bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rats in the city: implications for zoonotic disease risk in an urbanizing world
Authors: Blasdell Kim R. , Morand Serge , Laurance Susan G.W. , Doggett Stephen L , Hahs Amy , Perera David , Firth Cadhla 
Published: March 2021

AbstractUrbanization is rapidly transforming much of Southeast Asia, altering the structure and function of the landscape, as well as the frequency and intensity of the interactions between people, animals, and the environment. In this study, we began to explore the impact of urbanization on zoonotic disease risk by simultaneously characterizing changes in the abundance and diversity of reservoir hosts (rodents), ectoparasite vectors (ticks), and microbial pathogens across a gradient of urbanization in Malaysian Borneo. We found that although rodent species diversity decreased with increasing urbanization, two species appeared to thrive in anthropogenic environments: the invasive urban exploiter,Rattus rattusand the native urban adapter,Sundamys muelleri.R. rattuswas strongly associated with the presence of built infrastructure across the gradient and dominated the urban rodent community where it was associated with high microbial diversity and multi-host zoonoses capable of environmental transmission, includingLeptospiraspp., andToxoplasma gondii. In contrast,S. muelleriwas restricted to sites with a significant vegetative component where it was found at high densities in the urban location. This species was strongly associated with the presence of ticks, including the medically important generaAmbylomma,Haemaphysalis, andIxodes. Overall, our results demonstrate that the response to urbanization varies by species at all levels: host, ectoparasite, and microbe. This may lead to increased zoonotic disease risk in a subset of environments across urban and urbanizing landscapes that can be reduced through improved pest management and public health messaging.
Specific protein-membrane interactions promote the export of metallo-β-lactamases via outer membrane vesicles
Authors: López Carolina , Prunotto Alessio , Bahr Guillermo , Bonomo Robert A. , González Lisandro J. , Dal Peraro Matteo , Vila Alejandro J. 
Published: March 2021

ABSTRACTOuter membrane vesicles (OMVs) act as carriers of resistance determinants such as metallo-β-lactamases. The metallo-β-lactamase NDM-1 is present in OMVs produced by Gram-negative bacteria since it is a lipidated, membrane-anchored protein. The soluble domain of NDM-1 also forms electrostatic interactions with the membrane. Herein, we show that these interactions promote its export into OMVs produced by Escherichia coli. We report that favorable electrostatic protein-membrane interactions are also at work in the soluble enzyme IMP-1, while being absent in VIM-2. These interactions correlate with an enhanced secretion into OMVs of IMP-1 compared to VIM-2. Disruption of these interactions in NDM-1 and IMP-1 impairs export into vesicles, confirming their role in defining the protein cargo in OMVs. These results also indicate that export of metallo-β-lactamases into vesicles in their active form is a common phenomenon that involves cargo selection based on molecular features.
CNVxplorer: a web tool to assist clinical interpretation of CNVs in rare disease patients
Authors: Requena Francisco , Abdallah Hamza Hadj , García Alejandro , Nitschké Patrick , Romana Sergi , Malan Valérie , Rausell Antonio 
Published: March 2021

ABSTRACTCopy Number Variants (CNVs) are an important cause of rare diseases. Array-based Comparative Genomic Hybridization tests yield a ∼12% diagnostic rate, with ∼8% of patients presenting CNVs of unknown significance. CNVs interpretation is particularly challenging on genomic regions outside of those overlapping with previously reported structural variants or disease-associated genes. Recent studies showed that a more comprehensive evaluation of CNV features, leveraging both coding and non-coding impacts can significantly improve diagnostic rates. However, currently available CNV interpretation tools are mostly gene-centric or provide only non-interactive annotations difficult to assess in the clinical practice. Here we present CNVxplorer, a web server suited for the functional assessment of CNVs in a clinical diagnostic setting. CNVxplorer mines a comprehensive set of clinical, genomic, and epigenomic features associated with CNVs. It provides sequence constraint metrics, impact on regulatory elements and topologically associating domains, as well as expression patterns. Analyses offered cover (a) agreement with patient phenotypes; (b) visualizations of associations among genes, regulatory elements and transcription factors; (c) enrichment on functional and pathway annotations; and (d) co-occurrence of terms across PubMed publications related to the query CNVs. A flexible evaluation workflow allows dynamic re-interrogation in clinical sessions. CNVxplorer is publicly available athttp://cnvxplorer.com
Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations inPlasmodium vivaxpatients
Authors: Silva-Filho João L , Dos-Santos João CK , Judice Carla , Beraldi Dario , Venugopal Kannan , Lima Diogenes , Nakaya Helder , Paula Erich EV , Lopes Stefanie CP , Lacerda Marcus VG , Marti Matthias , Costa Fabio TM 
Published: March 2021

