bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 Patients Analysis using SuperHeat Map and Bayesian Network to identify Comorbidities Correlations under Different Scenarios
Authors: Nolasco-Jáuregui O. , Quezada-Téllez L. A. , Rodriguez-Torres E. E. , Fernández-Anaya G. 
Published: May 2021

AbstractBackgroundGiven the exposure risk of comorbidities in Mexican society, the new pandemic involves the highest risk for the population in the history.ObjectiveThis article presents an analysis of the COVID-19 risk from Mexico’s regions.MethodThe study period runs from April 12 to June 29, 2020 (220,667 patients). The method has a nature applied and according to its level of deepening in the object of study it is framed in a descriptive and explanatory analysis type. The data used here has a quantitative and semi-quantitative characteristic because they are the result of a questionnaire instrument made up of 34 fields and the virus test. The instrument is of a deliberate type. According to the manipulation of the variables, this research is a secondary type of practices, and it has a factual inference from an inductive method because it is emphasizing the concomitant variations for each region of the country.ResultsRegion 1 and Region 4 have a higher percentage of hospitalized patients, while Region 2 has a minimum of them. The average age of non-hospitalized patients is around 40 years old, while the hospitalized patients’ age it is close to 55 years. The most sensitive comorbidities in hospitalized patients are three principal: obesity, diabetes mellitus and hypertension. The patients whose needed the mechanical respirator were in ranged from 7.45% to 10.79%.ConclusionsThere is a higher risk of lose their lives in the Region 1 and Region 4 territories than in the Region 2, this information was dictated by the statistical analysis..
Cancer Metastases of 202 Kinds of Cancers via Cytocapsular Tubes
Authors: Yi Tingfang , Wagner Gerhard 
Published: May 2021

BACKGROUNDCancer metastasis is the primary source of solid cancer lethality, but the underlying mechanisms have essentially remained elusive. Recently, we found that cytocapsular tubes, a newly discovered organelle of mammalian cells, conduct cell translocation, suggesting an efficient pathway for cancer cell metastases.METHODSWe performed immunohistochemistry staining and fluorescence microscope imaging analyses of 6 kinds of normal organs (n=14 patients), 38 subtypes of benign tumors (n= 126 patients), and 8,061 clinical solid cancer tissue samples (covering 202 types and subtypes of cancers, and including cancers, paracancer tissues and metastatic cancers) taken from 7,125 cancer patients. These solid cancers cover 30 types of organs. We characterized cytocapsular tubes (CTs), cell migration in CTs, and CT quantity, density, network, superstructures and lifecycle in clinical samples of normal tissues, benign tumors, cancers, paracancer tissues, and metastatic cancers.RESULTSThere is no cytocapsular tubes (CTs) in normal organ tissues. Among the 126 benign tumor samples (covering 38 subtypes) from 126 patients, 86.6% do not have CTs and the other 13.4% show benign-to-malignancy transitions with CTs. Of the 8,061 solid cancer tissue and paracancer samples from 7,125 patients, 100% of cancers (including carcinomas in situ), 100% of paracancer tissues, and 100% of metastatic cancer tissues/organs, harbor large quantities (from thousands to hundreds of thousands) of CTs with many cancer cells in migration inside.CONCLUSIONCytocapsular tubes and networks provide membrane-enclosed physical freeway systems for clinical cancer cell metastasis to neighboring and far-distance tissues and organs.
The upper respiratory tract microbiome of Australian Aboriginal and Torres Strait Islander children in ear and nose health and disease
Authors: Coleman Andrea , Zaugg Julian , Wood Amanda , Cottrell Kyra , Håkansson Eva Grahn , Adams Jasmyn , Brown Matthew , Cervin Anders , Bialasiewicz Seweryn 
Published: May 2021

