bluuebunny/crossref_metadata_2025_split huggingface dataset:
Equatorial Electrojet (EEJ) Response to Interplanetary (IP) Shocks
Authors: Nilam B. , Tulasi Ram S. , Ankita M. , Oliveira Denny M. , Dimri A. P. 
Published: December 2023

AbstractInterplanetary (IP) shocks are known to cause significant modifications in Earth's magnetospheric and ionospheric current systems. The sudden enhancement of solar wind dynamic pressure (PDyn) associated with IP shocks could induce convection electric fields at high‐latitude ionosphere which can promptly penetrate to equatorial and low‐latitude regions. Additionally, prompt penetration electric field disturbances may also be induced due to the sudden southward/northward turnings of the Interplanetary Magnetic Field (IMF Bz) (eastward/westward turnings of the interplanetary electric field, IEFy) during IP shocks. The resultant electric field disturbances can significantly alter the ionospheric electrodynamics and equatorial electrojet (EEJ). In this study, the EEJ response to a large number of IP shocks that occurred during 2001–2021 has been investigated. The magnitude of the EEJ response to IP shocks shows a clear local time dependence and varies linearly with the change in solar wind dynamic pressure. The EEJ response is also found to depend considerably on the solar activity (F10.7 solar flux) and the polarity changes in IMF Bz associated with IP shocks. For the first time, an empirical relation is derived that can quantitatively estimate the EEJ response to IP shocks using a large number (306) of events that occurred over a span of two solar cycles. The derived empirical relation is found to be very accurate in predicting the response of the EEJ and exhibits an excellent correlation with observations.
The Effect of Magma Poor and Magma Rich Rifted Margins on Continental Collision Dynamics
Authors: Turino V. , Magni V. , Kjøll H. J. , Jakob J. 
Published: December 2023

AbstractThe transition between non‐rifted continental lithosphere and oceanic lithosphere in rifted margins can display a wide range of characteristics, depending on the regional tectonic evolution. The velocity and duration of the rifting process as well as the geodynamic setting influence the properties and geometry of the margins, which are often grouped into two main categories: magma‐poor and magma‐rich. We show how different types of rifted margins can influence the dynamics of continental collision, focusing on the time and depth of slab break‐off after collision and the fate of margin material. We find that rifted margins have a noticeable impact on subduction dynamics, as we observe large variability in slab break‐off times and depths. In particular, the presence of a rifted margin can delay slab break‐off to up to 60 Myr after the onset of collision. Our results show that a large portion of the weak crust of magma‐poor margins is likely to detach from the subducting plate and accrete to the upper plate, while the dense and strong mafic and ultramafic component of magma‐rich margins causes most of the margin to subduct and be lost into the mantle, leaving only a small fraction of transitional and oceanic crust at the surface. Therefore, the volume of accreted material is much larger when the margin is magma‐poor than magma‐rich, which is consistent with geological observations that fossil magma‐poor rifted margins are preserved in many mountain ranges, whereas remnants of magma‐rich rifted margins are scarce.
High‐Resolution, Multiproxy Speleothem Record of the 8.2 ka Event From Mainland Southeast Asia
Authors: Wood Christopher T. , Johnson Kathleen R. , Lewis Lindsey. E. , Wright Kevin , Wang Jessica K. , Borsato Andrea , Griffiths Michael L. , Mason Andrew , Henderson Gideon M. , Setera Jacob B. , Frisia Silvia , Keophanhya Sengphone , White Joyce C. 
Published: December 2023

AbstractThe 8.2 ka event is the most significant global climate anomaly of the Holocene epoch, but a lack of records from Mainland Southeast Asia (MSEA) currently limits our understanding of the spatial and temporal extent of the climate response. A newly developed speleothem record from Tham Doun Mai Cave, Northern Laos provides the first high‐resolution record of this event in MSEA. Our multiproxy record (δ18O, δ13C, Mg/Ca, Sr/Ca, and petrographic data), anchored in time by 9 U‐Th ages, reveals a significant reduction in local rainfall amount and weakening of the monsoon at the event onset at ∼8.29 ± 0.03 ka BP. This response lasts for a minimum of ∼170 years, similar to event length estimates from other speleothem δ18O monsoon records. Interestingly, however, our δ13C and Mg/Ca data, proxies for local hydrology, show that abrupt changes to local rainfall amounts began decades earlier (∼70 years) than registered in the δ18O. Moreover, the δ13C and Mg/Ca also show that reductions in rainfall continued for at least ∼200 years longer than the weakening of the monsoon inferred from the δ18O. Our interpretations suggest that drier conditions brought on by the 8.2 ka event in MSEA were felt beyond the temporal boundaries defined by δ18O‐inferred monsoon intensity, and an initial wet period (or precursor event) may have preceded the local drying. Most existing Asian Monsoon proxy records of the 8.2 ka event may lack the resolution and/or multiproxy information necessary to establish local and regional hydrological sensitivity to abrupt climate change.
The intrinsic defects of T cells impact the efficacy of CAR-T therapy in patients with diffuse large B-cell lymphoma
Authors: Zhao Jinrong , Wei Chong , Wang Shuqing , Zhang Yan , Wang Wei , Zhao Danqing , Wang Zi , Zhou Zhipeng , Bai Jing , Zhang Wei , Zhou Daobin 
Published: December 2023

