bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of SARS-CoV-2 ORF3a structure reveals chloride binding sites
Authors: Marquez-Miranda Valeria , Rojas Maximiliano , Duarte Yorley , Diaz-Franulic Ignacio , Holmgren Miguel , Cachau Raul E. , Gonzalez-Nilo Fernando D. 
Published: October 2020

AbstractSARS-CoV-2 ORF3a is believed to form ion channels, which may be involved in the modulation of virus release, and has been implicated in various cellular processes like the up-regulation of fibrinogen expression in lung epithelial cells, downregulation of type 1 interferon receptor, caspase-dependent apoptosis, and increasing IFNAR1 ubiquitination. ORF3a assemblies as homotetramers, which are stabilized by residue C133. A recent cryoEM structure of a homodimeric complex of ORF3a has been released. A lower-resolution cryoEM map of the tetramer suggests two dimers form it, arranged side by side. The dimer’s cryoEM structure revealed that each protomer contains three transmembrane helices arranged in a clockwise configuration forming a six helices transmembrane domain. This domain’s potential permeation pathway has six constrictions narrowing to about 1 Å in radius, suggesting the structure solved is in a closed or inactivated state. At the cytosol end, the permeation pathway encounters a large and polar cavity formed by multiple beta strands from both protomers, which opens to the cytosolic milieu. We modeled the tetramer following the arrangement suggested by the low-resolution tetramer cryoEM map. Molecular dynamics simulations of the tetramer embedded in a membrane and solvated with 0.5 M of KCl were performed. Our simulations show the cytosolic cavity is quickly populated by both K+ and Cl-, yet with different dynamics. K+ ions moved relatively free inside the cavity without forming proper coordination sites. In contrast, Cl- ions enter the cavity, and three of them can become stably coordinated near the intracellular entrance of the potential permeation pathway by an inter-subunit network of positively charged amino acids. Consequently, the central cavity’s electrostatic potential changed from being entirely positive at the beginning of the simulation to more electronegative at the end.
Immunogenicity of a new gorilla adenovirus vaccine candidate for COVID-19
Authors: Capone Stefania , Raggioli Angelo , Gentile Michela , Battella Simone , Lahm Armin , Sommella Andrea , Contino Alessandra Maria , Urbanowicz Richard A. , Scala Romina , Barra Federica , Leuzzi Adriano , Lilli Eleonora , Miselli Giuseppina , Noto Alessia , Ferraiuolo Maria , Talotta Francesco , Tsoleridis Theocharis , Castilletti Concetta , Matusali Giulia , Colavita Francesca , Lapa Daniele , Meschi Silvia , Capobianchi Maria , Soriani Marco , Folgori Antonella , Ball Jonathan K. , Colloca Stefano , Vitelli Alessandra 
Published: October 2020

ABSTRACTThe COVID-19 pandemic caused by the emergent SARS-CoV-2 coronavirus threatens global public health and there is an urgent need to develop safe and effective vaccines. Here we report the generation and the preclinical evaluation of a novel replication-defective gorilla adenovirus-vectored vaccine encoding the pre-fusion stabilized Spike (S) protein of SARS-CoV2. We show that our vaccine candidate, GRAd- COV2, is highly immunogenic both in mice and macaques, eliciting both functional antibodies which neutralize SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and a robust, Th1- dominated cellular response in the periphery and in the lung. We show here that the pre-fusion stabilized Spike antigen is superior to the wild type in inducing ACE2-interfering, SARS-CoV2 neutralizing antibodies. To face the unprecedented need for vaccine manufacturing at massive scale, different GRAd genome deletions were compared to select the vector backbone showing the highest productivity in stirred tank bioreactors. This preliminary dataset identified GRAd-COV2 as a potential COVID-19 vaccine candidate, supporting the translation of GRAd-COV2 vaccine in a currently ongoing Phase I clinical trial (NCT04528641).
Unveiling the sensory and interneuronal pathways of the neuroendocrine connectome inDrosophila
Authors: Hückesfeld Sebastian , Schlegel Philipp , Miroschnikow Anton , Schoofs Andreas , Zinke Ingo , Haubrich André N , Schneider-Mizell Casey M , Truman James W , Fetter Richard D , Cardona Albert , Pankratz Michael J 
Published: October 2020

