bluuebunny/crossref_metadata_2025_split huggingface dataset:
Listeria monocytogenes TcyKLMN cystine/cysteine transporter facilitates glutathione synthesis and virulence gene expression
Authors: Brenner Moran , Friedman Sivan , Haber Adi , Borovok Ilya , Sigal Nadejda , Lewinson Oded , Herskovits Anat A. 
Published: September 2021

AbstractListeria monocytogenes (Lm) is a saprophyte and a human intracellular pathogen. Upon invasion into mammalian cells, it senses multiple metabolic and environmental signals that collectively trigger its transition to the pathogenic state. One of these signals is the tripeptide glutathione, which acts as an allosteric activator of Lm’s master virulence regulator, PrfA. While glutathione synthesis by Lm was shown to be critical for PrfA activation and virulence gene expression, it remains unclear how this tripeptide is synthesized under changing environments, especially in light of the observation that Lm is auxotrophic to one of its precursors, cysteine. Here, we show that the ABC transporter TcyKLMN is a cystine/cysteine importer that supplies cysteine for glutathione synthesis, hence mediating the induction of the virulence genes. Further, we demonstrate that this transporter is negatively regulated by three metabolic regulators: CodY, CymR and CysK, which sense and respond to changing concentrations of branched chain amino acids (BCAA) and cysteine. The data indicate that under low concentrations of BCAA, TcyKLMN is up-regulated, driving the production of glutathione by supplying cysteine, thereby facilitating PrfA activation. These findings provide molecular insight into the coupling of Lm metabolism and virulence, connecting BCAA sensing to cysteine uptake and glutathione biosynthesis, as a mechanism that controls virulence gene expression. This study exemplifies how bacterial pathogens sense their intracellular environment and exploit essential metabolites as effectors of virulence.ImportanceBacterial pathogens sense the repertoire of metabolites in the mammalian niche and use this information to shift into a pathogenic state to accomplish successful infection. Glutathione is a virulence-activating signal that is synthesized by L. monocytogenes during infection of mammalian cells. In this study, we show that cysteine uptake via TcyKLMN drives glutathione synthesis and virulence gene expression. The data emphasize the intimate cross-regulation between metabolism and virulence in bacterial pathogens.
Artemisia annuahot-water extracts show potent activityin vitroagainst Covid-19 variants including delta
Authors: Nair M.S. , Huang Y. , Fidock D.A. , Towler M.J. , Weathers P.J. 
Published: September 2021

AbstractEthnopharmacological relevanceFor millennia in Southeast Asia,Artemisia annuaL. was used to treat “fever”. This medicinal plant is effective against numerous infectious microbial and viral diseases and is used by many global communities as a source of artemisinin derivatives that are first-line drugs to treat malaria.Aim of the StudyThe SARS-CoV-2 (Covid-19) global pandemic has killed millions and evolved numerous variants, with delta being the most transmissible to date and causing break-through infections of vaccinated individuals. We further queried the efficacy ofA. annuacultivars against new variants.Materials and MethodsUsing Vero E6 cells, we measured anti-SARS-CoV-2 activity of dried-leaf hot-waterA. annuaextracts of four cultivars, A3, BUR, MED, and SAM, to determine their efficacy against five fully infectious variants of the virus: alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), and kappa (B.1.617.1).ResultsIn addition to being effective against the original wild type WA1,A. annuacultivars A3, BUR, MED and SAM were also potent against all five variants. IC50and IC90values based on measured artemisinin content ranged from 0.3-8.4 μM and 1.4-25.0 μM, respectively. The IC50and IC90values based on dried leaf weight (DW) used to make the tea infusions ranged from 11.0-67.7 μg DW and 59.5-160.6 μg DW, respectively. Cell toxicity was insignificant at a leaf dry weight of ≤50 μg in the extract of any cultivar.ConclusionsResults suggest that oral consumption ofA. annuahot-water extracts (tea infusions), could provide a cost-effective therapy to help stave off the rapid global spread of these variants, buying time for broader implementation of vaccines.
Efficient transgenesis and homology-directed gene targeting in monolayers of primary human small intestinal and colonic epithelial stem cells
Authors: Breau Keith A. , Ok Meryem T. , Gomez-Martinez Ismael , Burclaff Joseph , Kohn Nathan P. , Magness Scott T. 
Published: September 2021

