bluuebunny/crossref_metadata_2025_split huggingface dataset:
Habitat types and megabenthos composition from three sponge-dominated high-Arctic seamounts
Authors: Stratmann Tanja , Simon-Lledó Erik , Morganti Teresa Maria , Vedenin Andrey , Purser Autun 
Published: June 2022

AbstractSeamounts are isolated underwater mountains often stretching >1,000 m above the seafloor. They are usually identified as biodiversity hotspots of marine life, and host benthos assemblages that may vary on regional (among seamounts) and local (within seamounts) scales. Here, we collected seafloor imagery of three seamounts at the Langseth Ridge in the central Arctic Ocean to assess habitats and megabenthos community composition at the Central Mount (CM), the Karasik Seamount (KS), and the Northern Mount (NM). The majority of seafloor across these seamounts comprised bare rock, covered with a mixed layer consisting of sponge spicule mat intermixed with detrital debris composed primarily of polychaete tubes as well as sand, gravel, and/ or rocks. The megabenthos assemblages consisted of in total 15 invertebrate epibenthos taxa and four fish taxa, contributing to mean megabenthos densities of 55,745 ind. ha-1 at CM, 110,442 ind. ha-1 at KS, and 65,849 ind. ha-1 at NM. The faunal assemblages at all three seamounts were dominated by demosponges of the order Tetractinellida that contributed between 66% (KS) and 85% (CM) to all megabenthos. Megabenthos assemblages living on bare rock or on mixed substrate differed among seamounts and across individual seamounts.
The Injured Sciatic Nerve Atlas (iSNAT), Insights into the Cellular and Molecular Basis of Neural Tissue Degeneration and Regeneration
Authors: Zhao Xiao-Feng , Huffman Lucas D. , Hafner Hannah , Athaiya Mitre , Finneran Matthew , Kalinski Ashley L. , Kohen Rafi , Flynn Corey , Passino Ryan , Johnson Craig , Kohrman David , Kawaguchi Riki , Yang Lynda , Twiss Jeff , Geschwind Daniel H. , Corfas Gabriel , Giger Roman J. 
Published: June 2022

AbstractUpon trauma, the adult murine PNS displays a remarkable degree of spontaneous anatomical and functional regeneration. To explore extrinsic mechanisms of neural repair, we carried out single cell analysis of naïve mouse sciatic nerve, peripheral blood mononuclear cells, and crushed sciatic nerves at 1-day, 3-days, and 7-days following injury. During the first week, monocytes and macrophages (Mo/Mac) rapidly accumulate in the injured nerve and undergo extensive metabolic reprogramming. Proinflammatory Mo/Mac in the injured nerve show high glycolytic flux compared to Mo/Mac in blood and dominate the early injury response. They subsequently give way to inflammation resolving Mac, programmed toward oxidative phosphorylation. Nerve crush injury causes partial leakiness of the blood-nerve-barrier, proliferation of endoneurial and perineurial stromal cells, and accumulation of select serum proteins. Micro-dissection of the nerve injury site and distal nerve, followed by single-cell RNA-sequencing, identified distinct immune compartments, triggered by mechanical nerve wounding and Wallerian degeneration, respectively. This finding was independently confirmed with Sarm1-/- mice, where Wallerian degeneration is greatly delayed. Experiments with chimeric mice showed that wildtype immune cells readily enter the injury site in Sarm1-/- mice, but are sparse in the distal nerve, except for Mo. We used CellChat to explore intercellular communications in the naïve and injured PNS and report on hundreds of ligand-receptor interactions. Our longitudinal analysis represents a new resource for nerve regeneration, reveals location specific immune microenvironments, and reports on large intercellular communication networks. To facilitate mining of scRNAseq datasets, we generated the injured sciatic nerve atlas (iSNAT): https://cdb-rshiny.med.umich.edu/Giger_iSNAT/
Habitat heterogeneity, environmental feedbacks, and species coexistence across timescales
Authors: Miller Zachary R. , Allesina Stefano 
Published: June 2022

