bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced protective efficacy of a novel, thermostable, RBD-S2 vaccine formulation against SARS-CoV-2 and its variants
Authors: Mittal Nidhi , Kumar Sahil , Rajmani Raju S , Singh Randhir , Lemoine Céline , Jakob Virginie , BJ Sowrabha , Jagannath Nayana , Bhat Madhuraj , Chakraborty Debajyoti , Pandey Suman , Jory Aurélie , S.A. Suba Soundarya , Kleanthous Harry , Dubois Patrice , Ringe Rajesh P. , Varadarajan Raghavan 
Published: March 2023

AbstractWith the rapid emergence of variants of concern (VOC), the efficacy of currently licensed vaccines has reduced drastically. VOC mutations largely occur in the S1 subunit of Spike. The S2 subunit of SARS-CoV-2 is conserved and thus more likely to elicit broadly protective immune responses. However, the contribution of the S2 subunit in improving the overall efficacy of vaccines remains unclear. Therefore, we designed, characterized, and evaluated the immunogenicity and protective potential of a stabilized SARS-CoV-2 Receptor Binding Domain (RBD) fused to a stabilized S2. Designed immunogens were expressed as soluble proteins with approximately fivefold higher purified yield than the Spike ectodomain and formulated along with Squalene-in-water emulsion (SWE) adjuvant. S2 immunization failed to elicit a neutralizing immune response but significantly reduced lung viral titers in mice challenged with the heterologous Beta variant. In hamsters, SWE-formulated RS2 showed enhanced immunogenicity and efficacy relative to corresponding RBD and Spike formulations. Despite being based on the ancestral Wuhan strain of SARS-CoV-2, RS2 exhibited broad neutralization, including against Omicron variants (BA.1, BA.5 and BF.7), as well as the clade 1a WIV-1 and SARS-CoV-1 strains. RS2 sera also showed enhanced competition with both S2 directed and RBD Class 4 directed broadly neutralizing antibodies, relative to RBD and Spike elicited sera. When lyophilized, RS2 retained antigenicity and immunogenicity even after incubation at 37 °C for a month. The data collectively suggest that the RS2 immunogen is a promising modality to combat SARS-CoV-2 variants.
ToxoplasmaMembrane Inositol Phospholipid Binding Protein TgREMIND Is Essential for Secretory Organelle Function and Host Infection
Authors: Houngue Rodrigue , Sangare Lamba Omar , Alayi Tchilabalo Dilezitoko , Dieng Aissatou , Bitard-Feildel Tristan , Boulogne Claire , Slomianny Christian , Atindehou Cynthia Menonve , Fanou Lucie Ayi , Hathout Yetrib , Saeij Jeroen PJ , Callebaut Isabelle , Tomavo Stanislas 
Published: March 2023

SummaryApicomplexan parasites have specialized secretory organelles called rhoptries, micronemes, and dense granules that are essential for host infection. Here, we show that TgREMIND, aToxoplasma gondiiprotein containing a membrane phospholipid interacting domain, is required for the biogenesis of rhoptries and dense granules. TgREMIND contains a Fes/CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain at the N-terminus, known to promote cell membrane bending, and a novel uncharacterized domain that we named REMIND forregulator ofmembraneinteractingdomain at the C-terminus. TgREMIND binds to PIP2 lipid species and both F-BAR and REMIND domains are necessary to ensure proper biological activitiesin vitroandin cellulo. Conditional depletion of TgREMIND results in the absence of dense granules and abnormal transparent rhoptries, leading to a severe inhibition of parasite motility, host invasion, and dissemination. Thus, our study demonstrates that TgREMIND is essential for the proper functioning of key secretory organelles required for successful infection byToxoplasma.
Pro-inflammatory feedback loops define immune responses to pathogenic lentivirus infection
Authors: Wilk Aaron J. , Marceau Joshua O. , Kazer Samuel W. , Fleming Ira , Miao Vincent , Galvez-Reyes Jennyfer , Shalek Alex K. , Holmes Susan , Overbaugh Julie , Blish Catherine A. 
Published: March 2023