AbstractCAR-T cell therapy did not achieve the desired efficacy in some patients with diffuse large B-cell lymphoma (DLBCL). We conducted single-cell RNA and TCR sequencing as well as methylation chip profiling of peripheral blood samples in DLBCL patients. Patients who achieved complete remission (CR) showed an upward trend in T-cell levels, especially CD8-effector T cells. The responders exhibited T-cell clone expansion, more active T-cell transformation, and frequent cell communication. Highly expressed genes in the CR group were enriched in functions like leukocyte-mediated cytotoxicity and activation of immune response, while the non-CR group was enriched in pathways related to DNA damage and P53-mediated intrinsic apoptotic. More differentially methylated probes (DMPs) were identified in the baseline of the non-CR group (779 vs 350). GSEA analysis revealed that the genes annotated by DMPs were associated with cellular immune functions in T cells, including the generation of chemokines, leukocyte-mediated cytotoxicity, and cell-killing functions. The genes with low expression in the non-CR group exhibited a high methylation status. There is heterogeneity in the cellular, molecular, and epigenetic characteristics of host T cells in patients with different clinical outcomes. Intrinsic defects in T cells are important factors leading to poor efficacy of CAR-T therapy.
Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40)
Authors: Li Junqin , Liu Bin , Wu Hao , Zhang Shuaishuai , Liang Zhuowen , Guo Shuo , Jiang Huijie , Song Yue , Lei Xing , Gao Yi , Cheng Pengzhen , Li Donglin , Wang Jimeng , Liu Yang , Wang Di , Zhan Nazhi , Xu Jing , Wang Lin , Xiao Guozhi , Yang Liu , Pei GuoXian 
Published: December 2023

AbstractGiven afferent functions, sensory nerves have recently been found to exert efferent effects and directly alter organ physiology. Additionally, several studies have highlighted the indirect but crucial role of sensory nerves in the regulation of the physiological function of osteoclasts. Nonetheless, evidence regarding the direct sensory nerve efferent influence on osteoclasts is lacking. In the current study, we found that high levels of efferent signals were transported directly from the sensory nerves into osteoclasts. Furthermore, sensory hypersensitivity significantly increased osteoclastic bone resorption, and sensory neurons (SNs) directly promoted osteoclastogenesis in an in vitro coculture system. Moreover, we screened a novel neuropeptide, Cyp40, using an isobaric tag for relative and absolute quantitation (iTRAQ). We observed that Cyp40 is the efferent signal from sensory nerves, and it plays a critical role in osteoclastogenesis via the aryl hydrocarbon receptor (AhR)-Ras/Raf-p-Erk-NFATc1 pathway. These findings revealed a novel mechanism regarding the influence of sensory nerves on bone regulation, i.e., a direct promoting effect on osteoclastogenesis by the secretion of Cyp40. Therefore, inhibiting Cyp40 could serve as a strategy to improve bone quality in osteoporosis and promote bone repair after bone injury.
PDIA6, which is regulated by TRPM2-AS/miR-424-5p axis, promotes endometrial cancer progression via TGF-beta pathway
Authors: Wang Pengling , Zhang Tianli , Jiang Nan , Wang Kun , Feng Liping , Liu Ting , Yang Xingsheng 
Published: December 2023

