossref_metadata_2025 huggingface dataset:
Single cell transcriptomic analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma
Authors: Ruan Haoyu , Wang Zhe , Zhai Yue , Xu Ying , Pi Linyu , Zheng Jihong , Zhou Yihang , Zhang Cong , Huang RuoFan , Chen Kun , Li Xiangyu , Ma Weizhe , Wu Zhiyuan , Shen Jie , Deng Xuan , Zhang Chao , Guan Ming
Published: April 2020

Diffuse large B-cell lymphoma (DLBCL) is the predominant type of central nervous system lymphoma (CNSL) including primary CNSL and secondary CNSL. Diffuse large B cells in cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of CNSL leptomeningeal involvement. To explore the distinct phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of 902 CSF-DLBCs from six CNSL-DLBCL patients using single-cell RNA sequencing technology. We defined CSF-DLBCs based on abundant expression of B-cell markers, as well as the enrichment of cell proliferation and energy metabolism pathways. CSF-DLBCs within individual patients exhibited monoclonality with similar variable region of light chains (VL) expression. It is noteworthy that we observed some CSF-DLBCs have double classes of VL (lambda and kappa) transcripts. We identified substantial heterogeneity in CSF-DLBCs, and found significantly greater among-patient heterogeneity compared to among-cell heterogeneity within a given patient. The transcriptional heterogeneity across CSF-DLBCs is manifested in cell cycle state and cancer-testis antigens expression. Our results will provide insight into the mechanism research and new diagnostic direction of CNSL-DLBCL leptomeningeal involvement.
Dissemination routes of the carbapenem resistance plasmid pOXA-48 in a hospital setting
Authors: León-Sampedro Ricardo , DelaFuente Javier , Díaz-Agero Cristina , Crellen Thomas , Musicha Patrick , Rodriguez-Beltran Jerónimo , de la Vega Carmen , Hernández-García Marta ,   R-GNOSIS WP5 Study Group, Lopez-Fresneña Nieves , Ruiz-Garbajosa Patricia , Canton Rafael , Cooper Ben S , Millan Alvaro San
Published: April 2020

Introductory paragraph

Infections caused by carbapenemase-producing enterobacteria (CPE) are a major concern in clinical settings worldwide. Two fundamentally different processes shape the epidemiology of CPE in hospitals: the dissemination of CPE clones from patient to patient (between-patient transfer), and the transfer of carbapenemase-encoding plasmids between enterobacteria in the gut microbiota of individual patients (within-patient transfer). The relative contribution of each process to the overall dissemination of carbapenem resistance in hospitals remains poorly understood. Here, we used mechanistic models combining epidemiological data from more than 9,000 patients with whole genome sequence information from 250 enterobacteria clones to characterise the dissemination routes of the carbapenemase-encoding plasmid pOXA-48 in a hospital setting over a two-year period. Our results revealed frequent between-patient transmission of high-risk pOXA-48-carrying clones, mostly ofKlebsiella pneumoniaeand sporadicallyEscherichia coli.The results also identified pOXA-48 dissemination hotspots within the hospital, such as specific wards and individual rooms within wards. Using high-resolution plasmid sequence analysis, we uncovered the pervasive within-patient transfer of pOXA-48, suggesting that horizontal plasmid transfer occurs in the gut of virtually every colonised patient. The complex and multifaceted epidemiological scenario exposed by this study provides new insights for the development of intervention strategies to control the in-hospital spread of CPE.
Interleukin-6 blockade for severe COVID-19
Authors: Roumier Mathilde , Paule Romain , Groh Matthieu , Vallée Alexandre , Ackermann Félix ,   for the Foch COVID-19 Study Group
Published: April 2020