AbstractA large body of ecological theory explains the coexistence of multiple species in variable environments. While spatial variation is often treated as an intrinsic feature of a landscape, it may be shaped and even generated by the resident community. All species modify their local environment to some extent, driving changes that can feed back to affect the composition and coexistence of the community, potentially over timescales very different from population dynamics. We introduce a simple, nested modeling framework that describes species coexistence in heterogeneous environments, as well as the evolution of this heterogeneity over time due to feedbacks from the biotic community. We derive analytical conditions for the coexistence of any number of species in environments with intrinsic heterogeneity or feedbacks, and identify essential differences between these scenarios. Our model is naturally simplified in the limit of very fast or very slow environmental feedbacks, allowing us to treat these two scenarios – which bookend the full range of dynamics – in detail. Among other results, we demonstrate how dispersal and environmental specialization interact to shape realized patterns of habitat association. We also show that environmental feedbacks can tune landscape conditions to promote stable coexistence, although feedbacks can give rise to complex dynamics such as limit cycles, priority effects, and episodic dynamics, as well. Our flexible modeling framework helps explain how and when each of these behaviors arise, and offers a generic mathematical platform for exploring the interplay between species and landscape diversity.
Artificial upwelling leads to a large increase in surface dissolved organic matter concentrations
Authors: Gómez-Letona Markel , Sebastián Marta , Baños Isabel , Fernanda Montero María , Pérez Barrancos Clàudia , Baumann Moritz , Riebesell Ulf , Arístegui Javier 
Published: June 2022

AbstractIn the face of climate change there is a need to reduce atmospheric CO2 concentrations. Artificial upwelling of nutrient-rich deep waters has been proposed as a method to enhance the biological carbon pump in oligotrophic oceanic regions in order to increase carbon sequestration. However, the fate of the newly produced organic matter, and specifically of its resulting dissolved fraction, is not clearly understood. Here we examine the effect of different upwelling intensities and modes (single pulse versus recurring pulses) on the dissolved organic matter pool (DOM). We introduced nutrient-rich deep water to large scale mesocosms (∼44 m3) in the oligotrophic subtropical North Atlantic and found that artificial upwelling strongly increased DOM concentrations and changed its characteristics. The magnitude of the observed changes was related to the upwelling intensity: more intense treatments led to higher accumulation of dissolved organic carbon (>70 μM of excess DOC over ambient waters for the most intense) and to comparatively stronger changes in DOM characteristics (increased proportions of chromophoric DOM (CDOM) and humic-like fluorescent DOM), suggesting a transformation of the DOM pool at the molecular level. Moreover, the single upwelling pulse resulted in higher CDOM quantities with higher molecular weight than the recurring upwelling mode. Together, our results indicate that under artificial upwelling, large DOM pools may accumulate in the surface ocean without being remineralised in the short-term. Possible reasons for this persistence could be a combination of the molecular diversification of DOM due to microbial reworking, nutrient limitation and reduced metabolic capabilities of the prokaryotic communities inside the mesocosms. Our study demonstrates the importance of the DOC pool when assessing the carbon sequestration potential of artificial upwelling.
Accuracy of haplotype estimation and whole genome imputation affects complex trait analyses in complex biobanks
Authors: Appadurai Vivek , Grauholm Jonas , Krebs Morten , Rosengren Anders , Buil Alfonso , Ingason Andrés , Mors Ole , Børglum Anders D. , Hougaard David M. , Nordentoft Merete , Mortensen Preben B. , Delaneau Olivier , Werge Thomas , Schork Andrew J. 
Published: June 2022

