bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic profiling of the large vessel vasculitis spectrum identifies shared signatures of innate immune activation and stromal remodelling
Authors: Maughan Robert T. , MacDonald-Dunlop Erin , Haroon-Rashid Lubna , Sorensen Louise , Chaddock Natalie , Masters Shauna , Porter Andrew , Peverelli Marta , Pericleous Charis , Hutchings Andrew , Robinson James , Youngstein Taryn , Luqmani Raashid A. , Mason Justin C. , Morgan Ann W. , Peters James E. 
Published: September 2024

AbstractTakayasu arteritis (TAK) and giant cell arteritis (GCA) are the primary forms of large vessel vasculitis (LVV) and can result in serious cardiovascular morbidity. Improved understanding of the molecular basis of these diseases is required to develop novel biomarkers and targeted treatments. Moreover, it is unclear whether shared or distinct pathogenic processes underpin the LVV spectrum. To address this, we performed plasma proteomic profiling, quantifying 184 plasma proteins using Olink immunoassays in two independent cohorts totalling 405 individuals. In Cohort 1, comparison of patients with TAK (N=96) and large vessel-GCA (LV-GCA) (N=35) versus healthy controls (HCs) (N=35) revealed 52 and 72 significant differentially abundant proteins, respectively. Correlation with disease activity status identified novel TAK and LV-GCA disease activity markers. Cohort 2 consisted of patients presenting acutely with possible cranial GCA (C-GCA); C-GCA was subsequently confirmed (n=150) or excluded (n=89). 31 proteins were associated with C-GCA. Analyses stratified by temporal artery biopsy results revealed enrichment of the proteomic signal in biopsy-proven GCA, suggesting the presence of distinct endotypes within C-GCA. Cross-disease comparison revealed that active TAK, LV-GCA and biopsy-proven C-GCA had highly similar plasma proteomic profiles. Twenty-six proteomic associations were shared across all three groups including IL6, monocyte/macrophage related proteins (CCL5, CCL7, CSF1), tissue remodelling proteins (VEGFA, TIMP1, TNC) and proteins not previously linked to LVV (TNFSF14, IL7R). We also observed disease-specific associations including increased CXCL9 in LV-GCA and C-GCA but not in TAK and decreases in the extracellular matrix protein COMP in TAK but not in LV-GCA or C-GCA. Evaluation of publicly available transcriptomic data from LV-GCA aortic tissue revealed that 47 of the 112 proteins significantly altered in ≥1 LVV type had significantly altered mRNA expression in LVV aortic tissue. Similarities in LVV proteomic profiles suggest shared pathobiology involving innate immunity, particularly monocyte/macrophages, lymphocyte homeostasis and tissue remodelling processes. Our results highlight a signature of immune-stromal cross talk in LVV and identify potential novel therapeutic targets in this axis (e.g. TNFSF14). The correspondence of plasma signatures to tissue phenotype highlights the potential for non-invasive monitoring of arterial inflammation and injury.
Knowledge mobilization with and for equity-deserving communities invested in research: A scoping review protocol
Authors: Barhouche Ramy , Tse Samson , Inglis Fiona , Chaves Debbie , Allison Erin , Colaco Tina , Morton Ninomiya Melody E. 
Published: September 2024

AbstractThe practice of putting research into action is known by various names, depending on disciplinary norms. Knowledge mobilization, translation, and transfer (collectively referred to as K*) are three common terminologies used in research literature. Knowledge-to-action opportunities and gaps in academic research often remain obscure to non-academic researchers in communities, policy and decision makers, and practitioners who could benefit from up-to-date information on health and wellbeing. Academic research training, funding, and performance metrics rarely prioritize or address non-academic community needs from research. We propose to conduct a scoping review on reported K* in community-driven research contexts, examining the governance, processes, methods, and benefits of K*, and mapping who, what, where, and when K* terminology is used. This protocol paper outlines our approach to gathering, screening, analyzing, and reporting on available published literature from four databases.
Development and calibration of a mathematical model of HIV outcomes among Rwandan adults: informing equitable achievement of targets in Rwanda
Authors: Kimmel April D. , Pan Zhongzhe , Brazier Ellen , Murenzi Gad , Muhoza Benjamin , Yotebieng Marcel , Anastos Kathryn , Nash Denis 
Published: September 2024

