bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in Spreading of Southeast Indian Subantarctic Mode Water During Argo Period
Authors: Qiu Zishan , Lan Jian , Wei Zexun , Xu Tengfei 
Published: June 2024

AbstractSubantarctic Mode Water (SAMW) is one of the most important water masses for the global ocean uptake and storage of heat and carbon. Based on Argo observations, this study focus on the Southeast Indian Subantarctic mode water (SEISAMW), and investigates the changes of SEISAMW spreading and associated mechanisms. SEISAMW is formed through air‐sea interaction as low potential vorticity water in late winter and subducts into permanent thermocline between outcrop lines of 26.6 σθ and 26.9 σθ in Southern Indian Ocean (SIO). After subduction, the SEISAMW spreads northwestward into subtropical gyre and southeastward into Antarctic Circumpolar Current (ACC) separately. During Argo period, the percentage of SEISAMW volume spreading into SIO subtropics decreases at light layer (26.6–26.7 σθ) while increases at medium (26.7–26.8 σθ) and dense (26.8–26.9 σθ) layer. These changes are attributed to the meridional shifts of outcrop lines. The outcrop lines of 26.6 σθ and 26.7 σθ in the central of SIO (75°–90°E), where light SEISAMW forms, shift poleward. The poleward shifts of outcrop lines result in less light SEISAMW spreading into subtropical gyre. In contrast, outcrop lines of 26.7 σθ and 26.8 σθ south of Australia shift equatorward and favor more medium and dense SEISAMWs spreading into subtropical gyre. The shifts of outcrop lines are closely related to the enhancement of Southern Annular Mode.
Tidal Forcing in Icy‐Satellite Oceans Drives Mean Circulation and Ice‐Shell Torques
Authors: Hay Hamish C. F. C. , Hewitt Ian , Katz Richard F. 
Published: June 2024

AbstractTidal forces generate time‐varying currents in bodies with fluid layers, such as the icy ocean moons of the outer solar system. The expectation has been that tidal currents are periodic—they average to zero over a forcing period—so that they are not associated with a mean flow. This expectation arises from the assumption of linearity. Here, we relax this assumption and develop a theory that predicts the emergence of mean currents driven by any periodic forcing. The theory, derived in the context of a global, uniform, shallow ocean, constitutes a set of mean flow equations forced by non‐linear eddy fluctuations. The latter are the canonical, periodic tidal currents predicted by the Laplace Tidal equations. We show that the degree‐2 tide‐raising potential due to obliquity and/or orbital eccentricity can drive time‐averaged currents with zonal wavenumbers from 0 to 4. The most prominent of these is a retrograde zonal jet driven by the obliquity‐forcing potential. Assuming Cassini state obliquities, this jet has speeds ranging from 0.01 to 1 mm s−1, which can exert torques up to roughly 1015 N m at the ice–ocean interfaces of Europa, Callisto, Titan, and Triton. Depending on the viscosity of the ice shell, these torques could drive ice shell drift rates of tens to potentially hundreds of meters a year. Thinner or stably stratified global oceans can experience much faster mean currents.
Pathology of pain and its implications for therapeutic interventions
Authors: Cao Bo , Xu Qixuan , Shi Yajiao , Zhao Ruiyang , Li Hanghang , Zheng Jie , Liu Fengyu , Wan You , Wei Bo 
Published: June 2024

AbstractPain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management is crucial for individuals suffering from pain. However, the current methods for pain assessment and treatment fall short of clinical needs. Benefiting from advances in neuroscience and biotechnology, the neuronal circuits and molecular mechanisms critically involved in pain modulation have been elucidated. These research achievements have incited progress in identifying new diagnostic and therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting the stage for the subsequent contents. The review next delves into the molecular mechanisms underlying pain disorders, including gene mutation, epigenetic modification, posttranslational modification, inflammasome, signaling pathways and microbiota. To better present a comprehensive view of pain research, two prominent issues, sexual dimorphism and pain comorbidities, are discussed in detail based on current findings. The status quo of pain evaluation and manipulation is summarized. A series of improved and innovative pain management strategies, such as gene therapy, monoclonal antibody, brain-computer interface and microbial intervention, are making strides towards clinical application. We highlight existing limitations and future directions for enhancing the quality of preclinical and clinical research. Efforts to decipher the complexities of pain pathology will be instrumental in translating scientific discoveries into clinical practice, thereby improving pain management from bench to bedside.
Depression and risk of infectious diseases: A mendelian randomization study
Authors: Shi Luchen , Ren Junsong , Jin Ke , Li Jun 
Published: June 2024

