bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans
Authors: Teuscher Alina C. , Statzer Cyril , Goyala Anita , Domenig Seraina A. , Schoen Ingmar , Hess Max , Hofer Alexander M. , Fossati Andrea , Vogel Viola , Goksel Orcun , Aebersold Ruedi , Ewald Collin Y. 
Published: January 2024

AbstractDysfunctional extracellular matrices (ECM) contribute to aging and disease. Repairing dysfunctional ECM could potentially prevent age-related pathologies. Interventions promoting longevity also impact ECM gene expression. However, the role of ECM composition changes in healthy aging remains unclear. Here we perform proteomics and in-vivo monitoring to systematically investigate ECM composition (matreotype) during aging in C. elegans revealing three distinct collagen dynamics. Longevity interventions slow age-related collagen stiffening and prolong the expression of collagens that are turned over. These prolonged collagen dynamics are mediated by a mechanical feedback loop of hemidesmosome-containing structures that span from the exoskeletal ECM through the hypodermis, basement membrane ECM, to the muscles, coupling mechanical forces to adjust ECM gene expression and longevity via the transcriptional co-activator YAP-1 across tissues. Our results provide in-vivo evidence that coordinated ECM remodeling through mechanotransduction is required and sufficient to promote longevity, offering potential avenues for interventions targeting ECM dynamics.
Muscle abnormalities worsen after post-exertional malaise in long COVID
Authors: Appelman Brent , Charlton Braeden T. , Goulding Richie P. , Kerkhoff Tom J. , Breedveld Ellen A. , Noort Wendy , Offringa Carla , Bloemers Frank W. , van Weeghel Michel , Schomakers Bauke V. , Coelho Pedro , Posthuma Jelle J. , Aronica Eleonora , Joost Wiersinga W. , van Vugt Michèle , Wüst Rob C. I. 
Published: January 2024

Abstract
A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.
Stalled response near thermal equilibrium in periodically driven systems
Authors: Dabelow Lennart , Reimann Peter 
Published: January 2024

AbstractThe question of how systems respond to perturbations is ubiquitous in physics. Predicting this response for large classes of systems becomes particularly challenging if many degrees of freedom are involved and linear response theory cannot be applied. Here, we consider isolated many-body quantum systems which either start out far from equilibrium and then thermalize, or find themselves near thermal equilibrium from the outset. We show that time-periodic perturbations of moderate strength, in the sense that they do not heat up the system too quickly, give rise to the following phenomenon of stalled response: While the driving usually causes quite considerable reactions as long as the unperturbed system is far from equilibrium, the driving effects are strongly suppressed when the unperturbed system approaches thermal equilibrium. Likewise, for systems prepared near thermal equilibrium, the response to the driving is barely noticeable right from the beginning. Numerical results are complemented by a quantitatively accurate analytical description and by simple qualitative arguments.
TRIM28-mediated nucleocapsid protein SUMOylation enhances SARS-CoV-2 virulence
Authors: Ren Jiang , Wang Shuai , Zong Zhi , Pan Ting , Liu Sijia , Mao Wei , Huang Huizhe , Yan Xiaohua , Yang Bing , He Xin , Zhou Fangfang , Zhang Long 
Published: January 2024