ABSTRACTBackgroundWe developed and calibrated the Central Africa-International epidemiology Databases to Evaluate AIDS (CA-IeDEA) HIV policy model to inform equitable achievement of global goals, overall and across sub-populations, in Rwanda.MethodsWe created a deterministic dynamic model to project adult HIV epidemic and care continuum outcomes, overall and for 25 subpopulations (age group, sex, HIV acquisition risk, urbanicity). Data came from the Rwanda cohort of CA-IeDEA, 2004–2020; Rwanda Demographic and Health Surveys, 2005, 2010, 2015; Rwanda Population-based HIV Impact Assessment, 2019; and the literature and reports. We calibrated the model to 47 targets by selecting the 50 best-fitting parameter sets among 20,000 simulations. Calibration targets reflected epidemic (HIV prevalence, incidence), global goals (percentage on antiretroviral therapy (ART) among diagnosed, percentage virally suppressed among on ART) and other (number on ART, percentage virally suppressed) indicators, overall and by sex. Best-fitting sets minimized the summed absolute value of the percentage deviation (AVPD) between model projections and calibration targets. Good model performance was mean AVPD<5% across the 50 best-fitting sets and/or projections within the target confidence intervals; acceptable was mean AVPD >5% and<15%.ResultsAcross indicators, 1,841 of 2,350 (78.3%) model projections were a good or acceptable fit to calibration targets. For HIV epidemic indicators, 256 of 300 (85.3%) projections were a good fit to targets, with the model performing better for women (83.3% a good fit) than for men (71.7% a good fit). For global goals indicators, 96 of 100 (96.0%) projections were a good fit; model performance was similar for women and men. For other indicators, 653 of 950 (68.7%) projections were a good or acceptable fit. Fit was better for women than for men (percentage virally suppressed only) and when restricting targets for number on ART to 2013 and beyond.ConclusionsThe CA-IeDEA HIV policy model fits historical data and can inform policy solutions for equitably achieving global goals to end the HIV epidemic in Rwanda. High-quality, unbiased population-based data, as well as novel approaches that account for calibration target quality, are critical to ongoing use of mathematical models for programmatic planning.
Industry differences in managers’ experiences of work capacity in employees with common mental disorders: a cross-sectional study on the Swedish labour market
Authors: Björk Lisa , Hultquist Jenny , Hensing Gunnel , Bertilsson Monica 
Published: September 2024

AbstractThe aim of this study was to assess industry differences in managers’ experiences and ratings of work capacity in employees with common mental disorders (CMDs). Swedish managers (N=1819) were grouped into three industry classifications. Differences between industries in managers’ experiences were investigated by chi-squared tests. The managers’ ratings of how work capacity was affected by CMDs were analysed using MANCOVA, adjusted for organizational size and managers’ span of control. The proportion of managers who had experienced several employees with CMDs was higher in municipalities and counties, and in pink-collar work, education, health and social care settings compared with other industries. There was no significant effect of industry on managers’ ratings of how work capacity may be affected by CMDs. Contrary to assumptions, there were no differences in how managers perceived capacity to work between industries. Therefore, it is more urgent that managers receive the support they need to handle employees with reduced work capacity due to CMDs rather than to tailor such support to different industries.
Transfer RNA levels are tuned to support differentiation during Drosophila neurogenesis
Authors: Wint Rhondene , Cleary Michael D. 
Published: September 2024

