bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct exosomal miRNA profiles from BALF and lung tissue from COPD and IPF patients
Authors: Kaur Gagandeep , Maremanda Krishna P , Campos Michael , Chand Hitendra S , Li Feng , Hirani Nikhil , Haseeb M.A. , Rahman Irfan 
Published: August 2021

AbstractBackgroundChronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) are chronic, progressive lung ailments which are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Exosomes are small extracellular vesicles attributed to carry proteins, mRNA, miRNA and sncRNA to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of BALF or the lung tissue derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF and lung tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD and IPF in independent cohorts.ResultsExosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were approximately 89.85 nm in size and ∼2.95 × 1010 particles/mL. Lung-derived exosomes were ∼146.04 nm in size and ∼2.38 × 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, three- and five-fold downregulation of miR-122-5p amongst the lung tissue-derived exosomes from COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were key 55 differentially expressed miRNAs in the lung tissue-derived exosomes of IPF patients compared to non-smoking controls.ConclusionsOverall, we identified specific miRNAs to develop as biomarkers or targets for pathogenesis of these chronic lung diseases.
Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots
Authors: Agrawal Saaket , Wang Minxian , Klarqvist Marcus D. R. , Shin Joseph , Dashti Hesam , Diamant Nathaniel , Choi Seung Hoan , Jurgens Sean J. , Ellinor Patrick T. , Philippakis Anthony , Ng Kenney , Claussnitzer Melina , Batra Puneet , Khera Amit V. 
Published: August 2021

ABSTRACTFor any given level of overall adiposity – as commonly quantified by body mass index (BMI) within clinical practice – individuals vary considerably in fat distribution. We and others have noted that increased visceral fat (VAT) is associated with increased cardiometabolic risk, while gluteofemoral fat (GFAT) may be protective. Familial partial lipodystrophy (FPLD) – often caused by rare variants in the LMNA gene – represents an extreme example of this paradigm, leading to a severe shift to visceral fat with subsequent insulin resistance and adverse metabolic profile. By contrast, the inherited basis of body fat distribution in the broader population is not fully understood. Here, we studied up to 38,965 UK Biobank participants with VAT, abdominal subcutaneous (ASAT), and GFAT volumes precisely quantified using abdominal MRI. Because genetic associations with these raw depot volumes were largely driven by variants known to affect BMI, we next studied six phenotypes of local adiposity: VAT adjusted for BMI (VATadjBMI), ASATadjBMI, GFATadjBMI, VAT/ASAT, VAT/GFAT, and ASAT/GFAT. We identify 178 unique loci associated with at least one adiposity trait, including 29 newly-identified loci. Rare variant association studies extend prior evidence of association for PDE3B as an important modulator of fat distribution. Sex-specific analyses of local adiposity traits noted overall higher estimated heritability in females, increased effect sizes for identified loci, and 25 female-specific associations. Individuals in the extreme tails of fat distribution phenotypes were highly enriched for predisposing common variants, as quantified using polygenic scores. Taking GFATadjBMI as an example, individuals with extreme values were 3.8-fold (95%CI 2.8 to 5.2) more likely to have a polygenic score within the top 5% of the distribution. These results – using more precise and BMI-independent measures of local adiposity – confirm fat distribution as a highly heritable trait with important implications for cardiometabolic health outcomes.
The efficacy and safety of bamlanivimab treatment against COVID-19: A meta-analysis
Authors: Xiang Huai-rong , He Bei , Li Yun , Cheng Xuan , Zhang Qi-zhi , Peng Wen-xing 
Published: August 2021

