bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Transfer Learning Method to Generate Synthetic Synoptic Magnetograms
Authors: Li Xiaoyue , Senthamizh Pavai Valliappan , Shukhobodskaia Daria , Butala Mark D. , Rodriguez Luciano , Magdalenic Jasmina , Delouille Véronique 
Published: January 2024

AbstractCurrent magnetohydrodynamics (MHD) models largely rely on synoptic magnetograms, such as the ones produced by the Global Oscillation Network Group (GONG). Magnetograms are currently available mostly from the front side of the Sun, which significantly reduces the accuracy of MHD modeling. Extreme Ultraviolet (EUV) images can instead be obtained from other vantage points. To investigate the potential, we explore the possibility of using EUV information from the Atmospheric Imaging Assembly (AIA) to directly generate the input for the state‐of‐the‐art 3D MHD model European Heliospheric FORecasting Information Asset (EUHFORIA). Toward this goal, we develop a method called Transfer‐Solar‐GAN which combines a conditional generative adversarial network with a transfer learning approach to overcome training data set limitations. The source domain data set is constructed from multiple pairs of the central portion of co‐registered AIA and Helioseismic and Magnetic Imager (HMI) line of sight (LOS) full‐disk images, while the target domain is constructed from pairs of portions of AIA and GONG sine‐latitude synoptic maps that we call segments. We evaluate Transfer‐Solar‐GAN by comparing modeled and measured solar wind velocity and magnetic field density parameters at the L1 Lagrange point and along the Parker Solar Probe (PSP) trajectory which were determined with EUHFORIA using both empirical GONG and artificial‐intelligence (AI)‐synthetic synoptic magnetograms as inputs. Our results demonstrate that the Transfer‐Solar‐GAN model can provide the necessary information to run solar physics models by EUV information. Our proposed model is trained with only 528 paired image segments and enforces a reliable data division strategy.
RNPS1 stabilizes NAT10 protein to facilitate translation in cancer via tRNA ac4C modification
Authors: Wang Xiaochen , Ling Rongsong , Peng Yurong , Qiu Weiqiong , Chen Demeng 
Published: January 2024

AbstractExisting studies have underscored the pivotal role of N-acetyltransferase 10 (NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma (HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1 (RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6 (ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac4C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel tRNA-ac4C modification sites, thereby providing a potent sequencing tool for tRNA-ac4C research. Our findings expand the repertoire of tRNA ac4C modifications and identify a role of tRNA ac4C in the regulation of mRNA translation in HNSCC.
Systematic reduction of gray matter volume in anorexia nervosa, but relative enlargement with clinical symptoms in the prefrontal and posterior insular cortices: a multicenter neuroimaging study
Authors: Tose Keima , Takamura Tsunehiko , Isobe Masanori , Hirano Yoshiyuki , Sato Yasuhiro , Kodama Naoki , Yoshihara Kazufumi , Maikusa Norihide , Moriguchi Yoshiya , Noda Tomomi , Mishima Ryo , Kawabata Michiko , Noma Shun’ichi , Takakura Shu , Gondo Motoharu , Kakeda Shingo , Takahashi Masatoshi , Ide Satoru , Adachi Hiroaki , Hamatani Sayo , Kamashita Rio , Sudo Yusuke , Matsumoto Koji , Nakazato Michiko , Numata Noriko , Hamamoto Yumi , Shoji Tomotaka , Muratsubaki Tomohiko , Sugiura Motoaki , Murai Toshiya , Fukudo Shin , Sekiguchi Atsushi 
Published: January 2024

