bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trypanosoma cruzi eIF4E3- and eIF4E4-containing complexes bind different mRNAs and may sequester inactive mRNAs during nutritional stress
Authors: Gabiatti Bernardo Papini , Freire Eden Ribeiro , Ferreira da Costa Jimena , Ferrarini Mariana Galvão , Reichert Assunção de Matos Tatiana , Preti Henrique , Munhoz da Rocha Isadora , Guimarães Beatriz Gomes , Kramer Susanne , Zanchin Nilson Ivo Tonin , Holetz Fabíola Barbieri 
Published: December 2024

Abstract
Many eIF4F and poly(A)-binding protein (PABP) paralogues are found in trypanosomes: six eIF4E, five eIF4G, one eIF4A and two PABPs. They are expressed simultaneously and assemble into different complexes, contrasting the situation in metazoans that use distinct complexes in different cell types/developmental stages. Each eIF4F complex has its own proteins, messenger RNAs (mRNAs) and, consequently, a distinct function. We set out to study the function and regulation of the two eIF4F complexes of the parasite Trypanosoma cruzi and identified the associated proteins and mRNAs of eIF4E3 and eIF4E4 in cells in exponential growth and in nutritional stress, an inducer of differentiation to an infective stage. Upon stress, eIF4G and PABP remain associated with the eIF4E, but the associations with other 43S pre-initiation factors decrease, indicating ribosome attachment is impaired. Most eIF4E3-associated mRNAs encode for proteins involved in anabolic metabolism, while eIF4E4 associate with mRNAs encoding ribosomal proteins as in Trypanosoma brucei. Interestingly, for both eIF4E3/4, more mRNAs were associated in stressed cells than in non-stressed cells, even though these have lower translational efficiencies in stress. In summary, trypanosomes have two co-existing eIF4F complexes associating to different mRNAs, but not stress/differentiation-associated mRNAs. Under stress, both complexes exit translation but remain bound to their mRNA targets
BASAL: a universal mapping algorithm for nucleotide base-conversion sequencing
Authors: Xu Moping , Liu Xiaoyang , Wang Miao , Luo Tingting , Gao Yawei , Liu Jun , Shi Jiejun 
Published: December 2024

Abstract
Utilizing base-conversion (BC) techniques, single-base resolution profiling of RNA and DNA modifications has significantly advanced. BC strategies range from one-way conversions (e.g. cytosine-to-thymine for 5-methylcytosine, adenine-to-guanine for N6-methyladenosine), to multi-way conversions (e.g. adenine to cytosine/guanine/thymine for N1-methyladenosine) and deletion-induced conversions (e.g. pseudouridine-to-deletion). Existing sequence aligners struggle with these diverse conversions, often leading to misaligning or inefficiency. We introduce BASAL (BAse-conversion Sequencing ALigner), which leverages bit-masking technology to accurately calculate mismatch penalties and supports all BC strategies. BASAL outperforms state-of-the-art tools in both mapping accuracy and efficiency. Through simulated and real data testing, along with experimental validation, we demonstrate that BASAL excels at identifying reliable modification sites. Moreover, BASAL enhances single-cell m6A analysis, revealing cell subpopulations and a cell evolutionary direction that align with biological functions, which other aligners fall short. BASAL’s versatility establishes it as a universal aligner for RNA and DNA modification sequencing, facilitating groundbreaking discoveries in epigenomics and epitranscriptomics.
Novel BRCA1–PLK1–CIP2A axis orchestrates homologous recombination-mediated DNA repair to maintain chromosome integrity during oocyte meiosis
Authors: Lee Crystal , Oh Jeong Su 
Published: December 2024

Abstract
Double-strand breaks (DSBs) are a formidable threat to genome integrity, potentially leading to cancer and various genetic diseases. The prolonged lifespan of mammalian oocytes increases their susceptibility to DNA damage over time. While somatic cells suppress DSB repair during mitosis, oocytes exhibit a remarkable capacity to repair DSBs during meiotic maturation. However, the precise mechanisms underlying DSB repair in oocytes remain poorly understood. Here, we describe the pivotal role of the BRCA1–PLK1–CIP2A axis in safeguarding genomic integrity during meiotic maturation in oocytes. We found that inhibition of homologous recombination (HR) severely impaired chromosome integrity by generating chromosome fragments during meiotic maturation. Notably, HR inhibition impaired the recruitment of CIP2A to damaged chromosomes, and the depletion of CIP2A led to chromosome fragmentation following DSB induction. Moreover, BRCA1 depletion impaired chromosomal recruitment of CIP2A, but not vice versa. Importantly, the impaired chromosomal recruitment of CIP2A could be rescued by PLK1 inhibition. Consequently, our findings not only underscore the importance of the chromosomal recruitment of CIP2A in preventing chromosome fragmentation, but also demonstrate the regulatory role of the BRCA1–PLK1–CIP2A axis in this process during oocyte meiotic maturation.
Imaging of endogenous RNA in live cells using sequence-activated fluorescent RNA probes
Authors: Zheng Haifeng , Liu Xiyu , Liu Luhui , Hu Jiarui , Chen Xianjun 
Published: December 2024

