bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of the parietal lobe in task-irrelevant suppression during learning
Authors: Contò F. , Tyler S , Paletta P. , Battelli L.
Published: August 2022

Background

Attention optimizes the selection of visual information, while suppressing irrelevant visual input through cortical mechanisms that are still unclear. We set to investigate these processes using an attention task with an embedded to-be-ignored interfering visual input.

Objective

We delivered electrical stimulation to attention-related brain areas to modulate these facilitatory/inhibitory attentional mechanisms. We asked whether training on a task while being simultaneously exposed to visual features from a different task tested at baseline and post-training might influence performance on the baseline task.

Methods

In Experiment one, subjects performed an orientation discrimination (OD) task using a pair of gratings presented at individual’s psychophysical threshold. We then trained participants over multiple sessions on a temporal order judgment task (TOJ), using the exact same gratings but presented with different time offsets. On the last session we re-tested OD. We coupled training with transcranial random noise stimulation (tRNS) over the parietal cortex, the human middle temporal area or sham, in three separate groups. In Experiment two, subjects performed the same OD task at baseline and post-training, while tRNS was delivered at rest during training.

Results

Results showed that tRNS over parietal cortex facilitated learning of the trained task. Moreover, we found a detrimental effect on OD when subjects received parietal tRNS coupled with training, but a benefit on OD when subjects received stimulation while at rest.

Conclusions

These results clearly indicate that task-irrelevant information is actively suppressed during learning, and that this prioritization mechanism of selection likely resides in the parietal cortex.
Exploring the principles of embryonic mammary gland branching morphogenesis
Authors: Lindström Riitta , Satta Jyoti P. , Myllymäki Satu-Marja , Lan Qiang , Trela Ewelina , Prunskaite-Hyyryläinen Renata , Kaczyńska Beata , Voutilainen Maria , Kuure Satu , Vainio Seppo J. , Mikkola Marja L.
Published: August 2022

Branching morphogenesis is a characteristic feature of many essential organs such as the lung, kidney, and most glands, and the net result of two tissue behaviors: branch point initiation and elongation. Each branched organ has a distinct architecture customized to its physiological function, but how patterning occurs in these ramified tubular structures is a fundamental problem of development. Here we use quantitative 3D morphometrics, time-lapse imaging, manipulation ofex vivocultured embryonic organs, and mice deficient in the planar cell polarity componentVangl2to address this question in the developing mammary gland. Our results show that the embryonic epithelial trees are highly complex in topology owing to the flexible use of two distinct modes of branch point initiation: lateral branching and tip bifurcation. This non-stereotypy was contrasted by the remarkably constant average branch frequency indicating a ductal growth-invariant, yet stochastic propensity to branch. The probability to branch was malleable and could be tuned by manipulating the Fgf10 and Tgf-β1 pathways. Finally, ourin vivoandex vivotime-lapse imaging suggested the involvement of tissue rearrangements in mammary branch elongation.
Invasion of forested areas in Gabon (Central Africa) by the Asian tiger mosquito and the potential consequences from the One Health perspective
Authors: Obame-Nkoghe Judicaël , Roiz David , Ngangue Marc-Flaubert , Costantini Carlo , Rahola Nil , Jiolle Davy , Lehmann David , Makaga Loïc , Ayala Diego , Kengne Pierre , Paupy Christophe
Published: August 2022

Since its first record in urban areas of Central-Africa in 2000s, the invasive mosquito, Aedes albopictus, has continued to spread across the region, including in remote rural areas, and promoted outbreaks of Aedes-borne diseases, such as dengue, chikungunya and Zika. From the One-Health perspective, such invasion might enhance Ae. albopictus interactions with wild animals in forest ecosystems and favor the spillover of zoonotic arboviruses to humans. From 2014 to 2018, we monitored the steady spread of this mosquito species in the wildlife reserve of La Lopé National Park (Gabon), and evaluated the magnitude of its colonization of the rainforest ecosystem using ovitraps, larval surveys, BG-Sentinel traps, and human landing catches following an anthropization gradient. We detected Ae. albopictus in forest galleries up to 15km away from La Lopé village. However, Ae. albopictus was significantly more abundant at anthropogenic sites than in less anthropized areas. The number of eggs laid by Ae. albopictus decreased progressively with the distance from the forest fringe up to 200m inside the forest, showing that its occurrence in forest ecosystems is restricted to anthropized-sylvatic interfaces with dense forest. This suggests that Ae. albopictus may act as bridge vector of zoonotic pathogens between wild and anthropogenic compartments.
BIN1 knockdown rescues systolic dysfunction in the aging heart
Authors: Westhoff Maartje , del Villar Silvia G. , Voelker Taylor L. , Thai Phung N. , Chiamvimonvat Nipavan , Dickson Eamonn J. , Dixon Rose E.
Published: August 2022

Cardiac dysfunction is a hallmark of aging in humans and mice. Here we report that a two-week treatment to restore youthful Bridging Integrator 1 (BIN1) levels in the hearts of 24-month-old mice rejuvenated cardiac function and substantially reversed the aging phenotype. Our data indicate that age-associated overexpression of BIN1 occurs alongside dysregulated endosomal recycling and disrupted trafficking of cardiac CaV1.2 and type 2 ryanodine receptors. These deficiencies affect channel function at rest and their upregulation during acute stress.In vivoechocardiography revealed reduced systolic function in old mice. BIN1 knockdown using an adeno-associated virus serotype 9 packaged shRNA-mBIN1 restored the nanoscale distribution and clustering plasticity of ryanodine receptors and recovered Ca2+transient amplitudes and cardiac systolic function toward youthful levels. Enhanced systolic function correlated with increased phosphorylation of the myofilament protein cardiac myosin binding protein-C. These results reveal BIN1 knockdown as a novel therapeutic strategy to rejuvenate the aging myocardium.

