bluuebunny/crossref_metadata_2025 huggingface dataset:
Ectodysplasin signaling via Xedar is required for mammary gland morphogenesis
Authors: Wark Abigail R. , Tomizawa Reiko , Aldea Daniel , Kokalari Blerina , Warder Bailey , Kamberov Yana G.
Published: September 2022

The Ectodysplasin A2 receptor (XEDAR), is a member of the tumor necrosis factor receptor subfamily and is a mediator of the Ectodysplasin (EDA) signaling pathway. EDA signaling plays evolutionarily conserved roles in the development of the ectodermal appendage organ class that includes hair, eccrine sweat glands, and mammary glands. Loss of function mutations in Eda, which encodes the two major ligand isoforms, EDA-A1 and EDA-A2, result in X-linked hypohidrotic ectodermal dysplasia (XLHED), which is characterized by defects in two or more ectodermal appendage types. EDA-A1 and EDA-A2 signal through the receptors EDAR and XEDAR, respectively. While the contributions of the EDA-A1/EDAR signaling pathway to ectodermal appendage phenotypes have been extensively characterized, the significance of the EDA-A2/XEDAR branch of the pathway has remained obscure. Herein, we report the phenotypic consequences of disrupting the EDA-A2/XEDAR pathway on mammary gland differentiation and growth. Using a mouse Xedar knock-out model, we show that Xedar has a specific and temporally restricted role in promoting post-pubertal growth and branching of the mammary epithelium that can be influenced by genetic background. Our findings are the first to implicate Xedar in ectodermal appendage development and suggest that the EDA-A2/XEDAR signaling axis contributes to the etiology of EDA-dependent mammary phenotypes.
Robust control of replication initiation in the absence of DnaA-ATP ↔ DnaA-ADP regulatory elements inEscherichia coli
Authors: Boesen Thias , Charbon Godefroid , Fu Haochen , Jensen Cara , Sandler Michael , Jun Suckjoon , Lobner-Olesen Anders
Published: September 2022

Investigating a long-standing conceptual question in bacterial physiology, we examine why DnaA, the bacterial master replication initiator protein, exists in both ATP and ADP forms, despite only the ATP form being essential for initiation. We engineered the Δ4Escherichia colistrain, devoid of all known external elements facilitating the DnaA-ATP/ADP conversion, and found that these cells display nearly wild-type behaviors under non-overlapping replication cycles. However, during rapid growth with overlapping cycles, Δ4 cells exhibit initiation instability. This aligns with our model predictions, suggesting that the intrinsic ATPase activity of DnaA alone is sufficient for robust initiation control inE. coliand the DnaA-ATP/ADP conversion regulatory elements extend the robustness to multifork replication, indicating an evolutionary adaptation. Moreover, our experiments revealed constant DnaA concentrations during steady-state cell elongation in both wild-type and Δ4 cells. These insights not only advance our understanding of bacterial cell-cycle regulation and DnaA, but also highlight a fundamental divergence from eukaryotic cell-cycle controls, emphasizing protein copy-number sensing in bacteria versus programmed protein concentration oscillations in eukaryotes.
Extracellular Carbonic Anhydrase Supports Constitutive HCO3− Uptake in Fragilariopsis cylindrus Regardless of Temperature Changes
Authors: Li Meng , Young Jodi N.
Published: September 2022

Diatoms, including Fragilariopsis cylindrus (Fcyl), are the major primary producers in productive polar oceans. Little is known about carbon concentrating mechanisms (CCMs) in polar diatoms and their sensitivity to ocean warming and acidification. Here we characterized the CCM response to temperature in Fcyl using Membrane Inlet Mass Spectrometry. Fcyl increases RuBisCO expression at lower temperatures to compensate slower catalytic rates but maintains a reliance on HCO3− uptake across different temperatures (−2 °C to 9 °C) despite higher CO2 solubility at colder temperatures. However, when external carbonic anhydrase (eCA) is inhibited, inorganic carbon usage switches from HCO3− uptake to a dependency on CO2 diffusion. Incorporating these measurements with modeling, we propose that relying on eCA supported HCO3− uptake is an adaptive strategy to the highly dynamic polar ocean environment which experience large fluctuations in [CO2] but where HCO3− is constantly available.
PlrA (MSMEG_5223) is an essential polar growth regulator in Mycobacterium smegmatis
Authors: Quintanilla Samantha Y. , Arejan Neda Habibi , Patel Parthvi B. , Boutte Cara C.
Published: September 2022

Mycobacteria expand their cell walls at the cell poles in a manner that is not well described at the molecular level. In this study, we identify a new factor, PlrA, involved in restricting peptidoglycan metabolism to the cell poles in Mycobacterium smegmatis. We show that PlrA localizes to the pole tips, and we identify its essential domain. We show that depletion of plrA pheno-copies depletion of polar growth factor Wag31, and that PlrA is involved in regulating polar peptidoglycan metabolism and the structure of the Wag31 polar foci.
Grasshopper genome reveals long-term conservation of the X chromosome and temporal variation in X chromosome evolution
Authors: Li Xinghua , Mank Judith E. , Ban Liping
Published: September 2022

