bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution and origin of sliding clamp in bacteria, archaea and eukarya
Authors: Acharya Sandesh , Dahal Amol , Bhattarai Hitesh Kumar 
Published: October 2020

AbstractReplication of DNA is an essential process in all domains of life. A protein often involved without exception in replication is the sliding clamp. The sliding clamp encircles the DNA and helps replicative polymerase stay attached to the replication machinery increasing the processivity of the polymerase. In eukaryotes and archaea the sliding clamp is called the Proliferating Cell Nuclear Antigen (PCNA) and consists of two domains. This PCNA forms a trimer encircling the DNA as a hexamer. In bacteria, the structure of the sliding clamp is highly conserved, but the protein itself, called beta clamp, contains three domains, which dimerize to form a hexamer. The bulk of literature touts a conservation of the structure of the sliding clamp, but fails to recognize conservation of protein sequence among sliding clamps. In this paper we have used PSI blast to the second interation in NCBI to show a statistically significant sequence homology betweenPyrococcus furiosusPCNA andKallipyga gabonensisbeta clamp. The last two domains of beta clamp align with the two domains of PCNA. This homology data demonstrates that PCNA and beta clamp arose from a common ancestor. In this paper, we have further used beta clamp and PCNA sequences from diverse bacteria, archaea and eukarya to build maximum likelihood phylogenetic tree. Most, but not all, species in different domains of life harbor one sliding clamp from vertical inheritance. Some of these species that have two or more sliding clamps have acquired them from gene duplication or horizontal gene transfer events.
Association between neurofibromatosis type 1 and cerebrovascular diseases in children: a systematic review
Authors: Barreto-Duarte Beatriz , Andrade-Gomes Fabiana H. , Arriaga María B. , Araújo-Pereira Mariana , Cubillos-Angulo Juan Manuel , Andrade Bruno B. 
Published: October 2020

ABSTRACTBackgroundNeurofibromatosis type 1 (NF-1) is an autosomal dominant disease that affects one in every 3000 individuals. This disease can present a wide range of clinical manifestations, ranging from skin abnormalities to severe vascular changes. Although little recognized, cerebrovascular diseases (CVD), often present since childhood and diagnosed late, may have clinical manifestations ranging from headache and cognitive deficits to aneurysm rupture causing death. Thus, the CVD play an important role in the clinical manifestations, the severity of the condition and the prognosis of patients with NF-1. This systematic review aims to summarize the body of evidence linking NF-1 and CVD the in children.MethodsTwo independent reviewers performed a systematic review on the PubMed and EMBASE search platforms, using the following key terms: “neurofibromatosis type 1”, “recklinghausen disease”, “children”, “adolescents”, “stroke”, “moyamoya disease”, “vascular diseases”, “cerebrovascular disorders”, “aneurysm” and “congenital abnormalities”. Studies focused on assessing the development of CVD in children with NF-1 were included.ResultsSeven studies met the inclusion criteria. Twelve different clinical manifestations have been associated with cerebrovascular changes in children with NF-1; 44,5% of diagnosed patients were asymptomatic.ConclusionThe available evidence suggests that cerebrovascular diseases are related with the progression of NF-1, even in the absence of a clear clinical manifestation. In addition, better prognosis was observed when imaging tests were performed to screen for cerebrovascular changes. This generated early interventions and consequently more favorable outcomes.
Complete mitogenome of endemic Plum-headed parakeetPsittacula cyanocephala– characterization and phylogenetic analysis
Authors: Dey Prateek , Sharma Sanjeev Kumar , Sarkar Indrani , Ray Swapna Devi , Pramod Padmnabhan , Sastry Kochiganti Venkata Hanumat , Quadros Goldin , Singh Renu , Singh Ram Pratap 
Published: October 2020