In the context of COVID-19 pandemic and growing tensions worldwide regarding healthcare facilities, there is an urgent need for effective treatments likely to reduce the crunch of ICU beds. Following the assumption by Mehta and colleagues who exhorted physicians to screen patients with severe COVID-19 for hyperinflammation and investigate immunomodulatory drugs in this setting, we relate our short-term - yet promising - experience regarding IL6 blockade with tocilizumab in 30 selected patients of less than 80 years of age, >5 days of prior disease duration, severe (i.e. requiring strictly over 6L/min of oxygen therapy) rapidly deteriorating (i.e. increase by more than 3L/min of oxygen flow within the previous 12 hours) COVID-19-related pneumonia. By comparison with a control group of patients (matched for age, gender and disease severity using the inverse probability of treatment weighted methodology) that did not receive tocilizumab. We demonstrate that, in highly selected patients, IL6 blockade could curb the “cytokine storm”, prevent ICU admission and the requirement for mechanical ventilation. Notwithstanding the shortcomings of this retrospective small sample-size study, we believe that these preliminary findings support the fostering of research efforts in the fight against COVID-19-induced inflammation, especially before patients require admission to the ICU.
Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications
Authors: Whitbeck J. Charles , Thomas Anu , Kadash-Edmondson Kathryn , Escuer Ariadna Grinyo i , Cheng Celine , Liao Grant C. , Holtsberg Frederick W. , Aman M. Javad , Simmons Graham , Davidson Edgar , Doranz Benjamin J.
Published: April 2020

The development of vaccines against flaviviruses, including Zika virus (ZIKV) and dengue virus (DENV), continues to be a major challenge, hindered by the lack of efficient and reliable methods for screening neutralizing activity of sera or antibodies. To address this need, we previously developed a plasmid-based, replication-incompetent DENV reporter virus particle (RVP) production system as an efficient and safe alternative to the Plaque Reduction Neutralization Test (PRNT). As part of the response to the 2015-2016 ZIKV outbreak, we recently developed pseudo-infectious ZIKV RVPs by modifying our DENV RVP system. The use of ZIKV RVPs as critical reagents in human clinical trials requires their further validation using stability and reproducibility metrics for large-scale applications. In the current study, we validated ZIKV RVPs using infectivity, neutralization, and enhancement assays with monoclonal antibodies (MAbs) and human ZIKV-positive patient serum. ZIKV RVPs are antigenically identical to live virus based on binding ELISA and neutralization results and are nonreplicating based on the results of plaque formation assays. We demonstrate reproducible neutralization titer data (NT50values) across different RVP production lots, volumes, time frames, and laboratories. We also show RVP stability across experimentally relevant time intervals and temperatures. Our results demonstrate that ZIKV RVPs provide a safe, rapid, and reproducible reagent for large-scale, long-term studies of neutralizing antibodies and sera, which can facilitate large-scale screening and epidemiological studies to help expedite ZIKV vaccine development.

AUTHOR SUMMARY

ZIKV is a mosquito-borne virus that can cause severe birth defects and other disorders. Large outbreaks of ZIKV occurred in 2015 and 2016 and there are still no drugs or vaccines available to protect against ZIKV infection. Vaccine development has been hindered by the lack of safe and efficient methods to screen ZIKV neutralizing properties of patient sera or antibodies, especially in the context of large clinical trials. To address this unmet need, we developed and validated the use of ZIKV reporter virus particles (RVPs), a safe, high-throughput and quantitative alternative to using live virus for neutralization studies. We show that ZIKV RVPs are stable, show lot-to-lot consistency and provide reproducible neutralization data that is suitable for large-scale studies are needed for development of a ZIKV vaccine, epidemiologic surveillance, and high-throughput screening.
Tendon and Motor Phenotypes in theCrtap-/-Mouse Model of Recessive Osteogenesis Imperfecta
Authors: Grol Matthew W. , Haelterman Nele A. , Lim Joohyun , Munivez Elda M. , Archer Marilyn , Hudson David M. , Tufa Sara F. , Keene Douglas R. , Lei Kevin , Park Dongsu , Eyre David R. , Lee Brendan H.
Published: April 2020

Osteogenesis imperfecta (OI) is characterized by short stature, skeletal deformities, low bone mass with bone fragility, and motor deficits. A subset of OI patients also present with joint hypermobility; however, the role of tendon/ligament dysfunction in OI pathogenesis is largely unknown. Using theCrtap-/-mouse model of severe, recessive OI, we found that mutant Achilles tendons and patellar ligaments were thinner with increased collagen cross-links and reduced collagen fibril size at 1- and 4-months compared to wildtype. Patellar ligaments fromCrtap-/-mice also had fewer progenitors with a concomitant increase in immature cells. RNA-seq analysis of Achilles tendons and patellar ligaments from 1-monthCrtap-/-mice revealed dysregulation in matrix gene expression concomitant with predicted alterations in TGF-β, inflammatory, and metabolic signaling. Finally, a series of behavioral tests revealed severe motor impairments and reduced grip strength in 4-monthCrtap-/-mice – a phenotype that correlates with the tendon/ligament pathology.
A New Resource for Genomics and Precision Health Information and Publications on the Investigation and Control of COVID-19 and other Coronaviruses
Authors: Yu Wei , Gwinn Marta , Khoury Muin J.
Published: April 2020

We developed a new online database that contains the most updated published scientific literature, online news and reports, CDC and National Institutes of Health (NIH) resources. The tool captures emerging discoveries and applications of genomics, molecular, and other precision medicine and precision public health tools in the investigation and control of coronavirus diseases, including COVID-19, MERS-CoV, and SARS.

