bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optogenetic activation of muscle contractionin vivo
Authors: Ganji Elahe , Chan C. Savio , Ward Christopher W. , Killian Megan L. 
Published: July 2020

AbstractOptogenetics is an emerging alternative to traditional electrical stimulation to initiate action potentials in activatable cells both ex vivo and in vivo. Optogenetics has been commonly used in mammalian neurons and more recently, it has been adapted for activation of cardiomyocytes and skeletal muscle. Therefore, the aim of this study was to evaluate the stimulation feasibility and sustain isometric muscle contraction and limit decay for an extended period of time (1s), using non-invasive transdermal light activation of skeletal muscle (triceps surae) in vivo. We used inducible Cre recombination to target expression of Channelrhodopsin-2 (ChR2(H134R)-EYFP) in skeletal muscle (Acta1-Cre) in mice. Fluorescent imaging confirmed that ChR2 expression is localized in skeletal muscle and does not have specific expression in sciatic nerve branch, therefore, allowing for non-nerve mediated optical stimulation of skeletal muscle. We induced muscle contraction using transdermal exposure to blue light and selected 10Hz stimulation after controlled optimization experiments to sustain prolonged muscle contraction. Increasing the stimulation frequency from 10Hz to 40Hz increased the muscle contraction decay during prolonged 1s stimulation, highlighting frequency dependency and importance of membrane repolarization for effective light activation. Finally, we showed that optimized pulsed optogenetic stimulation of 10 Hz resulted in comparable ankle torque and contractile functionality to that of electrical stimulation. Our results demonstrate the feasibility and repeatability of non-invasive optogenetic stimulation of muscle in vivo and highlight optogenetic stimulation as a powerful tool for non-invasive in vivo direct activation of skeletal muscle.
Parallel evolution of UbiA superfamily proteins into aromaticO-prenyltransferases in plants
Authors: Munakata Ryosuke , Olry Alexandre , Takemura Tomoya , Tatsumi Kanade , Ichino Takuji , Villard Cloé , Kageyama Joji , Kurata Tetsuya , Nakayasu Masaru , Jacob Florence , Koeduka Takao , Yamamoto Hirobumi , Moriyoshi Eiko , Matsukawa Tetsuya , Grosjean Jeremy , Krieger Célia , Sugiyama Akifumi , Mizutani Masaharu , Bourgaud Frédéric , Hehn Alain , Yazaki Kazufumi 
Published: July 2020

AbstractPlants produce approximately 300 aromatic molecules enzymatically linked to prenyl side chains via C-O bonds. TheseO-prenylated aromatics have been found in taxonomically distant plant taxa as compounds beneficial or detrimental to human health, withO-prenyl moieties often playing crucial roles in their biological activities. To date, however, no plant gene encoding an aromaticO-prenyltransferase (O-PT) has been described. This study describes the isolation of an aromaticO-PT gene,CpPT1, belonging to the UbiA superfamily, from grapefruit (Citrus×paradisi,Rutaceae). This gene is responsible for the biosynthesis ofO-prenylated coumarin derivatives that alter drug pharmacokinetics in the human body. Another coumarinO-PT gene of the same protein family was identified inAngelica keiskei, an apiaceous medicinal plant containing pharmaceutically activeO-prenylated coumarins. Phylogenetic analysis of theseO-PTs suggested that aromaticO-prenylation activity evolved independently from the same ancestral gene in these distant plant taxa. These findings shed light on understanding the evolution of plant secondary metabolites via the UbiA superfamily.
Enhanced Neuronal Activity and Asynchronous Calcium Transients Revealed in a 3D Organoid Model of Alzheimer’s Disease
Authors: Yin Juan , VanDongen Antonius M. 
Published: July 2020

AbstractAdvances in the development of three-dimensional (3D) brain organoids maintainedin vitrohave provided excellent opportunities to study brain development and neurodegenerative disorders, including Alzheimer’s disease (AD). However, there remains a need to generate AD organoids bearing patient-specific genomic backgrounds that can functionally recapitulate key features observed in the AD patient’s brain. To address this need, we successfully generated cerebral organoids from human pluripotent stem cells (hPSCs) derived from a familial AD patient with a mutation in presenilin 2 (PSEN2). An isogenic control hPSC line was generated using CRISPR-Cas9 technology. Both organoids were characterized by analysing their morphology, Aβ42/Aβ40 ratio and functional neuronal network activity. It was found that AD organoids had a higher Aβ42/Aβ40 ratio, asynchronous calcium transients and enhanced neuronal hyperactivity, successfully recapitulating some aspects of AD pathology. Therefore, our study presents a promising organoid-based biosystem for the study of the pathophysiology of AD and a platform for drug development for neurodegenerative disorders.
Pharmacological class interventions for benzodiazepine withdrawal discontinuation: a meta-analysis
Authors: Fluyau Dimy , Revadigar Neelambika , Mitra Paroma , Pierre Christopher G. 
Published: July 2020