AbstractPsittacula cyanocephalais a parakeet endemic to the Indian sub-continent, widespread in the illegal bird trade. Previous studies onPsittaculaparakeets have highlighted taxonomic ambiguities, warranting further studies to resolve such issues. Since the mitochondrial genome provides useful information about a species concerning its evolution and phylogenetics, we sequenced the complete mitogenome ofP. cyanocephalausing NGS, validated 38.86% of the mitogenome using Sanger Sequencing and compared it with other available whole mitogenomes ofPsittacula. The complete mitogenome of the species was 16814 bp in length with 54.08% AT composition.P. cyanocephala mitogenome comprises of 13 protein-coding genes, 2 rRNAs and 22 tRNAs.P. cyanocephalamitogenome organization was consistent with otherPsittaculamitogenomes. Comparative codon usage analysis indicated the role of natural selection onPsittaculamitogenomes. Strong purifying selection pressure was observed maximum onnad1andnad4lgenes. The mitochondrial control region of allPsittaculaspecies displayed the ancestral avian CR gene order. Phylogenetic analyses revealed thePsittaculagenus as paraphyletic nature, containing at least 4 groups of species within the same genus, suggesting its taxonomic reconsideration. Our results provide useful information for developing forensic tests to control the illegal trade of the species, scientific basis for phylogenetic revision of genusPsittacula.
Unravelling the evolutionary relationships of hepaciviruses within and across rodent hosts
Authors: Bletsa Magda , Vrancken Bram , Gryseels Sophie , Boonen Ine , Fikatas Antonios , Li Yiqiao , Laudisoit Anne , Lequime Sebastian , Bryja Josef , Makundi Rhodes , Meheretu Yonas , Akaibe Benjamin Dudu , Mbalitini Sylvestre Gambalemoke , Van de Perre Frederik , Van Houtte Natalie , Těšíková Jana , Wollants Elke , Van Ranst Marc , Drexler Jan Felix , Verheyen Erik , Leirs Herwig , de Bellocq Joelle Gouy , Lemey Philippe 
Published: October 2020

AbstractHepatitis C virus (HCV; genusHepacivirus) represents a major public health problem, infecting about 3 % of the human population (±185,000,000 people). Because no plausible animal reservoir carrying closely related hepaciviruses has been identified, the zoonotic origins of HCV still remain elusive. Motivated by recent findings of divergent hepaciviruses in rodents and a plausible African origin of HCV genotypes, we have screened a comprehensive collection of small mammals samples from seven sub-Saharan African countries. Out of 4,303 samples screened, 80 were found positive for the presence of hepaciviruses in 29 different host species. We here report 56 novel genomes that considerably increase the diversity of three divergent rodent hepacivirus lineages, which previously were almost exclusively represented by New World and European hepaciviruses. Further-more, we provide undisputable evidence for hepacivirus co-infections in rodents, which remarkably, we exclusively but repeatedly found in four sampled species of brush-furred mice. We also point at hepacivirus co-infections indirectly in different animal hosts by demonstrating evidence for recombination within specific host lineages. Our study considerably expands the available hepacivirus genomic data and elucidates the relatively deep evolutionary history that these pathogens have in rodents compared to other mammalian hosts. Overall, our results emphasize the importance of rodents as a potential hepacivirus reservoir and as models for investigating HCV infection dynamics.
Post-metamorphic skeletal growth in the sea urchinParacentrotus lividusand implications for body plan evolution
Authors: Thompson Jeffrey R. , Paganos Periklis , Benvenuto Giovanna , Arnone Maria Ina , Oliveri Paola 
Published: October 2020

AbstractUnderstanding the molecular and cellular processes that underpin animal development are crucial for understanding the diversity of body plans found on the planet today. Because of their abundance in the fossil record, and tractability as a model system in the lab, skeletons provide an ideal experimental model to understand the origins of animal diversity. We herein use molecular and cellular markers to understand the growth and development of the juvenile sea urchin (echinoid) skeleton. We developed a detailed staging scheme based off of the first ∼four weeks of post-metamorphic life of the regular echinoidParacentrotus lividus. We paired this scheme with immunohistochemical staining for neuronal, muscular, and skeletal tissues, and fluorescent assays of skeletal growth and cell proliferation to understand the molecular and cellular mechanisms underlying skeletal growth and development of the sea urchin body plan. Our experiments highlight the role of skeletogenic proteins in accretionary skeletal growth and cell proliferation in the addition of new metameric tissues. Furthermore, our work provides a framework for understanding the developmental evolution of sea urchin body plans on macroevolutionary timescales.
Deep Learning-Based Unlearning of Dataset Bias for MRI Harmonisation and Confound Removal
Authors: Dinsdale Nicola K. , Jenkinson Mark , Namburete Ana I. L. 
Published: October 2020