Availability

Coronavirus Disease Portal (CDP) can be freely accessed viahttps://phgkb.cdc.gov/PHGKB/coVInfoStartPage.action.

Contact

wyu@cdc.gov
VisEgg: A robust phenotyping tool to assess rainbow trout egg features and viability
Authors: Cardona Emilie , Bugeon Jérôme , Segret Emilien , Bobe Julien
Published: April 2020

Assessing female fish reproductive success requires a thorough evaluation of egg characteristics, including egg number, size and variability as well as egg developmental potential through the monitoring of embryo survival after fertilization. While embryonic success relies, at least in part, on paternal contribution, some parameters are strictly related to egg characteristics, one of the main ones being the viability of the egg when released into the water at spawning. It is however not necessarily possible, at least in salmonid fish that lay non-transparent eggs, to separate the different causes of egg/embryo failure.

In this context, our aim was i) to develop a simple and rapid system to capture images of rainbow trout eggs combined with computerized processing of these images to perform a fully automatic individual characterization of egg features including number and size ii) to estimate unfertilized egg viability through the monitoring of the percentage of eggs that will not survive to water hydration.

To evaluate the VisEgg system, unfertilized eggs (approximatively 400 eggs per batch) originating from 105 different females were hydrated in water. After 24h, a picture of the eggs was obtained using a dedicated shooting system consisting of a light source and a digital single-lens reflex (SLR) camera. An image processing algorithm was developed to allow the automatic detection and separation of the eggs and to perform automatic measurements of egg number and individual egg size. The presence of white egg was used as an indirect measure of egg integrity, the “whitening” being the result of water entry into the egg through the vitelline membrane. These white eggs were therefore considered as non-viable, as a result of their lack of physical integrity.

Fertilization assays were performed in parallel using a subsample of the same egg batch. Embryonic development was monitored and hatching rate was calculated. A significant correlation between white egg percentage after hydration and hatching rate was observed (Spearman coefficient =-0.557, p<0.001), in consistency with the fact that non-viable egg will not allow successful embryonic development. In contrast, the percentage of eggs that do not successfully hatched includes egg/embryo failures of different nature including egg viability, their capacity to be fertilized and to develop into an embryo. Using VisEgg, we were able to quantify the lack of viability of the eggs separately from the different other events that may occur during fertilization and incubation. VisEgg is a convenient and reliable tool to obtain individuals measures on trout eggs. It can be used to assess not only egg size and egg number but also unfertilized egg viability before fertilization.
Mitochondrial survivin reduces oxidative phosphorylation in cancer cells by inhibiting mitophagy
Authors: Townley Amelia R. , Wheatley Sally P.
Published: April 2020

Survivin is a cancer-associated protein that is pivotal for cellular life and death: it is an essential mitotic protein and an inhibitor of apoptosis. In cancer cells, a small pool of survivin localises to the mitochondria, the function of which remains to be elucidated. Here, we report that mitochondrial survivin inhibits the selective form of autophagy, called “mitophagy”, causing an accumulation of respiratory defective mitochondria. Mechanistically the data reveal that survivin prevents recruitment of the E3-ubiquitin ligase Parkin to mitochondria and their subsequent recognition by the autophagosome. The data also demonstrate that, as a consequence of this blockade, cells expressing high levels of survivin have an increased dependency on anaerobic glycolysis. As these effects were found exclusively in cancer cells they suggest that the primary act of mitochondrial survivin is to force cells to implement the “Warburg Effect” by inhibiting mitochondrial turnover.
TargetDB: A target information aggregation tool and tractability predictor
Authors: De Cesco Stephane P. , Davis John B. , Brennan Paul E.
Published: April 2020