AbstractViruses, as opportunistic intracellular parasites, hijack the cellular machinery of host cells to support their survival and propagation. Numerous viral proteins are subjected to host-mediated post-translational modifications. Here, we demonstrate that the SARS-CoV-2 nucleocapsid protein (SARS2-NP) is SUMOylated on the lysine 65 residue, which efficiently mediates SARS2-NP’s ability in homo-oligomerization, RNA association, liquid-liquid phase separation (LLPS). Thereby the innate antiviral immune response is suppressed robustly. These roles can be achieved through intermolecular association between SUMO conjugation and a newly identified SUMO-interacting motif in SARS2-NP. Importantly, the widespread SARS2-NP R203K mutation gains a novel site of SUMOylation which further increases SARS2-NP’s LLPS and immunosuppression. Notably, the SUMO E3 ligase TRIM28 is responsible for catalyzing SARS2-NP SUMOylation. An interfering peptide targeting the TRIM28 and SARS2-NP interaction was screened out to block SARS2-NP SUMOylation and LLPS, and consequently inhibit SARS-CoV-2 replication and rescue innate antiviral immunity. Collectively, these data support SARS2-NP SUMOylation is critical for SARS-CoV-2 virulence, and therefore provide a strategy to antagonize SARS-CoV-2.
Inhibition of iRhom1 by CD44-targeting nanocarrier for improved cancer immunochemotherapy
Authors: Luo Zhangyi , Huang Yixian , Batra Neelu , Chen Yuang , Huang Haozhe , Wang Yifei , Zhang Ziqian , Li Shichen , Chen Chien-Yu , Wang Zehua , Sun Jingjing , Wang Qiming Jane , Yang Da , Lu Binfeng , Conway James F. , Li Lu-Yuan , Yu Ai-Ming , Li Song 
Published: January 2024

AbstractThe multifaceted chemo-immune resistance is the principal barrier to achieving cure in cancer patients. Identifying a target that is critically involved in chemo-immune-resistance represents an attractive strategy to improve cancer treatment. iRhom1 plays a role in cancer cell proliferation and its expression is negatively correlated with immune cell infiltration. Here we show that iRhom1 decreases chemotherapy sensitivity by regulating the MAPK14-HSP27 axis. In addition, iRhom1 inhibits the cytotoxic T-cell response by reducing the stability of ERAP1 protein and the ERAP1-mediated antigen processing and presentation. To facilitate the therapeutic translation of these findings, we develop a biodegradable nanocarrier that is effective in codelivery of iRhom pre-siRNA (pre-siiRhom) and chemotherapeutic drugs. This nanocarrier is effective in tumor targeting and penetration through both enhanced permeability and retention effect and CD44-mediated transcytosis in tumor endothelial cells as well as tumor cells. Inhibition of iRhom1 further facilitates tumor targeting and uptake through inhibition of CD44 cleavage. Co-delivery of pre-siiRhom and a chemotherapy agent leads to enhanced antitumor efficacy and activated tumor immune microenvironment in multiple cancer models in female mice. Targeting iRhom1 together with chemotherapy could represent a strategy to overcome chemo-immune resistance in cancer treatment.
Temporal dendritic heterogeneity incorporated with spiking neural networks for learning multi-timescale dynamics
Authors: Zheng Hanle , Zheng Zhong , Hu Rui , Xiao Bo , Wu Yujie , Yu Fangwen , Liu Xue , Li Guoqi , Deng Lei 
Published: January 2024

AbstractIt is widely believed the brain-inspired spiking neural networks have the capability of processing temporal information owing to their dynamic attributes. However, how to understand what kind of mechanisms contributing to the learning ability and exploit the rich dynamic properties of spiking neural networks to satisfactorily solve complex temporal computing tasks in practice still remains to be explored. In this article, we identify the importance of capturing the multi-timescale components, based on which a multi-compartment spiking neural model with temporal dendritic heterogeneity, is proposed. The model enables multi-timescale dynamics by automatically learning heterogeneous timing factors on different dendritic branches. Two breakthroughs are made through extensive experiments: the working mechanism of the proposed model is revealed via an elaborated temporal spiking XOR problem to analyze the temporal feature integration at different levels; comprehensive performance benefits of the model over ordinary spiking neural networks are achieved on several temporal computing benchmarks for speech recognition, visual recognition, electroencephalogram signal recognition, and robot place recognition, which shows the best-reported accuracy and model compactness, promising robustness and generalization, and high execution efficiency on neuromorphic hardware. This work moves neuromorphic computing a significant step toward real-world applications by appropriately exploiting biological observations.
Cation-π interactions enabled water-stable perovskite X-ray flat mini-panel imager
Authors: Pan Wanting , He Yuhong , Li Weijun , Liu Lulu , Guo Keke , Zhang Jianglei , Wang Chao , Li Bao , Huang Hu , Zhang Junhu , Yang Bai , Wei Haotong 
Published: January 2024

