bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recovery of kicking kinematics and performance following intermittent high-intensity running bouts in young soccer players: can a local cooling intervention help?
Authors: Palucci Vieira Luiz H , Carling Christopher , Kalva-Filho Carlos A , Santinelli Felipe B , Velluto Lorenzo A G , da Silva João Pedro , Kellis Eleftherios , Barbieri Fabio A 
Published: March 2022

AbstractRepeated high-intensity running (RHIR) exercise is known to affect central and peripheral functioning. Declines in RHIR performance are exacerbated by environmental heat stress. Accordingly, the use of post-exercise cooling strategies (COOL) is recommended as it may assist recovery. The present study aimed to investigate, in a hot environment (> 30ºC), the effects of local COOL following RHIR on indices of soccer kicking movement and performance in youth soccer. Fifteen academy under-17 players (16.27 ± 0.86 years-old; all post-PHV), acting as their own controls, participated. In #Experiment 1, players completed an all-out RHIR protocol (10 × 30 m bouts interspersed with 30 s intervals). In #Experiment 2, the same players performed the same running protocol under two conditions, 1) 5 minutes of COOL where ice packs were applied to the quadriceps and hamstrings regions and, 2) a control condition involving only passive resting. In both experiments, perceptual measures [ratings of perceived exertion (RPE), pain and recovery], thigh temperature and kick-derived video kinematics (hip, knee, ankle and foot) and performance (ball speed and placement) were collected at baseline and post exercise and intervention. In the first experiment, RHIR led to moderate-to-large increases (p< 0.03) in RPE (d= 4.08), ankle eversion/inversion angle (d= 0.78) and mean radial error (d= 1.50) and small-to-large decreases (p< 0.04) in recovery (d= -1.83) and average/peak ball speeds (d= -0.42–-0.36). In the second experiment RPE (p< 0.01; Kendall’sW= 0.30) and mean radial error (p= 0.057; η2= 0.234) increased only post-control. Significant small declines in ball speed were also observed only post-control (p< 0.05;d= 0.35). Post-intervention CMfootvelocity was moderately faster in COOL as compared to control (p= 0.04;d= 0.60). RHIR acutely impaired kicking movement, ball speed and placement in youth soccer players. However, a short period of local cryotherapy may be beneficial in counteracting declines in indices of kicking performance in hot environment.Trial registration number#RBR-8prx2m - ReBEC Brazilian Clinical Trials Registry
13 cis retinoic acid improved the outcomes of COVID-19 patients. A randomized clinical trial
Authors: Elkazzaz Mahmoud , Abo-Amer Yousry Esam-Eldin , Ahmed Amr , Haydara Tamer 
Published: March 2022

AbstractThe COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 100 million people causing over 2.4 million deaths over the world, and it is still expanding. Given the urgency of the COVID-19 pandemic, the clinical investigation of approved drugs is a promising alternative to find a timely effective treatment. In this randomized trial, we investigated the activity of both oral and aerosolized 13 cis retinoic acid in the treatment of SARS-COV-2 added to standard of care treatment in patients with COVID-19 versus standard of care treatment alone. This was a randomized controlled trial conducted at Kafrelsheikh University’s Quarantine Hospitals, Egypt. After obtaining informed consent, forty patients with a confirmed diagnosis of COVID-19 were enrolled in the study. They were randomly assigned to one of two groups: Group I; 20 patients received aerosolized and oral 13 cis retinoic acid plus standard of care treatment (13 cis RA group) and Group II; 20 patients received only standard care treatment as a control group. The two groups were age and gender matched. There was no statistically significant difference between them in any of the baseline characteristics or laboratory parameters. The results showed that there was a high significant difference between the two groups regarding intensive care unit (ICU) admission, mortality and improvement (P<0.05). Only 10.52 % of patients in the 13 cis retinoic acid group needed ICU admission compared to 28.57 % in the control arm. There was no mortality in the 13 cis retinoic acid group, whereas about 14.35% were died in the group II. All patients who received 13 cis retinoic acid noticed a high improvement (P<0.001), and the mean value for clinical improvement was 16.3±4.5 days. There was no significant difference regarding the laboratory parameters before and after 14 days of treatment in the group of patients received the standard of care treatment (P=0.66). Univariate logistic regression analysis showed overall mortality was significantly related to the patient’s age, serum ferritin, C-reactive protein, oxygen saturation, the presence of diabetes mellitus, obesity, and abdominal pain. We conclude that 13 cis retinoic acid is a promising drug in the treatment of patients with COVID-19 infection, when added to the standard of care treatment.
SNARE assembly enlightened by cryo-EM structures of a synaptobrevin-Munc18-1-syntaxin-1 complex
Authors: Stepien Karolina P. , Xu Junjie , Zhang Xuewu , Bai Xiaochen , Rizo Josep 
Published: March 2022

