bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic dissimilarity determines the establishment of cross-feeding interactions in bacteria
Authors: Giri Samir , Oña Leonardo , Waschina Silvio , Shitut Shraddha , Yousif Ghada , Kaleta Christoph , Kost Christian 
Published: October 2020

SummaryThe exchange of metabolites among different bacterial genotypes profoundly impacts the structure and function of microbial communities. However, the factors governing the establishment of these cross-feeding interactions remain poorly understood. While shared physiological features may facilitate interactions among more closely related individuals, a lower relatedness should reduce competition and thus increase the potential for synergistic interactions. Here we investigate how the relationship between a metabolite donor and recipient affects the propensity of strains to engage in unidirectional cross-feeding interactions. For this, we performed pairwise cocultivation experiments between four auxotrophic recipients and 25 species of potential amino acid donors. Auxotrophic recipients grew in the vast majority of pairs tested (78%), suggesting metabolic cross-feeding interactions are readily established. Strikingly, both the phylogenetic distance between donor and recipient and the dissimilarity of their metabolic networks were positively associated with the growth of auxotrophic recipients. Analysing the co-growth of species from a gut microbial communityin-silicoalso revealed that recipient genotypes benefitted more from interacting with metabolically dissimilar partners, thus corroborating the empirical results. Together, our work identifies the metabolic dissimilarity between bacterial genotypes as key factor determining the establishment of metabolic cross-feeding interactions in microbial communities.HighlightsThe exchange of essential metabolites is common in microbial communitiesMetabolic cross-feeding interactions readily establish between auxotrophic and prototrophic bacterial strainsBoth the phylogenetic and the metabolic dissimilarity between donors and recipients determines the successful establishment of metabolic cross-feeding interactions
Exploring the variance in complex traits captured by DNA methylation assays
Authors: Battram Thomas , Gaunt Tom R. , Speed Doug , Timpson Nicholas J. , Hemani Gibran 
Published: October 2020

ABSTRACTFollowing years of epigenome-wide association studies (EWAS), traits analysed to date tend to yield few associations. Reinforcing this observation, we conducted EWAS on 400 traits and 16 yielded at least one association at the conventional significance threshold (P<1×10−7). To investigate why EWAS yield is low, we formally estimated the proportion of phenotypic variation captured by 421,693 blood derived DNA methylation markers (h2EWAS) across all 400 traits. The mean h2EWASwas zero, with evidence for regular cigarette smoking exhibiting the largest association with all markers (h2EWAS=0.42) and the only one surpassing a false discovery rate < 0.1. Though underpowered to determine the h2EWASvalue for any one trait, h2EWASwas predictive of the number of EWAS hits across the traits analysed (AUC=0.7). Modelling the contributions of the methylome on a per-site versus a per-region basis gave varied h2EWASestimates (r=0.47) but neither approach obtained substantially higher model fits across all traits. Our analysis indicates that most complex traits do not heavily associate with markers commonly measured in EWAS within blood. However, it is likely DNA methylation does capture variation in some traits and h2EWASmay be a reasonable way to prioritise traits that are likely to yield associations.
Age-related differences in network structure and dynamic synchrony of cognitive control
Authors: Hinault T. , Mijalkov M. , Pereira J.B. , Volpe Giovanni. , Bakker A. , Courtney S.M. 
Published: October 2020

AbstractCognitive trajectories vary greatly across older individuals, and the neural mechanisms underlying these differences remain poorly understood. Here, we propose a mechanistic framework of cognitive variability in older adults, linking the influence of white matter microstructure on fast and effective communications between brain regions. Using diffusion tensor imaging and electroencephalography, we show that individual differences in white matter network organization are associated with network clustering and efficiency in the alpha and high-gamma bands, and that functional network dynamics partly explain individual cognitive control performance in older adults. We show that older individuals with high versus low structural network clustering differ in task-related network dynamics and cognitive performance. These findings were corroborated by investigating magnetoencephalography networks in an independent dataset. This multimodal brain connectivity framework of individual differences provides a holistic account of how differences in white matter microstructure underlie age-related variability in dynamic network organization and cognitive performance.
Computational Model to Quantify the Growth of Antibiotic Resistant Bacteria in Wastewater
Authors: Sutradhar Indorica , Ching Carly , Desai Darash , Suprenant Mark , Briars Emma , Heins Zachary , Khalil Ahmad S. , Zaman Muhammad H. 
Published: October 2020