AbstractSensitive and stable perovskite X-ray detectors are attractive in low-dosage medical examinations. The high sensitivity, tunable chemical compositions, electronic dimensions, and low-cost raw materials make perovskites promising next-generation semiconductors. However, their ionic nature brings serious concerns about their chemical and water stability, limiting their applications in well-established technologies like crystal polishing, micro-processing, photolithography, etc. Herein we report a one-dimensional tryptamine lead iodide perovskite, which is stable in water for several months as the strong cation-π interactions between organic cations. The one-dimensional and two-dimensional tryptamine lead iodide perovskite tablets are switchable through thermal-annealing or water-soaking treatments to relax microstrains. The water-stable and microstrain-free one-dimensional perovskite tablets yield a large sensitivity of 2.5 × 106 μC Gyair−1 cm−2 with the lowest detectable dose rate of 5 nGyair s−1. Microelectrode arrays are realized by surface photolithography to construct high-performance X-ray flat mini-panels with good X-ray imaging capability, and a record spatial resolution of 17.2 lp mm−1 is demonstrated.
Dynamic predictors of COVID-19 vaccination uptake and their interconnections over two years in Hong Kong
Authors: Yuan Jiehu , Xu Yucan , Wong Irene Oi Ling , Lam Wendy Wing Tak , Ni Michael Y. , Cowling Benjamin J. , Liao Qiuyan 
Published: January 2024

AbstractThe global rollout of COVID-19 vaccines faces a significant barrier in the form of vaccine hesitancy. This study adopts a dynamic and network perspective to explore the determinants of COVID-19 vaccine uptake in Hong Kong, focusing on multi-level determinants and their interconnections. Following the framework proposed by the Strategic Advisory Group of Experts (SAGE), the study used repeated cross-sectional surveys to map these determinants at multiple levels and investigates their interconnections simultaneously in a sample of 15,179 over two years. The results highlight the dynamic nature of COVID-19 vaccine hesitancy in an evolving pandemic. The findings suggest that vaccine confidence attitudes play crucial roles in vaccination uptake, with their importance shifting over time. The initial emphasis on vaccine safety gradually transitioned to heightened consideration of vaccine effectiveness at a later stage. The study also highlights the impact of chronic condition, age, COVID-19 case numbers, and non-pharmaceutical preventive behaviours on vaccine uptake. Higher educational attainment and being married were associated with primary and booster vaccine uptake and it may be possible to leverage these groups as early innovation adopters. Trust in government acts as a crucial bridging factor linking various variables in the networks with vaccine confidence attitudes, which subsequently closely linked to vaccine uptake. This study provides insights for designing future effective vaccination programmes for changing circumstances.
Multimodal profiling reveals site-specific adaptation and tissue residency hallmarks of γδ T cells across organs in mice
Authors: du Halgouet Anastasia , Bruder Kerstin , Peltokangas Nina , Darbois Aurélie , Obwegs David , Salou Marion , Thimme Robert , Hofmann Maike , Lantz Olivier , Sagar  
Published: January 2024

Abstractγδ T cells perform heterogeneous functions in homeostasis and disease across tissues. However, it is unclear whether these roles correspond to distinct γδ subsets or to a homogeneous population of cells exerting context-dependent functions. Here, by cross-organ multimodal single-cell profiling, we reveal that various mouse tissues harbor unique site-adapted γδ subsets. Epidermal and intestinal intraepithelial γδ T cells are transcriptionally homogeneous and exhibit epigenetic hallmarks of functional diversity. Through parabiosis experiments, we uncovered cellular states associated with cytotoxicity, innate-like rapid interferon-γ production and tissue repair functions displaying tissue residency hallmarks. Notably, our observations add nuance to the link between interleukin-17-producing γδ T cells and tissue residency. Moreover, transcriptional programs associated with tissue-resident γδ T cells are analogous to those of CD8+ tissue-resident memory T cells. Altogether, this study provides a multimodal landscape of tissue-adapted γδ T cells, revealing heterogeneity, lineage relationships and their tissue residency program.
Transcription-induced domains form the elementary constraining building blocks of bacterial chromosomes
Authors: Bignaud Amaury , Cockram Charlotte , Borde Céline , Groseille Justine , Allemand Eric , Thierry Agnès , Marbouty Martial , Mozziconacci Julien , Espéli Olivier , Koszul Romain 
Published: January 2024