AbstractBackground & Aims2D monolayers of primary intestinal and colonic epithelial cells represent next-generation in vitro models of the gut. Efficient transgenesis and gene-editing in human intestinal stem cells (hISCs) would significantly improve utility of these models by enabling generation of reporter and loss/gain-of-function hISCs, but no published methods exist for transfecting 2D hISC monolayers. Electroporation has proven effective in other difficult-to-transfect cells; thus we applied this method to hISCs.MethodsTwenty-four electroporation parameters were tested, and the optimal condition for efficiency and viability was validated on hISCs from six anatomical regions along the small intestine and colon. PiggyBac™ transposase and Cas9 ribonucleoprotein (RNP) complexes were used for stable genomic integration of reporter genes. High-throughput methods for clone isolation, expansion, and screening were developed. An hISC OLFM4-emGFP reporter was generated and validated by qPCR, organoid assays, and hISC compartmentalization on a planar crypt-microarray (PCM) device.ResultsMaximum electroporation efficiency was 79.9% with a mean survival of 65%. Transfection of 105 hISCs produced ∼142 (0.14%) stable transposase-mediated clones. Transfection of OLFM4-targetting RNPs yielded ∼35% editing and 99/220 (45%) of antibiotic-resistant colonies analyzed expressed emGFP. OLFM4-emGFP hISCs applied to PCMs remained emGFP+ and proliferative in high-Wnt3a/R-spondin3/Noggin zones yet differentiated to emGFP-/KRT20+ cells outside engineered crypt zones. OLFM4-emGFP levels correlated with endogenous OLFM4. Olfm4-emGFPhigh cells were LGR5high/KRT20low, and demonstrated high organoid-forming potential.ConclusionsElectroporation of hISCs is highly efficient for stable transgenesis and transgenic lines can be generated in 3-4 weeks. Workflows mirror conventional culture methods, facilitating rapid integration into established tissue-culture operations. OLFM4high is a robust hISC marker with functional properties in culture.
An anti-SARS-CoV-2 non-neutralizing antibody with Fc-effector function defines a new NTD epitope and delays neuroinvasion and death in K18-hACE2 mice
Authors: Beaudoin-Bussières Guillaume , Chen Yaozong , Ullah Irfan , Prévost Jérémie , Tolbert William D. , Symmes Kelly , Ding Shilei , Benlarbi Mehdi , Gong Shang Yu , Tauzin Alexandra , Gasser Romain , Chatterjee Debashree , Vézina Dani , Goyette Guillaume , Richard Jonathan , Zhou Fei , Stamatatos Leonidas , McGuire Andrew T. , Charest Hughes , Roger Michel , Pozharski Edwin , Kumar Priti , Mothes Walther , Uchil Pradeep D. , Pazgier Marzena , Finzi Andrés 
Published: September 2021

SummaryEmerging evidence in animal models indicate that both neutralizing activity and Fc- mediated effector functions of neutralizing antibodies contribute to protection against SARS-CoV-2. It is unclear if antibody effector functions alone could protect against SARS-CoV-2. Here we isolated CV3-13, a non-neutralizing antibody from a convalescent individual with potent Fc-mediated effector functions that targeted the N- terminal domain (NTD) of SARS-CoV-2 Spike. The cryo-EM structure of CV3-13 in complex with SAR-CoV-2 spike revealed that the antibody bound from a distinct angle of approach to a novel NTD epitope that partially overlapped with a frequently mutated NTD supersite in SARS-CoV-2 variants. While CV3-13 did not alter the replication dynamics of SARS-CoV-2 in a K18-hACE2 transgenic mouse model, an Fc-enhanced CV3-13 significantly delayed neuroinvasion and death in prophylactic settings. Thus, we demonstrate that efficient Fc-mediated effector functions can contribute to the in vivo efficacy of anti-SARS-CoV-2 monoclonal antibodies in the absence of neutralization.
Organizational determinants as antecedent factors of export marketing strategy archetypes of agri-food firms: a three country analysis
Authors: Radojevic Predrag , Manic Slavica , Churlei Edward , Hatzithomas Leonidas , Suluburic Adam 
Published: September 2021

