bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiotherapists Use Different Motivational Strategies Tailored to an Individual’s Condition: A Qualitative Study
Authors: Oyake Kazuaki , Sue Keita , Sumiya Motofumi , Tanaka Satoshi 
Published: May 2022

ABSTRACTQuestionHow do physiotherapists use different motivational strategies for individuals in stroke rehabilitation?DesignA qualitative study using in-depth semi-structured online interviews.ParticipantsA criterion sample of 15 physiotherapists who have worked in rehabilitation for over 10 years and have an interest in an individual’s motivation.InterventionNot applicable.Outcome measuresPhysiotherapists’ perspectives and experiences regarding motivational strategies used depending on the individual’s condition.ResultsA total of nine themes emerged from the data upon thematic analysis and inductive coding. The participants used different strategies to encourage individuals’ active participation in physiotherapy depending on their (1) mental health problems, (2) physical difficulties, (3) level of cognitive function, (4) personality, (5) activities and participation, (6) age, (7) human environment, and (8) type of rehabilitation service where the individual undergoes treatment. For example, in cases where an individual lost self-confidence, participants offered practice tasks that the individual could achieve with little effort to make them experience success. Conversely, for individuals with overconfidence, participants would provide them with a relatively difficult practice task to help them realize the necessity of practice through the experience of failure. The interviews also revealed (9) motivational strategies used regardless of the individual’s condition. For instance, patient-centred communication was used to build a rapport with individuals, irrespective of their condition.ConclusionThis qualitative study is the first to demonstrate motivational strategies that physiotherapists use based on the individual’s condition. Our findings provide a deeper understanding of the selection of motivational strategies in stroke rehabilitation.
‘Ripple effects’ of urban environmental characteristics on cognitive performances in Eurasian red squirrels
Authors: Chow Pizza Ka Yee , Uchida Kenta , Koizumi Itsuro 
Published: May 2022

AbstractUrban areas are expanding exponentially, leading more wildlife species to reside and settle in this environment. Urban environmental characteristics, such as human disturbance or green coverage, have been shown to affect some cognitive abilities such as innovative problem-solving performance of wildlife species. However, an untested hypothesis is that due to the shared underlying cognitive mechanisms, these affected performances may induce a ‘ripple’ effect, and continue to affect other related cognitive processes (the ripple effect hypothesis).We tested this hypothesis by targeting two cognitive abilities, generalisation and memory, that overlap the cognitive mechanisms (learning and memory) of the original problem solving task in urban Eurasian red squirrels. These squirrels reside in 11 urban areas where they had previously repeatedly solved the original task (the innovators), and that their solving performance in the original task was affected by the selected urban environmental characteristics. We presented two established food-extraction tasks to the innovators to measure their performance in applying the learned successful solutions when solving a similar but novel problem (i.e., generalisation process) and recalling the learned solution of the original problem when solving the same task after an extended period of time (i.e., memory).Our results provide more detailed information to refine the hypothesis; the initial effects of urban environmental characteristics on the performance of the original task affect performance at individual level but not at population level. These affected performance includes individuals’ generalisation solving latency across successes as well as their first solving latency in the memory task.Urban environmental characteristics affect solving performance at both population and individual levels. Some environmental characteristics such as direct and indirect human disturbance affect the success of solving the generalisation task and the memory task at site level whereas other environmental characteristics such as green coverage affect the individuals’ solving latency in both tasks.Overall, our results support the ripple effect hypothesis, indicating that urban environmental characteristics have a more global impact on shaping cognitive performance than previously has shown, and thus provide a better understanding of the mechanism that supports wildlife in adapting to urban environments.
The nanoCUT&RUN technique visualizes telomeric chromatin in Drosophila
Authors: Chen Tao , Wei Xiaolu , Courret Cécile , Cui Min , Cheng Lin , Wu Jing , Ahmad Kami , Larracuente Amanda M. , Rong Yikang S. 
Published: May 2022