AbstractIncreasingly large MRI neuroimaging datasets are becoming available, including many highly multi-site multi-scanner datasets. Combining the data from the different scanners is vital for increased statistical power; however, this leads to an increase in variance due to nonbiological factors such as the differences in acquisition protocols and hardware, which can mask signals of interest.We propose a deep learning based training scheme, inspired by domain adaptation techniques, which uses an iterative update approach to aim to create scanner-invariant features while simultaneously maintaining performance on the main task of interest, thus reducing the influence of scanner on network predictions. We demonstrate the framework for regression, classification and segmentation tasks with two different network architectures.We show that not only can the framework harmonise many-site datasets but it can also adapt to many data scenarios, including biased datasets and limited training labels. Finally, we show that the framework can be extended for the removal of other known confounds in addition to scanner. The overall framework is therefore flexible and should be applicable to a wide range of neuroimaging studies.1.HighlightsWe demonstrate a flexible deep-learning-based harmonisation frameworkApplied to age prediction and segmentation tasks in a range of datasetsScanner information is removed, maintaining performance and improving generalisabilityThe framework can be used with any feedforward network architectureIt successfully removes additional confounds and works with varied distributions
C/EBPβ-LIP dually activates glycolysis and the malate aspartate shuttle to maintain NADH/NAD+ homeostasis
Authors: Ackermann Tobias , Zuidhof Hidde R. , Kortman Gertrud , Rutten Martijn G. S. , Broekhuis Mathilde , Zaini Mohamad Amr , Hartleben Götz , Calkhoven Cornelis F. 
Published: October 2020

AbstractOncogene-induced metabolic reprograming supports cell growth and proliferation. Yet, it also links cancer cell survival to certain metabolic pathways and nutrients. In order to synthesise amino acids and nucleotidesde novofor growth and proliferation, cancer cells depend on glycolysis, the cytoplasmic oxidation of glucose, which generates necessary metabolic intermediates and ATP. During glycolysis, NAD+ is used as the oxidizing agent and is thereby reduced into NADH. To ensure high glycolysis rates and maintain NADH/NAD+ homeostasis, cytoplasmic NAD+ has to be regenerated. The mitochondria are the major sites of NADH reoxidation into NAD+ where NADH-derived electrons enter the electron transport chain for ATP production. Since NADH/NAD+ cannot cross membranes, the malate-aspartate shuttle (MAS) or the glycerol-3-phosphate shuttle (GPS) are used as intermediate electron carriers. In addition, cytoplasmic NAD+ is generated by NADH-electron transfer to pyruvate, reducing it to lactate (the Warburg effect). NADH/NAD+ homeostasis plays a pivotal role in cancer cell survival, but our knowledge about the involved regulatory mechanisms is still limited. Here, we show that the proto-oncogenic transcription factor C/EBPβ-LIP stimulates both glycolysis and the MAS. Inhibition of glycolysis with ongoing C/EBPβ-LIP-induced MAS activity results in NADH depletion and apoptosis that can be rescued by inhibiting either the MAS or other NADH-consuming processes. Therefore, beyond the discovery of C/EBPβ-LIP as a dual activator of glycolysis and the MAS, this study indicates that simultaneous inhibition of glycolysis and lowering of the NADH/NAD+ ratio may be considered to treat cancer.
Unrestrained Gαi2Signaling Disrupts Normal Neutrophil Trafficking, Aging, and Clearance
Authors: Yan Serena Li-Sue , Hwang Il-Young , Kamenyeva Olena , Kabat Juraj , Kim Ji Sung , Park Chung , Kehrl John H. 
Published: October 2020

