bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity of markers and indexes of systemic inflammation in predicting mortality in COVID 19 infection : A hospital based cross sectional study
Authors: Archana B , Shyamsunder Shylaja , Das Rinki 
Published: March 2021

AbstractBackgroundCOVID-19 is an ongoing global pandemic. It is a systemic infection with a significant impact on the hematopoietic and the immune system. In this study we aimed to evaluate the different inflammatory markers and indexes of systemic inflammatory response in predicting the mortality in patients with COVID 19.MethodsIn this cross sectional study, various inflammatory markers like D-dimer, CRP, serum ferritin, LDH and CBC derived indexes of inflammation were analyzed in predicting mortality in COVID 19 infection.ResultsWe enrolled 302 COVID 19 patients who had a mean age of 54.51±15.39 yrs with 210 (69.5%) males. Among them 21% were asymptomatic and fever was the commonest among symptomatic patients. Majority of patients (66.7%) had no comorbidities and 20% had multiple comorbidities. On analyzing different hematological variables, survivors had statistically significant higher hemoglobin count, lymphocytes, monocytes, eosinophil and platelet count and lower leukocyte, neutrophil count. Inflammatory markers D-dimer, serum ferritin and LDH were significantly elevated among non survivors. Among the indexes of inflammation, only NLR showed significant higher values among non survivors.All the inflammatory markers were able to predict mortality among the COVID 19 infected cases with a sensitivity and specificity of 85% and 65% for d dimer levels, 85% and 72% for serum ferritin, 85% and 72% for LDH, 85% and 51% for CRP levels respectively. Among the indexes of inflammation, validity of NLR was best in predicting mortality with 85% sensitivity and 51% specificity.ConclusionAbnormalities in peripheral blood parameters and increase in inflammatory markers are common findings in COVID 19 infection. NLR was best at predicting mortality followed by D-dimer and serum ferritin levelsContribution details
Sex differences in opioid and psychostimulant craving and relapse: a critical review
Authors: Nicolas Céline , Zlebnik Natalie E. , Farokhnia Mehdi , Leggio Lorenzo , Ikemoto Satoshi , Shaham Yavin 
Published: March 2021

AbstractA widely held dogma in the preclinical addiction field is that females are more vulnerable than males to drug craving and relapse. Here, we first review clinical studies on sex differences in psychostimulant and opioid craving and relapse. Next, we review preclinical studies on sex differences in psychostimulant and opioid reinstatement of drug seeking after extinction of drug self-administration and incubation of drug craving (time-dependent increase in drug seeking during abstinence). We also discuss ovarian hormones’ role in relapse and craving in humans and animal models and speculate on brain mechanisms underlying their role in cocaine craving and relapse in rodent models. Finally, we discuss imaging studies on brain responses to cocaine cues and stress in men and women.The results of the clinical studies reviewed do not appear to support the notion that women are more vulnerable to psychostimulant and opioid craving and relapse. However, this conclusion is tentative because most of the studies reviewed were correlational, not sufficiently powered, and/or not a priori designed to detect sex differences. Additionally, fMRI studies suggest sex differences in brain responses to cocaine cues and stress. The results of the preclinical studies reviewed provide evidence for sex differences in stress-induced reinstatement and incubation of cocaine craving, but not cue- or cocaine priming-induced reinstatement of cocaine seeking. These sex differences are modulated in part by ovarian hormones. In contrast, the available data do not support the notion of sex differences in craving and relapse/reinstatement for methamphetamine or heroin in rodent models.
Kinetochore life histories reveal the origins of chromosome mis-segregation and correction mechanisms
Authors: Sen Onur , Harrison Jonathan U. , Burroughs Nigel J. , McAinsh Andrew D. 
Published: March 2021

