bluuebunny/crossref_metadata_2025_split huggingface dataset:
Few-shot in-context learning with large language models for antibody characterization
Authors: Fung Sin-Hang , Zhang Zhenghao , Wang Ran , Miao Chen , Wong Brian Shing-Hei , Li Kelly Yichen , Hong Chenyang , Zhou Jingying , Yip Kevin Y. , Tsui Stephen Kwok-Wing , Cao Qin 
Published: February 2025

AbstractLarge language models (LLMs) exhibit the emergent ability of few-shot in-context learning (ICL), allowing them to learn from demonstrations in simple prompts without task-specific training. However, applying few-shot ICL to biological sequences for classification, especially in computational immunology, remains underexplored. Here, we apply few-shot ICL with 18 general-purpose LLMs across five families to three antibody characterization scenarios, including predicting antibody humanness, specificity, and isotype. We evaluate performance under zero-shot, few-shot, and few-shot Chain-of-Thought ICL settings. We propose similarity-based few-shot demonstration selection strategies, which significantly improve performance of few-shot ICL compared to random selection. In all three scenarios, few-shot ICL, with as few as 32 examples, matches or exceeds the performance of established machine learning (ML) models trained on large datasets using traditional feature encodings. In two of the evaluated scenarios, few-shot ICL even matches or outperforms ML models that use state-of-the-art protein language model-based embeddings. Moreover, combining few-shot ICL with fine-tuning further enhances performance. We also demonstrate the reproducibility and stability of few-shot ICL results. Our findings establish few-shot ICL as a powerful method for efficiently characterizing antibody properties without task-specific training, enabling a single model to perform multiple tasks immediately. Its simplicity and versatility make few-shot ICL a promising approach to antibody characterization for researchers from diverse backgrounds, especially those without coding knowledge.
Draft genome of the marineEntamoebaspecies reveals reduction in the gene family repertoire associated with pathogenicity and lateral gene transfer for adaptation to the marine environment
Authors: Kawano-Sugaya Tetsuro , Izumiyama Shinji , Nozaki Tomoyoshi 
Published: February 2025

AbstractEntamoebais the amoebozoan parasite commonly found in the intestines of animals.E. marinais the first exception isolated from marine sediments, possibly adapting from animal intestines to the sea. However, the evolutionary process ofE. marinaremains uncertain due to the lack of a genome sequence. Here, we present thede novogenome and transcriptome ofE. marinausing Oxford Nanopore MinION and Illumina HiSeq/MiSeq. The genome ofE. marinais approximately 37.5 Mbp in length and consisted of 202 contigs, which is the second longest followed byE. invadens.E. marinashowed significant reduction in the major virulence-associated gene families, including cysteine proteases, lysosomal enzyme transporters, and surface galactose/N-acetylglucosamine-specific lectins, suggesting diversification, more specifically reduction of pathogenicity-related genes. Genome and RNA-seq analyses also indicated genes either conserved throughout eukaryotes or laterally transferred from prokaryotes, and potentially responsible for salt tolerance. Our study provides insights into the mechanism underlying the lifestyle changes in the evolution of parasitic eukaryotes.
Pex30-dependent membrane contacts sites maintain ER lipid homeostasis
Authors: Ferreira Joana Veríssimo , Ahmed Yara , Heunis Tiaan , Jain Aamna , Johnson Errin , Raeschle Markus , Ernst Robert , Vanni Stefano , Carvalho Pedro 
Published: February 2025

AbstractIn eukaryotic cells, communication between organelles and the coordination of their activities depend on membrane contact sites (MCS). How MCS are regulated under the dynamic cellular environment remains poorly understood. Here, we investigate how Pex30, a membrane protein localized to the endoplasmic reticulum (ER), regulates multiple MCS in budding yeast. We show that Pex30 is critical for the integrity of ER MCS with peroxisomes and vacuoles. This requires the Dysferlin domain (DysF) on Pex30 cytosolic tail. This domain binds to phosphatidic acid (PA) bothin vitroandin silico,and it is important for normal PA metabolismin vivo. The DysF domain is evolutionarily conserved and may play a general role in PA homeostasis across eukaryotes. We further show that ER-Vacuole MCS requires Pex30 C-terminal Domain of Unknown Function and that its activity is controlled by phosphorylation in response to metabolic cues. These findings provide new insights into the dynamic nature of MCS and their coordination with cellular metabolism.
A prioritized medium-throughput screen on human stem cell derived insulin secreting beta cells identifies FGF4, FGF5, FGF8F, FGF19 and FGF21 as protective factors
Authors: Chu Chieh Min Jamie , Kamal Sepehr , Huang Luo Ting , Bayly Carmen L. , Chen Sing-young , Omur Meltem E. , Wasserman Wyeth W. , Lynn Francis C. , Johnson James D. 
Published: February 2025