AbstractObjectiveTo examine the nasal microbiota in relation to otitis status and nose health in Indigenous Australian children.MethodsChildren aged 2-7 years were recruited from two northern Australian (Queensland) communities. Clinical histories were obtained through parent interview and review of the medical record. Nasal cavity swabs were obtained, and the child’s ears, nose and throat were examined. DNA was extracted and analysed by 16S rRNA amplicon next generation sequencing of the V3/V4 region in combination with previously generated culture data.Results103 children were recruited (mean 4.7 years), 17 (16.8%) were ‘healthy’, i.e. normal examination and no history of otitis media (OM). Nasal microbiota differed significantly in relation to otitis status and nose health. Children with historical OM had higher relative abundance of Moraxella compared to healthy children, despite both having healthy ears at the time of swabbing. Children with healthy noses had higher relative abundance of S. aureus compared to those with rhinorrhoea. Dolosigranulum was correlated to Corynebacterium in healthy children. Haemophilus and Streptococcus correlated across phenotypes. Ornithobacterium was absent/low relative abundance in healthy children and clustered around otopathogens. It correlated with Helcococcus and Dichelobacter.ConclusionsDolosigranulum and Corynebacterium form a synergism that promotes URT/ear health in Indigenous Australian children. Ornithobacterium likely represents Candidatus Ornithobacterium hominis and in this population is correlated with a novel bacterium which appears to be related to poor upper respiratory tract/ear health.ImportanceRecurring and chronic infections of the ear (otitis media) are disproportionately prevalent in disadvantaged communities across the globe, and in particular, within Indigenous communities. Despite numerous intervention strategies, otitis media persists as a major health issue and is the leading cause of preventable hearing loss. In disadvantaged communities, this hearing loss is associated with negative educational and social development outcomes, and consequently, poorer employment prospects and increased contact with the justice system in adulthood. Thus, a better understanding of the microbial ecology is needed in order to identify new targets to treat, as well as prevent the infections. This study used a powerful combination of 16S rRNA sequencing and extended culturomics to show that Dolosigranulum pigrum, a bacterium previously identified as a candidate protective species, may require co-colonisation with Corynebacterium pseudodiptheriticum in order to prevent otitis media. Additionally, emerging and potentially novel pathogens and bacteria were identified.
Conformational buffering underlies functional selection in intrinsically disordered protein regions
Authors: Gonzalez-Foutel Nicolas S. , Borcherds Wade M. , Glavina Juliana , Barrera-Vilarmau Susana , Sagar Amin , Estaña Alejandro , Barozet Amelie , Fernandez-Ballester Gregorio , Blanes-Mira Clara , Sánchez Ignacio E , de Prat-Gay Gonzalo , Cortés Juan , Bernadó Pau , Pappu Rohit V. , Holehouse Alex S. , Daughdrill Gary W. , Chemes Lucía B. 
Published: May 2021

ABSTRACTMany disordered proteins conserve essential functions in the face of extensive sequence variation. This makes it challenging to identify the forces responsible for functional selection. Viruses are robust model systems to investigate functional selection and they take advantage of protein disorder to acquire novel traits. Here, we combine structural and computational biophysics with evolutionary analysis to determine the molecular basis for functional selection in the intrinsically disordered adenovirus early gene 1A (E1A) protein. E1A competes with host factors to bind the retinoblastoma (Rb) protein, triggering early S-phase entry and disrupting normal cellular proliferation. We show that the ability to outcompete host factors depends on the picomolar binding affinity of E1A for Rb, which is driven by two binding motifs tethered by a hypervariable disordered linker. Binding affinity is determined by the spatial dimensions of the linker, which constrain the relative position of the two binding motifs. Despite substantial sequence variation across evolution, the linker dimensions are finely optimized through compensatory changes in amino acid sequence and sequence length, leading to conserved linker dimensions and maximal affinity. We refer to the mechanism that conserves spatial dimensions despite large-scale variations in sequence as conformational buffering. Conformational buffering explains how variable disordered proteins encode functions and could be a general mechanism for functional selection within disordered protein regions.
Integrative proteogenomics for differential expression and splicing variation in a DM1 mouse model
Authors: Solovyeva Elizaveta M. , Utzinger Stephan , Vissières Alexandra , Mitchelmore Joanna , Ahrné Erik , Hermes Erwin , Poetsch Tania , Ronco Marie , Bidinosti Michael , Merkl Claudia , Serluca Fabrizio C. , Fessenden James , Naumann Ulrike , Voshol Hans , Meyer Angelika S. , Hoersch Sebastian 
Published: May 2021

