bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rhamnose-mediated modulation of hair follicle growth: insights from chemical genomics
Authors: Li Xiu , Liu Ying , Li Lu , Jiang Wenjie , Ma Shize , Cao Rui , Zhang Yi , Xiao Ran , Wang Dong , Yang Zhigang 
Published: January 2025

AbstractPursuing compounds capable of stimulating hair follicle growth or regeneration presents a significant challenge in dermatological research. Dermal papilla (DP) cells, which serve as a dynamic niche for hair follicle stem cells, are often used to identify hair growth-promoting agents as a screening model. Here, we integrated human scalp single-cell RNA sequencing data with human DP cells (hDPCs) gene expression profiles to develop a gene panel for assessing hair follicle inductive potential, then applied a high-throughput sequencing-based high-throughput screening (HTS2) method to quantify the gene expressions of hDPCs perturbed by over 2000 small molecules. Notably, rhamnose was identified as a compound that restored the expression of hair-inducing genes in hDPCs. More importantly, the topical application of rhamnose accelerated hair follicle regeneration by promoting hair cycle into the anagen phase. Transcriptome and central carbon metabolism analyses revealed that rhamnose induced glucose metabolism remodeling favoring glycolysis in mice. A similar phenotype was also observed in rhamnose-treated hDPCs, as demonstrated by glycolysis and mitochondrial stress tests. The present study introduces a novel methodology for evaluating hair-inducing agents and provides valuable insights into the cellular and molecular mechanisms underlying the hair growth-promoting effects of rhamnose. These findings highlight the potential for the therapeutic application of rhamnose in the treatment of alopecia.
Dynamics of biofilm-formingBacillus subtilisinCaenorhabditis elegansgut
Authors: Saitoh Yasuaki , Qiu Tian (Autumn) 
Published: January 2025

AbstractBiofilm-formingBacillus subtilisstrain NCIB3610 has been reported to show biofilm-mediated beneficial effects when fed toCaenorhabditis elegans, including enhanced stress resistance, extended lifespan, and protection against neurotoxic agents. However, biofilm-formingB. subtilispresents multiple cell types, and thus a thorough characterization ofB. subtiliscell dynamics in theC. elegansgutin vivois necessary to understand mechanisms of the biofilm-mediated beneficial effects. In this study, we utilized an isogenic NCIB3610 strain expressing a biofilm reporter PtapA-mKate2to monitor matrix-producing components inC. elegansgut. Interestingly, our results revealed that in liveC. elegansgut, noB. subtilisbiofilms were formed but only free spores and diffused fluorescence, which were likely from dietary matrix-producing cells crushed by the pharynx. Additional data showed that spores can geminate into motile cells but not matrix-producing cells in livingC. elegansgut. Biofilm formation was found in gut afterC. elegansdeath, indicating that mechanistically, life-dependent functions of the worm inhibit the formation of matrix-producing cells in gut. These findings resolved a key piece of puzzle in understanding the fundamental mechanisms ofC. elegans-B. subtilisinteraction and highlighted the importance of characterizing cell dynamicsin vivoin host-microbe interaction research.
Long- term improvement in Alzheimer’s Disease with Transcranial Direct Current Stimulation
Authors: Aggarwal Anu 
Published: January 2025

AbstractThe goal of this work was to integrate results from clinical trials related to transcranial direct current stimulation (tDCS) treatment of Alzheimer’s disease (AD) into a machine learning model of the disease to understand its impact on disease progression over a decade. Themain contributionsof this work are- firstly, extension of otherwise sparse clinical data for tDCS stimulation in AD patients to predict patient outcomes over a decade. Secondly, it provides evidence of long-term improvement in AD with tDCS. Thirdly, it calculates an optimal tDCS regimen for improvement in cognitive function for patients with AD. This paper integrates data from an emerging field of research (tDCS treatment) into general guidelines for best stimulation practices and potential outcomes which can be replicated to other diseases and treatments.
Ovarian cancer cell cluster inhibits pancreatic cancer progression
Authors: Liang Maodi , Fan Rui , Wang Cuizhe , Gong Kejian , Lin Xiao , Zhao Mengyuan , Zhang Huizi , Xu Lili , Liu Qin , Su Yurui , Cui Chunmei , Liu Xingkai , Zhang Jun , Cui Qinghua 
Published: January 2025