When trying to identify new potential therapeutic targets, access to data and knowledge is increasingly important. In a field where new resources and data sources become available every day, it is crucial to be able to take a step back and look at the wider picture in order to identify potential drug targets. While this task is routinely performed by bespoke researchers, it is often time-consuming and lacks uniformity when one wants to compare multiple targets at the same time. Therefore we developed TargetDB, a tool that aggregates public information available on given target(s) (Links to disease, safety, 3D structures, ligandability, novelty,…) and assembles it in an easy to read output ready for the researcher to analyze. In this manuscript, we will present the methodology used to develop TargetDB as well as test cases.
Structural basis for human TRPC5 channel inhibition by two distinct inhibitors
Authors: Song Kangcheng , Wei Miao , Guo Wenjun , Kang Yunlu , Wu Jing-Xiang , Chen Lei
Published: April 2020

TRPC5 channel is a non-selective cation channel that participates diverse physiological processes. Human TRPC5 inhibitors show promise in the treatment of anxiety disorder, depression and kidney disease. Despite the high relevance of TRPC5 to human health, its inhibitor binding pockets have not been fully characterized due to the lack of structural information, which greatly hinders structure-based drug discovery. Here we show cryo-EM structures of human TRPC5 in complex with two distinct inhibitors, namely clemizole and HC-070, to the resolution of 2.7 Å. Based on the high-quality cryo-EM maps, we uncover the different binding pockets and detailed binding modes for these two inhibitors. Clemizole binds inside the voltage sensor-like domain of each subunit, while HC-070 binds close to the ion channel pore and is wedged between adjacent subunits. Both of them exert the inhibitory function by stabilizing the ion channel in a closed state. These structures provide templates for further design and optimization of inhibitors targeting human TRPC5.
A Structure-Based Mechanism for DNA Entry into the Cohesin Ring
Authors: Higashi Torahiko L. , Eickhoff Patrik , Simoes Joana S. , Locke Julia , Nans Andrea , Flynn Helen R. , Snijders Ambrosius P. , Papageorgiou George , O’Reilly Nicola , Chen Zhuo A. , O’Reilly Francis J. , Rappsilber Juri , Costa Alessandro , Uhlmann Frank
Published: April 2020

Despite key roles in sister chromatid cohesion and chromosome organization, the mechanism by which cohesin rings are loaded onto DNA is still unknown. Here, we combine biophysical approaches and cryo-EM to visualize a cohesin loading intermediate in which DNA is locked between two gates that lead into the cohesin ring. Building on this structural framework, we design biochemical experiments to establish the order of events during cohesin loading. In an initial step, DNA traverses an N-terminal kleisin gate that is first opened upon ATP binding and then closed as the cohesin loader locks the DNA against a shut ATPase gate. ATP hydrolysis leads to ATPase gate opening to complete DNA entry. Whether DNA loading is successful, or rather results in loop extrusion, might be dictated by a conserved kleisin N-terminal tail that guides the DNA through the kleisin gate. Our results establish the molecular basis for cohesin loading onto DNA.
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

Influenza 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.

Importance

Influenza 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

During 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

TRIM5α 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 STATEMENT

TRIM5α 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

Purpose

This 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/approach

This 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.

Findings

Younger 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/value

The 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

Purpose

This paper evaluates the economic, political and institutional determinants of variation in public investment in emerging Europe.

Design/methodology/approach

Panel 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).

Findings

Public 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 implications

To 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/value

The 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

Purpose

This 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/approach

The 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.

Findings

The 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/implications

The 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 data

Practical implications

In 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/value

This 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

Purpose

Globally, 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/approach

This 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.

Findings

The 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/value

Implications 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

Purpose

This 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/approach

Relying 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.

Findings

The 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/implications

This 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/value

This 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

Purpose

Knowledge 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/approach

The 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.

Findings

The 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/implications

The 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 implications

The 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/value

The 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

Vibrio 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

This 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

The 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.
Three‐dimensional modelling of computed tomography images of limb bones in gazelles (Gazella subgutturosa)
Authors: Demircioglu Ismail , Gezer Ince Nazan
Published: April 2020