Graphical Abstract
Monocular deprivation during the critical period alters neuronal tuning and the composition of visual circuitry
Authors: Brown Thomas C. , McGee Aaron W.
Published: August 2022

Abnormal visual experience during a developmental critical period degrades cortical responsiveness. Yet how experience-dependent plasticity alters the response properties of individual neurons and composition of visual circuitry is unclear. Here we measured with calcium imaging in alert mice how monocular deprivation (MD) during the developmental critical period affects binocularity, orientation, and spatial frequency tuning for neurons in primary visual cortex. Tracking the tuning properties for several hundred neurons revealed that the interconversion of monocular and binocular neurons relies on the quality of visual experience to determine the ratio of monocular neurons responsive to the contralateral and ipsilateral eye. In addition, a population of neurons more responsive to the closed eye were exchanged for neurons with tuning properties more similar to the responsive neurons altered by MD. Thus, plasticity during the critical period adapts to recent experience by both altering the tuning of responsive neurons and recruiting neurons with matching tuning properties.
Model Misspecification Misleads Inference of the Spatial Dynamics of Disease Outbreaks
Authors: Gao Jiansi , May Michael R. , Rannala Bruce , Moore Brian R.
Published: August 2022

Epidemiology has been transformed by the advent of Bayesian phylodynamic models that allow researchers to infer the geographic history of pathogen dispersal over a set of discrete geographic areas (1, 2). These models provide powerful tools for understanding the spatial dynamics of disease outbreaks, but contain many parameters that are inferred from minimal geographic information (i.e., the single area in which each pathogen was sampled). Consequently, inferences under these models are inherently sensitive to our prior assumptions about the model parameters. Here, we demonstrate that the default priors used in empirical phylodynamic studies make strong and biologically unrealistic assumptions about the underlying geographic process. We provide empirical evidence that these unrealistic priors strongly (and adversely) impact commonly reported aspects of epidemiological studies, including: (1) the relative rates of dispersal between areas; (2) the importance of dispersal routes for the spread of pathogens among areas; (3) the number of dispersal events between areas, and; (4) the ancestral area in which a given outbreak originated. We offer strategies to avoid these problems, and develop tools to help researchers specify more biologically reasonable prior models that will realize the full potential of phylodynamic methods to elucidate pathogen biology and, ultimately, inform surveillance and monitoring policies to mitigate the impacts of disease outbreaks.

Significance Statement

Bayesian phylodynamic models have revolutionized epidemiology by enabling researchers to infer key aspects of the geographic history of disease outbreaks. These models contain many parameters that must be estimated from minimal information (the area from which each pathogen was sampled), rendering inferences under this approach inherently sensitive to the choice of priors on the model parameters. Here, we demonstrate that: (1) the priors assumed in≈93% of surveyed phylodynamic studies make strong and biologically unrealistic assumptions, and; (2) these priors distort the conclusions of epidemiological studies. We offer strategies and tools to specify more reasonable priors that will enhance our ability to understand pathogen biology and, thereby, to mitigate disease.
ETDRS letter scoring method improves the accuracy of 1.25% low-contrast visual acuity measurement in optic neuritis secondary to MS
Authors: You Yuyi , Yan Peng , Graham Stuart L. , Klistorner Alexander
Published: August 2022

Objectives

To examine whether the dynamic range of 1.25% low-contrast visual acuity (LCVA) measurement in MS patients with optic neuritis (ON) can be improved by using the Early Treatment Diabetic Retinopathy Study (ETDRS) letter scoring method.

Methods

LCVA was tested using 2.5% and 1.25% low contrast ETDRS-style 4m Sloan letter charts. When ≥20 letters were read correctly, the letter score was equal to letter count plus 30. If <20 letters were read correctly, the letter score was equal to letter count at 4m plus the total number of letters read correctly at 1m.

Results

51 relapsing-remitting MS patients with unilateral ON were enrolled and 60.8% ON eyes had a 1.25% LCVA letter count worse than 1 line (5 letters). In ON eyes with <20 letter count, ETDRS letter score showed a significantly improved correlation with both macular GCIPL thickness (r=0.71, p<0.0001; vs r=0.31, p=0.08 for letter count) and VEP latency (r=-0.47, p=0.003; vs r=-0.15, p=0.4 for letter count).

