bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscle-directed mechanosensory feedback activates egg-laying circuit activity and behavior inC. elegans
Authors: Medrano Emmanuel , Collins Kevin M. 
Published: July 2022

SummaryMechanosensory feedback of internal reproductive state drives decisions about when and where to reproduce.1For instance, stretch in theDrosophilareproductive tract produced by artificial distention or from accumulated eggs regulates the attraction to acetic acid to ensure optimal oviposition.2How such mechanosensory feedback modulates neural circuits to coordinate reproductive behaviors is incompletely understood. We previously identified a stretch-dependent homeostat that regulates egg laying inCaenorhabditis elegans. Sterilized animals lacking eggs show reduced Ca2+transient activity in the presynaptic HSN command motoneurons that drive egg-laying behavior while animals forced to accumulate extra eggs show dramatically increased circuit activity that restores egg laying.3Interestingly, genetic ablation or electrical silencing of the HSNs delays, but does not abolish, the onset of egg laying3–5with animals recovering vulval muscle Ca2+transient activity upon egg accumulation.6Using an acute gonad microinjection technique to mimic changes in pressure and stretch resulting from germline activity and egg accumulation, we find that injection rapidly stimulates Ca2+activity in both neurons and muscles of the egg-laying circuit. Injection-induced vulval muscle Ca2+activity requires L-type Ca2+channels but is independent of presynaptic input. Conversely, injection-induced neural activity is disrupted in mutants lacking the vulval muscles, suggesting ‘bottom-up’ feedback from muscles to neurons. Direct mechanical prodding activates the vulval muscles, suggesting they are the proximal targets of the stretch-dependent stimulus. Our results show that egg-laying behavior inC. elegansis regulated by a stretch-dependent homeostat that scales postsynaptic muscle responses with egg accumulation in the uterus.
The Piks allele of the NLR immune receptor Pik breaks the recognition of AvrPik effectors of the rice blast fungus
Authors: Xiao Gui , Wang Wenjuan , Liu Muxing , Li Ya , Liu Jianbin , Franceschetti Marina , Yi Zhaofeng , Zhu Xiaoyuan , Zhang Zhengguang , Lu Guodong , Banfield Mark J. , Wu Jun , Zhou Bo 
Published: July 2022

AbstractArms race co-evolution of plant-pathogen interactions evolved sophisticated recognition mechanisms between host immune receptors and pathogen effectors. Different allelic haplotypes of an immune receptor in host mount distinct recognition against sequence or non-sequence related effectors in pathogens. We report the molecular characterization of the Piks allele of the rice immune receptor Pik against rice blast pathogen, which requires two head-to-head arrayed nucleotide binding site and leucine-rich repeat proteins. Like other Pik genes, both Piks-1 and Piks-2 are necessary and sufficient for Piks-mediated resistance. However, unlike other Pik alleles, Piks does not recognize any known AvrPik variants of M. oryzae. Sequence analysis of the genome of an avirulent isolate V86010 further revealed that its cognate avirulence (Avr) gene most likely has no significant sequence similarity to known AvrPik variants. We conclude that Piks breaks the canonical Pik/AvrPik recognition pattern. Piks-1 and Pikm-1 have only two amino acid differences within the integrated heavy metal-associated (HMA) domain. Pikm-1-HMA interact with AvrPik-A, -D and -E in vitro and in vivo, whereas Piks-1-HMA does not bind any AvrPik variants. Reciprocal exchanges of single amino acid residues between Piks-1 and Pikm-1 further reveal a dynamic recognition mechanism between Piks/Pikm alleles and their respective effectors. Piks-1E229Q/Pikm-1V261A can only activate immunity to AvrPik-D but not to other effectors, indicating that the amino acid change of E to Q at position 229 leads to its gain of a partial recognition spectrum of Pikm. By contrast, Piks-1A261V/Pikm-1Q229E confers immunity to the Piks cognate effector, indicating that the amino acid change of Q to E at position 229 leads to its shifts of the recognition from Pikm to Piks. Intriguingly, binding activities in both Y2H and analytical gel filtration assays are illustrated between Piks-1A261V/Pikm-1Q229E and AvrPik-D. However, it is unable to mount immunity against AvrPik-D, suggesting that biochemical activities based on in vitro and in vivo assays could be insufficient for sustaining biological function of receptor and effector pairs.
Improved Cladocopium goreaui genome assembly reveals features of a facultative coral symbiont and the complex evolutionary history of dinoflagellate genes
Authors: Chen Yibi , Shah Sarah , Dougan Katherine E. , van Oppen Madeleine J. H. , Bhattacharya Debashish , Chan Cheong Xin 
Published: July 2022