ABSTRACTNeural differentiation requires a multifaceted program to alter gene expression along the proliferation to differentiation axis. While critical changes occur at the level of transcription, post-transcriptional mechanisms allow fine-tuning of protein output. We investigated the role of tRNAs in regulating gene expression during neural differentiation by quantifying tRNA abundance in neural progenitor-biased and neuron-biasedDrosophilalarval brains. We found that tRNA profiles are largely consistent between progenitor-biased and neuron-biased brains but significant variation occurs for 10 cytoplasmic isodecoders (individual tRNA genes) and this establishes differential tRNA levels for 8 anticodon groups. We used these tRNA data to investigate relationships between tRNA abundance, codon optimality- mediated mRNA decay, and translation efficiency in progenitors and neurons. Our data reveal that tRNA levels strongly correlate with codon optimality-mediated mRNA decay within each cell type but generally do not explain differences in stabilizing versus destabilizing codons between cell types. Regarding translation efficiency, we found that tRNA expression in neural progenitors preferentially supports translation of mRNAs whose products are in high demand in progenitors, such as those associated with protein synthesis. In neurons, tRNA expression shifts to disfavor translation of proliferation-related transcripts and preferentially support translation of transcripts tied to neuron-specific functions like axon pathfinding and synapse formation. Overall, our analyses reveal that changes in tRNA levels along the neural differentiation axis support optimal gene expression in progenitors and neurons.AUTHOR SUMMARYWint et al. quantified tRNA expression inDrosophilalarval brains, using wildtype brains composed primarily of neurons and mutant brains composed primarily of neural progenitors (neuroblasts). These neuron-biased and neuroblast-biased tRNA measurements, combined with mRNA decay data and computational modeling of translation efficiency, revealed that: 1) tRNA abundance is largely constant between neural progenitors and neurons but significant variation exists for 10 nuclear tRNA genes and 8 corresponding anticodon groups, 2) tRNA abundance correlates with codon-mediated mRNA decay in neuroblasts and neurons but does not completely explain the different stabilizing or destabilizing effects of certain codons, and 3) changes in tRNA levels during differentiation shift translation optimization from a program supporting proliferation to a program supporting differentiation. These findings reveal coordination between tRNA expression and codon usage in transcripts that regulate neural development.
TheDrosophilamyogenic inhibitorHimgene is essential for adult muscle function and muscle stem cell maintenance
Authors: Mitchell-Gee Robert , Hoff Robert , Vishal Kumar , Hancock Daniel , McKitrick Sam , Newnes-Querejeta Cristina , Lovato TyAnna L. , Cripps Richard M. , Taylor Michael V. 
Published: September 2024

SummaryVertebrate muscle fibres have a population of Muscle Stem Cells (MuSCs), or “satellite cells”, vital to muscle growth, homeostasis and repair. InDrosophila, adult MuSCs with similar characteristics have only recently been described. This has opened up theDrosophilasystem for analysing how MuSCs operate in muscle maintenance, repair and ageing. Here we show that theHimgene is expressed in the adult muscle progenitors (AMPs), or myoblasts, that make the adultDrosophilathoracic flight and jump muscles. Notably, we also show that Him is expressed in the flight muscle MuSCs identifyingHimas only the second genetic marker of these insect MuSCs. We then exploredHimfunction.Himmutants have disrupted organisation of the thoracic jump muscle, resulting in reduced jumping ability.Himmutants also have a reduced pool of the myoblasts that will develop into the flight muscles. In the flight muscles themselves,Himmutants have an age-dependent decrease in the number of MuSCs, indicating thatHimis required for maintenance of the adult muscle stem cell population. Moreover, this decrease in MuSCs coincides with a functional effect: there is an age-dependent decline in flight ability. Overall,Himis a novel marker of theDrosophilaadult MuSC, and is required during ageing both to maintain MuSC number and flight ability.
ABBA, a novel tool for whole-brain mapping, reveals brain-wide differences in immediate early genes induction following learning
Authors: Chiaruttini Nicolas , Castoldi Carlo , Requie Linda Maria , Camarena-Delgado Carmen , dal Bianco Beatrice , Gräff Johannes , Seitz Arne , Silva Bianca A. 
Published: September 2024

AbstractUnbiased characterization of whole-brain cytoarchitecture represents an invaluable tool for understanding brain function. For this, precise mapping of histological markers from 2D sections onto 3D brain atlases is pivotal. Here, we present two novel software tools facilitating this process: Aligning Big Brains and Atlases (ABBA), designed to streamline the precise and efficient registration of 2D sections to 3D reference atlases, and BraiAn, an integrated suite for multi-marker automated segmentation, whole-brain statistical analysis, and data visualisation. Combining these tools, we performed a comprehensive comparative study of the whole-brain expression of three of the most widely used immediate early genes (IEGs). Thanks to their neural activity-dependent expression, IEGs have been used for decades as a proxy of neural activity to generate unbiased mapping of activity following behaviour, but their respective induction in response to neuronal activation across the entire brain remains unclear. To address this question, we systematically compared the brain-wide expression cFos, Arc and NPAS4, three abundantly used IEGs, across three different behavioural conditions related to memory. Our results highlight major differences in both their distribution and induction patterns, indicating that they do not represent equivalent markers across brain areas or activity states, but can provide instead complementary information.
Distinct Non-occluding Functions of Septate Junction Components in Signaling Pathway Regulation and Cell Polarity During Epithelial Development
Authors: Holtwick V. , Schubert A. , Rust K. 
Published: September 2024

