bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supramolecular assembly of theE. coliLdcI upon acid stress
Authors: Jessop Matthew , Liesche Clarissa , Felix Jan , Desfosses Ambroise , Baulard Megghane , Adam Virgile , Fraudeau Angélique , Huard Karine , Effantin Grégory , Kleman Jean-Philippe , Bacia-Verloop Maria , Bourgeois Dominique , Gutsche Irina 
Published: May 2020

AbstractPathogenic and commensal bacteria often have to resist the harsh acidity of the host stomach. The inducible lysine decarboxylase LdcI buffers the cytosol and the local extracellular environment to ensure enterobacterial survival at low pH. Here, we investigate the acid-stress response regulation ofE. coliLdcI by combining biochemical and biophysical characterisation with negative stain and cryo-electron microscopy, and wide-field and super-resolution fluorescence imaging. Due to deleterious effects of fluorescent protein fusions on native LdcI decamers, we opt for three-dimensional localisation of nanobody-labelled endogenous wild-type LdcI in acid-stressedE. colicells, and show that it organises into distinct patches at the cell periphery. Consistent with recent hypotheses thatin vivoclustering of metabolic enzymes often reflects their polymerisation as a means of stimulus-induced regulation, we show that LdcI assembles into filamentsin vitroat physiologically relevant low pH. We solve the structures of these filaments and of the LdcI decamer formed at neutral pH by cryo-electron microscopy, and reveal the molecular determinants of LdcI polymerisation, confirmed by mutational analysis. Finally, we propose a model for LdcI function inside the enterobacterial cell, providing a structural and mechanistic basis for further investigation of the role of its supramolecular organisation in the acid stress response.Significance statementBacteria possess a sophisticated arsenal of defence mechanisms that allow them to survive in adverse conditions. Adaptation to acid stress and hypoxia is crucial for the enterobacterial transmission in the gastrointestinal tract of their human host. When subjected to low pH,E. coliand many other enterobacteria activate a proton-consuming resistance system based on the acid-stress inducible lysine decarboxylase LdcI. Here we develop generally-applicable tools to uncover the spatial localisation of LdcI inside the cell by super-resolution fluorescence microscopy, and investigate thein vitrosupramolecular organisation of this enzyme by cryo-EM. We build on these results to propose a mechanistic model for LdcI function and offer tools for furtherin vivoinvestigations.
Upregulated-flotillins and sphingosine kinase 2 derail vesicular trafic to stabilize AXL and promote epithelial-mesenchymal transition
Authors: Genest Mallory , Comunale Franck , Planchon Damien , Govindin Pauline , Vacher Sophie , Bièche Ivan , Robert Bruno , Malhotra Himanshu , Schoenit Andreas , Tashireva Liubov A. , Gauthier-Rouvière Cécile , Bodin Stéphane 
Published: May 2020

AbstractAltered endocytosis and vesicular trafficking are major players during tumorigenesis. Flotillin overexpression, a feature observed in many invasive tumors, and identified as a marker of poor prognosis, induces a deregulated endocytic and trafficking pathway called Upregulated Flotillin-Induced Trafficking (UFIT). Here, we found that, in non tumoral mammary epithelial cells, induction of the UFIT pathway promotes epithelial-to-mesenchymal transition (EMT) and accelerates the endocytosis of several transmembrane receptors, including AXL, in flotillin-positive late endosomes. AXL overexpression, frequently observed in cancer cells, is linked to EMT and metastasis formation. In flotillin-overexpressing non-tumoral mammary epithelial cells and in invasive breast carcinoma cells, we found that the UFIT-pathway-mediated AXL endocytosis allows its stabilization and depends on sphingosine-kinase 2, a lipid kinase recruited in flotillin-rich plasma membrane-domains and endosomes.Thus, the deregulation of vesicular trafficking following flotillin upregulation, and through sphingosine kinase 2, emerges as a new mechanism of AXL overexpression and EMT-inducing signaling pathway activation.
Mediocremonas mediterraneus, a New Member within the Developea
Authors: Weiler Bradley A. , Sà Elisabet L. , Sieracki Michael E. , Massana Ramon , del Campo Javier 
Published: May 2020