AbstractDinoflagellates of the family Symbiodiniaceae are crucial photosymbionts in corals and other marine organisms. Of these algae, Cladocopium goreaui is one of the most dominant symbiont species in the Indo-Pacific. Here, we present an improved genome assembly of C. goreaui combining new long-read sequence data with earlier generated short-read data. Incorporating new full-length transcripts to guide gene prediction, the C. goreaui genome (1.2 Gb) exhibits a high extent of completeness (82.4% based on BUSCO protein recovery) and better resolution of repetitive sequence regions; 45,322 gene models were predicted, and 327 putative, topologically associated domains of the chromosomes were identified. Comparison with other Symbiodiniaceae genomes revealed a prevalence of repeats and duplicated genes in C. goreaui, and lineage-specific genes indicating functional innovation. Incorporating 2,841,408 protein sequences from 96 broadly sampled eukaryotes and representative prokaryotes in a phylogenomic approach, we assessed the evolutionary history of C. goreaui genes. Of the 5,246 phylogenetic trees inferred from homologous protein sets containing two or more phyla, 35-36% have putatively originated via horizontal gene transfer (HGT), predominantly (19-23%) via an ancestral Archaeplastida lineage implicated in the endosymbiotic origin of plastids: 10-11% are of green algal origin, including genes encoding photosynthetic functions. Our results demonstrate the utility of long-read sequence data in resolving structural features of a dinoflagellate genome and highlight how genetic transfer has shaped genome evolution of a facultative symbiont, and more broadly of dinoflagellates.
High dimensional flow cytometric analysis reveals distinct NK cell subsets but conserved response to cytokine stimulation in umbilical cord blood and adult peripheral blood
Authors: Buckle Irina , Weinert Vicky , Sester David P. , Radford Kristen , Guillerey Camille 
Published: July 2022

AbstractAdoptive cellular therapies using Natural Killer (NK) cells are of growing interest. NK cells can be obtained from various sources, including umbilical cord blood (UCB) and adult peripheral blood (APB). Understanding the diversity of NK cell populations and their receptor expression in both UCB and APB will guide future therapeutic designs. In this study, we used a 20-colour flow cytometry panel to compare unstimulated and cytokine-activated UCB and APB NK cells. Our analysis showed that UCB NK cells express slightly higher levels of the immune checkpoints PD-1, TIGIT and CD96 compared to their APB counterparts. Unsupervised hierarchical clustering and principal component analyses revealed previously unappreciated differences in NK cell populations from UCB and APB. UCB was characterised by an enrichment in CD56negas well as mature NKp46negand CD56+CD16+NK cell populations whereas CD57+terminally differentiated NK cells with variable expression of KIRs and CD16 were found in APB. These populations were conserved following two-days of IL-15 culture as well as overnight stimulation with IL-12, IL-15, and IL-18. Interestingly, cytokine stimulation was associated with the up-regulation of LAG-3 and DNAM-1 together with the downregulation of NKG2D, TIGIT and CD16 on multiple NK cell subsets in both UCB and APB. TIM-3 was also up-regulated with activation, but only in UCB. Overall, our data indicate that NK cells in UCB have a more immature phenotype than APB NK cells and UCB NK cells might be more amenable to immune checkpoint therapy.
Risk factors for severe COVID-19 among HIV-infected and-uninfected individuals in South Africa, April 2020- March 2022 – data from sentinel surveillance
Authors: Walaza Sibongile , Tempia Stefano , von Gottberg Anne , Wolter Nicole , Bhiman Jinal N. , Buys Amelia , Amoako Daniel , Moosa Fahima , Plessis Mignon du , Moyes Jocelyn , McMorrow Meredith L. , Dawood Halima , Variava Ebrahim , Reubenson Gary , Nel Jeremy , Zar Heather J , Makhasi Mvuyo , Meiring Susan , Quan Vanessa , Cohen Cheryl 
Published: July 2022