ABSTRACTBackgroundBamlanivimab is routinely used in the treatment of coronavirus disease 2019 (COVID-19) in worldwide. We performed a meta-analysis to investigate the efficacy and safety of bamlanivimab treatment in patients with COVID-19.MethodsWe searched articles from Web of Science, PubMed, Embase, the Cochrane Library and MedRxiv between 30 January 2020 and August 5, 2021. We selected randomized clinical trials (RCTs) and observational studies with a control group to assess the efficiency of bamlanivimab in treating patients with COVID-19.ResultsOur meta-analysis retrieved 3 RCTs and 7 cohort studies including 14461 patients. Bmlanivimab may help outpatients to prevent hospitalization or emergency department visit (RR 0.41 95%CI 0.29 to 0.58), reduce ICU admission (RR 0.47 95%CI 0.23 to 0.92) and mortality (RR 0.32 95%CI 0.13 to 0.77) from the disease. The combination of bamlanivimab and etesevimab may had a greater potential for positive treatment outcome.ConclusionBamlanivimab has demonstrated clinical efficacy on mild or moderate ill patients with COVID-19 to prevent hospitalization, reduce severity and mortality from the disease. Combinations of two or more monoclonal antibody increase the effect. Well-designed clinical trials to identify the clinical and biochemical characteristics in COVID-19 patients’ population that could benefit from bamlanivimab are warranted in the future.Key pointsQuestionCan bamlanivimab treat COVID-19 patients? What are the factors that have great impact on the treatment outcome?FindingsIn this meta-analysis that retrieved 3 RCTs and 7 cohort studies and included 14461 adults, Bmlanivimab may help outpatients to prevent hospitalization or emergency department visit (RR 0.41 95%CI 0.29 to 0.58), reduce ICU admission (RR 0.47 95%CI 0.23 to 0.92) and mortality (RR 0.32 95%CI 0.13 to 0.77) from the disease.MeaningIn COVID-19 pandemic, the use of bamlanivimab may be warranted. Combinations of two or more monoclonal antibody increase the effect.
Long-term precision editing of neural circuits in mammals using engineered gap junction hemichannels
Authors: Ransey Elizabeth , Chesnov Kirill , Thomas Gwenaëlle E. , Wisdom Elias , Almoril-Porras Agustin , Bowman Ryan , Rodriguez Tatiana , Adamson Elise , Walder-Christensen Kathryn K. , Hughes Dalton , Schwennesen Hannah , Mague Stephen D. , Colón-Ramos Daniel , Hultman Rainbo , Bursac Nenad , Dzirasa Kafui 
Published: August 2021

SummaryThe coordination of activity between brain cells is a key determinant of neural circuit function; nevertheless, approaches that selectively regulate communication between two distinct cellular components of a mammalian circuit remain sparse. To address this gap, we developed a novel class of gap junctions by selectively engineering two connexin proteins found inMorone americana(white perch fish): connexin34.7 (Cx34.7) and connexin35 (Cx35). By iteratively exploiting protein mutagenesis, a novelin vitroassay of connexin docking, and computational modeling of connexin hemichannel interactions, we uncovered a pattern of structural motifs that contribute to hemichannel docking compatibility. Targeting these motifs, we designed Cx34.7 and Cx35 hemichannels that dock with each other, but not with themselves, nor with other major connexins expressed in the mammalian central nervous system. We validated these hemichannelsin vivousingC. elegansand mice, demonstrating that they can facilitate communication across neural circuits composed of pairs of distinct cell types and modify behavior accordingly. Thus, we establish a potentially translational approach, ‘Long-termintegration ofCircuits using connexins’ (LinCx), for context-precise circuit-editing with unprecedented spatiotemporal specificity in mammals.
Genome-wide characterization of the R2R3-MYB transcription factors in pepper (Capsicum spp.) unveils the role of CaMYB101 as repressor in anthocyanin biosynthesis
Authors: Liu Ying , Wu Yi , Wang Zicheng , Zhang Shiya , Liu Xintong , Tikunov Yury , Visser Richard G.F. , Schouten Rob E. , Marcelis Leo F.M. , Zhang Zhao , Bovy Arnaud 
Published: August 2021