ABSTRACTThe Stramenopiles are a large and diverse group of eukaryotes that possess various lifestyles required to thrive in a broad array of environments. The stramenopiles branch with the alveolates, rhizarians, and telonemids, forming the supergroup TSAR. Here, we present a new genus and species of aquatic nanoflagellated stramenopile:Mediocremonas mediterraneus, a free-swimming heterotrophic predator.M. mediterraneuscell bodies measure between 2.0-4.0 μm in length and 1.2-3.7 μm in width, possessing two flagella and an oval body morphology. The growth and grazing rate ofM. mediterraneusin batch cultures ranges from 0.68 to 1.83 d-1and 1.99 to 5.38 bacteria h-1, respectively.M. mediterraneuswas found to be 93.9% phylogenetically similar withDevelopayella elegansand 94.7% withDevelorapax marinus, two members within the class Developea. The phylogenetic position of the Developea and the ability ofM. mediterraneusto remain in culture makes it a good candidate for further genomic studies that could help us to better understand phagotropy in marine systems as well as the transition from heterotrophy to phototrophy within the stramenopiles.
Retrograde transport defects inMunc18-1null neurons explain abnormal Golgi morphology
Authors: van Berkel Annemiek A. , Santos Tatiana C. , Shaweis Hesho , van Weering Jan R.T. , Toonen Ruud F. , Verhage Matthijs 
Published: May 2020

AbstractLoss of the exocytic Sec1/MUNC18 protein MUNC18-1 or its t-SNARE partners SNAP25 and syntaxin-1 results in rapid, cell-autonomous and unexplained neurodegeneration, which is independent of their known role in synaptic vesicle exocytosis.cis-Golgi abnormalities are the earliest cellular phenotypes before degeneration occurs. Here, we investigated whether these Golgi abnormalities cause defects in the constitutive and regulated secretory pathway that may explain neurodegeneration. Electron microscopy confirmed that loss of MUNC18-1 expression results in a smallercis-Golgi. In addition, we now show thatmedial-Golgi and thetrans-Golgi Network are also affected. However, stacking and cisternae ultrastructure of the Golgi were normal. Overall ultrastructure of null mutant neurons was remarkably normal just hours before cell death occurred. Anterograde ER-to-Golgi and Golgi exit of endogenous and exogenous proteins were normal. In contrast, loss of MUNC18-1 caused reduced retrograde Cholera Toxin transport from the plasma membrane to the Golgi. In addition, MUNC18-1-deficiency resulted in abnormalities in retrograde TrkB trafficking. We conclude that MUNC18-1 deficient neurons have normal anterograde yet reduced retrograde transport to the Golgi. This imbalance in transport routes provides a plausible explanation for the observed Golgi abnormalities and cell death in MUNC18-1 deficient neurons.Significance statementLoss of MUNC18-1 or its t-SNAREs SNAP25 and syntaxin-1 leads to massive, yet unexplained, neurodegeneration. Previous research showed that Golgi abnormalities are the earliest, shared phenotype. Golgi abnormalities are also an early feature in neurodegenerative diseases, such as Alzheimer’s Disease or Amyotrophic Lateral Sclerosis. This study elucidates the mechanism underlying the Golgi phenotype upon loss of MUNC18-1. By systematically assessing transport routes to and from the Golgi, we show that retrograde endosome-to-Golgi, but not anterograde transport from the Golgi, is disturbed. This imbalance in transport routes provides a plausible explanation for the Golgi phenotype, and may explain the neurodegeneration. The findings in this study contributes to new insights in cellular mechanisms of neurodegeneration.
Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence
Authors: Nguyen Thanh Thi , Abdelrazek Mohamed , Nguyen Dung Tien , Aryal Sunil , Nguyen Duc Thanh , Reddy Sandeep , Hung Nguyen Quoc Viet , Khatami Amin , Hsu Edbert B. , Yang Samuel 
Published: May 2020