AbstractPDIA6 have been reported to be involved in a variety of cancers, however, the underlying role in endometrial cancer is still unclear. In this study, we aimed to study the function of PDIA6 in endometrial cancer. Firstly, we verified that PDIA6 was significantly upregulated in endometrial cancer, which was correlated with the progression of endometrial cancer patients. Furthermore, we identified PDIA6 significantly altered the ability of endometrial cancer cells to proliferate and metastasize. In addition, our result illustrated the oncogene effects of PDIA6 in promoting malignant biological behavior of endometrial cancer cells by regulating TGF-β pathway and being modulated by TRPM2-AS/miR-424-5p axis for the first time. Taken together, this study suggested that PDIA6 may be a new candidate target for endometrial cancer therapy.
The E3 ubiquitin ligase NEDD4 regulates chemoresistance to 5-fluorouracil in colorectal cancer cells by altering JNK signalling
Authors: Anand Sushma , Nedeva Christina , Chitti Sai V. , Fonseka Pamali , Kang Taeyoung , Gangoda Lahiru , Tabassum Nishat I. , Abdirahman Suad , Arumugam Thiruma V. , Putoczki Tracy L. , Kumar Sharad , Mathivanan Suresh 
Published: December 2023

AbstractColorectal cancer (CRC) is the second leading cause of cancer deaths. Though chemotherapy is the main treatment option for advanced CRC, patients invariably acquire resistance to chemotherapeutic drugs and fail to respond to the therapy. Although understanding the mechanisms regulating chemoresistance has been a focus of intense research to manage this challenge, the pathways governing resistance to drugs are poorly understood. In this study, we provide evidence for the role of ubiquitin ligase NEDD4 in resistance developed against the most commonly used CRC chemotherapeutic drug 5-fluorouracil (5-FU). A marked reduction in NEDD4 protein abundance was observed in a panel of CRC cell lines and patient-derived xenograft samples that were resistant to 5-FU. Knockout of NEDD4 in CRC cells protected them from 5-FU-mediated apoptosis but not oxaliplatin or irinotecan. Furthermore, NEDD4 depletion in CRC cells reduced proliferation, colony-forming abilities and tumour growth in mice. Follow-up biochemical analysis highlighted the inhibition of the JNK signalling pathway in NEDD4-deficient cells. Treatment with the JNK activator hesperidin in NEDD4 knockout cells sensitised the CRC cells against 5-FU. Overall, we show that NEDD4 regulates cell proliferation, colony formation, tumour growth and 5-FU chemoresistance in CRC cells.
The deubiquitinating enzyme USP44 suppresses hepatocellular carcinoma progression by inhibiting Hedgehog signaling and PDL1 expression
Authors: Chen Sisi , Zhou Binghai , Huang Wei , Li Qing , Yu Ye , Kuang Xiuqing , Huang Huabin , Wang Wei , Xie Peiyi 
Published: December 2023

AbstractHepatocellular carcinoma (HCC) is one of the deadliest malignancies in the world. Research into the key genes that maintain the malignant behavior of cancer cells is crucial for the treatment of HCC. Here, we identified ubiquitin‐specific peptidase 44 (USP44), a member of the deubiquitinase family, as a novel regulator of HCC progression. The tumor suppressive function of USP44 was evaluated in a series of in vitro and in vivo experiments. Through quantitative proteomics examination, we demonstrated that USP44 inhibits HCC PDL1 expression by downregulating the Hedgehog (Hh) signaling pathway. Mechanistically, we found that USP44 directly interacts with Itch, an E3 ligase involved in Hh signaling, and promotes the deubiquitination and stabilization of Itch. These events result in the proteasomal degradation of Gli1 and subsequent inactivation of Hh signaling, which ultimately suppresses PDL1 expression and the progression of HCC. Furthermore, the HCC tissue microarray was analyzed by immunohistochemistry to evaluate the pathological relevance of the USP44/Itch/Gli1/PDL1 axis. Finally, the Gli1 inhibitor GANT61 was found to act in synergy with anti-PDL1 therapy. Overall, USP44 can act as a suppressive gene in HCC by modulating Hh signaling, and co-inhibition of Gli1 and PDL1 might be an effective novel combination strategy for treating HCC patients.
A novel circular RNA, circMAML3, promotes tumor progression of prostate cancer by regulating miR-665/MAPK8IP2 axis
Authors: Zhenhao Zeng , Ru Chen , Xiaofeng Cheng , Heng Yang , Gongxian Wang 
Published: December 2023

