bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Respiratory Distress Syndrome is associated with impaired alveolar macrophage efferocytosis
Authors: Mahida Rahul Y. , Scott Aaron , Parekh Dhruv , Lugg Sebastian T. , Hardy Rowan S. , Lavery Gareth G. , Matthay Michael A. , Naidu Babu , Perkins Gavin D. , Thickett David R. 
Published: March 2021

ABSTRACTBackgroundAlveolar macrophage dysfunction may contribute to Acute Respiratory Distress Syndrome (ARDS) pathogenesis, however this has been little studied. Objective: To investigate the pathophysiological link between alveolar macrophage efferocytosis, alveolar neutrophil apoptosis and clinical outcomes in ARDS patients, and to determine whether efferocytosis can be restored.MethodsVentilated sepsis patients with or without ARDS underwent broncho-alveolar lavage. Apoptosis of alveolar neutrophils was assessed using flow cytometry. Alveolar macrophages were isolated and used in flow cytometric efferocytosis assays with labelled apoptotic neutrophils. Alveolar macrophages were also isolated from the lung tissue of lobectomy patients, then treated with pooled ARDS BAL fluid prior to functional assessment. Rac1 gene expression was assessed using RT-qPCR.ResultsPatients with sepsis-related ARDS have decreased alveolar macrophage efferocytosis and increased alveolar neutrophil apoptosis compared to control ventilated sepsis patients. Across all ventilated sepsis patients, alveolar macrophage efferocytosis correlated negatively with alveolar cytokines (IL-8, IL-1ra), duration of ventilation and mortality. ARDS BAL treatment of alveolar macrophages decreased efferocytosis and Rac1 gene expression, however bacterial phagocytosis was preserved. Unexpectedly, alveolar macrophage efferocytosis receptor expression (MerTK, CD206) decreased and expression of the anti-efferocytosis receptor SIRPα increased following ARDS BAL treatment. Rho-associated kinase inhibition partially restored alveolar macrophage efferocytosis in an in vitro model of ARDS.ConclusionsPatients with sepsis-related ARDS have impaired AM efferocytosis, which potentially contributes to ARDS pathogenesis and negatively impacts clinical outcomes, including mortality. Strategies to upregulate AM efferocytosis may be of value for attenuating inflammation in ARDS.
Post-viral parenchymal lung disease following COVID-19 and viral pneumonitis hospitalisation: A systematic review and meta-analysis
Authors: Fabbri Laura , Moss Samuel , Khan Fasihul , Chi Wenjie , Xia Jun , Robinson Karen A. , Smyth Alan , Jenkins Gisli , Stewart Iain 
Published: March 2021

AbstractBackgroundApproximately half of COVID-19 survivors present persisting breathlessness, which may include development of pulmonary fibrosis.Research QuestionWhat is the prevalence of long-term radiological and functional pulmonary sequelae of parenchymal lung disease following hospitalisation with COVID-19 and other viral pneumonia?Study design and methodsWe performed systematic review and random effects meta-analysis of studies in adults hospitalised with SARS-CoV-2, SARS-CoV, MERS-CoV, or Influenza pneumonia and followed within 12 months from discharge. Searches were run on MEDLINE and Embase, updated 29 July 2021. Primary outcomes were proportion of 1) radiologic sequelae at CT scans; 2) restrictive impairment; 3) impaired gas transfer. Heterogeneity was explored in meta-regression.ResultsNinety-five studies were included for qualitative synthesis, of which 70 were suitable for meta-analysis, including 60 studies of SARS-CoV-2 with a median follow up of 3 months. In SARS-CoV-2 the overall estimated proportion of inflammatory changes during follow up was 0.50 (95%CI 0.41 to 0.58, I2=94.6%), whilst fibrotic changes were estimated at 0.29 (95%CI 0.22 to 0.37, I2=94.1%). Inflammatory changes reduced compared with CTs performed during hospitalisation (−0.47; 95%CI -0.56 to -0.37), whereas no significant resolution was observed in fibrotic changes (−0.09; 95%CI -0.25 to 0.07). Impaired gas transfer was estimated at 0.38 (95%CI 0.32 to 0.44, I2=92.1%), which was greater than estimated restrictive impairment (0.17; 95%CI 0.13 to 0.23, I2=92.5%). High heterogeneity means that estimates should be interpreted with caution. Confidence in the estimates was deemed low due to the heterogeneity and because studies were largely observational without controls.InterpretationA substantial proportion of radiological and functional sequelae consistent with parenchymal lung disease are observed following COVID-19 and other viral pneumonitis. Estimates of prevalence are limited by differences in case mix and initial severity. This highlights the importance of extended radiological and functional follow-up post hospitalisation.PROSPERO registrationCRD42020183139 (April 2020)
Quantitative Comparison of SARS-CoV-2 Nucleic Acid Amplification Test and Antigen Testing Algorithms: A Decision Analysis Simulation Model
Authors: Salvatore Phillip P. , Shah Melisa M. , Ford Laura , Delaney Augustina , Hsu Christopher H. , Tate Jacqueline E. , Kirking Hannah L. 
Published: March 2021

