bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and biophysical correlation of anti-NANP antibodies within vivoprotection againstP. falciparum
Authors: Pholcharee Tossapol , Oyen David , Flores-Garcia Yevel , Gonzalez-Paez Gonzalo , Han Zhen , Williams Katherine L. , Volkmuth Wayne , Emerling Daniel , Locke Emily , King C. Richter , Zavala Fidel , Wilson Ian A. 
Published: July 2020

AbstractThe most advancedP. falciparumcircumsporozoite protein (PfCSP)-based malaria vaccine, RTS,S/AS01 (RTS,S), confers partial protection but with antibody titers that wane relatively rapidly, highlighting the need to elicit more potent and durable antibody responses. Here, we elucidate crystal structures, binding affinities and kinetics, andin vivoprotection of eight anti-NANP antibodies (Abs) derived from an RTS,S phase 2a trial and encoded by three different heavy-chain germline genes. The structures reinforce the importance of homotypic Fab-Fab interactions in protective Abs and the overwhelmingly dominant preference for a germline-encoded aromatic residue for recognition of the NANP motif. A number of biophysical properties were analyzed and antibody affinity correlated best with protection in anin vivomouse model, with the more potent antibodies also recognizing epitopes with repeating secondary structural motifs of type I β- and Asn pseudo 310turns. Such insights can be incorporated into design of more effective immunogens as well as antibodies for passive immunization.
Haplotype Explorer: an infection cluster visualization tool for spatiotemporal dissection of the COVID-19 pandemic
Authors: Kawano-Sugaya Tetsuro , Yatsu Koji , Sekizuka Tsuyoshi , Itokawa Kentaro , Hashino Masanori , Tanaka Rina , Kuroda Makoto 
Published: July 2020

AbstractThe worldwide eruption of COVID-19 that began in Wuhan, China in late 2019 reached 10 million cases by late June 2020. In order to understand the epidemiological landscape of the COVID-19 pandemic, many studies have attempted to elucidate phylogenetic relationships between collected viral genome sequences using haplotype networks. However, currently available applications for network visualization are not suited to understand the COVID-19 epidemic spatiotemporally, due to functional limitations That motivated us to develop Haplotype Explorer, an intuitive tool for visualizing and exploring haplotype networks. Haplotype Explorer enables people to dissect epidemiological consequences via interactive node filters to provide spatiotemporal perspectives on multimodal spectra of infectious diseases, including introduction, outbreak, expansion, and containment, for given regions and time spans. Here, we demonstrate the effectiveness of Haplotype Explorer by showing an example of its visualization and features. The demo using SARS-CoV-2 genome sequences is available athttps://github.com/TKSjp/HaplotypeExplorerSummaryA lot of software for network visualization are available, but existing software have not been optimized to infection cluster visualization against the current worldwide invasion of COVID-19 started since 2019. To reach the spatiotemporal understanding of its epidemics, we developed Haplotype Explorer. It is superior to other applications in the point of generating HTML distribution files with metadata searches which interactively reflects GISAID IDs, locations, and collection dates. Here, we introduce the features and products of Haplotype Explorer, demonstrating the time-dependent snapshots of haplotype networks inferred from total of 4,282 SARS-CoV-2 genomes.
A systematic review and meta-analysis protocol on the association of malaria in pregnancy and adverse birth outcomes
Authors: Yadav Vikas , Bairwa Mohan , Dabar Deepti , Goel Akhil Dhanesh , Palepu Sarika , Joshi Ankur 
Published: July 2020