AbstractMunc18-1 forms a template to recruit and organize assembly of the SNARE complex that triggers neurotransmitter release, binding first to a closed conformation of syntaxin-1 where its N-terminal region interacts with the SNARE motif, and later binding to synaptobrevin. However, the mechanism of SNARE complex assembly remains unclear. Here we report two cryo-EM structures of Munc18-1 bound to cross-linked syntaxin-1 and synaptobrevin. The structures allow visualization of how syntaxin-1 opens and reveal how part of the syntaxin-1 N-terminal region can help nucleate interactions between the N-termini of the syntaxin-1 and synaptobrevin SNARE motifs while their C-termini bind to distal sites of Munc18-1. Mutagenesis, SNARE complex assembly assays and reconstitution experiments support a model whereby these interactions are critical to initiate SNARE complex assembly.One Sentence SummaryCryo-EM structures reveal key insights into the molecular mechanism of neuronal SNARE complex assembly templated by Munc18-1
Quantifying the immunological distinctiveness of emerging SARS-CoV-2 variants in the context of prior regional herd exposure
Authors: Niesen Michiel J.M. , Murugadoss Karthik , Lenehan Patrick J. , Marchler-Bauer Aron , Wang Jiyao , Connor Ryan , Brister J. Rodney , Venkatakrishnan AJ , Soundararajan Venky 
Published: March 2022

AbstractThe COVID-19 pandemic has seen the persistent emergence of immune-evasive SARS-CoV-2 variants under the selection pressure of natural and vaccination-acquired immunity. However, it is currently challenging to quantify how immunologically distinct a new variant is compared to all the prior variants to which a population has been exposed. Here we define ‘Distinctiveness’ of SARS-CoV-2 sequences based on a proteome-wide comparison with all prior sequences from the same geographical region. We observe a correlation between Distinctiveness relative to contemporary sequences and future change in prevalence of a newly circulating lineage (Pearson r = 0.75), suggesting that the Distinctiveness of emergent SARS-CoV-2 lineages is associated with their competitive fitness. We further show that the average Distinctiveness of sequences belonging to a lineage, relative to the Distinctiveness of other sequences that occur at the same place and time (n = 944 location/time data points), is predictive of future increases in prevalence (AUC = 0.88, 0.86-0.90 95% confidence interval). By assessing the Delta variant in India versus Brazil, we show that the same lineage can have different Distinctiveness-contributing positions in different geographical regions depending on the other variants that previously circulated in those regions. Finally, we find that positions that constitute epitopes contribute disproportionately (20-fold higher than the average position) to Distinctiveness. Overall, this study suggests that real-time assessment of new SARS-CoV-2 variants in the context of prior regional herd exposure via Distinctiveness can augment genomic surveillance efforts.
Bio-inspired neural networks implement different recurrent visual processing strategies than task-trained ones do
Authors: Lindsay Grace W. , Mrsic-Flogel Thomas D. , Sahani Maneesh 
Published: March 2022

AbstractBehavioral studies suggest that recurrence in the visual system is important for processing degraded stimuli. There are two broad anatomical forms this recurrence can take, lateral or feedback, each with different assumed functions. Here we add four different kinds of recurrence—two of each anatomical form—to a feedforward convolutional neural network and find all forms capable of increasing the ability of the network to classify noisy digit images. Specifically, we take inspiration from findings in biology by adding predictive feedback and lateral surround suppression. To compare these forms of recurrence to anatomically-matched counterparts we also train feedback and lateral connections directly to classify degraded images. Counter-intuitively, we find that the anatomy of the recurrence is not related to its function: both forms of task-trained recurrence change neural activity and behavior similarly to each other and differently from their bio-inspired anatomical counterparts. By using several analysis tools frequently applied to neural data, we identified the distinct strategies used by the predictive versus task-trained networks. Specifically, predictive feedback de-noises the representation of noisy images at the first layer of the network and decreases its dimensionality, leading to an expected increase in classification performance. Surprisingly, in the task-trained networks, representations are not de-noised over time at the first layer (in fact, they become ‘noiser’ and dimensionality increases) yet these dynamics do lead to de-noising at later layers. The analyses used here can be applied to real neural recordings to identify the strategies at play in the brain. Our analysis of an fMRI dataset weakly supports the predictive feedback model but points to a need for higher-resolution cross-regional data to understand recurrent visual processing..
On-Farm Genetic Diversity of Wheat (Triticum aestivum spp.) In Digalu Tijo District, Arsi Zone, Ethiopia
Authors: Gelelcha Fekadu , Kumsa Fikadu , Kuma Tolera 
Published: March 2022

