bluuebunny/crossref_metadata_2025_split huggingface dataset:
The long non-coding RNA TAZ-AS202 promotes lung cancer progression via regulation of the E2F1 transcription factor and activation of Ephrin signaling
Authors: Gobbi Giulia , Grieco Alessandra , Torricelli Federica , Sauta Elisabetta , Santandrea Giacomo , Zanetti Eleonora , Fantini Valentina , Reggiani Francesca , Strocchi Silvia , Paci Massimiliano , Vohra Manik , Saladi Srinivas Vinod , Ambrosetti Davide Carlo , Ciarrocchi Alessia , Sancisi Valentina 
Published: November 2023

AbstractLong non-coding RNAs (lncRNAs) are transcripts without coding potential that are pervasively expressed from the genome and have been increasingly reported to play crucial roles in all aspects of cell biology. They have been also heavily implicated in cancer development and progression, with both oncogenic and tumor suppressor functions. In this work, we identified and characterized a novel lncRNA, TAZ-AS202, expressed from the TAZ genomic locus and exerting pro-oncogenic functions in non-small cell lung cancer. TAZ-AS202 expression is under the control of YAP/TAZ-containing transcriptional complexes. We demonstrated that TAZ-AS202 is overexpressed in lung cancer tissue, compared with surrounding lung epithelium. In lung cancer cell lines TAZ-AS202 promotes cell migration and cell invasion. TAZ-AS202 regulates the expression of a set of genes belonging to cancer-associated pathways, including WNT and EPH-Ephrin signaling. The molecular mechanism underlying TAZ-AS202 function does not involve change of TAZ expression or activity, but increases the protein level of the transcription factor E2F1, which in turn regulates the expression of a large set of target genes, including the EPHB2 receptor. Notably, the silencing of both E2F1 and EPHB2 recapitulates TAZ-AS202 silencing cellular phenotype, indicating that they are essential mediators of its activity. Overall, this work unveiled a new regulatory mechanism that, by increasing E2F1 protein, modifies the non-small cell lung cancer cells transcriptional program, leading to enhanced aggressiveness features. The TAZ-AS202/E2F1/EPHB2 axis may be the target for new therapeutic strategies.
In-cell structural insight into the stability of sperm microtubule doublet
Authors: Tai Linhua , Yin Guoliang , Huang Xiaojun , Sun Fei , Zhu Yun 
Published: November 2023

AbstractThe propulsion for mammalian sperm swimming is generated by flagella beating. Microtubule doublets (DMTs) along with microtubule inner proteins (MIPs) are essential structural blocks of flagella. However, the intricate molecular architecture of intact sperm DMT remains elusive. Here, by in situ cryo-electron tomography, we solved the in-cell structure of mouse sperm DMT at 4.5–7.5 Å resolutions, and built its model with 36 kinds of MIPs in 48 nm periodicity. We identified multiple copies of Tektin5 that reinforce Tektin bundle, and multiple MIPs with different periodicities that anchor the Tektin bundle to tubulin wall. This architecture contributes to a superior stability of A-tubule than B-tubule of DMT, which was revealed by structural comparison of DMTs from the intact and deformed axonemes. Our work provides an overall molecular picture of intact sperm DMT in 48 nm periodicity that is essential to understand the molecular mechanism of sperm motility as well as the related ciliopathies.
Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B
Authors: Fu Yuhui , Ding Binbin , Liu Xiaoxia , Zhao Shangang , Chen Fang , Li Linsen , Zhu Yi , Zhao Jingxuan , Yuan Zhen , Shen Yafeng , Yang Chaofeng , Shao Mengle , Chen She , Bickel Perry E. , Zhong Qing 
Published: November 2023