AbstractAlthough wastewater and sewage systems are known to be significant reservoirs of antibiotic resistant bacterial populations and periodic outbreaks of drug resistant infection, there is little quantitative understanding of the drivers behind resistant population growth in these settings. In order to fill this gap in quantitative understanding of the development of antibiotic resistant infections in wastewater, we have developed a mathematical model synthesizing many known drivers of antibiotic resistance in these settings to help predict the growth of resistant populations in different environmental scenarios. A number of these drivers of drug resistant infection outbreak including antibiotic residue concentration, antibiotic interaction, chromosomal mutation and horizontal gene transfer, have not previously been integrated into a single computational model. We validated the outputs of the model with quantitative studies conducted on the eVOLVER continuous culture platform. Our integrated model shows that low levels of antibiotic residues present in wastewater can lead to increased development of resistant populations, and the dominant mechanism of resistance acquisition in these populations is horizontal gene transfer rather than acquisition of chromosomal mutations. Additionally, we found that synergistic antibiotic interactions lead to increased resistant population growth. These findings, consistent with recent experimental and field studies, provide new quantitative knowledge on the evolution of antibiotic resistant bacterial reservoirs, and the model developed herein can be adapted for use as a prediction tool in public health policy making, particularly in low income settings where water sanitation issues remain widespread and disease outbreaks continue to undermine public health efforts.ImportanceThe rate at which antimicrobial resistance (AMR) has developed and spread throughout the world has increased in recent years, and according to the Review on Antimicrobial Resistance in 2014 it is suggested that the current rate will lead several million people AMR-related deaths by 205025. One major reservoir of resistant bacterial populations that has been linked to outbreaks of drug resistant bacterial infections, but is not well understood, is in wastewater settings, where antibiotic pollution is often present. Using ordinary differential equations incorporating several known drivers of resistance in wastewater, we find that interactions between antibiotic residues and horizontal gene transfer significantly affect the growth of resistant bacterial reservoirs.
A selectable, plasmid-based system to generate CRISPR/Cas9 gene edited and knock-in mosquito cell lines
Authors: Rozen-Gagnon Kathryn , Yi Soon , Jacobson Eliana , Novack Sasha , Rice Charles M. 
Published: October 2020

AbstractAedes (Ae.) aegyptiandAe. albopictusmosquitoes transmit arthropod-borne diseases around the globe, causing ~700,000 deaths each year. Genetic mutants are valuable tools to interrogate both fundamental vector biology and mosquito host factors important for viral infection. However, very few genetic mutants have been described in mosquitoes in comparison to model organisms. The relative ease of applying CRISPR/Cas9 based gene editing has transformed genome engineering and has rapidly increased the number of available gene mutants in mosquitoes. Yet,in vivostudies may not be practical for screening large sets of mutants or possible for laboratories that lack insectaries. Thus, it would be useful to adapt CRISPR/Cas9 systems to common mosquito cell lines. In this study, we generated and characterized a mosquito optimized, plasmid based CRISPR/Cas9 system for use in U4.4 (Ae. albopictus) and Aag2 (Ae. aegypti)cell lines. We demonstrated highly efficient editing of theAGO1locus and isolated knock-down AGO1 cell lines. Further, we used homology-directed repair to establish knock-in Aag2 cell lines with a 3xFLAG-tag at the N-terminus of endogenousAGO1. These experimentally verified plasmids are versatile, cost-effective, and efficiently edit immune competent mosquito cell lines that are widely used in arbovirus studies.
Combinatorial CAR design improves target restriction
Authors: Köksal Hakan , Dillard Pierre , Juzeniene Asta , Kvalheim Gunnar , Smeland Erlend B. , Myklebust June H. , Inderberg Else Marit , Wälchli Sébastien 
Published: October 2020