We present the first chromosome-level genome assembly of the grasshopper, Locusta migratoria, one of the largest insect genomes. We use coverage differences between females (XX) and males (X0) to identify the X chromosome gene content, and find that the X chromosome shows both complete dosage compensation in somatic tissues and an underrepresentation of testes-expressed genes. Remarkably, X-linked gene content from L. migratoria is highly conserved across four insect orders, namely Orthoptera, Hemiptera, Coleoptera and Diptera, and the 800 Mb grasshopper X chromosome is homologous to the fly ancestral X chromosome despite 400 million years of divergence, suggesting either repeated origin of sex chromosomes with highly similar gene content, or long-term conservation of the X chromosome. We use this broad conservation of the X chromosome to test for temporal dynamics to Fast-X evolution, and find evidence of a recent burst evolution for new X-linked genes in contrast to slow evolution of X-conserved genes. Additionally, our results reveal the X chromosome represents a hotspot for adaptive protein evolution related migration and the locust swarming phenotype. Overall, our results reveal a remarkable case of conservation and adaptation on the X chromosome.
Fluorescence Lifetime: Beating the IRF and interpulse window
Authors: Fazel Mohamadreza , Vallmitjana Alexander , Scipioni Lorenzo , Gratton Enrico , Digman Michelle A. , Pressé Steve
Published: September 2022

Fluorescence lifetime imaging (FLIM) has been essential in capturing spatial distributions of chemical species across cellular environments employing pulsed illumination confocal setups. However, quantitative interpretation of lifetime data continues to face critical challenges. For instance, fluorescent species with knownin vitroexcited state lifetimes may split into multiple species with unique lifetimes when introduced into complex living environments. What is more, mixtures of species, that may be both endogenous and introduced into the sample, may exhibit; 1) very similar lifetimes; as well as 2) wide ranges of lifetimes including lifetimes shorter than the instrumental response function (IRF) or whose duration may be long enough to be comparable to the interpulse window. By contrast, existing methods of analysis are optimized for well-separated and intermediate lifetimes. Here we broaden the applicability of fluorescence lifetime analysis by simultaneously treating unknown mixtures of arbitrary lifetimes– outside the intermediate, goldilocks, zone–for data drawn from a single confocal spot leveraging the tools of Bayesian nonparametrics (BNP). We benchmark our algorithm, termed BNP-lifetime analysis of BNP-LA, using a range of synthetic and experimental data. Moreover, we show that the BNP-LA method can distinguish and deduce lifetimes using photon counts as small as 500.
Migrating mesoderm cells self-organize into a dynamic meshwork structure during chick gastrulation
Authors: Nakaya Yukiko , Tarama Mitsusuke , Tasaki Sohei , Isomura Ayako , Shibata Tatsuo
Published: September 2022

Migration of cell populations is a fundamental process in morphogenesis and disease. The mechanisms of collective cell migration of epithelial cell populations have been well studied. It remains unclear, however, how the highly motile mesenchymal cells, which migrate extensively throughout the embryo, are connected with each other and coordinated as a collective. During gastrulation in chick embryos, the mesoderm cells, that are formed by an epithelial-to-mesenchymal transition (EMT), migrate in the 3D space between ectoderm and endoderm of the embryo. Using live imaging and quantitative analysis, such as topological data analysis (TDA), we found that the mesoderm cells undergo a novel form of collective migration, in which they form a meshwork structure while moving away from the primitive streak. This meshwork is supported by N-cadherin-mediated cell-cell adhesion, which undergoes rapid reorganization. Overexpressing a mutant form of N-cadherin decreases the speed of tissue progression and the directionality of the collective cell movement, whereas the speed of individual cells remains unchanged. To investigate how this meshwork arises and how it contributes to the cell movement, we utilized an agent-based theoretical model, showing that cell elongation, cell-cell adhesion, and cell density are the key parameters for the meshwork formation. These data provide novel insights into how a supracellular structure of migrating mesenchymal cells forms and how it facilitates efficient migration during early mesoderm formation.
Functional characterization of the Co2+transporter AitP inSinorhizobium meliloti: a new player in Fe2+homeostasis
Authors: Mihelj Paula , Abreu Isidro , Moreyra Tomás , González-Guerrero Manuel , Raimunda Daniel
Published: September 2022

Co2+induces the increase of the labile-Fe pool (LIP) by Fe-S cluster damage, heme synthesis inhibition and “free” iron import, which affects cell viability. The N2-fixing bacteria,Sinorhizobium meliloti, is a suitable model to determine the roles of Co2+-transporting Cation diffusion facilitator exporters (Co-eCDF) in Fe2+homeostasis because it has a putative member of this sub-family, AitP, and two specific Fe2+-export systems. An insertional mutant of AitP showed Co2+sensitivity and accumulation, Fe accumulation and hydrogen peroxide sensitivity, but not Fe2+sensitivity, despite AitP being abona fidelow affinity Fe2+exporter as demonstrated by the kinetic analyses of Fe2+uptake into everted membrane vesicles. Suggesting concomitant Fe2+-dependent induced stress, Co2+sensitivity was increased in strains carrying mutations in AitP and Fe2+exporters which did not correlate with the Co2+accumulation. Growth in the presence of sub-lethal Fe2+and Co2+concentrations suggested that free Fe-import might contribute to Co2+toxicity. Supporting this, Co2+induced transcription of Fe-import system and genes associated with Fe homeostasis. Analyses of total protoporphyrin content indicates Fe-S cluster attack as the major source for LIP. AitP-mediated Fe2+-export is likely counterbalanced via a non-futile Fe2+-import pathway. Two lines of evidence support this: i) an increased hemin uptake in presence of Co2+was observed in WTvs. AitP mutant, and ii) hemin reversed the Co2+sensitivity in the AitP mutant. Thus, the simultaneous detoxification mediated by AitP aids cells to orchestrate an Fe-S cluster salvage response, avoiding the increase in the LIP caused by the disassembly of Fe-S clusters or free iron uptake.