AbstractNeuroendocrine systems in animals maintain organismal homeostasis and regulate stress response. Although a great deal of work has been done on the neuropeptides and hormones that are released and act on target organs in the periphery, the synaptic inputs onto these neuroendocrine outputs in the brain are less well understood. Here, we use the transmission electron microscopy reconstruction of a whole central nervous system in theDrosophilalarva to elucidate the sensory pathways and the interneurons that provide synaptic input to the neurosecretory cells projecting to the endocrine organs. Predicted by network modeling, we also identify a new carbon dioxide responsive network that acts on a specific set of neurosecretory cells and which include those expressing Corazonin (Crz) and Diuretic hormone 44 (DH44) neuropeptides. Our analysis reveals a neuronal network architecture for combinatorial action based on sensory and interneuronal pathways that converge onto distinct combinations of neuroendocrine outputs.
A Gut Microbial Peptide and Molecular Mimicry in the Pathogenesis of Type 1 Diabetes
Authors: Girdhar Khyati , Huang Qian , Chow I-Ting , Brady Claudia , Raisingani Amol , Autissier Patrick , Atkinson Mark A. , Kwok William W. , Ronald Kahn C. , Altindis Emrah 
Published: October 2020

ABSTRACTType 1 Diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells. One of the earliest aspects of this process is development of autoantibodies and T-cells directed at an epitope in the B-chain of insulin (insB:9-23). Analysis of microbial protein sequences with homology to insB:9-23 sequence revealed 17 peptides showing >50% identity to insB:9-23. Of these, one peptide, found in the normal human gut commensal Parabacteroides distasonis, activated both human T cell clones from T1D patients and T-cell hybridomas from non-obese diabetic (NOD) mice specific to insB:9-23. Immunization of NOD mice with P. distasonis insB:9-23 peptide mimic or insB:9-23 peptide verified immune cross-reactivity. Colonization of female NOD mice with P. distasonis accelerated the development of T1D, increasing macrophages, dendritic cells and destructive CD8+ T-cells, while decreasing FoxP3+ regulatory T-cells. Western blot analysis identified P. distasonis reacting antibodies in sera of NOD mice colonized with P. distasonis and human T1D patients. Furthermore, adoptive transfer of splenocytes from P. distasonis treated mice to NOD/SCID mice enhanced disease phenotype in the recipients. Finally, analysis of human infant gut microbiome data revealed that exposure of infants to P. distasonis may modulate disease pathogenesis. Taken together, these data demonstrate the potential role for an insB:9-23-mimimetic peptide from gut microbiota as a molecular trigger or modifier of T1D pathogenesis.SIGNIFICANCE STATEMENTIn Type 1 diabetes (T1D), immune cells destroy pancreatic β-cells. The trigger of this response, however, is unknown. Some sequences (epitopes) in the insulin molecule form a major target for this autoimmune response. We have identified a sequence in a human gut bacterium that can mimetic this insulin epitope. Immune cells specific to insulin cross-react with this bacterial mimetic. Further, this bacterium can accelerate diabetes onset in a mouse model of T1D, inducing destructive and decreasing protective immune cells. We found this mimetic in the gut of children developing T1D. Furthermore, T1D patients have a stronger immune response to this bacterium compared to healthy individuals. Taken together, this bacterial mimetic in human gut has the potential to trigger/modify T1D onset.
The main activatory and tension-sensitive transitions occur within Prozac sensitive down-states of the potassium selective TREK-2 channel
Authors: Clausen Michael V. , Ulstrup Jakob , Poulsen Hanne , Nissen Poul 
Published: October 2020