Discussion

Given ON with VEP monitoring has been frequently used as a model in MS remyelination clinical trials, our proposed ETDRS-style LCVA letter scoring method may be considered to enhance the functional outcome measure, which is necessary for regulatory approval.
Comparing the Safety and Immunogenicity of homologous (Sputnik V) and heterologous (BNT162B2) COVID-19 prime-boost vaccination
Authors: AlMadhi Marwa , AlAwadhi Abdulla , Stevenson Nigel , Greish Khalid , Jawad Jaleela , Alsayyad Adel , Mirza Afaf , Alsaffar Basma , AlAlawi Ejlal , Fakhroo Khulood , Alalawi Batool , Alabbasi Lana , Aljalahma Noora , AlQahtani Manaf
Published: August 2022

Studies have shown increased immunogenicity from heterologous boosting. This study specifically assessed boosting with Pfizer-BioNTech in Sputnik V vaccination regimens. Reactogenicity was assessed through adverse events. Immunogenicity was assessed by comparing serum anti-Spike (Anti-S) protein antibody and neutralizing antibody titers before booster administration and after 30 days. A total of 428 participants were recruited in the heterologous arm and 351 in the homologous arm. Adverse events were more frequent in the heterologous arm (p<0.001). No serious adverse events were reported in either arm. Amongst 577 individuals who completed the study, Anti-S antibodies were 14.8 times higher after heterologous boosting, and 3.1 times higher after homologous boosting (p<0.001). Similarly, heterologous boosting showed a 2 fold increase in neutralizing antibodies, compared to a 1.6 fold increase in homologous boosting (p<0.001). In conclusion, both boosting regimens elicited an immunological response, nonetheless heterologous Pfizer-BioNTech showed a higher immunological response, with more adverse effects.

ARTICLE SUMMARY LINE

Both homologous and heterologous boosting are effective in eliciting an immunological response, however heterologous boosting with Pfizer-BioNTech elicited a higher immunological response, with more adverse effects.
Dysphagia and shortness-of-breath as markers for treatment failure and survival in oropharyngeal cancer after radiation
Authors: Wang Jarey H. , McCoy Lance , Salama Vivian , Ajayi Temitayo , Dede Cem , Moreno Amy , Mohamed Abdallah S.R. , Hutcheson Katherine A. , Fuller Clifton David , van Dijk Lisanne V.
Published: August 2022

Background

Post-treatment symptoms are a focal point of follow-up visits for head and neck cancer patients. While symptoms such as dysphagia and shortness-of-breath early after treatment may motivate additional work up, their precise association with disease control and survival outcomes is not well established.

Methods

This prospective data cohort study of 470 oropharyngeal cancer patients analyzed patient-reported swallowing, choking and shortness-of-breath symptoms at 3-to-6 months following radiotherapy to evaluate their association with overall survival and disease control. Associations between the presence of moderate-to-severe swallowing, choking and mild-to-severe shortness-of-breath and treatment outcomes were analyzed via Cox regression and Kaplan-Meier. The main outcome was overall survival (OS), and the secondary outcomes were local, regional, and distant disease control.

Results

The majority of patients (91.3%) were HPV-positive. Median follow-up time was 31.7 months (IQR: 21.9-42.1). Univariable analysis showed significant associations between OS and all three symptoms of swallowing, choking, and shortness-of-breath. A composite variable integrating scores of all three symptoms was significantly associated with OS on multivariable Cox regression (p=0.0018). Additionally, this composite symptom score showed the best predictive value for OS (c-index=0.75). Multivariable analysis also revealed that the composite score was significantly associated with local recurrence/progression (p=0.025). Notably, the same significant associations with OS were seen for HPV-positive only subset analysis (p<0.01 for all symptoms).

Conclusions

Quantitative patient-reported measures of dysphagia and shortness-of-breath 3-to-6 months post-treatment are significant predictors of OS and disease recurrence/progression in OPC patients and in HPV-positive OPC only.
Phenome-wide Mendelian randomisation analysis identifies causal factors for age-related macular degeneration
Authors: Julian Thomas H , Cooper-Knock Johnathan , MacGregor Stuart , Guo Hui , Aslam Tariq , Sanderson Eleanor , Black Graeme C , Sergouniotis Panagiotis I
Published: August 2022

Background

Age-related macular degeneration (AMD) is a leading cause of blindness in the industrialised world and is projected to affect >280 million people worldwide by 2040. Aiming to identify causal factors and potential therapeutic targets for this common condition, we designed and undertook a phenome-wide Mendelian randomisation (MR) study.

Methods

We evaluated the effect of 4,591 exposure traits on early AMD using univariable MR. Statistically significant results were explored further using: validation in an advanced AMD cohort; MR Bayesian model averaging (MR-BMA); and multivariable MR.

Results

Overall, 44 traits were found to be putatively causal for early AMD in univariable analysis. Serum proteins that were found to have significant relationships with AMD included S100-A5 (odds ratio [OR]=1.07, p-value=6.80E-06), cathepsin F (OR=1.10, p-value=7.16E-05) and serine palmitoyltransferase 2 (OR=0.86, p-value=1.00E-03). Univariable MR analysis also supported roles for complement and immune cell traits. Although numerous lipid traits were found to be significantly related to AMD, MR-BMA suggested a driving causal role for serum sphingomyelin (marginal inclusion probability [MIP]=0.76; model-averaged causal effect [MACE]=0.29).

Conclusions

The results of this MR study support several putative causal factors for AMD and highlight avenues for future translational research.

Funding

This project was funded by the Wellcome Trust (224643/Z/21/Z); the University of Manchester’s Wellcome Institutional Strategic Support Fund (Wellcome ISSF) grant (204796/Z/16/Z); the UK National Institute for Health Research (NIHR) Academic Clinical Fellow and Clinical Lecturer Programmes; Retina UK and Fight for Sight (GR586); the Australian National Health and Medical Research Council (NHMRC) (1150144).