AbstractSample recruitment for research consortia, hospitals, biobanks, and personal genomics companies span years, necessitating genotyping in batches, using different technologies. As marker content on genotyping arrays varies systematically, integrating such datasets is non-trivial and its impact on haplotype estimation (phasing) and whole genome imputation, necessary steps for complex trait analysis, remains under-evaluated. Using the iPSYCH consortium dataset, comprising 130,438 individuals, genotyped in two stages, on different arrays, we evaluated phasing and imputation performance across multiple phasing methods and data integration protocols. While phasing accuracy varied both by choice of method and data integration protocol, imputation accuracy varied mostly between data integration protocols. We demonstrate an attenuation in imputation accuracy within samples of non-European origin, highlighting challenges to studying complex traits in diverse populations. Finally, imputation errors can modestly bias association tests and reduce predictive utility of polygenic scores. This is the largest, most comprehensive comparison of data integration approaches in the context of a large psychiatric biobank.
Evaluating a novel, integrative dashboard for health professionals’ performance in managing deteriorating patients:quality improvement project
Authors: Alhmoud Baneen , Melley Daniel , khan Nadeem , Bonnici Timothy , Patel Riyaz , Banerjee Amitava 
Published: June 2022

AbstractBackgroundThe quality of recording and documentation of deteriorating patient management by health professionals has been challenged at health system level during the COVID-19 pandemic. Non-adherence to monitoring and escalation guidelines and poor documentation increases risk of serious adverse events. Electronic health record (EHR)-integrated dashboards are real-time auditing tools of patients’ status and clinicians’ performance, but neither the views nor the performance of health professionals have been assessed, relating to management of deteriorating patients..ObjectiveTo develop and evaluate a real-time dashboard of deteriorating patients’ assessment, referral, and therapy by examining the perception of the dashboard and the performance of nurses and physicians.SettingsFive academic hospitals in the largest NHS trust in the UK (Barts Health NHS Trust).InterventionThe dashboard was developed from EHR data to investigate patients with NEWS2>5, assessment, and escalation of deteriorating patients. We adopted the Plan, Do, Study, Act model and followed the SQUIRE framework to evaluate the dashboard.DesignMixed methods: (i) Virtual, face-to-face, key informant interviews and (ii) Retrospective descriptive EHR data analysis to measure performance change over time.ResultsWe interviewed 3 nurses (2 quality and safety and 1 informatics specialists). Key themes were: (1) participants perceived the dashboard as a facilitator for auditing NEWS2 recording and escalation of care to improve clinicians practice; (2) There is a need for guiding clinicians and adjusting data sources and metrics which could enhance the functionality and usability. From EHR (2019 to 2022) data analysis showed: (1) NEWS2 recording has gradually improved in the implementation and evaluation phases (May 2021 to Apr 2022) from 64% to 83%; (2) Referral and nurses’ assessment forms completion increased (n: 170 to 6800 & 23 to 540, respectively).ConclusionThe deterioration dashboard is an effective real time data-driven method for improving the quality of managing deteriorating patients. Improving the dashboard by integrating multiple health systems, a wider analysis of further NEWS2 and escalation of care metrics, clinicians’ learning of digital solutions will enhance functionality and experience, potentially boosting its value. There is a need to examine the generalizability of the dashboard through further validation and quality improvement studies.
Exercise-induced hypoalgesia following proprioceptive neuromuscular facilitation and resistance training among individuals with shoulder myofascial pain: a pilot study
Authors: Xu Zi-Han , An Nan , Wang Zi-Ru 
Published: June 2022

AbstractObjectiveThe present study estimated the effect of proprioceptive neuromuscular facilitation (PNF) and resistance training on exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM) among patients with myofascial pain syndrome (MPS).MethodsA total of 76 female MPS patients (aged from 18-30) with a visual analog scale (VAS) score greater than 30/100 mm were enrolled in the study. Participants were randomly assigned into 3 intervention groups, including isometric (n=18), isotonic (n=19) and PNF (n=20) exercises, and 1 control group (n=19) with no intervention. Pressure pain threshold (PPT) and the CPM responses at myofascial trigger point, arm and leg sites were assessed before and after exercise session.ResultsThere was an increase in PPT and CPM responses at trigger point, arm and leg sites in participants performed PNF and isotonic exercise, while the isometric exercise only increased PPT at leg sites. Compared with control group, both isotonic and PNF group showed greater EIH responses at the trigger points. However, only the PNF exercise significantly improved PPT and CPM responses at arm and leg sites compared to the control group.ConclusionsPNF, isotonic and isometric exercises could lead to local and global EIH effect. The increase in CPM response after PNF and isotonic exercises indicated that the EIH mechanisms of different resistance exercises may be attributed to the enhancement of the endogenous pain modulation through the motor-sensory interaction from the additional eccentric and dynamic muscle contraction.
Molecular genomic studies of the obesogenic effects of tributyltin during adipogenic differentiation implicate a primary role for cytoskeletal damage
Authors: Thompson Taylor V. , Greally John M. 
Published: June 2022

