bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel protein encoded by circUBE4B promotes progression of esophageal squamous cell carcinoma by augmenting MAPK/ERK signaling
Authors: Lyu Yingcheng , Tan Binghua , Li Lin , Liang Ruihao , Lei Kai , Wang Kefeng , Wu Duoguang , Lin Huayue , Wang Minghui 
Published: June 2023

AbstractEsophageal squamous carcinoma (ESCC) is a common malignant cancer. Although the non-coding roles of circRNAs in the pathogenesis of human tumors have been well studied, whether circRNAs participate in the progression of ESCC by encoding novel proteins remains unclear. In this study, we identified an overexpression circRNA with protein-coding ability in ESCC tissues, called circUBE4B, whose expression level is correlated with tumor size and tumor differentiation level of ESCC patients. Moreover, a higher level of circUBE4B in ESCC patients is correlated with a worse prognosis. Functionally, we found that circUBE4B promoted the proliferation of ESCC cells by encoding a novel cancer-promoting protein, circUBE4B-173aa. Mechanistically, the circUBE4B-173aa protein interacts with MAPK1 and promotes the phosphorylation level of MAPK1 to eventually activate MAPK/ERK signaling pathway. The xenograft model revealed that overexpression of circUBE4B-173aa in ESCC cells significantly promoted the growth of grafts. Our study provides new insights into the mechanism of circRNA in the development of ESCC and circUBE4B-173aa has the potential to serve as a biomarker and a novel therapeutic target for ESCC therapy.
No evidence of sustained nonzoonotic Plasmodium knowlesi transmission in Malaysia from modelling malaria case data
Authors: Fornace Kimberly M. , Topazian Hillary M. , Routledge Isobel , Asyraf Syafie , Jelip Jenarun , Lindblade Kim A. , Jeffree Mohammad Saffree , Ruiz Cuenca Pablo , Bhatt Samir , Ahmed Kamruddin , Ghani Azra C. , Drakeley Chris 
Published: June 2023

AbstractReported incidence of the zoonotic malaria Plasmodium knowlesi has markedly increased across Southeast Asia and threatens malaria elimination. Nonzoonotic transmission of P. knowlesi has been experimentally demonstrated, but it remains unknown whether nonzoonotic transmission is contributing to increases in P. knowlesi cases. Here, we adapt model-based inference methods to estimate RC, individual case reproductive numbers, for P. knowlesi, P. falciparum and P. vivax human cases in Malaysia from 2012–2020 (n = 32,635). Best fitting models for P. knowlesi showed subcritical transmission (RC < 1) consistent with a large reservoir of unobserved infection sources, indicating P. knowlesi remains a primarily zoonotic infection. In contrast, sustained transmission (RC > 1) was estimated historically for P. falciparum and P. vivax, with declines in RC estimates observed over time consistent with local elimination. Together, this suggests sustained nonzoonotic P. knowlesi transmission is highly unlikely and that new approaches are urgently needed to control spillover risks.
Inefficient prioritization of task-relevant attributes during instrumental information demand
Authors: Rischall Isabella , Hunter Laura , Jensen Greg , Gottlieb Jacqueline 
Published: June 2023

AbstractIn natural settings, people evaluate complex multi-attribute situations and decide which attribute to request information about. Little is known about how people make this selection and specifically, how they identify individual observations that best predict the value of a multi-attribute situation. Here show that, in a simple task of information demand, participants inefficiently query attributes that have high individual value but are relatively uninformative about a total payoff. This inefficiency is robust in two instrumental conditions in which gathering less informative observations leads to significantly lower rewards. Across individuals, variations in the sensitivity to informativeness is associated with personality metrics, showing negative associations with extraversion and thrill seeking and positive associations with stress tolerance and need for cognition. Thus, people select informative queries using sub-optimal strategies that are associated with personality traits and influence consequential choices.
Cu-based high-entropy two-dimensional oxide as stable and active photothermal catalyst
Authors: Li Yaguang , Bai Xianhua , Yuan Dachao , Yu Chenyang , San Xingyuan , Guo Yunna , Zhang Liqiang , Ye Jinhua 
Published: June 2023