AbstractBackgroundData on risk factors for COVID-19-associated hospitalisation and mortality in high HIV prevalence settings are limited.MethodsUsing existing syndromic surveillance programs for influenza-like-illness and severe respiratory illness at sentinel sites in South Africa, we identified factors associated with COVID-19 hospitalisation and mortality.ResultsFrom April 2020 through March 2022, SARS-CoV-2 was detected in 24.0% (660/2746) of outpatient and 32.5% (2282/7025) of inpatient cases. Factors associated with COVID-19-associated hospitalisation included: older age (25-44 [adjusted odds ratio (aOR) 1.8, 95% confidence interval (CI) 1.1-2.9], 45-64 [aOR 6.8, 95%CI 4.2-11.0] and ≥65 years [aOR 26.6, 95%CI 14.4-49.1] vs 15-24 years); black race (aOR 3.3, 95%CI 2.2-5.0); obesity (aOR 2.3, 95%CI 1.4-3.9); asthma (aOR 3.5, 95%CI 1.4-8.9); diabetes mellitus (aOR 5.3, 95%CI 3.1-9.3); HIV with CD4 ≥200/mm3 (aOR 1.5, 95%CI 1.1-2.2) and CD4<200/mm3 (aOR 10.5, 95%CI 5.1-21.6) or tuberculosis (aOR 12.8, 95%CI 2.8-58.5). Infection with Beta (aOR 0.5, 95%CI 0.3-0.7) vs Delta variant and being fully vaccinated (aOR 0.1, 95%CI 0.1-0.3) were less associated with COVID-19 hospitalisation.In-hospital mortality was increased in older age (45-64 years [aOR 2.2, 95%CI 1.6-3.2] and ≥65 years [aOR 4.0, 95%CI 2.8-5.8] vs 25-44 years) and male sex (aOR1.3, 95%CI 1.0-1.6) and was lower in Omicron -infected (aOR 0.3, 95%CI 0.2-0.6) vs Delta-infected individuals.ConclusionActive syndromic surveillance encompassing clinical, laboratory and genomic data identified setting-specific risk factors associated with COVID-19 severity that will inform prioritization of COVID-19 vaccine distribution. Elderly, people with tuberculosis or people living with HIV, especially severely immunosuppressed should be prioritised for vaccination.Summary of article’s viewpointCompared to the Delta variant, the Omicron variant was associated with reduced risk of mortality and Beta associated with decreased risk of hospitalisation. Active syndromic surveillance combining clinical, laboratory and genomic data can be used to describe the epidemic timing, epidemiological characteristics of cases, early detection of variants of concern and how these impact disease severity and outcomes; and presents a viable surveillance approach in settings where national surveillance is not possible.
The use of artificial intelligence and machine learning methods in first trimester pre-eclampsia screening: a systematic review protocol
Authors: Hedley Paula L. , Hagen Christian M. , Wilstrup Casper , Christiansen Michael 
Published: July 2022

AbstractIntroductionPre-eclampsia (PE) is a leading cause of perinatal morbidity and mortality worldwide. Low-dose aspirin can prevent PE in high risk pregnancies if started early. However, despite intense research into the area, first-trimester screening for PE risk is still not a routine part of pregnancy care. Several studies have described the application of artificial intelligence (AI) and machine learning (ML) in risk prediction of PE and its subtypes. A systematic review of available literature is necessary to catalogue the current applications of AI/ML methods in early pregnancy screening for PE, in order to better inform the development of clinically relevant risk prediction algorithms which will enable timely intervention and the development of new treatment strategies. The aim of this systematic review is to identify and assess studies regarding the application of AI/ML methods in first-trimester screening for PE.MethodsA systematic review of peer-reviewed as well as the grey literature cohort or case-control studies will be conducted. Relevant information will be accessed from the following databases; PubMed, Google Scholar, Web of Science, Arxiv, BioRxiv, and MedRxiv. The studies will be evaluated by two reviewers in a parallel, blind assessment of the literature, a third reviewer will assess any studies in which the first two reviewers did not agree. The free online tool Rayyan, will be used in this literature assessment stage. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist will be used to guide the review process and the methods of the studies will be assessed using the Newcastle-Ottawa scale. Narrative synthesis will be conducted for all included studies. Meta-analysis will also be conducted where data quality and availability allow.Ethics and disseminationThe review will not require ethical approval and the findings will be published in a peer-reviewed journal using the PRISMA guidelines.
Generation of cardiomyocytes from human induced pluripotent stem cells resembling atrial cells with ability to respond to adrenoceptor agonists
Authors: Ahmad Faizzan S. , Jin Yongcheng , Grassam-Rowe Alexander , Zhou Yafei , Yuan Meng , Fan Xuehui , Zhou Rui , Mu-u-min Razik , O’Shea Christopher , Ibrahim Ayman M. , Hyder Wajiha , Aguib Yasmine , Yacoub Magdi , Pavlovic Davor , Zhang Yanmin , Tan Xiaoqiu , Terrar Derek A. , Lei Ming 
Published: July 2022