Abstract
RNA performs a remarkable range of functions, such as RNA processing, chromosome maintenance and dosage compensation. Technologies that robustly and specifically image RNA in its native state are highly desirable, as these technologies can help researchers clarify the localization and functionality of diverse RNAs. Here, we describe the development of a sequence-activated fluorescent RNA (SaFR) technique. In SaFR, in the absence of target RNA, the structure of fluorogenic RNA is disrupted by the invader sequence, and the ability to activate the Pepper’s cognate fluorophores is lost as a result. In the presence of target RNA, SaFR undergoes conformational reorganization and transforms into the fluorogenic conformation of Pepper, enabling the activation of fluorophores to produce fluorescent signals. SaFR exhibits favourable properties, such as large dynamic ranges, high specificity and fast fluorescence generation. Further studies showed that exogenous or endogenous RNAs can be tracked in live and fixed cells through SaFR. We further demonstrated the usefulness of SaFR in monitoring the assembly and disassembly of stress granules in real-time. Overall, this study offers a robust and versatile tool for labelling and imaging endogenous RNA in cells, which will be useful for clarifying the functionality and molecular mechanism of RNA.
Hypoxia increases methylated histones to prevent histone clipping and heterochromatin redistribution during Raf-induced senescence
Authors: Chang Soojeong , Moon Ramhee , Nam Dowoon , Lee Sang-Won , Yoon Insoo , Lee Dong-Sung , Choi Seunghyuk , Paek Eunok , Hwang Daehee , Hur Junho K , Nam Youhyun , Chang Rakwoo , Park Hyunsung 
Published: December 2024

Abstract
Hypoxia enhances histone methylation by inhibiting oxygen- and α-ketoglutarate-dependent demethylases, resulting in increased methylated histones. This study reveals how hypoxia-induced methylation affects histone clipping and the reorganization of heterochromatin into senescence-associated heterochromatin foci (SAHF) during oncogene-induced senescence (OIS) in IMR90 human fibroblasts. Notably, using top-down proteomics, we discovered specific cleavage sites targeted by Cathepsin L (CTSL) in H3, H2B and H4 during Raf activation, identifying novel sites in H2B and H4. Hypoxia counteracts CTSL-mediated histone clipping by promoting methylation without affecting CTSL’s activity. This increase in methylation under hypoxia protects against clipping, reshaping the epigenetic landscape and influencing chromatin accessibility, as shown by ATAC-seq analysis. These insights underscore the pivotal role of hypoxia-induced histone methylation in protecting chromatin from significant epigenetic shifts during cellular aging.
The farnesoid X receptor activates transcription independently of RXR at non-canonical response elements
Authors: van der Veen Suzanne W , Dijkstra Jelmer J , Willemsen Ellen C L , Houtman René , Milona Alexandra , Marchet Nikolas , Spit Maureen , Hollman Danielle , Zwartkruis Fried J T , Vermeulen Michiel , Ramos Pittol Jose M , van Mil Saskia W C 
Published: December 2024