AbstractNeutrophil trafficking, homeostatic and pathogen elicited, depends upon chemoattractant receptor triggered heterotrimeric G-protein Gαiβγ signaling, whose magnitude and kinetics are governed by RGS protein/Gαiinteractions. Yet how in totality RGS proteins shape neutrophil chemoattractant receptor activated responses remains unclear. Here, we show that C57Bl/6 neutrophils with genomic knock-in of a mutation that disables all RGS protein-Gαi2interactions (G184S) cannot properly balance chemoattractant receptor signaling, nor appropriately respond to inflammatory insults. Mutant neutrophils accumulate in bone marrow, spleen, lung, and liver; despite neutropenia and an intrinsic inability to properly mobilize from bone marrow.In vitrothey rapidly adhere to ICAM-1 coated plates, but poorly adhere to blood vessel endotheliumsin vivo. Those few neutrophils that cross endotheliums migrate haphazardly. Following Concanavalin-A administration fragmented G184S neutrophils accumulate in liver sinusoids leading to thrombo-inflammation and perivasculitis. Thus, neutrophil Gαi2/RGS protein interactions limit and facilitate Gαi2signaling allowing normal neutrophil trafficking, aging, and clearance.
Efficient mixed model approach for large-scale genome-wide association studies of ordinal categorical phenotypes
Authors: Bi Wenjian , Zhou Wei , Dey Rounak , Mukherjee Bhramar , Sampson Joshua N , Lee Seunggeun 
Published: October 2020

AbstractIn genome-wide association studies (GWAS), ordinal categorical phenotypes are widely used to measure human behaviors, satisfaction, and preferences. However, due to the lack of analysis tools, methods designed for binary and quantitative traits have often been used inappropriately to analyze categorical phenotypes, which produces inflated type I error rates or is less powerful. To accurately model the dependence of an ordinal categorical phenotype on covariates, we propose an efficient mixed model association test, Proportional Odds Logistic Mixed Model (POLMM). POLMM is demonstrated to be computationally efficient to analyze large datasets with hundreds of thousands of genetic related samples, can control type I error rates at a stringent significance level regardless of the phenotypic distribution, and is more powerful than other alternative methods. We applied POLMM to 258 ordinal categorical phenotypes on array-genotypes and imputed samples from 408,961 individuals in UK Biobank. In total, we identified 5,885 genome-wide significant variants, of which 424 variants (7.2%) are rare variants with MAF < 0.01.
Coming together – symbiont acquisition and early development ofBathymodiolusmussels
Authors: Franke Maximilian , Geier Benedikt , Hammel Jörg U. , Dubilier Nicole , Leisch Nikolaus 
Published: October 2020

AbstractSymbiotic associations between animals and microorganisms are widespread and have a profound impact on the ecology, behaviour, physiology, and evolution of the host. Research on deep-sea mussels of the genusBathymodiolushas revealed how chemosynthetic symbionts sustain their host with energy, allowing them to survive in the nutrient-poor environment of the deep ocean. However, to date, we know little about the initial symbiont colonization and how this is integrated into the early development of these mussels. Here we analysed the early developmental life stages ofB. azoricus, “B”. childressiandB. puteoserpentisand the changes that occur once the mussels are colonized by symbionts. We combined synchrotron-radiation based µCT, correlative light and electron microscopy and fluorescence in situ hybridization to show that the symbiont colonization started when the animal settled on the sea floor and began its metamorphosis into an adult animal. Furthermore, we observed aposymbiotic life stages with a fully developed digestive system which was streamlined after symbiont acquisition. This suggests that bathymodiolin mussels change their nutritional strategy from initial filter-feeding to relying on the energy provided by their symbionts. After ∼35 years of research on bathymodiolin mussels, we are beginning to answer fundamental ecological questions concerning their life cycle and the establishment of symbiosis.
Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2
Authors: Gasser Romain , Cloutier Marc , Prévost Jérémie , Fink Corby , Ducas Éric , Ding Shilei , Dussault Nathalie , Landry Patricia , Tremblay Tony , Laforce-Lavoie Audrey , Lewin Antoine , Beaudoin-Bussières Guillaume , Laumaea Annemarie , Medjahed Halima , Larochelle Catherine , Richard Jonathan , Dekaban Gregory A. , Dikeakos Jimmy D. , Bazin Renée , Finzi Andrés 
Published: October 2020

AbstractCharacterization of the humoral response to SARS-CoV-2, the etiological agent of Covid-19, is essential to help control the infection. In this regard, we and others recently reported that the neutralization activity of plasma from COVID-19 patients decreases rapidly during the first weeks after recovery. However, the specific role of each immunoglobulin isotype in the overall neutralizing capacity is still not well understood. In this study, we selected plasma from a cohort of Covid-19 convalescent patients and selectively depleted immunoglobulin A, M or G before testing the remaining neutralizing capacity of the depleted plasma. We found that depletion of immunoglobulin M was associated with the most substantial loss of virus neutralization, followed by immunoglobulin G. This observation may help design efficient antibody-based COVID-19 therapies and may also explain the increased susceptibility to SARS-CoV-2 of autoimmune patients receiving therapies that impair the production of IgM.
Smaller Hippocampal Volume among Black and Latinx Youth Living in High-Stigma Contexts
Authors: Hatzenbuehler Mark L , Weissman David G , McKetta Sarah , Lattanner Micah R , Ford Jessie V , Barch Deanna M , McLaughlin Katie A 
Published: October 2020