IMPACT STATEMENT

A phenome-wide Mendelian randomisation analysis revealed a causal link between age-related macular degeneration and a number of lipid, complement, immune cell, and serum protein traits, highlighting potential treatment targets.
Sex-stratified RNA-seq analysis reveals traumatic brain injury-induced transcriptional changes in the female hippocampus conducive to dementia
Authors: Fiorini Michael R. , Dilliott Allison A. , Farhan Sali M.K.
Published: August 2022

Traumatic brain injury (TBI), resulting from a violent force that causes functional changes in the brain, is the foremost environmental risk factor for developing dementia. While previous studies have identified specific candidate genes that may instigate worse outcomes following TBI when mutated, TBI-induced changes in gene expression conducive to dementia are critically understudied. Additionally, biological sex seemingly influences TBI outcomes, but the discrepancies in post-TBI gene expression leading to progressive neurodegeneration between the sexes have yet to be investigated. We conducted a whole-genome RNA sequencing analysis of post-mortem brain tissue from the parietal neocortex, temporal neocortex, frontal white matter, and hippocampus of 107 donors characterized by the Aging, Dementia, and Traumatic Brain Injury Project. Our analysis was sex-stratified and compared gene expression patterns between TBI donors and controls, a subset of which presented with dementia. Here we report three candidate gene modules from the female hippocampus whose expression correlated with dementia in female TBI donors. Enrichment analyses revealed that the candidate modules were notably enriched in cardiac processes and the immune-inflammatory response, among other biological processes. In addition, multiple candidate module genes showed a significant positive correlation with hippocampal concentrations of monocyte chemoattractant protein-1 in females with post-TBI dementia, which has been previously described as a potential biomarker for TBI and susceptibility to post-injury dementia. We concurrently examined the expression profiles of these candidate modules in the hippocampus of males with TBI and found no apparent indicator that the identified candidate modules contribute to post-TBI dementia in males. Here, we present the first sex-stratified RNA sequencing analysis of TBI-induced changes to the transcriptome that may be conducive to dementia. This work contributes to our current understanding of the pathophysiological link between TBI and dementia and emphasizes the growing interest in sex as a biological variable affecting TBI outcomes.
Identification of novel plasma lipid markers of cardiovascular disease risk in White and Black women
Authors: Jain Raghav , Davidson Jessica , Gonzalez Paula , Coe Chris , King Camille , Ryff Carol , Bersh Andrew , Mohsin Sheher , Love Gayle D. , Nimityongskul Francesca , Malecki Kristen , Simcox Judith
Published: August 2022

Rationale

Cardiovascular disease (CVD) is the leading cause of mortality for women in the USA. Current clinical biomarkers are inadequate to determine CVD risk in women, especially Black women, who disproportionately suffer from CVD.

Methods

Clinical data and LC-MS lipidomics from two independent study cohorts were used to identify novel circulating markers of CVD risk in White and Black women. Machine learning assessed predictive efficacy of identified lipids, and targeted oxylipid analysis provided insight into dysregulated inflammatory pathways.

Results

Select phospholipids and triglycerides containing acyl chains in the arachidonic acid (ARA) pathway were predictive of systolic blood pressure (BP) after adjusting for biological factors including age, obesity, and glycemic status in White and Black women. Oxylipid levels indicated increased conversion of ARA through the COX and LOX enzymes to pro-inflammatory cytokines in Black women.

Conclusion

ARA-containing phospholipid are independent predictors of CVD risk in White and Black women. Predisposition to CVD risk in Black women may further be explained by increased production of pro-inflammatory oxylipids relative to White women, regardless of blood pressure status. Future studies investigating the clinical utility of phospholipid ARA abundance as a marker of CVD risk in White and Black women are warranted.
TRENDS IN CASES, HOSPITALISATION AND MORTALITY RELATED TO THE OMICRON BA.4/BA.5 SUB-VARIANTS IN SOUTH AFRICA
Authors: Jassat Waasila , Abdool Karim Salim S , Ozougwu Lovelyn , Welch Richard , Mudara Caroline , Masha Maureen , Rousseau Petro , Wolmarans Milani , Selikow Anthony , Govender Nevashan , Walaza Sibongile , Gottberg Anne von , Wolter Nicole , Pisa Pedro Terrence , Sanne Ian , Govender Sharlene ,   DATCOV author group, Blumberg Lucille , Cohen Cheryl , Groome Michelle J.
Published: August 2022

Introduction

The Omicron BA.1/BA.2 wave in South Africa had lower hospitalisation and mortality than previous SARS-CoV-2 variants and was followed by an Omicron BA.4/BA.5 wave. This study compared admission incidence risk across waves, and the risk of mortality in the Omicron BA.4/BA.5 wave, to the Omicron BA.1/BA.2 and Delta waves.

Methods

Data from South Africa’s national hospital surveillance system, SARS-CoV-2 case linelist and Electronic Vaccine Data System were linked and analysed. Wave periods were defined when the country passed a weekly incidence of 30 cases/100,000 people. Mortality rates in the Delta, Omicron BA.1/BA.2 and Omicron BA.4/BA.5 wave periods were compared by post-imputation random effect multivariable logistic regression models.