AbstractLipid droplets (LDs) are dynamic lipid storage organelles that can sense and respond to changes in systemic energy balance. The size and number of LDs are controlled by complex and delicate mechanisms, among which, whether and which SNARE proteins mediate LD fusion, and the mechanisms governing this process remain poorly understood. Here we identified a SNARE complex, syntaxin 18 (STX18)–SNAP23–SEC22B, that is recruited to LDs to mediate LD fusion. STX18 targets LDs with its transmembrane domain spanning the phospholipid monolayer twice. STX18–SNAP23–SEC22B complex drives LD fusion in adiposome lipid mixing and content mixing in vitro assays. CIDEC/FSP27 directly binds STX18, SEC22B, and SNAP23, and promotes the lipid mixing of SNAREs-reconstituted adiposomes by promoting LD clustering. Knockdown of STX18 in mouse liver via AAV resulted in smaller liver and reduced LD size under high-fat diet conditions. All these results demonstrate a critical role of the SNARE complex STX18–SNAP23–SEC22B in LD fusion.
A smooth tubercle bacillus from Ethiopia phylogenetically close to the Mycobacterium tuberculosis complex
Authors: Yenew Bazezew , Ghodousi Arash , Diriba Getu , Tesfaye Ephrem , Cabibbe Andrea Maurizio , Amare Misikir , Moga Shewki , Alemu Ayinalem , Dagne Binyam , Sinshaw Waganeh , Mollalign Hilina , Meaza Abyot , Tadesse Mengistu , Gamtesa Dinka Fikadu , Abebaw Yeshiwork , Seid Getachew , Zerihun Betselot , Getu Melak , Chiacchiaretta Matteo , Gaudin Cyril , Marceau Michael , Didelot Xavier , Tolera Getachew , Abdella Saro , Kebede Abebaw , Getahun Muluwork , Mehammed Zemedu , Supply Philip , Cirillo Daniela Maria 
Published: November 2023

AbstractThe Mycobacterium tuberculosis complex (MTBC) includes several human- and animal-adapted pathogens. It is thought to have originated in East Africa from a recombinogenic Mycobacterium canettii-like ancestral pool. Here, we describe the discovery of a clinical tuberculosis strain isolated in Ethiopia that shares archetypal phenotypic and genomic features of M. canettii strains, but represents a phylogenetic branch much closer to the MTBC clade than to the M. canettii strains. Analysis of genomic traces of horizontal gene transfer in this isolate and previously identified M. canettii strains indicates a persistent albeit decreased recombinogenic lifestyle near the emergence of the MTBC. Our findings support that the MTBC emergence from its putative free-living M. canettii-like progenitor is evolutionarily very recent, and suggest the existence of a continuum of further extant derivatives from ancestral stages, close to the root of the MTBC, along the Great Rift Valley.
Assessing the value of integrating national longitudinal shopping data into respiratory disease forecasting models
Authors: Dolan Elizabeth , Goulding James , Marshall Harry , Smith Gavin , Long Gavin , Tata Laila J. 
Published: November 2023

AbstractThe COVID-19 pandemic led to unparalleled pressure on healthcare services. Improved healthcare planning in relation to diseases affecting the respiratory system has consequently become a key concern. We investigated the value of integrating sales of non-prescription medications commonly bought for managing respiratory symptoms, to improve forecasting of weekly registered deaths from respiratory disease at local levels across England, by using over 2 billion transactions logged by a UK high street retailer from March 2016 to March 2020. We report the results from the novel AI (Artificial Intelligence) explainability variable importance tool Model Class Reliance implemented on the PADRUS model (Prediction of Amount of Deaths by Respiratory disease Using Sales). PADRUS is a machine learning model optimised to predict registered deaths from respiratory disease in 314 local authority areas across England through the integration of shopping sales data and focused on purchases of non-prescription medications. We found strong evidence that models incorporating sales data significantly out-perform other models that solely use variables traditionally associated with respiratory disease (e.g. sociodemographics and weather data). Accuracy gains are highest (increases in R2 (coefficient of determination) between 0.09 to 0.11) in periods of maximum risk to the general public. Results demonstrate the potential to utilise sales data to monitor population health with information at a high level of geographic granularity.
Inferring mitochondrial and cytosolic metabolism by coupling isotope tracing and deconvolution
Authors: Stern Alon , Fokra Mariam , Sarvin Boris , Alrahem Ahmad Abed , Lee Won Dong , Aizenshtein Elina , Sarvin Nikita , Shlomi Tomer 
Published: November 2023

AbstractThe inability to inspect metabolic activities within distinct subcellular compartments has been a major barrier to our understanding of eukaryotic cell metabolism. Previous work addressed this challenge by analyzing metabolism in isolated organelles, which grossly bias metabolic activity. Here, we describe a method for inferring physiological metabolic fluxes and metabolite concentrations in mitochondria and cytosol based on isotope tracing experiments performed with intact cells. This is made possible by computational deconvolution of metabolite isotopic labeling patterns and concentrations into cytosolic and mitochondrial counterparts, coupled with metabolic and thermodynamic modelling. Our approach lowers the uncertainty regarding compartmentalized fluxes and concentrations by one and three orders of magnitude compared to existing modelling approaches, respectively. We derive a quantitative view of mitochondrial and cytosolic metabolic activities in central carbon metabolism across cultured cell lines without performing cell fractionation, finding major variability in compartmentalized malate-aspartate shuttle fluxes. We expect our approach for inferring metabolism at a subcellular resolution to be instrumental for a variety of studies of metabolic dysfunction in human disease and for bioengineering.
A knowledge-guided pre-training framework for improving molecular representation learning
Authors: Li Han , Zhang Ruotian , Min Yaosen , Ma Dacheng , Zhao Dan , Zeng Jianyang 
Published: November 2023

