bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-184, a downregulated ovary-elevated miRNA transcriptionally activated by SREBF2, exerts anti-apoptotic properties in ovarian granulosa cells through inducing SMAD3 expression
Authors: Shan Baosen , Huo Yangan , Guo Zhennan , Li Qiqi , Pan Zengxiang , Li Qifa , Du Xing 
Published: December 2024

AbstractFollicular atresia is the primary threat to female fertility. miRNAs are dysregulated in granulosa cells (GCs) during follicular atresia, and have emerged as crucial regulators of the initiation and progression of follicular atresia. However, the downregulated ovary-elevated (OE) miRNAs and their biological functions in ovary remain elusive. Here, 13 downregulated OE miRNAs were systematically identified by integrating tissue expression high-throughput data and comparative transcriptome analyses, among which miR-184 was specifically highly expressed in ovary but dramatically downregulated during follicular atresia. Low miR-184 levels were also positively correlated with follicular atresia. Based on the in vitro GC and follicle culture system, we found that miR-184 suppressed GC apoptosis and follicular atresia. Mechanistically, miR-184 induced SMAD3 transcription by acting as a saRNA, and also stabilized SMAD3 mRNA by directly binding to its 5′-UTR, which promoted TGF-β pathway activity and its anti-apoptotic effect. In addition, miR-184 was transcribed independently of host gene, which was activated by SREBF2 in an H3K4me3-dependent manner. Comparative analysis revealed that SREBF2 expression and H3K4me3 enrichment on miR-184 promoter in GCs from atretic follicles were dramatically reduced, which leads to the downregulation of miR-184 during follicular atresia. Moreover, the expression pattern, function, target, and regulatory mechanism of miR-184 among mammals are highly conserved and universal. Taken together, our findings demonstrate that miR-184, transcriptionally activated by SREBF2 in an H3K4me3-dependent manner, exerts anti-atretic effects by inducing SMAD3 expression, highlighting that it is a promising regulator for improving follicular development, ovarian health and female fertility.
Downregulation of tRNA methyltransferase FTSJ1 by PM2.5 promotes glycolysis and malignancy of NSCLC via facilitating PGK1 expression and translation
Authors: Wang Yiling , Wen Yuxin , Chen Qianqian , Huang Yongyi , Zhou Duanyang , Yang Wenhan , Yang Lin , Xiong Juan , Gao Kaiping , Sun Liyuan , Zhai Rihong 
Published: December 2024

AbstractFine particulate matter (PM2.5) exposure has been associated with increased incidence and mortality of lung cancer. However, the molecular mechanisms underlying PM2.5 carcinogenicity remain incompletely understood. Here, we identified that PM2.5 suppressed the expression of tRNA methyltransferase FTSJ1 and Am modification level of tRNA in vitro and in vivo. FTSJ1 downregulation enhanced glycolytic metabolism of non-small cell lung cancer (NSCLC) cells, as indicated by increased levels of lactate, pyruvate, and extracellular acidification rate (ECAR). Whereas treatment with glycolytic inhibitor 2-DG reversed this effect. In contrast, upregulation of FTSJ1 significantly suppressed glycolysis of NSCLC cells. Mechanistically, the silencing of FTSJ1 increased NSCLC cell proliferation and glycolysis through enhancing the expression and translation of PGK1. In human NSCLC tumor samples, FTSJ1 expression was negatively correlated with PGK1 expression level and the SUVmax value of PET/CT scan. In summary, our work reveals a previously unrecognized function of PM2.5-downregulated FTSJ1 on PGK1-mediated glycolysis in NSCLC, suggesting that targeted upregulation of FTSJ1 may represent a potential therapeutic strategy for NSCLC.
A20 negatively regulates necroptosis-induced microglia/macrophages polarization and mediates cerebral ischemic tolerance via inhibiting the ubiquitination of RIP3
Authors: Qiu Meiqian , Zhang Wenhao , Dai Jiahua , Sun Weiwen , Lai Meijing , Tang Shiyi , Xu En , Ning Yuping , Zhan Lixuan 
Published: December 2024