AbstractInsulin is produced by pancreatic β cells, whose dysfunction and death are hallmarks of diabetes. Stem cell-derived β-like cells (SCβ cells) are a potential alternative to cadaveric islets for replacement therapy. However, SCβ cells face a multitude of stresses, including hypoxia, hyperglycemia, ER stress, inflammation, and autoimmunity that must be overcome for this treatment to cure diabetes. Pancreatic β cells and SCβ cells reside in complex microtissues (islets or spheroids) and can therefore be potentially modulated by hundreds of autocrine and paracrine signals. Here, we leveraged scRNAseq, bulk RNAseq, and bulk proteomics data from late stage SCβ cells and human islets to map potential ligand-receptor pairs in these tissues and generate a prioritized list of ligands for high-content SCβ cell survival screening. We tracked cell number with Hoechst 33342, cell death using propidium iodide incorporation, andINSactivity fromINS-EGFP knock-in reporter human embryonic stem cells over several days using high throughput imaging. Members of the fibroblast growth factor (FGF) family significantly prevented cytokine induced cell death, with the top validated hits being FGF4, FGF5, FGF19, FGF21, and FGF8F. These results have the potential to improve SCβ cell survival with pathways that are readily targetable and translatable to the clinic.
The role of MKI67 in the regulation of 60S pre-ribosome nucleolar export, transcripts, energy supply, and apoptosis
Authors: Iuchi Shiro , Paulo Joao A. 
Published: February 2025

ABSTRACTMKI67 (Ki67) is expressed exclusively in proliferating cells in human tissues, rendering it as a valuable diagnostic marker for cancer. However, the function of this protein in cells remains unclear. In this study, we present the findings on the regulatory functions of MKI67 in conjunction with its partner proteins GNL2 and MDN1, which are involved in pre-ribosome processing, as well as the regulatory functions in its absence. In proliferating HEK293T cells, MKI67 binds contiguously to the chromatin in conjunction with GNL2 and MDN1, localizing most densely to the nucleolar periphery to regulate 60S pre-ribosome export. On the other hand, RNA-seq analysis reveals that these three proteins can independently regulate many target transcripts, but they often share their target transcripts, yet often regulate them at different expression levels. MDN1 depletion strongly downregulates RNA gene transcripts involved in ribosome biogenesis and splicing. In contrast, MKI67 depletion strongly upregulates transcripts of protein-coding genes, including synapse-specific proteins and the mitosis-related protein NEK7. Furthermore, MKI67 depletion coordinately up-or down-regulates the levels of transcripts of several pathways, thereby enabling MKI67-depleted cells to adapt to less active metabolic states. The underlying mechanism by which MKI67 depletion upregulates transcripts appears to involve attenuation of transcript levels in cooperation with mRNA degradation systems, as evidenced by analysis of NEK7 and UNC13A translations. In conclusion, the present results indicate that MKI67 contributes to proliferation via nucleolar export of 60S pre-ribosome particles and high energy supply. Conversely, its absence leads the cells to adapt to the senescent and differentiated conditions.
Neuropeptide CRH prevents premature differentiation of OPCs following CNS injury and in early postnatal development
Authors: Ries Clemens , Stark Tibor , Boulat Benoit , Ruhwedel Torben , Delling Jan Philipp , Infante Antonio Miralles , von Poblotzki Julia T. , Ulivi Alessandro , von Mücke-Heim Iven-Alex , Chang Simon , Sakimura Kenji , Itoi Keiichi , Nestvogel Dennis B. , Attardo Alessio , Czisch Michael , Nave Klaus-Armin , Möbius Wiebke , Dimou Leda , Deussing Jan M. 
Published: February 2025