AbstractIntroductionMalaria in pregnancy contributes to significant adverse birth outcomes. This study is aimed to quantify the relationship between malaria in pregnancy and occurrence of adverse birth outcomes, including preterm delivery, low birth weight, small for gestational age, miscarriages, and stillbirth.Methods and analysisObservational studies and Randomised controlled trials reporting data on selected birth outcomes separately for pregnancies, with or without malaria will be included. We will search for studies over various information sources and data extraction will be done from included studies. Pooled odds ratio (OR) will be calculated for each birth outcomes using fixed effect model or random effects models, based on the level of heterogeneity. Forest plot will be prepared with effect size (with 95 percent confidence interval) of each study and pooled effect size. The methodological quality will be assessed for included observational studies using the Newcastle-Ottawa scale (NOS). Cochrane Risk of Bias tool will be used to evaluate bias in randomised controlled trials. For publication bias, funnel plot will be prepared and assessed for asymmetry, along with Egger’s test.DiscussionThis study will provide an estimate of the risk of adverse birth outcomes in pregnancies with malaria. Results of this study will contribute towards planning effective service delivery in areas with a higher risk of malaria transmission.Ethics and disseminationThe current study is a review of published literature, and it does not require ethical committee approval. Results of this review will be published in a peer-reviewed journal.PROSPERO registration numberCRD42020153009Article summaryStrengths and limitations of this studyTo the best of reviewers’ knowledge, this will be a first-ever comprehensive review on the relationship between malaria in pregnancy and occurrence of most frequent adverse birth outcomes, i.e. preterm delivery, low birth weight, small for gestational age and miscarriages.The finding of this review will be very crucial for the governments of malaria-endemic countries.All the leading information sources will be included in this study to perform searches.The protocol is prepared in adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines (PRISMA-P).A limitation of this study will be, various definition criteria used to define adverse birth outcomes among the included studies. Due to which, it will be challenging to interpret and extrapolate the findings of this study.
A satellite-based spatio-temporal machine learning model to reconstruct daily PM2.5 concentrations across Great Britain
Authors: Santos Rochelle Schneider dos , Vicedo-Cabrera Ana M. , Sera Francesco , Masselot Pierre , Stafoggia Massimo , de Hoogh Kees , Kloog Itai , Reis Stefan , Vieno Massimo , Gasparrini Antonio 
Published: July 2020

AbstractEpidemiological studies on health effects of air pollution usually rely on measurements from fixed ground monitors, which provide limited spatio-temporal coverage. Data from satellites, reanalysis and chemical transport models offer additional information used to reconstruct pollution concentrations at high spatio-temporal resolution. The aim of this study is to develop a multi-stage satellite-based machine learning model to estimate daily fine particulate matter (PM2.5) levels across Great Britain during 2008-2018. This high-resolution model consists of random forest (RF) algorithms applied in four stages. Stage-1 augments monitor-PM2.5 series using co-located PM10 measures. Stage-2 imputes missing satellite aerosol optical depth observations using atmospheric reanalysis models. Stage-3 integrates the output from previous stages with spatial and spatiotemporal variables to build a prediction model for PM2.5. Stage-4 applies Stage-3 models to estimate daily PM2.5 concentrations over a 1 km grid. The RF architecture performed well in all stages, with results from Stage-3 showing an average cross-validated R2 of 0.767 and minimal bias. The model performed better over the temporal scale when compared to the spatial component, but both presented good accuracy with an R2 of 0.795 and 0.658, respectively. The high spatio-temporal resolution and relatively high precision allows this dataset (approximately 950 million points) to be used in epidemiological analyses to assess health risks associated with both short- and long-term exposures to PM2.5.
The genetic architecture of human infectious diseases and pathogen-induced cellular phenotypes
Authors: Hale Andrew T. , Zhou Dan , Sale Rebecca L. , Bastarache Lisa , Wang Liuyang , Zinkel Sandra S. , Schiff Steven J. , Ko Dennis C. , Gamazon Eric R. 
Published: July 2020

AbstractHere, we develop a genetics-anchored framework to decipher mechanisms of infectious disease (ID) risk and infer causal effect on potential complications. We perform transcriptome-wide association studies (TWAS) of 35 ID traits in 27,615 individuals in a broad collection of human tissues, identifying 70 gene-level associations with 26 ID traits, with replication in two large-scale biobanks. A phenome-scale scan and Mendelian Randomization of the 70 gene-level associations across 197 traits proposes a molecular basis for known complications of the ID traits. This rich resource of host genetic associations with pathogen cultures and 16S-rRNA-based microbiome variation provides a platform to investigate host-pathogen interactions. To identify relevant cellular processes, we develop a TWAS repository of 79 pathogen-exposure induced cellular phenotypes. Our study will facilitate mechanistic insights into the role of host genetic variation on ID risk and pathophysiology, with important implications for our molecular understanding of severe phenotypic outcomes.
Concerns with the use of imputation to assign HLA allele-level typing in research predicting transplant outcomes
Authors: Tambur Anat R , Gmeiner Michael , Manski Charles F 
Published: July 2020