AbstractAlthough brain morphological abnormalities have been reported in anorexia nervosa (AN), the reliability and reproducibility of previous studies were limited due to insufficient sample sizes, which prevented exploratory analysis of the whole brain as opposed to regions of interest (ROIs). Objective was to identify brain morphological abnormalities in AN and the association with severity of AN by brain structural magnetic resonance imaging (MRI) in a multicenter study, and to conduct exploratory analysis of the whole brain. Here, we conducted a cross-sectional multicenter study using T1-weighted imaging (T1WI) data collected between May 2014 and February 2019 in Japan. We analyzed MRI data from 103 female AN patients (58 anorexia nervosa restricting type [ANR] and 45 anorexia nervosa binge-purging type [ANBP]) and 102 age-matched female healthy controls (HC). MRI data from five centers were preprocessed using the latest harmonization method to correct for intercenter differences. Gray matter volume (GMV) was calculated from T1WI data of all participants. Of the 205 participants, we obtained severity of eating disorder symptom scores from 179 participants, including 87 in the AN group (51 ANR, 36 ANBP) and 92 HC using the Eating Disorder Examination Questionnaire (EDE-Q) 6.0. GMV reduction were observed in the AN brain, including the bilateral cerebellum, middle and posterior cingulate gyrus, supplementary motor cortex, precentral gyrus medial segment, and thalamus. In addition, the orbitofrontal cortex (OFC), ventromedial prefrontal cortex (vmPFC), rostral anterior cingulate cortex (ACC), and posterior insula volumes showed positive correlations with severity of symptoms. This multicenter study was conducted with a large sample size to identify brain morphological abnormalities in AN. The findings provide a better understanding of the pathogenesis of AN and have potential for the development of brain imaging biomarkers of AN. Trial Registration: UMIN000017456. https://center6.umin.ac.jp/cgi-open-bin/icdr/ctr_view.cgi?recptno=R000019303.
Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss
Authors: Xie Xudong , Cheng Peng , Hu Liangcong , Zhou Wu , Zhang Detai , Knoedler Samuel , Liu Guodong , Xiong Yuan , Xue Hang , Hu Yiqiang , Kern Barbara , Obed Doha , Panayi Adriana C. , Chen Lang , Yan Chenchen , Lin Ze , Dai Guandong , Mi Bobin , Zhang Yingze , Liu Guohui 
Published: January 2024

AbstractThe clinical role and underlying mechanisms of valproic acid (VPA) on bone homeostasis remain controversial. Herein, we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density (BMD) in both patients and mice. This effect was attributed to VPA-induced elevation in osteoclast formation and activity. Through RNA-sequencing, we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro, and further, a marked upregulation of mature miR-6359 (miR-6359) in vivo was demonstrated using quantitative real-time PCR (qRT-PCR) and miR-6359 fluorescent in situ hybridization (miR-6359-FISH). Specifically, the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils, T lymphocytes, monocytes and bone marrow-derived mesenchymal stem cells (BMSCs) following VPA stimulation, which influenced osteoclast differentiation and bone-resorptive activity. Additionally, VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species (ROS) production by silencing the SIRT3 protein expression, followed by activation of the MAPK signaling pathway, which enhanced osteoclast formation and activity, thereby accelerating bone loss. Currently, there are no medications that can effectively treat VPA-induced bone loss. Therefore, we constructed engineered small extracellular vesicles (E-sEVs) targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif (CGGGAGC) in the 3’-end of the anti-miR-6359 sequence. We confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss, but not on ovariectomy (OVX) and glucocorticoid-induced osteoporotic models, deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.
Synaptic and mitochondrial mechanisms behind alcohol-induced imbalance of excitatory/inhibitory synaptic activity and associated cognitive and behavioral abnormalities
Authors: Arzua Thiago , Yan Yasheng , Liu Xiaojie , Dash Ranjan K. , Liu Qing-Song , Bai Xiaowen 
Published: January 2024