AbstractFruit colour is one of the most important commercial traits of pepper (Capsicum spp.), a major horticultural crop worldwide. Some pepper accessions temporarily accumulate anthocyanins during fruit development and gradually lose them upon fruit ripening. Meanwhile, anthocyanin biosynthesis gradually stops. However, how this process is exactly regulated is still largely unknown. R2R3-MYB is one of the largest plant transcription factor families, and it is considered the most important regulator for the biosynthesis of anthocyanins and other flavonoids. Although R2R3-MYBs are widely studied in many plants, research in pepper has been limited. In this study, we performed a genome-wide analysis of R2R3-MYBs across three cultivated pepper species (C. annuum, C. baccatum, and C. chinense ) involving identification, chromosome localization, gene structure analysis, phylogenetic analysis and collinearity analysis. Candidate R2R3-MYB repressors were further identified based on repression motifs. An R2R3-MYB gene, CaMYB101, was selected based on its high homology with anthocyanin biosynthesis repressors in tomato and petunia as well as its high expression level in fruit when purple pigmentation started to discolour. By using virus-induced gene silencing, CaMYB101 was characterized as an anthocyanin biosynthesis repressor. To our knowledge, CaMYB101 is the first transcriptional repressor associated with anthocyanin biosynthesis identified in pepper.
Top-down, knowledge-based genetic reduction of yeast central carbon metabolism
Authors: Postma Eline D. , Couwenberg Lucas G.F. , van Roosmalen Roderick N. , Geelhoed Jordi , de Groot Philip A. , Daran-Lapujade Pascale 
Published: August 2021

AbstractSaccharomyces cerevisiae, whose evolutionary past includes a whole-genome duplication event, is characterised by a mosaic genome configuration with substantial apparent genetic redundancy. This apparent redundancy raises questions about the evolutionary driving force for genomic fixation of ‘minor’ paralogs and complicates modular and combinatorial metabolic engineering strategies. While isoenzymes might be important in specific environments, they could be dispensable in controlled laboratory or industrial contexts. The present study explores the extent to which the genetic complexity of the central carbon metabolism (CCM) in S. cerevisiae, here defined as the combination of glycolysis, pentose phosphate pathway, tricarboxylic acid cycle and a limited number of related pathways and reactions, can be reduced by elimination of (iso)enzymes without major negative impacts on strain physiology. Cas9-mediated, groupwise deletion of 35 from the 111 genes yielded a ‘minimal CCM’ strain, which despite the elimination of 32 % of CCM-related proteins, showed only a minimal change in phenotype on glucose-containing synthetic medium in controlled bioreactor cultures relative to a congenic reference strain. Analysis under a wide range of other growth and stress conditions revealed remarkably few phenotypic changes of the reduction of genetic complexity. Still, a well-documented context-dependent role of GPD1 in osmotolerance was confirmed. The minimal CCM strain provides a model system for further research into genetic redundancy of yeast genes and a platform for strategies aimed at large-scale, combinatorial remodelling of yeast CCM.
Prediction-error neurons in circuits with multiple neuron types: Formation, refinement and functional implications
Authors: Hertäg Loreen , Clopath Claudia 
Published: August 2021

AbstractPredictable sensory stimuli do not evoke significant responses in a subset of cortical excitatory neurons. Some of those neurons, however, change their activity upon mismatches between actual and predicted stimuli. Different variants of these prediction-error neurons exist and they differ in their responses to unexpected sensory stimuli. However, it is unclear how these variants can develop and co-exist in the same recurrent network, and how they are simultaneously shaped by the astonishing diversity of inhibitory interneurons. Here, we study these questions in a computational network model with three types of inhibitory interneurons. We find that balancing excitation and inhibition in multiple pathways gives rise to heterogeneous prediction-error circuits. Dependent on the network’s initial connectivity and distribution of actual and predicted sensory inputs, these circuits can form different variants of prediction-error neurons that are robust to network perturbations and generalize to stimuli not seen during learning. These variants can be learned simultaneously via homeostatic inhibitory plasticity with low baseline firing rates. Finally, we demonstrate that prediction-error neurons can support biased perception, we illustrate a number of functional implications, and we discuss testable predictions.
Cell competition between wild-type and JAK2V617F mutant cells prevents disease relapse after stem cell transplantation in a murine model of myeloproliferative neoplasm
Authors: Zhang Haotian , Castiglione Melissa , Zheng Lei , Zhan Huichun 
Published: August 2021