AbstractDysregulated mRNA splicing is involved in the pathogenesis of many diseases including cancer, neurodegenerative diseases, and muscular dystrophies such as myotonic dystrophy type 1 (DM1). Comprehensive assessment of dysregulated splicing on the transcriptome and proteome level has been methodologically challenging, and thus investigations have often been targeting only few genes.Here, we performed a large-scale coordinated transcriptomic and proteomic analysis to characterize a DM1 mouse model (HSALR) in comparison to wild-type. Our integrative proteogenomics approach comprised gene- and splicing-level assessments for mRNAs and proteins. It recapitulated many known instances of aberrant mRNA splicing in DM1 and identified new ones. It enabled the design and targeting of splicing-specific peptides and confirmed the translation of known instances of aberrantly spliced disease-related genes (e.g.Atp2a1, Bin1, Ryr1), complemented by novel findings (e.g.Ywhae, Flnc, Svil). Comparative analysis of large-scale mRNA and protein expression data showed quantitative agreement of differentially expressed genes and splicing patterns between disease and wild-type.We hence propose this work as a suitable blueprint for a robust and scalable integrative proteogenomic strategy geared towards advancing our understanding of splicing-based disorders. With such a strategy, splicing-based biomarker candidates emerge as an attractive and accessible option, as they can be efficiently asserted on the mRNA and protein level in coordinated fashion.Graphical abstract
Reactive oxygen species mediate thylakoid membrane remodeling and triacylglycerol synthesis under nitrogen starvation in the alga Chlorella sorokiniana
Authors: Vijayan Jithesh , Wase Nishikant , Liu Kan , Zhang Chi , Riekhof Wayne R. 
Published: May 2021

ABSTRACTMany microbes accumulate energy storage molecules such as triglycerides and starch during nutrient limitation. In eukaryotic green algae grown under nitrogen limiting conditions, triglyceride accumulation is coupled with chlorosis and growth arrest. In this study we show that accumulation of reactive oxygen species (ROS) under nitrogen limitation in the microalga Chlorella sorokiniana is involved in thylakoid membrane remodeling, leading to chlorosis. We show that ROS accumulation under nitrogen limitation is an active process involving downregulation of expression of ROS-quenching enzymes, such as superoxide dismutases, catalase, peroxiredoxin, and glutathione peroxidase-like, and upregulation of enzymes involved in generating ROS, such as NADPH oxidase, xanthine oxidase and amine oxidases. Expression of enzymes involved in ascorbate and glutathione metabolism are also affected under these conditions. Quenching ROS under nitrogen limitation reduces TAG accumulation, adding additional evidence for the role of ROS signaling in the process.
Ubiquity and origins of structural maintenance of chromosomes (SMC) proteins in eukaryotes
Authors: Yoshinaga Mari , Inagaki Yuji 
Published: May 2021

ABSTRACTStructural maintenance of chromosomes (SMC) protein complexes are common in Bacteria, Archaea, and Eukaryota. SMC proteins, together with the proteins related to SMC (SMC-related proteins), constitute a superfamily of ATPases. Bacteria/Archaea and Eukaryotes are distinctive from one another in terms of the repertory of SMC proteins. A single type of SMC protein is dimerized in the bacterial and archaeal complexes, whereas eukaryotes possess six distinct SMC subfamilies (SMC1-6), constituting three heterodimeric complexes, namely cohesin, condensin, and SMC5/6 complex. Thus, to bridge the homodimeric SMC complexes in Bacteria and Archaea to the heterodimeric SMC complexes in Eukaryota, we need to invoke multiple duplications of an SMC gene followed by functional divergence. However, to our knowledge, the evolution of the SMC proteins in Eukaryota had not been examined for more than a decade. In this study, we reexamined the ubiquity of SMC1-6 in phylogenetically diverse eukaryotes that cover the major eukaryotic taxonomic groups recognized to date and provide two novel insights into the SMC evolution in eukaryotes. First, multiple secondary losses of SMC5 and SMC6 occurred in the eukaryotic evolution. Second, the SMC proteins constituting cohesin and condensin (i.e., SMC1-4), and SMC5 and SMC6 were derived from closely related but distinct ancestral proteins. Based on the above-mentioned findings, we discuss how SMC1-6 have diverged from the archaeal homologs.
SARS-CoV-2 convergent evolution cannot be reliably inferred from phylogenetic analyses
Authors: Jo Yoon-Seo , Tamuri Asif U. , Towers Greg J. , Goldstein Richard A. 
Published: May 2021