AbstractPrevious observational inquiries have revealed a correlation between depression and infectious maladies. This study seeks to elucidate the causal linkages between depression, specifically Major Depressive Disorder (MDD), and infectious diseases. Nevertheless, the causative nature of the association between MDD and infectious diseases remains elusive. Two-sample Mendelian Randomization (MR) analyses was executed utilizing single nucleotide polymorphisms (SNPs) significantly connected with MDD and infectious diseases as instrumental variables (IVs). A series of sensitivity analyses were subsequently conducted. Genetic variants linked to MDD were employed as instrumental variables sourced from a genome-wide meta-analyses comprising 500,199 individuals. Summary-level data on five infectious diseases, including candidiasis, pneumonia, skin and soft tissue infections (SSTI), upper respiratory tract infections (URTI), and urinary tract infections (UTI), were acquired from the UK Biobank and FinnGen study. Our findings evinced that genetically predicted MDD exhibited a heightened risk of candidiasis (OR = 1.52, 95% CI 1.06–2.17; P = 2.38E-02), pneumonia (OR = 1.14, 95% CI 1.01–1.29; P = 3.16E-02), URTI (OR = 1.23, 95% CI 1.12–1.36; P = 3.71E-05), and UTI (OR = 1.26, 95% CI 1.12–1.42; P = 8.90E-05). Additionally, we identified bidirectional causal relationships between UTI and MDD. The associations between MDD and the risk of URTI and UTI remained consistent in multivariable MR analyses, accounting for genetically predicted smoking and body mass index. In conclusion, this investigation ascertained a causal connection between MDD and the susceptibility to infectious diseases, particularly URTI and UTI.
Association of post-COVID phenotypic manifestations with new-onset psychiatric disease
Authors: Coleman Ben , Casiraghi Elena , Callahan Tiffany J. , Blau Hannah , Chan Lauren E. , Laraway Bryan , Clark Kevin B. , Re’em Yochai , Gersing Ken R. , Wilkins Kenneth J. , Harris Nomi L. , Valentini Giorgio , Haendel Melissa A. , Reese Justin T. , Robinson Peter N. 
Published: June 2024

AbstractAcute COVID-19 infection can be followed by diverse clinical manifestations referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Studies have shown an increased risk of being diagnosed with new-onset psychiatric disease following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of new-onset psychiatric disease following COVID-19. A retrospective electronic health record (EHR) cohort study of 2,391,006 individuals with acute COVID-19 was performed to evaluate whether non-psychiatric PASC-AMs are associated with new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 76 clinical organizations. EHR codes were mapped to 151 non-psychiatric PASC-AMs recorded 28–120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. Association of newly diagnosed psychiatric disease with age, sex, race, pre-existing comorbidities, and PASC-AMs in seven categories was assessed by logistic regression. There were significant associations between a diagnosis of any psychiatric disease and five categories of PASC-AMs with odds ratios highest for neurological, cardiovascular, and constitutional PASC-AMs with odds ratios of 1.31, 1.29, and 1.23 respectively. Secondary analysis revealed that the proportions of 50 individual clinical features significantly differed between patients diagnosed with different psychiatric diseases. Our study provides evidence for association between non-psychiatric PASC-AMs and the incidence of newly diagnosed psychiatric disease. Significant associations were found for features related to multiple organ systems. This information could prove useful in understanding risk stratification for new-onset psychiatric disease following COVID-19. Prospective studies are needed to corroborate these findings.
Proteomic profiling reveals ACSS2 facilitating metabolic support in acute myeloid leukemia
Authors: Mochmann Liliana H. , Treue Denise , Bockmayr Michael , Silva Patricia , Zasada Christin , Mastrobuoni Guido , Bayram Safak , Forbes Martin , Jurmeister Philipp , Liebig Sven , Blau Olga , Schleich Konstanze , Splettstoesser Bianca , Nordmann Thierry M. , von der Heide Eva K. , Isaakidis Konstandina , Schulze Veronika , Busch Caroline , Siddiq Hafsa , Schlee Cornelia , Hester Svenja , Fransecky Lars , Neumann Martin , Kempa Stefan , Klauschen Frederick , Baldus Claudia D. 
Published: June 2024