Importance

Cross-talk between iron and cobalt has been long recognized in biological systems. This is due to the capacity of cobalt to interfere with proper iron utilization. Cells can detoxify cobalt by exporting mechanisms involving membrane proteins known as exporters. Highlighting the cross-talk, the capacity of several cobalt exporters to also export iron is emerging. Although biologically less important than Fe2+, Co2+induces toxicity by promoting intracellular Fe release, which ultimately causes additional toxic effects. In this work, we describe how the N2-fixating rhizobial cells solve this perturbation by clearing Fe through a Co2+-exporter, in order to reestablish intracellular Fe-levels by importing non-free Fe, heme. This piggyback-ride type of transport may aid bacterial cells to survive in free-living conditions where high anthropogenic Co2+content may be encountered.
Effectiveness of BNT162b2 and CoronaVac against pediatric COVID-19-associated hospitalization and moderate-to-severe disease
Authors: Rosa Duque Jaime S. , Leung Daniel , Yip Ka Man , Lee Derek H.L. , So Hung-kwan , Wong Wilfred H.S. , Lau Yu Lung
Published: September 2022

Background

Vaccine effectiveness (VE) of BNT162b2 and CoronaVac against COVID-19-associated hospitalization and moderate-to-severe disease due to SARS-CoV-2 Omicron BA.2 for pediatric populations that had low exposure to prior SARS-CoV-2 variants needs to be further clarified. This can be studied from the 1.36 million vaccine doses had been administered to 766,601 of 953,400 children and adolescents in Hong Kong (HK) since March 2021 to April 2022.

Methods

Using an ecological design leveraging the HK vaccination coverage statistics and public hospital records, this study investigated the VE for children aged 3-11 years and adolescents aged 12-18 years at the population level during the Omicron BA.2 wave from January to April 2022.

Findings

VE against COVID-19-associated hospitalization for children was 65.3% for 1 dose of BNT162b2 and 13.0% and 86.1% for 1 and 2 doses of CoronaVac, respectively. For adolescents, VE against COVID-19-associated hospitalization was 60.2% and 82.4% after 1 and 2 doses of BNT162b2 and 30.8% and 90.7% after 1 and 2 doses of CoronaVac, respectively. Protection against moderate-to-severe disease for aged 3-18 was high, with VE of 93.1% and 95.8% after 2 doses of BNT162b2 and CoronaVac, respectively. No COVID-19-associated hospitalization or moderate-to-severe disease occurred for 68,565 children and adolescents who received their third dose. Estimated hospitalizations of children and adolescents averted by vaccination were 68 and 999, respectively, and were 45 and 147 for moderate-to-severe cases.

Conclusions

BNT162b2 or CoronaVac provide substantial protection from COVID-19-associated hospitalization and moderate-to-severe disease due to a SARS-CoV-2 variant of concern.

Funding

The Providence Foundation.
Parental experiences of the impacts of COVID-19 on the care of young children; qualitative interview findings from the Nairobi Early Childcare in Slums (NECS) Project
Authors: Hughes Robert C , Muendo Ruth , Bhopal Sunil S , Onyango Silas , Kimani-Murage Elizabeth , Kirkwood Betty R , Hill Zelee , Kitsao-Wekulo Patricia
Published: September 2022

Introduction

The Covid-19 pandemic, and societal attempts to control it, have touched almost every aspect of people’s lives around the world, albeit in unequal ways. In particular, there is considerable concern about the way that stringent ‘lockdowns’, as implemented in Kenya and many other countries, affected young children, especially those living in informal settlements. However, to date, there has been little research attempting to unpack and understand how the pandemic has impacted on the care of young children.

Methods

In-depth telephone interviews were conducted with 21 parents/carers of children aged under five years living in three Nairobi slums between May and September 2021 exploring the ways in which covid-19, and policies to control the pandemic, impacted on their household and the care of their child/children.

Results

The impacts of covid-19 control measures on the care of children have been widely felt, deep and multiple. The impact of economic hardship has been significant, reportedly undermining food security and access to services including healthcare and childcare. Respondents reported an associated increase in domestic and community violence. Many people relied on help from others; this was most commonly reported to be in the form of variable levels of flexibility from landlords and help from other community members. No direct harms from covid-19 disease were reported by respondents.

Conclusion

The impacts of covid-19 control measures on the care of young children in informal settlements have been indirect but dramatic. Given the breadth and depth of these reported impacts, and the particular vulnerability of young children, deeper consideration ought to inform decisions about approaches to implementation of stringent disease control measures in future. In addition, these findings imply a need for both short- and long-term policy responses to ameliorate the impacts described.

Key messages

Young children living in slums, while at low direct risk from Covid-19, are highly vulnerable to early childhood adversity, so may be at great risk from economic and other hardships that are a likely ‘side effect’ of blunt pandemic control measures like stringent ‘lockdowns’.

