bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards genetic modification of plant-parasitic nematodes: delivery of macromolecules to adults and expression of exogenous mRNA in second stage juveniles
Authors: Kranse Olaf , Beasley Helen , Adams Sally , da Silva Andre Pires , Bell Chris , Lilley Catherine , Urwin Peter , Bird David , Miska Eric , Smant Geert , Gheysen Godelieve , Jones John , Viney Mark , Abad Pierre , Maier Thomas R. , Baum Thomas J. , Siddique Shahid , Williamson Valerie , Akay Alper , den Akker Sebastian Eves-van 
Published: July 2020

AbstractPlant-parasitic nematodes are a continuing threat to food security, causing an estimated 100 billion USD in crop losses each year. The most problematic are the obligate sedentary endoparasites (primarily root knot nematodes and cyst nematodes). Progress in understanding their biology is held back by a lack of tools for functional genetics: forward genetics is largely restricted to studies of natural variation in populations, and reverse genetics is entirely reliant on RNA interference. There is an expectation that the development of functional genetic tools would accelerate the progress of research on plant-parasitic nematodes, and hence the development of novel control solutions. Here, we develop some of the foundational biology required to deliver a functional genetic tool kit in plant-parasitic nematodes. We characterise the gonads of maleHeterodera schachtiiandMeloidogyne haplain the context of spermatogenesis. We test and optimise various methods for the delivery, expression, and/or detection of exogenous nucleic acids in plant-parasitic nematodes. We demonstrate that delivery of macromolecules to cyst and root knot nematode male germlines is difficult, but possible. Similarly, we demonstrate the delivery of oligonucleotides to root knot nematode gametes. Finally, we develop a transient expression system in plant-parasitic nematodes by demonstrating the delivery and expression of exogenous mRNA encoding various reporter genes throughout the body ofH. schachtiijuveniles using lipofectamine-based transfection. We anticipate these developments to be independently useful, will expedite the development of genetic modification tools for plant-parasitic nematodes, and ultimately catalyze research on a group of nematodes that threaten global food security.
Acidosis, Zinc and HMGB1 in Sepsis: A Common Connection Involving Sialoglycan Recognition
Authors: Siddiqui Shoib S. , Dhar Chirag , Sundaramurthy Venkatasubramaniam , Sasmal Aniruddha , Yu Hai , Bandala-Sanchez Esther , Li Miaomiao , Zhang Xiaoxiao , Chen Xi , Harrison Leonard C. , Xu Ding , Varki Ajit 
Published: July 2020

AbstractBlood pH is tightly regulated between 7.35-7.45, with values below 7.3 during sepsis being associated with lactic acidosis, low serum zinc, and release of proinflammatory HMGB1 from activated and/or necrotic cells. Using anex vivowhole blood system to model lactic acidosis, we show that while HMGB1 does not engage leukocyte receptors at physiological pH, lowering pH with lactic acid facilitates binding. At normal pH, micromolar zinc supports plasma sialoglycoprotein binding by HMGB1, which is markedly reduced when pH is adjusted with lactic acid to sepsis levels. Glycan array studies confirmed zinc and pH-dependent HMGB1 binding to sialoglycans typical of plasma glycoproteins. Thus, proinflammatory effects of HMGB1 are suppressed via plasma sialoglycoproteins until drops in pH and zinc release HMGB1 to trigger downstream immune activation.Significance StatementHMGB1 sequestered by plasma sialoglycoproteins at physiological pH is released when pH and zinc concentrations fall in sepsis.
A small-molecule inhibitor of the BRCA2-RAD51 interaction modulates RAD51 assembly and potentiates DNA damage-induced cell death
Authors: Scott Duncan E. , Francis-Newton Nicola J. , Marsh May E. , Coyne Anthony G. , Fischer Gerhard , Moschetti Tommaso , Bayly Andrew R. , Sharpe Timothy D. , Haas Kalina T. , Barber Lorraine , Valenzano Chiara R. , Srinivasan Rajavel , Huggins David J. , Ehebauer Matthias , Esposito Alessandro , Pellegrini Luca , Perrior Trevor , McKenzie Grahame , Blundell Tom L. , Hyvönen Marko , Skidmore John , Venkitaraman Ashok R. , Abell Chris 
Published: July 2020