AbstractBackgroundAntigen tests for SARS-CoV-2 offer advantages over nucleic acid amplification tests (NAATs, such as RT-PCR), including lower cost and rapid return of results, but show reduced sensitivity. Public health organizations continue to recommend different strategies for utilizing NAATs and antigen tests in various settings. There has not yet been a quantitative comparison of the expected performance of these strategies.MethodsWe utilized a decision analysis approach to simulate the expected outcomes of six algorithms for implementing NAAT and antigen testing, analogous to testing strategies recommended by public health organizations. Each algorithm was simulated 50,000 times for four SARS-CoV-2 infection prevalence levels ranging from 5% to 20% in a population of 100000 persons seeking testing. Primary outcomes were number of missed cases, number of false-positive diagnoses, and total test volumes. Outcome medians and 95% uncertainty ranges (URs) were reported.ResultsAlgorithms that use NAATs to confirm all negative antigen results minimized missed cases but required high NAAT capacity: 92,200 (95% UR: 91,200-93,200) tests (in addition to 100,000 antigen tests) at 10% prevalence. Substituting repeat antigen testing in lieu of NAAT confirmation of all initial negative antigen tests resulted in 2,280 missed cases (95% UR: 1,507-3,067) at 10% prevalence. Selective use of NAATs to confirm antigen results when discordant with symptom status (e.g., symptomatic persons with negative antigen results) resulted in the most efficient use of NAATs, with 25 NAATs (95% UR: 13-57) needed to detect one additional case at 10% prevalence compared to exclusive use of antigen tests.ConclusionsNo single SARS-CoV-2 testing algorithm is likely to be optimal across settings with different levels of prevalence and for all programmatic priorities; each presents a trade-off between prioritized outcomes and resource constraints. This analysis provides a framework for selecting setting-specific strategies to achieve acceptable balances and trade-offs between programmatic priorities and constraints.DisclaimerThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention.
A Longitudinal Analysis of COVID-19 Lockdown Stringency on Sleep and Resting Heart Rate Measures across 20 Countries
Authors: Ong Ju Lynn , Lau TeYang , Karsikas Mari , Kinnunen Hannu , Chee Michael WL 
Published: March 2021

AbstractLockdowns imposed to stem the spread of COVID-19 massively disrupted the daily routines of many worldwide, but studies to date are mostly confined to observations within a limited number of countries, based on subjective reports and survey from specific time periods during the pandemic. We investigated associations between lockdown stringency and objective sleep and resting-heart rate measures in 113,000 users of a consumer sleep tracker across 20 countries from Jan-Jul 2020. With stricter lockdown measures, midsleep times were universally delayed, particularly on weekdays, while midsleep variability and resting heart rate declined. These shifts (midsleep: +0.09 to +0.58 hours; midsleep variability: –0.12 to –0.26 hours; resting heart rate: –0.35 to –2.08 bpm) correlated with the severity of lockdown across different countries and highlight the graded influence of mobility restriction and social isolation on human physiology.
A map of binary SARS-CoV-2 protein interactions implicates host immune regulation and ubiquitination
Authors: Kim Dae-Kyum , Weller Benjamin , Lin Chung-Wen , Sheykhkarimli Dayag , Knapp Jennifer J. , Kishore Nishka , Sauer Mayra , Rayhan Ashyad , Young Veronika , Marin-de la Rosa Nora , Pogoutse Oxana , Spirohn Kerstin , Strobel Alexandra , Laval Florent , Schwehn Patrick , Li Roujia , Rothballer Simin , Altmann Melina , Cassonnet Patricia , Dugied Guillaume , Cote Atina G. , Vergara Lena Elorduy , Hazelwood Isaiah , Liu Bingruo B. , Nguyen Maria , Pandiarajan Ramakrishnan , Rodriguez Coloma Patricia A. , Willems Luc , Twizere Jean-Claude , Demeret Caroline , Jacob Yves , Hao Tong , Hill Dave E. , Falter Claudia , Vidal Marc , Calderwood Michael A. , Roth Frederick P. , Falter-Braun Pascal 
Published: March 2021