AbstractLearning effective molecular feature representation to facilitate molecular property prediction is of great significance for drug discovery. Recently, there has been a surge of interest in pre-training graph neural networks (GNNs) via self-supervised learning techniques to overcome the challenge of data scarcity in molecular property prediction. However, current self-supervised learning-based methods suffer from two main obstacles: the lack of a well-defined self-supervised learning strategy and the limited capacity of GNNs. Here, we propose Knowledge-guided Pre-training of Graph Transformer (KPGT), a self-supervised learning framework to alleviate the aforementioned issues and provide generalizable and robust molecular representations. The KPGT framework integrates a graph transformer specifically designed for molecular graphs and a knowledge-guided pre-training strategy, to fully capture both structural and semantic knowledge of molecules. Through extensive computational tests on 63 datasets, KPGT exhibits superior performance in predicting molecular properties across various domains. Moreover, the practical applicability of KPGT in drug discovery has been validated by identifying potential inhibitors of two antitumor targets: hematopoietic progenitor kinase 1 (HPK1) and fibroblast growth factor receptor 1 (FGFR1). Overall, KPGT can provide a powerful and useful tool for advancing the artificial intelligence (AI)-aided drug discovery process.
CDC7 inhibition induces replication stress-mediated aneuploid cells with an inflammatory phenotype sensitizing tumors to immune checkpoint blockade
Authors: Morita Tomoko Yamamori , Yu Jie , Kashima Yukie , Kamata Ryo , Yamamoto Gaku , Minamide Tatsunori , Mashima Chiaki , Yoshiya Miyuki , Sakae Yuta , Yamauchi Toyohiro , Hakozaki Yumi , Kageyama Shun-ichiro , Nakamura Akito , Lightcap Eric , Tanaka Kosuke , Niu Huifeng , Kannan Karuppiah , Ohashi Akihiro 
Published: November 2023

AbstractSerine/threonine kinase, cell division cycle 7 (CDC7) is critical for initiating DNA replication. TAK-931 is a specific CDC7 inhibitor, which is a next-generation replication stress (RS) inducer. This study preclinically investigates TAK-931 antitumor efficacy and immunity regulation. TAK-931 induce RS, generating senescence-like aneuploid cells, which highly expressed inflammatory cytokines and chemokines (senescence-associated secretory phenotype, SASP). In vivo multilayer-omics analyses in gene expression panel, immune panel, immunohistochemistry, RNA sequencing, and single-cell RNA sequencing reveal that the RS-mediated aneuploid cells generated by TAK-931 intensively activate inflammatory-related and senescence-associated pathways, resulting in accumulation of tumor-infiltrating immune cells and potent antitumor immunity and efficacy. Finally, the combination of TAK-931 and immune checkpoint inhibitors profoundly enhance antiproliferative activities. These findings suggest that TAK-931 has therapeutic antitumor properties and improved clinical benefits in combination with conventional immunotherapy.
Balancing elementary steps enables coke-free dry reforming of methane
Authors: Yu Jiaqi , Le Tien , Jing Dapeng , Stavitski Eli , Hunter Nicholas , Lalit Kanika , Leshchev Denis , Resasco Daniel E. , Sargent Edward H. , Wang Bin , Huang Wenyu 
Published: November 2023

AbstractBalancing kinetics, a crucial priority in catalysis, is frequently achieved by sacrificing activity of elementary steps to suppress side reactions and enhance catalyst stability. Dry reforming of methane (DRM), a process operated at high temperature, usually involves fast C-H activation but sluggish carbon removal, resulting in coke deposition and catalyst deactivation. Studies focused solely on catalyst innovation are insufficient in addressing coke formation efficiently. Herein, we develop coke-free catalysts that balance kinetics of elementary steps for overall thermodynamics optimization. Beginning from a highly active cobalt aluminum oxide (CoAl2O4) catalyst that is susceptible to severe coke formation, we substitute aluminum (Al) with gallium (Ga), reporting a CoAl0.5Ga1.5O4-R catalyst that performs DRM stably over 1000 hours without observable coke deposition. We find that Ga enhances DRM stability by suppressing C-H activation to balance carbon removal. A series of coke-free DRM catalysts are developed herein by partially substituting Al from CoAl2O4 with other metals.
Mechanically-primed voltage-gated proton channels from angiosperm plants
Authors: Zhao Chang , Webster Parker D. , De Angeli Alexis , Tombola Francesco 
Published: November 2023