ABSTRACTDisease relapse after allogeneic stem cell transplantation is a major cause of treatment-related morbidity and mortality in patients with myeloproliferative neoplasms (MPNs). The cellular and molecular mechanisms for MPN relapse are not well understood. Here, we established a murine model of MPN relapse, in which ∼60% of the MPN recipient mice develop disease relapse after receiving stem cell transplantation with wild-type marrow donor. Using this model, we find that impaired wild-type cell function is associated with MPN disease relapse. We also show that competition between wild-type and JAK2V617F mutant cells can modulate the immune cell composition and PD-L1 expression induced by the JAK2V617F oncogene. These results suggest that cell competition between wild-type donor cells and JAK2V617F mutant recipient cells can prevent MPN disease relapse after stem cell transplantation.
Community-Based Accompaniment for Adolescents Transitioning to Adult HIV Care in Urban Peru: a Pilot Study
Authors: Vargas Valentina , Wong Milagros , Rodriguez Carly A. , Sanchez Hugo , Galea Jerome , Ramos Alicia , Senador Liz , Kolevic Lenka , Matos Eduardo , Sanchez Eduardo , Errea Renato A. , Ramos Karen , Beckhorn Catherine , Lindeborg Andrew , Benites Carlos , Lecca Leonid , Shin Sonya , Franke Molly F. 
Published: August 2021

AbstractIntroductionAdolescents living with HIV (ALWH) face an elevated risk of poor health outcomes when transitioning into adult-oriented care; however, evidence-based interventions to support ALWH during this high-risk period are lacking, especially in Latin America. We conducted a pilot study of a community-based intervention designed to improve outcomes among ALWH transitioning to adult HIV care in Lima, Peru.MethodsFrom October 2019 to January 2020, we enrolled adolescents transitioning to adult HIV care, either due to a recent diagnosis or having aged out of their pediatric clinic. ALWH previously lost from care during the transition process were also invited to participate. The nine-month intervention consisted of (1) logistical, adherence and social support delivered by entry-level health workers who accompanied adolescents during their transition to adult HIV care and (2) group sessions to improve health-related knowledge, skills and social support. We assessed intervention feasibility and effectiveness in improving medication adherence, psycho-social outcomes, and transition readiness after 6, 9, and 12 months.ResultsWe enrolled 30 ALWH, ages 15-21 years; 11 were recently diagnosed and 19 had been living with HIV since infancy or early childhood. Participants included ten men who have sex with men, four young pregnant women and six adolescents who were previously lost during the transition to adult HIV care. Intervention participation was high with 90% of ALWH attending at least one in-person social support session and all attending at least one live online session. No ALWH withdrew from the intervention, study, or antiretroviral therapy. In transition readiness, we observed within-person improvements related to personal health (+1.9 points, p<0.001), healthcare usage (+2.4 points, p<0.001), knowledge (+3.3 points, p=0.001), and behavior (+3 points, p=0.003) at the end of the intervention, relative to baseline. We also observed strong evidence of improvements in medication adherence, social support, self-efficacy, and perceived stress, which were generally sustained three months after intervention cessation.ConclusionWe identified a community-based intervention that is feasible and potentially effective for bridging the transition to adult HIV care among a diverse group of ALWH in Peru. A larger-scale effectiveness evaluation, including biological endpoints, is warranted.
Attitudes to health promotion among teaching staff in South West England: a qualitative study
Authors: Currie Jonny 
Published: August 2021

AbstractBackgroundYoung people spend much of their formative years in education, making schools appealing environments for health promotion. The World Health Organisation’s Health Promoting Schools framework has been proposed as a useful model. We sought to explore secondary school teachers’ experiences of implementing this model and their attitudes to health promotion.ObjectivesTo explore teachers’ experiences and perceptions of health promotion and compare practice with the HPS framework for school health.DesignQualitative study with semi-structured interviewsSettingNine state comprehensive schools in Bristol and surrounding areas.Participants25 teaching staff from school senior leadership teams, those working in health education and other subject teachers.AnalysisThematic analysis using NVivo 10.ResultsTeachers largely described educational approaches with less emphasis on school ethos or environment. Staff supported a role for schools in promoting health but felt restrained by limited family engagement, contradictory school practices, resource constraints and conflicting government policies.ConclusionsFuture reforms should ensure health is mainstreamed across school strategies, if we are to create the conditions that promote future generations’ health. Public health must build alliances with educationalists to support the priority-setting of health in school inspections, policy and practice.Strengths and limitations of the studyIn-depth exploration with teachers from different schools, levels of seniority and with varying experience of health promotionPurposive sampling to ensure representation from schools of different geography, Ofsted rating and proportions of students from disadvantaged backgroundsPossibility that schools with greater enthusiasm for health promotion disproportionately participatedTrend towards schools in more affluent areas participating
Adar-mediated A-to-I editing is required for establishment of embryonic body axes in zebrafish
Authors: Niescierowicz Katarzyna , Pryszcz Leszek , Navarrete Cristina , Tralle Eugeniusz , Kasprzyk Marta Elżbieta , Nahia Karim Abu , Misztal Katarzyna , Bochtler Matthias , Winata Cecilia 
Published: August 2021

