bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telerehabilitation services have declined post-COVID-19
Authors: May Anthony K , Holland Anne E , Alison Jennifer A , Herrmann Kelcie , Cox Narelle S 
Published: July 2024

AbstractObjectiveTo characterize Pulmonary rehabilitation (PR) service delivery, investigate the impact of the pandemic on PR services, and describe centre-based PR (CBPR) and telerehabilitation with reference to PR essential components.DesignOnline national cross-sectional survey.SettingAustralian PR services.ParticipantsRepresentatives of PR programs listed within the Lung Foundation Australia national database (n=295).InterventionsNot applicable.Main Outcome Measure(s)Availability of PR in CBPR and telerehabilitation settings.Results97% of Australian PR services (n=114/117) delivered CBPR, similarly to pre-COVID-19 pandemic availability (96%). 43% (n=50/116) of services delivered telerehabilitation, which was significantly less than availability during COVID-19 restrictions (74%; p<0.001). CBPR was primarily delivered in a group setting (99%; median (IQR) 7 (6-8) participants/group), and telerehabilitation primarily via individual telephone calls (94%). 39% of respondents report CBPR group size has reduced. PR essential components of initial centre-based assessments and individually prescribed/progressed endurance and resistance training were achieved by most CBPR and telerehabilitation programs. Staff training in delivery of telerehabilitation models was undertaken in 33% of services.ConclusionsPR essential components are generally met in current Australian programs. However, telerehabilitation services and CBPR program capacity have declined indicating reduced program capacity. Sustainability of effective PR programs is required to support access for people with chronic respiratory diseases.
Systematic Multi-Omics Investigation of Androgen Receptor Driven Gene Expression and Epigenetics changes in Prostate Cancer
Authors: Li Lin , Cho Kyung Hyun , Yu Xiuping , Cheng Siyuan 
Published: July 2024

AbstractBackground:Prostate cancer, a common malignancy, is driven by androgen receptor (AR) signaling. Understanding the function of AR signaling is critical for prostate cancer research.Methods:We performed multi-omics data analysis for the AR+, androgen-sensitive LNCaP cell line, focusing on gene expression (RNAseq), chromatin accessibility (ATACseq), and transcription factor binding (ChIPseq). High-quality datasets were curated from public repositories and processed using state-of-the-art bioinformatics tools.Results:Our analysis identified 1004 up-regulated and 707 down-regulated genes in response to androgen deprivation therapy (ADT) which diminished AR signaling activity. Gene-set enrichment analysis revealed that AR signaling influences pathways related to neuron differentiation, cell adhesion, P53 signaling, and inflammation. ATACseq and ChIPseq data demonstrated that as a transcription factor, AR primarily binds to distal enhancers, influencing chromatin modifications without affecting proximal promoter regions. In addition, the AR-induced genes maintained higher active chromatin states than AR-inhibited genes, even under ADT conditions. Furthermore, ADT did not directly induce neuroendocrine differentiation in LNCaP cells, suggesting a complex mechanism behind neuroendocrine prostate cancer development. In addition, a publicly available online application LNCaP-ADT (https://pcatools.shinyapps.io/shinyADT/) was launched for users to visualize and browse data generated by this study.Conclusion:This study provides a comprehensive multi-omics dataset, elucidating the role of AR signaling in prostate cancer at the transcriptomic and epigenomic levels. The reprocessed data is publicly available, offering a valuable resource for future prostate cancer research.
Linking stomatal size and density to water use efficiency and leaf carbon isotope ratio in juvenile and mature trees
Authors: Petrík Peter , Petek-Petrík Anja , Lamarque Laurent J. , Link Roman M. , Waite Pierre-André , Ruehr Nadine K. , Schuldt Bernhard , Maire Vincent 
Published: July 2024