AbstractNeuronal necroptosis appears to be suppressed by the deubiquitinating enzyme A20 and is capable to regulate the polarization of microglia/macrophages after cerebral ischemia. We have demonstrated that hypoxic preconditioning (HPC) can alleviate receptor interacting protein 3 (RIP3)-induced necroptosis in CA1 after transient global cerebral ischemia (tGCI). However, it is still unclear whether HPC serves to regulate the phenotypic polarization of microglia/macrophages after cerebral ischemia by mitigating neuronal necroptosis. We hence aim to elucidate the underlying mechanism(s) by which the ubiquitination of RIP3-dependent necroptosis regulated by A20 affects microglia/macrophages phenotype after cerebral ischemic tolerance. We found that microglia/macrophages in CA1 of rats underwent M1 and M2 phenotypic polarization in response to tGCI. Notably, the treatment with HPC, as well as inhibitors of necroptosis, including Nec-1 and mixed lineage kinase domain-like (MLKL) siRNA, attenuated neuroinflammation associated with M1 polarization of microglia/macrophages induced by tGCI. Mechanistically, HPC was revealed to upregulate A20 and in turn enhance the interaction between A20 and RIP3, thereby reducing K63-linked polyubiquitination of RIP3 in CA1 after tGCI. Consequently, RIP3-dependent necroptosis and the M1 polarization of microglia/macrophages were blocked either by HPC or via overexpression of A20 in neurons, which ultimately mitigated cerebral injury in CA1 after tGCI. These data support that A20 serves as a crucial mediator of microglia/macrophages polarization by suppressing neuronal necroptosis in a RIP3 ubiquitination-dependent manner after tGCI. Also, a novel mechanism by which HPC functions in cerebral ischemic tolerance is elucidated.
CUL4B protects kidneys from acute injury by restraining p53/PAI-1 signaling
Authors: Liu Kaixuan , Hao Xiaoyu , Gao Yangfan , Cao Zhiyuan , Hou Min , Qin Lining , Song Yu , Wang Molin , Jiang Baichun , Liu Qiao , Zou Yongxin , Gong Yaoqin , Liu Guangyi , Sun Gongping 
Published: December 2024

AbstractAcute kidney injury (AKI) caused by nephrotoxins, ischemia reperfusion (IR) or sepsis is associated with high morbidity and mortality. Unveiling new mechanisms underlying AKI can help develop new therapeutic strategy. Cullin 4B (CUL4B) is a scaffold protein in the CUL4B-RING E3 ubiquitin ligase (CRL4B) complex. Here, we demonstrate that CUL4B can protect kidneys from acute injury induced by cisplatin and IR. CUL4B is upregulated in mouse tubular epithelial cells (TECs) after cisplatin treatment or IR. Loss of CUL4B in kidneys exacerbates renal injury, inflammation, and apoptosis of TECs caused by cisplatin and IR. Transcriptome analysis reveals that Cul4b deficiency enhances injury-induced PAI-1 expression. CUL4B suppresses PAI-1 expression by promoting polyubiquitination and degradation of p53. Inhibition of either PAI-1 or p53 can prevent the aggravated renal injury and inflammation caused by loss of CUL4B. Our work has identified the kidney-protective role of CUL4B against acute injury.
DARPins as a novel tool to detect and degrade p73
Authors: Münick Philipp , Zielinski Jasmin , Strubel Alexander , Gutfreund Niklas , Dreier Birgit , Schaefer Jonas V. , Schäfer Birgit , Gebel Jakob , Osterburg Christian , Chaikuad Apirat , Knapp Stefan , Plückthun Andreas , Dötsch Volker 
Published: December 2024

AbstractThe concept of Targeted Protein Degradation (TPD) has been introduced as an attractive alternative to the development of classical inhibitors. TPD can extend the range of proteins that can be pharmacologically targeted beyond the classical targets for small molecule inhibitors, as a binding pocket is required but its occupancy does not need to lead to inhibition. The method is based on either small molecules that simultaneously bind to a protein of interest and to a cellular E3 ligase and bring them in close proximity (molecular glue) or a bi-functional molecule synthesized from the chemical linkage of a target protein-specific small molecule and one that binds to an E3 ligase (Proteolysis Targeting Chimeras (PROTAC)). The further extension of this approach to bioPROTACs, in which a small protein-based binding module is fused directly to an E3 ligase or an E3 ligase adaptor protein, makes virtually all proteins amenable to targeted degradation, as this method eliminates the requirement for binding pockets for small molecules. Designed Ankyrin Repeat Proteins (DARPins) represent a very attractive class of small protein-based binding modules that can be used for the development of bioPTOTACS. Here we describe the characterization of two DARPins generated against the oligomerization domain and the SAM domain of the transcription factor p73, a member of the p53 protein family. The DARPins can be used for (isoform-)selective pulldown experiments both in cell culture as well as primary tissue lysates. We also demonstrate that they can be used for staining in cell culture experiments. Fusing them to the speckle type POZ protein (SPOP), an adaptor protein for cullin-3 E3 ligase complexes, yields highly selective and effective degraders. We demonstrate that selective degradation of the ΔNp73α isoform reactivates p53.
SMURF1 and SMURF2 directly target GLI1 for ubiquitination and proteasome-dependent degradation
Authors: Bordin Fabio , Terriaca Gloria , Apostolico Adriano , Di Fiore Annamaria , Mir Faranak Taj , Bellardinelli Sara , Bufalieri Francesca , Bordone Rosa , Bellardinilli Francesca , Giannini Giuseppe , Canettieri Gianluca , Di Marcotullio Lucia , Ferretti Elisabetta , Moretti Marta , De Smaele Enrico 
Published: December 2024