ABSTRACTKey steps in viral propagation, immune suppression, and pathology are mediated by direct, binary, physical interactions between viral and host proteins. To understand the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we generated an unbiased systematic map of binary interactions between viral and host proteins, complementing previous co-complex association maps by conveying more direct mechanistic understanding and potentially enabling targeted disruption of direct interactions. To this end, we deployed two parallel strategies, identifying 205 virus-host and 27 intraviral binary interactions amongst 171 host and 19 viral proteins, and confirming high quality of these interactions via a calibrated orthogonal assay. Host proteins interacting with SARS-CoV-2 proteins are enriched in various cellular processes, including immune signaling and inflammation, protein ubiquitination, and membrane trafficking. Specific subnetworks provide new hypotheses related to viral modulation of host protein homeostasis and T-cell regulation. The binary virus-host protein interactions we identified can now be prioritized as targets for therapeutic intervention. More generally, we provide a resource of systematic maps describing which SARS-CoV-2 and human proteins interact directly.
A simple coloring method to distinguish colonies of the yeastsLachancea thermotoleransandSaccharomyces cerevisiaeon agar media
Authors: Melkonian Chrats , Haver Auke , Wagner Marijke , Kalmoua Zakaria , Hellmuth Anna-Sophia , Mendoza Sebastián N. , Molenaar Douwe 
Published: March 2021

AbstractThe yeastLachancea thermotoleransconverts consumed sugar partly to lactic acid instead of ethanol and is therefore used together withSaccharomyces cerevisiaeto produce wines with a lower alcohol content. Being able to distinguish these yeasts is important for quality control and quantitative assessment of the contributions of both yeasts to wine fermentations. Commonly used methods to routinely distinguish these organisms are indirect or rely on commercial products of undisclosed composition. Here we describe that adding bromocresol purple to agar media inducesLachanceacolonies to develop a brown color, whereasSaccharomycescolonies remain white.
Histone H3 clipping is a novel signature of human neutrophil extracellular traps
Authors: Tilley Dorothea O , Abuabed Ulrike , Arndt Ursula Zimny , Schmid Monika , Florian Stefan , Jungblut Peter R. , Brinkmann Volker , Herzig Alf , Zychlinsky Arturo 
Published: March 2021

AbstractNeutrophils are critical to host defence, executing diverse strategies to perform their antimicrobial and regulatory functions. One tactic is the production of neutrophil extracellular traps (NETs). In response to certain stimuli neutrophils decondense their lobulated nucleus and release chromatin into the extracellular space through a process called NETosis. However, NETosis, and the subsequent degradation of NETs, can become dysregulated. NETs are proposed to play a role in infectious as well as many non-infection related diseases including cancer, thrombosis, autoimmunity and neurological disease. Consequently, there is a need to develop specific tools for the study of these structures in disease contexts. In this study, we identified a NET-specific histone H3 cleavage event and harnessed this to develop a cleavage site-specific antibody for the detection of human NETs. By microscopy, this antibody distinguishes NETs from chromatin in purified and mixed cell samples. It also detects NETs in tissue sections. We propose this antibody as a new tool to detect and quantify NETs.
The phosphoproteome of rice leaves responds to water and nitrogen supply
Authors: Hamzelou Sara , Melino Vanessa J. , Plett Darren C. , Kamath Karthik Shantharam , Nawrocki Arkadiusz , Larsen Martin R. , Atwell Brian J. , Haynes Paul A. 
Published: March 2021