SummaryThe role of neuropeptides and their receptors in oligodendrocyte progenitor cells (OPCs) has largely been overlooked so far. Here, we describe a new subpopulation of corticotropin-releasing hormone (CRH)-expressing OPCs that aggregate around acute brain injuries and exhibit an elevated capacity to differentiate into myelinating oligodendrocytes (OLs). We found that CRH expression in OPCs is rapidly inducedde novoas a transient response within the first 72 hours after injury. As target cells, we identified CRH receptor type 1 (CRHR1)-expressing OPCs which show a decreased differentiation velocity. We demonstrate that CRH/CRHR1 system inactivation increases the speed of OL generation compromising the long-term survival of OLs after acute injury. Furthermore, we prove that a CRH/CRHR1 system deficiency under non-injury conditions leads to increased early postnatal oligodendrogenesis and alterations in adult myelination. Altogether, we show that OPC-derived CRH not only actively influences the injury environment through the interaction with CRHR1-expressing OPCs, but also identify the G-protein coupled receptor CRHR1 as a critical modulator of oligodendrogenesis at early postnatal stages with lasting effects on adult myelination.
Sex Differences in VEGF and PDGF Ligand and Receptor Protein Expression during Adipose Tissue Expansion and Regression
Authors: Fang Yingye , Gonzales-Nieves Silvia , Cifarelli Vincenza , Imoukhuede P.I. 
Published: February 2025

ABSTRACTInadequate angiogenesis in obesogenic adipose tissue (AT) has been implicated in disrupted adipogenesis and metabolic disorders. Yet, key cellular and molecular regulators of AT angiogenesis remain largely unidentified. This study sought to identify the dysregulated elements within the Vascular Endothelial Growth Factor (VEGF) and Platelet-Derived Growth Factor (PDGF) systems during obesity progression. We employ a mouse model, comprising both male and female mice, to investigate the changes in the VEGF/PDGF concentration and their receptor distribution in AT during short- and long-term weight gain and weight loss. Our results reveal pronounced sex-specific differences in obesity progression, with male and female mice exhibiting distinct angiogenic ligand and receptor profiles under identical dietary interventions. This data also lays the groundwork for developing computational models of VEGF/PDGF signaling networks in AT, allowing for the simulation of complex biological interactions and the prediction of therapeutic outcomes.
Capicua refines mossy fiber–CA3 axon targeting in the late postnatal hippocampus
Authors: van Bruggen Rebekah , Wang Mi , Tan Qiumin 
Published: February 2025

AbstractProper brain wiring relies on the precise distribution of axonal projections to specific subcellular domains of their target neurons. These spatially confined connections establish the anatomical foundation for neural circuit assembly. The mossy fiber (MF)–CA3 pathway in the hippocampus is an excellent system to study the mechanisms underlying lamina-specific connectivity. In rodents, MF projections develop postnatally and reach their mature configuration by the end of the second postnatal week. MF axons synapse on the proximal segments of the dendrites but avoid the somas of CA3 pyramidal neurons. As dentate gyrus granule neurons are continuously generated and integrated into the existing hippocampal circuit throughout the postnatal period and adulthood, the mechanisms that guide MF axons to achieve lamina-specific targeting of these later-born granule neurons remain unclear. Here, we show that deletion of the neurodevelopmental disorder-associated protein capicua (CIC) results in abnormal MF targeting in the mouse hippocampus. Notably, this defect emerges after the second postnatal week and persists into adulthood, distinguishing it from classical MF guidance defects, which typically manifest during the first postnatal week. We also demonstrate that this miswiring is due to CIC loss in dentate gyrus granule neurons rather than CA3 pyramidal neurons. Single-nucleus transcriptomics and trajectory analysis reveal a loss of a mature granule neuron subtype and dysregulation of axon guidance genes that are normally downregulated as granule neurons mature. Our findings uncover a previously unrecognized role for CIC in hippocampus development and offer insights into the regulation of lamina-specific MF connectivity in the postnatal brain.
STAT3 expression is reduced in cardiac pericytes in HFpEF and its loss reduces cellular adhesion and induces pericyte senescence
Authors: Vanicek Leah Rebecca , Fischer Ariane , Ruz Jurado Mariano , Procida-Kowalski Tara , Wilhelm Jochen , Merten Maximilian , Escher Felicitas , Kattih Badder , Puntmann Valentina , John David , Nagel Eike , Dimmeler Stefanie , Luxán Guillermo 
Published: February 2025