AbstractBackgroundLong-term benzodiazepine (BZD) use may lead to dependence, addiction, and neuropsychiatric disturbances. BZD discontinuation can cause severe withdrawal symptoms and resurgence of premorbid conditions. There are guidelines on how to stop BZD if it is necessary.Pharmacological management is an option among several other recommendations, but its benefit remains unclear. This study investigates whether certain pharmacological classes can manage or facilitate BZD withdrawal beyond BZD itself.MethodsData collected from (1985 to 2018) in Google Scholar, Medline Ovid, Scopus, PsychInfo, ClinicalTrials.gov, Cochrane Review Database, Embase, Scopus, Pubmed, and Proquest databases: involved controlled clinical trials on drugs studied for BZD withdrawal discontinuation. Single drugs were clustered into their pharmacological class (domain). The Oxford Quality Scoring System assessed the quality of a trial. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) was used for clinical practice recommendations. For publication bias, we visually inspected the Funnel plot. We adopted the Cochrane Risk of Bias Tool to assess biases inherent to individual trials. The standardized mean difference measured the magnitude of the benefit of a pharmacological class.ResultsWe analyzed forty-nine controlled trials of 2815 assigned participants. Of fourteen classes, the BZD receptor antagonist class (d 0.671, CI 0.199 -1.143, p=0.005, I2=0),5-HT1A receptor partial agonist, and the glutamate class seemed to have the potentiality to manage BZD withdrawal discontinuation clinically. Around 61 % of the trials received an Oxford Quality score of three, 86% of the trials were granted a GRADE recommendation low. About 29 trials were at low risk of bias in general.ConclusionsEven though we could not prove that the pharmacological classes of drugs we analyzed for the clinical management of BZD withdrawal discontinuation were efficacious, our investigation showed that some of these classes have the potentiality to manage BZD withdrawal discontinuation and clinically facilitate the process when it is necessary, relevant, and recommended based on established guidelines. Further investigations are warranted to support our findings.
Variation of the vaginal microbiome during and after pregnancy in Chinese women
Authors: Zhang Xiaoai , Zhai Qingzhi , Wang Jinfeng , Ma Xiuling , Xing Bo , Fan Hang , Gao Zhiying , Zhao Fangqing , Liu Wei 
Published: July 2020

AbstractA more complete profiling of vaginal microbial communities and their variability enables a more accurate description of women microbiome. However, there is a distinct lack of information regarding the Chinese women. Composition of the vaginal microbiota during pregnancy and 6 weeks postpartum of 454 Chinese women thus was characterized in this study by sequencing V3-V4 regions of the 16S ribosomal RNA (rRNA). It showed that the vaginal microbiome varied during pregnancy and postpartum in response to abortion history, hypertensive disorders (HBP), delivery mode and maternal age. Co-variation of 21 bacterial taxa, including Lactobacillus and two of its species, may account for the common characteristics of vaginal microbiome under different medical histories and pregnancy outcomes. On the contrary, discriminant bacteria were significantly different between premature rupture of membranes related preterm birth (PROM-PTB) and non-PROM related PTB, and community state type (CST) I without any predominant Lactobacillus species in microbiota was more prevalent during pregnancy in PROM-PTB, suggesting that specific bacteria could be considered to distinguish different types of PTB. Through adding the data from Chinese women, the study will enrich the knowledge of human microbiome and likewise contribute to a better understanding of the association between the vaginal microbiome and reproductive health.
The everyday acoustic environment and its association with human heart rate: evidence from real-world data logging with hearing aids and wearables
Authors: Christensen Jeppe H. , Saunders Gabrielle H. , Porsbo Michael , Pontoppidan Niels H. 
Published: July 2020