ABSTRACTHIV causes chronic inflammation and AIDS in humans, though the rate of disease progression varies between individuals. Similarly, simian lentiviruses vary in their pathogenicity based on characteristics of both the host (simian species) and virus strain. Here, we profile immune responses in pig-tailed macaques infected with variants of SIV that differ in virulence to understand the immune mechanisms underlying lentiviral pathogenicity. Compared to a minimally pathogenic lentiviral variant, infection with a highly pathogenic variant results in a more delayed, broad, and sustained activation of inflammatory pathways, including an extensive global interferon signature. Conversely, individual cells infected with highly pathogenic lentivirus upregulated fewer interferon-stimulated genes at a lower magnitude, indicating that highly pathogenic lentivirus has evolved to partially escape from interferon responses. Further, we identified distinct gene co-expression patterns and cell-cell communication pathways that implicateCXCL10andCXCL16as important molecular drivers of inflammatory pathways specifically in response to highly pathogenic lentivirus infection. Immune responses to highly pathogenic lentivirus infection are characterized by amplifying regulatory circuits of pro-inflammatory cytokines with dense longitudinal connectivity. Our work presents a model of lentiviral pathogenicity where failures in early viral control mechanisms lead to delayed, sustained, and amplifying pro-inflammatory circuits, which has implications for other viral infections with highly variable disease courses.
Cationic Polymers Enable Internalization of Negatively Charged Chemical Probe into Bacteria
Authors: Lembke Hannah K. , Espinasse Adeline , Hanson Mckenna G. , Grimme Christian J. , Tan Zhe , Reineke Theresa M. , Carlson Erin E. 
Published: March 2023

AbstractThe bacterial cell envelope provides a protective barrier that is challenging for small molecules and biomolecules to cross. Given the anionic nature of both Gram-positive and Gramnegative bacterial cell envelopes, negatively charged molecules are particularly difficult to deliver into these organisms. Many strategies have been employed to penetrate bacteria ranging from reagents such as cell-penetrating peptides, enzymes, and metal-chelating compounds, to physical perturbations. While cationic polymers are known antimicrobial agents, their ability to permeabilize bacterial cells without causing high levels of toxicity and cell lysis has not been demonstrated. Here, we evaluate the ability of four cationic polymers, two linear and two micellar (from self-assembled amphiphilic block copolymers), to facilitate the internalization of an anionic ATP-based chemical probe intoEscherichia coliandBacillus subtilis. Not only did we observe the permeabilization of these organisms, but also found that labeled cells were able to continue to grow and divide. In particular, the micelle-based polymers yielded effective internalization of the negatively charged chemical probe better than their linear analogues.
Protein Phosphorylation Orchestrates Acclimations ofArabidopsisPlants to Environmental pH
Authors: Jain Dharmesh , Schmidt Wolfgang 
Published: March 2023

ABSTRACTEnvironment pH (pHe) is a key parameter that dictates a surfeit of conditions critical to plant survival and fitness. To elucidate the mechanisms that recalibrate cytoplasmic and apoplastic pH homeostasis, we conducted a comprehensive proteomic/phosphoproteomic inventory of plants subjected to transient exposure to acidic or alkaline pH, an approach that covered the majority of protein-coding genes of the model plantArabidopsis thaliana. Our survey revealed a large set so far undocumented pHe-dependent and potentially pH-specific phospho-sites, indicative of extensive post-translational regulation of proteins involved in the acclimation to pHe. Changes in pHealtered both electrogenic H+pumping via P-type ATPases and H+/anion co-transport processes, leading to massively altered net trans-plasma membrane translocation of H+ions. In pH 7.5 plants, transport (but not the assimilation) of nitrogen via NRT2-type nitrate and AMT1- type ammonium transporters was induced, conceivably to increase the cytosolic H+concentration. Exposure to acidic pH resulted in a marked repression of primary root elongation. No such cessation was observed innrt2.1mutants, suggesting a role of NRT2.1 in negatively regulating root growth in response to acidic pH. Sequestration of iron into the vacuole via phosphorylation and abundance of the vacuolar iron transporter VTL5 was inversely regulated in response to high and low pHe, presumptively in anticipation of changes in iron availability associated with alterations of pHein the soil. A pH-dependent ‘phospho-switch’ was also observed for the ABC transporter PDR7, suggesting changes in activity and, possibly, substrate specificity. Unexpectedly, the effect of pHewas not restricted to roots and provoked pronounced changes in the leaf proteome. In both roots and shoots, the plant-specific TPLATE complex components AtEH1 and AtEH2 – essential for clathrin-mediated endocytosis – were differentially phosphorylated at multiple sites in response to pHe, indicating that the endocytic cargo protein trafficking is orchestrated by pHe.
Transferability of European-derived cardiometabolic polygenic risk scores in the South Asians and their interplay with family history
Authors: Hassanin Emadeldin , Maj Carlo , Krawitz Peter , May Patrick , Bobbili Dheeraj Reddy 
Published: March 2023