AbstractIncomplete information on HLA allele typing is a persistent problem when analyzing the role of Human Leukocyte Antigen (HLA) in transplantation. To refine the predictions possible with partial knowledge of HLA typing, some researchers use HaploStats statistics on the frequencies of haplotypes within specified ethnic/national populations to impute complete HLA allele typing. We evaluated methods that use imputation to predict patient outcomes after organ transplantation, with focus on prediction of graft survival conditional on typing information of the donor and recipient. Logical arguments show that imputation yields no predictive power when predictions are conditioned on all observed HLA typing data. Computational experiments indicate that imputation does not have predictive power when applied to risk-assessment models that make predictions conditional on only part of the observable HLA data. We therefore caution against reliance on imputation to overcome incomplete measurement. We encourage high-resolution typing of HLA antigens to improve prediction of transplant outcomes and matching of donors with recipients. Similar considerations should likely apply in other clinical settings.
The different functions of exercise, supplementary resveratrol, and the combination of exercise and supplementary resveratrol in young and old SAMP8 mice liver
Authors: Suchkov Sergey , Wu Jia-Ping 
Published: July 2020

AbstractThe senescence-accelerated mouse prone 8 (SAMP8) has about half the normal lifespan of a rodent. Therefore, we determined whether the different age degrees has rapid physiological senescence with the same interaction function and mechanism of exercise and supplementary resveratrol intake by SAMP8 mice liver. Histological of aging related liver disease was examined SAMP8 mice by hematoxylin-eosin and Masson’s trichrome staining.Apoptosis was determined by TUNEL staining. The mechanism proteins expression of p-PI3K/PI3K, p-Akt/Akt, Bad, cytochrome c, Bcl 2, ERK1, IL-6, STAT3, MEK5, p-ERK5/ERK5, FGF2, and MMP2/9 were examined by western blot. Results showed that the 3- and 6-month-old SAMP8 mice liver, the senescence-accelerated liver cross-sections observed adipocytes, collagen, and apoptosis cells appear, but lower occurs by exercise, supplementary resveratrol, and their combination. Combination exercise and supplementary resveratrol at the 6-month-old SAMP8 mice has significant increase ratio by p-PI3K/PI3K compared to 3-month-old SAMP8 mice liver (p<0.01), and compared with without treatment SAMP8 mice liver. Exercise, supplementary resveratrol intake, and combined of exercise and resveratrol has facilitated p-Akt/Akt ratio increases, and ERK1/Bcl2 increases, but Bad/Cytochrome c decreases at the 6-month-old SAMP8 by western blot. IL-6/STAT3/MEK5 and p-ERK5/ERK5 ratio have good functions at 6-month-old SAMP8 mice better than 3-month-old SAMP8. FGF2/MMP2 decreases and MMP9 increases observed at the 3-month-old SAMP8 by exercise, supplementary resveratrol, and combination. Indeed, we suggest supplementary resveratrol can help exercise therapy ageing related liver diseases.
microRNAs (miR 9, 124, 155 and 224) transdifferentiate macrophages to neurons
Authors: Challagundla Naveen , Agrawal-Rajput Reena 
Published: July 2020