AbstractThe transcription factor GLI1 is the main and final effector of the Hedgehog signaling pathway, which is involved in embryonic development, cell proliferation and stemness. Whether activated through canonical or non-canonical mechanisms, GLI1 aberrant activity is associated with Hedgehog-dependent cancers, including medulloblastoma, as well as other tumoral contexts. Notwithstanding a growing body of evidence, which have highlighted the potential role of post translational modifications of GLI1, the complex mechanisms modulating GLI1 stability and activity have not been fully elucidated. Here, we present a novel role played by SMURF1 and SMURF2 in the suppression of the Hedgehog/GLI signaling pathway through a direct targeting of GLI1. Indeed, the two SMURFs can interact with GLI1, exploiting the proline rich regions present on GLI1 protein, and trigger its polyubiquitination and proteasomal degradation, leading to a suppression of the Hedgehog pathway activity and a reduction of Hh-dependent tumor cell proliferation. Overall, this study adds new relevance to a tumor suppressive role of SMURFs on the Hedgehog pathway and confers upon them the status of potential therapeutic tools, either in canonical or non-canonical Hedgehog pathway aberrant activation.
Structural mechanism of CB1R binding to peripheral and biased inverse agonists
Authors: Kumari Punita , Dvorácskó Szabolcs , Enos Michael D. , Ramesh Karthik , Lim Darrix , Hassan Sergio A. , Kunos George , Cinar Resat , Iyer Malliga R. , Rosenbaum Daniel M. 
Published: December 2024

AbstractThe cannabinoid receptor 1 (CB1R) regulates synaptic transmission in the central nervous system, but also has important roles in the peripheral organs controlling cellular metabolism. While earlier generations of brain penetrant CB1R antagonists advanced to the clinic for their effective treatment of obesity, such molecules were ultimately shown to exhibit negative effects on central reward pathways that thwarted their further therapeutic development. The peripherally restricted CB1R inverse agonists MRI-1867 and MRI-1891 represent a new generation of compounds that retain the metabolic benefits of CB1R inhibitors while sparing the negative psychiatric effects. To understand the mechanism of binding and inhibition of CB1R by peripherally restricted antagonists, we developed a nanobody/fusion protein strategy for high-resolution cryo-EM structure determination of the GPCR inactive state, and used this method to determine structures of CB1R bound to either MRI-1867 or MRI-1891. These structures reveal how these compounds retain high affinity and specificity for CB1R’s hydrophobic orthosteric site despite incorporating polar functionalities that lead to peripheral restriction. Further, the structure of the MRI-1891 complex along with accompanying molecular dynamics simulations shows how differential engagement with transmembrane helices and the proximal N-terminus can propagate through the receptor to contribute to biased inhibition of β-arrestin signaling.
On the equilibrium limit of liquid stability in pressurized aqueous systems
Authors: Zarriz Arian , Journaux Baptiste , Powell-Palm Matthew J. 
Published: December 2024

AbstractPhase stability, and the limits thereof, are a central concern of materials thermodynamics. However, the temperature limits of equilibrium liquid stability in chemical systems have only been widely characterized under constant (typically atmospheric) pressure conditions, whereunder these limits are represented by the eutectic. At higher pressures, the eutectic will shift in both temperature and chemical composition, opening a wide thermodynamic parameter space over which the absolute limit of liquid stability, i.e., the limit under arbitrary values of the thermodynamic forces at play (here pressure and concentration), might exist. In this work, we use isochoric freezing and melting to measure this absolute limit for the first time in several binary aqueous brines, and nodding to the etymology of “eutectic”, we name it the “cenotectic” (from Greek “κοινός-τῆξῐς”, meaning “universal-melt”). We discuss the implications of our findings on ocean worlds within our solar system and cold ocean exoplanets; estimate thermodynamic limits on ice crust thickness and final ocean depth (of the cenotectic or “endgame” ocean) using measured cenotectic pressures; and finally provide a generalized thermodynamic perspective on (and definition for) this fundamental thermodynamic invariant point.
Protein purification with light via a genetically encoded azobenzene side chain
Authors: Mayrhofer Peter , Anneser Markus R. , Schira Kristina , Sommer Carina A. , Theobald Ina , Schlapschy Martin , Achatz Stefan , Skerra Arne 
Published: December 2024