AbstractAlcohol consumption during pregnancy can significantly impact the brain development of the fetus, leading to long-term cognitive and behavioral problems. However, the underlying mechanisms are not well understood. In this study, we investigated the acute and chronic effects of binge-like alcohol exposure during the third trimester equivalent in postnatal day 7 (P7) mice on brain cell viability, synapse activity, cognitive and behavioral performance, and gene expression profiles at P60. Our results showed that alcohol exposure caused neuroapoptosis in P7 mouse brains immediately after a 6-hour exposure. In addition, P60 mice exposed to alcohol during P7 displayed impaired learning and memory abilities and anxiety-like behaviors. Electrophysiological analysis of hippocampal neurons revealed an excitatory/inhibitory imbalance in alcohol-treated P60 mice compared to controls, with decreased excitation and increased inhibition. Furthermore, our bioinformatic analysis of 376 dysregulated genes in P60 mouse brains following alcohol exposure identified 50 synapse-related and 23 mitochondria-related genes. These genes encoded proteins located in various parts of the synapse, synaptic cleft, extra-synaptic space, synaptic membranes, or mitochondria, and were associated with different biological processes and functions, including the regulation of synaptic transmission, transport, synaptic vesicle cycle, metabolism, synaptogenesis, mitochondrial activity, cognition, and behavior. The dysregulated synapse and mitochondrial genes were predicted to interact in overlapping networks. Our findings suggest that altered synaptic activities and signaling networks may contribute to alcohol-induced long-term cognitive and behavioral impairments in mice, providing new insights into the underlying synaptic and mitochondrial molecular mechanisms and potential neuroprotective strategies.
Unexpected inhibition of the lipid kinase PIKfyve reveals an epistatic role for p38 MAPKs in endolysosomal fission and volume control
Authors: Wible Daric J. , Parikh Zalak , Cho Eun Jeong , Chen Miao-Der , Jeter Collene R. , Mukhopadhyay Somshuvra , Dalby Kevin N. , Varadarajan Shankar , Bratton Shawn B. 
Published: January 2024

Abstractp38 mitogen-activated protein kinases (MAPKs) participate in autophagic signaling; and previous reports suggest that pyridinyl imidazole p38 MAPK inhibitors, including SB203580 and SB202190, induce cell death in some cancer cell-types through unrestrained autophagy. Subsequent studies, however, have suggested that the associated cytoplasmic vacuolation resulted from off-target inhibition of an unidentified enzyme. Herein, we report that SB203580-induced vacuolation is rapid, reversible, and relies on the class III phosphatidylinositol 3-kinase (PIK3C3) complex and the production of phosphatidylinositol 3-phosphate [PI(3)P] but not on autophagy per se. Rather, vacuolation resulted from the accumulation of Rab7 on late endosome and lysosome (LEL) membranes, combined with an osmotic imbalance that triggered severe swelling in these organelles. Inhibition of PIKfyve, the lipid kinase that converts PI(3)P to PI(3,5)P2 on LEL membranes, produced a similar phenotype in cells; therefore, we performed in vitro kinase assays and discovered that both SB203580 and SB202190 directly inhibited recombinant PIKfyve. Cancer cells treated with either drug likewise displayed significant reductions in the endogenous levels of PI(3,5)P2. Despite these results, SB203580-induced vacuolation was not entirely due to off-target inhibition of PIKfyve, as a drug-resistant p38α mutant suppressed vacuolation; and combined genetic deletion of both p38α and p38β dramatically sensitized cells to established PIKfyve inhibitors, including YM201636 and apilimod. The rate of vacuole dissolution (i.e., LEL fission), following the removal of apilimod, was also significantly reduced in cells treated with BIRB-796, a structurally unrelated p38 MAPK inhibitor. Thus, our studies indicate that pyridinyl imidazole p38 MAPK inhibitors induce cytoplasmic vacuolation through the combined inhibition of both PIKfyve and p38 MAPKs, and more generally, that p38 MAPKs act epistatically to PIKfyve, most likely to promote LEL fission.
Self-encapsulated ionic fibers based on stress-induced adaptive phase transition for non-contact depth-of-field camouflage sensing
Authors: Liu Ying , Wang Chan , Liu Zhuo , Qu Xuecheng , Gai Yansong , Xue Jiangtao , Chao Shengyu , Huang Jing , Wu Yuxiang , Li Yusheng , Luo Dan , Li Zhou 
Published: January 2024

