bluuebunny/crossref_metadata_2025_split huggingface dataset:
The chondrocyte “mechanome”: Activation of the mechanosensitive ion channels TRPV4 and PIEZO1 drives unique transcriptional signatures
Authors: Nims Robert , Palmer Daniel R. , Kassab Jordan , Zhang Bo , Guilak Farshid 
Published: July 2024

AbstractThe mechanosensitive ion channels Transient Receptor Potential Vanilloid 4 (TRPV4) and PIEZO1 transduce physiologic and supraphysiologic magnitudes of mechanical signals in the chondrocyte, respectively. TRPV4 activation promotes chondrogenesis, while PIEZO1 activation by supraphysiologic deformations drives cell death. The mechanisms by which activation of these channels discretely drives changes in gene expression to alter cell behavior remain to be determined. To date, no studies have contrasted the transcriptomic response to activation of these channels nor has any published data attempted to correlate these transcriptomes to alterations in cellular function. This study used RNA sequencing to comprehensively investigate the transcriptomes associated with activation of TRPV4 or PIEZO1, revealing that TRPV4 and PIEZO drive distinct transcriptomes and also exhibit unique co‐regulated clusters of genes. Notably, activation of PIEZO1 through supraphysiologic deformation induced a transient inflammatory profile that overlapped with the interleukin (IL)‐1‐responsive transcriptome and contained genes associated with cartilage degradation and osteoarthritis progression. However, both TRPV4 and PIEZO1 were also shown to elicit anabolic effects. PIEZO1 expression promoted a pro‐chondrogenic transcriptome under unloaded conditions, and daily treatment with PIEZO1 agonist Yoda1 significantly increased sulfated glycosaminoglycan deposition in vitro. These findings emphasize the presence of a broad “mechanome” with distinct effects of TRPV4 and PIEZO1 activation in chondrocytes, suggesting complex roles for PIEZO1 in both the physiologic and pathologic responses of chondrocytes. The identification of transcriptomic profiles unique to or shared by PIEZO1 and TRPV4 (distinct from IL‐1‐induced inflammation) could inform future therapeutic designs targeting these channels for the management and treatment of osteoarthritis.
Association Between Telecommuting Preference-Frequency Mismatch and Insomnia Among Japanese Workers in the COVID-19 Pandemic
Authors: Hamada Shinsuke , Okawara Makoto , Tateishi Seiichiro , Eguchi Hisashi , Tsuji Mayumi , Ogami Akira , Mori Koji , Matsuda Shinya , Yoshimura Reiji , Fujino Yoshihisa ,   for the CORoNaWork Project
Published: July 2024

Objective
We hypothesized that telecommuting's impact on sleep varied based on preference-frequency mismatch. Here, we evaluated this relationship in a large cohort of Japanese workers.

Methods
We collected data from 33,302 Japanese workers through an online survey and analyzed participant preferences and frequency of telecommuting in 9425 individuals who responded to a follow-up survey. We evaluated sleep using the Athens Insomnia Scale and estimated odds ratios of insomnia using multilevel logistic regression.

Results
Workers preferring telecommuting had a higher risk of insomnia as telecommuting frequency decreased. OR for insomnia was 1.87 (P < 0.001) in those who telecommuted less than once per week.

Conclusion
Telecommuting's impact on workers' sleep depends on preference mismatch, with a higher risk of insomnia among those who prefer telecommuting but are unable to utilize it.
Cardiovascular Responses to Occupational Physical Activity Are Exaggerated by Work-Related Stress and Low Fitness
Authors: Quinn Tyler D. , Bruehwiler Timothy , Chantler Paul D. , Gibbs Bethany Barone 
Published: July 2024

Objectives
Paradoxical associations between high occupational physical activity (OPA) and cardiovascular disease may be explained by exaggerated cardiovascular responses from high work-related stress or low worker fitness.

Methods
OPA, blood pressure (BP), heart rate (HR), and rate-pressure product (RPP; HR × BP) were measured objectively for 24 hours in 19 male workers. Work-related stress was measured using the Stress in General Scale. Fitness was estimated using a submaximal treadmill test. Effect modification by work-related stress and fitness on associations between OPA and cardiovascular responses was examined using mixed models with interactions.