AbstractOccluding junctions are essential for tissue integrity and barrier function in epithelial tissues. Here we identify several non-occluding functions of septate junction components, the invertebrate occluding junctions, in follicle epithelium development. We show that the morphogenesis of the follicular stalk is an actin-driven process that requires intact apical-basal cell polarity, which is controlled by septate junction components. Septate junction components further regulate signaling pathways in a cell-type specific manner. In undifferentiated stem cells and immediate daughters, septate junction components promote effective Wnt signaling to control proliferation, while they limit Jak-STAT signaling activity induced by polar cells. Together, our data emphasize the multiple roles of septate junction components independent of their classical role in forming the paracellular barrier.
PIEZO-dependent mechano-sensing of the niche is essential for intestinal stem cell fate decision and maintenance
Authors: Baghdadi Meryem B. , Houtekamer Ronja M. , Perrin Louisiane , Rao-Bhatia Abilasha , Whelen Myles , Decker Linda , Bergert Martin , Pérez-Gonzàlez Carlos , Bouras Réda , Gropplero Giacomo , Loe Adrian KH , Afkhami-Poostchi Amin , Chen Xin , Huang Xi , Descroix Stephanie , Wrana Jeffrey L. , Diz-Muñoz Alba , Gloerich Martijn , Ayyaz Arshad , Vignjevic Danijela Matic , Kim Tae-Hee 
Published: September 2024

ABSTRACTStem cells continuously perceive and respond to various environmental signals to maintain homeostasis. In addition to biochemical factors, the stem cell niche is subjected to mechanical and physical cues. However, it remains unclear how stem cells can sense mechanical signals from their nichein vivo. Since intestinal stem cells constantly and directly face the external environment, we investigated the roles of mechano-sensing PIEZO ion channels in the gut stem cell niche. By employing mouse genetics and performing single-cell RNAseq analysis, we revealed the absolute requirement for PIEZO channels in intestinal stem cell (ISC) state dynamics and maintenance.In vivomeasurement of basement membrane region stiffness demonstrated that ISCs reside in a more rigid microenvironment at the bottom of the crypt. Using 3D and 2D organoid systems combined with bioengineered substrates and a cell stretching device, we found that PIEZO channels are activated by high extracellular matrix stiffness and tissue tension to modulate ISC behavior. This study delineates the mechanistic cascade of PIEZO channel activation in ISCs from the upstream extracellular stimuli through the downstream signaling activation that coordinates stem cell fate decision and maintenance.
Like sisters but not twins – vasopressin and oxytocin excite BNST neurons via cell type-specific expression of oxytocin receptor to reduce anxious arousal
Authors: Francesconi Walter , Olivera-Pasilio Valentina , Berton Fulvia , Olson Susan L. , Chudoba Rachel , Monroy Lorena M. , Krabichler Quirin , Grinevich Valery , Dabrowska Joanna 
Published: September 2024

AbstractInteroceptive signals dynamically interact with the environment to shape appropriate defensive behaviors. Hypothalamic hormones arginine-vasopressin (AVP) and oxytocin (OT) regulate physiological states, including water and electrolyte balance, circadian rhythmicity, and defensive behaviors. Both AVP and OT neurons project to dorsolateral bed nucleus of stria terminalis (BNSTDL), which expresses oxytocin receptors (OTR) and vasopressin receptors and mediates fear responses. However, understanding the integrated role of neurohypophysial hormones is complicated by the cross-reactivity of AVP and OT and their mutual receptor promiscuity. Here, we provide evidence that the effects of neurohypophysial hormones on BNST excitability are driven by input specificity and cell type-specific receptor selectivity. We show that OTR-expressing BNSTDLneurons, excited by hypothalamic OT and AVP inputs via OTR, play a major role in regulating BNSTDLexcitability, overcoming threat avoidance, and reducing threat-elicited anxious arousal. Therefore, OTR-BNSTDLneurons are perfectly suited to drive the dynamic interactions balancing external threat risk and physiological needs.Graphical abstractHighlightsExogenous and light-evoked vasopressin (AVP) peptide excites neurons of the bed nucleus of the stria terminalis (BNST) via oxytocin receptor (OTR) in male ratsAVP excites OTR- and Corticotropin-releasing factor (CRF)-expressing neurons, most of which are classified as Type III neurons of the BNSTOTR-expressing BNST neurons increase exploration of open spaces and reduce anxious arousal in fear-potentiated startle in male ratsThe dorsolateral BNST receives vasopressinergic inputs from suprachiasmatic, supraoptic, and paraventricular nuclei of the hypothalamusInternal signal-sensitive hypothalamic inputs directly impact BNST excitability via OTR to balance interoceptive signals and defensive behaviors
A universal limit for mammalian lifespan revealed by epigenetic entropy
Authors: Alba-Linares Juan José , Tejedor Juan Ramón , Fernández Agustín F. , Pérez Raúl F. , Fraga Mario F. 
Published: September 2024