ABSTRACTBackgroundTo determine whether being raised in a stigmatizing context influences neurodevelopment in children.MethodsWe drew data from one of the first national, multi-site neuroimaging studies with substantial variability in sociopolitical contexts: the Adolescent Brain and Cognitive Development study (N=11,534;M=9.9 years). We measured structural stigma surrounding gender, race, and Latinx ethnicity using objective state-level indicators of social policies and prejudicial attitudes and individual-level experiences of perceived discrimination, and examined associations with two neural markers: hippocampal volume and amygdala reactivity to threat.ResultsIn a pre-registered analysis, we find that Black (B=−57.27,p=0.025) and Latinx (B=−41.02,p=0.037) youths raised in higher-stigma environments have smaller hippocampal volume than youths raised in low-stigma contexts, controlling for demographics and family socioeconomic status. This association was marginal among girls (p=0.082). The magnitude of the observed difference in hippocampal volume between high and low structural stigma contexts was equivalent to a $20,000 difference in annual family income. Stigmatizing environments were unrelated to hippocampal volume in non-stigmatized youth, providing evidence of specificity. Perceived discrimination was unrelated to hippocampal volume among any of the stigmatized groups. No associations between individual or structural forms of stigma and amygdala reactivity to threat were observed in the stigmatized groups.ConclusionsWe provide novel evidence that an objective measure of stigma at the contextual level (structural stigma) may have a stronger influence on neurodevelopment than subjective perceptions of stigma measured at the individual level, suggesting that contextual approaches may yield new insights into neurodevelopment.
Identification of signaling pathways, matrix-digestion enzymes, and motility components controllingVibrio choleraebiofilm dispersal
Authors: Bridges Andrew A. , Fei Chenyi , Bassler Bonnie L. 
Published: October 2020

AbstractBacteria alternate between being free-swimming and existing as members of sessile multicellular communities called biofilms. The biofilm lifecycle occurs in three stages: cell attachment, biofilm maturation, and biofilm dispersal.Vibrio choleraebiofilms are hyper-infectious and biofilm formation and dispersal are considered central to disease transmission. While biofilm formation is well-studied, almost nothing is known about biofilm dispersal. Here, we conduct an imaging screen forV. choleraemutants that fail to disperse, revealing three classes of dispersal components: signal transduction proteins, matrix-degradation enzymes, and motility factors. Signaling proteins dominated the screen and among them, we focused on an uncharacterized two-component sensory system that we name DbfS/DbfR for Dispersal of Biofilm Sensor/Regulator. Phospho-DbfR represses biofilm dispersal. DbfS dephosphorylates and thereby inactivates DbfR, which permits dispersal. Matrix degradation requires two enzymes: LapG, which cleaves adhesins, and RbmB, which digests matrix polysaccharide. Reorientations in swimming direction, mediated by CheY3, are necessary for cells to escape from the porous biofilm matrix. We suggest that these components act sequentially: signaling launches dispersal by terminating matrix production and triggering matrix digestion and, subsequently, cell motility permits escape from biofilms. This study lays the groundwork for interventions that modulateV. choleraebiofilm dispersal to ameliorate disease.Significance statementThe pathogenVibrio choleraealternates between the free-swimming state and existing in sessile multicellular communities known as biofilms. Transitioning between these lifestyles is key for disease transmission.V. choleraebiofilm formation is well studied, however, almost nothing is known about howV. choleraecells disperse from biofilms, precluding understanding of a central pathogenicity step. Here, we conducted a high-content imaging screen forV. choleraemutants that failed to disperse. Our screen revealed three classes of components required for dispersal: signal transduction, matrix degradation, and motility factors. We characterized these components to reveal the sequence of molecular events that choreographV. choleraebiofilm dispersal. Our report provides a framework for developing strategies to modulate biofilm dispersal to prevent or treat disease.