AbstractHeart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure cases and is characterised by reduced pericyte coverage. While the contributions of other cardiac cell types to HFpEF are well-studied, the role of pericytes remains less understood. Using murine single-nucleus RNA sequencing to study cardiac pericytes in HFpEF, we identified reducedSTAT3expression as a hallmark of HFpEF pericytes. Mechanistic studiesin vitrorevealed thatSTAT3deletion induces cellular senescence and impairs pericyte adhesion, recapitulating HFpEF-like characteristics. These findings suggest thatSTAT3is crucial for maintaining pericyte homeostasis and highlight its reduction as a potential driver of pericyte loss, a defining feature of HFpEF.
Exploring mutational possibilities of KPC variants to reach high level resistance to cefiderocol
Authors: Hanna Sidonie , La Kevin , Yoshii Yutaka , Gits-Muselli Maud , Meouche Imane El , Benhadid-brahmi Yasmine , Bonacorsi Stéphane , Birgy André 
Published: February 2025

AbstractIntroductionKlebsiella pneumoniae carbapenemase (KPC)is one of the most widespread carbapenemases, with over 242 variants identified. Some, like KPC-33 (D179Y), resist both ceftazidime-avibactam (CZA) and cefiderocol but show only a moderate cefiderocol MIC increase. KPC’s success stems from its genetic adaptability, enabling mutation accumulation and necessitating proactive resistance monitoring. This study investigates the mutational possibilities for three KPC variants to develop high-level cefiderocol resistance.MethodUsing random mutagenesis and enrichment selection over a 10-day cefiderocol exposure at increasing concentration, we investigated the mutational potential of KPC-2, KPC-3, and KPC-33 to develop high-level cefiderocol resistance. Resistance mechanisms were then analyzed through phenotypic testing and sequencing.ResultsRandom mutagenesis generated 10⁵, 10⁴, and 105mutants forblaKPC-2,blaKPC-3, andblaKPC-33, respectively. After ten days of increasing cefiderocol exposure, MICs rose significantly, with KPC-2 mutants reaching >32 mg/L. Phenotypic analysis revealed a common resistance profile across all tested mutants, with resistance to ceftazidime, ceftazidime-avibactam, cefixime, and piperacillin, but restored susceptibility to carbapenems and most other β-lactams. Sequencing identified key mutations (D179Y- D209V in KPC-2, L169P in KPC-3), while chromosomal changes, particularlycirA andybiX disruptions, played a crucial role in resistance evolution.DiscussionOur results show that the enriched mutations in KPC genes are not sufficient to confer high cefiderocol MICs, suggesting that, in the studied variants, no simple mutational pathway allows the KPC enzyme to efficiently hydrolyze cefiderocol. These findings underscore the interplay between enzymatic and iron transport mutations in cefiderocol resistance, highlighting the importance of surveillance to anticipate emerging resistance in KPC-producing pathogens.
Linguistic coupling between neural systems for speech production and comprehension during real-time dyadic conversations
Authors: Zada Zaid , Nastase Samuel A. , Speer Sebastian , Mwilambwe-Tshilobo Laetitia , Tsoi Lily , Burns Shannon , Falk Emily , Hasson Uri , Tamir Diana 
Published: February 2025

AbstractThe core use of human language is communicating complex ideas from one mind to another in everyday conversations. In conversations, comprehension and production processes are intertwined, as speakers soon become listeners, and listeners become speakers. Nonetheless, the neural systems underlying these faculties are typically studied in isolation using paradigms that cannot fully engage our capacity for interactive communication. Here, we used an fMRI hyperscanning paradigm to measure neural activity simultaneously in pairs of subjects engaged in real-time, interactive conversations. We used contextual word embeddings from a large language model to quantify the linguistic coupling between production and comprehension systems within and across individual brains. We found a highly overlapping network of regions involved in both production and comprehension spanning much of the cortical language network. Our findings reveal that shared representations for both processes extend beyond the language network into areas associated with social cognition. Together, these results suggest that the specialized neural systems for speech perception and production align on a common set of linguistic features encoded in a broad cortical network for language and communication.
Single nucleotide polymorphisms associated with cytotoxicity ofBacillus cereusgroup strains in Caco-2 cells
Authors: Prince Cassidy , Chung Taejung , Kimble Kayla , Chandross-Cohen Tyler , Wiedmann Martin , Johler Sophia , Kovac Jasna 
Published: February 2025