ABSTRACTChromosome mis-segregation during mitosis leads to daughter cells with deviant karyotypes (aneuploidy) and an increased mutational burden through chromothripsis of mis-segregated chromosomes. The rate of mis-segregation and the aneuploidy state are hallmarks of cancer and linked to cancer genome evolution. Errors can manifest as “lagging chromosomes” in anaphase, although the mechanistic origins and likelihood of correction are incompletely understood. Here we combine lattice light sheet microscopy, endogenous protein labelling and computational analysis to define the life history of > 104kinetochores throughout metaphase and anaphase from over 200 cells. By defining the “laziness” of kinetochores in anaphase, we reveal that chromosomes are at a considerable and continual risk of mis-segregation. We show that the majority of kinetochores are corrected rapidly in early anaphase through an Aurora B dependent process. Moreover, quantitative analyses of the kinetochore life histories reveal a unique dynamic signature of metaphase kinetochore oscillations that forecasts their fate in the subsequent anaphase. We propose that in diploid human cells chromosome segregation is fundamentally error prone, with a new layer of early anaphase error correction required for stable karyotype propagation.
Eosinophils restrict diesel exhaust particles induced cell proliferation of lung epithelial A549 cells, vial interleukin-13 mediated mechanisms: implications for tissue remodelling and fibrosis
Authors: Niranjan Rituraj , Subramanian Muthukumaravel , Panneer D. , Ojha Sanjay Kumar 
Published: March 2021

AbstractDiesel exhaust particulates (DEPs) affect lung physiology and cause serious damage to the lungs. A number of studies have demonstrated that eosinophils play a very important role in the development of lung tissue remodelling and fibrosis. However, the exact mechanism of its pathogenesis is not known. We for the first time demonstrate that, Interleukin-13 plays a very important role in the development of tissue remodelling and fibrosis. We demonstrate that, Diesel exhaust particle significantly induce eosinophils cell proliferation and interleukin-13 release in invitro culture conditions. Supernatant collected from DEP induced eosinophils cells significantly restrict cell proliferation of epithelial cells due to exposure of diesel exhast particles. Furthermore, purified interleukin-13 decreases the proliferation of A549 cells. Notably, Etoricoxib (selective COX-2 inhibitor) did not inhibit DEP-triggered release of interleukin-13, suggesting another cell signalling pathway. In, vivo exposer of DEP to the mice lung, resulted in the high level of eosinophils degranulation as depicted by the EPX-1 immunostaining and altered level of mRNA expressions of inflammatory genes. We also found that, a-SMA, fibroblast specific protein (FSP-1) has been changed in response to DEP in the mice lungs along with the mediators of inflammation. Altogether, we elucidated the mechanistic role of eosinophils in the DEP triggered proliferation of lungs cells thus providing an inside in the pathophysiology of tissue remodelling and fibrosis of lungs.
Severity of SARS-CoV-2 infection as a function of the interferon landscape across the respiratory tract of COVID-19 patients
Authors: Sposito Benedetta , Broggi Achille , Pandolfi Laura , Crotta Stefania , Ferrarese Roberto , Sisti Sofia , Clementi Nicola , Ambrosi Alessandro , Liu Enju , Frangipane Vanessa , Saracino Laura , Marongiu Laura , Facchini Fabio A , Bottazzi Andrea , Fossali Tommaso , Colombo Riccardo , Clementi Massimo , Tagliabue Elena , Pontiroli Antonio E , Meloni Federica , Wack Andreas , Mancini Nicasio , Zanoni Ivan 
Published: March 2021

SummaryThe COVID-19 outbreak driven by SARS-CoV-2 has caused more than 2.5 million deaths globally, with the most severe cases characterized by over-exuberant production of immune-mediators, the nature of which is not fully understood. Interferons of the type I (IFN-I) or type III (IFN-III) families are potent antivirals, but their role in COVID-19 remains debated. Our analysis of gene and protein expression along the respiratory tract shows that IFNs, especially IFN-III, are over-represented in the lower airways of patients with severe COVID-19, while high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity; also, IFN expression varies with abundance of the cell types that produce them. Our data point to a dynamic process of inter- and intra-family production of IFNs in COVID-19, and suggest that IFNs play opposing roles at distinct anatomical sites.
Colonial choanoflagellate isolated from Mono Lake harbors a microbiome
Authors: Hake K. H. , West P.T. , McDonald K. , Laundon D. , Garcia De Las Bayonas A. , Feng C. , Burkhardt P. , Richter D.J. , Banfield J.F. , King N. 
Published: March 2021