AbstractA homoplasy is a trait shared between individuals that did not arise in a common ancestor, but rather is the result of convergent evolution. SARS-CoV-2 homoplasic mutations are important to characterise, because the evidence for a mutation conferring a fitness advantage is strengthened if this mutation has evolved independently and repeatedly in separate viral lineages. Yet detecting homoplasy is difficult due to insufficient variation between sequences to construct reliable phylogenetic trees. Here, we develop a method to more robustly identify confident homoplasies. We derive a maximum likelihood (ML) tree, with taxa bearing seemingly recurrent mutations dispersed across the tree, and then, for each potentially homoplasic mutation, we derive an alternative tree where the same taxa are constrained to one clade such that the mutation is no longer homoplasic. We then compare how well the two trees fit the sequence data. Applying this method to SARS-CoV-2 yields only a few instances where the constrained trees have significantly less statistical support than unconstrained tree, suggesting phylogenetics can provide limited support for homoplasy in SARS-CoV-2 and that caution is needed when inferring evidence of convergent evolution from phylogenetic methods in the absence of evidence from other sources.
A toolbox for efficient proximity-dependent biotinylation in zebrafish embryos
Authors: Rosenthal Shimon M. , Misra Tvisha , Abdouni Hala , Branon Tess C. , Ting Alice Y. , Scott Ian C. , Gingras Anne-Claude 
Published: May 2021

AbstractUnderstanding how proteins are organized in compartments is essential to elucidating their function. While proximity-dependent approaches such as BioID have enabled a massive increase in information about organelles, protein complexes and other structures in cell culture, to date there have been only a few studies in living vertebrates. Here, we adapted proximity labeling for protein discovery in vivo in the vertebrate model organism, zebrafish. Using lamin A (LMNA) as bait and green fluorescent protein (GFP) as a negative control, we developed, optimized, and benchmarked in vivo TurboID and miniTurbo labeling in early zebrafish embryos. We developed both an mRNA injection protocol and a transgenic system in which transgene expression is controlled by a heat shock promoter. In both cases, biotin is provided directly in the egg water, and we demonstrate that 12 hours of labeling are sufficient for biotinylation of prey proteins, which should permit time-resolved analysis of development. After statistical scoring, we found that the proximal partners of LMNA detected in each system were enriched for nuclear envelope and nuclear membrane proteins, and included many orthologs of human proteins identified as proximity partners of lamin A in mammalian cell culture. The tools and protocols developed here will allow zebrafish researchers to complement genetic tools with powerful proteomics approaches.
Modular origins of high-amplitude co-fluctuations in fine-scale functional connectivity dynamics
Authors: Pope Maria , Fukushima Makoto , Betzel Richard F. , Sporns Olaf 
Published: May 2021

AbstractThe topology of structural brain networks shapes brain dynamics, including the correlation structure of brain activity (functional connectivity) as estimated from functional neuroimaging data. Empirical studies have shown that functional connectivity fluctuates over time, exhibiting patterns that vary in the spatial arrangement of correlations among segregated functional systems. Recently, an exact decomposition of functional connectivity into frame-wise contributions has revealed fine-scale dynamics that are punctuated by brief and intermittent episodes (events) of high-amplitude co-fluctuations involving large sets of brain regions. Their origin is currently unclear. Here, we demonstrate that similar episodes readily appear in silico using computational simulations of whole-brain dynamics. As in empirical data, simulated events contribute disproportionately to long-time functional connectivity, involve recurrence of patterned co-fluctuations, and can be clustered into distinct families. Importantly, comparison of event-related patterns of co-fluctuations to underlying patterns of structural connectivity reveals that modular organization present in the coupling matrix shape patterns of event-related co-fluctuations. Our work suggests that brief, intermittent events in functional dynamics are partly shaped by modular organization of structural connectivity.Significance StatementBrain regions engage in complex patterns of activation and co-activation over time. Relating these patterns to rest or task-related neural processing is a central challenge in cognitive neuroscience. Recent work has identified brief intermittent bursts of brain-wide signal co-fluctuations, called events, and shown that events drive functional connectivity. The origins of events are still unclear. Here, we address this gap in knowledge by implementing computational models of neural oscillators coupled by anatomical connections derived from maps of the human cerebral cortex. Analysis of the emerging large-scale brain dynamics reveals brief episodes with high system-wide signal amplitudes. Simulated events closely correspond to those seen recently in empirical recordings. Notably, simulated events are significantly aligned with underlying structural modules, thus suggesting an important role of modular network organization.
Human fetal neural stem cell-derived astrocytes maintain glutamate transport after hypoxic injury in vitro
Authors: Shrivastava Vadanya , Dey Devanjan , Singh Singal Chitra Mohinder , Jaiswal Paritosh , Singh Ankit , Sharma JB , Chattopadhyay Parthaprasad , Palanichamy Jayanth Kumar , Sinha Subrata , Seth Pankaj , Sen Sudip 
Published: May 2021