The objective of the present study was to model in 3D the detailed morphometric features of the thoracic and pelvic limb bones of the gazelle (Gazella subgutturosa), whose natural habitat is only in the Sanliurfa province, by using multidetector computerized tomography (MDCT) images. Materials from 14 (7 male and 7 female) dead gazelles were collected from the Harran University Veterinary Medicine Faculty clinics during or after treatment. MDCT images of the gazelles were taken and saved as DICOM (Digital Imaging and Communications in Medicine) files. MIMICS 20.1 software was used to generate a 3D reconstruction of the data, and morphological and morphometrical evaluation was performed. In respect of morphological features, the combined metacarpus (Mc) III and metacarpus Mc IV were the main weight‐bearing metacarpal bone, while Mc II and Mc V were rudimentary. On the femur, the lateral condyle was bigger than the medial condyle at the caudodistal end and the medial wing of the trochlea femoris was larger than the lateral. As with the thoracic limb, the combined metatarsus (Mt) III and metatarsus Mt IV were the main weight‐bearing metacarpal bone and they displayed a synostosis structure. There was no secondary metatarsus in the gazelles’ pelvic limb. Based on digital measurements, the tibia was the longest bone of the gazelles’ skeletal system, and there was a statistically significant sexual dimorphism throughout the skeleton at the levels of p < .05, p < .01 and p < .001. As a result, the present study's findings are useful as reference data for further studies on anatomy, surgery and archaezoology, while also being useful for classifying species and for forensic sciences.
Can Simple Nudges and Workshops Improve Diet Quality? Evidence from a Randomized Trial in Bangladesh
Authors: Davidson Kelly A. , Kropp Jaclyn D. , Mullally Conner , Rahman Md. Wakilur
Published: April 2020

Despite improvements in food access and affordability around the world, low‐quality diets persist. Public policy affecting food choice may have a role to play alongside efforts to improve access to healthy foods. This study uniquely explores the potential for dietary interventions to encourage healthy food choice among adults in a developing country. We evaluate two dietary interventions using a randomized control trial in Bangladesh: a behavioral change communication workshop that emphasized national dietary guidelines and a “nudge” in the form of a plate printed with nutrition recommendations. We study the performance of both interventions in two environments: a lab‐in‐the‐field experiment where food choices are discreetly observed at two lunch events and in the home using household survey data. The workshop improves diet quality in the lab and the home, although its impact is less precisely estimated in the latter setting. We find no effect of the plate in the lab during the same lunch event when the plate is received. The plate is effective at home, and the nudge effects of in‐home exposure persist in the lab even when the plate is not being used. Receipt of the plate at the first lunch event followed by one month of subsequent in‐home access to the plate improves food choice at the second event. Combining treatments does not increase their effectiveness. We conclude that nudges improve diet quality in our study context, but more evidence is needed to determine the effects of workshop messages in the home.
Glucocorticoid receptor sensitivity in early pregnancy in an African American cohort
Authors: Clarke Lasha S. , Corwin Elizabeth J. , Dunlop Anne L. , Hankus Allison , Bradner Joshua M. , Paul Sudeshna , Jiao Yunshen , Smith Alicia K. , Patrushev Nikolay , Mulle Jennifer G. , Read Timothy D. , Hogue Carol J. R. , Pearce Bradley D.
Published: April 2020

Problem

Disruption in homeostatic feedback loops between inflammatory mediators and the hypothalamic‐pituitary‐adrenal (HPA) axis is a key mechanism linking chronic stress to inflammation and adverse health outcomes, including those occurring during pregnancy. In particular, alterations in glucocorticoid sensitivity may occur as a result of chronic stress, including that due to racial discrimination, and may be implicated in the persistent adverse maternal and infant health outcomes experienced by African Americans. While there are a few large‐scale studies in human pregnancy that measure both cytokines and HPA axis hormones, to our knowledge, none directly measure glucocorticoid sensitivity at the cellular level, especially in an African American population.

Method of study

We measured the full range of the dexamethasone (DEX) dose‐response suppression of TNF‐α in first‐trimester blood samples from 408 African American women and estimated leukocyte cell type contribution to the production of TNF‐α.

Results

The mean (SD) DEX level needed to inhibit TNF‐α production by 50% (ie, DEX IC50) was 9.8 (5.8) nmol/L. Monocytes appeared to be the main driver of Uninhibited TNF‐α production, but monocyte counts explained only 14% of the variation. Monocyte counts were only weakly correlated with the DEX IC50 (r = −.11, P < .05). Moreover, there was no statistically significant correlation between the DEX IC50 and circulating pro‐inflammatory (CRP, IL‐6, IFN‐γ) or anti‐inflammatory (IL‐10) mediators (P > .05).

Conclusion

These findings challenge some prior assumptions and position this comprehensive study of glucocorticoid sensitivity as an important anchor point in the growing recognition of interindividual variation in maternal HPA axis regulation and inflammatory responses.