Parent/carers described a set of indirect impacts of covid-19 control efforts that were broad, deep and protracted. Core to these impacts was widespread economic hardship, with knock on effects on household food security, wellbeing and community safety.

Considering the particular risks and vulnerability that blunt pandemic control measures present to young children, especially those in slums, needs to be central to policy discussions about if and how to implement stringent disease-control measures. In addition, more research is required to quantify the issues identified in this qualitative inquiry.
A dynamic template complex mediates Munc18-chaperoned SNARE assembly
Authors: Yang Jie , Jin Huaizhou , Liu Yihao , Guo Yaya , Zhang Yongli
Published: September 2022

Munc18 chaperones assembly of three membrane-anchored soluble N-ethylmaleimide- sensitive factor attachment protein receptors (SNAREs) into a four-helix bundle to mediate membrane fusion between vesicles and plasma membranes, leading to neurotransmitter or insulin release, GLUT4 translocation, or other exocytotic processes. Yet, the molecular mechanism underlying chaperoned SNARE assembly is not well understood. Recent evidence suggests that Munc18-1 and Munc18-3 simultaneously bind their cognate SNAREs to form ternary template complexes - Munc18-1:Syntaxin-1:VAMP2 for synaptic vesicle fusion and Munc18-3:Syntaxin-4:VAMP2 for GLUT4 translocation and insulin release, which facilitate binding of SNAP-25 or SNAP-23 to conclude SNARE assembly. Here, we further investigate the structure, dynamics, and function of the template complexes using optical tweezers. Our results suggest that the synaptic template complex transitions to an activated state with a rate of ∼0.05 s−1 and ∼6.8 kBT higher energy for efficient SNAP-25 binding. The transition depends upon the linker region of syntaxin-1 upstream of its helical bundle-forming SNARE motif. In addition, the template complex is stabilized by a poorly characterized disordered loop region in Munc18-1. While the synaptic template complex efficiently binds both SNAP-25 and SNAP-23, the GLUT4 template complex strongly favors SNAP-23 over SNAP-25, despite similar stabilities of their assembled SNARE bundles. Together, our data demonstrate that a highly dynamic template complex mediates efficient and specific SNARE assembly.

Significance

Munc18-1 chaperones coupled folding and assembly of three synaptic SNAREs, syntaxin-1, VAMP2, and SNAP-25, into a four-helix bundle to mediate membrane fusion and neurotransmitter release. Recent evidence suggests that Munc18-1, syntaxin-1, and VAMP2 first form a weak template complex and then bind to SNAP-25 to complete SNARE assembly. However, the dynamics and function of the template complex are not well understood. Using optical tweezers, we found that the template complex undergoes a conformational change to bind SNAP-25 in a way dependent upon the syntaxin linker region and that Munc18 kinetically proofreads SNARE pairing not governed by its thermodynamic stability. Our study reveals a more dynamic template complex than that seen in its cryo-EM structure.
Mistle: bringing spectral library predictions to metaproteomics with an efficient search index
Authors: Nowatzky Yannek , Benner Philipp , Reinert Knut , Muth Thilo
Published: September 2022

Motivation

Deep learning has moved to the forefront of tandem mass spectrometry-driven proteomics and authentic prediction for peptide fragmentation is more feasible than ever. Still, at this point spectral prediction is mainly used to validate database search results or used for confined search spaces. Fully predicted spectral libraries have not yet been efficiently adapted to large search space problems that often occur in metaproteomics or proteogenomics.

Results

In this study, we showcase a workflow that uses Prosit for spectral library predictions on two common metaproteomes and implement an indexing and search algorithm, Mistle, to efficiently identify experimental mass spectra within the library. Hence, the workflow emulates a classic protein sequence database search with protein digestion but builds a searchable index from spectral predictions as an in-between step. We compare Mistle to popular search engines, both on a spectral and database search level, and provide evidence that this approach is more accurate than a database search using MSFragger. Mistle outperforms other spectral library search engines in terms of run time and proves to be extremely memory efficient with an 8 to 22-fold decrease in RAM usage. This makes Mistle universally applicable to large search spaces, e.g. covering comprehensive sequence databases of diverse microbiomes.

Availability

Mistle is freely available on GitHub at https://github.com/BAMeScience/Mistle.

Contact

thilo.muth@bam.de
Apelin Stimulation of the Perivascular MuSC Niche Enhances Endogenous Repair in Muscular Dystrophy
Authors: Le Moal Emmeran , Liu Yuguo , Collerette-Tremblay Jasmin , Dumontier Simon , Boutin Joël , Dort Junio , Orfi Zakaria , Michaud Joris , Giguère Hugo , Desroches Alexandre , Trân Kien , Vézina François , Bedard Sonia , Raynaud Catherine , Balg Frederic , Sarret Philippe , Scott Michelle S. , Feige Jerome N. , Denault Jean-Bernard , Dumont Nicolas A. , Marsault Eric , Auger-Messier Mannix , Bentzinger C. Florian
Published: September 2022