Results

In-hospital deaths declined 6-fold from 37,537 in the Delta wave to 6,074 in the Omicron BA.1/BA.2 wave and a further 7-fold to 837 in the Omicron BA.4/BA.5 wave. The case fatality ratio (CFR) was 25.9% (N=144,798), 10.9% (N=55,966) and 7.1% (N=11,860) in the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves respectively. After adjusting for age, sex, race, comorbidities, health sector and province, compared to the Omicron BA.4/BA.5 wave, patients had higher risk of mortality in the Omicron BA.1/BA.2 wave (adjusted odds ratio [aOR] 1.43; 95% confidence interval [CI] 1.32-1.56) and Delta (aOR 3.22; 95% CI 2.98-3.49) wave. Being partially vaccinated (aOR 0.89, CI 0.86-0.93), fully vaccinated (aOR 0.63, CI 0.60-0.66) and boosted (aOR 0.31, CI 0.24-0.41); and prior laboratory-confirmed infection (aOR 0.38, CI 0.35-0.42) were associated with reduced risks of mortality.

Conclusion

Overall, admission incidence risk and in-hospital mortality, which had increased progressively in South Africa’s first three waves, decreased in the fourth Omicron BA.1/BA.2 wave and declined even further in the fifth Omicron BA.4/BA.5 wave. Mortality risk was lower in those with natural infection and vaccination, declining further as the number of vaccine doses increased.
A balance between actin and Eps8/IRSp53 utilization in branched versus linear actin networks determines tunneling nanotube formation
Authors: Henderson J. Michael , Ljubojevic Nina , Chaze Thibault , Castaneda Daryl , Battistella Aude , Gianetto Quentin Giai , Matondo Mariette , Descroix Stéphanie , Bassereau Patricia , Zurzolo Chiara
Published: August 2022

Tunneling nanotubes (TNTs) connect distant cells and mediate cargo transfer for intercellular communication in physiological and pathological contexts. How cells generate these actin-mediated protrusions to span lengths beyond those attainable by canonical filopodia remains unknown. Through a combination of micropatterning, microscopy and optical tweezer-based approaches, we demonstrate that TNTs forming through the outward extension of actin (not through cellular dislodgement) achieve distances greater than the mean length of filopodia, and that branched Arp2/3-dependent pathways attenuate the extent to which actin polymerizes in nanotubes, limiting TNT occurrence. Proteomic analysis using Epidermal growth factor receptor kinase substrate 8 (Eps8) as a positive effector of TNTs showed that upon Arp2/3 inhibition, proteins enhancing filament turnover and depolymerization were reduced and Eps8 instead exhibited heightened interactions with the inverted Bin/Amphiphysin/Rvs (I-BAR) domain protein IRSp53 that provides a direct connection with linear actin polymerases. Our data reveals how common protrusion players (Eps8 and IRSp53) form TNTs, and that when competing pathways overutilizing such proteins and monomeric actin in Arp2/3 networks are inhibited, processes promoting linear actin growth dominate to favour TNT formation. Thus, this work reinforces a general principle for actin network control for cellular protrusions where simple shifts in the balance between processes that inhibit actin growth versus those that promote growth dictate protrusion formation and the ultimate length scales protrusions achieve.
Whether the ADP-ribosyltransferase activity of Ta-sro1, a noncanonical PARP protein, contributes to its function in salinity-stress tolerance?
Authors: Liu Shu-Wei , Liu Shu-Peng , Wang Wen-Long , Wang Mei , Wang Meng , Xia Guang-Min
Published: August 2022

ADP-ribosylation mediated by ADP-ribosyltransferases (ARTs) is an intricate modification that regulates diverse cellular processes including DNA repair, chromatin remodeling and gene transcription responding to stresses. In addition to the canonical poly(ADP-ribose) polymerases (PARPs), plant specific SRO (Similar to RCD One) family also contain the catalytic core of the PARP domain. However, whether the PARP domains in SROs execute the ART function is still under debate. In 2014, we reported a wheat SRO, Ta-sro1, had the ADP-ribosyltransferase activity and enhanced wheat seedling growth and abiotic stress resistance, however, a recent work by Vogt et al. showed that Ta-sro1 without ADP-ribosyltransferase activity. Based on the recent progress on PARPs and SROs in relation to ADP-ribosyltransferase activity, along with our former and recent evolving results, we argued that Ta-sro1 is a non-canonical ADP-ribosyltransferase with the enzymatic activity. Although we have revealed the novel mechanism of Ta-sro1 regulate redox homeostasis and enhance salinity stress tolerance through interacting with TaSIP1, it is of interest to further clarify whether and how the enzymatic activity of Ta-sro1 responsible for the salinity tolerance of wheat. Our study raises some interesting points and caveats that helpful for understanding the research progresses and debates about the enzymatic activity of SROs.
The diversity of the glycan shield of sarbecoviruses closely related to SARS-CoV-2
Authors: Allen Joel D. , Ivory Dylan , Song Sophie Ge , He Wan-ting , Capozzola Tazio , Yong Peter , Burton Dennis R. , Andrabi Raiees , Crispin Max
Published: August 2022