AbstractMany studies have now demonstrated that circRNAs are aberrantly expressed in cancer and are involved in the regulation of malignant tumor progression. However, the role of circMAML3 (hsa_circ_0125392) in prostate cancer has not been reported. circMAML3 was selected from public data through screening. The circMAML3 circular characterization was performed using Sanger sequencing, agarose gel electrophoresis assay, RNase R assay and actinomycin D assay. The expression of circMAML3 in prostate cancer tissues and cells was detected by qRT-PCR. In vivo and in vitro experiments were conducted to investigate the biological functions of circMAML3 in prostate cancer. Finally, the underlying mechanism of circMAML3 was revealed by qRT-PCR, luciferase reporter assay, miRNA Pulldown, RNA immunoprecipitation, western blotting, and rescue assay. Compared to normal prostate tissue and prostate epithelial cells, circMAML3 is highly expressed in prostate cancer tissues and cell lines. CircMAML3 overexpression promotes prostate cancer proliferation and metastasis, while knockdown of circMAML3 exerts the opposite effect. Mechanistically, circMAML3 promotes prostate cancer progression by upregulating MAPK8IP2 expression through sponge miR-665. Our research indicates that circMAML3 promotes prostate cancer progression through the circMAML3/miR-665/MAPK8IP2 axis. circMAML3 and MAPK8IP2 are upregulated in prostate cancer expression and play an oncogenic role, whereas miR-665 is downregulated in prostate cancer and plays an oncogenic role. Therefore, CircMAML3 may be a potential biomarker for prostate cancer diagnosis, treatment and prognosis.
Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease
Authors: Ding Chengyi , Ng Fat Linda , Britton Annie , Im Pek Kei , Lin Kuang , Topiwala Anya , Li Liming , Chen Zhengming , Millwood Iona Y. , Bell Steven , Mehta Gautam 
Published: December 2023

AbstractAlcohol-related liver disease (ARLD) represents a major public health burden. Identification of high-risk individuals would allow efficient targeting of public health interventions. Here, we show significant interactions between pattern of drinking, genetic predisposition (polygenic risk score, PRS) and diabetes mellitus, and risk of incident ARLD, in 312,599 actively drinking adults in UK Biobank. Binge and heavy binge drinking significantly increase the risk of alcohol-related cirrhosis (ARC), with higher genetic predisposition further amplifying the risk. Further, we demonstrate a pronounced interaction between heavy binge drinking and high PRS, resulting in a relative excess risk due to interaction (RERI) of 6.07. Diabetes consistently elevates ARC risk across all drinking and PRS categories, and showed significant interaction with both binge patterns and genetic risk. Overall, we demonstrate synergistic effects of binge drinking, genetics, and diabetes on ARC, with potential to identify high-risk individuals for targeted interventions.
A computational toolbox for the assembly yield of complex and heterogeneous structures
Authors: Curatolo Agnese I. , Kimchi Ofer , Goodrich Carl P. , Krueger Ryan K. , Brenner Michael P. 
Published: December 2023

AbstractThe self-assembly of complex structures from a set of non-identical building blocks is a hallmark of soft matter and biological systems, including protein complexes, colloidal clusters, and DNA-based assemblies. Predicting the dependence of the equilibrium assembly yield on the concentrations and interaction energies of building blocks is highly challenging, owing to the difficulty of computing the entropic contributions to the free energy of the many structures that compete with the ground state configuration. While these calculations yield well known results for spherically symmetric building blocks, they do not hold when the building blocks have internal rotational degrees of freedom. Here we present an approach for solving this problem that works with arbitrary building blocks, including proteins with known structure and complex colloidal building blocks. Our algorithm combines classical statistical mechanics with recently developed computational tools for automatic differentiation. Automatic differentiation allows efficient evaluation of equilibrium averages over configurations that would otherwise be intractable. We demonstrate the validity of our framework by comparison to molecular dynamics simulations of simple examples, and apply it to calculate the yield curves for known protein complexes and for the assembly of colloidal shells.
Dietary circadian rhythms and cardiovascular disease risk in the prospective NutriNet-Santé cohort
Authors: Palomar-Cros Anna , Andreeva Valentina A. , Fezeu Léopold K. , Julia Chantal , Bellicha Alice , Kesse-Guyot Emmanuelle , Hercberg Serge , Romaguera Dora , Kogevinas Manolis , Touvier Mathilde , Srour Bernard 
Published: December 2023