AbstractAstrocytes are the most abundant glial cells that play many critical roles in the central nervous system physiology including the uptake of excess glutamate from the synapse by Excitatory Amino Acid Transporters (EAATs). Among the EAATs, EAAT2 are predominantly functional, astrocyte-specific glutamate transporters in the forebrain. Hypoxic brain injury is a pathological phenomenon seen in various clinical conditions including stroke and neonatal hypoxic ischemic encephalopathy. Glutamate excitotoxicity is an important cause of neuronal cell death in disorders involving hypoxic brain injury. As findings from rodent models cannot always be reliably extrapolated to humans, we aimed to develop a homogenous population of primary human astrocytes to study the effect of hypoxic injury on astrocyte function, especially glutamate uptake. We successfully isolated, established and characterized cultures of human fetal neural stem cells (FNSCs) from aborted fetal brains. FNSCs were differentiated into astrocytes, and characterized by increased expression of the astrocyte markers, glial fibrillary acidic protein (GFAP), EAAT1 and EAAT2. A concomitant decrease in neural stem cell marker, Nestin, was observed. Differentiated astrocytes were exposed to various oxygen concentrations mimicking normoxia (20% and 6%), moderate and severe hypoxia (2% and 0.2% respectively). Interestingly, no change was observed in the expression of glutamate transporter, EAAT2 and glutamate uptake by astrocytes, even after exposure to hypoxia. Our novel model of human FNSC derived astrocytes exposed to hypoxic injury, establishes that astrocytes are able to maintain glutamate uptake even after exposure to severe hypoxia for 48 hours, and thus provides evidence for the neuroprotective role of astrocytes in hypoxic injury.
Three new species of nematodes from the syconia of Ficus racemosa in southern India
Authors: Gupta Satyajeet , Tahseen Qudsia , Borges Renee M. 
Published: May 2021

SummaryFicus racemosa with an Indo-Australasian distribution, has so far been recorded to harbour in its fruits, nematode species of the aphelenchoid genera Schistonchus, Ficophagus and Martininema, and species of diplogastrid genera Teratodiplogaster and Pristionchus. The Indian species reported so far from Ficus racemosa lack comprehensive details on morphology and molecular characterization. In this paper, we describe three new species of nematodes obtained from syconia (enclosed globular infructescence or fruit) of Ficus racemosa found in southern India. Ficophagus glomerata n. sp. is characterised by small body having b=5.2-9.6, c= 18-23; slightly set-off lip region having well developed cephalic framework; secretory-excretory pore opens near the head; slender stylet with small, rounded/ sloping knobs; ovoid median bulb with relatively posteriorly-placed valve plates; males with sickle-shaped spicules having spatulate or hammer-shaped capitulum, represented by an elongate-ovoid condylus and long digitate rostrum and tail conoid with fine, hair-like terminal spike. Teratodiplogaster glomerata n. sp. is characterised by long tubular and narrow stoma with fractal pieces in prostegostom; long rectangular metacorpus; female reproductive system with conspicuous spermatheca and amoeboid sperms; males having short, arcuate spicules and keeled gubernaculum; genital papillae in the configuration of P1, P2, C, P3, P4, P5d, (P6d, P7), P8d, Ph and tail conoid with a terminal or subterminal mucro. Pristionchus glomerata n. sp. is characterised by four morphotypes mainly with variations in lip region, stoma, spicules, gubernaculum, and the position of genital papillae. Phylogenetic analyses based upon near-full-length small subunit (SSU) and D2–D3 expansion segments of large subunit (LSU) rRNA genes confirmed affinities with sister species of corresponding genera.