AbstractAdenosine deaminases (ADARs) catalyze the deamination of adenosine to inosine, also known as A-to-I editing, in RNA. Although A-to-I editing occurs widely across animals, and is well studied, new biological roles are still being discovered. Here, we study the role of A-to-I editing in early zebrafish development. We demonstrate that Adar, the zebrafish orthologue of mammalian ADAR1, is essential for establishing the antero-posterior and dorso-ventral axes and patterning. Genome-wide editing discovery revealed pervasive editing in maternal and the earliest zygotic transcripts, the majority of which occurred in the 3’-UTR. Interestingly, transcripts implicated in gastrulation as well as dorso-ventral and antero-posterior patterning were found to contain multiple editing sites. Adar knockdown or overexpression affected gene expression and global editing patterns at 12 hpf, but not earlier. Our study established that RNA editing by Adar is necessary for the earliest steps of embryonic patterning along the zebrafish antero-posterior and dorso-ventral axes.
Synovial Fluid Mitochondrial DNA Concentration Reflects the Degree of Cartilage Damage After Naturally Occurring Articular Injury
Authors: Seewald Lindsay A. , Sabino Isabella G. , Montney Kaylee L. , Delco Michelle L. 
Published: August 2021

AbstractPosttraumatic osteoarthritis (PTOA) is a debilitating sequela to joint injury with no current therapeutics that can slow its progression. Early intervention, prior to the development of degenerative joint changes, has the potential for greater therapeutic success but requires early detection of joint injury. In other tissue types, trauma is associated with the extracellular release of mitochondrial DNA (mtDNA), which serves as a mitochondria-specific Damage Associated Molecular Pattern (mDAMP) to perpetuate inflammation. We demonstrated that chondrocytes release mtDNA following cellular stress and that mtDNA is increased in equine synovial fluid following experimental and naturally occurring mechanical injury to the joint surface. Moreover, we found a strong correlation between the degree of cartilage damage and mtDNA concentration. Finally, impact-induced mtDNA release was mitigated by mitoprotective treatment. These data suggest synovial fluid mtDNA may represent a sensitive marker of early articular injury, prior to the onset of changes on standard diagnostic imaging modalities.One Sentence SummarySynovial fluid mitochondrial DNA increases after articular injury, is associated with the degree of cartilage damage, and is mitigated by mitoprotective treatment.
Post-stroke dendritic arbor regrowth – a cortical repair process requiring the actin nucleator Cobl
Authors: Ji Yuanyuan , Koch Dennis , Delgado Jule González , Günther Madlen , Witte Otto W. , Kessels Michael M. , Frahm Christiane , Qualmann Britta 
Published: August 2021

AbstractIschemic stroke is a major cause of death and long-term disability. We demonstrate that middle cerebral artery occlusion in mice leads to a strong decline in dendritic arborization of penumbral neurons. These defects were subsequently repaired by an ipsilateral recovery process requiring the actin nucleator Cobl. Ischemic stroke and excitotoxicity, caused by calpain-mediated proteolysis, significantly reduced Cobl levels. In an apparently unique manner among excitotoxicity-affected proteins, this Cobl decline was rapidly restored by increased mRNA expression and Cobl then played a pivotal role in post-stroke dendritic arbor repair in peri-infarct areas. In Cobl KO mice, the dendritic repair window determined to span day 2-4 post-stroke in WT strikingly passed without any dendritic regrowth. Instead, Cobl KO penumbral neurons of the primary motor cortex continued to show the dendritic impairments caused by stroke. Our results thereby highlight a powerful post-stroke recovery process and identified causal molecular mechanisms critical during post-stroke repair.