AbstractPancreatic cancer is the most lethal cancer and all of the current cancer treatment strategies fail at this disease. It is thus urgently important to explore novel therapeutics. We previously revealed that it can be significantly inhibited by ovarian cancer cell by bothin vitroandin vivoexperiments. It was reported that cancer cell cluster can greatly enhance the efficiency in metastasis model compared to single cancer cell. Given this observation, here we proposed that ovarian cancer cell cluster could inhibit pancreatic cancer more efficiently than single ovarian cancer cell. As a result, animal experiments demonstrated that the injection of both low and high doses of SKOV3 ovarian cancer cluster show significantly higher efficiency in inhibiting pancreatic cancer xenografts than single SKOV3 ovarian cancer cell. Moreover, single cell RNA-sequencing analysis revealed that ovarian cancer cell cluster treatment inhibited pancreatic cancer by promoting inflammation response by both activating the NF-κB pathway in pancreatic cancer cells and substantially shifting macrophages in tumor microenvironments (TME) to M1 phenotype. In summary, this study proposed and validated a novel potential therapeutic for pancreatic cancer.
Multiple losses of ecdysone receptor genes in nematodes: an alternative evolutionary scenario of molting regulation
Authors: Yamakawa Shumpei , Barf Lisa-Marie , Hejnol Andreas 
Published: January 2025

AbstractMolting is a hallmark feature of ecdysozoans, including arthropods, tardigrades, and nematodes. Ecdysone hormones play a crucial role in regulating the molting process of different ecdysozoan taxa. Interestingly, despite this highly conserved function of ecdysone, the model nematodeCaenorhabditis eleganshas lost the ecdysone receptor (ECR) genes and their molting appears to be ecdysone-independent. The loss ofecrhas only been reported inCaenorhabditiswithin ecdysozoans, and the evolutionary background behind this loss has remained enigmatic. Here, we show that loss ofecris not exceptional inCaenorhabditis, but has occurred at least three times in Rhabditina and Tylenchina nematodes. Our genome-wide analysis of 160 nematode species revealed the multiple losses ofecrand its typical heterodimer partneruspduring nematode evolution. Furthermore, using genomic and transcriptomic analyses, we identified two factors that likely underlie and buffer the loss of ECR gene/function: molting regulation by an alternative nuclear receptor HR3 (NHR-23) and a lineage-specific expansion of nuclear receptors in theecr-deficient taxa. Taken together, it is suggested that ecdysone/ECR function in nematodes is only minor or redundant. We propose a novel scenario for the evolution of molting regulation, highlighting the importance of HR3 as the potential core regulator.
Slow oscillation-sleep spindle coupling is associated with fear extinction retention in trauma-exposed individuals
Authors: Denis Dan , Bottary Ryan , Cunningham Tony J. , Davidson Per , Yuksel Cagri , Milad Mohammed R. , Pace-Schott Edward F. 
Published: January 2025

AbstractPosttraumatic stress disorder (PTSD) can be characterized as a disorder of fear learning and memory, in which there is a failure to retain memory for the extinction of conditioned fear. Sleep has been implicated in successful extinction retention. The coupling of sleep spindles to slow oscillations (SOs) during non-rapid eye movement sleep has been shown to broadly underpin sleep’s beneficial effect on memory consolidation. However, the role of this oscillatory coupling in the retention of extinction memories is unknown. In a large sample of 124 trauma-exposed individuals, we investigated SO-spindle coupling in relation to fear extinction memory. We found that participants with a PTSD diagnosis, relative to trauma-exposed controls, showed significantly altered SO-spindle timing, such that PTSD participants exhibited spindle coupling further away from the peak of the SO. Across participants, the amount of coupling significantly predicted extinction retention, with coupled spindles uniquely predicting successful extinction retention compared to uncoupled spindles. These results suggest that SO-spindle coupling is critical for successful retention of extinguished fear, and that SO-spindle coupling dynamics are altered in PTSD. These alterations in the mechanics of sleep may have substantial clinical implications, meriting further investigation.
Self-Contemplating In-Context Learning Enhances T Cell Receptor Generation for Novel Epitopes
Authors: Zhang Pengfei , Bang Seojin , Lee Heewook 
Published: January 2025