Results
Associations between OPA and RPP, HR, and BP were stronger with high stress (P < 0.05). Associations of work-time moderate and vigorous physical activity and RPP were attenuated with higher fitness (P < 0.05).

Conclusions
OPA performed under high work-related stress or by workers with low fitness may exaggerate cardiovascular responses to OPA.
Injection-induced basement seismicity beneath the Raton Basin: constraints from refined fault architectures and basin structure
Authors: Wang Ruijia , Onyango Evans A. , Schmandt Brandon , Worthington Lindsay 
Published: June 2024

Intraplate earthquakes induced by anthropogenic fluid injection present unexpected seismic risk to previously quiescent or low seismicity-rate regions. Despite many studies of induced seismicity, there are relatively few with detailed openly accessible constraints on the interaction between seismic sources and subsurface structures. In this study of the Raton Basin, we refine source observations from a dense nodal array and constrain basin structure using teleseismic receiver functions. The cross-correlation-based relocated hypocentres and a new set of focal mechanisms light up active fault segments and show clear spatiotemporal patterns. The geometric complexity of reactivated fault clusters appears greatest near higher rate injection wells. Simpler normal fault structure is found farther from injection wells and near abrupt structural transitions suggested by receiver functions. While less induced seismicity in the crystalline basement is expected when injection is >1 km from the top of the basement (like Raton), our receiver function analysis identified a basin thickness ~3 km beneath the nodal array and lateral variations in sedimentary structures. Our results explain potential fluid connectivity between the injection depths focused at ~1–1.5 km below the surface and basement fault activity that begins at ~3 km and reaches peak activity at ~4–8 km depths.
This article is part of the theme issue ‘Induced seismicity in coupled subsurface systems’.
Fluid-driven aseismic fault slip with permeability enhancement and dilatancy
Authors: Dunham Eric M. 
Published: June 2024

Injection-induced seismicity and aseismic slip often involve the reactivation of long-dormant faults, which may have extremely low permeability prior to slip. In contrast, most previous models of fluid-driven aseismic slip have assumed linear pressure diffusion in a fault zone of constant permeability and porosity. Slip occurs within a frictional shear crack whose edge can either lag or lead pressure diffusion, depending on the dimensionless stress-injection parameter that quantifies the prestress and injection conditions. Here, we extend this foundational work by accounting for permeability enhancement and dilatancy, assumed to occur instantaneously upon the onset of slip. The fault zone ahead of the crack is assumed to be impermeable, so fluid flow and pressure diffusion are confined to the interior, slipped part of the crack. The confinement of flow increases the pressurization rate and reduction of fault strength, facilitating crack growth even for severely understressed faults. Suctions from dilatancy slow crack growth, preventing propagation beyond the hydraulic diffusion length. Our new two-dimensional and three-dimensional solutions can facilitate the interpretation of induced seismicity data sets. They are especially relevant for faults in initially low permeability formations, such as shale layers serving as caprock seals for geologic carbon storage, or for hydraulic stimulation of geothermal reservoirs.
This article is part of the theme issue ‘Induced seismicity in coupled subsurface systems’.
High efficient chromatin conformation capture without pre-enrichment (HiChew) in single cells
Authors: Chen Zhichao , Xie Yeming , Tan Chen , Ruan Fengying , Luo Meng , Zhang Chen , Guo Mei , Fang Yitong , Tang Chong 
Published: June 2024

AbstractThis study presents HiChew, a cutting-edge technique for high-efficiency chromatin conformation capture in single cells, without the need for pre-enrichment. This unique approach minimizes the risk of cell or DNA loss. When compared to Dip-C, HiChew captures valid pairs with 4-8 times more efficiency, reducing wastage and saving significant sequencing budget. Furthermore, HiChew delivers a lower false positive ratio, ensuring data accuracy. It also achieves more contacts per cell, enhancing resolution in single cell. HiChew’s superior performance not only enhances single-cell Hi-C but also streamlines conventional Hi-C, making it more robust than conventional HiC methods. This study also unveils a fascinating mechanism of gene activation in the B compartment of chromatin, providing insight into the elusive aspect of gene expression within this region.
Striking Long Term Beneficial Effects of Single Dose Psilocybin and Psychedelic Mushroom Extract in the SAPAP3 Rodent Model of OCD-Like Excessive Self-Grooming
Authors: Brownstien Michal , Lazar Michal , Botvinnik Alexander , Shevakh Chloe , Blakolmer Karin , Lerer Leonard , Lifschytz Tzuri , Lerer Bernard 
Published: June 2024