AbstractIntroductoryThis study was undertaken to assess the on-farm genetic diversity of wheat Landraces (Triticum aestivum spp) in Digalu and Tijo District.MethodsFor this study, three farmer households kebeles were selected by cluster sampling (area sampling) method because they are found in the most dominant wheat landraces growing agro-ecological areas. Data for this study was collected using questionnaires, field observation, interviews, focus group discussion, and document analysis.Results and DiscussionsIn total, 27 wheat landraces were reported to be grown before two decades to the present day. Of these, only 9 of wheat landraces are still cultivated by farmers. Among these, ‘Qamadi guracha’ is the most common growing landraces in the study area. The Shannon diversity index (H’) of growing wheat landraces ranges from 1.09 to 1.37 among the groups. The estimated genetic erosion for wheat landraces was found to be 66.7% due to the major factors: improved wheat varieties; the introduction of other more productive crops and wheat landraces low productivity.ConclusionsFood quality, Pests (example, birds), diseases resistance, market value, and straw quality were factors that initiated the farmers to maintain the genetic diversity of landraces on their farmlands. However, the preservation of wheat landraces are influenced by bottlenecks like the seed selection system, and insufficient crop yield.RecommendationRegeneration of soil fertility, restoring of lost landraces, improvement of landraces, on-farm conservation by re-sowing, saving of seeds for future, and ex-situ conservation is suggested for the restoration of wheat landraces diversity in Digalu and Tijo District.
ImputAccur: fast and user-friendly calculation of genotype-imputation accuracy-measures
Authors: Thormann Kolja A , Tozzi Viola , Starke Paula , Bickeböller Heike , Baum Marcus , Rosenberger Albert 
Published: March 2022

AbstractSummaryImputAccur is a software tool for genotype-imputation accuracy-measures. Imputation of untyped markers is a standard approach in genome-wide association studies to close the gap between directly genotyped and other known DNA variants. However high accuracy for imputed genotypes is fundamental. Several accuracy measures have been proposed, but unfortunately, they are implemented on different platforms, which is impractical. With ImputAccur the accuracy measures info, Iam-hiQ and r²based indices can be derived from standard output-files of imputation software. Sample/probe and marker filtering is possible. This allows e.g. accurate marker filtering ahead of data analysis. A Python code is available but also a stand-alone executable file.Availability and ImplementationThe source code (Python version 3.9.4), a stand-alone executive file, and example data for ImputAccur are freely available at https://gitlab.gwdg.de/kolja.thormann1/imputationquality.git.Supplementary InformationSupplementary information is available at Bioinformatics online.Contactarosenb@gwdg.de or koljaalexander.thormann@uni-goettingen.de
RUNX1 isoform disequilibrium in the development of trisomy 21 associated myeloid leukemia
Authors: Gialesaki Sofia , Bräuer-Hartmann Daniela , Bhayadia Raj , Alejo-Valle Oriol , Issa Hasan , Regenyi Enikő , Beyer Christoph , Labuhn Maurice , Ihling Christian , Sinz Andrea , Glaß Markus , Hüttelmaier Stefan , Matzk Sören , Schmid Lena , Strüwe Farina Josepha , Kadel Sofie-Katrin , Reinhardt Dirk , Yaspo Marie-Laure , Heckl Dirk , Klusmann Jan-Henning 
Published: March 2022