AbstractDaily eating/fasting cycles synchronise circadian peripheral clocks, involved in the regulation of the cardiovascular system. However, the associations of daily meal and fasting timing with cardiovascular disease (CVD) incidence remain unclear. We used data from 103,389 adults in the NutriNet-Santé study. Meal timing and number of eating occasions were estimated from repeated 24 h dietary records. We built multivariable Cox proportional-hazards models to examine their association with the risk of CVD, coronary heart disease and cerebrovascular disease. In this study, having a later first meal (later than 9AM compared to earlier than 8AM) and last meal of the day (later than 9PM compared to earlier than 8PM) was associated with a higher risk of cardiovascular outcomes, especially among women. Our results suggest a potential benefit of adopting earlier eating timing patterns, and coupling a longer nighttime fasting period with an early last meal, rather than breakfast skipping, in CVD prevention.
Chronic exposure to environmental temperature attenuates the thermal sensitivity of salmonids
Authors: González-Ferreras Alexia M. , Barquín Jose , Blyth Penelope S. A. , Hawksley Jack , Kinsella Hugh , Lauridsen Rasmus , Morris Olivia F. , Peñas Francisco J. , Thomas Gareth E. , Woodward Guy , Zhao Lei , O’Gorman Eoin J. 
Published: December 2023

AbstractMetabolism, the biological processing of energy and materials, scales predictably with temperature and body size. Temperature effects on metabolism are normally studied via acute exposures, which overlooks the capacity for organisms to moderate their metabolism following chronic exposure to warming. Here, we conduct respirometry assays in situ and after transplanting salmonid fish among different streams to disentangle the effects of chronic and acute thermal exposure. We find a clear temperature dependence of metabolism for the transplants, but not the in-situ assays, indicating that chronic exposure to warming can attenuate salmonid thermal sensitivity. A bioenergetic model accurately captures the presence of fish in warmer streams when accounting for chronic exposure, whereas it incorrectly predicts their local extinction with warming when incorporating the acute temperature dependence of metabolism. This highlights the need to incorporate the potential for thermal acclimation or adaptation when forecasting the consequences of global warming on ecosystems.
Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms
Authors: Hall Steven R. , Rasmussen Sean A. , Crittenden Edouard , Dawson Charlotte A. , Bartlett Keirah E. , Westhorpe Adam P. , Albulescu Laura-Oana , Kool Jeroen , Gutiérrez José María , Casewell Nicholas R. 
Published: December 2023

AbstractMorbidity from snakebite envenoming affects approximately 400,000 people annually. Tissue damage at the bite-site often leaves victims with catastrophic life-long injuries and is largely untreatable by current antivenoms. Repurposed small molecule drugs that inhibit specific snake venom toxins show considerable promise for tackling this neglected tropical disease. Using human skin cell assays as an initial model for snakebite-induced dermonecrosis, we show that the drugs 2,3-dimercapto-1-propanesulfonic acid (DMPS), marimastat, and varespladib, alone or in combination, inhibit the cytotoxicity of a broad range of medically important snake venoms. Thereafter, using preclinical mouse models of dermonecrosis, we demonstrate that the dual therapeutic combinations of DMPS or marimastat with varespladib significantly inhibit the dermonecrotic activity of geographically distinct and medically important snake venoms, even when the drug combinations are delivered one hour after envenoming. These findings strongly support the future translation of repurposed drug combinations as broad-spectrum therapeutics for preventing morbidity caused by snakebite.
On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging
Authors: Dang Hope , Castro-Portuguez Raul , Espejo Luis , Backer Grant , Freitas Samuel , Spence Erica , Meyers Jeremy , Shuck Karissa , Gardea Emily A. , Chang Leah M. , Balsa Jonah , Thorns Niall , Corban Caroline , Liu Teresa , Bean Shannon , Sheehan Susan , Korstanje Ron , Sutphin George L. 
Published: December 2023

AbstractTryptophan metabolism through the kynurenine pathway influences molecular processes critical to healthy aging including immune signaling, redox homeostasis, and energy production. Aberrant kynurenine metabolism occurs during normal aging and is implicated in many age-associated pathologies including chronic inflammation, atherosclerosis, neurodegeneration, and cancer. We and others previously identified three kynurenine pathway genes—tdo-2, kynu-1, and acsd-1—for which decreasing expression extends lifespan in invertebrates. Here we report that knockdown of haao-1, a fourth gene encoding the enzyme 3-hydroxyanthranilic acid (3HAA) dioxygenase (HAAO), extends lifespan by ~30% and delays age-associated health decline in Caenorhabditis elegans. Lifespan extension is mediated by increased physiological levels of the HAAO substrate 3HAA. 3HAA increases oxidative stress resistance and activates the Nrf2/SKN-1 oxidative stress response. In pilot studies, female Haao knockout mice or aging wild type male mice fed 3HAA supplemented diet were also long-lived. HAAO and 3HAA represent potential therapeutic targets for aging and age-associated disease.