AbstractPlasmodium vivaxis the major cause of human malaria in the Americas. HowP. vivaxinfection can lead to poor clinical outcomes, despite low peripheral parasitaemia remains a matter of intense debate. Estimation of totalP. vivaxbiomass based on circulating markers indicates existence of a predominant parasite population outside of circulation. In this study we investigate associations between both peripheral and total parasite biomass and host response in vivax malaria. We analysed parasite and host signatures in a cohort of uncomplicated vivax malaria patients from Manaus, Brazil, combining clinical and parasite parameters, multiplexed analysis of host responses andex vivoassays. Patterns of clinical features, parasite burden and host signatures measured in plasma across the patient cohort were highly heterogenous. Further data deconvolution revealed two patient clusters, here termed Vivaxlowand Vivaxhigh. These patient subgroups were defined based on differences in total parasite biomass but not peripheral parasitaemia. Overall Vivaxlowpatients clustered with healthy donors and Vivaxhighpatients showed more profound alterations in haematological parameters, endothelial cell (EC) activation and glycocalyx breakdown and levels of cytokines regulating different haematopoiesis pathways compared to Vivaxlow. Vivaxhighpatients presented more severe thrombocytopenia and lymphopenia, along with enrichment of neutrophils in the peripheral blood and increased neutrophil-to-lymphocyte ratio (NLCR). When patients’ signatures were combined, high association of total parasite biomass with a subset of markers of EC activation, thrombocytopenia and lymphopenia severity was observed. Finally, machine learning models defined a combination of host parameters measured in the circulation that could predict the extent of parasite infection outside of circulation. Altogether, our data show that total parasite biomass is a better predictor of perturbations in host homeostasis inP. vivaxpatients than peripheral parasitaemia. This supports the emerging paradigm of aP. vivaxtissue reservoir, in particular in the hematopoietic niche of bone marrow and spleen.
Positioning zoonotic disease research in forced migration: a systematic literature review of theoretical frameworks and approaches
Authors: Tasker Alex , Braam Dorien 
Published: March 2021

AbstractBackgroundThe emergence and transmission of zoonotic diseases are driven by complex interactions between health, environmental, and socio-political systems. Human movement is considered a significant and increasing factor in these processes, yet forced migration remains an understudied area of zoonotic research – due in part to the complexity of conducting interdisciplinary research in these settings.ObjectivesWe conducted a systematic review to identify and analyze theoretical frameworks and approaches used to study linkages between forced migration and zoonotic diseases.MethodsWe searched within eight electronic databases: ProQuest, SCOPUS, Web of Science, PubMed, PLoSOne, Science Direct, JSTOR, and Google Scholar, to identify a) research articles focusing on zoonoses considering forced migrants in their study populations, and b) forced migration literature which engaged with zoonotic disease. Both authors conducted a full-text review, evaluating the quality of literature reviews and primary data using the Critical Appraisal Skills Programme (CASP) model, while theoretical papers were evaluated for quality using a theory synthesis adapted from Bonell and Fletcher (2013). Qualitative data were synthesized thematically according to the method suggested by Noblit and Hare (1988).ResultsAnalyses of the 23 included articles showed the increasing use of interdisciplinary frameworks and approaches over time, the majority of which stemmed from political ecology. Approaches such as EcoHealth and One Health were increasingly popular, but were more often linked to program implementation and development than broader contextual research. The majority of research failed to acknowledge the heterogeneity of migrant populations, lacked contextual depth, and insufficient acknowledgement of migrant agency in responding to zoonotic threats.ConclusionsAddressing the emergence and spread of zoonoses in forced migration contexts requires more careful consideration and use of interdisciplinary research to integrate the contributions of social and natural science approaches. Robust interdisciplinary theoretical frameworks are an important step for better understanding the complex health, environment, and socio-political drivers of zoonotic diseases in forced migration. Lessons can be learned from the application of these approaches in other hard-to-reach or seldom-heard populations.
Sarcopenic obesity and the risk of hospitalisation or death from COVID-19: findings from UK Biobank
Authors: Wilkinson Thomas J. , Yates Thomas , Baker Luke A. , Zaccardi Francesco , Smith Alice C. 
Published: March 2021