AbstractBackground & AimsWe aimed to investigate the effect of polygenic risk scores (PRSs) derived from individuals of European (EUR) ancestry on common diseases among individuals of South Asian (SAS) ancestry in the UK Biobank (UKB). Additionally, we studied the interaction between PRS and family history (FH) in the same population.MethodsTo calculate the PRS, we used a previously published panel of SNPs derived from the EUR population and applied it to the individuals of SAS ancestry from the UKB study. We applied the PRS using summary statistics from genome-wide association studies (GWAS) for cardiometabolic and lifestyle diseases such as coronary artery disease (CAD), obesity, and type 2 diabetes (T2D). Each PRS was adjusted according to an individual’s predicted genetic ancestry to derive an adjusted PRS (aPRS). We calculated the percentiles based on aPRS and divided them according to the percentiles into three categories: low, intermediate, and high. Considering the intermediate-aPRS percentile as a reference, we compared the low and high aPRS categories and generated the odds ratio (OR) estimates.ResultsThe risk of developing severe obesity for individuals of SAS ancestry was almost threefold higher for individuals with high aPRS than for those with intermediate aPRS, with an OR of 3.67 (95% CI = 2.47-5.48, P < 0.01). While the risk of severe obesity was lower in the low-aPRS group (OR = 0.19, CI = 0.05–0.52, P < 0.01). Comparable results were found in the EUR data, where the low-PRS group had an OR of 0.26 (95% CI= 0.24-0.3, P < 0.01) and the high-PRS group had an OR of 3.2 (95% CI = 3.1-3.3, P < 0.01). We observed similar results for CAD and T2D. Further, we show that SAS individuals with a familial history of CAD and T2D with high-aPRS exhibit further higher risk to these diseases, thereby implying a greater genetic predisposition to these conditions.ConclusionOur findings suggest that using CAD, obesity, and T2D GWAS summary statistics predominantly from the EUR population have sufficient power to identify SAS individuals with higher genetic risk. With future GWAS recruiting more SAS participants and tailoring the PRSs towards SAS ancestry, we believe that the predictive power of PRS would improve.
Defining drivers of under-immunisation and vaccine hesitancy in refugee and migrant populations globally to support strategies to strengthen vaccine uptake for COVID-19: a rapid review
Authors: Deal Anna , Crawshaw Alison F , Carter Jessica , Knights Felicity , Iwami Michiyo , Darwish Mohammad , Hossain Rifat , Immordino Palmira , Kaojaroen Kanokporn , Severoni Santino , Hargreaves Sally 
Published: March 2023