AbstractObsessive compulsive disorder (OCD) is a highly prevalent disorder that causes serious disability. Available treatments leave 40% or more of people with OCD significantly symptomatic. There is an urgent need for novel therapeutic approaches. Mice that carry a homozygous deletion of the SAPAP3 gene (SAPAP3 KO) manifest a phenotype of excessive self-grooming, tic-like head-body twitches and anxiety. These behaviors closely resemble pathological self-grooming behaviors observed in humans in conditions that overlap with OCD. Following a preliminary report that the tryptaminergic psychedelic, psilocybin, may reduce symptoms in patients with OCD, we undertook a randomized controlled trial of psilocybin in 50 SAPAP3 KO mice (28 male, 22 female). Mice that fulfilled inclusion criteria were randomly assigned to a single intraperitoneal injection of psilocybin (4.4 mg/kg), psychedelic mushroom extract (encompassing the same psilocybin dose) or vehicle control and were evaluated after 2, 4 and 21 days by a rater blind to treatment allocation for grooming characteristics, head-body twitches, anxiety and other behavioral features. Mice treated with vehicle (n=18) manifested a 118.71+95.96 % increase in total self-grooming (the primary outcome measure) over the 21-day observation period. In contrast, total self-grooming decreased by 14.60%+17.90% in mice treated with psilocybin (n=16) and by 19.20+20.05% in mice treated with psychedelic mushroom extract (n=16) (p=.001 for effect of time; p=.0001 for time X treatment interaction). 5 mice were dropped from the vehicle group because they developed skin lesions; 4 from the psilocybin group and none from the psychedelic mushroom extract group. Secondary outcome measures such as head-body twitches and anxiety all showed a significant improvement over 21 days. Notably, in mice that responded to psilocybin (n=12) and psychedelic mushroom extract (n=13), the beneficial effect of a single treatment persisted up to 7 weeks. Mice initially treated with vehicle and non-responsive, showed a clear and lasting therapeutic response when treated with a single dose of psilocybin or psychedelic mushroom extract and followed for a further 3 weeks. While equivalent to psilocybin in overall effect on self-grooming, psychedelic mushroom extract showed superior effects in alleviating head-body twitches and anxiety. These findings strongly justify clinical trials of psilocybin in the treatment of OCD and further studies aimed at elucidating mechanisms that underlie the long-term effects to alleviate excessive self-grooming observed in this study.Graphical AbstractPrepared with BioRender (https://www.biorender.com/)
First Draft Genome of the Corn LeafhopperDalbulus maidis: A Transparent, Open, and Updateable Resource in the Context of Agricultural Emergence
Authors: Debat Humberto Julio , Fernández Franco 
Published: June 2024

AbstractThe corn leafhopper,Dalbulus maidis, is a significant pest affecting maize crops, causing extensive economic losses and posing a threat to food security. This study presents the first draft genome ofD. maidisas part of a comprehensive initiative to generate critical information for effective pest management and long-term control strategies. The genome sequencing is being conducted using a hybrid approach that integrates Oxford Nanopore Technologies (ONT) and Illumina platforms, ensuring high accuracy and depth. The initial genome assembly comprises approximately 580 Mb, with an N50 of 50,453 bp, indicating a draft assembly quality. The genome’s completeness, evaluated using BUSCO, stands at 68.6%, underscoring the thoroughness of the assembly. This first draft genome is designed to be a “living genome,” subject to continuous updates as new sequencing data become available. By providing an open and updatable genomic resource, this study aims to facilitate ongoing research and foster collaborative efforts in developing innovative solutions to mitigate the impact ofD. maidison maize cultivation.
Single-nucleus multiomics reveals the disrupted regulatory programs in three brain regions of sporadic early-onset Alzheimer’s disease
Authors: Liu Andi , Citu Citu , Enduru Nitesh , Chen Xian , Manuel Astrid M. , Sinha Tirthankar , Gorski Damian , Fernandes Brisa S. , Yu Meifang , Schulz Paul E. , Simon Lukas M. , Soto Claudio , Zhao Zhongming 
Published: June 2024