AbstractThe two-pore domain potassium selective (K2P) ion-channels TREK-1, TREK-2, and TRAAK essential mechanical stimulation sensors, and TREK-1/2 also targets for the antidepressant Nor-fluoxetine (Prozac). They respond directly to membrane tension by moving from the “down” to “up” conformation, a transition that is associated with a rise in open-probability. However, the mechanosensitive K2P (mK2P) channels can also open while occupying the down conformation, and although these channels are mostly closed, all structural models represent seemingly open conformations. To understand the dynamics between open/closed and up/down states and determine how membrane tension influences transitions between specific conformations, we use a novel method to analyze tension-driven activation of single purified and reconstituted TREK-2 channels. We screen a panel of prospective schemes to find the mechanism that best accounts for specific TREK-2 characteristics as tension-driven activation, suppression by Nor-fluoxetine, and single-channel kinetics.To adequately describe TREK-2 behavior, mechanistic schemes require two separate tension-sensitive transitions, one that occurs between distinct down conformations and one that moves the channel between down and up states. As membrane tension activates TREK-2, it is a transition within the structural down conformations that account for the major increase in open-probability (> 100 fold); the move from down to up further promotes channel opening, but with much lower potency (~3 fold activation).
Structural and biochemical characterization of the class II fructose-1,6-bisphosphatase from Francisella tularensis
Authors: Selezneva Anna I. , Gutka Hiten J. , Wolf Nina M. , Qurratulain Fnu , Movahedzadeh Farahnaz , Abad-Zapatero Celerino 
Published: October 2020

The crystal structure of the class II fructose-1,6-bisphosphatase (FBPaseII) from the important pathogen Francisella tularensis is presented at 2.4 Å resolution. Its structural and functional relationships to the closely related phosphatases from Mycobacterium tuberculosis (MtFBPaseII) and Escherichia coli (EcFBPaseII) and to the dual phosphatase from Synechocystis strain 6803 are discussed. FBPaseII from F. tularensis (FtFBPaseII) was crystallized in a monoclinic crystal form (space group P21, unit-cell parameters a = 76.30, b = 100.17, c = 92.02 Å, β = 90.003°) with four chains in the asymmetric unit. Chain A had two coordinated Mg2+ ions in its active center, which is distinct from previous findings, and is presumably deactivated by their presence. The structure revealed an approximate 222 (D
2) symmetry homotetramer analogous to that previously described for MtFBPaseII, which is formed by a crystallographic dyad and which differs from the exact tetramer found in EcFBPaseII at a 222 symmetry site in the crystal. Instead, the approximate homotetramer is very similar to that found in the dual phosphatase from Synechocystis, even though no allosteric effector was found in FtFBPase. The amino-acid sequence and folding of the active site of FtFBPaseII result in structural characteristics that are more similar to those of the previously published EcFBPaseII than to those of MtFBPaseII. The kinetic parameters of native FtFBPaseII were found to be in agreement with published studies. Kinetic analyses of the Thr89Ser and Thr89Ala mutations in the active site of the enzyme are consistent with the previously proposed mechanism for other class II bisphosphatases. The Thr89Ala variant enzyme was inactive but the Thr89Ser variant was partially active, with an approximately fourfold lower K
m and V
max than the native enzyme. The structural and functional insights derived from the structure of FtFBPaseII will provide valuable information for the design of specific inhibitors.
Rheology of hydromagnetic viscoelastic fluid subjected to dissipation aspect
Authors: Waqas Muhammad , Nisar Ubaid Ahmed , Khan Muhammad Ijaz , Shehzad Sabir Ali 
Published: October 2020

Purpose
The purpose of this paper is to address the impact of gravity induced stretching flow of second grade liquid subject to thermal radiation. The flow is generated by the stretching of an impermeable cylinder. Stagnation point flow is considered. Convective type boundary conditions are applied on temperature and concentration. The present investigation further includes the aspects of magnetohydrodynamics, Joule heating, chemical reaction and viscous dissipation and heat generation/absorption.

Design/methodology/approach
The ordinary differential expressions are formed using suitable similarity transformations from the governing partial differential expressions. The subsequent nonlinear ordinary differential expressions are solved analytically using homotopy concept to report the consequences of different dimensionless physical parameters in graphical and tabular forms.