AbstractAdvances in genomic technology led to a more focused pattern for the distribution of chromosomal proteins and a better understanding of their functions. The recent development of the CUT&RUN technique marks one of the important such advances. Here we develop a modified CUT&RUN technique that we termed nanoCUT&RUN, in which a high affinity nanobody to GFP is used to bring micrococcal nuclease to the binding sites of GFP-tagged chromatin proteins. Subsequent activation of the nuclease cleaves the chromatin, and sequencing of released DNA identifies binding sites. We show that nanoCUT&RUN efficiently produces high quality data for the TRL transcription factor in Drosophila embryos, and distinguishes binding sites specific between two TRL isoforms. We further show that nanoCUT&RUN dissects the distributions of the HipHop and HOAP telomere capping proteins, and uncovers unexpected binding of telomeric proteins at centromeres. nanoCUT&RUN can be readily applied to any system in which a chromatin protein of interest, or its isoforms, carries the GFP tag.
Myeloid-Derived Suppressor Cells are relevant factors to predict the severity of multiple sclerosis
Authors: Ortega María Cristina , Lebrón-Galán Rafael , Machín-Díaz Isabel , Naughton Michelle , Pérez-Molina Inmaculada , García-Arocha Jennifer , García-Domínguez Jose Manuel , Goicoechea-Briceño Haydee , Vila-del Sol Virginia , Quintanero-Casero Víctor , García-Montero Rosa , Galán Victoria , Camacho-Toledano Celia , Martínez-Ginés María Luisa , Fitzgerald Denise C. , Clemente Diego 
Published: May 2022

ABSTRACTMultiple Sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Previous retrospective investigations in the MS model, experimental autoimmune encephalomyelitis (EAE), highlighted the important relationship between monocytic-myeloid-derived suppressor cells (M-MDSCs) and the experimented severity of the clinical course. In this work, we show for the first time cells resembling M-MDSCs associated to MS lesions, whose abundance was related to milder MS clinical courses. Moreover, Ly-6Chi cells (which are indistinguishable from circulating M-MDSCs in mice) are useful biomarkers to predict a milder severity of the EAE disease course and a lesser tissue damage extent. Finally, the abundance of M-MDSCs in blood from untreated MS patients at their first relapse was inversely correlated with EDSS at baseline and relapse recovery one-year later. In summary, our data point to M-MDSC load as a promising biomarker of patient’s clinical course severity.TeaserThe abundance of myeloid-derived suppressor cells is related to a milder clinical course in multiple sclerosis patients.
Vision-dependent and -independent molecular maturation of mouse retinal ganglion cells
Authors: Whitney Irene E. , Butrus Salwan , Dyer Michael A. , Rieke Fred , Sanes Joshua R. , Shekhar Karthik 
Published: May 2022

ABSTRACTThe development and connectivity of retinal ganglion cells (RGCs), the retina’s sole output neurons, are patterned by activity-independent transcriptional programs and activity-dependent remodeling. To inventory the molecular correlates of these influences, we applied high-throughput single-cell RNA sequencing (scRNA-seq) to mouse RGCs at six embryonic and postnatal ages. We identified temporally regulated modules of genes that correlate with, and likely regulate, multiple phases of RGC development, ranging from differentiation and axon guidance to synaptic recognition and refinement. Some of these genes are expressed broadly while others, including key transcription factors and recognition molecules, are selectively expressed by one or a few of the 45 transcriptomically distinct types defined previously in adult mice. Next, we used these results as a foundation to analyze the transcriptomes of RGCs in mice lacking visual experience due to dark rearing from birth or to mutations that ablate either bipolar or photoreceptor cells. 98.5% of visually deprived (VD) RGCs could be unequivocally assigned to a single RGC type based on their transcriptional profiles, demonstrating that visual activity is dispensable for acquisition and maintenance of RGC type identity. However, visual deprivation significantly reduced the transcriptomic distinctions among RGC types, implying that activity is required for complete RGC maturation or maintenance. Consistent with this notion, transcriptomic alternations in VD RGCs significantly overlapped with gene modules found in developing RGCs. Our results provide a resource for mechanistic analyses of RGC differentiation and maturation, and for investigating the role of activity in these processes.
Endogenous production of hyaluronan, PRG4, and cytokines is sensitive to cyclic loading in synoviocytes
Authors: Pendyala Meghana , Woods Paige S , Brubaker Douglas K , Blaber Elizabeth A , Schmidt Tannin A , Chan Deva D 
Published: May 2022