AbstractCu-based nanocatalysts are the cornerstone of various industrial catalytic processes. Synergistically strengthening the catalytic stability and activity of Cu-based nanocatalysts is an ongoing challenge. Herein, the high-entropy principle is applied to modify the structure of Cu-based nanocatalysts, and a PVP templated method is invented for generally synthesizing six-eleven dissimilar elements as high-entropy two-dimensional (2D) materials. Taking 2D Cu2Zn1Al0.5Ce5Zr0.5Ox as an example, the high-entropy structure not only enhances the sintering resistance from 400 °C to 800 °C but also improves its CO2 hydrogenation activity to a pure CO production rate of 417.2 mmol g−1 h−1 at 500 °C, 4 times higher than that of reported advanced catalysts. When 2D Cu2Zn1Al0.5Ce5Zr0.5Ox are applied to the photothermal CO2 hydrogenation, it exhibits a record photochemical energy conversion efficiency of 36.2%, with a CO generation rate of 248.5 mmol g−1 h−1 and 571 L of CO yield under ambient sunlight irradiation. The high-entropy 2D materials provide a new route to simultaneously achieve catalytic stability and activity, greatly expanding the application boundaries of photothermal catalysis.
Rio1 downregulates centromeric RNA levels to promote the timely assembly of structurally fit kinetochores
Authors: Smurova Ksenia , Damizia Michela , Irene Carmela , Stancari Stefania , Berto Giovanna , Perticari Giulia , Iacovella Maria Giuseppina , D’Ambrosio Ilaria , Giubettini Maria , Philippe Réginald , Baggio Chiara , Callegaro Elisabetta , Casagranda Andrea , Corsini Alessandro , Polese Vincenzo Gentile , Ricci Anna , Dassi Erik , De Wulf Peter 
Published: June 2023

AbstractKinetochores assemble on centromeres via histone H3 variant CENP-A and low levels of centromere transcripts (cenRNAs). The latter are ensured by the downregulation of RNA polymerase II (RNAPII) activity, and cenRNA turnover by the nuclear exosome. Using S. cerevisiae, we now add protein kinase Rio1 to this scheme. Yeast cenRNAs are produced either as short (median lengths of 231 nt) or long (4458 nt) transcripts, in a 1:1 ratio. Rio1 limits their production by reducing RNAPII accessibility and promotes cenRNA degradation by the 5’−3’exoribonuclease Rat1. Rio1 similarly curtails the concentrations of noncoding pericenRNAs. These exist as short transcripts (225 nt) at levels that are minimally two orders of magnitude higher than the cenRNAs. In yeast depleted of Rio1, cen- and pericenRNAs accumulate, CEN nucleosomes and kinetochores misform, causing chromosome instability. The latter phenotypes are also observed with human cells lacking orthologue RioK1, suggesting that CEN regulation by Rio1/RioK1 is evolutionary conserved.
Detecting lithium plating dynamics in a solid-state battery with operando X-ray computed tomography using machine learning
Authors: Huang Ying , Perlmutter David , Fei-Huei Su Andrea , Quenum Jerome , Shevchenko Pavel , Parkinson Dilworth Y. , Zenyuk Iryna V. , Ushizima Daniela 
Published: June 2023

AbstractOperando X-ray micro-computed tomography (µCT) provides an opportunity to observe the evolution of Li structures inside pouch cells. Segmentation is an essential step to quantitatively analyzing µCT datasets but is challenging to achieve on operando Li-metal battery datasets due to the low X-ray attenuation of the Li metal and the sheer size of the datasets. Herein, we report a computational approach, batteryNET, to train an Iterative Residual U-Net-based network to detect Li structures. The resulting semantic segmentation shows singular Li-related component changes, addressing diverse morphologies in the dataset. In addition, visualizations of the dead Li are provided, including calculations about the volume and effective thickness of electrodes, deposited Li, and redeposited Li. We also report discoveries about the spatial relationships between these components. The approach focuses on a method for analyzing battery performance, which brings insight that significantly benefits future Li-metal battery design and a semantic segmentation transferrable to other datasets.
Lipid droplet-associated lncRNA LIPTER preserves cardiac lipid metabolism
Authors: Han Lei , Huang Dayang , Wu Shiyong , Liu Sheng , Wang Cheng , Sheng Yi , Lu Xiongbin , Broxmeyer Hal E. , Wan Jun , Yang Lei 
Published: June 2023