ABSTRACTEnvironmental obesogens are being studied for their potential role in the increasing prevalence of obesity globally. A major focus in this field of research has been on the mechanism by which these agents act. In this study we focused on the obesogenic organotin tributyltin (TBT), which is believed to act by binding to the PPARγ nuclear receptor in a heterodimer with RXR to alter gene regulation. To test whether this was the dominant mechanism for TBT activity, we performed time-course studies of transcription and chromatin accessibility in mesenchymal stem cells differentiating to adipocytes. We found limited evidence for PPARγ effects by TBT, but a strong response by Ras-related GTPases and evidence for the loss of TEAD transcription factor activity during differentiation. These observations combine to implicate a known property of organotins, to cause cytoskeletal cytoskeletal damage as the primary event in an updated model for TBT effects, leading to the loss of YAP co-regulator activity and the consequent failure of TEAD repression of adipogenesis.
Short-term Rho-associated kinase inhibitor treatment accelerates primary keratinocyte growth while preserving stem cell characteristics
Authors: Jayarajan Vignesh , Hall George T. , Xenakis Theodoros , Bulstrode Neil , Moulding Dale , Castellano Sergi , Di Wei-Li 
Published: June 2022

AbstractSomatic stem cells can be cultured in-vitro and are attractive for cell and gene therapies, but their slow growth in in-vitro culture affects survival and stemness and hinders clinical applications. Rho-associated kinase inhibitor (ROCKi) has been used to overcome these obstacles. However, it risks changing the characteristics of stem cells. We found that primary keratinocyte stem cells (KSCs) cultured with the ROCKi Y-27632 for six days exhibited rapid proliferation while maintaining the ability to differentiate. Importantly, after discontinuation of ROCKi treatment, KSC numbers and characteristics were indistinguishable from those in non-treated cultures. We further confirmed that ROCKi treatment resulted in the activation of AKT and ERK pathways, which could support cell survival and proliferation in keratinocytes. We thus concluded that accelerating keratinocyte expansion with short-term ROCKi treatment does not exhaust KSCs’ self-renewal and differentiation capacities, presenting a safe avenue for clinical applications.
Tissue specific LRRK2 interactomes reveal a distinct functional unit within the striatum
Authors: Zhao Yibo , Vavouraki Nikoleta , Lovering Ruth C , Escott-Price Valentina , Harvey Kirsten , Lewis Patrick A , Manzoni Claudia 
Published: June 2022

AbstractMutations in LRRK2 are the most common genetic cause of Parkinson’s disease. Despite substantial research efforts, the physiological and pathological role of this multidomain protein remains poorly defined. In this study, we used a systematic approach to construct the general protein-protein interactome around LRRK2, which was then differentiated into 15 tissue-specific interactomes taking into consideration the differential expression patterns and the co-expression behaviours of the LRRK2 interactors in different healthy tissues. The LRRK2 interactors exhibited distinct expression features in the brain as compared to the peripheral tissues analysed. Moreover, a high degree of similarity was found for the LRRK2 interactors in putamen, caudate and nucleus accumbens, thus defining a potential LRRK2 functional cluster within the striatum. We also explored the functions highlighted by the “core LRRK2 interactors” within each tissue and illustrated how the LRRK2 interactomes can be used as a tool to trace the relationship between LRRK2 and specific interactors of interest, here exemplified with a study focused on the LRRK2 interactors belonging to the Rab protein family.
Nanocontainer derived from silkworm carotenoprotein for carotenoid extraction and presentation in biotechnology and biomedical applications
Authors: Sluchanko Nikolai N. , Slonimskiy Yury B. , Egorkin Nikita A. , Varfolomeeva Larisa A. , Kleymenov Sergey Yu. , Minyaev Mikhail E. , Moysenovich Anastasia M. , Parshina Evgenia Yu. , Friedrich Thomas , Maksimov Eugene G. , Boyko Konstantin M. , Popov Vladimir O. 
Published: June 2022