AbstractSynovial fluid is composed of hyaluronan and proteoglycan-4 (PRG4 or lubricin), which work synergistically to maintain joint lubrication. In diseases like osteoarthritis, hyaluronan and PRG4 concentrations can be altered, resulting in lowered synovial fluid viscosity, and pro-inflammatory cytokine concentrations within the synovial fluid increase. Synovial fibroblasts within the synovium are responsible for contributing to synovial fluid and can be targeted to improve endogenous production of hyaluronan and PRG4 and to alter the cytokine profile. We cyclically loaded SW982 synoviocytes to 0%, 5%, 10%, or 20% strain for three hours at 1 Hz. To assess the impact of substrate stiffness, we compared the 0% strain group to cells grown on tissue culture plastic. We measured the expression of hyaluronan turnover genes, hyaluronan localization within the cell layer, hyaluronan concentration, PRG4 concentration, and the cytokine profile within the media. Our results show that the addition of cyclic loading increased HAS3 expression, but not in a magnitude-dependent response. Hyaluronidase expression was impacted by strain magnitude, which is exemplified by the decrease in hyaluronan concentration due to cyclic loading. We also show that PRG4 concentration is increased at 5% strain, while higher strain magnitude decreases overall PRG4 concentration. Finally, 10% and 20% strain show a distinct, more pro-inflammatory cytokine profile when compared to the unloaded group. Multivariate analysis showed distinct separation between certain strain groups in being able to predict strain group, hyaluronan concentration, and PRG4 concentration from gene expression or cytokine concentration data, highlighting the complexity of the system. Overall, this study shows that cyclic loading can be used tool to modulate the endogenous production of hyaluronan, PRG4, and cytokines from synovial fibroblasts.
Microbiota-induced active translocation of peptidoglycan across the intestinal barrier dictates its within-host dissemination
Authors: Wheeler Richard , Bastos Paulo A. D. , Disson Olivier , Rifflet Aline , Spielbauer Julia , Lecuit Marc , Boneca Ivo Gomperts 
Published: May 2022

AbstractPeptidoglycan, the major structural polymer forming the cell wall of bacteria, is an important mediator of physiological and behavioral effects in mammalian hosts. These effects are frequently linked to its translocation from the intestinal lumen to host tissues. However, the modality and regulation of this translocation across the gut barrier has not been precisely addressed. In this study, we characterized the absorption of peptidoglycan across the intestine and its systemic dissemination. We report that peptidoglycan has a distinct tropism for host organs when absorbed via the gut, most notably by favoring access to the brain. We demonstrate that intestinal translocation of peptidoglycan occurs through a microbiota-induced active process. This process is regulated by the parasympathetic pathway via the muscarinic acetylcholine receptors. Together, this study reveals fundamental parameters concerning the uptake of a major microbiota molecular signal from the steady-state gut.
Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Authors: Li Shuang , Schmid Katharina T. , de Vries Dylan , Korshevniuk Maryna , Oelen Roy , van Blokland Irene ,   BIOS Consortium,   sc-eQTLgen Consortium, Groot Hilde E. , Swertz Morris , van der Harst Pim , Westra Harm-Jan , van der Wijst Monique , Heinig Matthias , Franke Lude 
Published: May 2022