AbstractWater-use efficiency (WUE) is affected by multiple leaf traits, including stomatal morphology. However, the impact of stomatal morphology on WUE across different ontogenetic stages of tree species is not well-documented. Here, we investigated the relationship between stomatal morphology intrinsic water-use efficiency (iWUE=A/gs) and leaf carbon isotope ratio (δ13C). We sampled 190 individuals including juvenile and mature trees belonging to 18 temperate broadleaved tree species and 9 genera. We measured guard cell length (GCL), stomatal density (SD), specific leaf area (SLA), gas-exchange, iWUE and leaf δ13C as a proxy for long-term WUE. Leaf δ13C correlated positively with iWUE for both juvenile and mature trees. Across species, GCL showed a negative and SD a positive effect on iWUE and leaf δ13C of both juvenile and mature trees. Within species, however, only GCL was significantly associated with iWUE and leaf δ13C. Pioneer species (Populus,Prunus,Betula) showed a significantly lower leaf δ13C than climax forest species (Fagus,Quercus,Tilia), but the differentiation was not clear for iWUE. We conclude that GCL and SD can be considered as functional morphological traits impacting the iWUE and leaf δ13C of trees, highlighting their potential for rapid phenotyping approaches in ecological studies.
Aerobic methane production by methylotrophicMethylotenerain groundwater
Authors: Li Shengjie , Dong Xiaoli , Humez Pauline , Borecki Joanna , Birks Jean , McClain Cynthia , Mayer Bernhard , Strous Marc , Diao Muhe 
Published: July 2024

AbstractMethyloteneraare signature denitrifiers and methylotrophs commonly found together with methanotrophic bacteria in lakes and freshwater sediments. Here we show that three distinctMethyloteneraecotypes were abundant in methane-rich, Pleistocene-aged groundwaters. Just like in surface water biomes, groundwaterMethyloteneraoften co-occurred with methane-oxidizing bacteria, even though they were generally unable to denitrify. One abundantMethyloteneraecotype expressed a pathway for aerobic methane production from methylphosphonate. This phosphate-acquisition strategy was recently found to contribute to methane production in the oligotrophic, oxic upper ocean. Gene organization, phylogeny and 3D protein structure of the key enzyme, C-P lyase subunit PhnJ were consistent with a role in phosphate uptake. We conclude that phosphate may be a limiting nutrient in productive, methane rich aquifers and that methylphosphonate degradation can contribute to groundwater methane production.
Unusual traits shape the architecture of the Ig ancestor molecule
Authors: Urdiciain Alejandro , Madej Thomas , Wang Jiyao , Song James , Erausquin Elena , Youkharibache Philippe , López-Sagaseta Jacinto 
Published: July 2024

AbstractUnderstanding the ancestral Ig domain’s molecular structure and tracing the evolution of Ig-like proteins are fundamental components missing from our comprehension of their evolutionary trajectory and function. We have elucidated the molecular structures of two Ig-like proteins from the evolutionary most ancestralphylum, Porifera, revealing previously unidentified Ig-domain features that highlight the concomitant presence of a novel Ig “Early Variable” (EV)-set in tandem with a C1-set domain. The latter, to our knowledge, has never been reported before in non-vertebrates. The IgV and IgC1 sets and their combination into functional Ig-like receptors are part of the adaptive immune system in higher vertebrates, which allows for highly specific immune responses. These observations in the ancientPorifera phylumcould indicate the presence of primitive forms of adaptive immunity or a foundational immune strategy that has been conserved through evolution. By unveiling important clues into the molecular configuration of ancestral Ig domains, these findings challenge and expand our understanding of how immunity has evolved within its current landscape.
Arterial arcades and collaterals regress under hemodynamics-based diameter adaptation: a computational and mathematical analysis
Authors: Rottschäfer Vivi , Kuppers Willem G.N. , Chen Jiao , van Bavel Ed 
Published: July 2024