Impaired skeletal muscle stem cell (MuSC) function has long been suspected to contribute to the pathogenesis of muscular dystrophy (MD). Here we describe that defects in the endothelial cell (EC) compartment of the perivascular stem cell niche in three different types of MD are associated with inefficient mobilization of MuSCs following tissue damage. Using chemoinformatic analysis, we identified the 13 amino acid form of the peptidic hormone apelin (AP-13) as a candidate for systemic stimulation of skeletal muscle ECs. In dystrophic mice, administration of AP-13 generates a pro-myogenic EC-rich niche that supports MuSC function and markedly improves tissue regeneration, muscle strength, and physical performance. Moreover, we demonstrate that EC specific knockout of the AP-13 receptor leads to regenerative defects that phenocopy major pathological features of MD. Altogether, we provide in vivo proof-of-concept that enhancing endogenous repair by targeting the perivascular niche is a viable therapeutic avenue for MD and characterize AP-13 as a novel drug candidate for systemic treatment of stem cell dysfunction.
G-quadruplexes rescuing protein folding
Authors: Son Ahyun , Huizar Cabral Veronica , Litberg Theodore J , Horowitz Scott
Published: September 2022

Maintaining the health of the proteome is a critical cellular task. Recently, we found G-quadruplex (G4) nucleic acids are especially potent at preventing protein aggregation in vitro and could at least indirectly improve the protein folding environment of E. coli. However, the roles of G4s in protein folding were not yet explored. Here, through in vitro protein folding experiments, we discover that G4s can accelerate protein folding by rescuing kinetically trapped intermediates to both native and near-native folded states. Time-course folding experiments in E. coli further demonstrate that these G4s primarily improve protein folding quality in E. coli as opposed to preventing protein aggregation. The ability for a short nucleic acid to rescue protein folding opens up the possibility of nucleic acids and ATP-independent chaperones to play considerable roles in dictating the ultimate folding fate of proteins.
Regulatory annotation identifies KAN1, MYB44 and PIF4 as regulators of Arabidopsis lincRNAs expressed in root
Authors: Liu Li , Heidecker Michel , Depuydt Thomas , Perez Nicolas Manosalva , Crespi Martin , Blein Thomas , Vandepoele Klaas
Published: September 2022

Thousands of long intergenic noncoding RNAs (lincRNAs) have been identified in plant genomes. While some lincRNAs have been characterized as important regulators in different biological processes, little is known about the transcriptional regulation for most plant lincRNAs. Through the integration of eight annotation resources, we defined 6,599 high-confidence lincRNA loci inArabidopsis thaliana. For lincRNAs belonging to different evolutionary age categories, we identified major differences in sequence and chromatin features, as well as in the level of conservation and purifying selection acting during evolution. Spatiotemporal gene expression profiles combined with transcription factor (TF) chromatin immunoprecipitation data were used to construct a TF- lincRNA regulatory network containing 2,659 lincRNAs and 15,686 interactions. We found that properties characterizing lincRNA expression, conservation and regulation differ between plants and animals. Experimental validation confirmed the role of three TFs, KAN1, MYB44, and PIF4, as key regulators controlling root- specific lincRNA expression, demonstrating the predictive power of our network. Furthermore, we identified 58 lincRNAs, regulated by these TFs, showing strong root cell-type specific expression or chromatin accessibility, which are linked with GWAS genetic associations related to root system development and growth. The multi-level genome-wide characterization covering chromatin state information, promoter conservation, and ChIP-based TF binding, for all detectable lincRNAs across 769 expression samples, permits to rapidly define the biological context and relevance of lincRNAs in Arabidopsis regulatory networks.

One-line sentence

A multi-level Arabidopsis gene regulatory network identifies novel regulators controlling root-specific lincRNA expression, offering a promising strategy to identify lincRNAs involved in plant biology.
Disability in Multiple Sclerosis is Associated with Vascular Factors: An Ultrasound study
Authors: Kemp Merlisa , Johannes Clint , van Rensburg Susan J , Kidd Martin , Isaacs Ferial , Kotze Maritha J , Engel-Hills Penelope
Published: September 2022

Background

Although multiple sclerosis (MS) is an immune-related disorder, pharmaceutical interventions targeting the immune system do not stop or reverse disability progression; the major challenge for this condition. Studies show that disability progression in MS is associated with vascular comorbidity and brain volume loss, indicating that a multi-targeted approach is required to prevent debilitation. The aim of the present study was to examine the associations between vascular ultrasound, disability, biochemistry and lifestyle data in people with MS (pwMS).

Methods

Extracranial vascular ultrasound was performed on 51 pwMS and 25 age-matched controls. Sonographic interrogation determined carotid intima-media thickness (cIMT) and abnormal blood flow patterns. Disability was assessed using the Expanded Disability Status Scale (EDSS). Biochemical and lifestyle data were obtained for all participants.

Results

The EDSS had a highly significant positive association with the cIMT of the right (r = 0.63; p = 0.001) and left (r = 0.49; p = 0.001) common carotid arteries and negative associations with the peak systolic blood flow velocity of the right vertebral artery (r = -0.42; p = 0.01) as well as end-diastolic velocity of the left internal carotid artery (r = -0.47; p = 0.01). These associations were significantly influenced by biochemical and lifestyle factors. Both cIMT and age showed significant associations with the EDSS. When cIMT was adjusted for age in a regression analysis, the association between the EDSS and the cIMT remained significant (p < 0.01), while the age association was reduced to being significant only at 10% (p = 0.06). There was no association between the use of MS medication and the EDSS (p = 0.56).