AbstractThe scarcity of freshwater is an increasing concern in flood-irrigated rice, whilst excessive use of nitrogen fertilizers is both costly and contributes to environmental pollution. To co-ordinate growth adaptation under prolonged exposure to limited water or excess nitrogen supply, plants have processes for signalling and regulation of metabolic processes. There is limited information on the involvement of one of the most important post-translational modifications (PTMs), protein phosphorylation, on plant adaptation to long-term changes in resource supply.Oryza sativacv. Nipponbare was grown under two regimes of nitrogen from the time of germination to final harvest. Twenty-five days after germination, water was withheld from half the pots in each nitrogen treatment and low water supply continued for an additional 26 days, while the remaining pots were well watered. Leaves from all four groups of plants were harvested after 51 days in order to test whether phosphorylation of leaf proteins responded to prior abiotic events. The dominant impact of these resources is exerted in leaves, where PTMs have been predicted to occur. Proteins were extracted and phosphopeptides were analysed by nanoLC-MS/MS analysis, coupled with label-free quantitation. Water and nitrogen regimes triggered extensive changes in phosphorylation of proteins involved in membrane transport, such as the aquaporin OsPIP2-6, a water channel protein. Our study reveals phosphorylation of several peptides belonging to proteins involved in RNA-processing and carbohydrate metabolism, suggesting that phosphorylation events regulate the signalling cascades that are required to optimize plant response to resource supply.
Borreliainfection in rodent host has dramatic effects on the microbiome of ticks
Authors: Hamilton Phineas T. , Maluenda Elodie , Sarr Anouk , Belli Alessandro , Hurry Georgia , Duron Olivier , Plantard Olivier , Voordouw Maarten J. 
Published: March 2021

AbstractBackgroundVector-borne diseases remain major causes of human morbidity and mortality. It is increasingly recognized that the community of microbes inhabiting arthropods can strongly affect their vector competence, but the role of the tick microbiome inBorreliatransmission – the cause of Lyme disease – remains unclear.ResultsHere, we use a large-scale experiment to clarify the reciprocal interactions betweenBorrelia afzeliiand the microbiome ofIxodes ricinus, its primary vector. In contrast to other reports, we find that depletion of the bacterial microbiome in larval ticks has no effect on their subsequent acquisition ofB. afzeliiduring blood feeding on infected mice. Rather, exposure toB. afzelii-infected hosts drives pervasive changes to the tick microbiome, decreasing overall bacterial abundance, shifting bacterial community composition, and increasing bacterial diversity. These effects appear to be independent of the acquisition ofB. afzeliiby ticks, suggesting they are mediated by physiological or immunological aspects ofB. afzeliiinfection in the rodent host.ConclusionsManipulation of the microbiome ofI. ricinuslarvae had no effect on their ability to acquireB. afzelii. In contrast,B. afzeliiinfection in the mouse had dramatic effects on the composition of the gut microbiome inI. ricinusnymphs. Our study demonstrates that vector-borne infections in the vertebrate host shape the microbiome of the arthropod vector.
Sub-second multi-channel magnetic control of select neural circuits in behaving flies
Authors: Sebesta Charles , Torres Daniel , Wang Boshuo , Asfouri Joseph , Li Zhongxi , Duret Guillaume , Jiang Kaiyi , Xiao Zhen , Zhang Linlin , Zhang Qingbo , Colvin Vicki , Goetz Stefan M , Peterchev Angel V , Dierick Herman , Bao Gang , Robinson Jacob T. 
Published: March 2021

AbstractPrecisely timed activation of genetically targeted cells is a powerful tool for studying neural circuits and controlling cell-based therapies. Magnetic control of cell activity or “magnetogenetics” using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and studies of freely behaving animals. However, thein vivoresponse time of thermal magnetogenetics is currently tens of seconds, which prevents the precise temporal modulation of neural activity similar to light-based optogenetics. Moreover, magnetogenetics has not provided a means to selectively activate multiple channels to drive behavior. Here we produce sub-second behavioral responses inDrosophila melanogasterby combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A). Furthermore, by tuning the properties of magnetic nanoparticles to respond to different magnetic field strengths and frequencies, we can achieve sub-second, multichannel stimulation, analogous to multi-color optogenetic stimulation. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation only possible by magnetic control.
Precartilage condensation during limb skeletogenesis occurs by tissue phase separation controlled by a bistable cell-state switch with suppressed oscillatory dynamics
Authors: Glimm T. , Kaźmierczak B. , Cui C. , Newman S.A. , Bhat R. 
Published: March 2021