AbstractWe investigate the short-term association between multidimensional acoustic characteristics of everyday ambient sound and continuous mean heart rate. We used in-market data from hearing aid users who logged ambient acoustics via smartphone-connected hearing aids and continuous mean heart rate in five-minute intervals from their own wearables.We find that acoustic characteristics explain approximately 4% of the fluctuation in mean heart rate throughout the day. Specifically, increases in ambient sound pressure intensity are significantly related to increases in mean heart rate, corroborating prior laboratory and short-term real-world data. In addition, increases in ambient sound quality - that is, more favourable signal to noise ratios – are associated with decreases in mean heart rate.Our findings document a previously unrecognized mixed influence of everyday sounds on cardiovascular stress, and that the relationship is more complex than is seen from examination of sound intensity alone. Thus, our findings highlight the relevance of ambient environmental sound in models of human ecophysiology.
The anxiety and ethanol intake controlling GAL5.1 enhancer is epigenetically modulated by, and controls preference for, high fat diet
Authors: McEwan Andrew , Erickson Johanna Celene , Davidson Connor , Heijkoop Jenny , Turnbull Yvonne , Delibegovic Mirela , Murgatroyd Chris , MacKenzie Alasdair 
Published: July 2020

AbstractExcess maternal fat intake and obesity increase offspring susceptibility to conditions such as chronic anxiety and substance abuse. We hypothesised that these susceptibilities are established through environmentally modulated DNA-methylation (5mC/5hmC) changes in regions of the genome that modulate mood and consumptive behaviours. We explored the effects of environmental factors on 5mC/5hmC levels within the GAL5.1 enhancer that controls anxiety-related behaviours and alcohol intake. We first observed that 5mC/5hmC levels within the GAL5.1 enhancer differed significantly in different parts of the brain. Moreover, we noted that early life stress had no significant effect of 5mC/5hmC levels within GAL5.1. By contrast, we identified that allowing access of pregnant mothers to high-fat diet (>60% calories from fat) had a significant effect on 5mC/5hmC levels within GAL5.1 in hypothalamus and amygdala of resulting male offspring. Cell transfection based studies using GAL5.1 reporter plasmids showed that 5mC has a significant repressive effect on GAL5.1 activity and its response to known stimuli such as EGR1 expression and PKC agonism. Intriguingly, CRISPR driven disruption of GAL5.1 from the mouse genome, although having negligible effects on metabolism, significantly decreased intake of high fat diet suggesting that GAL5.1, in addition to being epigenetically modulated by high-fat diet, also actively contributes to the consumption of high-fat diet suggesting its involvement in an environmentally-influenced regulatory-loop. Furthermore, considering that GAL5.1 also controls alcohol preference and anxiety these studies may provide a first glimpse into an epigenetically controlled mechanism that links maternal high-fat diet with transgenerational susceptibility to alcohol abuse and anxiety.
Active Strategies for Multisensory Conflict Suppression in the Virtual Hand Illusion
Authors: Lanillos Pablo , Franklin Sae , Maselli Antonella , Franklin David W. 
Published: July 2020

AbstractThe perception of our body in space is flexible and manipulable. The predictive brain hypothesis explains this malleability as a consequence of the interplay between incoming sensory information and our body expectations. However, given the interaction between perception and action, we might also expect that actions would arise due to prediction errors, especially in conflicting situations. Here we describe a computational model, based on the free-energy principle, that forecasts involuntary movements in sensorimotor conflicts. We experimentally confirm those predictions in humans using a virtual reality rubber-hand illusion. Participants generated movements (forces) towards the virtual hand, regardless of its location with respect to the real arm, with little to no forces produced when the virtual hand overlaid their physical hand. The congruency of our model predictions and human observations indicates that the brain-body is generating actions to reduce the prediction error between the expected arm location and the new visual arm. This observed unconscious mechanism is an empirical validation of the perception-action duality in body adaptation to uncertain situations and evidence of the active component of predictive processing.
Phylogenetically conserved peritoneal fibrosis response to an immunologic adjuvant in ray-finned fishes
Authors: Vrtílek Milan , Bolnick Daniel I. 
Published: July 2020