ABSTRACTCardiovascular disease is the leading cause of global mortality and morbidity. Cardiac dysrhythmias contribute significantly to this disease burden. Atrial fibrillation (AF) is the most common chronic dysrhythmia. Human induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-AMs) present an exciting new model for AF but currently fail to reach maturity and so are limited in translational potential currently. We report a new approach using a combination of Gremlin 2 and retinoic acid treatment of human iPSCs for generating cardiomyocytes resembling atrial cells. More than 40% of myocytes generated by this approach showed rod-shaped morphology, expression of cardiomyocyte proteins (including RyR2 receptors, a-actinin-2, F-actin) and typically a striated appearance, all of which were broadly similar to the characteristics of adult atrial myocytes. Isolated myocytes were electrically quiescent until stimulated to fire action potentials with an atrial myocyte profile and an amplitude of approximately 100 mV, arising from a resting potential of approximately −70 mV. Single-cell RNA sequence (scRNASeq) analysis showed a high level of expression of several atrial specific transcripts including NPPA, MYL7, HOXA3, SLN, KCNJ4, KCNJ5 and KCNA5. Amplitudes of calcium transients recorded from spontaneously beating cultures were increased by the stimulation of α-adrenoceptors (activated by phenylephrine and blocked by prazosin) or β-adrenoceptors (activated by isoproterenol and blocked by CGP20712A). Thus, our new method provides an efficient approach for differentiating human atrial myocytes with mature characteristics from hiPSCs. This preparation will be very useful for studying signalling pathways in human atrial myocytes, and provides a valuable model for investigating atrial fibrillation and drug discovery.
When mechanical engineering inspired from physiology improves postural-related somatosensory processes
Authors: Sutter Chloé , Fabre Marie , Massi Francesco , Blouin Jean , Mouchnino Laurence 
Published: July 2022

ABSTRACTBeing the first stimulated by the relative movement of foot skin and the underneath moving support surface, the plantar tactile receptors (i.e., mechanoreceptors) play an important role in the sensorimotor transformation giving rise to a postural reaction. In this light, a biomimetic surface, i.e., complying with the characteristics of the mechanoreceptors and the skin dermatoglyphs (i.e., pattern of the ridges) should facilitate the cortical processes in response to the somatosensory stimulation involved in the balance recovery motor control. Healthy young adults (n = 21) were standing still either on a biomimetic surface or on two control surfaces (i.e., grooved or smooth), when a sudden but low acceleration of the supporting surface along the lateral direction was triggered. A shorter and more robust evoked somatosensory response (i.e., SEP) was observed when participants were standing on the biomimetic surface. As well, a lower oscillatory response in the theta (5-7 Hz) time-frequency domain in the left posterior parietal cortex (PPC) was observed with the biomimetic surface. The greater shear forces induced by the interaction between the feet and the biomimetic surface during the platform motion was likely at the origin of the increased SEP. Besides, the decrease of theta power suggests that the balance task became less challenging. This interpretation was tested in a second experiment by adding a cognitive task, which should be less detrimental for the postural reaction when standing on a biomimetic surface. Consistent with this hypothesis, a more efficient postural reaction (i.e., shorter latency and greater amplitude) was observed when the cognitive task was performed while standing on the biomimetic surface.
Full epistatic interaction maps retrieve part of missing heritability and improve phenotypic prediction
Authors: Carré Clément , Carluer Jean Baptiste , Chaux Christian , Roche Nicolas , Mas André , Krouk Gabriel 
Published: July 2022

AbstractThe first Genome Wide Association Studies (GWAS) shed light on the concept of missing heritability. It constitutes a mystery with transcending consequences from plant to human genetics. This mystery lies in the fact that a large proportion of phenotypes are not explained by unique or simple genomic modifications. One has to invoke genetic interactions among different loci, also known as epistasis, to partly account for it. However, current GWAS statistical models are moderately scalable, very sensitive to False Discovery Rate (FDR) corrections and, even combined with High Performance Computing (HPC), they can take years to evaluate for a full combinatorial epistatic space for a single phenotype. Here we propose a modeling approach, named Next-Gen GWAS (NGG) that evaluates, within hours, >60 billions of single nucleotide polymorphism (SNP) combinatorial first-order interactions, on a reasonable computer power. We first benchmark NGG on state of the art GWAS model results, and applied this toArabidopsis thalianaproviding 2D epistatic maps at gene resolution. We demonstrate on several phenotypes that a large proportion of the missing heritability can i) be retrieved with this modeling approach, ii) indeed lies in epistatic interactions and iii) can be used to improve phenotype prediction.
Ageing disrupts MANF-mediated immune modulation during skeletal muscle regeneration
Authors: Sousa Neuza S. , Brás Margarida F. , Antunes Inês B. , Lindholm Päivi , Neves Joana , Sousa-Victor Pedro 
Published: July 2022

