bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting vertical ground reaction forces from 3D accelerometry using reservoir computers leads to accurate gait event detection
Authors: Bach Margit M. , Dominici Nadia , Daffertshofer Andreas 
Published: February 2022

AbstractAccelerometers are low-cost measurement devices that can readily be used outside the lab. However, determining isolated gait events from accelerometer signals, especially foot-off events during running, is an open problem. We outline a two-step approach where machine learning serves to predict vertical ground reaction forces from accelerometer signals, followed by force-based event detection.We collected shank accelerometer signals and ground reaction forces from 21 adults during comfortable walking and running on an instrumented treadmill. We trained one common reservoir computer using segmented data using both walking and running data. Despite being trained on just a small number of strides, this reservoir computer predicted vertical ground reaction forces in continuous gait with high quality. The subsequent foot contact and foot off event detection proved highly accurate when compared to the golden standard based on co-registered ground reaction forces. Our proof-of-concept illustrates the capacity of combining accelerometry with machine learning for detecting isolated gait events irrespective of mode of locomotion.
OsIRO3 negatively regulates Fe homeostasis by repressing the expression of OsIRO2
Authors: Li Chenyang , Li Yang , Xu Peng , Liang Gang 
Published: February 2022

ABSTRACTIron (Fe) is crucial for crop productivity and quality. However, Fe deficiency is prevalent worldwide, especially in alkaline soil. Plants have evolved sophisticated mechanisms to withstand Fe deficiency conditions. Oryza sativa IRON-RELATED BHLH TRANSCRIPTION FACTOR 3 (OsIRO3/OsbHLH63) has been identified as a negative regulator of Fe deficiency response signaling, however, the underlying mechanism remains unclear. In the present study, we constructed two iro3 mutants which generated leaves with necrotic lesions under Fe deficient conditions. Loss-of-function of OsIRO3 caused upregulation of Fe deficiency-associated genes in the root under Fe deficient conditions. Fe concentration measurement showed that the iro3 mutants had increased shoot Fe concentration only under Fe deficient conditions. Further analysis revealed that OsIRO3 directly regulated the expression of IRON-RELATED BHLH TRANSCRIPTION FACTOR 2 (OsIRO2) which encodes a positive regulator of Fe uptake system. Protein interaction tests indicated that OsIRO3 interacted with OsPRI1 and OsPRI2. Further investigation demonstrated that OsIRO3 repressed the transactivation of OsPRI1 and OsPRI2 towards OsIRO2. OsIRO3 contains an EAR motif which recruits the TOPLESS/TOPLESS-RELATED (OsTPL/OsTPRs) corepressors. Mutation of the EAR motif attenuated the repression ability of OsIRO3. This work sheds light on the molecular mechanism by which OsIRO3 modulates Fe homeostasis in rice.
Super-resolution analyzing spatial organization of lysosomes with an organic fluorescent probe
Authors: Wang Lei , Chen Rui , Han Guanqun , Liu Xuan , Huang Taosheng , Diao Jiajie , Sun Yujie 
Published: February 2022

AbstractLysosomes are multifunctional organelles involved in macromolecule degradation, nutrient sensing and autophagy. Live imaging has revealed lysosome subpopulations with dynamics and characteristic cellular localization. An as-yet unanswered question is whether lysosomes are spatially organized to coordinate and integrate their functions. Combined with super-resolution microscopy, we designed a small organic fluorescent probe, TPAE, that targeted lysosomes with a large Stokes shift. When we analyzed the spatial organization of lysosomes against mitochondria in different cell lines with this probe, we discovered different distance distribution patterns between lysosomes and mitochondria during increased autophagy flux. By usingSLC25A46mutation fibroblasts derived from patients containing highly fused mitochondria with low oxidative phosphorylation, we concluded that unhealthy mitochondria redistributed the subcellular localization of lysosomes, which implies a strong connection between mitochondria and lysosomes.
Early zygotic gene product Dunk interacts with anillin to regulate Myosin II during Drosophila cleavage
Authors: Chen Jiayang , He Bing 
Published: February 2022