AbstractCAR T cells targeting the B-lymphocyte antigen CD19 have led to remarkable clinical results in B-cell leukemia and lymphoma, but eliminate all B-lineage cells, leading to increased susceptibility to severe infections. As malignant B cells will express either immunoglobulin (Ig) light chain κ or λ, we designed a second-generation CAR targeting Igκ, IGK CAR. This construct demonstrated high target specificity, but displayed reduced efficacy in the presence of serum IgG. Since CD19 CAR is insensitive to serum IgG, we designed various combinatorial CAR constructs in order to maintain the CD19 CAR T cell efficacy, but with IGK CAR target selectivity. The Kz-19BB design, combining CD19 CAR containing a 4-1BB co-stimulatory domain with an IGK CAR containing a CD3zeta stimulatory domain, maintained the target specificity of IgK CAR and was resistant to the presence of soluble IgG. Our results demonstrate that a combinatorial CAR approach can improve target selectivity and efficacy.
Integrative Analysis the characterization of peroxiredoxins in pan-cancer
Authors: Gao Lei , Meng Jialin , Yue Chuang , Wu Xingyu , Su Quanxin , Wu Hao , Zhang Ze , Yu Qinzhou , Gao Shenglin , Fan Song , Zuo Li 
Published: October 2020

AbstractPeroxiredoxins (PRDXs) are antioxidant enzymes protein family members that involves the process of several biological functions, such as differentiation, cell growth. Considerable evidence demonstrates that PRDXs play critical roles in the occurrence and development of carcinomas. However, a systematic analysis of PRDXs in cancers is deficiency. Therefore, we perform a comprehensive analysis of PRDXs in 33 cancer types including mRNA expression profiles, genetic alterations, methylation, prognostic values, potential biological pathways and target drugs. Moreover, we validated that PRDX6 could regulate cancer cell proliferation via JAK2-STAT3 pathway and involve into the process of cell cycle in bladder cancer.
piRPheno: a manually curated database to prioritize and analyze human disease related piRNAs
Authors: Zhang Wenliang , Wu Song , Zhang Haiyue , Guan Wen , Zeng Binghui , Wei Yanjie , Chan Godfrey Chi-Fung , Li Weizhong 
Published: October 2020

ABSTRACTMany studies have uncovered that piRNAs (PIWI-interacting RNA) are associated with a broad range of diseases and might be a novel type of biomarkers and targets for precision medicine. However, public resource of high-quality curated human disease-associated piRNAs remains unavailable. Therefore, we developed the piRPheno (http://www.biomedical-web.com/pirpheno) database to provide an up-to-date, interactive and extensible data reference for human piRNA-disease associations. piRPheno includes 9057 experimentally supported associations between 474 piRNAs and 204 diseases through a manual curation of publications. To prioritize the piRNA-disease associations, each association in piRPheno is assigned with a confidence score and clinical correlations based on the experimentally supported evidences. piRPheno is freely available with user-friendly interface and novel applications to enable easy exploration and analysis of the human disease related piRNAs.
Subclinical left ventricular disfunction in obese children: are we late?
Authors: Riaño-Mendez B , Ruiz del Campo M , Garcia-Navas P , Amiama-Perez de Villarreal CM , Ruiz del Prado MY 
Published: October 2020

ABSTRACTAimLongitudinal global strain (LGS) is reduced in obese patients with normal ejection fraction of the left ventricle. TAPSE/PAPS ratio, recently described, may be a step forward a more efficient RV function evaluation.There are still few publications in the application of these methods in pediatric patients.MethodsThis case-control study compared 104 children aged 5-18 years between October 2017 and February 2019, 52 obese children with body mass index (BMI) > +2 SD, and 52 matched controls.They were screened for other cardiovascular risk factors like insulin resistance or hypercholesterolemia. A complete echocardiography including standard and functional parameters was performed.ResultsWe found that obese children presented poor systolic function (LGS −15,90 ± 3,84 %) in comparison with non-obese children (−19,44 ± 5,75 %, p=0,001). LGS correlated positively with body mass index (BMI).Standard echocardiography also revealed cardiomegaly and hypertrophy.TAPSE/PASP ratio correlated negatively with triglycerides levels (β −0,402, p=0,014). Diastolic function was poor in those with HOMA-IR (β −0,375, p=0,016) and hypertriglyceridemia (β −0,375 p=0,024).ConclusionWe think that is necessary to perform a standarised cardiovascular evaluation in obese children for early identification of subclinical dysfunction especially in those with insulin resistance and dyslipidemia
The landscape of antibody binding in SARS-CoV-2 infection
Authors: Heffron Anna S. , McIlwain Sean J. , Amjadi Maya F. , Baker David A. , Khullar Saniya , Sethi Ajay K. , Palmenberg Ann C. , Shelef Miriam A. , O’Connor David H. , Ong Irene M. 
Published: October 2020