ABSTRACTBacillus cereus sensu lato(s.l.) encompasses strains with diverse impacts, ranging from foodborne illness and anthrax to beneficial applications in agriculture and industry. While the risk of anthrax and emetic intoxication can be reliably predicted by the presence of specific virulence genes, predicting diarrheal foodborne illness risk based solely on enterotoxin gene presence has proven unreliable. In this study, we evaluated cytotoxicity against Caco-2 human gut cells using a diverse collection ofB. cereus s.l.isolates representing all eightpanCphylogenetic groups and conducted genomic analyses to identify predictive markers of cytotoxicity. Isolates frompanCgroups I, IV, and V exhibited significantly higher cytotoxicity compared to other groups, although individual isolates from otherpanCgroups have also been linked to illness. Logistic and random forest regression models revealed that while the presence of enterotoxin genes was a sensitive indicator of cytotoxicity, it lacked specificity. Logistic regression analysis identified 21 nonsynonymous single nucleotide polymorphisms (SNPs) within enterotoxin (Nhe and Hbl) gene sequences that were more effective predictors of cytotoxicity, providing higher specificity with comparable sensitivity. These SNPs achieved accuracy and precision values exceeding 0.7. Random forest models highlighted the importance ofpanCgroup, enterotoxin gene SNPs, and the presence of the fullhbloperon as key predictors of cytotoxicity. The strong sensitivity, specificity, and biological relevance of these SNPs position them as promising markers for improving strain-based risk assessment ofB. cereus s.l.IMPORTANCEEnterotoxin genes have been associated withB. cereus sensu lato(s.l.) diarrheal foodborne illness; however, their mere presence in a genome is an unreliable predictor of an isolate’s cytotoxicity towards human gut epithelial cells. To improve food safety risk assessment, more specific markers of cytotoxicity are required. In this study, we identified nonsynonymous SNPs within the coding sequences of the enterotoxins Nhe and Hbl. These SNPs offer potential targets for rapid molecular tests to identifyB. cereus s.l.isolates with an elevated food safety risk due to their capacity to inflict cytotoxic damage on human gut epithelial cells. Implementation of such markers upon validation could improve consumer safety while reducing food waste.
The sperm specific Na+,K+-ATPase α4 shows a highly structured and dynamic distribution at the sperm flagellum
Authors: Oishee Mumtarin J , McDermott Jeffrey P. , Sánchez Gladis , Blanco Gustavo 
Published: February 2025

AbstractNa+,K+-ATPase α4 is a unique cell plasma membrane Na+and K+transporter of spermatozoa, which is essential for male fertility. Previous studies have shown that Na+,K+-ATPase α4 is highly expressed in the sperm flagellum; however, the spatial arrangement of Na+,K+-ATPase α4 at the subcellular level and its relationship to the functional state of the cells are unknown. We studied this here using stimulated emission depletion (STED) super-resolution microscopy. We show that, under non-capacitated conditions, Na+,K+-ATPase α4 is distributed in a trilinear pattern along the midpiece and as a scattered single line along the principal piece segment of the sperm flagellum. Under capacitated conditions, Na+,K+-ATPase α4 pattern undergoes remodelling and its distribution shifts into a single line along the entire length of the flagellum. On the other hand, Na+,K+-ATPase α1 the somatic isoform of Na+,K+-ATPase also present in sperm, exhibits a similar trilaminar localization at the flagellar midpiece but a bilinear pattern in the principal piece. This distribution, unlike that of Na+,K+-ATPase α4, does not change during sperm capacitation. These differences in the localization pattern and spatial dynamics of Na+,K+- ATPase isoform expression highlights the dissimilarities in the roles of both ion transporters. The specific modulation of Na+,K+-ATPase α4 distribution, combined with the unique role that it has in sperm function, stresses the importance of Na+,K+-ATPase α4 for male fertility.Significance statementThis is the first demonstration of the highly structured nature of Na+,K+-ATPase in the plasma membrane of sperm, including the sperm specific Na+,K+-ATPase α4 isoform, which is key for male fertility, and the somatic Na+,K+-ATPase α1, which is present in all cells. Utilizing stimulated emission depletion (STED) super resolution microscopy, we discovered that Na+,K+- ATPase α4 and Na+,K+-ATPase α1 have different distributions along the sperm flagellum. Moreover, only Na+,K+-ATPase α4 undergoes remodelling during sperm capacitation. These specific patterns of localization that are dependent on the sperm functional state in combination with the different function and regulation of Na+,K+-ATPase isoforms highlights the sophisticated mechanisms that cells have evolved to fulfil their unique function.