Conclusion

PwMS who had increased cIMT, a surrogate marker for atherosclerosis, and reduced carotid artery blood flow velocities were at risk for greater disability over and above the effect of aging. These findings provide important information for disease management and disability prevention in pwMS. Modification of diet and lifestyle may promote the unhindered flow of essential nutritional factors into the brain in pwMS.
Multicentre diagnostic evaluation of OnSite COVID-19 Rapid Test (CTK Biotech) among symptomatic individuals in Brazil and The United Kingdom
Authors: Thompson Caitlin R , Torres Pablo Muñoz , Kontogianni Konstantina , Byrne Rachel L ,   LSTM Diagnostic group, Noguera Saidy Vásconez , Luna-Muschi Alessandra , Marchi Ana Paula , Andrade Pâmela S , Santos Barboza Antonio dos , Nishikawara Marli ,   CONDOR steering group, Body Richard , de Vos Margaretha , Escadafal Camille , Adams Emily , Costa Silvia Figueiredo , Cubas Atienzar Ana I
Published: September 2022

The COVID-19 pandemic has given rise to numerous commercially available antigen rapid diagnostic tests (Ag-RDTs). To generate and share accurate and independent data with the global community, multi-site prospective diagnostic evaluations of Ag-RDTs are required. This report describes the clinical evaluation of OnSite COVID-19 Rapid Test (CTK Biotech, California, USA) in Brazil and The United Kingdom.

A total of 496 paired nasopharyngeal (NP) swabs were collected from symptomatic healthcare workers at Hospital das Clínicas in São Paulo, and 211 NP swabs were collected from symptomatic participants at a COVID-19 drive-through testing site in Liverpool, England. These swabs were analysed by Ag-RDT and results were compared to RT-qPCR.

The clinical sensitivity of the OnSite COVID-19 Rapid test in Brazil was 90.3% [95% Cl 75.1 – 96.7%] and in the United Kingdom was 75.3% [95% Cl 64.6 – 83.6%]. The clinical specificity in Brazil was 99.4% [95% Cl 98.1 – 99.8%] and in the United Kingdom was 95.5% [95% Cl 90.6 – 97.9%]. Analytical evaluation of the Ag-RDT was assessed using direct culture supernatant of SARS-CoV-2 strains from Wild-Type (WT), Alpha, Delta, Gamma and Omicron lineages. Analytical limit of detection was 1.0×103pfu/mL, 1.0×103pfu/mL, 1.0×102pfu/mL, 5.0×103pfu/mL and 1.0×103pfu/mL, giving a viral copy equivalent of approximately 2.1×105copies/mL, 2.1×104copies/mL, 1.6×104copies/mL, 3.5×106copies/mL and 8.7 × 104for the Ag-RDT, when tested on the WT, Alpha, Delta, Gamma and Omicron lineages, respectively.

This study provides comparative performance of an Ag-RDT across two different settings, geographical areas, and population. Overall, the OnSite Ag-RDT demonstrated a lower clinical sensitivity than claimed by the manufacturer… Sensitivity and specificity from the Brazil study fulfilled the performance criteria determined by the World Health Organisation but the performance obtained from the UK study failed to. Further evaluation of the use of Ag-RDTs should include harmonised protocols between laboratories to facilitate comparison between settings.
Crystal structure and antidiabetic activity of 2-aminospiropyrazolinium tosylates and the product of O-tosylation of β-(benzimidazol-1-yl)propioamidoxime
Authors: Kayukova Lyudmila A. , Vologzhanina Anna V. , Yergaliyeva Elmira M. , Baitursynova Gulnur P. , Shulgau Zarina T. , Sergazy Shynggys
Published: September 2022

2-Amino-1,5-diazaspiro[4.5]dec-1-en-5-ium salts possess bioactivity tuned by the nature of the heteroatoms in the six-membered ring and the counter-ion. The molecular environment of these cations in solids provides an opportunity to establish the conformations and hydrogen-bonding patterns typical for this family. β-Aminopropioamidoxime tosylation products [2-amino-1,5-diazaspiro[4.5]dec-1-en-5-ium tosylates and the product of the O-tosylation of β-(benzimidazol-1-yl)propioamidoxime, namely, 2-amino-1,5-diazaspiro[4.5]dec-1-en-5-ium tosylate, C8H16N3
+·C7H7O3S− (6), 2-amino-8-oxa-1,5-diazaspiro[4.5]dec-1-en-5-ium tosylate, C7H14N3O+·C7H7O3S− (7), the monohydrate of 7, C7H14N3O+·C7H7O3S−·H2O (7a), 2-amino-8-thia-1,5-diazaspiro[4.5]dec-1-en-5-ium tosylate, C7H14N3S+·C7H7O3S− (8), 2-amino-8-phenyl-1,5,8-triazaspiro[4.5]dec-1-en-5-ium tosylate, C13H19N4
+·C7H7O3S− (9), and 3-(1H-benzimidazol-1-yl)-N′-(tosyloxy)propanimidamide, C17H18N4O3S (10)] were investigated using X-ray diffraction to study peculiarities of their molecular geometry and intermolecular interactions. In vitro antitubercular and antidiabetic screening of the β-aminopropioamidoxime tosylation products was also carried out. It was revealed that this series of compounds does not have activity against drug-sensitive and multidrug-resistant M. tuberculosis strains, and exhibits high and moderate antidiabetic α-amylase and α-glucosidase activity. Using the hydrogen-bond propensity tool, we found that the inclination of counter-ions and atoms to act as acceptors of hydrogen bonds for the amino group decreases passing from tosylate O atoms to water molecules and the N atoms of five-membered rings. This fact is probably the reason for the formation in the solids of hydrogen-bonded tetramers consisting of two anions and two cations, and the rare occurrence of 2-aminospiropyrazolinium salt hydrates.
Synthesis and spectroscopic and structural characterization of three new 2-methyl-4-styrylquinolines formed using Friedländer reactions between (2-aminophenyl)chalcones and acetone
Authors: Vera Diana Rocío , Mantilla Juan P. , Palma Alirio , Cobo Justo , Glidewell Christopher
Published: September 2022