ABSTRACTChoanoflagellates offer key insights into bacterial influences on the origin and early evolution of animals. Here we report the isolation and characterization of a new colonial choanoflagellate species,Barroeca monosierra,that, unlike previously characterized species, harbors a microbiome.B. monosierrawas isolated from Mono Lake, California and forms large spherical colonies that are more than an order of magnitude larger than those formed by the closely relatedSalpingoeca rosetta. By designing fluorescencein situhybridization probes from metagenomic sequences, we found thatB. monosierracolonies are colonized by members of the halotolerant and closely relatedSaccharospirillaceaeandOceanospirillaceae,as well as purple sulfur bacteria (Ectothiorhodospiraceae) and non-sulfurRhodobacteraceae.This relatively simple microbiome in a close relative of animals presents a new experimental model for investigating the evolution of stable interactions among eukaryotes and bacteria.IMPORTANCEThe animals and bacteria of Mono Lake (California) have evolved diverse strategies for surviving the hypersaline, alkaline, arsenic-rich environment. We sought to investigate whether the closest living relatives of animals, the choanoflagellates, exist among the relatively limited diversity of organisms in Mono Lake. We repeatedly isolated members of a single species of choanoflagellate, which we have namedBarroeca monosierra,suggesting that it is a stable and abundant part of the ecosystem. Characterization ofB. monosierrarevealed that it forms large spherical colonies that each contain a microbiome, providing an opportunity to investigate the evolution of stable physical associations between eukaryotes and bacteria.
Can Stephen Curry really know? - Conscious access to outcome prediction of motor actions
Authors: Maurer Lisa K. , Maurer Heiko , Hegele Mathias , Müller Hermann 
Published: March 2021

AbstractThe NBA player Stephen Curry has a habit of turning away from the basket right after taking three-point shots, presumably because he can predict the success of his shot. For such a consciously accessible prediction to be possible, Stephen Curry needs access to internal processes of outcome prediction and valuation. Computational simulations and empirical data suggest that the quality of internal prediction processes is related to motor expertise. Whether the results of internal predictions can reliably be consciously accessed is less clear. In the current study, 30 participants each practiced a virtual goal-oriented throwing task for 1000 trials. Every second trial, they were required to verbally predict the success of the current throw. Results showed that on average, conscious prediction accuracy was above an individually computed chance level, taking into account individual success rates and response strategies. Furthermore, prediction accuracy was related to throwing performance. Participants with better performance predicted the success of their throws more accurately than participants with poorer performance. Moreover, for the poorer performing individuals, movement execution was negatively affected by the verbalized predictions required, and they did not show variation in speech characteristics (response latency) between correct and incorrect predictions. This indicates reduced quality of conscious access to internal processes of outcome prediction.
ATP allosterically stabilizes Integrin-linked kinase for efficient force generation
Authors: Martin Isabel M. , Nava Michele M. , Wickström Sara A. , Gräter Frauke 
Published: March 2021

AbstractFocal adhesions link the actomyosin cytoskeleton to the extracellular matrix regulating cell adhesion, shape, and migration. Adhesions are dynamically assembled and disassembled in response to extrinsic and intrinsic forces, but how the essential adhesion component intergrin-linked kinase (ILK) dynamically responds to mechanical force and what role ATP bound to this pseudokinase plays remains elusive. Here, we apply force-probe molecular dynamics simulations of human ILK:α-parvin coupled to traction force microscopy to explore ILK mechanotransducing functions. We identify two key saltbridge-forming arginines within the allosteric, ATP-dependent force-propagation network of ILK. Disrupting this network by mutation impedes parvin binding, focal adhesion stabilization, force generation, and thus migration. Under tension, ATP shifts the balance from rupture of the complex to protein unfolding, indicating that ATP increases the force threshold required for focal adhesion disassembly. Our study proposes a new role of ATP as an obligatory binding partner for structural and mechanical integrity of the pseudokinase ILK, ensuring efficient cellular force generation and migration.
Effects on brain activity after creative mathematical reasoning when considering individual differences in cognitive ability
Authors: Wirebring Linnea Karlsson , Wiklund-Hörnqvist Carola , Stillesjö Sara , Granberg Carina , Lithner Johan , Andersson Micael , Nyberg Lars , Jonsson Bert 
Published: March 2021