AbstractThe tetrapod limb skeleton is initiated in unpatterned limb bud mesenchyme by the formation of precartilage condensations. Here, based on time-lapse videographic analysis of a forming condensation in a high-density culture of chicken limb bud mesenchyme, we observe a phase transition to a more fluidized state for cells within spatial compacted foci (protocondensations that will progress to condensations), as reflected in their spatial confinement, cell-substratum interaction and speed of motion. Previous work showed that galectin-8 and galectin-1A, two proteins of the galactoside-binding galectin family, are the earliest determinants of this process in the chicken limb bud, and that their interactions in forming skeletogenic patterns of condensations can be interpreted mathematically through a reaction-diffusion-adhesion framework. Based on this framework, we use an ordinary differential equation-based approach to analyze the core switching modality of the galectin reaction network and characterize the states of the network independent of the diffusive and adhesive arms of the patterning mechanism. We identify two steady states where the concentrations of both galectins are respectively, negligible, and very high. An explicit Lyapunov function shows that there are no periodic solutions. For sigmoidal galectin production terms, the model exhibits a bistable switch that arises from a monostable state via saddle-node bifurcation. Our model therefore predicts that the galectin network exists in low and high expression states separated in space or time without any intermediate states. This provides a causal basis for the observed outside vs. inside transition observed in the in vitro video data. We performed a quantitative analysis of the distribution of galectin-1A in cultures of condensing chick limb mesenchymal cells and found that the interior of the protocondensations had concentrations of this protein (compared to the immediate exterior) over and above that expected from its higher cell density, consistent with the model’s predictions. The galectin-based patterning network is thus suggested, on theoretical grounds, to incorporate a core switch independent of any spatial or temporal dynamics, that drives the chondrogenic cell state transition in limb skeletogenesis.
Simple morphometrics for predicting lordosis-induced deviations of body-shape in reared Gilthead seabream (Sparus aurataL.)
Authors: Fragkoulis Stefanos , Koumoundouros George 
Published: March 2021

AbstractHaemal lordosis, V-shape bending of the haemal vertebrae, is a frequent abnormality of reared fish. Lordosis severity ranges from light deformations of vertebral axis, with insignificant effects on external morphology, to severe axis deformations with significant impact on body-shape. In the present study, we developed a simple morphometric index (PrAn) that links lordosis severity at the juvenile stage with fish body-shape at harvesting, without requiring to radiograph or sacrifice the samples. Examined seabream specimens were part of our previous study (Fragkoulis et al. 2019, Sci. Rep. 9, 9832), which monitored the effects of lordosis on the external morphology of pit-tagged seabream juveniles during their growth, up to harvest size. At both juvenile and adult stages, PrAn was effective in discriminating the normal fish from ca the 70% of lordotic fish. Our results suggest the PrAn as a valuable scale of quality, which quantifies the lordosis effects on fish external morphology, both at the juvenile stage and at harvest. Depending on the lordosis rates, and the hatchery strategy on the maximum allowed abnormality rates, this scale can cull out different rates of lordotic fish, without affecting the fish with normal phenotype or the lordotic fish with high recovery potential.
Structure, Mechanism and Crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase
Authors: Newman Joseph A , Douangamath Alice , Yazdani Setayesh , Yosaatmadja Yuliana , Aimon Anthony , Brandão-Neto José , Dunnett Louise , Gorrie-stone Tyler , Skyner Rachel , Fearon Daren , Schapira Matthieu , von Delft Frank , Gileadi Opher 
Published: March 2021

AbstractThe global COVID-19 pandemic is caused by the SARS-CoV-2 virus and has infected over 100 million and caused over 2 million fatalities worldwide at the point of writing. There is currently a lack of effective drugs to treat people infected with SARS-CoV-2. The SARS-CoV-2 Non-structural protein 13 (NSP13) is a superfamily1B helicase that has been identified as a possible target for anti-viral drugs due to its high sequence conservation and essential role in viral replication. In this study we present crystal structures of SARS-CoV-2 NSP13 solved in the APO form and in the presence of both phosphate and the non-hydrolysable ATP analogue (AMP-PNP). Comparisons of these structures reveal details of global and local conformational changes that are induced by nucleotide binding and hydrolysis and provide insights into the helicase mechanism and possible modes of inhibition. Structural analysis reveals two pockets on NSP13 that are classified as “druggable” and include one of the most conserved sites in the entire SARS-CoV-2 proteome. To identify possible starting points for anti-viral drug development we have performed a crystallographic fragment screen against SARS-CoV-2 NSP13 helicase. The fragment screen reveals 65 fragment hits across 52 datasets, with hot spots in pockets predicted to be of functional importance, including the druggable nucleotide and nucleic acid binding sites, opening the way to structure guided development of novel antiviral agents.