PurposeThis paper researches export marketing strategy (EMS) archetypes of agri-food exporters and organizational determinants that pose as their antecedent factors, using resource-based, dynamic capabilities and contingency theories as theoretical framework in a multi-county research setting. A twofold objective is specified – to explore hitherto used EMS and to examine differences between agri-food exporters based on organizational determinants.Design/methodology/approachComparative research design, quantitative methodology, an etic/emic approach, descriptive and causal data analyses were employed. EMS archetypes were portrayed on radial plots, while six hypotheses were tested using MANOVA.FindingsThe tactical coordinator was identified as a universal EMS archetype. Diversity of archetypes was found as results of the effect of organizational determinants, confirming their ambivalent impacts rooted in the resources, capabilities and contingencies exporters have to face.Research limitations/implicationsMain limitations arise from the sample choice in international business, concentration only on organizational determinants, survey as a data collection technique and reliance on self-report data from managers. Nevertheless, several theoretical and practical implications are defined.Originality/valueTo the authors’ knowledge, this paper is the first to apply the EMS archetype perspective to the agri-food industry in a developing country context and in an economic crisis context. Its multi-theory approach is supplemented with researched countries' national culture perspective and institutional background to extend understanding of agri-food firms' EMS archetypes.
4D-printed parametric façade in architecture: prototyping a self-shaping skin using programmable two-way shape memory composite (TWSMC)
Authors: Yi Hwang 
Published: September 2021

PurposeThis study aims to present an architectural application of 4D-printed climate-adaptive kinetic architecture and parametric façade design.Design/methodology/approachThis work investigates experimental prototyping of a reversibly self-shaping façade, by integrating the parametric design approach, smart material and 4D-printing techniques. Thermo-responsive building skin modules of two-way shape memory composite (TWSMC) was designed and fabricated, combining the shape memory alloy fibers (SMFs) and 3D-printed shape memory polymer matrices (SMPMs). For geometry design, deformation of the TWSMC was simulated with a dimension-reduced mathematical model, and an optimal arrangement of three different types of TWSMC modules were designed and fabricated into a physical scale model.FindingsModel-based experiments show robust workability and formal reversibility of the developed façade. Potential utility of this module for adaptive building design and construction is discussed based on the results. Findings help better understand the shape memory phenomena and presented design-inclusive technology will benefit architectural communities of smart climate-adaptive building.Originality/valueTwo-way reversibility of 4D-printed composites is a topic of active research in material science but has not been clearly addressed in the practical context of architectural design, due to technical barriers. This research is the first architectural presentation of the whole design procedure, simulation and fabrication of the 4D-printed and parametrically movable façade.
“Through their eyes, I can work” – rural physicians' perceptions about mobile phone use among community health workers – a qualitative analysis
Authors: Venkataraghavan Manjula , Rani Padma , Ashok Lena , Rao Chythra R. , Chandra Sekaran Varalakshmi , Krishnapriya T.K. 
Published: September 2021

PurposePhysicians who are primary care providers in rural communities form an essential stakeholder group in rural mobile health (mHealth) delivery. This study was exploratory in nature and was conducted in Udupi district of Karnataka, India. The purpose of this study is to examine the perceptions of rural medical officers (MOs) (rural physicians) regarding the benefits and challenges of mobile phone use by community health workers (CHWs).Design/methodology/approachIn-depth interviews were conducted among 15 MOs belonging to different primary health centers of the district. Only MOs with a minimum five years of experience were recruited in the study using purposive and snowball sampling. This was followed by thematic analysis of the data collected.FindingsThe perceptions of MOs regarding the CHWs' use of mobile phones were largely positive. However, they reported the existence of some challenges that limits the potential of its full use. The findings were categorized under four themes namely, benefits of mobile phone use to CHWs, benefits of mobile phone-equipped CHWs, current mobile phone use by CHWs and barriers to CHWs' mobile phone use. The significant barriers reported in the CHWs' mobile phone use were poor mobile network coverage, technical illiteracy, lack of consistent technical training and call and data expense of the CHWs. The participants recommend an increased number of mobile towers, frequent training in mobile phone use and basic English language for the CHWs as possible solutions to the barriers.Originality/valueStudies examining the perceptions of doctors who are a primary stakeholder group in mHealth as well as in the public health system scenario are limited. To the authors’ knowledge, this is one of the first studies to examine the perception of rural doctors regarding CHWs' mobile phone use for work in India.
Lecture-based, virtual reality game-based and their combination: which is better for higher education?
Authors: Sanzana Mirza Rayana , Abdulrazic Mostafa Osama Mostafa , Wong Jing Ying , Ng Kher Hui , Ghazy Shams 
Published: September 2021