Findings
The results witnessed that increasing values of curvature parameter corresponds to higher temperature and concentration. Besides this, the impacts of destructive and constructive chemical processes on the concentration distribution are noted opposite.

Originality/
No such analysis has yet been reported.
A citizen-centred approach to CSR in banking
Authors: van Hierden Yannick Thomas , Dietrich Timo , Rundle-Thiele Sharyn 
Published: October 2020

PurposeThis study aims to demonstrate how banks can align their CSR investment to community needs and citizen preferences. A grounded theory inductive approach is applied to deliver a community-centred process that banks can apply to inform CSR investment decisions.Design/methodology/approachThis study employed a sequential mixed-method research design to identify areas of need from the perspective of community leaders and members through depth interviews. Following thematic analysis, citizen preferences for eight priority areas were elicited using best-worst scaling (BWS).FindingsClear investment preferences emerged with citizens preferring six community investment causes, namely, (1) infrastructure, (2) crisis and prevention support, (3) community groups, (4) youth facilities and activities, (5) initiatives that support the local environment, and (6) physical activity promotion. The forming of community advisory committees emerged as one approach that banks could apply to ensure long-term citizen-centred CSR investment decisions.Research limitations/implicationsThis study is limited to one community and one community bank and a small convenience, cross-sectional data sample.Social implicationsCommunity-oriented financial institutions should centre investment decisions on community need and citizen preferences ensuring investments made deliver the greatest societal benefit and community support for the banks is garnered.Originality/valueThis paper provides important contributions to improve the effectiveness of CSR initiatives, providing an inductive, methodological approach that financial institutions can follow to better align their CSR investment to community needs and preferences.
Friction characteristics of moving joint surface from the micro and macro scale
Authors: Hai Lixin , Gao Feng , Li Yan , Yang Bo , Zhu Yanyan 
Published: October 2020

Purpose
The nonlinear friction disturbance of the moving joint surface of the feed system can lead to the residual vibration of the system, prolong the stability time of the system and reduce the motion precision and machining precision of the machine tool. This paper aims to concern the vibration between joint surfaces caused by nonlinear friction.

Design/methodology/approach
The model is established from the micro and macro scale based on the LuGre model. The friction characteristics of the moving joint surface are explored. The friction experiment of GCr15 pin and 45 steel disk is designed and the influence of lubrication condition, speed, acceleration and normal load on friction characteristics are studied.

Findings
Among the drive speed, damping and stiffness, the negative gradient effect of friction, which is characterized by the difference of static and dynamic friction coefficient Δµ, is the main cause of friction vibration between moving joint surfaces. Sufficient lubrication, a proper increase of speed and acceleration, a reasonable reduction of normal load can reduce the negative gradient effect, which can weaken the vibration caused by the nonlinear friction and improve the friction characteristics of the moving joint surface.

Originality/value
In the past studies, more attention has been paid to revealing the relationship between the relative speed and friction, while the acceleration is often ignored. The negative gradient effect of friction is improved in this paper by changing the contact conditions. Research findings of this paper effectively improve the friction characteristics of the moving interface and provide the basis for restraining the nonlinear vibration between the moving interfaces.

Peer review
The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-11-2019-0476/
The impact of method choice on the risk of contraceptive discontinuation: Egypt 2014
Authors: Khalifa Mona , Abdel Aziz Hussein Wafaa , Metwally Soha 
Published: October 2020

Purpose
In Egypt, the IUD is the most common contraceptive method since 1988 and has remained so despite a recent drop in its share from 59.9% in 2008 to 51.5% in 2014 in favour of hormonal methods, which increased from 19.7% for pills and 12.3% for injectables in 2008 to 27.4% and 14.5% in 2014 according to 2014 Egypt demographic and health survey (EDHS). The recent shift away from intrauterine contraceptive device (IUDs) to hormonal methods have contributed to increased discontinuation. This paper aims to answer three questions: To what extent does the method type influence the hazard of contraceptive discontinuation in Egypt? Is the interaction between method type and duration of use a predictor of the probability of discontinuation after controlling other variables? What are the other important background variables that affect the hazard of contraceptive discontinuation?