AbstractVoltage-gated and mechanically-gated ion channels are distinct classes of membrane proteins that conduct ions across gated pores and are turned on by electrical or mechanical stimuli, respectively. Here, we describe an Hv channel (a.k.a voltage-dependent H+ channel) from the angiosperm plant A. thaliana that gates with a unique modality as it is turned on by an electrical stimulus only after exposure to a mechanical stimulus, a process that we call priming. The channel localizes in the vascular tissue and has homologs in vascular plants. We find that mechanical priming is not required for activation of non-angiosperm Hvs. Guided by AI-generated structural models of plant Hv homologs, we identify a set of residues playing a crucial role in mechanical priming. We propose that Hvs from angiosperm plants require priming because of a network of hydrophilic/charged residues that locks the channels in a silent resting conformation. Mechanical stimuli destabilize the network allowing the conduction pathway to turn on. In contrast to many other channels and receptors, Hv proteins are not thought to possess mechanisms such as inactivation or desensitization. Our findings demonstrate that angiosperm Hv channels are electrically silent until a mechanical stimulation turns on their voltage-dependent activity.
H3.1K27me1 loss confers Arabidopsis resistance to Geminivirus by sequestering DNA repair proteins onto host genome
Authors: Wang Zhen , Castillo-González Claudia M. , Zhao Changjiang , Tong Chun-Yip , Li Changhao , Zhong Songxiao , Liu Zhiyang , Xie Kaili , Zhu Jiaying , Wu Zhongshou , Peng Xu , Jacob Yannick , Michaels Scott D. , Jacobsen Steven E. , Zhang Xiuren 
Published: November 2023

AbstractThe H3 methyltransferases ATXR5 and ATXR6 deposit H3.1K27me1 to heterochromatin to prevent genomic instability and transposon re-activation. Here, we report that atxr5 atxr6 mutants display robust resistance to Geminivirus. The viral resistance is correlated with activation of DNA repair pathways, but not with transposon re-activation or heterochromatin amplification. We identify RAD51 and RPA1A as partners of virus-encoded Rep protein. The two DNA repair proteins show increased binding to heterochromatic regions and defense-related genes in atxr5 atxr6 vs wild-type plants. Consequently, the proteins have reduced binding to viral DNA in the mutant, thus hampering viral amplification. Additionally, RAD51 recruitment to the host genome arise via BRCA1, HOP2, and CYCB1;1, and this recruitment is essential for viral resistance in atxr5 atxr6. Thus, Geminiviruses adapt to healthy plants by hijacking DNA repair pathways, whereas the unstable genome, triggered by reduced H3.1K27me1, could retain DNA repairing proteins to suppress viral amplification in atxr5 atxr6.
Simultaneous and independent topological control of identical microparticles in non-periodic energy landscapes
Authors: Stuhlmüller Nico C. X. , Farrokhzad Farzaneh , Kuświk Piotr , Stobiecki Feliks , Urbaniak Maciej , Akhundzada Sapida , Ehresmann Arno , Fischer Thomas M. , de las Heras Daniel 
Published: November 2023

AbstractTopological protection ensures stability of information and particle transport against perturbations. We explore experimentally and computationally the topologically protected transport of magnetic colloids above spatially inhomogeneous magnetic patterns, revealing that transport complexity can be encoded in both the driving loop and the pattern. Complex patterns support intricate transport modes when the microparticles are subjected to simple time-periodic loops of a uniform magnetic field. We design a pattern featuring a topological defect that functions as an attractor or a repeller of microparticles, as well as a pattern that directs microparticles along a prescribed complex trajectory. Using simple patterns and complex loops, we simultaneously and independently control the motion of several identical microparticles differing only in their positions above the pattern. Combining complex patterns and complex loops we transport microparticles from unknown locations to predefined positions and then force them to follow arbitrarily complex trajectories concurrently. Our findings pave the way for new avenues in transport control and dynamic self-assembly in colloidal science.
ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury
Authors: Zhang Yankun , Fan Yuchen , Hu Huili , Zhang Xiaohui , Wang Zehua , Wu Zhuanchang , Wang Liyuan , Yu Xiangguo , Song Xiaojia , Xiang Peng , Zhang Xiaodong , Wang Tixiao , Tan Siyu , Li Chunyang , Gao Lifen , Liang Xiaohong , Li Shuijie , Li Nailin , Yue Xuetian , Ma Chunhong 
Published: November 2023