PurposeThis paper presents an educational virtual reality (VR) game and experiments with different methods of including it into the teaching process. The purpose of this research study is to discover if immersive VR games can be used as an effective pedagogical tool if blended with traditional lectures by assisting learning gain, memory and knowledge retention while increasing edutainment value.Design/methodology/approachThis research design comprises three different methods of learning: lecture-based involving lecture slides, infographics, and a video, game-based involving an immersive VR game of oil rig exploration, and the combination of lecture and game-based. Participants of each method filled up a questionnaire before and after participation to measure the learning gain, memory, and knowledge retention.FindingsFrom the predominant findings of the study, the combined method demonstrated a significant increase in learning gain, memory, and knowledge retention and maybe a potentially suitable pedagogical tool.Research limitations/implicationsLimitations of the study include findings based on one VR game with a specific educational topic, additionally, it is suspected that having different participants for each of the three methods may have slightly affected the results, albeit to a limited extent.Practical implicationsFindings of this study will provide evidence that VR games can be used alongside traditional lectures to aid in the learning process. Educators can choose to include VR games into their curriculums to improve the educational delivery process.Originality/valueThis research contributes to ways of incorporating VR games into educational curriculums through findings of this study highlighting the combination of VR games with lectures.
Entrepreneurial and market orientation interactive effects on SME performance within transitional economies
Authors: Zacca Robert , Alhoqail Saad 
Published: September 2021

Purpose
The purpose of this study is to examine how the adaptive nature of market orientation (MO) and the risk-taking nature of entrepreneurial orientation (EO) might be integrated for a complementary and reinforcing synergetic effect on firm performance within transitional economies.

Design/methodology/approach
The paper suggests links between the EO and MO concepts and develops propositions informed by prior research and reasonable assumptions. The propositions aim to spur future research to uncover further evidence that validates the testable hypothesis.

Findings
In particular, the study calls for investigating the interaction effect of EO with MO on new product entry, market intelligence collection and processing competence. In addition, the study proposes research studies on whether EO’s interaction effect with MO will tend to mitigate risk in the development of breakthrough innovation and whether the interacting strategic orientations are creating a synergetic effect towards firm performance. Finally, the study recommends that research models should be tested and understood in consideration of conditions and circumstances from varying contexts, such as the small and medium enterprise sector within transitional economies and the media industry.

Originality/value
Whilst the performance implications of EO and MO, when modelled separately, have been extensively studied in developed and diversified market economies, studies are in the early stages of investigating the joint effect of EO and MO on firm performance, especially within transitional economies.
Do CEOs get rewarded for CSR activities in the director labor market?
Authors: Dunham Lee M. , Obonyo Tirimba , Wei Sijing 
Published: September 2021