Three new 2-methyl-4-styrylquinoline derivatives have been synthesized in high yields using Friedländer reactions between chalcones [1-(2-aminophenyl)-3-arylprop-2-en-1-ones] and acetone, and characterized using IR, 1H and 13C NMR spectroscopy, and mass spectrometry, and by crystal structure analysis. In (E)-4-(4-fluorostyryl)-2-methylquinoline, C18H14FN, (I), the molecules are joined into cyclic centrosymmetric dimers by C—H...N hydrogen bonds and these dimers are linked into sheets by π–π stacking interactions. The molecules of (E)-2-methyl-4-[4-(trifluoromethyl)styryl]quinoline, C19H14F3N, (II), are linked into cyclic centrosymmetric dimers by C—H...π hydrogen bonds and these dimers are linked into chains by a single π–π stacking interaction. There are no significant hydrogen bonds in the structure of (E)-4-(2,6-dichlorostyryl)-2-methylquinoline, C18H13Cl2N, (III), but molecules related by translation along [010] form stacks with an intermolecular spacing of only 3.8628 (2) Å. Comparisons are made with the structures of some related compounds.
Drivers for agility in times of crisis
Authors: Solheim Marte C.W. , Aadland Torgeir , Eide Ann Elida , Haneberg Dag Håkon
Published: September 2022

Purpose

Agile organisations do not arise from a single characteristic but comprise a combination of various aspects. Thus, this study aims to examine the combined effects on organisational agility regarding firms’ utilisation of digital technology to create value during the COVID-19 pandemic, how firms perceive uncertainty related to their own organisational response and the degree to which they have an entrepreneurial mindset.

Design/methodology/approach

Using a fuzzy-set qualitative comparative analysis, this study investigates 355 established firms and start-ups in Norway.

Findings

This study finds digitalisation is required for agility to develop, but that it needs to be combined with having an entrepreneurial mindset or being a start-up and lower levels of perceived uncertainty. Hence, entrepreneurial mindset and low uncertainty are important factors for digitalisation, and in turn, for agility to be developed.

Originality/value

Agility is recognised as being pivotal for firms’ competitiveness and innovation and argued to be significant in overcoming sudden economic shocks. However, lacking empirical scrutiny are investigations into the relationship between digitalisation and agility, and how digitalisation might act as a driver for building agility, which the authors tackle herein.
Charting value creation strategies B2B salespeople use throughout the sales process: learning from social media influencers
Authors: Cheng Zixuan , Plangger Kirk , Cai Feng , Campbell Colin L. , Pitt Leyland
Published: September 2022

Purpose

This paper aims to explore how business-to-business (B2B) salespeople use social media and emulate value creation strategies used by social media influencers.

Design/methodology/approach

Using 28 interviews with salespeople, this paper develops six propositions and a conceptual framework that outlines when and how B2B salespeople use social media in value-creating sales.

Findings

This study’s findings provide a critical analysis of when social media are most effective and beneficial in supporting salespeople’s value-creating sales in various stages in the sales process (e.g. prospecting, opening relationships, qualifying prospects and serving accounts) and when they are less effective (e.g. presenting sales messages and closing sales).

Research limitations/implications

This research yields a substantive understanding of the evolving role that social media play in B2B sales by examining B2B salespeople’s value creation strategies through the lens of social media influencers’ practice and outlines ideas for future research on B2B salespeople’s social media strategies.

Practical implications

The findings of this research can be used by B2B organizations to structure the training of B2B salespeople to use social media to the fullest extent by aligning specific strategies with different parts of the sales process.

Originality/value

This paper contributes by summarizing the B2B sales literature on social media and integrating recent insights from the social media influencer literature; empirically identifying how B2B salespeople use social media to create value, thus validating previous findings and extending understanding by offering a set of six theoretical propositions; and delineating B2B salespeople’s social media practice into 11 value creation strategies that are critically explored for their place in the sales process.
Implementing data analysis based on the mixed clustering technique for sustainable participatory waste management in a low-budget area
Authors: Warintarawej Pattaraporn , Nillaor Pichetwut
Published: September 2022

Purpose

The research objectives are as follows: to understand the situation of solid waste management in the Makham Tia Subdistrict Administrative Organization, Surat Thani Province, Thailand; identify the patterns in household waste generation and 3Rs behavior (recycle, reuse and reduce waste); and formulate sustainable municipal solid waste management guidelines.

Design/methodology/approach

This study aimed to propose the solution by using data analysis and a participatory research approach to set the guidelines for sustainable community waste management in a low-budget area. A survey of household behavior was done with questionnaires. Mixed clustering using the Gower coefficient was performed to assess the categorical socio-demographic variables along with the numeric variables related to the 3Rs behavior. The guidelines for waste management were generated based on the characteristics of the household groups.