Abstract
The farnesoid X receptor (FXR) is a nuclear receptor (NR) known to obligately heterodimerize with the retinoid X receptor (RXR). FXR is expressed as four isoforms (α1–α4) that drive transcription from IR-1 (inverted repeat-1) response elements (REs). Recently, we found that FXR isoforms α2/α4 also activate transcription from non-canonical ER-2 (everted repeat-2) REs, mediating most metabolic effects of general FXR activation. Here, we explored molecular determinants of regulation by FXRα2 from ER-2 REs through quantitative interaction proteomics, site-directed mutagenesis and transcriptomics. We discovered FXRα2 binds to and activates ER-2 elements in vitro and in reporter assays independently of RXR. Genome-wide binding analysis in mouse liver revealed higher ER-2 motif enrichment in FXR sites lacking RXR. Abrogation of FXRα2:RXR heterodimerization abolished IR-1, but preserved ER-2 transactivation. Transcriptome-wide, RXR overexpression inhibited 25% of FXRα2 targets in HepG2. These genes were specifically activated by the heterodimerization-deficient mutant FXRα2L434R, enriched for ER-2 motifs at their promoters, and involved in lipid metabolism and ammonia detoxification. In conclusion, RXR acts as a molecular switch, inhibiting FXRα2 activation from ER-2 while enhancing it from canonical IR-1 REs. Our results showcase FXR as the first NR with isoform-specific RXR-independent REs, highlighting a new layer of regulation and complexity for RXR-heterodimerizing NRs.
The 2025 Nucleic Acids Research database issue and the online molecular biology database collection
Authors: Rigden Daniel J , Fernández Xosé M 
Published: December 2024

Abstract
The 2025 Nucleic Acids Research database issue contains 185 papers spanning biology and related areas. Seventy three new databases are covered, while resources previously described in the issue account for 101 update articles. Databases most recently published elsewhere account for a further 11 papers. Nucleic acid databases include EXPRESSO for multi-omics of 3D genome structure (this issue’s chosen Breakthrough Resource and Article) and NAIRDB for Fourier transform infrared data. New protein databases include structure predictions for human isoforms at ASpdb and for viral proteins at BFVD. UniProt, Pfam and InterPro have all provided updates: metabolism and signalling are covered by new descriptions of STRING, KEGG and CAZy, while updated microbe-oriented databases include Enterobase, VFDB and PHI-base. Biomedical research is supported, among others, by ClinVar, PubChem and DrugMAP. Genomics-related resources include Ensembl, UCSC Genome Browser and dbSNP. New plant databases cover the Solanaceae (SolR) and Asteraceae (AMIR) families while an update from NCBI Taxonomy also features. The Database Issue is freely available on the Nucleic Acids Research website (https://academic.oup.com/nar). At the NAR online Molecular Biology Database Collection (http://www.oxfordjournals.org/nar/database/c/), 932 entries have been reviewed in the last year, 74 new resources added and 226 discontinued URLs eliminated bringing the current total to 2236 databases.
Mechanistic insights into Sindbis virus infection: noncapped genomic RNAs enhance the translation of capped genomic RNAs to promote viral infectivity
Authors: Karki Deepa , LaPointe Autumn T , Isom Cierra , Thomas Milton , Sokoloski Kevin J 
Published: December 2024

Abstract
Alphaviruses are globally distributed, vector-borne RNA viruses with high outbreak potential and no clinical interventions, posing a significant global health threat. Previously, the production and packaging of both viral capped and noncapped genomic RNAs (cgRNA and ncgRNA) during infection was reported. Studies have linked ncgRNA production to viral infectivity and pathogenesis, but its precise role remains unclear. To define the benefits of ncgRNAs, pure populations of capped and noncapped Sindbis virus (SINV) gRNAs were synthesized and transfected into host cells. The data showed that mixtures of cgRNAs and ncgRNAs had higher infectivity compared to pure cgRNAs, with mixtures containing low cgRNA proportions exceeding linear infectivity expectations. This enhancement depended on co-delivery of cgRNAs and ncgRNAs to the same cell and required the noncapped RNAs to be viral in origin. Contrary to the initial hypothesis that the ncgRNAs serve as replication templates, the cgRNAs were preferentially replicated. Further analysis revealed that viral gene expression, viral RNA (vRNA) synthesis and particle production were enhanced in the presence of ncgRNAs, which function to promote cgRNA translation early in infection. Our findings highlight the importance of ncgRNAs in alphaviral infection, showing they enhance cgRNA functions and significantly contribute to viral infectivity.
Precision medicine: an intrahepatic cholangiocarcinoma with a novel RBPMS-MET fusion sensitive to crizotinib
Authors: Wan Wei , Liu Xueqin , Zhang Yamin , Shen Rui , Xia Weihu , Li Shuangni , Tan Yuan , Duan Qianqian , Liu Jinpeng , Wang Wuping 
Published: December 2024

Abstract

Background
Intrahepatic cholangiocarcinoma is a malignant tumor that starts from the epithelium of the bile duct and has a poor prognosis. They are characterized by poor response to chemotherapy and lack of effective targeted therapies; thus, therapeutic options are limited.