AbstractIonically conductive fibers have promising applications; however, complex processing techniques and poor stability limit their practicality. To overcome these challenges, we proposed a stress-induced adaptive phase transition strategy to conveniently fabricate self-encapsulated hydrogel-based ionically conductive fibers (se-HICFs). se-HICFs can be produced simply by directly stretching ionic hydrogels with ultra-stretchable networks (us-IHs) or by dip-drawing from molten us-IHs. During this process, stress facilitated the directional migration and evaporation of water molecules in us-IHs, causing a phase transition in the surface layer of ionic fibers to achieve self-encapsulation. The resulting sheath-core structure of se-HICFs enhanced mechanical strength and stability while endowing se-HICFs with powerful non-contact electrostatic induction capabilities. Mimicking nature, se-HICFs were woven into spider web structures and camouflaged in wild environments to achieve high spatiotemporal resolution 3D depth-of-field sensing for different moving media. This work opens up a convenient route to fabricate stable functionalized ionic fibers.
A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer
Authors: Eglenen-Polat Buse , Kowash Ryan R. , Huang Hai-Cheng , Siteni Silvia , Zhu Mingrui , Chen Kenian , Bender Matthew E. , Mender Ilgen , Stastny Victor , Drapkin Benjamin J. , Raj Prithvi , Minna John D. , Xu Lin , Shay Jerry W. , Akbay Esra A. 
Published: January 2024

AbstractThere are few effective treatments for small cell lung cancer (SCLC) underscoring the need for innovative therapeutic approaches. This study focuses on exploiting telomerase, a critical SCLC dependency as a therapeutic target. A prominent characteristic of SCLC is their reliance on telomerase activity, a key enzyme essential for their continuous proliferation. Here we utilize a nucleoside analog, 6-Thio-2’-deoxyguanosine (6TdG) currently in phase II clinical trials, that is preferentially incorporated by telomerase into telomeres leading to telomere dysfunction. Using preclinical mouse and human derived models we find low intermittent doses of 6TdG inhibit tumor growth and reduce metastatic burden. Anti-tumor efficacy correlates with a reduction in a subpopulation of cancer initiating like cells (CICs) identified by their expression of L1CAM/CD133 and highest telomerase activity. 6TdG treatment also leads to activation of innate and adaptive anti-tumor responses. Mechanistically, 6TdG depletes CICs and induces type-I interferon signaling leading to tumor immune visibility by activating tumor cell STING signaling. We also observe increased sensitivity to irradiation after 6TdG treatment in both syngeneic and humanized SCLC xenograft models both of which are dependent on the presence of host immune cells. This study underscores the immune-enhancing and metastasis-reducing effects of 6TdG, employing a range of complementary in vitro and in vivo SCLC preclinical models providing a potential therapeutic approach to SCLC.
Structure of the M. tuberculosis DnaK−GrpE complex reveals how key DnaK roles are controlled
Authors: Xiao Xiansha , Fay Allison , Molina Pablo Santos , Kovach Amanda , Glickman Michael S. , Li Huilin 
Published: January 2024

AbstractThe molecular chaperone DnaK is essential for viability of Mycobacterium tuberculosis (Mtb). DnaK hydrolyzes ATP to fold substrates, and the resulting ADP is exchanged for ATP by the nucleotide exchange factor GrpE. It has been unclear how GrpE couples DnaK’s nucleotide exchange with substrate release. Here we report a cryo-EM analysis of GrpE bound to an intact Mtb DnaK, revealing an asymmetric 1:2 DnaK−GrpE complex. The GrpE dimer ratchets to modulate both DnaK nucleotide-binding domain and the substrate-binding domain. We further show that the disordered GrpE N-terminus is critical for substrate release, and that the DnaK−GrpE interface is essential for protein folding activity both in vitro and in vivo. Therefore, the Mtb GrpE dimer allosterically regulates DnaK to concomitantly release ADP in the nucleotide-binding domain and substrate peptide in the substrate-binding domain.
Molecular quantitative trait loci in reproductive tissues impact male fertility in cattle
Authors: Mapel Xena Marie , Kadri Naveen Kumar , Leonard Alexander S. , He Qiongyu , Lloret-Villas Audald , Bhati Meenu , Hiltpold Maya , Pausch Hubert 
Published: January 2024