Findings

The guidelines for waste management were generated based on the characteristics of the household groups. An appropriate practical plan for municipal solid waste management in Makham Tia Subdistrict was proposed in this work. The study showed that the guidelines were implemented and revised by members of the community, and this led to the development of sustainable community solid waste management for the future.

Originality/value

The goal of this study was to provide a solution for sustainable community waste management in a low-budget location by using data mining techniques and a participatory research approach. The study showed that the guidelines were implemented and revised by members of the community, and this led to the development of sustainable community solid waste management for the future.
Strategic technological determinant in smart destinations: obtaining an automatic classification of the quality of the destination
Authors: Díaz-González Sergio , Torres Jesus M. , Parra-López Eduardo , Aguilar Rosa M.
Published: September 2022

Purpose

Smart tourist destinations (STDs) make use of new technologies to facilitate and improve the experience of tourists. So why not use these technologies to efficiently manage the destination? The aim of this work is to define and implement a methodology that provides value to STDs by defining their most important characteristics to monitor and quantify them automatically in real time.

Design/methodology/approach

The authors developed a conceptual framework to the smart tourism approach presented in previous studies, the latest technologies and the application of the smart tourism system (STS). Based on the focus group method with stakeholders from the tourism industry of the Spanish tourist municipality of Puerto de la Cruz, they defined the main KPIs for a municipal STD. Likewise, the authors specified the necessary technologies to obtain, manage and represent the data, and the method for quantifying the quality of the STD by using the AHP method. Lastly, they implemented the framework for the aforementioned municipality.

Findings

The implementation in a real context of the STS proposed for Puerto de la Cruz demonstrates its validity and the possibility of adapting it to any other municipal destination. In addition, the authors corroborate how this STS improves on other versions.

Originality/value

This paper provides a theoretical methodology to improve STD management and implements it. Other studies have focused only on the theoretical aspect. Moreover, automated management tools are emerging for STDs, but they lack the quality provided by the scientific approach employed herein.
Data and care integration for post-acute intensive care program of stroke patients: effectiveness assessment using a disease-matched comparator cohort
Authors: Vela Emili , Plaza Aina , Carot-Sans Gerard , Contel Joan Carles , Salvat-Plana Mercè , Fabà Marta , Giralt Andrea , Ribera Aida , Santaeugènia Sebastià , Piera-Jiménez Jordi
Published: September 2022

Purpose

To assess the effectiveness of an integrated care program for post-acute care of stroke patients, the return home program (RHP program), deployed in Barcelona (North-East Spain) between 2016 and 2017 in a context of health and social care information systems integration.

Design/methodology/approach

The RHP program was built around an electronic record that integrated health and social care information (with an agreement for coordinated access by all stakeholders) and an operational re-design of the care pathways, which started upon hospital admission instead of discharge. The health outcomes and resource use of the RHP program participants were compared with a population-based matched control group built from central healthcare records of routine care data.

Findings

The study included 92 stroke patients attended within the RHP program and the patients' matched controls. Patients in the intervention group received domiciliary care service, home rehabilitation, and telecare significantly earlier than the matched controls. Within the first two years after the stroke episode, recipients of the RHP program were less frequently institutionalized in a long-term care facility (5 vs 15%). The use of primary care services, non-emergency transport, and telecare services were more frequent in the RHP group.

Originality/value

The authors' analysis shows that an integrated care program can effectively promote and accelerate delivery of key domiciliary care services, reducing institutionalization of stroke patients in the mid-term. The integration of health and social care information allows not only a better coordination among professionals (thus avoiding redundant assessments) but also to monitor health and resource use outcomes of care delivery.
Islamic religiosity and green purchase intention: a perspective of food selection in millennials
Authors: Alotaibi Adel , Abbas Aamir
Published: September 2022

Purpose

The study aims to investigate the effect of Islamic religiosity on green purchase intention. The environmental dimension of spiritual well-being (i.e. environmental well-being) was analyzed as a mediator and green skepticism as a moderator.

Design/methodology/approach

The millennial generation was considered for data collection, and their preference toward green food was investigated by using a questionnaire. The responses were analyzed by using AMOS.

Findings

The results highlighted that Islamic religiosity significantly effects the green food purchase intention of the millennial generation. This relation is positively mediated by the environmental dimension of spiritual well-being (i.e. environmental well-being). Moreover, the green skepticism weakens the relationship between Islamic religiosity and green purchase intention.

Research limitations/implications

The main emphasis of this research was on the millennial generation, and only their selection criteria for green food were considered. Moreover, the study has only considered the environmental dimension of spiritual well-being (i.e. environmental well-being) and ignored the other dimensions, including transcendental and personal/communal well-being. Therefore, future studies can focus on these dimensions while highlighting the purchase behavior toward other green or eco-friendly products.

Practical implications

The research has discussed the broader areas, and it can help marketers, religious scholars, farmers and managers to make efficient strategies for the millennial generation. The researchers focusing on green consumer behavior and sustainable issues can consider this study as a guideline for investigating the Muslim millennial generation’s behavior.

Originality/value

The study is to investigate the effect Islamic religiosity on green purchase intention. It has focused on all sustainable aspects, including green well-being, green skepticism to analyze the green purchase intention of millennial generation.