AbstractAffinity chromatography is the method of choice for the rapid purification of proteins from cell extracts or culture supernatants. Here, we present the light-responsive Azo-tag, a short peptide comprising p-(phenylazo)-L-phenylalanine (Pap), whose side chain can be switched from its trans-ground state to the metastable cis-configuration by irradiation with mild UV light. Since only trans-Pap shows strong affinity to α-cyclodextrin (α-CD), a protein exhibiting the Azo-tag selectively binds to an α-CD chromatography matrix under daylight or in the dark but elutes quickly under physiological buffer flow when illuminating the column at 355 nm. We demonstrate the light-controlled single-step purification – termed Excitography – of diverse proteins, including enzymes and antibody fragments, without necessitating competing agents or harsh buffer conditions as normally applied. While affinity chromatography has so far been governed by chemical interactions, introducing control by electromagnetic radiation as a physical principle adds another dimension to this widely applied separation technique.
Enabling dynamic 3D coherent diffraction imaging via adaptive latent space tuning of generative autoencoders
Authors: Scheinker Alexander , Pokharel Reeju 
Published: December 2024

AbstractCoherent diffraction imaging (CDI) is an advanced non-destructive 3D X-ray imaging technique for measuring a sample’s electron density. The main challenge of CDI is loss of phase information in diffraction intensity measurements, resulting in lengthy iterative reconstruction processes that can return non-unique solutions, which pose challenges for experiments attempting to track dynamic sample evolution through multiple states. As the increased brightness of fourth-generation light sources enables faster sample measurements and drives operando experiments with Bragg CDI, there is a growing need for faster reconstruction techniques that can keep pace. We have developed an adaptive generative autoencoder approach for uniquely tracking a sample’s electron density as it dynamically evolves. Our approach adaptively tunes the low-dimensional latent embedding of a generative autoencoder, enabling a computationally efficient manner to account for time-varying shifting distributions in real-time. Analytic proof of convergence is provided as well as numerical demonstration of sample tracking with noisy measurements.
Two decades of three-dimensional movement data from adult female northern elephant seals
Authors: Costa Daniel P. , Holser Rachel R. , Keates Theresa R. , Adachi Taiki , Beltran Roxanne S. , Champagne Cory D. , Crocker Daniel E. , Favilla Arina B. , Fowler Melinda A. , Gallo-Reynoso Juan Pablo , Goetsch Chandra , Hassrick Jason L. , Hückstädt Luis A. , Kendall-Bar Jessica M. , Kienle Sarah S. , Kuhn Carey E. , Maresh Jennifer L. , Maxwell Sara M. , McDonald Birgitte I. , McHuron Elizabeth A. , Morris Patricia A. , Naito Yasuhiko , Pallin Logan J. , Peterson Sarah H. , Robinson Patrick W. , Simmons Samantha E. , Takahashi Akinori , Teuschel Nicole M. , Tift Michael S. , Tremblay Yann , Villegas-Amtmann Stella , Yoda Ken 
Published: December 2024

AbstractNorthern elephant seals (Mirounga angustirostris) have been integral to the development and progress of biologging technology and movement data analysis, which continue to improve our understanding of this and other species. Adult female elephant seals at Año Nuevo Reserve and other colonies along the west coast of North America were tracked annually from 2004 to 2020, resulting in a total of 653 instrument deployments. This paper outlines the compilation and curation process of these high-resolution diving and location data, now accessible in two Dryad repositories. The code used for data processing alongside the corresponding workflow is available through GitHub and Zenodo. This data set represents 3,844,927 dives and 596,815 locations collected from 475 individual seals with 178 repeat samplings over 17 years. We anticipate that these data will stimulate further analysis and investigation into elephant seal biology and aid in developing new analytical approaches for large marine predators.
Active and passive organic carbon fluxes during a bloom in the Southern Ocean (South Georgia)
Authors: Major William , Giering Sarah L. C. , Ainsworth Joanna , Belcher Anna , Blackbird Sabena , Bridger Martin , Briggs Nathan , Carvalho Filipa , Clément Louis , Cook Kathryn , Dumousseaud Cynthia , Espinola Benoit , Evans Claire , Fielding Sophie , Hartmann Manuela , Henson Stephanie , Iversen Morten , Kiriakoulakis Konstadinos , Lampitt Richard , Lovecchio Elisa , Martin Adrian , Mayor Dan , Moore Mark , Pabortsava Katsiaryna , Pebody Corinne , Peel Kate , Preece Calum , Poulton Alex , Rayne Rachel , Saw Kevin , Stinchcombe Mark , Stowasser Gabriele , Tarling Geraint A. , Thomalla Sandy , Villa-Alfageme María , Wolff George A. , Sanders Richard 
Published: December 2024