Case Presentation
A 59-year-old man was admitted to the hospital for a workup of abnormal CA19-9 levels. He was diagnosed with ICC, underwent surgery and was found to have pT1bNx disease. He developed rapid disease recurrence on adjuvant gemcitabine + capecitabine. Following recurrence, he received first-line systemic pembrolizumab + lenvatinib and second-line pembrolizumab + lenvatinib + chemotherapy and had mild tumor regression followed by progression. Next-generation sequencing was performed on the baseline surgical sample. This revealed a novel RBPMS-MET fusion, and based on the literature, crizotinib 250 mg twice a day was administered. After 3 months of crizotinib treatment, magnetic resonance imaging revealed a significant reduction in liver lesions, and 4 months after initiating treatment, scans demonstrated a partial response.

Conclusion
Our case report strengthens the evidence that crizotinib may be a viable treatment option for patients with ICC with a c-MET tyrosine kinase fusion, necessitating additional clinical investigation.
Associations of frailty with survival, hospitalization, functional decline, and toxicity among older adults with advanced non-small cell lung cancer
Authors: Lee Howard J , Boscardin John , Walter Louise C , Smith Alexander K , Cohen Harvey J , Giri Smith , Williams Grant R , Presley Carolyn J , Singhal Surbhi , Huang Li-Wen , Velazquez Ana I , Gubens Matthew A , Blakely Collin M , Mulvey Claire K , Cheng Michael L , Sakoda Lori C , Kushi Lawrence H , Quesenberry Charles , Liu Raymond , Fleszar-Pavlovic Sara , Eskandar Caroline , Cutler Edward , Mercurio Anne Marie , Wong Melisa L 
Published: December 2024

Abstract

Introduction
Among older adults with cancer receiving chemotherapy, frailty indices predict OS and toxicity. Given the increased use of immunotherapy and targeted therapy for advanced non-small cell lung cancer (aNSCLC), we evaluated frailty and Karnofsky Performance Status (KPS) among older adults with aNSCLC receiving chemotherapy, immunotherapy, and/or targeted therapy.

Methods
Patients aged ≥ 65 with aNSCLC starting systemic therapy with non-curative intent underwent geriatric assessments over 6 months. We developed a deficit-accumulation frailty index to categorize patients as robust, pre-frail, or frail. To evaluate associations between frailty and KPS with OS, we used Cox proportional hazards models adjusted for race, insurance, and treatment. We used logistic regression to evaluate hospitalizations, functional decline, and severe toxicity.

Results
Among 155 patients (median age 73), 45.8% were robust, 36.1% pre-frail, and 18.2% frail; 34.8% had a KPS ≥ 90, 32.9% had a KPS of 80, and 32.3% had a KPS ≤ 70. The median OS was 17.9 months. Pre-frail/frail patients had worse OS compared to robust patients (adjusted hazard ratio [HR] 2.09, 95% CI, 1.31-3.34) and were more likely to be hospitalized (adjusted odds ratio [OR] 2.21, 95% CI, 1.09-4.48), functionally decline (adjusted OR 2.29, 95% CI, 1.09-4.78), and experience grade ≥ 3 hematologic toxicity (adjusted OR 5.18, 95% CI, 1.02-26.03). KPS was only associated with OS.

Conclusions
Our frailty index was associated with OS, hospitalization, functional decline, and hematologic AEs among older adults with aNSCLC receiving systemic therapies, while KPS was only associated with OS. Pretreatment frailty assessment may help identify older adults at risk for poor outcomes to optimize decision-making and supportive care.
The BRAHMA-associated SWI/SNF chromatin remodeling complex controls Arabidopsis seed quality and physiology
Authors: Wrona Magdalena , Zinsmeister Julia , Krzyszton Michal , Villette Claire , Zumsteg Julie , Mercier Pierre , Neveu Martine , Sacharowski Sebastian P , Archacki Rafał , Collet Boris , Buitink Julia , Schaller Hubert , Swiezewski Szymon , Yatusevich Ruslan 
Published: December 2024