AbstractBackgroundCoronavirus disease□2019 (COVID□19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS□CoV□2 virus). The role of skeletal muscle mass in modulating immune response is well documented. Whilst obesity is well-established as a key factor in COVID-19 infection and outcome, no study has examined the influence of both sarcopenia (low muscle mass) and obesity, termed ‘sarcopenic obesity’ on COVID-19 risk.MethodsThis study uses data from UK Biobank. Probable sarcopenia was defined as low handgrip strength. Sarcopenic obesity was mutually exclusively defined as the presence of obesity and low muscle mass (based on two established criteria: appendicular lean mass (ALM) adjusted for either: 1) height and 2) body mass index (BMI)). ‘Severe COVID-19’ was defined by a positive test result in a hospital setting or death with a primary cause reported as COVID-19. Fully adjusted logistic regression models were used to analyse the associations between sarcopenic status and severe COVID-19. This work was conducted under UK Biobank application number 52553.ResultsWe analysed data from 490,301 UK Biobank participants. 2203 (0.4%) had severe COVID-19 infection. Individuals with probable sarcopenia were 64% more likely to have had severe COVID-19 infection (odds ratio (OR) 1.638; P<.001). Obesity increased the likelihood of severe COVID-19 infection by 76% (P<.001). Using either ALM index and ALM/BMI index to define low muscle mass, those with sarcopenic obesity were 2.6 times more likely to have severe COVID-19 (OR: 2.619; P<.001). Sarcopenia alone did not increase the risk of COVID-19.ConclusionsSarcopenic obesity may increase the risk of severe COVID-19 infection, over that of obesity alone. The mechanisms for this are complex but could be a result of a reduction in respiratory functioning, immune response, and ability to respond to metabolic stress.
The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the Spike protein
Authors: Resende Paola Cristina , Naveca Felipe G , Lins Roberto D. , Dezordi Filipe Zimmer , Ferraz Matheus V. F. , Moreira Emerson G. , Coêlho Danilo F. , Motta Fernando Couto , Paixão Anna Carolina Dias , Appolinario Luciana , Lopes Renata Serrano , Mendonça Ana Carolina da Fonseca , da Rocha Alice Sampaio Barreto , Nascimento Valdinete , Souza Victor , Silva George , Nascimento Fernanda , Neto Lidio Gonçalves Lima , da Silva Fabiano Vieira , Riediger Irina , Debur Maria do Carmo , Leite Anderson Brandao , Mattos Tirza , da Costa Cristiano Fernandes , Pereira Felicidade Mota , dos Santos Cliomar Alves , Rovaris Darcita Buerger , Fernandes Sandra Bianchini , Abbud Adriano , Sacchi Claudio , Khouri Ricardo , Bernardes André Felipe Leal , Delatorre Edson , Gräf Tiago , Siqueira Marilda Mendonça , Bello Gonzalo , Wallau Gabriel L 
Published: March 2021

AbstractMutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the SARS-CoV-2 Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. Importantly, we detected communitary transmission of four lineages bearing NTD indels: a P.1 Δ69-70 lineage (which can impact several SARS-CoV-2 diagnostic protocols), a P.1 Δ144 lineage, a P.1-like lineage carrying ins214ANRN, and the VOI N.10 derived from the B.1.1.33 lineage carrying three deletions (Δ141-144, Δ211 and Δ256-258). These findings support that the ongoing widespread transmission of SARS-CoV-2 in Brazil is generating new viral lineages that might be more resistant to antibody neutralization than parental variants of concern.
The effects of physical distancing and lockdown to restrain SARS-CoV-2 outbreak in the Italian Municipality of Cogne
Authors: Truc F. , Gervino G. 
Published: March 2021

ABSTRACTThe outbreak of SARS-CoV-2 started in Wuhan, China, and is now a pandemic. An understanding of the prevalence and contagiousness of the disease, and of whether the strategies used to contain it to date have been successful, is important for understanding future containment strategies. One strategy for controlling the spread of SARS-CoV-2 is to adopt strong social distancing policies. The Municipality of Cogne (I), adopted strict lockdown rules from March 4, 2020 up to May 18, 2020. This first wave of the pandemic impressed by the extremely low impact of the SARS-CoV-2 on the locals, compared to the number accused on all the Italian territory. Starting from October 2020 up to the end of December, when the second wave hit Italy and Cogne territory, heavier effects were observed. In order to cast light on the effectiveness of the adopted strategy 74,5% of the local population underwent to a blood screening to detect IgM and IgG antibodies and after six months all the people tested positive were again investigated to establish the longitudinal changes in antibodies level. Moreover, within the context of this survey a rare and interesting case of secondary infection has been identified and here presented.
Common dandelion (Taraxacum officinale) efficiently blocks the interaction between ACE2 cell surface receptor and SARS-CoV-2 spike protein D614, mutants D614G, N501Y, K417N and E484Kin vitro
Authors: Tran Hoai Thi Thu , Le Nguyen Phan Khoi , Gigl Michael , Dawid Corinna , Lamy Evelyn 
Published: March 2021

AbstractOn 11th March 2020, coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, was declared as a global pandemic by the World Health Organization (WHO). To date, there are rapidly spreading new “variants of concern” of SARS-CoV-2, the United Kingdom (B.1.1.7), the South African (B.1.351) or Brasilian (P.1) variant. All of them contain multiple mutations in the ACE2 receptor recognition site of the spike protein, compared to the original Wuhan sequence, which is of great concern, because of their potential for immune escape. Here we report on the efficacy of common dandelion (Taraxacum officinale) to block protein-protein interaction of spike S1 to the human ACE2 cell surface receptor. This could be shown for the original spike D614, but also for its mutant forms (D614G, N501Y, and mix of K417N, E484K, N501Y) in human HEK293-hACE2 kidney and A549-hACE2-TMPRSS2 lung cells. High molecular weight compounds in the water-based extract account for this effect. Infection of the lung cells using SARS-CoV-2 spike pseudotyped lentivirus particles was efficiently prevented by the extract and so was virus-triggered pro-inflammatory interleukin 6 secretion. Modern herbal monographs consider the usage of this medicinal plant as safe. Thus, thein vitroresults reported here should encourage further research on the clinical relevance and applicability of the extract as prevention strategy for SARS-CoV-2 infection.Significance statementSARS-CoV-2 is steadily mutating during continuous transmission among humans. This might eventually lead the virus into evading existing therapeutic and prophylactic approaches aimed at the viral spike. We found effective inhibition of protein-protein interaction between the human virus cell entry receptor ACE2 and SARS-CoV-2 spike, including five relevant mutations, by water-based common dandelion (Taraxacum officinale) extracts. This was shownin vitrousing human kidney (HEK293) and lung (A549) cells, overexpressing the ACE2 and ACE2/TMPRSS2 protein, respectively. Infection of the lung cells using SARS-CoV-2 pseudotyped lentivirus was efficiently prevented by the extract. The results deserve more in-depth analysis of dandelions’ effectiveness in SARS-CoV-2 prevention and now require confirmatory clinical evidence.
Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood
Authors: Siu Jacqueline H.Y. , Pitcher Michael J. , Tull Thomas J. , Guesdon William , Montorsi Lucia , Armitage Charles W. , Mahbubani Krishnaa T. , Ellis Richard , Dhami Pawan , Todd Katrina , Kadolsky Ulrich D. , Kleeman Michelle , D’Cruz David P. , Saeb-Parsy Kourosh , Bemark Mats , Pettigrew Gavin J. , Spencer Jo 
Published: March 2021