AbstractThe Controls Over Mesopelagic Interior Carbon Storage (COMICS) cruise DY086 took place aboard the RRS Discovery in the South Atlantic during November and December, 2017. Physical, chemical, biogeochemical and biological data were collected during three visits to ocean observatory station P3, off the coast of South Georgia, during an austral spring bloom. A diverse range of equipment including CTD-rosette, Acoustic Doppler Current Profiler (ADCP), net deployments, marine snow catchers (MSCs), Stand Alone Pump System (SAPS) and PELAGRA Sediment Traps were used to produce a comprehensive, high-quality dataset. The data can provide excellent insight into regional biological carbon pump (BCP) processes; it is recommended for use by observational scientists and modellers to enhance understanding of ecosystem interactions relating to mesopelagic carbon storage.
Chromosome-scale assembly of the African yam bean genome
Authors: Waweru Bernice , Njaci Isaac , Paliwal Rajneesh , Maranga Mary , Muli Collins , Murungi Edwin , Kaimenyi Davies , Lyimo Beatus , Nigussie Helen , Ahadi Bwihangane Birindwa , Assefa Ermias , Ishag Hassan , Olomitutu Oluwaseyi , Abberton Michael , Darby Christopher , Uauy Cristobal , Yao Nasser , Adewale Daniel , Emmrich Peter , Entfellner Jean-Baka Domelevo , Shorinola Oluwaseyi 
Published: December 2024

AbstractGenomics-informed breeding of locally adapted, nutritious, albeit underutilised African crops can help mitigate food and nutrition insecurity challenges in Africa, particularly against the backdrop of climate change. However, utilisation of modern genome-assisted crop improvement tools including genomic selection and genome editing for many African indigenous crops is hampered by the scarcity of genomic resources. Here we report on the assembly of the genome of African yam bean (Sphenostylis stenocarpa), a tuberous legume crop that is indigenous to Africa. By combining Nanopore-based assembly with Hi-C scaffolding, we produced a high-quality chromosome-scale assembly with an N50 of 69.5 Mbp. Using transcriptome evidence from Nanopore RNASeq and protein homology evidence from related crops, we predicted and annotated 31,614 putative protein coding genes. We also show how this genome substantially improves anchoring of genetic markers from African yam bean, confirming its significance as a resource for genetic research in African yam bean.
A dataset for 15N natural abundance of soil ammonia volatilization
Authors: Peng Lingyun , Ti Chaopu , Yin Bin , Bai Xiao , Li Miao , Tao Limin , Yan Xiaoyuan 
Published: December 2024

AbstractInvestigating the sources of ammonia (NH3) in the atmosphere and the contribution of each source is essential for environmental pollution control. The presented dataset aims to provide 15N natural abundance (δ15N) data collected from different controlled treatments to fill the knowledge gap between insufficient data of soil δ15N-NH3 and accurately identifying atmospheric NH3 source apportionments. Our results showed that the overall δ15N-NH3 values emitted from soil ranged from −46.09 to 10.22‰, with an average of −26.81 ± 11.17‰. The mean δ15N-NH3 values under different nitrogen (N) application rates, N fertilizer types, air temperatures, soil moisture, soil pH, soil types, and land use types were −29.41 ± 10.91, −32.43 ± 6.86, −29.10 ± 10.04, −30.31 ± 6.18, −24.84 ± 13.76, −23.53 ± 7.66, and −14.57 ± 12.54‰, respectively. Significant correlations were observed between δ15N-NH3 values and soil pH, soil NO3−-N concentration, and NH3 volatilization. This unique database provides basic data and evidence for the qualification of atmospheric NH3 source apportionments under different study area conditions.