AbstractThe search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which one epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the six other known human CoVs. We also confirm reactivity against four of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to nine SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.
Genotype-free individual genome reconstruction of Multiparental Population Models by RNA sequencing data
Authors: Choi Kwangbom , He Hao , Gatti Daniel M. , Philip Vivek M. , Raghupathy Narayanan , Gyuricza Isabela Gerdes , Munger Steven C. , Chesler Elissa J. , Churchill Gary A. 
Published: October 2020

AbstractMulti-parent populations (MPPs), genetically segregating model systems derived from two or more inbred founder strains, are widely used in biomedical and agricultural research. Gene expression profiling by direct RNA sequencing (RNA-Seq) is commonly applied to MPPs to investigate gene expression regulation and to identify candidate genes. In genetically diverse populations, including most MPPs, quantification of gene expression is improved when the RNA-Seq reads are aligned to individualized transcriptomes that incorporate known polymorphic loci. However, the process of constructing and analyzing individual genomes can be computationally demanding and error prone. We propose a new approach, genome reconstruction by RNA-Seq (GBRS), that relies on simultaneous alignment of RNA-Seq reads to the founder strain transcriptomes. GBRS can reconstruct the diploid genome of each individual and quantify both total and allele-specific gene expression. We demonstrate that GBRS performs as well as methods that rely on high-density genotyping arrays to reconstruct the founder haplotype mosaic of MPP individuals. Using GBRS in addition to other genotyping methods provides quality control for detecting sample mix-ups and improves power to detect expression quantitative trait loci.GBRSsoftware is freely available athttps://github.com/churchill-lab/gbrs.
A crocodylian-style cloaca in a non-avialan dinosaur
Authors: Bell Phil R. , Pittman Michael , Kaye Thomas G. , Hendrickx Christophe 
Published: October 2020

AbstractOur knowledge of the reproductive biology of dinosaurs covers a range of aspects, from brooding behaviour to nesting style and the timing of sexual maturity. Yet, the basic anatomy and function of the cloaca in non-avialan dinosaurs remains unknown. Here, we describe the outer morphology of the only known non-avialan dinosaur cloaca, preserved in an exceptional specimen of the early-diverging ceratopsian dinosaurPsittacosaurus. We clarify the position of the cloaca with respect to the ischia and caudal vertebrae and document the scales immediately adjacent to the abdomen and tail. We find that the cloaca is from a near-sexually mature subadult individual and is most similar to the cloaca of crocodylians, to the exclusion of lepidosaurians and birds. However, the sex of SMF R 4970 could not be determined as the cloaca and the rest of the specimen does not yield any sexually dimorphic information. This study highlights the ongoing role of exceptional specimens in providing rare soft tissues that help to bridge longstanding gaps in our knowledge of the basic biology of dinosaurs and other extinct reptiles.
Endothelial-secreted Endocan protein acts as a PDGFR alpha ligand and regulates vascularity, radioresistance, and regional phenotype in glioblastoma
Authors: Bastola Soniya , Pavlyukov Marat S. , Ghochani Yasmin , Sharma Neel , Nakano Mayu A. , Muthukrishnan Sree Deepthi , Yu Sang Yul , Kim Min Soo , Sohrabi Alireza , Biscola Natalia P. , Yamashita Daisuke , Anufrieva Ksenia S. , Kawaguchi Riki , Qin Yue , Seidlits Stephanie K. , Burlingame Alma L , Oses-Prieto Juan A. , Havton Leif A. , Goldman Steven A. , Hjelmeland Anita B. , Nakano Ichiro , Kornblum Harley I. 
Published: October 2020