AbstractAneuploidy is a hallmark of cancer, but its complex nature limits our understanding of how it drives oncogenesis. Gain of chromosome 21 (Hsa21) is among the most frequent aneuploidies in leukemia and is associated with markedly increased leukemia risk. Here, we propose that disequilibrium of the RUNX1 isoforms is key to the pathogenesis of trisomy 21 (i.e. Down syndrome)-associated myeloid leukemia (ML-DS). Hsa21-focused CRISPR-Cas9 screens uncovered a strong and specific RUNX1 dependency in ML-DS. Mechanistic studies revealed that excess of RUNX1A isoform – as seen in ML-DS patients – synergized with the pathognomonic Gata1s mutation in leukemogenesis by displacing RUNX1C from its endogenous binding sites and inducing oncogenic programs in complex with the MYC cofactor MAX. These effects were reversed by restoring the RUNX1A:RUNX1C equilibrium or pharmacological interference with MYC:MAX dimerization. Our study highlights the importance of alternative splicing in leukemogenesis, even on a background of aneuploidies, and opens new avenues for developing specific and targeted therapies.Graphical Abstract
Effects of chronic cannabidiol in a mouse model of naturally occurring neuroinflammation, neurodegeneration, and spontaneous seizures
Authors: Dearborn Joshua T. , Nelvagal Hemanth R. , Rensing Nicholas R. , Hughes Stephanie M. , Wishart Thomas M , Cooper Jonathan D. , Wong Michael , Sands Mark S. 
Published: March 2022

AbstractCannabidiol (CBD) has gained attention as a therapeutic agent and is purported to have immunomodulatory, neuroprotective, and anti-seizure effects. Here, we determined the effects of chronic CBD administration in a mouse model of CLN1 disease (Cln1-/-) that simultaneously exhibits neuroinflammation, neurodegeneration, and spontaneous seizures. Proteomic analysis showed that putative CBD receptors are expressed at similar levels in the brains ofCln1-/-mice compared to normal animals.Cln1-/-mice received an oral dose (100mg/kg/day) of CBD for six months and were evaluated for changes in pathological markers of disease and seizures. Chronic cannabidiol administration was well-tolerated, high levels of CBD were detected in the brain, and markers of astrocytosis and microgliosis were reduced. However, CBD had no apparent effect on seizure frequency or neuron survival. These data are consistent with CBD having immunomodulatory effects. It is possible that a higher dose of CBD could also reduce neurodegeneration and seizure frequency.
Extensive neutralization against SARS-CoV-2 variants elicited by Omicron-specific subunit vaccine booster
Authors: Peng Pai , Feng Chengqian , Hu Jie , He Chang-long , Deng Hai-jun , Fan Qinghong , Xiang Jin , Tang Guofang , Jiang Mengling , Hu Fengyu , Li Feng , Wang Kai , Tang Ni , Tang Xiaoping , Huang Ai-long 
Published: March 2022

AbstractThe currently dominant variant of SARS-CoV-2 Omicron, carrying a great number of mutations, has been verified its strong capacity of immune escape in COVID-19 convalescents and vaccinated individuals. An increased risk of SARS-CoV-2 reinfection or breakthrough infection should be concerned. Here we reported higher humoral immune response elicited by Delta and Omicron variants after breaking through previous infection and cross-neutralization against VOCs, compared to the ancestral wild-type (WT) virus infection. To overcome the immune escape of Omicron, Omicron-specific vaccine was considered as a novel and potential strategy. Mouse models were used to verify whether Omicron-specific RBD subunit boost immune response by immunizing Omicron-RBD recombinant proteins. Three doses of Omicron-RBD immunization elicit comparable neutralizing antibody (NAb) titers with three doses of WT-RBD immunization, but the neutralizing activity was not cross-active. By contrast, two doses of WT-RBD with an Omicron-RBD booster increased the NAb geometric mean titers against Omicron by 9 folds. Moreover, an additional boost vaccination with Omicron-RBD protein could increase humoral immune response against both WT and current VOCs. These results suggest that the Omicron-specific subunit booster shows its advantages in the immune protection from both WT and current VOCs, and that SARS-CoV-2 vaccines administration using two or more virus lineages as antigens might improve the NAb response.
The importance of environmental parameters and mixing zone in shaping estuarine microbial communities along a freshwater-marine gradient
Authors: Da Silva R.R.P. , White C.A. , Bowman J.P. , Bodrossy L. , Bissett A. , Revill A. , Eriksen R. , Ross D.J. 
Published: March 2022