AbstractDrosophila cellularization is a special form of cleavage that converts syncytial embryos into cellular blastoderms by partitioning the peripherally localized nuclei into individual cells. An early event in cellularization is the recruitment of non-muscle myosin II (“myosin”) to the basal tip of cleavage furrows, where myosin forms an interconnected basal array before reorganizing into individual cytokinetic rings. The initial recruitment and organization of basal myosin are regulated by a cellularization-specific gene, dunk, but the underlying mechanism is unclear. Through a genome-wide yeast two-hybrid screen, we identified anillin (Scraps in Drosophila), a conserved scaffolding protein in cytokinesis, as the primary binding partner of Dunk. We show that Dunk regulates the localization of anillin at the cleavage furrows during early cellularization and functionally interacts with anillin in regulating basal myosin. Furthermore, we show that anillin colocalizes with myosin since the onset of cellularization and is required for the initial recruitment and maintenance of myosin at the basal array, prior to the well-documented function of anillin in regulating cytokinetic ring assembly. Based on these results, we propose that Dunk regulates myosin recruitment and organization during early cellularization by interacting with and regulating anillin.
Accurate models of substrate preferences of post-translational modification enzymes from a combination of mRNA display and deep learning
Authors: Vinogradov Alexander A. , Chang Jun Shi , Onaka Hiroyasu , Goto Yuki , Suga Hiroaki 
Published: February 2022

AbstractPromiscuous post-translational modification (PTM) enzymes often display non-obvious substrate preferences by acting on diverse yet well-defined sets of peptides and/or proteins. Thorough understanding of substrate fitness landscapes for promiscuous PTM enzymes is important because they play key roles in many areas of contemporary science, including natural product biosynthesis, molecular biology and biotechnology. Here, we report the development of an integrated platform for accurate profiling of substrate preferences for PTM enzymes. The platform features a combination of i) mRNA display with next generation sequencing as an ultrahigh throughput technique for data acquisition and ii) deep learning for data analysis. The high accuracy (>0.99 in each of two studies) and generalizability of the resulting deep learning models enables comprehensive analysis of enzymatic substrate preferences. The models can be utilized to quantify fitness across sequence space, map modification sites, and identify important amino acids in the substrate. To benchmark the platform, we perform substrate specificity profiling of a Ser dehydratase (LazBF) and a Cys/Ser cyclodehydratase (LazDEF), two enzymes from the lactazole biosynthesis pathway. In both studies, our results point to highly complex enzymatic preferences, which, particularly for LazBF, cannot be reduced to a set of simple rules. The ability of the constructed models to dissect and analyze such complexity suggests that the developed platform can facilitate the wider study of PTM enzymes.
The interplay between sulfur metabolism and desulfurization profile in Rhodococcus: Unraveling the role of the transsulfuration pathway
Authors: Martzoukou Olga , Glekas Panayiotis , Avgeris Margaritis , Mamma Diomi , Scorilas Andreas , Kekos Dimitris , Amillis Sotiris , Hatzinikolaou Dimitris G. 
Published: February 2022

AbstractBiodesulfurization (BDS) is a process that selectively removes sulfur from dibenzothiophene and its derivatives. Several natural biocatalysts have been isolated, all harboring the highly conserved desulfurization operon dszABC. Even though the desulfurization phenotype is known to be significantly repressed by methionine, cysteine, and inorganic sulfate, the available information on the metabolic regulation of gene expression is still limited. In this study, scarless knockouts of the sulfur metabolism-related cbs and metB genes are constructed in the desulfurizing strain Rhodococcus sp. IGTS8. We provide sequence analyses for both enzymes of the reverse transsulfuration pathway and report their involvement in the sulfate- and methionine-dependent repression of the biodesulfurization phenotype, based on desulfurization assays in the presence of different sulfur sources. Additionally, the positive effect of cbs and metB gene deletions on dsz gene expression in the presence of both sulfate and methionine, but not cysteine, is uncovered and highlighted.
The impact of changes in mental health services in response to COVID-19 on people with mental health conditions: protocol for a rapid review
Authors: Yu G , Craig D , Fu Y 
Published: February 2022