AbstractLipid droplets (LDs) are cellular organelles critical for lipid homeostasis, with intramyocyte LD accumulation implicated in metabolic disorder-associated heart diseases. Here we identify a human long non-coding RNA, Lipid-Droplet Transporter (LIPTER), essential for LD transport in human cardiomyocytes. LIPTER binds phosphatidic acid and phosphatidylinositol 4-phosphate on LD surface membranes and the MYH10 protein, connecting LDs to the MYH10-ACTIN cytoskeleton and facilitating LD transport. LIPTER and MYH10 deficiencies impair LD trafficking, mitochondrial function and survival of human induced pluripotent stem cell-derived cardiomyocytes. Conditional Myh10 deletion in mouse cardiomyocytes leads to LD accumulation, reduced fatty acid oxidation and compromised cardiac function. We identify NKX2.5 as the primary regulator of cardiomyocyte-specific LIPTER transcription. Notably, LIPTER transgenic expression mitigates cardiac lipotoxicity, preserves cardiac function and alleviates cardiomyopathies in high-fat-diet-fed and Leprdb/db mice. Our findings unveil a molecular connector role of LIPTER in intramyocyte LD transport, crucial for lipid metabolism of the human heart, and hold significant clinical implications for treating metabolic syndrome-associated heart diseases.
Expanding the substrate scope of pyrrolysyl-transfer RNA synthetase enzymes to include non-α-amino acids in vitro and in vivo
Authors: Fricke Riley , Swenson Cameron V. , Roe Leah Tang , Hamlish Noah Xue , Shah Bhavana , Zhang Zhongqi , Ficaretta Elise , Ad Omer , Smaga Sarah , Gee Christine L. , Chatterjee Abhishek , Schepartz Alanna 
Published: June 2023

AbstractThe absence of orthogonal aminoacyl-transfer RNA (tRNA) synthetases that accept non-l-α-amino acids is a primary bottleneck hindering the in vivo translation of sequence-defined hetero-oligomers and biomaterials. Here we report that pyrrolysyl-tRNA synthetase (PylRS) and certain PylRS variants accept α-hydroxy, α-thio and N-formyl-l-α-amino acids, as well as α-carboxy acid monomers that are precursors to polyketide natural products. These monomers are accommodated and accepted by the translation apparatus in vitro; those with reactive nucleophiles are incorporated into proteins in vivo. High-resolution structural analysis of the complex formed between one PylRS enzyme and a m-substituted 2-benzylmalonic acid derivative revealed an active site that discriminates prochiral carboxylates and accommodates the large size and distinct electrostatics of an α-carboxy substituent. This work emphasizes the potential of PylRS-derived enzymes for acylating tRNA with monomers whose α-substituent diverges substantially from the α-amine of proteinogenic amino acids. These enzymes or derivatives thereof could synergize with natural or evolved ribosomes and/or translation factors to generate diverse sequence-defined non-protein heteropolymers.
Candidatus Alkanophaga archaea from Guaymas Basin hydrothermal vent sediment oxidize petroleum alkanes
Authors: Zehnle Hanna , Laso-Pérez Rafael , Lipp Julius , Riedel Dietmar , Benito Merino David , Teske Andreas , Wegener Gunter 
Published: June 2023

AbstractMethanogenic and methanotrophic archaea produce and consume the greenhouse gas methane, respectively, using the reversible enzyme methyl-coenzyme M reductase (Mcr). Recently, Mcr variants that can activate multicarbon alkanes have been recovered from archaeal enrichment cultures. These enzymes, called alkyl-coenzyme M reductase (Acrs), are widespread in the environment but remain poorly understood. Here we produced anoxic cultures degrading mid-chain petroleum n-alkanes between pentane (C5) and tetradecane (C14) at 70 °C using oil-rich Guaymas Basin sediments. In these cultures, archaea of the genus Candidatus Alkanophaga activate the alkanes with Acrs and completely oxidize the alkyl groups to CO2. Ca. Alkanophaga form a deep-branching sister clade to the methanotrophs ANME-1 and are closely related to the short-chain alkane oxidizers Ca. Syntrophoarchaeum. Incapable of sulfate reduction, Ca. Alkanophaga shuttle electrons released from alkane oxidation to the sulfate-reducing Ca. Thermodesulfobacterium syntrophicum. These syntrophic consortia are potential key players in petroleum degradation in heated oil reservoirs.
Open science resources from the Tara Pacific expedition across coral reef and surface ocean ecosystems
Authors: Lombard Fabien , Bourdin Guillaume , Pesant Stéphane , Agostini Sylvain , Baudena Alberto , Boissin Emilie , Cassar Nicolas , Clampitt Megan , Conan Pascal , Da Silva Ophélie , Dimier Céline , Douville Eric , Elineau Amanda , Fin Jonathan , Flores J. Michel , Ghiglione Jean-François , Hume Benjamin C. C. , Jalabert Laetitia , John Seth G. , Kelly Rachel L. , Koren Ilan , Lin Yajuan , Marie Dominique , McMinds Ryan , Mériguet Zoé , Metzl Nicolas , Paz-García David A. , Pedrotti Maria Luiza , Poulain Julie , Pujo-Pay Mireille , Ras Joséphine , Reverdin Gilles , Romac Sarah , Rouan Alice , Röttinger Eric , Vardi Assaf , Voolstra Christian R. , Moulin Clémentine , Iwankow Guillaume , Banaigs Bernard , Bowler Chris , de Vargas Colomban , Forcioli Didier , Furla Paola , Galand Pierre E. , Gilson Eric , Reynaud Stéphanie , Sunagawa Shinichi , Sullivan Matthew B. , Thomas Olivier P. , Troublé Romain , Thurber Rebecca Vega , Wincker Patrick , Zoccola Didier , Allemand Denis , Planes Serge , Boss Emmanuel , Gorsky Gaby 
Published: June 2023