AbstractAcute myeloid leukemia (AML) is a heterogeneous disease characterized by genomic aberrations in oncogenes, cytogenetic abnormalities, and an aberrant epigenetic landscape. Nearly 50% of AML cases will relapse with current treatment. A major source of therapy resistance is the interaction of mesenchymal stroma with leukemic cells resulting in therapeutic protection. We aimed to determine pro-survival/anti-apoptotic protein networks involved in the stroma protection of leukemic cells. Proteomic profiling of cultured primary AML (n = 14) with Hs5 stroma cell line uncovered an up-regulation of energy-favorable metabolic proteins. Next, we modulated stroma-induced drug resistance with an epigenetic drug library, resulting in reduced apoptosis with histone deacetylase inhibitor (HDACi) treatment versus other epigenetic modifying compounds. Quantitative phosphoproteomic probing of this effect further revealed a metabolic-enriched phosphoproteome including significant up-regulation of acetyl-coenzyme A synthetase (ACSS2, S30) in leukemia-stroma HDACi treated cocultures compared with untreated monocultures. Validating these findings, we show ACSS2 substrate, acetate, promotes leukemic proliferation, ACSS2 knockout in leukemia cells inhibits leukemic proliferation and ACSS2 knockout in the stroma impairs leukemic metabolic fitness. Finally, we identify ACSS1/ACSS2-high expression AML subtype correlating with poor overall survival. Collectively, this study uncovers the leukemia-stroma phosphoproteome emphasizing a role for ACSS2 in mediating AML growth and drug resistance.
Sponging of five tumour suppressor miRNAs by lncRNA-KCNQ1OT1 activates BMPR1A/BMPR1B-ACVR2A/ACVR2B signalling and promotes chemoresistance in hepatocellular carcinoma
Authors: Majumdar Swagata , Chakraborty Anannya , Das Sumit , Gorain Mahadeo , Chatterjee Soumyabrata , Dey Indrashish , Bhowmik Sayantani , Ghosh Suchandrima , Banerjee Sanjana , Ahammed Sk. Mahiuddin , Chowdhury Abhijit , Datta Simanti , Kundu Gopal , Banerjee Soma 
Published: June 2024

AbstractDiverse mechanisms have been established to understand the chemoresistance of hepatocellular carcinoma (HCC), but the contribution of non-coding RNAs is not surveyed well. Here, we aimed to explore the lncRNA-miRNA axis in Hepatitis C and B virus (HCV and HBV) infected HCC to investigate the molecular mechanism of chemoresistance and to identify a potential therapeutic target for HCC. The small RNA transcriptome analysis followed by qRT-PCR validation with the liver tissues of both HCV and HBV infected HCC patients revealed that miR-424-5p, miR-136-3p, miR-139-5p, miR-223-3p, and miR-375-3p were the most downregulated miRNAs in HCC compared to normal (log2 fold change ≤−1.5, Padj ≤ 0.05). In silico pathway analysis with the validated targets of each miRNA revealed that the signalling pathway regulating pluripotency of stem cells is commonly targeted by these five miRNAs. Subsequent validation by 3′UTR-luciferase assay and western blot analysis unveiled that these five miRNAs impeded either same or diverse genes, but all linked to BMP signalling pathway such as BMPR1A/BMPR1B by miR-139-5p, miR-136-3p, and miR-375-3p, and ACVR2A/ACVR2B by miR-424-5p and miR-223-3p. Furthermore, restoration of each miRNA in Huh7/SNU449 cells inhibited phosphorylation of downstream SMAD1/5 and ERK1/2, and attenuated Epithelial-mesenchymal transition, stemness, spheroid formation, chemoresistance, invasion and migration of cells. To investigate the mechanism of suppression of these miRNAs, “DIANA” tool was employed and lncRNA-KCNQ1OT1 was retrieved as interacting partner of all the five miRNAs. In vitro RNA pull-down assay revealed that lncRNA-KCNQ1OT1 physically interacted and sequestered these five miRNAs in the cytoplasm. Hence, KCNQ1OT1 was suppressed in Huh7/SNU449 cells using CRISPR technology and observed regression of oncogenic properties with enhanced chemosensitivity and reduced metastasis in cancer cells. Shrinkage of tumour size and volume in NOD-SCID mice injected with KCNQ1OT1-sgRNA cells further strengthened our observations. Thus, lncRNA-KCNQ1OT1 is the main regulator, which reduces the level of beneficiary miRNAs in the tumour milieu and modulates BMP signalling pathway to promote chemoresistance in HCC, suggesting lncRNA-KCNQ1OT1 might have robust potential to be a therapeutic target in HCC.
An oncogenic role of lncRNA SNHG1 promotes ATG7 expression and autophagy involving tumor progression and sunitinib resistance of Renal Cell Carcinoma
Authors: Tian Pei , Wei Jinxing , Li Jing , Ren Junkai , He Chaohong 
Published: June 2024