AbstractMicrobial communities are important elements in the marine environment, contributing to nutrient cycling and biogeochemical processes. Estuaries comprise environments exhibiting characteristics from freshwater to marine, leading to distinct microbial communities across this environmental gradient. Here, we examine the spatial dynamics of microbial communities in Macquarie Harbour, an estuarine system on the West coast of Tasmania, Australia. Water was sampled along the estuary to explore the structure and composition of the microbial communities using 16S/18S rRNA gene amplicon sequencing. Multivariate analyses showed environmental variables and community compositions varying along a longitudinal (river to adjacent ocean) gradient at the surface. In the harbour, differences in the microbial community were observed between surface (0-1 m) and intermediate depths (4.5-11 m depth). The results of differential abundance, network and Partial Least Square analyses suggest that Macquarie Harbour is a mixing zone, where the distributions of archaeal, bacterial and eukaryotic communities are influenced by oceanic and riverine inputs. Coupled with the natural characteristics of the Harbour, the heterotrophic component of this microbial communities inhabiting the surface and intermediate waters may play important roles in the nutrient cycle in the studied area. These results provide critical insights into the Macquarie Harbour environment and the importance of understanding the role of microbial communities for similar systems elsewhere.
In situ architecture of the lipid transport protein VPS13C at ER-lysosomes membrane contacts
Authors: Cai Shujun , Wu Yumei , Guillen-Samander Andres , Hancock-Cerutti William , Liu Jun , De Camilli Pietro 
Published: March 2022

AbstractVPS13 is a eukaryotic lipid transport protein localized at membrane contact sites. Previous studies suggested that it may transfer lipids between adjacent bilayers by a bridge-like mechanism. Direct evidence for this hypothesis from a full-length structure and from EM studies in situ, however, is still missing. Here we have capitalized on AlphaFold predictions to complement the structural information already available about VPS13 and to generate a full-length model of human VPS13C, the Parkinson’s disease-linked VPS13 paralog localized at contacts between the ER and endo/lysosomes. Such model predicts a ~30-nm rod with a hydrophobic groove that extends throughout its length. We further investigated whether such a structure can be observed in situ at ER-endo/lysosome contacts. To this aim, we combined genetic approaches with cryo-focused-ion-beam (cryo-FIB) milling and cryo-electron tomography (cryo-ET) to examine HeLa cells overexpressing this protein (either full length or with an internal truncation) along with VAP, its anchoring binding partner at the ER. Using these methods we identified rod-like densities that span the space separating the two adjacent membranes and that match the predicted structures of either full length VPS13C or its shorter truncated mutant, thus providing the first in-situ evidence for a bridge-model of VPS13 in lipid transport. Intriguingly, the majority of the VPS13C rods were separated from the ER membranes by a narrow gap, suggesting that while VAP anchors the protein to the ER, direct contact of the VPS13C rod with the ER bilayer to allow lipid transport may be independently regulated.
CD47-SIRPα controls ADCC killing of primary T cells by PMN through a combination of trogocytosis and NADPH oxidase activation
Authors: Gondois-Rey Françoise , Miller Thomas W. , Nunès Jacques A. , Olive Daniel 
Published: March 2022

AbstractImmunotherapies targeting the “don’t eat me” myeloid checkpoint constituted by CD47 SIRPα interaction have promising clinical potential but are limited by toxicities associated with the destruction of non-tumor cells. These dose-limiting toxicities demonstrate the need to highlight the mechanisms of anti-CD47-SIRPα therapy effects on non-tumor CD47-bearing cells. Given the increased incidence of lymphopenia in patients receiving anti-CD47 antibodies, and the strong ADCC effector function of Poly Morpho Nuclear Cells (PMNs), we investigated the behavior of primary PMNs cocultured with primary T cells in the presence of anti-CD47 mAbs. PMNs killed T cells in a CD47-mAb-dependent manner and at a remarkably potent PMN to T cell ratio of 1:1. The observed cytotoxicity was produced by a novel combination of both trogocytosis and a strong respiratory burst induced by classical ADCC and CD47-SIRPα checkpoint blockade. The complex effect of the CD47 blocking mAb could be recapitulated by combining its individual mechanistic elements: ADCC, SIRPα blockade and ROS induction. Although previous studies had concluded that disruption of SIRPα signaling in PMNs was limited to trogocytosis-specific cytotoxicity, our results suggest that SIRPα also tightly controls activation of NADPH oxidase, a function demonstrated during differentiation of immature PMNs but not so far in mature PMNs. Together, our results highlight the need to integrate PMNs in the development of molecules targeting the CD47-SIRPα immune checkpoint and to design agents able to enhance myeloid cells function while limiting adverse effects to healthy cells able to participate in the anti-tumor immune response.SynopsisDose-limiting toxicities demonstrate the need to investigate anti-CD47-SIRPα therapy effects on non-tumor CD47-bearing cells. We demonstrate that anti-CD47 mAbs stimulate potent killing of T cells by PMN through a novel combination of trogocytosis and ROS regulated by SIRPα.Graphical Abstract