AbstractBackgroundSome refugee and migrant populations have been disproportionately impacted by the COVID-19 pandemic, yet evidence suggests lower uptake of COVID-19 vaccines. They are also an under-immunised group for many routine vaccines. We did a rapid review to explore drivers of under-immunisation and vaccine hesitancy among refugee and migrant populations globally to define strategies to strengthen both COVID-19 and routine vaccination uptake.MethodsWe collected global literature (01/01/2010 - 05/05/2022) pertaining to drivers of under-immunisation and vaccine hesitancy in refugees and migrants, incorporating all vaccines. We searched MEDLINE, Embase, Global Health PsycINFO and the WHO’s ‘Global Research on COVID-19’ database and grey literature. Qualitative data were analysed thematically to identify drivers of under-immunisation and vaccine hesitancy, then categorised using the ‘Increasing Vaccination Model’.Results63 papers were included in this review, reporting data on diverse population groups, including refugees, asylum seekers, labour and undocumented migrants from 22 countries, with six papers reporting on a regional or global scale. Drivers of under-immunisation and vaccine hesitancy pertaining to a wide range of vaccines were covered, including COVID-19 (n=27), HPV (13), measles or MMR (3), influenza (3), tetanus (1), and vaccination in general. We found a range of factors driving under-immunisation and hesitancy in refugee and migrant groups, including unique awareness and access factors that need to be better considered in policy and service delivery. Acceptability of vaccination was often deeply rooted in social and historical context and influenced by personal risk perception.ConclusionsThese findings hold direct relevance to current efforts to ensure high levels of global immunisation coverage, key to which is to ensure marginalised refugees and migrant populations are included in national vaccination plans of low-middle- and high-income countries. We found a stark lack of research from low- and middle-income and humanitarian contexts on vaccination in mobile groups, a situation that needs to be urgently rectified to ensure high coverage for COVID-19 and routine vaccinations.
The aerial epidermis is a major site of quinolizidine alkaloid biosynthesis in narrow-leafed lupin
Authors: Frick Karen Michiko , Lorensen Marcus Daniel Brandbjerg Bohn , Esteban Eddi , Pasha Asher , Schulz Alexander , Provart Nicholas James , Janfelt Christian , Nour-Eldin Hussam Hassan , Geu-Flores Fernando 
Published: March 2023

SummaryLupins are promising legume crops that accumulate toxic alkaloids in the seeds, complicating their use as high-protein crops. The alkaloids are synthesized in green organs (leaves, stems, and pods) and a subset of them is transported to the seeds during fruit development. The exact sites of biosynthesis and accumulation remain unknown, however mesophyll cells have been proposed as sources, and epidermal cells have been suggested as sinks. We examined the spatial localization of the alkaloids in biosynthetic organs of narrow-leafed lupin using mass spectrometry-based imaging (MSI). The alkaloids that accumulate in seeds (“core” alkaloids) were evenly distributed across tissues, however their esterified versions accumulated primarily in the epidermis. In addition, we generated a tissue-specific RNAseq dataset of biosynthetic organs using laser-capture microdissection. The dataset revealed that alkaloid biosynthetic genes are strongly expressed in the epidermis. To confirm the biosynthetic capacity of the leaf epidermis, we combined precursor feeding studies with mass spectrometry imaging, which showed that the lower epidermis is highly biosynthetic. Our work challenges the current assumptions on the precise sites of lupin alkaloid biosynthesis, with direct implications for the elucidation of the alkaloid biosynthesis pathway and the long-distance transport network from source to seed.
A frictional contact problem with normal damped response conditions and thermal effects for a thermo-electro-viscoelastic material
Authors: Djabi Abdelmoumene 
Published: March 2023