AbstractThe Tara Pacific expedition (2016–2018) sampled coral ecosystems around 32 islands in the Pacific Ocean and the ocean surface waters at 249 locations, resulting in the collection of nearly 58 000 samples. The expedition was designed to systematically study warm-water coral reefs and included the collection of corals, fish, plankton, and seawater samples for advanced biogeochemical, molecular, and imaging analysis. Here we provide a complete description of the sampling methodology, and we explain how to explore and access the different datasets generated by the expedition. Environmental context data were obtained from taxonomic registries, gazetteers, almanacs, climatologies, operational biogeochemical models, and satellite observations. The quality of the different environmental measures has been validated not only by various quality control steps, but also through a global analysis allowing the comparison with known environmental large-scale structures. Such publicly released datasets open the perspective to address a wide range of scientific questions.
Discovery of the allosteric inhibitor from actinomyces metabolites to target EGFRCSTMLR mutant protein: molecular modeling and free energy approach
Authors: Saini Ravi , Kumari Sonali , Bhatnagar Aditi , Singh Amit , Mishra Abha 
Published: June 2023

AbstractEGFR (epidermal growth factor receptor), a surface protein on the cell, belongs to the tyrosine kinase family, responsible for cell growth and proliferation. Overexpression or mutation in the EGFR gene leads to various types of cancer, i.e., non-small cell lung cancer, breast, and pancreatic cancer. Bioactive molecules identified in this genre were also an essential source of encouragement for researchers who accomplished the design and synthesis of novel compounds with anticancer properties. World Health Organization (WHO) report states that antibiotic resistance is one of the most severe risks to global well-being, food safety, and development. The world needs to take steps to lessen this danger, such as developing new antibiotics and regulating their use. In this study, 6524 compounds derived from Streptomyces sp. were subjected to drug-likeness filters, molecular docking, and molecular dynamic simulation for 1000 ns to find new triple mutant EGFRCSTMLR (EGFR-L858R/T790M/C797S) inhibitors. Docking outcomes revealed that five compounds showed better binding affinity (− 9.074 to − 9.3 kcal/mol) than both reference drug CH7233163 (− 6.11 kcal/mol) and co-crystallized ligand Osimertinib (− 8.07 kcal/mol). Further, molecular dynamic simulation confirmed that ligand C_42 exhibited the best interaction at the active site of EGFR protein and comprised a better average radius of gyration (3.87 Å) and average SASA (Solvent Accessible Surface Area) (82.91 Å2) value than co-crystallized ligand (4.49 Å, 222.38 Å2). Additionally, its average RMSD (Root Mean Square Deviation) (3.25 Å) and RMSF (Root Mean Square Fluctuation) (1.54 Å) values were highly similar to co-crystallized ligand (3.07 Å, 1.54 Å). Compared to the reference ligand, it also demonstrated conserved H-bond interactions with the residues MET_793 and GLN_791 with strong interaction probability. In conclusion, we have found a potential drug with no violation of the rule of three, Lipinski's rule of five, and 26 other vital parameters having great potential in medicinal and pharmaceutical industries applications and can overcome synthetic drug issues.
Genomic and molecular landscape of homologous recombination deficiency across multiple cancer types
Authors: Shi Zhiwen , Chen Bolin , Han Xiao , Gu Weiyue , Liang Shuzhi , Wu Lin 
Published: June 2023