AbstractMitochondria dysfunction contributes to acute liver injuries, and mitochondrial regulators, such as PGC-1α and MCJ, affect liver regeneration. Therefore, identification of mitochondrial modulators may pave the way for developing therapeutic strategies. Here, ZHX2 is identified as a mitochondrial regulator during acute liver injury. ZHX2 both transcriptionally inhibits expression of several mitochondrial electron transport chain genes and decreases PGC-1α stability, leading to reduction of mitochondrial mass and OXPHOS. Loss of Zhx2 promotes liver recovery by increasing mitochondrial OXPHOS in mice with partial hepatectomy or CCl4-induced liver injury, and inhibition of PGC-1α or electron transport chain abolishes these effects. Notably, ZHX2 expression is higher in liver tissues from patients with drug-induced liver injury and is negatively correlated with mitochondrial mass marker TOM20. Delivery of shRNA targeting Zhx2 effectively protects mice from CCl4-induced liver injury. Together, our data clarify ZHX2 as a negative regulator of mitochondrial OXPHOS and a potential target for developing strategies for improving liver recovery after acute injuries.
Reduced glutathione level in the aqueous humor of patients with primary open-angle glaucoma and normal-tension glaucoma
Authors: Sato Kota , Saigusa Daisuke , Kokubun Taiki , Fujioka Amane , Feng Qiwei , Saito Ritsumi , Uruno Akira , Matsukawa Naomi , Ohno-Oishi Michiko , Kunikata Hiroshi , Yokoyama Yu , Yasuda Masayuki , Himori Noriko , Omodaka Kazuko , Tsuda Satoru , Maekawa Shigeto , Yamamoto Masayuki , Nakazawa Toru 
Published: November 2023

AbstractGlaucoma is a leading cause of blindness worldwide in older people. Profiling the aqueous humor, including the metabolites it contains, is useful to understand physiological and pathological conditions in the eye. In the current study, we used mass spectrometry (MS) to characterize the aqueous humor metabolomic profile and biological features of patients with glaucoma. Aqueous humor samples were collected during trabeculectomy surgery or cataract surgery and analyzed with global metabolomics. We included 40 patients with glaucoma (32 with POAG, 8 with NTG) and 37 control subjects in a discovery study. VIP analysis revealed five metabolites that were elevated and three metabolites that were reduced in the glaucoma patients. The identified metabolomic profile had an area under the receiver operating characteristic curve of 0.953. Among eight selected metabolites, the glutathione level was significantly decreased in association with visual field defects. Moreover, in a validation study to confirm the reproducibility of our findings, the glutathione level was reduced in NTG and POAG patients compared with a cataract control group. Our findings demonstrate that aqueous humor profiling can help to diagnose glaucoma and that various aqueous humor metabolites are correlated with clinical parameters in glaucoma patients. In addition, glutathione is clearly reduced in the aqueous humor of glaucoma patients with both IOP-dependent and IOP-independent disease subtypes. These findings indicate that antioxidant agents in the aqueous humor reflect glaucomatous optic nerve damage and that excessive oxidative stress may be involved in the pathogenesis of glaucoma.
Approximate symmetries and quantum error correction
Authors: Liu Zi-Wen , Zhou Sisi 
Published: November 2023

AbstractQuantum error correction (QEC) is a key concept in quantum computation as well as many areas of physics. There are fundamental tensions between continuous symmetries and QEC. One vital situation is unfolded by the Eastin–Knill theorem, which forbids the existence of QEC codes that admit transversal continuous symmetry actions (transformations). Here, we systematically study the competition between continuous symmetries and QEC in a quantitative manner. We first define a series of meaningful measures of approximate symmetries motivated from different perspectives, and then establish a series of trade-off bounds between them and QEC accuracy utilizing multiple different methods. Remarkably, the results allow us to derive general quantitative limitations of transversally implementable logical gates, an important topic in fault-tolerant quantum computation. As concrete examples, we showcase two explicit types of quantum codes, obtained from quantum Reed–Muller codes and thermodynamic codes, respectively, that nearly saturate our bounds. Finally, we discuss several potential applications of our results in physics.