PurposeThe paper presents a mathematical problem involving quasistatic contact between a thermo-electro-viscoelastic body and a lubricated foundation, where the contact is described using a version of Coulomb’s law of friction that includes normal damped response conditions and heat exchange with a conductive foundation. The constitutive law for the material is thermo-electro-viscoelastic. The problem is formulated as a system that includes a parabolic equation of the first kind for the temperature, an evolutionary elliptic quasivariational inequality for the displacement and a variational elliptic equality for the electric stress. The author establishes the existence of a unique weak solution to the problem by utilizing classical results for evolutionary quasivariational elliptic inequalities, parabolic differential equations and fixed point arguments.Design/methodology/approachThe author establishes a variational formulation for the model and proves the existence of a unique weak solution to the problem using classical results for evolutionary quasivariational elliptic inequalities, parabolic difierential equations and fixed point arguments.FindingsThe author proves the existence of a unique weak solution to the problem using classical results for evolutionary quasivariational elliptic inequalities, parabolic difierential equations and fixed point arguments.Originality/valueThe author studies a mathematical problem between a thermo-electro-viscoelastic body and a lubricated foundation using a version of Coulomb’s law of friction including the normal damped response conditions and the heat exchange with a conductive foundation, which is original and requires a good understanding of modeling and mathematical tools.
Viewpoint on what may be considered as evidence and how to obtain it when designing health-promoting and inclusive green spaces
Authors: Stigsdotter Ulrika Karlsson , Zhang Gaochao , Gramkow Marie Christoffersen , Sidenius Ulrik 
Published: March 2023

PurposeThe point of departure for this viewpoint paper is the current development in which landscape architects are working towards achieving the United Nations sustainable development goals and the associated cross-cutting pledge “Leave No One Behind”. The sustainable development goals 3 and 11 can be achieved through landscape projects that are inclusive and health promoting, and the authors argue that an evidence-based design process is needed to ensure that project designs deliver what they promise. However, most landscape architects are not trained in evidence-based design and are therefore unsure of what can be used as evidence. A further challenge is the lack of relevant and applicable research evidence for design processes.Design/methodology/approachThe authors present a process model for evidence-based health design in landscape architecture as an overall framework on which the authors base their arguments. The model includes four topics of evidence: target group, human health, environment and use of nature. For each topic, the authors present their view on what may be considered as evidence and where it can be found or generated. The study view is supported by a detailed presentation of where and how evidence was found and generated in a design project for an accessible and health-promoting forest trail for people with mobility disabilities.FindingsThe authors suggest a broad definition of evidence, and that the design process should draw on evidence from relevant research and practice disciplines. Evidence can be found in multiple sources, for example, scientific articles, theoretical works and design guidelines. It can also be generated by landscape architects themselves, for example, through landscape analyses and stakeholder workshops. The evidence should guide and support the landscape architect and not dictate the design process.Practical implicationsThe authors hope that the knowledge provided on the evidence-based health design process and on where to collect or how to generate evidence may inspire landscape architects in their future health design projects.Originality/valuePeople with mobility disabilities face many health challenges and should potentially be able to benefit from visiting green spaces. The authors hope that the knowledge provided on the evidence-based health design process and on where to collect or how to generate evidence may inspire landscape architects in their future health design projects.
Towards understanding the relationships between economics, tribalism and the use of thewastainformal network in the workplace
Authors: Alsarhan Fadi , Al-Twal Arwa 
Published: March 2023

PurposeThe aim of this study is to understand the relationship between economic challenges, tribalism and the use of the wasta informal network in the workplace across Middle East and North Africa (MENA) organizations, with Jordanian public organizations taken as an illustrative case.Design/methodology/approachA qualitative approach was applied, and a total of 28 semi-structured interviews were conducted with human resource (HR) officials working in different public organizations such as state-owned enterprises (SOEs), ministries, government agencies (GAs) the military forces and security agencies.FindingsThe authors' findings show that employees who live in rural areas are more likely to use wasta in public organizations than the counterparts living in the capital Amman. This contrast is accounted for by major differences between mentalities, the strength of tribalism, norms and living standards among residents of urban and rural areas. The authors argue that these differences play a pivotal role on the use of wasta informal networks in the workplace.Originality/valueThe outcomes obtained in this study have proven to be unique and important due to the authors' holistic theoretical understanding of wasta, which offers important insights into its emergence, evolution and use in the workplace. The outcomes of this study also serve as guidance for organizations in understanding the “hidden force” of wasta and the extent to which the organizations' businesses may be impacted by this, based on the type of employees the organizations already have or intend to hire and employees' tribal ties. This study accounts for the wide use of informal networks in managerial activities, based on important social and economic realities that have not been previously explored in the literature.