The animal reservoirs of sarbecoviruses represent a significant risk of emergent pandemics, as evidenced by the impact of SARS-CoV-2. Vaccines remain successful at limiting severe disease and death, however the continued emergence of SARS-CoV-2 variants, together with the potential for further coronavirus zoonosis, motivates the search for pan-coronavirus vaccines that induce broadly neutralizing antibodies. This necessitates a better understanding of the glycan shields of coronaviruses, which can occlude potential antibody epitopes on spike glycoproteins. Here, we compare the structure of several sarbecovirus glycan shields. Many N-linked glycan attachment sites are shared by all sarbecoviruses, and the processing state of certain sites is highly conserved. However, there are significant differences in the processing state at several glycan sites that surround the receptor binding domain. Our studies reveal similarities and differences in the glycosylation of sarbecoviruses and show how subtle changes in the protein sequence can have pronounced impacts on the glycan shield.
Synergistic stabilization of microtubules by BUB-1, HCP-1 and CLS-2 controls meiotic spindle assembly in C. elegans oocytes
Authors: Macaisne Nicolas , Bellutti Laura , Laband Kimberley , Edwards Frances , Pitayu-Nugroho Laras , Gervais Alison , Ganeswaran Thadshagine , Geoffroy Hélène , Maton Gilliane , Canman Julie C. , Lacroix Benjamin , Dumont Julien
Published: August 2022

During cell division, chromosome segregation is orchestrated by a microtubule-based spindle. Interaction between spindle microtubules and kinetochores is central to the bi-orientation of chromosomes. Initially dynamic to allow spindle assembly and kinetochore attachments, which is essential for chromosome alignment, microtubules are eventually stabilized for efficient segregation of sister chromatids and homologous chromosomes during mitosis and meiosis I respectively. Therefore, the precise control of microtubule dynamics is of utmost importance during mitosis and meiosis. Here, we study the assembly and role of a kinetochore module, comprised of the kinase BUB-1, the two redundant CENP-F orthologs HCP-1/2, and the CLASP family member CLS-2 (hereafter termed the BHC module), in the control of microtubule dynamics in Caenorhabditis elegans oocytes. Using a combination of in vivo structure-function analyses of BHC components and in vitro microtubule-based assays, we show that BHC components stabilize microtubules, which is essential for meiotic spindle formation and accurate chromosome segregation. Overall, our results show that BUB-1 and HCP-1/2 do not only act as targeting components for CLS-2 at kinetochores, but also synergistically control kinetochore-microtubule dynamics by promoting microtubule pause. Together, our results suggest that BUB-1 and HCP-1/2 actively participate in the control of kinetochore-microtubule dynamics in the context of the BHC module to promote accurate chromosome segregation in meiosis.
Safety switch optimization enhances antibody-mediated elimination of CAR T cells
Authors: Shabaneh Tamer B , Moffett Howell F , Stull Sylvia M , Derezes Thomas , Tait Leah J , Park Spencer , Riddell Stan R , Lajoie Marc J
Published: August 2022

Activation of a conditional safety switch has the potential to reverse serious toxicities arising from the administration of engineered cellular therapies, including chimeric antigen receptor (CAR) T cells. The functionally inert, non-immunogenic cell surface marker derived from human epidermal growth factor receptor (EGFRt) is a promising safety switch that has been used in multiple clinical constructs and can be targeted by cetuximab, a clinically available monoclonal antibody. However, this approach requires high and persistent cell surface expression of EGFRt to ensure that antibody mediated depletion of engineered cells is rapid and complete. Here we show that incorporating a short juxtamembrane sequence into the EGFRt polypeptide enhances its expression on the surface of T cells and their susceptibility to antibody-dependent cellular cytotoxicity (ADCC). Incorporating this optimized variant (EGFRopt) into bicistronic and tricistronic CAR designs results in more rapid in vivo elimination of CAR T cells and robust termination of their effector activity compared to EGFRt. These studies establish EGFRopt as a superior safety switch for the development of next-generation cell-based therapeutics.
T cell responses to SARS-CoV-2 vaccination in people with multiple sclerosis differ between disease-modifying therapies
Authors: Wolf Asia-Sophia , Ravussin Anthony , König Marton , Øverås Mathias H. , Solum Guri , Kjønstad Ingrid Fadum , Chopra Adity , Holmøy Trygve , Harbo Hanne F. , Syversen Silje Watterdal , Jørgensen Kristin Kaasen , Høgestøl Einar August , Vaage Jon Torgils , Celius Elisabeth G. , Lund-Johansen Fridtjof , Munthe Ludvig A. , Nygaard Gro Owren , Mjaaland Siri
Published: August 2022

Immune responses in people with multiple sclerosis (pwMS) on disease-modifying therapies (DMTs) have been of significant interest throughout the COVID-19 pandemic. Lymphocyte-targeting immunotherapies including anti-CD20 treatments and sphingosine-1-phosphate receptor (S1PR) modulators attenuate antibody responses after vaccination. Evaluation of cellular responses after vaccination is therefore of particular importance in these populations. In this study, we analysed CD4 and CD8 T cell functional responses to SARS-CoV-2 spike peptides in healthy controls and pwMS on five different DMTs by flow cytometry. Although pwMS on anti-CD20 and S1PR therapies had low antibody responses after both 2 and 3 vaccine doses, T cell responses in pwMS on anti-CD20 therapies were preserved after a third vaccination, even when additional anti-CD20 treatment was administered between vaccine doses 2 and 3. PwMS taking S1PR modulators had low detectable T cell responses in peripheral blood. CD4 and CD8 T cell responses to SARS-CoV-2 variants of concern Delta and Omicron were lower than to the ancestral Wuhan-Hu-1 variant. Our results indicate the importance of assessing both cellular and humoral responses after vaccination and suggest that even in the absence of robust antibody responses vaccination can generate immune responses in pwMS.
Phenotypic evolution of SARS-CoV-2: a statistical inference approach
Authors: Benhamou Wakinyan , Lion Sébastien , Choquet Rémi , Gandon Sylvain
Published: August 2022