AbstractB cells generate antibodies that are essential for immune protection. Major events driving B cell responses occur in lymphoid tissues, which guide antigen acquisition and support cellular interactions, yet complexities of B cell subsets in human lymphoid tissues are poorly understood. Here we perform undirected, global profiling of B cells in matched human lymphoid tissues from deceased transplant organ donors and tracked dissemination of B cell clones. In addition to identifying unanticipated features of tissue-based B cell differentiation, we resolve two clonally independent subsets of marginal zone B cells that differ in cell surface and transcriptomic profiles, tendency to disseminate, distribution bias within splenic marginal zone microenvironment and immunoglobulin repertoire diversity and hypermutation frequency. Each subset is represented in spleen, gut-associated lymphoid tissue, mesenteric lymph node, and also blood. Thus, we provide clarity and diffuse controversy surrounding human MZB - the ‘elephant in the room’ of human B cell biology.
DHA but not EPA induces the trans-differentiation of C2C12 cells into white-like adipocytes phenotype
Authors: Ghnaimawi Saeed , Rebello Lisa , Baum Jamie , Huang Yan 
Published: March 2021

AbstractMuscle derived stem cells (MDSCs) and myoblast play an important role in myotube regeneration when muscle tissue is injured. However, these cells can be induced to differentiate into adipocytes once exposed to PPARγ activator like EPA and DHA that are highly suggested during pregnancy. The objective of this study aims at determining the identity of trans-differentiated cells by exploring the effect of EPA and DHA on C2C12 undergoing differentiation into brown and white adipocytes. DHA but not EPA committed C2C12 cells reprograming into white like adipocyte phenotype. Also, DHA promoted the expression of lipolysis regulating genes but had no effect on genes regulating β-oxidation referring to its implication in lipid re-esterification. Furthermore, DHA impaired C2C12 cells differentiation into brown adipocytes through reducing the thermogenic capacity and mitochondrial biogenesis of derived cells independent of UCP1. Accordingly, DHA treated groups showed an increased accumulation of lipid droplets and suppressed mitochondrial maximal respiration and spare respiratory capacity. EPA, on the other hand, reduced myogenesis regulating genes, but no significant differences were observed in the expression of adipogenesis key genes. Likewise, EPA suppressed the expression of WAT signature genes indicating that EPA and DHA have an independent role on white adipogeneis. Unlike DHA treatment, EPA supplementation had no effect on the differential of C2C12 cells into brown adipocytes. In conclusion, DHA is a potent adipogenic and lipogenic factor that can change the metabolic profile of muscle cells by increasing myocellular fat.
Systematicin vivoquantification of microRNA affinities
Authors: Brosig Sebastian , Sladitschek Hanna L. , Neveu Pierre A. 
Published: March 2021

AbstractThe majority of mammalian genes are under regulation by microRNAs, yet predicting the extent of miRNA-mediated repression has remained elusive. Here we systematically quantified the biological impact of miRNAs conserved in vertebrates using stable mouse embryonic stem cell lines expressing sensitive fluorescent reporters. Differentiation of these 163 lines to the three germ layers revealed that the majority of conserved miRNAs have detectable changes in activity. We determinedin vivotarget affinity KDof 115 miRNAs by integrating activity measurements, CRISPR/Cas miRNA knockouts and miRNA sequencing. Target affinities of individual miRNAs spanned several orders of magnitude, with highly expressed miRNAs having overall higher KD. Scaling miRNA expression levels by their respective KDrecapitulated the relative number of Argonaute-bound targets for individual miRNA families. Our results provide a rationale to determine the set of miRNAs with a biological activity in a given cell type, KDvalues setting expression thresholds for target repression.