AbstractOrigin of the COVID-19 virus (SARS-CoV-2) has been intensely debated in the scientific community since the first infected cases were detected in December 2019. The disease has caused a global pandemic, leading to deaths of thousands of people across the world and thus finding origin of this novel coronavirus is important in responding and controlling the pandemic. Recent research results suggest that bats or pangolins might be the hosts for SARS-CoV-2 based on comparative studies using its genomic sequences. This paper investigates the SARS-CoV-2 origin by using artificial intelligence (AI) and raw genomic sequences of the virus. More than 300 genome sequences of COVID-19 infected cases collected from different countries are explored and analysed using unsupervised clustering methods. The results obtained from various AI-enabled experiments using clustering algorithms demonstrate that all examined SARS-CoV-2 genomes belong to a cluster that also contains bat and pangolin coronavirus genomes. This provides evidence strongly supporting scientific hypotheses that bats and pangolins are probable hosts for SARS-CoV-2. At the whole genome analysis level, our findings also indicate that bats are more likely the hosts for the COVID-19 virus than pangolins.
Platelet Derived Growth Factor Receptor β (PDGFRβ) is a Host Receptor for the human malaria parasite adhesin TRAP
Authors: Steel Ryan W. J. , Vigdorovich Vladimir , Dambrauskas Nicholas , Wilder Brandon K. , Arredondo Silvia A. , Goswami Debashree , Kumar Sudhir , Carbonetti Sara , Swearingen Kristian E. , Nguyen Thao , Betz Will , Camargo Nelly , Fisher Bridget S. , Soden Jo , Thomas Helen , Freeth Jim , Moritz Robert L. , Sather D. Noah , Kappe Stefan H.I. 
Published: May 2020

AbstractFollowing their inoculation by the bite of an infectedAnophelesmosquito, the malaria parasite sporozoite forms travel from the bite site in the skin into the bloodstream, which transports them to the liver. The thrombospondin-related anonymous protein (TRAP) is a type 1 transmembrane protein that is released from secretory organelles and relocalized on the sporozoite plasma membrane. TRAP is required for sporozoite motility and host infection, and its extracellular portion contains adhesive domains that are predicted to engage host receptors. Here, we identified the human platelet-derived growth factor receptor β (hPDGFRβ) as one such protein receptor. Deletion mutants showed that the von Willebrand factor type A and thrombospondin repeat domains of TRAP are both required for optimal binding to hPDGFRβ-expressing cells. We also demonstrate that this interaction is conserved in the human-infective parasitePlasmodium vivax, but not the rodent-infective parasitePlasmodium yoelii. We observed expression of hPDGFRβ mainly in cells associated with the vasculature suggesting that TRAP:hPDGFRβ interaction may play a role in the recognition of blood vessels by invading sporozoites.
High-throughputin vitrospecificity profiling of natural and high-fidelity CRISPR-Cas9 variants
Authors: Murugan Karthik , Seetharam Arun S. , Severin Andrew J. , Sashital Dipali G. 
Published: May 2020

AbstractCas9 is an RNA-guided endonuclease in the bacterial CRISPR-Cas immune system and a popular tool for genome editing. The most commonly used Cas9 variant,Streptococcus pyogenesCas9 (SpCas9), is relatively non-specific and prone to off-target genome editing. Other Cas9 orthologs and engineered variants of SpCas9 have been reported to be more specific than wild-type (WT) SpCas9. However, systematic comparisons of the cleavage activities of these Cas9 variants have not been reported. In this study, we employed our high-throughputin vitrocleavage assay to compare cleavage activities and specificities of two natural Cas9 variants (SpCas9 andStaphylococcus aureusCas9) and three engineered SpCas9 variants (SpCas9 HF1, HypaCas9, and HiFi Cas9). We observed that all Cas9s tested were able to cleave target sequences with up to five mismatches. However, the rate of cleavage of both on-target and off-target sequences varied based on the target sequence and Cas9 variant. For targets with multiple mismatches, SaCas9 and engineered SpCas9 variants are more prone to nicking, while WT SpCas9 creates double-strand breaks (DSB). These differences in cleavage rates and DSB formation may account for the varied specificities observed in genome editing studies. Our analysis reveals mismatch position-dependent, off-target nicking activity of Cas9 variants which have been underreported in previousin vivostudies.
Corporate social responsibility strategies in Nigeria: a tinged shareholder model
Authors: Adegbite Emmanuel , Amaeshi Kenneth , Nakpodia Franklin , Ferry Laurence , Yekini Kemi C. 
Published: May 2020