ABSTRACTAge-associated DNA methylation patterns have shown strong associations with species lifespan. However, it remains unclear whether epigenetic noise levels can account for the observed differences between mammalian species. In this study, we examined the rate of loss of epigenetic information with age by measuring entropy at mammalian conserved CpG sites across a diverse range of species. Longer-lived mammals tend to gain fewer noisy CpGs with age, irrespective of whether these originate from hyper- or hypomethylation processes. Importantly, we found that the rate of epigenetic entropy gain declines in a linear fashion with species maximum lifespan, pointing to the existence of a universal limit for mammalian lifespan in the vicinity of 220 years.
GDF11 secreting cell transplant efficiently ameliorates age-related pulmonary fibrosis
Authors: Guo Li , Duchesneau Pascal , Sawula Evan , Jong Eric D. , Li Chengjin , Waddell Thomas K , Nagy Andras 
Published: September 2024

AbstractHere, we present a combination of cell and gene therapy that harnesses the regenerative properties of GDF11 in age-related pulmonary fibrosis. Our genome-edited FailSafeTM-GDF11 mouse ESC line provides controlled proliferation and efficient derivation to lung progenitors while inducibly expressing GDF11. When these cells were transplanted into bleomycin-injured aged mice, they acted as a source of reparative cells, restoring the damaged alveolar epithelium. Furthermore, the transplanted cells acted as an “in situ factory”, enabling the production of GDF11 in response to the inducer drug. This approach attenuated age-associated senescence and led to the successful resolution of fibrosis. Our study presents a promising method for treating pulmonary fibrosis. Additionally, this approach offers a versatile tool that can be expanded to incorporate other regenerative and anti-aging factors. This helps overcome limitations such as high production costs and a short half-life of therapeutic factors. One of the strengths of our system is its ability to allow precise regulation of factor-expression when needed to address specific aging phenotypes.
Exploring the Exclusive Isolation ofPseudomonas syringaeinPeltigeraLichens via metabolite analysis and growth assays
Authors: Ramírez Natalia , Vinchira-Villarraga Diana , Rabiey Mojgan , Sigurbjörnsdóttir Margrét Auður , Heidmarsson Starri , Vilhelmsson Oddur , Jackson Robert W. 
Published: September 2024

AbstractThe specific association of the potentially plant-pathogenicPseudomonas syringaewithPeltigeralichens raises questions about the factors driving this host specificity. To explore this, the metabolic profile of seven lichen species belonging to three genera (Cladonia, Peltigera, andStereocaulon) was analysed using LC-MSMS. Additionally, we assessed the growth ofP. syringaestrains in media supplemented with extracts from each lichen species. This revealed thatPeltigeraexhibits lower metabolite richness compared to other genera, but shows a higher chemical investment in specific compounds. Growth kinetics showed comparableP. syringaegrowth across lichen-supplemented media, except forC. arbusculaandCladoniasp., where the former exhibited lower growth rates. Inhibition assays with lichen extracts showed no inhibition ofP. syringae. The lichen metabolome is predominantly composed of lipids and organic acids. Furthermore, specific compounds, such as aminoglycosides, may facilitateP. syringaepresence inPeltigeraby inhibitingBacillus subtilisand other antagonists. Additionally, compounds absent inPeltigera, like anthracene, might serve as a carbon source inhibitors likeB. velezensis.