AbstractRenal cell carcinoma (RCC) is a malignant tumor with high incidence in adult kidney. Long non-coding RNAs (lncRNAs) have recently been recognized as important regulators in the development of RCC. However, whether lncRNA SNHG1 is associated with RCC progression remains to be elucidated. Here, the role of SNHG1 in RCC autophagy and sunitinib resistance was evaluated. Expression of SNHG1 in RCC tissues and cells was assessed using RT-qPCR. Western blot was utilized to measure the levels of autophagy-related molecules and ATG7. RNA pull-down and RIP assays were performed to confirm the molecular axis between SNHG1/PTBP1/ATG7. Cell proliferation, migration, invasion and apoptosis were analyzed by CCK-8, EdU, transwell and flow cytometry, respectively. The subcellular localization of SNHG1 was determined by an intracellular fractionation assay. The fluorescence intensity of GFP-LC3 autophagosome in RCC cells was detected. IHC staining was performed to test ATG7 expression in tumor tissues from nude mice. Here, a positive correlation of upregulated SNHG1 with poor prognosis of RCC patients was observed in RCC tissues and cells. SNHG1 knockdown suppressed tumor growth and reversed sunitinib resistance and autophagy of RCC cells. Additionally, SNHG1 was found to directly bind to PTBP1, thereby positively regulating ATG7 expression. Furthermore, we verified that SNHG1 mediated the malignant behavior of RCC cells through the PTBP1/ATG7 axis. To sum up, SNHG1 regulates RCC cell autophagy and sunitinib resistance through the PTBP1/ATG7 axis, which highlights a promising therapeutic target for RCC treatment.
The TAS1R2 G-protein-coupled receptor is an ambient glucose sensor in skeletal muscle that regulates NAD homeostasis and mitochondrial capacity
Authors: Serrano Joan , Boyd Jordan , Brown Ian S. , Mason Carter , Smith Kathleen R. , Karolyi Katalin , Maurya Santosh K. , Meshram Nishita N. , Serna Vanida , Link Grace M. , Gardell Stephen J. , Kyriazis George A. 
Published: June 2024

AbstractThe bioavailability of nicotinamide adenine dinucleotide (NAD) is vital for skeletal muscle health, yet the mechanisms or signals regulating NAD homeostasis remain unclear. Here, we uncover a pathway connecting peripheral glucose sensing to the modulation of muscle NAD through TAS1R2, the sugar-sensing G protein-coupled receptor (GPCR) initially identified in taste perception. Muscle TAS1R2 receptor stimulation by glucose and other agonists induces ERK1/2-dependent phosphorylation and activation of poly(ADP-ribose) polymerase1 (PARP1), a major NAD consumer in skeletal muscle. Consequently, muscle-specific deletion of TAS1R2 (mKO) in male mice suppresses PARP1 activity, elevating NAD levels and enhancing mitochondrial capacity and running endurance. Plasma glucose levels negatively correlate with muscle NAD, and TAS1R2 receptor deficiency enhances NAD responses across the glycemic range, implicating TAS1R2 as a peripheral energy surveyor. These findings underscore the role of GPCR signaling in NAD regulation and propose TAS1R2 as a potential therapeutic target for maintaining muscle health.
Emergent dynamics due to chemo-hydrodynamic self-interactions in active polymers
Authors: Kumar Manoj , Murali Aniruddh , Subramaniam Arvin Gopal , Singh Rajesh , Thutupalli Shashi 
Published: June 2024

AbstractThe field of synthetic active matter has, thus far, been led by efforts to create point-like, isolated (yet interacting) self-propelled objects (e.g. colloids, droplets, microrobots) and understanding their collective dynamics. The design of flexible, freely jointed active assemblies from autonomously powered sub-components remains a challenge. Here, we report freely-jointed active polymers created using self-propelled droplets as monomeric units. Our experiments reveal that the self-shaping chemo-hydrodynamic interactions between the monomeric droplets give rise to an emergent rigidity (the acquisition of a stereotypical asymmetric C-shape) and associated ballistic propulsion of the active polymers. The rigidity and propulsion of the chains vary systematically with their lengths. Using simulations of a minimal model, we establish that the emergent polymer dynamics are a generic consequence of quasi two-dimensional confinement and auto-repulsive trail-mediated chemical interactions between the freely jointed active droplets. Finally, we tune the interplay between the chemical and hydrodynamic fields to experimentally demonstrate oscillatory dynamics of the rigid polymer propulsion. Altogether, our work highlights the possible first steps towards synthetic self-morphic active matter.
Advanced methods for gene network identification and noise decomposition from single-cell data
Authors: Fang Zhou , Gupta Ankit , Kumar Sant , Khammash Mustafa 
Published: June 2024