PurposeThe purpose of this paper is to determine if Chief Executive Officers (CEOs) are rewarded or punished in the corporate director labor market for engaging in corporate social responsibility (CSR) activities.Design/methodology/approachThe authors empirically examine the relation between CEOs' CSR engagement and their corporate board appointments in retirement using logit, ordinary least squares (OLS) and Poisson regression models.FindingsResults indicate that CSR engagement has significant director labor market consequences for retiring CEOs. Specifically, CSR engagement has a favorable impact on the ability of retired CEOs to obtain board seats and board seats at larger firms generally associated with higher pay, even after controlling for firm performance and other determinants previously documented to explain director selection. The authors also find evidence that CEOs of firms with high CSR engagement build up their firms' CSR scores over time as they approach retirement, which is consistent with the labor market for directors providing incentives to attract CEOs to board service in retirement.Originality/valueBy examining the relationship between a CEO's CSR engagement and their external corporate board directorships, this paper advances the understanding of the determinants of corporate board appointments. Further, while most prior research assesses the value of CSR engagement by looking at the relation between CSR engagement and that firm's performance, this is the first study to our knowledge to look outside the firm to determine if CSR engagement has value to the CEO.
Abiotic factors influence species co‐occurrence patterns of lake fishes
Authors: Cordero Ruben D. , Jackson Donald A. 
Published: September 2021

Abstract

Abiotic factors are recognized for their strong influence on community structure. Habitat diversity is related to resource availability that influences species richness and abundance. In lakes, surface area and depth have been used as measures of the size and diversity of habitat, and have strong effects on the structure of entire communities.

We tested whether abiotic variables, related to habitat size, influence co‐occurrence patterns of species pairs of fishes by analysing groups of lakes within a specific area and depth categories in two regions in Ontario, Canada.

We used null models to obtain co‐occurrence patterns and standard effect sizes for each species pair within each area and depth category. We estimated standard effect sizes relative to lake area or depth and determined whether species co‐occurrence patterns change systematically as these measures of habitat increase. We evaluated groups of species where factors such as predation and habitat filtering have been shown to structure those assemblages, and we tested whether area and depth alter the species associations and our interpretation of these relationships.

We found significant differences between the observed and expected distributions of regression slopes relating co‐occurrences to area and depth in both regions across all species, which indicated the strong influence of both variables on the overall co‐occurrence patterns. We observed a significant negative trend of the co‐occurrence patterns across lake area categories for the predator–prey species, indicating that the effect of predation was stronger in smaller lakes, but it was reduced in larger lakes, possibly due to increased habitat and resource availability. We show that pooling results as done in standard community null models can lead to Type II errors due to the ‘cancellation’ of opposing ecological signals.

Our results demonstrate the effect of environmental variables on species co‐occurrence patterns, but the divergent results obtained between geographical regions suggest that such patterns are context‐dependent. This study emphasizes the importance of considering abiotic factors in null models of species co‐occurrence to obtain reliable and detailed information about the association patterns between species.
The current situation and potential effects of climate change on the microbial load of marine bivalves of the Greek coastlines: an integrative review
Authors: Zgouridou Aikaterini , Tripidaki Eirini , Giantsis Ioannis A. , Theodorou John A. , Kalaitzidou Maria , Raitsos Dionysios E. , Lattos Athanasios , Mavropoulou Apostolia‐Maria , Sofianos Sarantis , Karagiannis Dimitrios , Chaligiannis Ilias , Anestis Andreas , Papadakis Nikos , Feidantsis Konstantinos , Mintza Dionysia , Staikou Alexandra , Michaelidis Basile 
Published: September 2021

SummaryGlobal warming affects the aquatic ecosystems, accelerating pathogenic microorganisms' and toxic microalgae's growth and spread in marine habitats, and in bivalve molluscs. New parasite invasions are directly linked to oceanic warming. Consumption of pathogen‐infected molluscs impacts human health at different rates, depending, inter alia, on the bacteria taxa. It is therefore necessary to monitor microbiological and chemical contamination of food. Many global cases of poisoning from bivalve consumption can be traced back to Mediterranean regions. This article aims to examine the marine bivalve's infestation rate within the scope of climate change, as well as to evaluate the risk posed by climate change to bivalve welfare and public health. Biological and climatic data literature review was performed from international scientific sources, Greek authorities and State organizations. Focusing on Greek aquaculture and bivalve fisheries, high‐risk index pathogenic parasites and microalgae were observed during summer months, particularly in Thermaikos Gulf. Considering the climate models that predict further temperature increases, it seems that marine organisms will be subjected in the long term to higher temperatures. Due to the positive linkage between temperature and microbial load, the marine areas most affected by this phenomenon are characterized as ‘high risk’ for consumer health.