ABSTRACTIntroductionThe COVID-19 pandemic has caused disruptions to mental health services, forcing the rapid implementation of alternative ways of delivering services alongside a greater immediate, and continuously growing, demand across those services. The care and level of mental health service provided are felt to be inadequate to respond to the increasing demand for mental health conditions in the time of the pandemic, leading to an urgent need to learn from service change and consequences to inform solutions and plans to support the NHS post-pandemic plan in the UK. This rapid review aims to understand the changes in mental health services during the pandemic and summarise the impact of these changes on the health outcomes of people with mental health conditions.Methods and analysisCochrane CENTRAL, MEDLINE, EMBASE, and PsycInfowill be searched for eligible studies with key terms indicating mental health AND COVID-19 AND health services. Studies will be included if objective and subjective effects of changes to mental health services in response to COVID-19 are reported on adults with mental health conditions, peer-reviewed and published in the English language. Study selection and data extraction will be undertaken dependently by two reviewers. Evidence will be summarised narratively and in a logic model.Ethics and disseminationEthics approval is not required for this review. A list of interventions/services/models of care delivered to people with mental health conditions will be grouped as “Do”, “Don’t” and “Don’t know” based on the evidence on effectiveness and acceptability. The results will be written for publication in an open-access peer-reviewed journal and disseminated to the public and patients, clinicians, commissioners, funders, and academic conferences.PROSPERO registration numberCRD42022306923Strengths and limitations of this studyThis is a rapid review with a systematic search of literatureEvidence on changes to mental health services and associated health outcomes will be examined to make practice recommendationsThis review will provide the evidence base to inform solutions and plans to support the mental health service provision for the post-pandemic periodSome limitations to the study design include limited to OECD studies, exclusion of non-English studies, publication bias, quality of data, selection bias, and no quality assessment in the rapid evidence review.
Occupational safety and health aspects of corporate social responsibility reporting in Japan: comparison between 2012 and 2020
Authors: Shimizu Takahiro , Nagata Tomohisa , Fujimoto Ayumi , Inoue Shunsuke , Nagata Masako , Mori Koji 
Published: February 2022

AbstractBackgroundWe aimed to survey the content of occupational safety and health (OSH) disclosed in corporate social responsibility (CSR)-related reports and integrated reports in 2020 and to compare the changes between 2012 and 2020 according to industry and company size.MethodsWe surveyed the websites of all 2,172 companies listed in the first section of the Tokyo Stock Exchange in 2020 and examined their CSR-related reports and integrated reports. CSR-related reports contain only non-financial information or are posted on webpages addressing sustainability and CSR. Integrated reports include financial information in addition to non-financial information or are posted in the investor relations section. We calculated the proportion of each report type and the proportion of OSH content in each report by industry sector and company size. To increase the reliability of the survey, five experts independently surveyed the same 40 companies and discussed any differing results. We prepared a survey manual based on these discussions. Twenty-five researchers assessed the presence or absence of each type of report and of OSH.ResultsAmong all companies, 441 (20.3%) companies issued CSR-related reports and 590 (28.1%) issued integrated reports. The number (percentage) of companies that issued either CSR-related reports or integrated reports was 880 (40.5%). The percentages of both CSR-related reports and integrated reports increased with increased company size. The number (percentage) of companies reporting OSH in CSR-related reports was 391 (88.7%) and that in integrated reports was 493 (83.6%). The percentage of OSH reporting in CSR-related reports and integrated reports was high in secondary industries and low in tertiary industries.ConclusionsThe companies that issued either a CSR-related report or an integrated report increased by 1.9% in 2020 compared with 2012. The percentage of companies that had described OSH in CSR-related reports and integrated reports were increased in 2020 compared with 2012. Many companies in Japan are emphasizing OSH in their CSR-related and integrated reports.
Linking CFTR modulators to opportunistic bacterial infections in cystic fibrosis
Authors: Cigana Cristina , Giannella Ruggero , Colavolpe Alice , Alcalá-Franco Beatriz , Mancini Giulia , Francesca Colombi , Bigogno Chiara , Bastrup Ulla , Bertoni Giovanni , Bragonzi Alessandra 
Published: February 2022