AbstractBackgroundExpression quantitative trait loci (eQTL) studies have shown how genetic variants affect downstream gene expression. To identify the upstream regulatory processes, single-cell data can be used. Single-cell data also offers the unique opportunity to reconstruct personalized co-expression networks—by exploiting the large number of cells per individual, we can identify SNPs that alter co-expression patterns (co-expression QTLs, co-eQTLs) using a limited number of individuals.ResultsTo tackle the large multiple testing burden associated with a genome-wide analysis (i.e. the need to assess all combinations of SNPs and gene pairs), we conducted a co-eQTL meta-analysis across four scRNA-seq peripheral blood mononuclear cell datasets from three studies (reflecting 173 unique participants and 1 million cells) using a novel filtering strategy followed by a permutation-based approach. Before analysis, we evaluated the co-expression patterns to be used for co-eQTL identification using different external resources. The subsequent analysis identified a robust set of cell-type-specific co-eQTLs for 72 independent SNPs that affect 946 gene pairs, which we then replicated in a large bulk cohort. These co-eQTLs provide novel insights into how disease-associated variants alter regulatory networks. For instance, one co-eQTL SNP, rs1131017, that is associated with several autoimmune diseases affects the co-expression of RPS26 with other ribosomal genes. Interestingly, specifically in T cells, the SNP additionally affects co-expression of RPS26 and a group of genes associated with T cell-activation and autoimmune disease. Among these genes, we identified enrichment for targets of five T-cell-activation-related transcriptional factors whose binding sites harbor rs1131017. This reveals a previously overlooked process and pinpoints potential regulators that could explain the association of rs1131017 with autoimmune diseases.ConclusionOur co-eQTL results highlight the importance of studying gene regulation at the context-specific level to understand the biological implications of genetic variation. With the expected growth of sc-eQTL datasets, our strategy—combined with our technical guidelines—will soon identify many more co-eQTLs, further helping to elucidate unknown disease mechanisms.
A Quantum Dot Biomimetic for SARS-CoV-2 to Interrogate Dysregulation of the Neurovascular Unit Relevant to Brain Inflammation
Authors: Chiang Wesley , Stout Angela , Yanchik-Slade Francine , Li Herman , Nilsson Bradley , Gelbard Harris , Krauss Todd 
Published: May 2022

ABSTRACTDespite limited evidence for competent infection and viral replication of SARS-CoV-2 in the central nervous system (CNS), neurologic dysfunction is a common post-acute medical condition reported in “recovered” COVID-19 patients. To identify a potential noninfectious route for SARS-CoV-2-mediated neurological damage, we constructed colloidal nanocrystal quantum dots linked to micelles decorated with spike protein (COVID-QDs) as a biomimetic to interrogate how blood-brain barrier (BBB) dysregulation may subsequently induce neuroinflammation in the absence of infection. In transwell co-culture of endothelial bEnd.3 monolayers and primary neuroglia, we exposed only the bEnd.3 monolayers to COVID-QDs and examined by fluorescence microscopy whether such treatment led to (i) increased inflammation and leakage across the bEnd.3 monolayers, (ii) permeability of the COVID-QDs across the monolayers, and (iii) induction of neuroinflammation in neuroglial cultures. The results of our study provide evidence of neuroinflammatory hallmarks in cultured neurons and astrocytes without direct exposure to SARS-CoV-2-like nanoparticles. Additionally, we found that pre-treatment of our co-cultures with a small-molecule, broad-spectrum inhibitor of mixed lineage and leucine rich repeat kinases led to reversal of the observed dysregulation in endothelial monolayers and resulted in neuroglial protection. The results reported here may serve to guide future studies into the potential mechanisms by which SARS-CoV-2 mediates neurologic dysfunction.
Heavy metals in moss guide environmental justice investigation: a case study using community science in Seattle, WA, USA
Authors: Jovan Sarah E. , Zuidema Christopher , Derrien Monika M. , Bidwell Amanda L. , Brinkley Weston , Smith Robert J. , Blahna Dale , Barnhill Roseann , Gould Linn , Rodríguez Alberto J. , Amacher Michael C. , Abel Troy D. , López Paulina 
Published: May 2022