Abstract
The SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complex is involved in various aspects of plant development and stress responses. Here, we investigated the role of BRM (BRAHMA), a core catalytic subunit of the SWI/SNF complex, in Arabidopsis thaliana seed biology. brm-3 seeds exhibited enlarged size, reduced yield, increased longevity, and enhanced secondary dormancy, but did not show changes in primary dormancy or salt tolerance. Some of these phenotypes depended on the expression of DOG1, a key regulator of seed dormancy, as they were restored in the brm-3 dog1-4 double mutant. Transcriptomic and metabolomic analyses revealed that BRM and DOG1 synergistically modulate the expression of numerous genes. Some of the changes observed in the brm-3 mutant, including increased glutathione levels, depended on a functional DOG1. We demonstrated that the BRM-containing chromatin remodeling complex directly controls secondary dormancy through DOG1 by binding and remodeling its 3′ region, where the promoter of the long noncoding RNA asDOG1 is located. Our results suggest that BRM and DOG1 cooperate to control seed physiological properties and that BRM regulates DOG1 expression through asDOG1. This study reveals chromatin remodeling at the DOG1 locus as a molecular mechanism controlling the interplay between seed viability and dormancy.
Optimized single-cell gates for yeast display screening
Authors: Pan Xiaoli , de Souza Matheus O , Figueiras Francisco M , Huang Aric , Banach Bailey B , Wolfe Jacy R , Pirhanov Azady , Madan Bharat , DeKosky Brandon J 
Published: December 2024

Abstract
Yeast display is a widely used technology in antibody discovery and protein engineering. The cell size of yeast enables fluorescence-activated cell sorting (FACS) to precisely screen gene libraries, including for multi-parameter selection of protein phenotypes. However, yeast cells show a broader size distribution than mammalian cells that complicates single-cell gate determination for FACS. In this report, we analyze several yeast display gating options in detail and present an optimized strategy to select single yeast cells via flow cytometry. These data reveal optimized single-cell gating strategies to support robust and high-efficiency yeast display studies.
Cross-Subsidization of Bad Credit in a Lending Crisis
Authors: Artavanis Nikolaos , Lee Brian Jonghwan , Panageas Stavros , Tsoutsoura Margarita 
Published: December 2024

Abstract
We study the corporate-loan pricing decisions of a major, systemic bank during the Greek financial crisis. A unique aspect of our data set is that we observe both the actual interest rate and the “break-even rate” (BE rate) of each loan, as computed by the bank’s own loan-pricing department (in effect, the loan’s marginal cost). We document that low-BE-rate (safer) borrowers are charged significant markups, whereas high-BE-rate (riskier) borrowers are charged smaller and even negative markups. We rationalize this de facto cross-subsidization through the lens of a dynamic model featuring depressed collateral values, impaired capital-market access, and limit pricing.
A protocol for targeted B-lymphocyte depletion for the treatment of IgG4-related disease
Authors: Colquhoun Matthew , Barwick Tara D , Bolton Eva , Gibbons Norma , Hughes-Hallett Archie , Levy Jeremy B , McAdoo Stephen P , Parisinos Constantinos A , Philips Natalie , Tam Frederick W K , Wernig Florian , Youngstein Taryn , Tomlinson James A P 
Published: December 2024

Abstract

Objectives
To determine the clinical outcomes of patients with immunoglobulin 4-related disease (IgG4-RD) treated with a defined B-cell depletion protocol using rituximab.

Methods
Patients were included if they had (i) an IgG4-RD diagnosis at Imperial College Healthcare NHS Trust between February 2017 and October 2022, and (ii) &gt;9 months of follow-up data available following the first rituximab dose. The rituximab protocol targeted B-cell depletion to &lt;10 cells/microliter for a maintenance period of two years. Electronic records were used to define patient demographics, serological and radiological variables and treatment responses according to the IgG4-RD responder index (RI).

Results
Forty-five patients received induction treatment with rituximab. Two patients had insufficient follow-up data for outcome analysis. All patients responded to rituximab therapy according to the IgG4-RD RI. Most patients (25/43, 58%) were also treated with low-dose glucocorticoids at the time of rituximab induction (median prednisolone dose 5 mg daily) and 4/25 (16%) remained on prednisolone at two years (median prednisolone dose 5 mg daily). Disease flares occurred in 11/43 (26%) patients; 9/11 flares occurred in the presence of B-cell repopulation; 2/11 (18.1%) flares occurred in the absence of B-cell repopulation (&gt;10 cells/uL). All flares re-treated with rituximab (7/7, 100%) responded positively.

Conclusion
Rituximab administration targeting B-cell depletion for a two-year period is an effective treatment strategy for IgG4-RD and can limit the cumulative glucocorticoid exposure. Flares are uncommon and typically occur in the setting of B-cell repopulation, with good clinical responses to further rituximab administration.