AbstractMany learning opportunities of mathematical reasoning in school encourage imitative learning procedures (algorithmic reasoning, AR) instead of engaging in more constructive reasoning processes (e.g.,creative mathematical reasoning, CMR). Here, we employed a within-subject intervention in the classroom with pupils in upper secondary schools followed by a test situation during brain imaging with fMRI one week later. We hypothesized that learning with CMR compared to AR should lead to a CMR-effect, characterized by better performance and differential brain activity during test. We observed higher brain activity in key regions for mathematical cognition such as left angular gyrus and left inferior frontal gyrus on tasks previously learnt with CMR compared to AR. The effects remained when controlling for individual differences in cognitive abilities, as well as performance and response time differences between the two conditions. Encouraging pupils to engage in constructive processes when learning mathematical reasoning might thus have lasting beneficial effects.
To catch a hijacker: abundance, evolution and genetic diversity of P4-like bacteriophage satellites
Authors: Sousa Jorge A. Moura de , Rocha Eduardo P.C. 
Published: March 2021

AbstractBacteriophages (phages) are bacterial parasites that can themselves be parasitized by phage satellites. The molecular mechanisms used by satellites to hijack phages are sometimes understood in great detail, but the origins, abundance, distribution, and composition of these elements are poorly known. Here, we show that P4-like elements are present in more than 10% of the genomes of Enterobacterales, and in almost half of those ofEscherichia coli, sometimes in multiple distinct copies. We identified over 1000 P4-like elements with very conserved genetic organization of the core genome and a few hotspots with highly variable genes. These elements are never found in plasmids and have very little homology to known phages, suggesting an independent evolutionary origin. Instead, they are scattered across chromosomes, possibly because their integrases are often exchanged with other elements. The rooted phylogenies of hijacking functions are correlated and suggest longstanding co-evolution. They also reveal broad host ranges in P4-like elements, since almost identical elements can be found in distinct bacterial genuses. Our results show that P4-like phage satellites constitute a very distinct, widespread and ancient family of mobile genetic elements. They pave the way for studying the molecular evolution of antagonistic interactions between phages and their satellites.
Epigenetic clock and methylation studies in dogs
Authors: Horvath Steve , Lu Ake T. , Haghani Amin , Zoller Joseph A. , Brooke Robert T. , Raj Ken , Plassais Jocelyn , Hogan Andrew N. , Ostrander Elaine A. 
Published: March 2021

ABSTRACTDNA methylation profiles have been used to develop biomarkers of aging known as epigenetic clocks, which predict chronological age with remarkable accuracy and show promise for inferring health status as an indicator of biological age. Epigenetic clocks were first built to monitor human aging but the principles underpinning them appear to be evolutionarily conserved, as they have now been successfully developed for over 120 mammalian species. Here we describe reliable and highly accurate epigenetic clocks shown to apply to 51 domestic dog breeds. The methylation profiles were generated using a custom array with DNA sequences that are conserved across all mammalian species (HorvathMammalMethylChip40). Canine epigenetic clocks were constructed to estimate age and also predict mortality risk by estimating average time-to-death. We also present two highly accurate human-dog dual species epigenetic clocks (R=0.97), which may facilitate the ready translation from canine to human use (or vice versa) of anti-aging treatments being developed for longevity and preventive medicine. Finally, epigenome-wide association studies herein reveal individual methylation sites that may underlie the inverse relationship between breed weight and lifespan. Overall, we describe robust biomarkers to measure aging and potentially health status in canines.
Inhibition of selective autophagy by members of the herpesvirus ubiquitin-deconjugase family
Authors: Ylä-Anttila Päivi , Masucci Maria G. 
Published: March 2021