Since its emergence in late 2019, the SARS-CoV-2 virus has spread globally, causing the ongoing COVID-19 pandemic. In the fall of 2020, the Alpha variant (lineage B.1.1.7) was detected in England and spread rapidly, outcompeting the previous lineage. Yet, very little is known about the underlying modifications of the infection process that can explain this selective advantage. Here, we try to quantify how the Alpha variant differed from its predecessor on two phenotypic traits: the transmission rate and the duration of infectiousness. To this end, we analysed the joint epidemiological and evolutionary dynamics as a function of the Stringency Index, a measure of the amount of Non-Pharmaceutical Interventions. Assuming that these control measures reduce contact rates and transmission, we developed a two-step approach based onSEIRmodels and the analysis of a combination of epidemiological and evolutionary information. First, we quantify the link between Stringency Index and the reduction in viral transmission. Secondly, based on a novel theoretical derivation of the selection gradient in anSEIRmodel, we infer the phenotype of the Alpha variant from its frequency changes. We show that its selective advantage is more likely to result from a higher transmission than from a longer infectious period.
Communication interventions to promote vaccination uptake: A systematic review protocol
Authors: Castro-Barbudo Daniella , Franco-Suárez Oscar , Pastrana Nathaly Aya , Agudelo-Londoño Sandra , Guzman-Tordecilla Deivis Nicolas , Maniar Vidhi , Vecino-Ortiz Andres
Published: August 2022

Background

The use of communication interventions to promote vaccination has been more frequent in this century. These types of interventions have proven to be effective in reaching the majority of the population. Knowing the characteristics and results of communication interventions to foster vaccine uptake is important, especially with the outbreak of new infectious diseases such as the novel coronavirus (SARS CoV-2). This protocol will guide the development of a systematic review of the literature aiming to identify and analyze the evidence of communication interventions to incentivize vaccine uptake among populations living in low and middle-income countries (LMICs).

Methods

This systematic review protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). The searches for the systematic review will be carried out through five electronic databases PubMed, Scopus, Web of Science, Redalyc and PyscInfo. Two individuals will review each paper individually and in parallel using the software Rayyan. Duplicate elimination, title and abstract screening, and full text screening will be performed by the two reviewers. A matrix constructed in Excel will be used to extract data and to review the quality of the studies Quality assessment will be conducted using the QATSDD Critical Appraisal Tool.

Discussion

The results of this systematic review will contribute to the public health literature in the area of behavior change communication in general, and vaccination communication in particular. Findings from this study would also inform the development of communication interventions to improve vaccination uptake in LMICs.

Systematic review registration

PROSPERO CRD42022355541
How emotions from content social relevance mediate social media engagement: evidence from European supermarkets during the COVID-19 pandemic
Authors: Ballerini Jacopo , Alam Gazi Mahabubul , Zvarikova Katarina , Santoro Gabriele
Published: August 2022

Purpose

The purpose of this study is to examine the antecedents of consumer engagement with supermarkets' social media accounts. Drawing on regulatory fit theory and social sharing of emotions theory, the authors test if the content posted on the social media brand pages of supermarkets dealing with a topic of high social relevance, such as the COVID-19 pandemic, stimulates social media consumer engagement and if and how the engagement is mediated by the arousal of positive and negative emotions.

Design/methodology/approach

The authors retrieved data from the Facebook accounts of the top 20 European supermarkets identified in the Deloitte 2020 Global Powers of Retailing report during the first wave of the pandemic from 1 March to 30 June 2020, collecting a sample of 2,524 posts from 8 different countries. After a content analysis to classify COVID-19 content, the authors applied the Baron and Kenny (1986) methodology to verify the hypothesised relationships.

Findings

The findings highlight a positive direct relationship between the social relevance of a topic (COVID-19) and social media consumer engagement mediated by the arousal of positive and negative emotions.

Originality/value

To the best of the authors’ knowledge, this is one of the earliest empirical research using Facebook data to investigate the role of the social relevance of content as an antecedent of social media consumer engagement with a specific focus on supermarkets. The paper contributes to the stream of social media literature investigating the antecedents of social media engagement behaviour, exploring the role of topics' choice and aroused emotions, which to date are both under-investigated.
Impact of asynchronous Web-based learning environment on students' interest and motivation in mathematics: a quantitative research study
Authors: Asad Muhammad Mujtaba , Khan Sidra , Sherwani Fahad , Banerjee Jyoti Sekhar
Published: August 2022

Purpose

Internet technology in the classroom has become the primary demand of every student in this era. Moreover, information and communication technology aids students' learning involvement and progress by providing learning assistance by improved instructor, pupil and interactions with fellows. Using an asynchronous Web-based learning environment (WBLE) is one way to manage such assistance. This study aims to identify to what extent the asynchronous WBLE affects students' interest and motivation in learning mathematics at Shah Abdul Latif University (SALU), Khairpur.

Design/methodology/approach

This research uses a survey research design under a quantitative approach. Therefore, data are collected through a questionnaire about students' motivation and interest in learning mathematics via asynchronous WBLE. Data are collected from the students of four departments (BEd, BSCS, BBA, BS Mathematics) of SALU, Khairpur. However, as the nature of this study is quantitative, both descriptive and inferential statistics were used in the results and discussion, and a one-way ANOVA test was used. The Cronbach alpha test was also used to assess the item's reliability, and the items were found to be acceptable.