SUMMARYBRCA2 controls RAD51 recombinase during homologous DNA recombination (HDR) through eight evolutionarily-conserved BRC repeats, which individually engage RAD51 via the motif Phe-x-x-Ala. Using structure-guided molecular design, templated on a monomeric thermostable chimera between human RAD51 and archaeal RadA, we identify CAM833, a 529 Da orthosteric inhibitor of RAD51:BRC with a Kdof 366 nM. The quinoline of CAM833 occupies a hotspot, the Phe-binding pocket on RAD51 and the methyl of the substituted α-methylbenzyl group occupies the Ala-binding pocket. In cells, CAM833 diminishes formation of damage-induced RAD51 nuclear foci; inhibits RAD51 molecular clustering, suppressing extended RAD51 filament assembly; potentiates cytotoxicity by ionising radiation, augmenting4Ncell-cycle arrest and apoptotic cell death and works with poly-ADP ribose polymerase (PARP)1 inhibitors to suppress growth in BRCA2-wildtype cells. Thus, chemical inhibition of the protein-protein interaction between BRCA2 and RAD51 disrupts HDR and potentiates DNA damage-induced cell death, with implications for cancer therapy.
Early Improvement of Acute Respiratory Distress Syndrome in Patients with COVID-19: Insights from the Data of ICU Patients in Chongqing, China
Authors: Zhan Zhu , Yang Xin , Du Hu , Zhang Chuanlai , Song Yuyan , Ran Xiaoyun , Zhang An , Yang Mei 
Published: July 2020

AbstractAcute respiratory distress syndrome (ARDS) may be the main cause of death in patients with coronavirus disease 2019 (COVID-19). Herein, we retrospect clinical features, outcomes and ARDS characteristics of 75 intensive care unit (ICU) patients with COVID-19 in Chongqing, China. We found a 5.3% case fatality rate of the ICU patients in Chongqing. 93% patients developed ARDS during the intensive care, and more than half were moderate. However, most of the patients (55%) supported with high flow nasal cannula (HFNC) oxygen therapy, but not mechanical ventilation. Nearly one third of patients with ARDS got an early improvement (eiARDS), and the rate is much higher than the other causes of ARDS in a previous study. Patients with eiARDS had a higher survival rate and lower length of ICU stay. The age (< 55 years) is an independent predictor for the eiARDS, and stratification of COVID-19 patients by age is recommended.
The amplified second outbreaks of global COVID-19 pandemic
Authors: Huang Jianping , Liu Xiaoyue , Zhang Li , Yang Kehu , Chen Yaolong , Huang Zhongwei , Liu Chuwei , Lian Xinbo , Wang Danfeng 
Published: July 2020

AbstractCOVID-19 is now in an epidemic phase, with a second outbreak likely to appear at any time. The intensity and timing of a second outbreak is a common concern worldwide. In this study, we made scenario projections of the potential second outbreak of COVID-19 using a statistical-epidemiology model, which considers both the impact of seasonal changes in meteorological elements and human social behaviors such as protests and city unblocking. Recent street protests in the United States and other countries are identified as a hidden trigger and amplifier of the second outbreak. The scale and intensity of subsequent COVID-19 outbreaks in the U.S. cities where the epidemic is under initial control are projected to be much greater than those of the first outbreak. For countries without reported protests, lifting the COVID-19 related restrictions prematurely would accelerate the spread of the disease and place mounting pressure on the local medical system that is already overloaded. We anticipate these projections will support public health planning and policymaking by governments and international organizations.
The impact of host resistance on cumulative mortality and the threshold of herd immunity for SARS-CoV-2
Authors: Lourenço José , Pinotti Francesco , Thompson Craig , Gupta Sunetra 
Published: July 2020