AbstractCystic fibrosis transmembrane conductance regulator (CFTR) modulators improve clinical outcomes with variable efficacy in patients with cystic fibrosis (CF). However, changes produced by bacterial persistence and adaptation in addition to antibiotic regimens could influence CFTR modulator efficacy and vice versa and hence clinical outcomes. We first evaluated the effects of ivacaftor (IVA), lumacaftor (LUM), tezacaftor, elexacaftor and elexacaftor/tezacaftor/ivacaftor (ETI), alone or combined with antibiotics, on sequential Staphylococcus aureus and Pseudomonas aeruginosa CF isolates. IVA and ETI showed the most potent direct antimicrobial activity against S. aureus, while P. aeruginosa was not affected. Additive effects or synergies were observed between the CFTR modulators and antibiotics against both S. aureus and P. aeruginosa, independently of the stage of colonization. IVA and LUM were the most effective in potentiating antibiotic activity against S. aureus, while IVA and ETI enhanced mainly polymyxins activity against P. aeruginosa. Next, we evaluated the effect of P. aeruginosa pneumonia on the pharmacokinetics of IVA in mice. The time-concentration curves of IVA and its metabolites in plasma, lung and epithelial lining fluid were influenced by P. aeruginosa infection. The area under the concentration-time curve showed that airway exposure to IVA was greater in infected than non-infected mice. These results suggest that CFTR modulators can have direct antimicrobial properties and/or enhance antibiotic activity against S. aureus and P. aeruginosa. Furthermore, bacterial infection impacts the IVA concentration and airway exposure, potentially affecting its efficacy. Our findings suggest optimizing host- and pathogen-directed drug regimens to improve efficacy for personalized treatment.
The Drosophila melanogaster enzyme glycerol-3-phosphate dehydrogenase 1 is required for oogenesis, embryonic development, and amino acid homeostasis
Authors: Rai Madhulika , Carter Sarah M. , Shefali Shefali A. , Mahmoudzadeh Nader H. , Pepin Robert , Tennessen Jason M. 
Published: February 2022

ABSTRACTAs the fruit fly, Drosophila melanogaster, progresses from one life stage to the next, many of the enzymes that compose intermediary metabolism undergo substantial changes in both expression and activity. These predictable shifts in metabolic flux allow the fly meet stage-specific requirements for energy production and biosynthesis. In this regard, the enzyme Glyerol-3-phosphate dehydrogenase (GPDH1) has been the focus of biochemical genetics studies for several decades, and as a result, is one of the most well characterized Drosophila enzymes. Among the findings of these earlier studies is that GPDH1 acts throughout the fly lifecycle to promote mitochondrial energy production and triglyceride accumulation while also serving a key role in maintaining redox balance. Here we expand upon the known roles of GPDH1 during fly development by examining how depletion of both the maternal and zygotic pools of this enzyme influences development, metabolism, and viability. Our findings not only confirm previous observations that Gpdh1 mutants exhibit defects in larval development, lifespan, and fat storage but also reveal that GPDH1 serves essential roles in oogenesis and embryogenesis. Moreover, metabolomics analysis reveals that a Gpdh1 mutant stock maintained in a homozygous state exhibits larval metabolic defects that significantly differ from those observed in the F1 mutant generation. Overall, our findings highlight unappreciated roles for GPDH1 in early development and uncover previously undescribed metabolic adaptations that could allow flies to survive loss of this key enzyme.
Active site structure of the Shigella flexneri effector OspI
Authors: Nishide Akira , Takagi Kenji , Kim Minsoo , Mizushima Tsunehiro 
Published: February 2022

AbstractUbc13 is a critical ubiquitin-conjugating enzyme involved in the nuclear factor-κB (NF-κB) signalling pathway. The Shigella flexneri effector OspI targets the host Ubc13 and modifies this enzyme by deamidation of Gln100 into Glu100. This modification inhibits the tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6)-catalyzed ubiquitination and diacylglycerol-CBM (CARD–Bcl10– Malt1)-TRAF6-NF-κB signal activation. We have previously reported the wild-type OspI crystal structure, but the catalytic triad does not form the canonical active site. Here, the crystal structure of OspI with a C62S mutation was determined at a resolution of 2.2 Å. This C62S mutant structure provided the active site conformation with the catalytic site of OspI.
Centriole growth is not limited by a finite pool of components, but is limited by the Cdk1/Cyclin-dependent phosphorylation of Ana2/STIL
Authors: Steinacker Thomas L. , Wong Siu-Shing , Novak Zsofia A. , Saurya Saroj , Gartenmann Lisa , van Houtum Eline J.H. , Sayers Judith R. , Lagerholm B. Christoffer , Raff Jordan W. 
Published: February 2022