AbstractSegments in the arterial network have a >1000-fold span of radii. This is believed to result from adaptation of each segment to the wall shear stress (WSS), with outward respectively inward remodeling if WSS is higher or lower than some reference value. While this seems a straightforward mechanism for arterial tree design, the arterial network is not a tree but contains numerous arcades, collaterals and other looping structures. In this theoretical study, we analyzed stability of looping structures in arterial networks under WSS control.Simulation models were based on very simple network topologies as well as on published human coronary and mouse cerebral arterial networks. Adaptation was implemented as a rate of change of structural radius of each segment that is proportional to the deviation from its reference WSS. A more generalized model was based on adaptation to a large range of other local hemodynamic stimuli, including velocity, flow and power dissipation.For over 12,000 tested parameter sets, the simulations invariably predicted loss of loops due to regression of one or more of the segments. In the small networks, this was the case for both the WSS and the generalized model, and for a large range of initial conditions and model parameters. Loss of loopiness also was predicted by models that included direction-dependent adaptation rates, heterogeneous reference WSS or adaptation rates among the adapting segments, and adaptation under dynamic conditions. Loss of loops was also found in the coronary and cerebral artery networks subjected to adaptation to WSS.In a mathematical analysis we proved that loss of loops is a direct consequence of Kirchhoff’s circuit law, which for each loop leads to a positive eigenvalue in the Jacobian matrix of partial derivatives in the adaptation model, and therefore to unstable equilibria in the presence of loops.Loss of loops is an inherent property of arterial networks that adapt to local hemodynamics. Additional mechanisms are therefore needed to explain their presence, including direct communication between connected segments.
Cortical integration of tactile inputs distributed across timescales
Authors: Wan Wenyu , Ridderinkhof K. Richard , Ghosh Arko 
Published: July 2024

AbstractSensory experiences in the real world cut across timescales from milliseconds to seconds. Emerging evidence suggests that somatosensory processing is sensitive to the temporal structure of the stimuli in the sub-second scale, yet only a few select ranges within this scale have been studied. To process real-world information, the integration of tactile inputs must occur over a much broader temporal range. To address temporal integration across timescales, we recorded scalp EEG signals from somatosensory cortex in response to a train of tactile pulses presented to the fingertips with varying inter-stimulus intervals (ISI) spanning 100 to 10,000 ms. To capture a rich variety of influences of the temporal structure on the cortical signals, we used a multi-dimensional event-related potential where the stimulations are separated according to the next interval structure. We tracked cortical tactile processing through its early (<75 ms), intermediate (75 to 150 ms) and late stages (150 to 300 ms). We find that the early and late stages of cortical activity were similarly dominated by the preceding ISI; EEG signals were suppressed with ISIs < 500 ms and enhanced with longer ISIs, with this effect persisting even when ISIs were approximately 8 seconds. The intermediate stage of cortical activity was sensitive to both the previous and the penultimate ISIs. Our findings suggest that the specific somatosensory cortical networks integrate temporal structure across timescales to enable complex sensory experiences.
Transformer Graph Variational Autoencoder for Generative Molecular Design
Authors: Nguyen Trieu , Karolak Aleksandra 
Published: July 2024

ABSTRACTIn the field of drug discovery, the generation of new molecules with desirable properties remains a critical challenge. Traditional methods often rely on SMILES (Simplified Molecular Input Line Entry System) representations for molecular input data, which can limit the diversity and novelty of generated molecules. To address this, we present the Transformer Graph Variational Autoencoder (TGVAE), an innovative AI model that employs molecular graphs as input data, thus captures the complex structural relationships within molecules more effectively than string models. To enhance molecular generation capabilities, TGVAE combines a Transformer, Graph Neural Network (GNN), and Variational Autoencoder (VAE). Additionally, we address common issues like over-smoothing in training GNNs and posterior collapse in VAE to ensure robust training and improve the generation of chemically valid and diverse molecular structures. Our results demonstrate that TGVAE outperforms existing approaches, generating a larger collection of diverse molecules and discovering structures that were previously unexplored. This advancement not only brings more possibilities for drug discovery but also sets a new level for the use of AI in molecular generation.
Control of cholesterol-induced adipocyte inflammation by the Nfe2l1-Atf3 pathway
Authors: Jethwa Carolin , Hoffmann Anne , Kotschi Stefan , Caesar Janina , Kern Matthias , Worthmann Anna , Schlein Christian , Khani Sajjad , Arús Bernardo A. , Bruns Oliver T. , Ghosh Adhideb , Wolfrum Christian , Döring Yvonne , Herzig Stephan , Weber Christian , Blüher Matthias , Widenmaier Scott B. , Hotamışlıgil Gökhan S. , Bartelt Alexander 
Published: July 2024