AbstractHomologous recombination deficiency (HRD) causes faulty double-strand break repair and is a prevalent cause of tumorigenesis. However, the incidence of HRD and its clinical significance in pan-cancer patients remain unknown. Using computational analysis of Single-nucleotide polymorphism array data from 10,619 cancer patients, we demonstrate that HRD frequently occurs across multiple cancer types. Analysis of the pan-cancer cohort revealed that HRD is not only a biomarker for ovarian cancer and triple-negative breast cancer, but also has clinical prognostic value in numerous cancer types, including adrenocortical cancer and thymoma. We discovered that homologous recombination–related genes have a high mutation or deletion frequency. Pathway analysis shows HRD is positively correlated with the DNA damage response and the immune-related signaling pathways. Single cell RNA sequencing of tumor-infiltrating lymphocytes reveals a significantly higher proportion of exhausted T cells in HRD patients, indicating pre-existing immunity. Finally, HRD could be utilized to predict pan-cancer patients’ responses to Programmed cell death protein 1 immunotherapy. In summary, our work establishes a comprehensive map of HRD in pan-cancer. The findings have significant implications for expanding the scope of Poly ADP-ribose polymerase inhibitor therapy and, possibly, immunotherapy.
Physical and chemical characterization of smokeless tobacco products in India
Authors: Sharma Priyamvada , Cheah Nuan Ping , Kaur Jagdish , Sathiya Kumar Sandhya , Rao Vijayashree , Morsed Faridatul Akmam , Choo Michelle Yong Bing , Murthy Pratima 
Published: June 2023

AbstractThe rapid proliferation of smokeless tobacco (SLT) in India has occurred without adequate information on the possible dangers and toxicity of these products. Tobacco flavors as well as nicotine (both protonated and un-protonated) are responsible for health dangers and addiction. The study aimed to offer information on the physical characteristics of commonly used smokeless tobacco products (including microscopic analysis), along with nicotine content (both total and un-protonated), pH, moisture, and flavors. The Standard Operating Procedures (SOPs) validated by the World Health Organization (WHO) recognized Tobacco Testing Laboratory TobLabNet) were applied for the analysis of various constituents of the SLTs. The microscopic analysis indicated that some of the SLT products like khaini were finely processed and available in filter pouches for users’ convenience and prolonged use leading to prolonged retention and addiction potential. Nicotine absorption and availability (both protonated and un-protonated) are affected by moisture and pH. Essences provide a pleasant aroma and flavor, with an increased risk of misuse and other health problems. Few chewing tobacco and Zarda had the lowest levels of un-protonated nicotine (0.10–0.52% and 0.15–0.21%, respectively), whereas Gul, Gudhaku, and Khaini had the highest levels, ranging from 95.33 to 99.12%. Moisture and pH ranged from 4.54 to 50.19% and 5.25–10.07 respectively. Menthol (630.74–9681.42 µg/g) was the most popular flavour, followed by Eucalyptol (118.16–247.77 µg/g) and camphor (148.67 and 219.317 µg/g). SLT’s health concerns and addiction dangers are exacerbated by the high proportion of bioavailable nicotine coupled with flavors. The findings of this study have important implications for the regulation and use of SLT in countries where use of SLT is prevalent.
Evaluation of epigenetic methylation biomarkers for the detection of colorectal cancer using droplet digital PCR
Authors: Petit J. , Carroll G. , Zhao J. , Roper E. , Pockney P. , Scott R. J. 
Published: June 2023

AbstractColorectal cancer (CRC) is the third most common cancer worldwide. Screening programs allow early diagnosis and have improved the clinical management of this disease. Aberrant DNA methylation is increasingly being explored as potential biomarkers for many types of cancers. In this study we investigate the methylation of ten target genes in 105 CRC and paired normal adjacent colonic tissue samples using a MethylLight droplet digital PCR (ML-ddPCR) assay. Receiver operator characteristic (ROC) curves were used to determine the diagnostic performance of all target genes individually and in combination. All 515 different combinations of genes showed significantly higher levels of methylation in CRC tissue. The combination of multiple target genes into a single test generally resulted in greater diagnostic accuracy when compared to single target genes. Our data confirms that ML-ddPCR is able to reliably detect significant differences in DNA methylation between CRC tissue and normal adjacent colonic tissue in a specific selection of target genes.