AbstractTranscription generates local topological and mechanical constraints on the DNA fiber, leading to the generation of supercoiled chromosome domains in bacteria. However, the global impact of transcription on chromosome organization remains elusive, as the scale of genes and operons in bacteria remains well below the resolution of chromosomal contact maps generated using Hi-C (~5–10 kb). Here we combined sub-kb Hi-C contact maps and chromosome engineering to visualize individual transcriptional units. We show that transcriptional units form discrete three-dimensional transcription-induced domains that impose mechanical and topological constraints on their neighboring sequences at larger scales, modifying their localization and dynamics. These results show that transcriptional domains constitute primary building blocks of bacterial chromosome folding and locally impose structural and dynamic constraints.
Dynamic network curvature analysis of gene expression reveals novel potential therapeutic targets in sarcoma
Authors: Elkin Rena , Oh Jung Hun , Dela Cruz Filemon , Norton Larry , Deasy Joseph O. , Kung Andrew L. , Tannenbaum Allen R. 
Published: January 2024

AbstractNetwork properties account for the complex relationship between genes, making it easier to identify complex patterns in their interactions. In this work, we leveraged these network properties for dual purposes. First, we clustered pediatric sarcoma tumors using network information flow as a similarity metric, computed by the Wasserstein distance. We demonstrate that this approach yields the best concordance with histological subtypes, validated against three state-of-the-art methods. Second, to identify molecular targets that would be missed by more conventional methods of analysis, we applied a novel unsupervised method to cluster gene interactomes represented as networks in pediatric sarcoma. RNA-Seq data were mapped to protein-level interactomes to construct weighted networks that were then subjected to a non-Euclidean, multi-scale geometric approach centered on a discrete notion of curvature. This provides a measure of the functional association among genes in the context of their connectivity. In confirmation of the validity of this method, hierarchical clustering revealed the characteristic EWSR1-FLI1 fusion in Ewing sarcoma. Furthermore, assessing the effects of in silico edge perturbations and simulated gene knockouts as quantified by changes in curvature, we found non-trivial gene associations not previously identified.
Evodiae Fructus extract suppresses inflammatory response in HaCaT cells and improves house dust mite-induced atopic dermatitis in NC/Nga mice
Authors: Jin Seong Eun , Seo Chang-Seob , Jeon Woo-Young , Oh Yong Jin , Shin Hyeun-Kyoo , Jeong Hye Gwang , Ha Hyekyung 
Published: January 2024

AbstractThis study was conducted to assess the effect of Evodiae Fructus 70% ethanol extract (EFE) on the pathology of atopic dermatitis using in vitro and in vivo models. The major compounds in EFE were identified by ultra-performance liquid chromatography with tandem mass spectrometry as rutaecarpine, evodiamine, evodol, dehydroevodiamine, limonin, synephrine, evocarpine, dihydroevocarpine, and hydroxyevodiamine. EFE significantly decreased chemokine levels in tumor necrosis factor-α/interferon-γ-stimulated HaCaT cells. In house dust mite-treated NC/Nga mice, topical application of EFE significantly decreased the dermatitis score, epidermal hyperplasia and thickening, mast cell infiltration, and plasma levels of histamine and corticosterone. Thymic stromal lymphopoietin, CD4+ T cells, interleukin-4, and intercellular adhesion molecule-1 expression in the lesioned skin was reduced in the treated mice. The mechanism of EFE was elucidated using transcriptome analysis, followed by experimental validation using Western blotting in HaCaT cells. EFE down-regulated the activation of Janus kinase (JAK)-signal transducers and activators of transcription (STAT) and mitogen-activated protein kinases (MAPK) signaling pathways in HaCaT cells. EFE improves atopic dermatitis-like symptoms by suppressing inflammatory mediators, cytokines, and chemokines by regulating the JAK-STAT and MAPK signaling pathways, suggesting its use as a potential agent for the treatment of atopic dermatitis.
Estimating the effects of vegetation and increased albedo on the urban heat island effect with spatial causal inference
Authors: Calhoun Zachary D. , Willard Frank , Ge Chenhao , Rodriguez Claudia , Bergin Mike , Carlson David 
Published: January 2024