AbstractDevelopment is an irreversible process of differentiating the undifferentiated cells to functional cells. Brain development involves generation of cells with varied phenotype and functions, which is limited during adulthood, stress, damage/degeneration. Cellular reprogramming makes differentiation reversible process with reprogramming somatic/stem cells to alternative fate with/without stem cells. Exogenously expressed transcription factors or small molecule inhibitors have driven reprogramming of stem/somatic cells to neurons providing alternative approach for pre-clinical/clinical testing and therapeutics. Here in, we report a novel approach of microRNA (miR)-induced trans-differentiation of macrophages (CD11b high) to induced neuronal cells (iNCs) (neuronal markers high-Nestin, Nurr1, Map2, NSE, Tubb3 and Mash1) without exogenous use of transcription factors. miR 9, 124, 155 and 224 successfully transdifferentiated macrophages to neurons with transient stem cell-like phenotype. We report trans differentiation efficacy 18% and 21% with miR 124 and miR 155.in silico(String 10.0, miR gator, mESAdb, TargetScan 7.0) and experimental analysis indicate that the reprogramming involves alteration of pluripotency genes likeOct4, Sox2, Klf4, Nanogand pluripotency miR,miR 302. iNCs also shifted to G0 phase indicating manipulation of cell cycle by these miRs. Further, CD133+ intermediate cells obtained during current protocol could be differentiated to iNCs using miRs. The syanpsin+neurons were functionally active and displayed intracellular Ca+2evoke on activation. miRs could also transdifferentiate bone marrow-derived macrophages and peripheral blood mononuclear cells to neuronal cells. The current protocol could be employed for directin vivoreprogramming of macrophages to neurons without teratoma formation for transplantation and clinical studies.HighlightsmiR 9, miR 124 and miR155 could reprogramme macrophages to mature neurons.miR-induced neuronal reprogramming involves stem cell like intermediate phenotype.Graphical AbstractMacrophages transfected with miR 9, 124, 155 and 224 alter pluripotency genes and neuronal differentiation genes via various mechanisms as elucidated. NIM components may also manipulate driving neuronal differentiation gene expression inducing formation of neuronal cells.
Once upon a time in the far south: Influence of local drivers and functional traits on plant invasion in the harsh sub-Antarctic islands
Authors: Bazzichetto Manuele , Massol François , Carboni Marta , Lenoir Jonathan , Jonas J Lembrechts , Joly Rémi , Renault David 
Published: July 2020

AbstractAimHere, we aim to: (i) investigate the local effect of environmental and human-related factors on alien plant invasion in sub-Antarctic islands; (ii) explore the relationship between alien species features and their dependence on anthropogenic propagule pressure; and (iii) unravel key traits conferring invasiveness in the sub-Antarctic.LocationPossession Island, Crozet archipelago (French sub-Antarctic islands).TaxonNon-native vascular plants (Poaceae, Caryophyllaceae, Juncaceae).MethodsSingle-species distribution models were used to explore the effect of high-resolution topoclimatic and human-related variables on the occurrence of six of the most aggressive alien plants colonizing French sub-Antarctic islands. Furthermore, the interaction between alien species traits and their response to anthropogenic propagule pressure was analysed by means of a multi-species distribution model. This allowed identifying the features of species that were associated to low dependence on human-assisted introductions, and were thus potentially more invasive.ResultsWe observed two main invasion patterns: low-spread species strongly dependent on anthropogenic propagule pressure and high-spread species limited mainly by harsh climatic conditions. Differences in invasiveness across species mostly related to their residence time, life history and plant height, with older introductions, perennial and low-stature species being more invasive.Main conclusionsThe availability of high-resolution data improved our understanding of the role of environmental and human-related factors in driving alien species distribution on sub-Antarctic islands. At the same time, the identification of alien species features conferring invasiveness may help anticipating future problematic invasions.
CAMSAP3 is required for mTORC1-dependent ependymal cell growth and lateral ventricle shaping in mouse brains
Authors: Kimura Toshiya , Saito Hiroko , Kawasaki Miwa , Takeichi Masatoshi 
Published: July 2020