AbstractAutophagy is an important component of the innate immune response that restricts infection by different types of pathogens. Viruses have developed multiple strategies to avoid autophagy to complete their replication cycle and promote spreading to new hosts. Here we report that the ubiquitin deconjugases encoded in the N-terminal domain of the large tegument proteins of Epstein-Barr virus (EBV), Kaposi Sarcoma herpesvirus (KSHV) and human cytomegalovirus (HCMV), but not herpes simplex virus-1 (HSV-1), regulate selective autophagy by inhibiting the activity of the autophagy receptor SQSTM1/p62. We found that all the homologs bind to and deubiquitinate SQSTM1/p62 but with variable efficiency, which correlates with their capacity to prevent the colocalization of LC3 with SQSTM1/p62 aggregates and promote the accumulation of a model autophagy substrate. The findings highlight important differences in the strategies by which herpesviruses interfere with selective autophagy.
Are narrow-ranging species doomed to extinction? Projected dramatic decline in future climate suitability of two highly threatened species
Authors: Dubos Nicolas , Montfort Frederique , Grinand Clovis , Nourtier Marie , Deso Gregory , Probst Jean-Michel , Razafimanahaka Julie Hanta , Andriantsimanarilafy Raphali Rodlis , Rakotondrasoa Eddie Fanantenana , Razafindraibe Pierre , Jenkins Richard , Crottini Angelica 
Published: March 2021

AbstractNarrow-ranging species are usually omitted from Species distribution models (SDMs) due to statistical constraints, while they are predicted to be particularly vulnerable to climate change. The recently available high-resolution environmental predictors, along with recently developed methods enable to increase the eligibility of narrow-ranging species for SDMs, provided their distribution is well known. We fill a gap of knowledge on the effect of predicted climate change on narrow-ranging species. We modelled the distribution of the golden mantella frog Mantella aurantiaca and the Manapany day gecko Phelsuma inexpectata, for which the distribution of their occurrence records is well documented. Our modelling scheme included a range of processes susceptible to address statistical issues related to narrow-ranging species. We predict an alarming decline in climate suitability in the whole current distribution area of both species by 2070, potentially leading to a complete extinction in most scenarios. We identified the areas with the best climate suitability in the future, but these remain largely suboptimal regarding species climatic niche. The high level of habitat fragmentation suggests that both species likely need to be at least partly translocated. Climate change may not only drive range contractions or distribution shifts in narrow-ranging species, but may lead to the complete extirpation of suitable environments across their entire region. This study suggests that the level of threats of narrow-ranging species already identified as threatened may be underestimated, especially in heterogeneous tropical areas. We stress the need to develop sampling campaigns and implement proactive actions for narrow-ranging species in the tropics.
Drift correction in localization microscopy using entropy minimization
Authors: Cnossen Jelmer , Cui Tao Ju , Joo Chirlmin , Smith Carlas 
Published: March 2021

AbstractLocalization microscopy offers resolutions down to a single nanometer, but currently requires additional dedicated hardware or fiducial markers to reduce resolution loss from drift of the sample. Drift estimation without fiducial markers is typically implemented using redundant cross correlation (RCC). We show that RCC has sub-optimal precision and bias, which leaves room for improvement. Here, we minimize a bound on the entropy of the obtained localizations to efficiently compute a precise drift estimate. Within practical compute-time constraints, simulations show a 5x improvement in drift estimation precision over the widely used RCC algorithm. The algorithm operates directly on fluorophore localizations and is tested on simulated and experimental datasets in 2D and 3D. An open source implementation is provided, implemented in Python and C++, and can utilize a GPU if available.