AbstractFound in many organisms, soluble carotenoproteins are considered as antioxidant nanocarriers for biomedical applications, although the structural basis for their carotenoid transfer function, a prerequisite for rational bioengineering, is largely unknown. We report crystal structures of the Carotenoid-Binding Protein from Bombyx mori (BmCBP) in apo- and zeaxanthin (ZEA)-bound forms. We use spectroscopy and calorimetry to characterize how ZEA and BmCBP mutually affect each other in the complex, identify key carotenoid-binding residues, confirm their roles by crystallography and carotenoid-binding capacity of BmCBP mutants and reconstitute BmCBP complexes with biomedically-relevant xanthophylls lutein, zeaxanthin, canthaxanthin and astaxanthin. By cost-effectively and scalably solubilizing xanthophylls from various crude herbal extracts, His-tagged BmCBP remains monomeric and forms a dynamic nanocontainer delivering carotenoids to liposomes and to other carotenoid-binding proteins, which in particular makes the Orange Carotenoid Protein, a promising optogenetic tool, photoactive. Furthermore, BmCBP(ZEA) administration stimulates fibroblast growth, which paves the way for its biomedical applications.
Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir
Authors: Hu Yanmei , Lewandowski Eric M. , Tan Haozhou , Zhang Xiaoming , Morgan Ryan T. , Zhang Xiujun , Jacobs Lian M. C. , Butler Shane G. , Gongora Maura V. , Choy John , Deng Xufang , Chen Yu , Wang Jun 
Published: June 2022

ABSTRACTThe SARS-CoV-2 main protease (Mpro) is the drug target of Pfizer’s oral drug Paxlovid. The emergence of SARS-CoV-2 variants with mutations in Mpro raised the alarm of potential drug resistance. In this study, we identified 100 naturally occurring Mpro mutations located at the nirmatrelvir binding site, among which 20 mutants, including S144M/F/A/G/Y, M165T, E166G, H172Q/F, and Q192T/S/L/A/I/P/H/V/W/C/F, showed comparable enzymatic activity to the wild-type (kcat/Km <10-fold change) and resistance to nirmatrelvir (Ki >10-fold increase). X-ray crystal structures were determined for seven representative mutants with and/or without GC-376/nirmatrelvir. Viral growth assay showed that Mpro mutants with reduced enzymatic activity led to attenuated viral replication. Overall, our study identified several drug resistant hot spots that warrant close monitoring for possible clinical evidence of Paxlovid resistance.One Sentence SummaryPaxlovid resistant SARS-CoV-2 viruses with mutations in the main protease have been identified from clinical isolates.
Solution-based orientation as an element in selecting videos on social issues
Authors: Al Bulushi Zawan 
Published: June 2022

PurposeThis study aims to explore students’ interests in multimodal texts by focusing on videos of social issues.Design/methodology/approachData from 50 students in a first-year multilingual composition course were analyzed in two phases. Phase One examined 14 students’ reasons for self-selecting videos for multimodal analysis essays in one section of the course. Phase Two explored 50 students’ selected videos in four sections of the course across four semesters. The videos were classified as either problem- or solution-oriented to examine the students’ interests.FindingsAnalyzing the students’ responses in Phase One revealed that most of the selected videos included solutions to a social problem, and the students advocated the compelling ways in which the characters therein dealt with those problems. The findings for Phase Two revealed that the students’ selections were equally divided between problem- and solution-oriented videos. Nevertheless, a gradual increase in the selection of solution-oriented videos was observed over time.Practical implicationsA significant implication of this study is that it can help teachers expand their understanding of interesting and meaningful texts and make more engaging and effective instructional decisions.Originality/valueThe study contributes to the literature on text selection as it highlights students’ inclination toward what type of learning content interests them.