AbstractMicrotubules (MTs) regulate numerous cellular processes, but their roles in brain morphogenesis are not well known. Here we show that CAMSAP3, a non-centrosomal microtubule regulator, is important for shaping the lateral ventricles. In differentiating ependymal cells, CAMSAP3 became concentrated at the apical domains, serving to generate MT networks at these sites.Camsap3-mutated mice showed abnormally narrow lateral ventricles, in which excessive stenosis or fusion was induced, leading to a decrease of neural stem cells at the ventricular and subventricular zones. This defect was ascribed at least in part to a failure of neocortical ependymal cells to broaden their apical domain, a process necessary for expanding the ventricular cavities. mTORC1 was required for ependymal cell growth but its activity was downregulated in mutant cells. Lysosomes, which mediate mTORC1 activation, tended to be reduced at the apical regions of the mutant cells, along with disorganized apical MT networks at the corresponding sites. These findings suggest that CAMSAP3 supports mTORC1 signaling required for ependymal cell growth via MT network regulation, and, in turn, shaping of the lateral ventricles.Summary statementCAMSAP3, which mediates non-centrosomal microtubule assembly, is required for mTORC1-dependent maturation of ependymal cells at the neocortex of developing mouse brains. Loss of CAMSAP3 causes deformation of the lateral ventricles.
BMP signalling directs a fibroblast-to-myoblast conversion at the connective tissue/muscle interface to pattern limb muscles
Authors: de Lima Joana Esteves , Blavet Cédrine , Bonnin Marie-Ange , Hirsinger Estelle , Comai Glenda , Yvernogeau Laurent , Bellenger Léa , Mella Sébastien , Nassari Sonya , Robin Catherine , Schweitzer Ronen , Fournier-Thibault Claire , Tajbakhsh Shahragim , Relaix Frédéric , Duprez Delphine 
Published: July 2020

AbstractPositional information driving limb muscle patterning is contained in lateral plate mesoderm-derived tissues, such as tendon or muscle connective tissue but not in myogenic cells themselves. The long-standing consensus is that myogenic cells originate from the somitic mesoderm, while connective tissue fibroblasts originate from the lateral plate mesoderm. We challenged this model using cell and genetic lineage tracing experiments in birds and mice, respectively, and identified a subpopulation of myogenic cells at the muscle tips close to tendons originating from the lateral plate mesoderm and derived from connective tissue gene lineages. Analysis of single-cell RNA-sequencing data obtained from limb cells at successive developmental stages revealed a subpopulation of cells displaying a dual muscle and connective tissue signature, in addition to independent muscle and connective tissue populations. Active BMP signalling was detected in this junctional cell sub-population and at the tendon/muscle interface in developing limbs. BMP gain- and loss-of-function experiments performedin vivoandin vitroshowed that this signalling pathway regulated a fibroblast-to-myoblast conversion. We propose that localised BMP signalling converts a subset of lateral plate mesoderm-derived fibroblasts to a myogenic fate and establishes a boundary of fibroblast-derived myonuclei at the muscle/tendon interface to control the muscle pattern during limb development.
The Splicing Factor XAB2 interacts with ERCC1-XPF and XPG for RNA-loop processing during mammalian development
Authors: Goulielmaki Evi , Tsekrekou Maria , Batsiotos Nikos , Ascensão-Ferreira Mariana , Ledaki Eleftheria , Stratigi Kalliopi , Chatzinikolaou Georgia , Topalis Pantelis , Kosteas Theodore , Altmüller Janine , Demmers Jeroen A. , Barbosa-Morais Nuno L. , Garinis George A. 
Published: July 2020

AbstractRNA splicing, transcription and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using anin vivobiotinylation tagging approach in mice, we show that the splicing factor XAB2 interacts with the core spliceosome and that it binds to spliceosomal U4 and U6 snRNAs and pre-mRNAs in developing livers. XAB2 depletion leads to aberrant intron retention, R-loop formation and DNA damage in cells. Studies in illudin S-treated cells andCsbm/mdeveloping livers reveal that transcription-blocking DNA lesions trigger the release of XAB2 from all RNA targets tested. Immunoprecipitation studies reveal that XAB2 interacts with ERCC1-XPF and XPG endonucleases outside nucleotide excision repair and that the trimeric protein complex binds RNA:DNA hybrids under conditions that favor the formation of R-loops. Thus, XAB2 functionally links the spliceosomal response to DNA damage with R-loop processing with important ramifications for mammalian development and transcription-coupled DNA repair disorders.
Monitoring Autophagy: Not All LC3s Are Created Equal
Authors: Fouad Yousef A , El-Naggar Shahenda 
Published: July 2020

AbstractThe heightened interest in monitoring autophagy comes with discrepant results in different settings. We examined the specificity of reporting in previous studies regarding the isoforms of the most commonly monitored autophagy-related protein, LC3. An ambiguous picture emerged reflecting confusion in design and/or reporting. In light of our current understanding of the different LC3 isoforms, it has become important to specify the targeted isoform when reporting methods and results of studies attempting to monitor autophagy.