AbstractWhile adipocytes are critical pillars of energy metabolism, their dysfunction is linked to adipose tissue (AT) inflammation, insulin resistance, and ectopic lipotoxicity in cardiometabolic diseases. However, the mechanisms causing adipocyte inflammation and insulin resistance remain unclear. Here, we show that excess cholesterol induces adipocyte dysfunction, which is suppressed by the transcription factor Nfe2l1 (nuclear factor erythroid derived-2, like-1). Nfe2l1 is required to sustain proteasome function in adipocytes and proteotoxic stress induces adipocyte inflammation via the activation of Atf3. In humans, the Nfe2l1-proteasome pathway is inversely correlated to body mass index (BMI) in an adipose-depot specific manner. In mice, loss of adipocyte Nfe2l1 caused AT inflammation with a pronounced infiltration of macrophages and T cells. Mice lacking adipocyte Nfe2l1 displayed severe adipocyte dysfunction during diet-induced obesity (DIO), characterized by lower adipokine levels, steatosis, glucose intolerance and insulin resistance.Nfe2l1ΔATmice on an Apoe-deficient (Apoe−/−) background fed a cholesterol-rich Western Diet (WD), developed a lipoatrophy-like syndrome, dyslipidemia, and enhanced atherosclerosis. Our results reveal an important role for proteasome-mediated proteostasis in adipocytes and indicate that Nfe2l1 is linked to metabolic health in humans and preclinical mouse models. Promoting proteostasis in adipocytes may thus alleviate inflammation in obesity, potentially averting adverse cardiometabolic outcomes.Graphical abstract
Integratingin silicopredictions with an engineered tissue assay identifies Perlecan as an age-perturbed re-quiescence cue for muscle stem cells
Authors: Jacques Erik , Garcia Pauline , Mercier Orane , Hu Yechen , Degletagne Cyril , Ravent Jade , Fall Sidy , Almeida Maira P. , Wheeler Aaron R. , Angers Stephane , Gilbert Penney M. , Le Grand Fabien 
Published: July 2024

AbstractSkeletal muscle regeneration is mediated by resident muscle stem cells that produce progeny to repair or recreate muscle. Critical to this function is the ability to transition between states of proliferation and quiescence. This balancing act is disrupted with age, leading to eroded regenerative capacity. Notwistanding, mechanisms by which the regenerating niche directs MuSCs return to the dormant state are largely unknown. Since single-cell RNAseq methods exclude the analysis of multinucleated cells, we generated single-nuclei RNAseq datasets of regenerating muscle to capture the full breadth of myogenic progression. With this, we uncovered new transition states between differentiating myocytes and syncytial multinucleated cells. Using cell communication inference tools, we highlighted receptor-ligand interactions between MuSCs and fusing nuclei. We leveraged a bespoke biomimetic 3D niche that induces MuSC quiescence, to filter the predicted interactions using a Cas9-based functional genomics approach. We found the proteoglycan Perlecan (Hspg2) promotes MuSC re-quiescence.Hspg2silencingin vivo, during muscle regeneration, induced an aging-like phenotype and perturbed MuSC re-quiescence. Notably, the temporal profile and overall levels of Perlecan were altered with age. Exogenous supplementation with Endorepellin (truncated Perlecan) rescued MuSC decline following aged muscle regeneration, offering a new therapeutic target. Thus, couplingin silicopredictions with a 3Din vitroassay followed byin vivoinvestigations revealed a previously inaccessible window of biology; that spatiotemporal coordination of MuSC re-quiescence is directed by fusing myonuclei.
Parallel selection in domesticated Atlantic salmon from divergent founders including parallel selection on WGD-derived homeologous regions
Authors: Buso Pauline , Diblasi Célian , Manousi Domniki , Kwak Jun Soung , de Leon Arturo Vera Ponce , Stenløkk Kristina , Barson Nicola , Saitou Marie 
Published: July 2024