AbstractSporadic early-onset Alzheimer’s disease (sEOAD) represents a significant but less-studied subtype of Alzheimer’s disease (AD). Here, we generated a single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal cortex, and hippocampus of nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type-specific transcriptomic changes and linked candidatecis-regulatory elements (cCREs) across brain regions. We prioritized seven conservative transcription factors in glial cells in multiple brain regions, including RFX4 in astrocytes and IKZF1 in microglia, which are implicated in regulating sEOAD-associated genes. Moreover, we identified the top 25 altered intercellular signaling between glial cells and neurons, highlighting their regulatory potential on gene expression in receiver cells. We reported 38 cCREs linked to sEOAD-associated genes overlapped with late-onset AD risk loci, and sEOAD cCREs enriched in neuropsychiatric disorder risk loci. This atlas helps dissect transcriptional and chromatin dynamics in sEOAD, providing a key resource for AD research.
Post-transcriptional regulation by the CCR4-NOT deadenylase complex maintains redox homeostasis in insulin biosynthesis in mouse pancreatic β cells
Authors: Yanagiya Akiko , Stoney Patrick N. , Tara Yuki , Takaoka Shohei , Vares Guillaume , Higa Rei , Friedman Nicholas R. , Villar-Briones Alejandro , Yamamoto Tadashi 
Published: June 2024

SUMMARYPancreatic β cells synthesize insulin to maintain glucose homeostasis. In diabetes, elevated blood glucose and insulin resistance compel β cells to produce insulin, and hence β cells are vulnerable to oxidative stress by glucotoxicity. In insulin biosynthesis, the conversion of proinsulin to insulin is initiated by forming disulfide bonds in proinsulin for oxidative protein folding. Insulin content and insulin secretion in β cells are decreased by deletion of CNOT7, a catalytic subunit of the CCR4-NOT complex, and accompanied by increased proinsulin, implying the impaired conversion of proinsulin to insulin. We found that PRDX4 essential for disulfide bond formation in proinsulin, is reduced inCnot7-KO β cells. Moreover, protein expression of CNOT8, a paralog of CNOT7, is increased inCnot7-KO β cells and binds toPrdx4mRNA via MSI2. Here, we demonstrate the post-transcriptional regulation ofPrdx4mRNA by the CCR4-NOT complex to maintain oxidative-reductive homeostasis in insulin biosynthesis.HIGHLIGHTSInsulin content and secretion are decreased inCnot7-KO pancreatic β cells.PRDX4, needed for proinsulin folding, is decreased inCnot7-KO pancreatic islets.The conversion of proinsulin to insulin is impaired inCnot7-KO β cells.CNOT8, but not CNOT7, interacts with MSI2 that binds toPrdx4mRNA
Synthetic augmentation of cancer cell line multi-omic datasets using unsupervised deep learning
Authors: Cai Zhaoxiang , Apolinário Sofia , Baião Ana R. , Pacini Clare , Sousa Miguel D. , Vinga Susana , Reddel Roger R , Robinson Phillip J. , Garnett Mathew J. , Zhong Qing , Gonçalves Emanuel 
Published: June 2024

AbstractMulti-omic characterization and integration remains a challenge due to data complexity and sparsity. Addressing this, our study introduces an unsupervised deep learning model, MOVE (Multi-Omic Variational Encoder), specifically designed to integrate and augment the Cancer Dependency Map (DepMap). Harnessing orthogonal multi-omic information, this model successfully generates molecular and phenotypic profiles, resulting in an increase of 32.7% in the number of multi-omic profiles and thereby generating a complete DepMap for 1,523 cancer cell lines. The synthetically enhanced data increases statistical power, uncovering less studied mechanisms associated with drug resistance, and refines the identification of genetic associations and clustering of cancer cell lines. By applying SHAP for model interpretation, MOVE reveals multi-omic features essential for cell clustering and biomarker identification related to drug and gene dependencies. This understanding is crucial for the development of much-needed, effective strategies in prioritizing cancer targets.
Exploring DNA movement through the application of droplet based high efficient chromatin conformation capture (DropHiChew) and loop velocity
Authors: Zhang Chen , Xie Yeming , Tan Chen , Chen Zhichao , Guo Mei , Tang Chong 
Published: June 2024