AbstractIt is widely believed that the herd immunity threshold (HIT) required to prevent a resurgence of SARS-CoV-2 is in excess of 50% for any epidemiological setting. Here, we demonstrate that HIT may be greatly reduced if a fraction of the population is unable to transmit the virus due to innate resistance or cross-protection from exposure to seasonal coronaviruses. The drop in HIT is proportional to the fraction of the population resistant only when that fraction is effectively segregated from the general population; however, when mixing is random, the drop in HIT is more precipitous. Significant reductions in expected mortality can also be observed in settings where a fraction of the population is resistant to infection. These results help to explain the large degree of regional variation observed in seroprevalence and cumulative deaths and suggest that sufficient herd-immunity may already be in place to substantially mitigate a potential second wave.
Moderate to vigorous physical activity and sedentary behavior change in self-isolating adults during the COVID-19 pandemic in Brazil: A cross-sectional survey exploring correlates
Authors: Schuch Felipe B. , Bulzing Rugero A. , Meyer Jacob , López-Sánchez Guillermo F. , Grabovac Igor , Willeit Peter , Vancampfort Davy , Caperchione Cristina M. , Sadarangani Kabir P. , Werneck André O. , Ward Philip B. , Tully Mark , Smith Lee 
Published: July 2020

AbstractBackgroundSelf-distancing measures imposed major changes in daily life. This study aimed to (i) evaluate the changes (pre-versus during pandemic) in time spent in moderate to vigorous physical activity (MVPA) and sedentary behavior (SB) in self-isolating Brazilians during the COVID-19 pandemic, and (ii) to explore correlates of MVPA and SB.MethodsA cross-sectional self-report online survey, evaluating the time spent in MVPA and SB pre and during the COVID-19 pandemic. Sociodemographic, behavioral, clinical, variables, and time in self-isolation were also obtained. Changes in MVPA and SB and their correlates were explored using generalized estimating equations (GEE).ResultsA total of 877 participants (72.7% women, 53.7% young adults [18-34 years]) were included. Overall, participants reported a 59.7% reduction (95%CI:35.6 to 82.2) in time spent on MVPA during the pandemic. Time spent in SB increased 42.0% (95%CI:31.7 to 52.5). Greater reductions in MVPA and/or increases in SB were seen in younger adults, those not married, those employed and those with a self-reported previous diagnosis of a mental disorder.ConclusionsPeople in self-isolation significantly reduced MVPA levels and increased SB. Public health strategies should be implemented during epidemic times to mitigate the impact of self-isolation on MVPA and SB, particularly in vulnerable groups.
Controlling COVID-19 via test-trace-quarantine
Authors: Kerr Cliff C. , Mistry Dina , Stuart Robyn M. , Rosenfeld Katherine , Hart Gregory R. , Núñez Rafael C. , Cohen Jamie A. , Selvaraj Prashanth , Abeysuriya Romesh G. , Jastrzębski Michał , George Lauren , Hagedorn Brittany , Panovska-Griffiths Jasmina , Fagalde Meaghan , Duchin Jeffrey , Famulare Michael , Klein Daniel J. 
Published: July 2020

AbstractInitial COVID-19 containment in the United States focused on limiting mobility, including school and workplace closures. However, these interventions have had enormous societal and economic costs. Here we demonstrate the feasibility of an alternative control strategy, test-trace-quarantine: routine testing of primarily symptomatic individuals, tracing and testing their known contacts, and placing their contacts in quarantine. We performed this analysis using Covasim, an open-source agent-based model, which was calibrated to detailed demographic, mobility, and epidemiological data for the Seattle region from January through June 2020. With current levels of mask use and schools remaining closed, we found that high but achievable levels of testing and tracing are sufficient to maintain epidemic control even under a return to full workplace and community mobility and with low vaccine coverage. The easing of mobility restrictions in June 2020 and subsequent scale-up of testing and tracing programs through September provided real-world validation of our predictions. Although we show that test-trace-quarantine can control the epidemic in both theory and practice, its success is contingent on high testing and tracing rates, high quarantine compliance, relatively short testing and tracing delays, and moderate to high mask use. Thus, in order for test-trace-quarantine to control transmission with a return to high mobility, strong performance in all aspects of the program is required.
Transcriptional response of the calcification and stress response toolkits in an octocoral under heat and pH stress
Authors: Vargas Sergio , Zimmer Thorsten , Conci Nicola , Lehmann Martin , Wörheide Gert 
Published: July 2020