AbstractAge-related decline in skeletal muscle regenerative capacity is multifactorial, yet, the contribution of immune dysfunction to regenerative failure is unknown. Here, we uncover a new mechanism of immune modulation operating during skeletal muscle regeneration that is disrupted in aged animals and relies on the regulation of macrophage function. The immune modulator MANF is induced following muscle injury in young mice, but not in aged animals, and its expression is essential for regenerative success. Regenerative impairments in the aged muscle are associated with defects in the repair-associated myeloid response similar to those found in MANF-deficient models and could be improved through MANF delivery. We propose that restoring the myeloid response through immune modulation is a promising therapeutic strategy to improve the regenerative capacity of aged muscles.
The structure of arginyltransferase 1 (ATE1)
Authors: Van Verna , Ejimogu Nna-Emeka , Bui Toan S. , Smith Aaron T. 
Published: July 2022

AbstractEukaryotic post-translational arginylation, mediated by the family of enzymes known as the arginyltransferases (ATE1s), is an important post-translational modification that can alter protein function and even dictate cellular protein half-life. Multiple major biological pathways are linked to the fidelity of this process, including neural and cardiovascular developments, cell division, and even the stress response. Despite this significance, the structural, mechanistic, and regulatory mechanisms that govern ATE1 function remain enigmatic. To that end, we have used X-ray crystallography to solve the first crystal structure of ATE1 from Saccharomyces cerevisiae ATE1 (ScATE1) to 2.85 Å resolution. The three-dimensional structure of ScATE1 reveals a bilobed protein containing a GCN5-related N-acetyltransferase (GNAT) fold, and this crystalline behavior is faithfully recapitulated in solution based on size-exclusion chromatography-coupled small angle X-ray scattering (SEC-SAXS) analyses and cryo-EM 2D class averaging. Structural superpositions and electrostatic analyses indicate this domain as the location of catalytic activity and tRNA binding, and these comparisons strongly suggest a mechanism for post-translational arginylation. Additionally, our structure reveals the spatial connectivity of the N-terminal domain, which we have previously shown to bind a regulatory [Fe-S] cluster, and the enzymatic active site, hinting at the atomic-level details of the cluster’s regulatory influence. When taken together, these insights into the first structure of ATE1 bring us closer to answering pressing questions regarding the molecular-level mechanism of eukaryotic post-translational arginylation.
A Non-invasive, Biomarker Assay for Detecting Chronic Wasting Disease Pathology in White-tailed Deer
Authors: Bradley Robert D. , Roberts Emma K. , Worsham Asha E. , Ashton Megan N. , Wright Emily A. , Saleh Ned , Hardy Daniel M. 
Published: July 2022

ABSTRACTWe describe a blood test that exploits differences in the abundance of diagnostic miRNA biomarkers associated with prion infections in cervids. Using sera from 93 pen-raised white-tailed deer euthanized after unintentional exposure to Chronic Wasting Disease (CWD), quantification of candidate reference and diagnostic miRNAs revealed sensitivity of the q-RT-PCR method to interference from sample degradation, requiring exclusion of 60 specimens that exhibited excessive hemolysis or yielded poor amplification of reference or diagnostic miRNAs. Subsequent quantification of three potentially diagnostic and two control miRNAs in the 33 remaining, minimally degraded sera established diagnostic criteria congruent (100% sensitivity, 92.3% specificity, 93.9% accuracy) with results from standard CWD diagnosis by microscopic detection of immunoreactivity in obex and/or medial retropharyngeal lymph nodes (conducted by the National Veterinary Services Laboratory, NVSL, Ames, IA). Overall, the miRNA assay proved to be at least as accurate and sensitive as other CWD testing alternatives to immunohistochemical diagnosis, albeit supported by data from relatively few animals owing to the challenge of acquiring usable specimens from animals euthanized in a mass depopulation. Nevertheless, for sera acquired antemortem, this biomarker-based test may represent a useful new resource for managing spread of CWD that offers the advantages of being rapid, sensitive, non-invasive, and amenable to high throughput scaling.