Design/methodology/approach
Using data from EDHS2014, separate multilevel discrete-time proportional hazard models for events of interest (abandoned use while in need, switched to another method in the month following discontinuation and method failure) were built.

Findings
Only IUD users are significantly less likely to abandon use while in need and to experience method failure and a reduced risk of switching. During the first 6–10 months of use, all types of discontinuation can be significantly reduced for all three methods. Demographic variables do not significantly affect abandonment but strongly affect switching and significantly affect failure. Socio-economic variables do not significantly affect abandonment and switching. Exposure to media has a significant effect on abandonment but not on switching. Community contraceptive prevalence rate strongly affects switching.

Originality/value
Results confirm that the counselling should be more intense during the first year of method use and should pay special attention to women who are 25 years old and above and those who have two or more children. Also, media campaigns are important and especially those addressing the issue of abandoning while in need.
Bridging job search and perceived employability in the labour market – a mediation model of job search, perceived employability and learning goal orientation
Authors: K.A. Zakkariya , P.M. Nimmi , A. Smitha Pradeep 
Published: October 2020

Purpose
Perceived employability (PE) is considered as a significant psychological resource that aids individuals in tackling the complex career snags he/she faces. The purpose of this study is to develop and empirically test a theoretical model that explains how PE affects two types of job search behaviour (JSB) by bringing in job search learning goal orientation (JSLGO) as mediator and work experience as a moderator. The model is conceptualised in the backdrop of self-regulation theory and conservation of resource theory.

Design/methodology/approach
Using a cross-sectional study of 319 management graduates, the authors examined the effect of JSLGO and PE on both active and preparatory job search of graduates. Structural equation modelling (SEM) using IBM-AMOS was conducted on the cross-sectional data collected from management graduates in India.

Findings
An empirical analysis using SEM unravelled that JSLGO mediated the relationship between preparatory job search and PE but did not intervene in the relationship between active job search and PE. The study also looked into the moderating role of work experience and it was found to be a significant moderator in the PE and job search – active relationship.

Practical implications
Work experience helps students in active job search stage which can lead to quick employment gains. Real job experience could be gained through work-integrated learning and on the job training, as they will enhance the exposure of students to real-life work situations. Higher levels of JSLGO indicate a more strategic approach and aiming a quality career. Learning goal orientation training should be embedded in the curriculum, as management education is all about preparing students for the world of work.

Originality/value
The current research has uniquely contributed to the limited literature on the importance of developing PE amongst management graduates and its consequence on job search. The study makes an important contribution to the theory and practices on job search by enhancing our understanding of the mechanism that governs PE and JSB relationship through goal orientation.
Implementing ‘cleanliness is half of faith’ in re-designing tourists, experiences and salvaging the hotel industry in Malaysia during COVID-19 pandemic
Authors: Awan Maheen Iqbal , Shamim Amjad , Ahn Jiseon 
Published: October 2020

Purpose
In the prevailing COVID-19 pandemic, organizations now are expected to serve customers who are highly conscious of safety and sanitation. Among others, the hospitality industry is significantly and negatively influenced by this pandemic. Given the unique characteristics of services, using advanced technology is not enough to create a memorable experience without physical interaction between service providers and customers. Thus, this study aims to define the “new normal” for service customers and to explore the “new service design” for the hotel industry.

Design/methodology/approach
As most of the Southeast Asian countries heavily rely on the tourism industry, this study focuses on one of the emerging tourism destinations in this region, Malaysia. The data is collected through in-depth interviews with 17 potential national and international tourists.

Findings
The results suggest that considering the “new normal” for customers, there is an immediate need for the hotel industry to revamp their service design by mainly practicing disinfection and sanitation activities, re-designing overall infrastructure and introducing promotional offers.

Originality/value
This study is novel in its kind as it provides useful guidelines for both practitioners and academicians/researchers. Under this crucial time, very few research is conducted specifically focusing on the hotel industry and tourists’ behaviors amidst the COVID-19 pandemic. The study will provide in-depth knowledge about tourists’ expectations from the hotel services, especially in their own voices.