PurposeThis paper aims to examine two important issues in corporate social responsibility (CSR) scholarship. First, the study problematises CSR as a form of self-regulation. Second, the research explores how CSR strategies can enable firms to recognise and internalise their externalities while preserving shareholder value.Design/methodology/approachThis study uses a tinged shareholder model to understand the interactions between an organisation’s CSR approach and the effect of relevant externalities on its CSR outcomes. In doing this, the case study qualitative methodology is adopted, relying on data from one Fidelity Bank, Nigeria.FindingsBy articulating a tripodal thematic model – governance of externalities in the economy, governance of externalities in the social system and governance of externalities in the environment, this paper demonstrates how an effective combination of these themes triggers the emergence of a robust CSR culture in an organisation.Research limitations/implicationsThis research advances the understanding of the implication of internalising externalities in the CSR literature in a relatively under-researched context – Nigeria.Originality/valueThe data of this study allows to present a governance model that will enable managers to focus on their overarching objective of shareholder value without the challenges of pursuing multiple and sometimes conflicting goals that typically create negative impacts to non-shareholding stakeholders.
Prioritizing psychosocial services for children, youth and families postdisaster
Authors: Fulton Amy Elizabeth , Drolet Julie , Lalani Nasreen , Smith Erin 
Published: May 2020

PurposeThis article explores the community recovery and resilience element of “building back better” (BBB) through the perspectives and experiences of community influencers who provided psychosocial supports after the 2013 floods in southern Alberta, Canada.Design/methodology/approachThe Alberta Resilient Communities (ARC) project adopted a community-based research methodology to examine the lived realities of children, youth, families and their communities postflood. In-depth semistructured interviews were conducted with 37 community influencer participants representing a range of organizations including not-for-profit agencies, community organizations, social service agencies and government departments.FindingsThe findings were drawn from the interviews held with community influencers in flood-affected communities. Major themes include disaster response challenges, insufficient funding for long-term disaster recovery, community partnerships and collaborations and building and strengthening social capital.Practical implicationsFindings demonstrate the need to build better psychosocial services, supports and resources in the long term to support community recovery and resilience postdisaster for children, youth and families to “build back better” on a psychosocial level.Social implicationsLocal social service agencies play a key role in the capacity of children, youth and families to “build back better” postdisaster. These organizations need to be resourced and prepared to respond to psychosocial needs in the long term in order to successfully contribute to postdisaster recovery.Originality/valueThe findings illustrate that adopting a psychosocial framework for disaster recovery can better inform social service disaster response and long-term recovery plans consistent with the BBB framework. Implications for social service agencies and policymakers interested in fostering postdisaster community recovery and resilience, particularly with children and youth, are presented.
Identifying the key factors in construction projects that affect neighbourhood social sustainability
Authors: Almahmoud Essam , Doloi Hemanta Kumar 
Published: May 2020

Purpose
Construction projects have huge impacts on the social sustainability of the neighbouring community. The purpose of this paper is to identify and understand the key factors of a construction project that contribute to the social sustainability of a neighbourhood.

Design/methodology/approach
Questionnaire surveys relating to two case studies of regeneration projects in Saudi Arabia were carried out to ascertain and analyse the perceptions of residents of the neighbourhood communities in which the projects were built.

Findings
The results derived from factor analysis suggested five significant underlying social factors: health and physical comfort, accessibility, integration, economy and participation. These are defined as the core social functions necessary for enhancing social sustainability in the neighbourhood community as a result of new construction.