AbstractCentrioles duplicate once per cell cycle but it is unclear how daughter centrioles assemble at the right time and place and grow to the right size. Here we show that in early Drosophila embryos the cytoplasmic concentrations of the key centriole assembly proteins Asl, Plk4, Ana2, Sas-6 and Sas-4 are low, but remain constant throughout the assembly process— indicating that none of them are limiting for centriole assembly. The cytoplasmic diffusion rate of Ana2/STIL, however, increased significantly towards the end of S-phase as Cdk/Cyclin activity in the embryo increased. A mutant form of Ana2 that cannot be phosphorylated by Cdk/Cyclins did not exhibit the diffusion rate change, and allowed daughter centrioles to grow for an extended period. Thus, the Cdk/Cyclin-dependent phosphorylation of cytoplasmic Ana2 seems to reduce the efficiency of daughter centriole assembly towards the end of S-phase. This helps to ensure that daughter centrioles stop growing at the correct time, and presumably also helps to explain why centrioles cannot duplicate during mitosis when Cdk/Cyclin activity is high.
Bioassay evaluation, GC-MS Analysis and Acute Toxicity Assessment of Methanolic Extracts of Trichoderma species in an Animal Model
Authors: Mulatu Afrasa , Megersa Negussie , Tolcha Teshome , Alemu Tesfaye , Vetukuri Ramesh R. 
Published: February 2022

AbstractFungi of the genus Trichoderma have been marketed for the control of crop pests, weeds, and diseases. However, some Trichoderma species may produce toxic secondary metabolites; the existence of these compounds in bioformulated products, along with their relative risk, should receive due attention to ensure human safety. In this study, we investigated the in vitro antagonistic potential of T. asperellum AU131 and T. longibrachiatum AU158 as a biocontrol agent against F. xylarioides and the associated antagonistic mechanism with bioactive substances. Swiss albino mice were used to evaluate the in vivo toxicity and pathogenicity of T. asperellum AU131 and T. longibrachiatum AU158 methanolic crude extracts and spore suspensions, respectively, in a preliminary safety assessment for use as biofungicides. Metabolite profiling of the crude extracts were performed by Gas Chromatography-Mass Spectrometry (GC-MS). The agar diffusion assay of the crude extracts from both T. asperellum AU131 and T. longibrachiatum AU158 were the most effective at a concentration of 200μg/mL, causing 62.5%, and 74.3% inhibition, respectively. A GC-MS analysis of crude extracts from both bioagents identified 23 volatile secondary metabolites classified as alcohols, acids, sesquiterpenes, ketones and aromatic compounds. The oral administration of crude extracts (doses of 600, 1200, 2000 and 5000 mg/kg body weight) and spore suspensions (doses of 1 × 106, 1 × 107, 1 × 108 and 1 × 109 spores/mL) to female Swiss albino mice over 14 days did not show any significant signs of toxicity, mortality or changes to body weight. The highest dose, 5000 mg/kg, can be used to determine the no observed effect level of crude extracts and spore suspensions of T. asperellum AU131 and T. longibrachiatum AU158 when calculating safety margins. It can be concluded that these two Trichoderma species can serve as a biocontrol agents against F. xylarioides and the mechanism for this function was due to the secondary metabolites with effective bioactive substance. Moreover, the tested spore suspensions and crude extracts were not pathogenic or toxic, respectively, when administered to Swiss albino mice at various doses.
Single-cell characterization of neovascularization using hiPSC-derived endothelial cells in a 3D microenvironment
Authors: Rosowski Simon , Brähler Caroline , Marder Maren , Akishiba Misao , Platen Alina , Ussar Siegfried , Theis Fabian , Wiedenmann Sandra , Meier Matthias 
Published: February 2022

AbstractThe formation of vascular structures is fundamental forin vitrotissue engineering. Vascularization can enable the nutrient supply within larger structures and increase transplantation efficiency, which are currently limiting factors in organoid research. We differentiated human induced pluripotent stem cells toward endothelial cells in 3D suspension culture. To investigatein vitroneovascularization and various 3D microenvironmental approaches, we designed a comprehensive single-cell transcriptomic study. Time-resolved single-cell transcriptomics of the endothelial and co-evolving mural cells gave insights into cell type development, stability, and plasticity. Transfer to a 3D hydrogel microenvironment induced neovascularization and facilitated tracing of sprouting, coalescing, and tubulogenic endothelial cells states. During maturation, we monitored two pericyte subtypes evolving of mural cells. Profiling cell-cell interactions between pericytes and endothelial cells confirmedin vivoangiogenic signaling and emphasized new cytokine signals during tubulogenesis. Our data, analyses, and results provide anin vitroroadmap to guide vascularization in future tissue engineering.