ABSTRACTAntagonistic interactions between hosts and parasites may drive the evolution of novel host defenses, or new parasite strategies. Host immunity is therefore one of the fastest evolving traits. But where do the novel immune traits come from? Here, we test for phylogenetic conservation in a rapidly evolving immune trait – peritoneal fibrosis. Peritoneal fibrosis is a costly defense against novel specialist tapewormSchistocephalussolidus (Cestoda) expressed in some freshwater populations of threespine stickleback fish (Gasterosteus aculeatus, Perciformes). We asked whether stickleback fibrosis is a derived species-specific trait or an ancestral immune response that was widely distributed across ray-finned fish (Actinopterygii) only to be employed by threespine stickleback against the specialist parasite. We combined literature review on peritoneal fibrosis with a comparative experiment using either parasite-specific, or non-specific, immune challenge in deliberately selected species across fish tree of life. We show that ray-finned fish are broadly, but not universally, able to induce peritoneal fibrosis when challenged with a generic stimulus (Alum adjuvant). The experimental species were, however, largely indifferent to the tapeworm antigen homogenate. Peritoneal fibrosis, thus, appears to be a common and deeply conserved fish immune response that was co-opted by stickleback to adapt to a new selective challenge.
Single-cell morphometrics reveals ancestral principles of notochord development
Authors: Andrews Toby G R , Pönisch Wolfram , Paluch Ewa , Steventon Benjamin J , Benito-Gutierrez Elia 
Published: July 2020

ABSTRACTDuring development, embryonic tissues are formed by the dynamic behaviours of their constituent cells, whose collective actions are tightly regulated in space and time. To understand such cell behaviours and how they have evolved, it is necessary to develop quantitative approaches to map out morphogenesis, so comparisons can be made across different tissues and organisms. With this idea in mind, here we sought to investigate ancestral principles of notochord development, by building a quantitative portrait of notochord morphogenesis in the amphioxus embryo – a basally-branching member of the chordate phylum. To this end, we developed a single-cell morphometrics pipeline to comprehensively catalogue the morphologies of thousands of notochord cells, and to project them simultaneously into a common mathematical space termed morphospace. This approach revealed complex patterns of cell-type specific shape trajectories, akin to those obtained using single-cell genomic approaches. By spatially mapping single-cell shape trajectories in whole segmented notochords, we found evidence of spatial and temporal variation in developmental dynamics. Such variations included temporal gradients of morphogenesis spread across the anterior-posterior axis, divergence of trajectories to different morphologies, and the convergence of different trajectories onto common morphologies. Through geometric modelling, we also identified an antagonistic relationship between cell shape regulation and growth that enables convergent extension to occur in two steps. First, by allowing growth to counterbalance loss of anterior-posterior cell length during cell intercalation. Secondly, by allowing growth to further increase cell length once cells have intercalated and aligned to the axial midline, thereby facilitating a second phase of tissue elongation. Finally, we show that apart from a complex coordination of individual cellular behaviours, posterior addition from proliferating progenitors is essential for full notochord elongation in amphioxus, a mechanism previously described only in vertebrates. This novel approach to quantifying morphogenesis paves the way towards comparative studies, and mechanistic explanations for the emergence of form over developmental and evolutionary time scales.
Assessment of SARS-CoV-2 Specific CD4(+) and CD8 (+) T Cell Responses Using MHC Class I and II Tetramers
Authors: Poluektov Yuri , Daftarian Pirouz , Delcommenne Marc C. 
Published: July 2020

AbstractThe success of SARS-CoV-2 (CoV-2) vaccines is measured by their ability to mount immune memory responses that are long-lasting. To achieve this goal, it is important to identify surrogates of immune protection, namely, CoV-2 MHC Class I and II immunodominant pieces/epitopes and methodologies to measure them. Here, we present results of flow cytometry-based MHC Class I and II QuickSwitch™ platforms for assessing SARS-CoV-2 peptide binding affinities to various human alleles as well as the H-2 Kb mouse allele. Multiple SARS-CoV-2 potential MHC binders were screened and validated by QuickSwitch testing. While several predicted peptides with acceptable theoretical Kd showed poor MHC occupancies, fourteen MHC class II and a few MHC class I peptides showed promiscuity in that they bind with multiple MHC molecule types. With the peptide exchange generated MHC tetramers, scientists can assess CD4+ and CD8+ immune responses to these different MHC/peptide complexes. Results obtained with several SARS-CoV-2 MHC class I and II peptides are included and discussed.
Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients
Authors: Elshazli Rami M. , Toraih Eman A , Elgaml Abdelaziz , El-Mowafy Mohammed , El-Mesery Mohamed , Amin Mohamed Nasreldien , Hussein Mohammad H , Killackey Mary T. , Fawzy Manal S , Kandil Emad 
Published: July 2020