AbstractThe urban heat island effect causes increased heat stress in urban areas. Cool roofs and urban greening have been promoted as mitigation strategies to reduce this effect. However, evaluating their efficacy remains a challenge, as potential temperature reductions depend on local characteristics. Existing methods to characterize their efficacy, such as computational fluid dynamics and urban canopy models, are computationally burdensome and require a high degree of expertise to employ. We propose a data-driven approach to overcome these hurdles, inspired by recent innovations in spatial causal inference. This approach allows for estimates of hypothetical interventions to reduce the urban heat island effect. We demonstrate this approach by modeling evening temperature in Durham, North Carolina, using readily retrieved air temperature, land cover, and satellite data. Hypothetical interventions such as lining streets with trees, cool roofs, and changing parking lots to green space are estimated to decrease evening temperatures by a maximum of 0.7–0.9 $$^{\circ } \hbox {C}$$

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, with reduced effects on temperature as a function of distance from the intervention. Because of the ease of data access, this approach may be applied to other cities in the U.S. to help them come up with city-specific solutions for reducing urban heat stress.
Transcriptome analysis in a humanized mouse model of familial dysautonomia reveals tissue-specific gene expression disruption in the peripheral nervous system
Authors: Harripaul Ricardo , Morini Elisabetta , Salani Monica , Logan Emily , Kirchner Emily , Bolduc Jessica , Chekuri Anil , Currall Benjamin , Yadav Rachita , Erdin Serkan , Talkowski Michael E. , Gao Dadi , Slaugenhaupt Susan 
Published: January 2024

AbstractFamilial dysautonomia (FD) is a rare recessive neurodevelopmental disease caused by a splice mutation in the Elongator acetyltransferase complex subunit 1 (ELP1) gene. This mutation results in a tissue-specific reduction of ELP1 protein, with the lowest levels in the central and peripheral nervous systems (CNS and PNS, respectively). FD patients exhibit complex neurological phenotypes due to the loss of sensory and autonomic neurons. Disease symptoms include decreased pain and temperature perception, impaired or absent myotatic reflexes, proprioceptive ataxia, and progressive retinal degeneration. While the involvement of the PNS in FD pathogenesis has been clearly recognized, the underlying mechanisms responsible for the preferential neuronal loss remain unknown. In this study, we aimed to elucidate the molecular mechanisms underlying FD by conducting a comprehensive transcriptome analysis of neuronal tissues from the phenotypic mouse model TgFD9; Elp1Δ20/flox. This mouse recapitulates the same tissue-specific ELP1 mis-splicing observed in patients while modeling many of the disease manifestations. Comparison of FD and control transcriptomes from dorsal root ganglion (DRG), trigeminal ganglion (TG), medulla (MED), cortex, and spinal cord (SC) showed significantly more differentially expressed genes (DEGs) in the PNS than the CNS. We then identified genes that were tightly co-expressed and functionally dependent on the level of full-length ELP1 transcript. These genes, defined as ELP1 dose-responsive genes, were combined with the DEGs to generate tissue-specific dysregulated FD signature genes and networks. Within the PNS networks, we observed direct connections between Elp1 and genes involved in tRNA synthesis and genes related to amine metabolism and synaptic signaling. Importantly, transcriptomic dysregulation in PNS tissues exhibited enrichment for neuronal subtype markers associated with peptidergic nociceptors and myelinated sensory neurons, which are known to be affected in FD. In summary, this study has identified critical tissue-specific gene networks underlying the etiology of FD and provides new insights into the molecular basis of the disease.