AbstractOne of the hallmarks of glioblastoma (GBM) is extensive neovascularization. In addition to supplying blood and nutrients, vascular endothelial (VE) cells provide trophic support to GBM cells via paracrine signaling, the precise mechanisms of which are being unraveled. Here, using patient-derived GBM and VE cells as well as orthotopic GBM mouse models, we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity. Mechanistically, Endocan exerts at least part of its functions via direct binding and activation of the PDGFRA receptor. Subsequent downstream signaling enhances chromatin accessibility of the Myc promoter and upregulates Myc expression inducing highly stable phenotypic changes in GBM cells. Furthermore, Endocan confers a radioprotection phenotype in GBM cells, bothin vitroandin vivo. Inhibition of Endocan-PDGFRA signaling with ponatinib increases survival in theEsm1wild-type but not in theEsm1knock-out mouse GBM model. Our findings identify Endocan and its downstream signaling axis as a potential target to subdue the recurrence of GBM and further highlight the importance of vascular to tumor cell signaling for GBM biology.Significance statementIdentification of the Endocan/PDGFRA/Myc axis demonstrates an important role of VE cells in GBM malignancy. The contribution of Endocan to the development of GBM cell populations with different phenotypes reveal an additional pathway underlying the origin of GBM intratumoral heterogeneity. Targeting Endocan-mediated crosstalk may enhance the efficacy of GBM treatment.
Interdigitated dynamic actin protrusions maintain stable cadherin adhesion
Authors: Li John Xiao He , Tang Vivian W. , Brieher William M. 
Published: October 2020

AbstractCadherins build stable, cohesive sheets of cells using paradoxically weak bonds. Actin is thought to convert weak binding into strong adhesion either by transmitting myosin dependent pulling forces to adhesive junctions or by clustering cadherins in the plane of the membrane. Here, however, we show that continuous actin polymerization stabilizes cadherin adhesion by directly driving membrane protrusions, not by promoting contractility or cadherin clustering. Lateral membranes of epithelial cells are continuously pushed against each another by protrusions. Micrometer sized cadherin puncta, long thought to be clusters of cadherins, turn out to be patches of microspikes interlocked by cadherin homophilic bonds to hold neighboring cells together. When actin polymerization is blocked, protrusions cease, puncta disappear, and lateral membranes detach from one another. In contrast, inhibiting myosin II contractility has no effect on adhesion.One Sentence SummaryStronger together: membrane interdigitations keep cells attached.
Dialogical and situated accountability to the public. The reporting of nuclear incidents
Authors: Kerveillant Marie , Lorino Philippe 
Published: October 2020

PurposeThe paper aims to investigate how far the pragmatist concept of inquiry (Dewey, 1916, 1938) makes it possible to develop a processual and relational approach to accountability, moving the focus away from a representational conception of truth and subjectivist/individualist views on meaning-making, toward collective exploration and understanding of an issue by stakeholders with the aim of transforming social practices. The paper studies an accountability process in action, namely nuclear incident reporting, and its role in the construction of a community of inquiry investigating nuclear safety.Design/methodology/approachThis research opts for a case study methodology including 36 in-depth interviews, field observation and document analyses. The data are drawn from a three-year field study of a “Local Information Commission”, a body set up to represent the public living near a nuclear site.FindingsThe object of accountability needs to be constructed through a joint exploratory inquiry by accountors and accountees into reports of incidents as originally presented, to advance their understanding and capacity for action.Research limitations/implicationsIt will be important to test this processual and relational approach to accountability in other types of situation, involving different governance issues than nuclear safety.Practical implicationsTo turn theoretical stakeholders such as the public into real stakeholders (e.g. in the studied case, active participants in safety inquiries), specific social and managerial conditions must be fulfilled (concerning time, resources, commitment to open, taboo-free dialogue and legitimacy).Originality/valueThe paper argues that Dewey's concept of inquiry makes a valuable contribution to the processual and dialogical view of accountability.