Originality/value
Ideally, a construction project will create spaces where people can interact socially, develop a sense of community and grow and prosper. This study reveals how the neighbours of the project felt about it and what sort of input they wanted to have in the design, construction and operation of the facility. For developers emphasising sustainability, this is the essential data.
Gender and internal control systems in Spanish local governments
Authors: Gras-Gil Ester , Moreno-Enguix María del Rocío , Henández-Fernández Joaquín 
Published: May 2020

PurposeThe presence of women is lower than that of men in positions of responsibility in economic management in public administration, although there has been a more significant increase in local administration. The purpose of this study is to determine whether the application and development of the internal control system in local governments improves through the presence of women in positions of management and responsibility in these institutions.Design/methodology/approachThe authors use a multivariate model that allows them to verify the predictive capability of their previously defined explanatory variable gender in 1,527 Spanish local governments. They analyze the empirical relation between the gender and internal control system by multivariate regression models.FindingsThe authors find that the presence of women in management positions in local governments affects internal control system influences as well as a series of financial and non-financial variables. They conclude that in local governments of more than 50,000 inhabitants, the presence of women in the management has a positive influence on internal control systems and also promotes transparency and a more effective fight against corruption, thus enhancing internal control systems.Research limitations/implicationsThe presence of women in positions of management and responsibility in local government will favor a decrease of corruption in local governments and increase their efficiency and transparency. This study can facilitate women’s access to positions of more economic and financial responsibility in public administration, as well as improve the management and efficiency in these institutions.Originality/valueThis research is novel in that it determines whether the application and development of the internal control system in local governments improves through the presence of women in the position of management and responsibility in these institutions.
Exploring the overlooked: women, work and criminal history
Authors: Young Nicole Carrie Jones , Anazodo Kemi Salawu 
Published: May 2020

PurposeThis paper aims to explore how incarcerated women prepare to manage the stigma of a criminal history as they look to re-enter the workforce after release from incarceration.Design/methodology/approachThis paper uses a qualitative, case study research design including interviews and observations to explore the experiences and self-perceptions of incarcerated women within the context of employment.FindingsFive themes that emerged and influenced the perception of stigma as these incarcerated women prepared for release into the labor market were career self-efficacy, the intersection of identity (women and criminal history), self-perceptions of prison identity, stigma disclosure and social support for employment.Research limitations/implicationsAs the management literature expands to include more diverse and marginalized populations, current understanding of theories and concepts, such as multiple identities and stigma disclosure, may operate differently as compared to traditional management samples.Practical implicationsOrganizations can collaborate with correctional facilities to ensure that individuals with a criminal history are trained and prepared to re-enter the workplace upon release.Social implicationsAs employment is one of the biggest determinants of recidivism (i.e. return to incarceration) for individuals with a criminal history, organizations have the unique ability to assist in substantially decreasing the incarcerated population.Originality/valueThis study explores criminal history and highlights some of the nuances to consider when exploring an understudied and marginalized population, such as women with a criminal history.
The functioning of rescue workers in life tasks: development of a test
Authors: Bakker Heilwine , van Veldhoven Marc , Gaillard Tony , Hertogs Remy , Feenstra Margot 
Published: May 2020

Purpose
Since policemen have a highly demanding job, they have a high risk of developing mental health problems, which may have a negative influence on their private life. The purpose of this paper is to present a new questionnaire for measuring the functioning of rescue workers in life tasks outside of work.

Design/methodology/approach
The internal consistency, factor structure and concurrent validity of this life tasks test (LTT) were examined in a group of 108 policemen.

Findings
The test measures perceived effectiveness in the following five domains: social life, maintaining mental health, household and finance, giving meaning and maintaining positivity. Cronbach’s α was acceptable for two scales (>0.60) and good for the other three (>0.70). The hypothesized five-factor structure of the LTT was corroborated in a confirmatory factor analysis. Concurrent validity was examined by correlating the scores on the LTT with two established questionnaires, one for personality characteristics and one for work characteristics and work stress. All LTT scales, with the exception of social life, showed significant correlations with social support, workload and personality.

Research limitations/implications
This provides support for the concurrent validity of the questionnaire. Practical uses and future research are discussed.

Practical implications
The items are close to everyday clinical practice. It adds valuable information to the commonly used questionnaires on mental health complaints. The test may also provide insight on which life tasks domains are functioning well and which are in need of attention to improve the effectiveness.

Social implications
In both preventive and curative mental health support, it is important to enhance the effectiveness in life tasks, because it works as a buffer for the adversity of rescue work. Moreover, it gives rescue workers mastery of their personal life, makes self-management stronger, as well as it gives feelings of confidence and positive energy.

Originality/value
This is the first questionnaire to be designed and implemented for rescue workers.