Findings

The findings of this study discovered that asynchronous WBLE has a significant impact on students' intrinsic, extrinsic and interest levels. The results indicated that there is a positive impact based on the level of mean range of asynchronous WBLE on mathematics students.

Research limitations/implications

The outcome of this study can be used as a guideline to understand and further plan or develop educational interventions based on the level of motivation and interest of mathematics students towards asynchronous WBLE in other contexts.

Originality/value

This is first study of its nature in the context of Khairpur district of Sindh that emphasizes on the motivation and interest of mathematics students toward asynchronous WBLE.
2008's mistrust vs 2020's panic: can ESG hold your institutional investors?
Authors: Giakoumelou Anastasia , Salvi Antonio , Bertinetti Giorgio Stefano , Micheli Anna Paola
Published: August 2022

Purpose

The authors compare two market collapse incidents, focusing on their role as turning points for ESG considerations among investors that do not fall under the SRI class. The authors draw from the signaling theory to posit that ESG performance acts as a buffer to retain institutional shareholders under stress conditions.

Design/methodology/approach

The authors collect extensive data on institutional shareholdings and corporate performance during the pandemic and the 2008 financial crisis to examine the potential of ESG to act as a downward risk hedging mechanism. The authors test whether superior ESG scores function as insurance and resilience signals that lock investors in through times of high probability of divestments.

Findings

Findings indicate that ESG weighs in investment decisions during economic downturn and poor returns. The nature of this positive relationship is not static but dynamic contingent on overall risk materiality considerations.

Research limitations/implications

The authors update regulators, firms, investors and academics on ESG, risk and crisis management. The shifting materiality and the altering impact of ESG practices is our core implication, as well as limitation, in terms of metrics, temporal evolution and interaction with institutional factors, along with portfolio alpha and safe haven potential in ESG asset classes.

Originality/value

The authors extend current literature focusing on portfolio returns and firm valuations to highlight the role of ESG in shareholder retention during poor return periods. The authors further add to existing studies by examining the shifting materiality of ESG pillars during different crisis settings.
The association of screen time with physical activity and weight status of autistic children in Kuala Lumpur, Malaysia
Authors: Rozaini Muhammad Adeeb Najmi , Sariman Sarina , Abd Rashed Aswir , Shari Norshafarina
Published: August 2022

Purpose

The purpose of this study was to evaluate the screen time used by Autism Spectrum Disorder (ASD) children and its association with their physical activity and weight status.

Design/methodology/approach

This cross-sectional study was conducted among 100 purposive sampled children registered under the National Autism Society of Malaysia centres in Kuala Lumpur. Parents-administered questionnaire composed of socio-demographic, anthropometric data (height and weight of the children), Autism Severity Questionnaire, Screen Time Questionnaire and Physical Activity Questionnaire for Older Children (PAQ-C) was used in this study.

Findings

Respondents in this study were categorised as having mild ASD (55%). Most of the respondents had higher screen time (78%), with average (4.14 ± 3.19) h spent using the devices. The respondents had low physical activity level (54%), with average PAQ-C scores of (2.38 ± 0.79). Average BMI-for-age z-scores was 1.06 ± 2.15, which was in the normal category. Approximately, 34% of the respondents were overweight and obese. BMI-for-age was positively associated with screen time during weekdays (χ2 = 11.06; p < 0.05) but not during weekend (χ2 = 3.14; p > 0.05). Spearman correlation test showed negative relationships between screen time on weekdays (rs = −0.30 and p < 0.01) and weekend (rs = −0.21 and p < 0.05) with PAQ-C of this group of ASD children.

Practical implications

Screen time was directly associated with the BMI-for-age z-score but was inversely associated with physical activity. Future studies could implement a structured physical activity intervention among children with ASD, which may increase physical activity and decrease screen time behaviours while addressing the overweight/obesity and cognitive aspects of these ASD children.

Originality/value

This study measured the amount of screen time, level of physical activity and weight status but not dietary intake of autistic children.
Can digital economy alleviate CO2 emissions in the transport sector? Evidence from provincial panel data in China
Authors: Lee Chien‐Chiang , Yuan Ying , Wen Huwei
Published: August 2022

The existing literature mainly focuses on the impact of information communication technologies on carbon emissions, but little attention has been paid to the role of the digital economy in transporting carbon emissions. This paper calculates the index of the digital economy through the entropy weight Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) method and constructs the panel data of 30 provinces in China from 2008 to 2017. By extending the Stochastic Impacts by Regression on Population, Affluence and Technology model, this study explores the potential linear and non‐linear relationship between digital economy and carbon emissions in the transport sector. Empirical results show that the digital economy has the alleviating effect on carbon emissions in the transportation sector, and a change in the digital economy of one unit standard deviation resulted in a 6.14% reduction in carbon emissions. In terms of sub‐regions, the digital economy has a significant negative impact on transport carbon emissions in the eastern and central regions, while it is insignificant in the western regions. This paper further investigates the threshold effect of urbanization on the relationship between the digital economy and transportation‐related carbon emissions. The digital economy accelerates the transport sector's carbon emissions in the low urbanization stage, while it reduces the carbon emissions in the high urbanization stage.