AbstractObjectiveEvidence-based characterization of the diagnostic and prognostic value of the hematological and immunological markers related to the epidemic of Coronavirus Disease 2019 (COVID-19) is critical to understand the clinical course of the infection and to assess in development and validation of biomarkers.MethodsBased on systematic search in Web of Science, PubMed, Scopus, and Science Direct up to April 22, 2020, a total of 52 eligible articles with 6,320 laboratory-confirmed COVID-19 cohorts were included. Pairwise comparison between severeversusmild disease, Intensive Care Unit (ICU)versusgeneral ward admission, and expiredversussurvivors were performed for 36 laboratory parameters. The pooled standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using the DerSimonian Laird method/random effects model and converted to Odds ratio (OR). The decision tree algorithm was employed to identify the key risk factor(s) attributed to severe COVID-19 disease.ResultsCohorts with elevated levels of white blood cells (WBCs) (OR=1.75), neutrophil count (OR=2.62), D-dimer (OR=3.97), prolonged prothrombin time (PT) (OR=1.82), fibrinogen (OR=3.14), erythrocyte sedimentation rate (OR=1.60), procalcitonin (OR=4.76), IL-6 (OR=2.10), and IL-10 (OR=4.93) had higher odds of progression to severe phenotype. Decision tree model (sensitivity=100%, specificity=81%) showed the high performance of neutrophil count at a cut-off value of more than 3.74□x109/L for identifying patients at high risk of severe COVID□19. Likewise, ICU admission was associated with higher levels of WBCs (OR=5.21), neutrophils (OR=6.25), D-dimer (OR=4.19), and prolonged PT (OR=2.18). Patients with high IL-6 (OR=13.87), CRP (OR=7.09), D-dimer (OR=6.36), and neutrophils (OR=6.25) had the highest likelihood of mortality.ConclusionsSeveral hematological and immunological markers, in particular neutrophilic count, could be helpful to be included within the routine panel for COVID-19 infection evaluation to ensure risk stratification and effective management.
Sleep quality, mental health and circadian rhythms during COVID lockdown – Results from the SleepQuest Study
Authors: Carrigan Neil , Wearn Alfie , Meky Saba , Selwood James , Piggins Hugh D. , Turner Nicholas , Greenwood Rosemary , Coulthard Elizabeth 
Published: July 2020

AbstractBehavioural responses to COVID-19 lockdown will define the long-term impact of psychological stressors on sleep and brain health. Here we tease apart factors that help protect against sleep disturbance. We capitalise on the unique restrictions during COVID-19 to understand how time of day of daylight exposure and outside exercise interact with chronotype and sleep quality. 3474 people from the UK (median age 62, range 18-91) completed our online ‘SleepQuest’ Study between 29th April and 13th May 2020 – a set of validated questionnaires probing sleep quality, depression, anxiety and attitudes to sleep alongside bespoke questions on the effect of COVID-19 lockdown on sleep, time spent outside and exercising and self-help sleep measures. Significantly more people (n=1252) reported worsened than improved sleep (n=562) during lockdown (p<0.0001). Factors significantly associated with worsened sleep included low mood (p<0.001), anxiety (p<0.001) and suspected, proven or at risk of COVID-19 symptoms (all p<0.03). Sleep improvement was related to the increased length of time spent outside (P<0.01). Older people’s sleep quality was less affected than younger people by COVID lockdown (p<0.001). Better sleep quality was associated with going outside and exercising earlier, rather than later, in the day. However, the benefit of being outside early is driven by improved sleep in ‘owl’ (p=0.0002) and not ‘lark’ (p=0.27) chronotype, whereas, the benefit of early exercise (inside or outside) did not depend on chronotype. Defining the interaction between chronotype, mental health and behaviour will be critical for targeted lifestyle adaptations to protect brain health through current and future crises.
G6PD Deficiency Overrepresented Among Pediatric COVID-19 Cases in One Saudi Children Hospital
Authors: Al-Aamri Maryam , Al-Khalifa Fatima , Al-Nahwi Fawatim , Al-Ameer Heba , Al-Abdi Sameer 
Published: July 2020

AbstractFluorescent spot test for glucose-6-phosphate dehydrogenase (G6PD) deficiency was performed in 5 boys and 14 girls who had confirmed COVID-19. Out of those, 4 (80%) boys and 5 (36%) girls were found to be G6PD deficient.