AbstractUp to one-third of all described marine species inhabit coral reefs, but the future of these hyperdiverse ecosystems is insecure due to local and global threats, such as overfishing, eutrophication, ocean warming, and acidification. Although these impacts are expected to have a net detrimental effect on reefs, it has been shown that some organisms like octocorals may remain unaffected, or benefit from, anthropogenically induced environmental change, and may replace stony corals in future reefs. Despite their potential importance in future shallow-water coastal environments, the molecular mechanisms leading to the resilience to anthropogenic-induced stress observed in octocorals remain unknown. Here, we use manipulative experiments, proteomics, and transcriptomics to show that the molecular toolkit used by Pinnigorgia flava, a common Indo-Pacific gorgonian octocoral, to deposit its calcium-carbonate skeleton is resilient to heat and seawater acidification stress. Sublethal heat stress triggered a stress response in P. flava but did not affect the expression of 27 transcripts encoding Skeletal Organic Matrix (SOM) proteins. Exposure to seawater acidification did not cause a stress response but triggered the downregulation of many transcripts, including an osteonidogen homolog present in the SOM. The observed transcriptional decoupling of the skeletogenic and stress-response toolkits provides insights into the mechanisms of resilience to anthropogenically-driven environmental change observed in octocorals.
Definition and Signatures of Lung Fibroblast Populations in Development and Fibrosis in Mice and Men
Authors: Liu Xue , Rowan Simon C. , Liang Jiurong , Yao Changfu , Huang Guanling , Deng Nan , Xie Ting , Wu Di , Wang Yizhou , Burman Ankita , Parimon Tanyalak , Borok Zea , Chen Peter , Parks William C. , Hogaboam Cory M. , Weigt S. Samuel , Belperio John , Stripp Barry R. , Noble Paul W. , Jiang Dianhua 
Published: July 2020

AbstractThe heterogeneity of fibroblasts in the murine and human lung during homeostasis and disease is increasingly recognized. It remains unclear if the different phenotypes identified to date are characteristic of unique subpopulations with unique progenitors or whether they arise by a process of differentiation from common precursors. Our understanding of this ubiquitous cell type is limited by an absence of well validated, specific, markers with which to identify each cell type and a clear consensus on the distinct populations present in the lung. Here we describe single cell RNA sequencing (scRNA-seq) analysis on mesenchymal cells from the murine lung throughout embryonic (E) development (E9.5 – 17.5), at post-natal day (P1 – 15), as well as in the adult and the aged murine lungs before and after bleomycin-induced fibrosis. We carried out complementary scRNA-seq on human lung tissue from a P1 lung, a month 21 lung and lung tissue from healthy donors and patients with idiopathic pulmonary fibrosis (IPF). The murine and human data were supplemented with publicly available scRNA-seq datasets. We consistently identified lipofibroblasts, myofibroblasts, pericytes, mesothelial cells and smooth muscle cells. In addition, we identified a novel population delineated by Ebf1 (early B-cell factor 1) expression and an intermediate subtype. Comparative analysis with human mesenchymal cells revealed homologous mesenchymal subpopulations with remarkably conserved transcriptomic signatures. Comparative analysis of changes in gene expression in the fibroblast subpopulations from age matched non-fibrotic and fibrotic lungs in the mouse and human demonstrates that many of these subsets contribute to matrix gene expression in fibrotic conditions. Subtype selective transcription factors were identified and putative divergence of the clusters during development were delineated. Prospective isolation of these fibroblast subpopulations, localization of signature gene markers, and lineage-tracing each cluster are under way in the laboratory. This analysis will enhance our understanding of fibroblast heterogeneity in homeostasis and fibrotic disease conditions.
Identifying differences in gait adaptability across various speeds using movement synergy analysis
Authors: Ó’Reilly David , Federolf Peter 
Published: July 2020