AbstractBreeding bulls are well suited to investigate inherited variation in male fertility because they are genotyped and their reproductive success is monitored through semen analyses and thousands of artificial inseminations. However, functional data from relevant tissues are lacking in cattle, which prevents fine-mapping fertility-associated genomic regions. Here, we characterize gene expression and splicing variation in testis, epididymis, and vas deferens transcriptomes of 118 mature bulls and conduct association tests between 414,667 molecular phenotypes and 21,501,032 genome-wide variants to identify 41,156 regulatory loci. We show broad consensus in tissue-specific and tissue-enriched gene expression between the three bovine tissues and their human and murine counterparts. Expression- and splicing-mediating variants are more than three times as frequent in testis than epididymis and vas deferens, highlighting the transcriptional complexity of testis. Finally, we identify genes (WDR19, SPATA16, KCTD19, ZDHHC1) and molecular phenotypes that are associated with quantitative variation in male fertility through transcriptome-wide association and colocalization analyses.
Pangenome graphs improve the analysis of structural variants in rare genetic diseases
Authors: Groza Cristian , Schwendinger-Schreck Carl , Cheung Warren A. , Farrow Emily G. , Thiffault Isabelle , Lake Juniper , Rizzo William B. , Evrony Gilad , Curran Tom , Bourque Guillaume , Pastinen Tomi 
Published: January 2024

AbstractRare DNA alterations that cause heritable diseases are only partially resolvable by clinical next-generation sequencing due to the difficulty of detecting structural variation (SV) in all genomic contexts. Long-read, high fidelity genome sequencing (HiFi-GS) detects SVs with increased sensitivity and enables assembling personal and graph genomes. We leverage standard reference genomes, public assemblies (n = 94) and a large collection of HiFi-GS data from a rare disease program (Genomic Answers for Kids, GA4K, n = 574 assemblies) to build a graph genome representing a unified SV callset in GA4K, identify common variation and prioritize SVs that are more likely to cause genetic disease (MAF < 0.01). Using graphs, we obtain a higher level of reproducibility than the standard reference approach. We observe over 200,000 SV alleles unique to GA4K, including nearly 1000 rare variants that impact coding sequence. With improved specificity for rare SVs, we isolate 30 candidate SVs in phenotypically prioritized genes, including known disease SVs. We isolate a novel diagnostic SV in KMT2E, demonstrating use of personal assemblies coupled with pangenome graphs for rare disease genomics. The community may interrogate our pangenome with additional assemblies to discover new SVs within the allele frequency spectrum relevant to genetic diseases.
Persistent warm-eddy transport to Antarctic ice shelves driven by enhanced summer westerlies
Authors: Gao Libao , Yuan Xiaojun , Cai Wenju , Guo Guijun , Yu Weidong , Shi Jiuxin , Qiao Fangli , Wei Zexun , Williams Guy D. 
Published: January 2024

AbstractThe offshore ocean heat supplied to the Antarctic continental shelves by warm eddies has the potential to greatly impact the melting rates of ice shelves and subsequent global sea level rise. While featured in modeling and some observational studies, the processes around how these warm eddies form and overcome the dynamic sub-surface barrier of the Antarctic Slope Front over the upper continental slope has not yet been clarified. Here we report on the detailed observations of persistent eddies carrying warm modified Circumpolar Deep Water (CDW) onto the continental shelf of Prydz Bay, East Antarctica, using subsurface mooring and hydrographic section data from 2013-2015. We show the warm-eddy transport is most active when the summer westerlies strengthen, which promotes the upwelling of CDW and initiates eddy formation and intrusions. Our study highlights the important role of warm eddies in the melting of Antarctica’s ice shelves, both now and into the future.
Electrophotocatalytic hydrogenation of imines and reductive functionalization of aryl halides
Authors: Kang Wen-Jie , Zhang Yanbin , Li Bo , Guo Hao 
Published: January 2024

AbstractThe open-shell catalytically active species, like radical cations or radical anions, generated by one-electron transfer of precatalysts are widely used in energy-consuming redox reactions, but their excited-state lifetimes are usually short. Here, a closed-shell thioxanthone-hydrogen anion species (3), which can be photochemically converted to a potent and long-lived reductant, is generated under electrochemical conditions, enabling the electrophotocatalytic hydrogenation. Notably, TfOH can regulate the redox potential of the active species in this system. In the presence of TfOH, precatalyst (1) reduction can occur at low potential, so that competitive H2 evolution can be inhibited, thus effectively promoting the hydrogenation of imines. In the absence of TfOH, the reducing ability of the system can reach a potency even comparable to that of Na0 or Li0, thereby allowing the hydrogenation, borylation, stannylation and (hetero)arylation of aryl halides to construct C−H, C−B, C−Sn, and C−C bonds.