AbstractThis study presents a novel approach to understanding DNA movement dynamics through the development of a droplet-based, high-efficient chromatin conformation capture method, known as DropHiChew, and a new algorithm, loop velocity. DropHiChew, a user-friendly and cost-effective technique, employs the 10X single-cell systems allowing for easy experimental implementation. The loop velocity algorithm, on the other hand, enables the estimation of the speed and direction of cell development, providing a dynamic perspective on chromatin movement. Even with shallow sequencing, our loop velocity algorithm accurately gauges the trajectory of DNA motion and cellular states. The combined use of DropHiChew and loop velocity offers potential for a wide array of applications in future chromatin capture studies, including disease modeling, cellular differentiation studies, and developmental biology.
Massively Parallel Binding Assay (MPBA) reveals limited transcription factor binding cooperativity, challenging models of specificity
Authors: Lang Tamar Jana , Brodsky Sagie , Manadre Wajd , Vidavski Matan , Valinsky Gili , Mindel Vladimir , Ilan Guy , Carmi Miri , Barkai Naama 
Published: June 2024

AbstractDNA binding domains (DBDs) within transcription factors (TFs) recognize short sequence motifs that are highly abundant in genomes.In vivo, TFs bind only a small subset of motif occurrences, which is often attributed to the cooperative binding of interacting TFs at proximal motifs. However, large-scale testing of this model is still lacking. Here, we describe a novel method allowing parallel measurement of TF binding to thousands of designed sequences within yeast cells and apply it to quantify the binding of dozens of TFs to libraries of regulatory regions containing clusters of binding motifs, systematically mutating all motif combinations. With few exceptions, TF occupancies were well explained by independent binding to individual motifs, with motif cooperation being of only limited effects. Our results challenge the general role of motif combinatorics in directing TF genomic binding and open new avenues for exploring the basis of protein-DNA interactions within cells.
A Message Passing Framework for Precise Cell State Identification with scClassify2
Authors: Ding Wenze , Cao Yue , Fu Xiaohang , Torkel Marni , Yang Jean 
Published: June 2024

AbstractIn single-cell analysis, the ability to accurately annotate cells is crucial for downstream exploration. To date, a wide range of approaches have been developed for cell annotation, spanning from classic statistical models to the latest large language models. However, most of the current methods focus on annotating distinct cell types and overlook the identification of sequential cell populations such as transitioning cells. Here, we propose a message-passing-neural-network-based cell annotation method, scClassify2, to specifically focus on adjacent cell state identification. By incorporating prior biological knowledge through a novel dual-layer architecture and employing ordinal regression and conditional training to differentiate adjacent cell states, scClassify2 achieves superior performance compared to other state-of-the-art methods. In addition to single-cell RNA-sequencing data, scClassify2 is generalizable to annotation from different platforms including subcellular spatial transcriptomics data. To facilitate ease of use, we provide a web server hosting over 30 human tissues.
Single-cell RNA Sequencing Reveals Methamphetamine Inhibits the Liver Immune Response with Involvement of the Dopamine D1 Receptor
Authors: Zhou Jin-Ting , Xu Yungang , Liu Xiao-Huan , Cheng Cheng , Fan Jing-Na , Li Xiaoming , Yu Jun , Li Shengbin 
Published: June 2024

AbstractMethamphetamine (METH) is a highly addictive psychostimulant that causes physical and psychological damage and immune system disorder, especially in the liver, which contains a significant number of immune cells. Dopamine, which is a key neurotransmitter in METH addiction and immune regulation, plays a crucial role in this process. In this study, we developed a chronic METH administration model and conducted single-cell RNA sequencing to investigate the effect of METH on liver immune cells and the involvement of the dopamine receptor D1 (DRD1) in this process. Our findings revealed that chronic exposure to METH induced an immune cell shift from Ifitm3+Mac and Ccl5+Mac to Cd14+Mac, and from Fyn+CD4+Teff, CD8+T, and NKT to Fos+CD4+T and Rora+ILC2, along with suppression of multiple immune functional pathways. DRD1 was implicated in the regulation of some of these pathways and the shifts of hepatic immune cells. This research provides valuable insights into the development of therapies aimed at mitigating METH-induced immune impairment.