AbstractIntroductionThe aim of this study was to identify movement synergies during normal-walking that can differentiate healthy adults in terms of gait adaptability at various speeds. To this end, the association between movement synergies and lower-limb coordination variability or Deviation Phase (DP) was investigated. A secondary aim of this study included an investigation into the moderating effect of these movement synergies on the relationship between DP and the smoothness of arm-swing motion quantified as the normalised jerk index (NJI).MethodA principal component analysis of whole-body marker trajectories from normal-walking treadmill trials at 0.8m/s, 1.2m/s and 1.6m/s was undertaken. Both DP and NJI were derived from approx. 8 minutes of perturbed-walking treadmill trials. Principal movement components, PMk, were derived and the RMS of the 2nd-order differentiation of these PMk(PAkRMS) were included as independent variables representing the magnitude of neuromuscular control in each PMk. The PAkRMS were input into separate maximal linear mixed-effects regression models to explain the variance in DP and (DP × NJI). A stepwise elimination of terms and comparison of models using Anova identified optimal models for both aims.ResultsAmong the first 7 validated PMk, PA4RMS (double-support phase) was identified as an optimal model and demonstrated a significant negative effect on DP however this effect may differ considerably across walking-speeds. An optimal model for describing the variance in (DP × NJI) included a fixed-effect of PA6RMS (Left – Right side weight transfer). Within-participant clustering was prevalent within both optimal models.InterpretationThe hypotheses that individuals who exhibited greater control on specific kinematic synergies would exhibit variations during perturbed walking was substantiated. Supporting evidence for the role of movement synergies during the double-support phase of gait in proactively correcting balance was presented. The potential influence of leg dominance on gait adaptability was also discussed. Future studies should investigate further the role of walking-speed and leg dominance on movement synergies and look to generalize these findings to patient populations.HighlightsBaseline movement synergies representing terminal-swing and double-support phases of gait were found to have significant negative effects on lower-limb coordination variability during perturbed-walking trials at various speeds.Movement synergies related to the double-support phase and weight transfer events of gait were determined to have a negative moderating effect on the translation of lower-limb coordination variability into upper-limb postural corrections.Evidence was presented for the important role of the double-stance phase of gait in gait adaptability while leg dominance was shown to play a potential role in differentiating healthy adults in this study.
Actin and an unconventional myosin motor, TgMyoF control the organization and dynamics of the endomembrane network inToxoplasma gondii
Authors: Carmeille Romain , Heaslip Aoife T. 
Published: July 2020

AbstractToxoplasma gondiiis an obligate intracellular parasite that relies on three distinct secretory organelles, the micronemes, rhoptries and dense granules, for parasite survival and disease pathogenesis. Secretory proteins destined for these organelles are synthesized in the endoplasmic reticulum (ER) and sequentially trafficked through a highly polarized endomembrane network that consists of the Golgi and multiple post-Golgi compartments. Currently, little is known about how the parasite cytoskeleton controls the positioning of the organelles in this pathway, or how vesicular cargo is trafficked between organelles. Here we show that F-actin and an unconventional myosin motor, TgMyoF, control the dynamics and organization of the organelles in the secretory pathway, specifically ER tubule movement, apical positioning of the Golgi and post-Golgi compartments, apical positioning of the rhoptries and finally, the directed transport of Rab6-positive and Rop1-positive vesicles. Thus, this study identifies TgMyoF and actin as the key cytoskeletal components that organize the endomembrane system inT. gondii.Author SummaryEndomembrane trafficking is a vital cellular process in all eukaryotic cells. In most cases the molecular motors myosin, kinesin and dynein transport cargo including vesicles, organelles and transcripts along actin and microtubule filaments in a manner analogous to a train moving on its tracks. For the unicellular eukaryoteToxoplasma gondii, the accurate trafficking of proteins through the endomembrane system is vital for parasite survival and pathogenicity. However, the mechanisms of cargo transport in this parasite are poorly understood. In this study, we fluorescently labeled multiple endomembrane organelles and imaged their movements using live cell microscopy. We demonstrate that filamentous actin and an unconventional myosin motor named TgMyoF control both the positioning of organelles in this pathway and the movement of transport vesicles throughout the parasite cytosol. This data provides new insight into the mechanisms of cargo transport in this important pathogen and expands are understanding of the biological roles of actin in the intracellular phase of the parasite’s growth cycle.