AbstractHeavy metals concentrations often vary at small spatial scales not captured by air monitoring networks, with implications for environmental justice in industrial-adjacent communities. Pollutants measured in moss tissues are commonly used as a screening tool to guide use of more expensive resources, like air monitors. Such studies, however, rarely address environmental justice issues or involve the residents and other decision-makers expected to utilize results. Here, we piloted a community science approach, engaging over 55 people from nine institutions, to map heavy metals using moss in two industrial-adjacent neighborhoods. This area, long known for disproportionately poor air quality, health outcomes, and racial inequities, has only one monitor for heavy metals. Thus, an initial understanding of spatial patterns is critical for gauging whether, where, and how to invest further resources towards investigating heavy metals. Local youth led sampling of the moss Orthotrichum lyellii from trees across a 250×250-m sampling grid (n = 79) and generated data comparable to expert-collected samples (n = 19). We mapped 21 chemical elements measured in moss, including 6 toxic ‘priority’ metals: arsenic, cadmium, chromium, cobalt, lead, and nickel. Compared to other urban O. lyellii studies, local moss had substantially higher priority metals, especially arsenic and chromium, encouraging community members to investigate further. Potential hotspots of priority metals varied somewhat but tended to peak near the central industrial core where many possible emissions sources, including legacy contamination, converge. Informed by these findings, community members successfully advocated regulators for a second study phase – a community-directed air monitoring campaign to evaluate residents’ exposure to heavy metals – as is needed to connect moss results back to the partnership’s core goal of understanding drivers of health disparities. This follow-up campaign will measure metals in the PM10 fraction owing to clues in the current study that airborne soil and dust may be locally important carriers of priority metals. Future work will address how our approach combining bioindicators and community science ultimately affects success addressing longstanding environmental justice concerns. For now, we illustrate the potential to co-create new knowledge, to help catalyze and strategize next steps, in a complex air quality investigation.
Evolutionary investigations of the biosynthetic diversity in the skin microbiome usinglsaBGC
Authors: Salamzade Rauf , Cheong J.Z. Alex , Sandstrom Shelby , Swaney Mary Hannah , Stubbendieck Reed M. , Starr Nicole Lane , Currie Cameron R. , Singh Anne Marie , Kalan Lindsay R. 
Published: May 2022

AbstractWe developedlsaBGC, a bioinformatics suite that introduces several new methods to expand on the available infrastructure for genomic and metagenomic-based comparative and evolutionary investigation of biosynthetic gene clusters (BGCs). Through application of the suite to four genera commonly found in skin microbiomes, we uncover multiple novel findings on the evolution and diversity of their BGCs. We show that the virulence associated carotenoid staphyloxanthin inStaphylococcus aureusis ubiquitous across theStaphylococcusgenus but has largely been lost in the skin-commensal speciesStaphylococcus epidermidis. We further identify thousands of novel single nucleotide variants (SNVs) within BGCs from theCorynebacterium tuberculostearicumsp. complex, which we describe here to be a narrow, multi-species clade that features the most prevalentCorynebacteriumin healthy skin microbiomes. Although novel SNVs were approximately ten times as likely to correspond to synonymous changes when located in the top five percentile of conserved sites,lsaBGCidentified SNVs which defied this trend and are predicted to underlie amino acid changes within functionally key enzymatic domains. Ultimately, beyond supporting evolutionary investigations,lsaBGC provides important functionalities to aid efforts for the discovery or synthesis of natural products.
Strong basal/tonic TCR signals are associated with negative regulation of naive CD4+ T cells
Authors: Zinzow-Kramer Wendy M. , Eggert Joel , Scharer Christopher D. , Au-Yeung Byron B. 
Published: May 2022

ABSTRACTTonic TCR signaling occurs constitutively in response to self-peptides presented by MHC (pMHC). Tonic TCR signal intensity correlates with Nur77-GFP reporter transgene expression. A broad range of Nur77-GFP is first detectable in post-selection thymocytes and persists in mature T cells. Nur77-GFPHI Ly6C− CD4+ T cells experience the strongest tonic TCR signaling and exhibit functional hypo-responsiveness to foreign pMHC stimulation. Gene expression analyses suggest similarities between the programs induced by strong tonic TCR signaling and T cell activation. However, the strongest tonic TCR signals also appear to induce expression of negative regulators, including coinhibitory receptors. Analysis of chromatin accessibility similarly suggest that strong tonic TCR signaling correlates with differentially higher accessibility of over 3000 chromatin regions in or near genes that encode positive and negative regulators of T cell activation. We propose that very strong tonic TCR signaling induces mechanisms of negative feedback to recalibrate T cell sensitivity.