ABSTRACTAquaculture has a considerably shorter history compared to the domestication of plants and animals. Among aquatic species, those that have undergone whole genome duplication events (WGD) seem particularly successful. This suggests that genetic redundancy from WGD is important for domestication, possibly similar to plant domestication. Atlantic salmon (Salmo salar), which has experienced a lineage-specific WGD, has undergone rapid domestication through intensive breeding since the 1960s.Here, we examined the genomic responses to the domestication of Atlantic salmon, including the impacts of WGD, by comparing the whole genome sequence data of aquaculture and wild populations from two lineages: the Eastern and Western Atlantic (Western Norway and North America). Our analysis revealed shared selective sweeps on identical SNPs in major histocompatibility complex (MHC) genes across distinct aquaculture populations compared to their wild counterparts. This SNP level parallelism suggests that a combination of long-term balancing selection and recent human-induced selection has significantly shaped the evolutionary trajectory of MHC genes. In addition, we observed selective sweeps on gene pairs in the homeologous regions originating from WGD, highlighting WGD’s role in maintaining genomic variation and potentially reducing pleiotropy through sub-functionalization.This unique type of “parallel” selection contributes to adapting to the intensive artificial conditions of aquaculture. These findings provide valuable insights into the genetic mechanisms of domestication and adaptive responses in Atlantic salmon, suggesting that the salmonid whole genome duplication has underpinned their successful rapid domestication. Our research emphasizes the importance of maintaining genetic diversity to support sustainable aquaculture practices.
T6SS-mediated competition byStenotrophomonas rhizophilashapes seed-borne bacterial communities and seed-to-seedling transmission dynamics
Authors: Garin Tiffany , Brault Agathe , Marais Coralie , Briand Martial , Préveaux Anne , Simonin Marie , Barret Matthieu , Sarniguet Alain 
Published: July 2024

ABSTRACTSeeds harbor diverse microbial communities important for plant growth and health. During germination, seed exudation triggers intense microbial competition, shaping the communities transmitted to seedlings. This study explores the role of the bacterial type VI secretion system (T6SS)-mediated interference competition in seed microbiota transmission to seedlings. Distribution of T6SS within 180 genome sequences of seed-borne bacterial strains enabled the construction of SynCom with different levels of phylogenetic diversity and T6SS richness. These SynComs were inoculated withStenotrophomonas rhizophilaCFBP13503, a bacterial strain which possesses a T6SS activein vitroandin planta. SynComs compositions were comparedin vitrowith CFBP13503 wild-type strain or its isogenic T6SS-deficient mutant. Additionally, the effects of T6SS on the whole bacterial community dynamics during seed-to-seedling transmission were examined following seed-inoculation. The T6SS ofS. rhizophilaCFBP13503 targeted a large number of bacteria belonging to 5 different families The phylogenetic proximity and metabolic overlap of preys with CFBP13503 partly explains the sensitivity phenotype observed. The T6SS of CFBP13503 modulates the abundance of a few specific bacterial taxa during seed-to-seedling transmission depending on seed microbial initial inoculation and plant stage. Depending on the sensitivity of the co-inoculated competitors, the T6SS can provide a competitive advantage to CFBP13503, resulting in an increase in population size.ImportanceThe high prevalence of T6SS in seed-borne bacteria supports the importance of T6SS-mediated competition for seed microbiota assembly.In vitro,S. rhizophilaCFBP13503 T6SS exerts a strong impact on bacterial community dynamics. The susceptibility to T6SS increases with the phylogenetic and metabolic proximity of bacteria to CFBP13503, suggesting an influence of interspecies trophic patterns in T6SS-mediated competitions.In plantaand in soil, CFBP13503 T6SS influences specific bacterial taxa, leading to shifts in bacterial interactions and distinct community dynamics. T6SS-mediated competition plays a pivotal role in shaping seed bacterial communities and the dynamics of seed-to-seedling transitions.