AbstractCentral to analyzing noisy gene expression systems is solving the Chemical Master Equation (CME), which characterizes the probability evolution of the reacting species’ copy numbers. Solving CMEs for high-dimensional systems suffers from the curse of dimensionality. Here, we propose a computational method for improved scalability through a divide-and-conquer strategy that optimally decomposes the whole system into a leader system and several conditionally independent follower subsystems. The CME is solved by combining Monte Carlo estimation for the leader system with stochastic filtering procedures for the follower subsystems. We demonstrate this method with high-dimensional numerical examples and apply it to identify a yeast transcription system at the single-cell resolution, leveraging mRNA time-course experimental data. The identification results enable an accurate examination of the heterogeneity in rate parameters among isogenic cells. To validate this result, we develop a noise decomposition technique exploiting time-course data but requiring no supplementary components, e.g., dual-reporters.
Tobacco-induced hyperglycemia promotes lung cancer progression via cancer cell-macrophage interaction through paracrine IGF2/IR/NPM1-driven PD-L1 expression
Authors: Jang Hyun-Ji , Min Hye-Young , Kang Yun Pyo , Boo Hye-Jin , Kim Jisung , Ahn Jee Hwan , Oh Seung Ho , Jung Jin Hwa , Park Choon-Sik , Park Jong-Sook , Kim Seog-Young , Lee Ho-Young 
Published: June 2024

AbstractTobacco smoking (TS) is implicated in lung cancer (LC) progression through the development of metabolic syndrome. However, direct evidence linking metabolic syndrome to TS-mediated LC progression remains to be established. Our findings demonstrate that 4-(methylnitrosamino)−1-(3-pyridyl)−1-butanone and benzo[a]pyrene (NNK and BaP; NB), components of tobacco smoke, induce metabolic syndrome characteristics, particularly hyperglycemia, promoting lung cancer progression in male C57BL/6 J mice. NB enhances glucose uptake in tumor-associated macrophages by increasing the expression and surface localization of glucose transporter (GLUT) 1 and 3, thereby leading to transcriptional upregulation of insulin-like growth factor 2 (IGF2), which subsequently activates insulin receptor (IR) in LC cells in a paracrine manner, promoting its nuclear import. Nuclear IR binds to nucleophosmin (NPM1), resulting in IR/NPM1-mediated activation of the CD274 promoter and expression of programmed death ligand-1 (PD-L1). Restricting glycolysis, depleting macrophages, or blocking PD-L1 inhibits NB-mediated LC progression. Analysis of patient tissues and public databases reveals elevated levels of IGF2 and GLUT1 in tumor-associated macrophages, as well as tumoral PD-L1 and phosphorylated insulin-like growth factor 1 receptor/insulin receptor (pIGF-1R/IR) expression, suggesting potential poor prognostic biomarkers for LC patients. Our data indicate that paracrine IGF2/IR/NPM1/PD-L1 signaling, facilitated by NB-induced dysregulation of glucose levels and metabolic reprogramming of macrophages, contributes to TS-mediated LC progression.
FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer
Authors: Wang Zifeng , Townley Scott L. , Zhang Songqi , Liu Mingyu , Li Muqing , Labaf Maryam , Patalano Susan , Venkataramani Kavita , Siegfried Kellee R. , Macoska Jill A. , Han Dong , Gao Shuai , Risbridger Gail P. , Taylor Renea A. , Lawrence Mitchell G. , He Housheng Hansen , Selth Luke A. , Cai Changmeng 
Published: June 2024

AbstractFOXA family proteins act as pioneer factors by remodeling compact chromatin structures. FOXA1 is crucial for the chromatin binding of the androgen receptor (AR) in both normal prostate epithelial cells and the luminal subtype of prostate cancer (PCa). Recent studies have highlighted the emergence of FOXA2 as an adaptive response to AR signaling inhibition treatments. However, the role of the FOXA1 to FOXA2 transition in regulating cancer lineage plasticity remains unclear. Our study demonstrates that FOXA2 binds to distinct classes of developmental enhancers in multiple AR-independent PCa subtypes, with its binding depending on LSD1. Moreover, we reveal that FOXA2 collaborates with JUN at chromatin and promotes transcriptional reprogramming of AP-1 in lineage-plastic cancer cells, thereby facilitating cell state transitions to multiple lineages. Overall, our findings underscore the pivotal role of FOXA2 as a pan-plasticity driver that rewires AP-1 to induce the differential transcriptional reprogramming necessary for cancer cell lineage plasticity.