AbstractComputational design of T cell receptors (TCRs) that bind to epitopes holds the potential to revolutionize targeted immunotherapy. However, computational design of TCRs for novel epitopes is challenging due to the scarcity of training data, and the absence of known cognate TCRs for novel epitopes. In this study, we aim to generate high-quality cognate TCRs particularly fornovel epitopeswith no known cognate TCRs, a problem that remains under-explored in the field. We propose to incorporate in-context learning, successfully used with large language models to perform new generative tasks, to the task of TCR generation for novel epitopes. By providing cognate TCRs as additional context, we enhance the model’s ability to generate high-quality TCRs for novel epitopes. We first unlock the power of in-context learning by training a model to generate new TCRs based on both a target epitope and a small set of its cognate TCRs, so-called in-context training (ICT). We then self-generate its own TCR contexts based on a target epitope, as novel epitopes lack known binding TCRs, and use it as an inference prompt, referred to as self-contemplation prompting (SCP). Our experiments first demonstrate that aligning training and inference distribution by ICT is critical for effectively leveraging context TCRs. Subsequently, we show that providing context TCRs significantly improves TCR generation for novel epitopes. Furthermore, we show TCR generation using SCP-synthesized context TCRs achieves performance comparable to, and sometimes surpassing, ground-truth context TCRs, especially when combined with refined prompt selection based on binding affinity and authenticity metrics.
Cross-species comparative modelling of antimicrobial host responsesex vivoin human and murine precision cut lung slices andin vivoin mice
Authors: Choltus Hélèna , Prados Julien , Bianchi Niccolo , Heikkila Nelli , Beinier Veronique Serre , Karenovics Wolfram , Bédat Benoit , Eberhardt Christiane , Becattini Simone , Schmolke Mirco 
Published: January 2025

AbstractIn biomedical infectious disease research new models to bridge preclinical and clinical research are needed. Mouse models are still one of the most-interrogated experimental systems with the caveat of biological differences in pathogen-host-interaction for some human-relevant pathogens and increasing ethical concerns. Arguably one of the most complex cell culture models are precision cut organ slices, volume defined tissue blocks which can be cultured ex vivo and exposed to various stimuli including human pathogens. They could be applied as 3R model system. However, their response to infectious agents in comparison toin vivomodels is understudied. To understand species and model specific differences in the host response (here: influenza A virus (IAV) andStreptococcus pneumoniae(Spn)), we interrogate here the transcriptional reaction of human PCLS (hPCLS) compared to that of murine precision cut lung slices (mPCLS) and a murinein vivoinfection model. A direct comparison of hPCLS and mPCLS revealed a more complex early innate immune response against viral and bacterial pathogens in the human model, which beyond this informs about secondary cell-to-cell communicationin situand bystander cell responses to proinflammatory and antiviral cytokines secreted by tissue resident immune cells. In contrast, the murine PCLS model revealed substantial deficits in responding to viral challenge, reproducing only a small fraction of the murinein vivohost response. Our study provides the first cross-species comparison of early transcriptomic responses to relevant human pathogens.
Comparative Evaluation of Targeted RNA Sequencing Protocols for Gene Expression Quantification With and Without Unique Molecular Indices (UMIs)
Authors: Gosch Annica , Courts Cornelius 
Published: January 2025

AbstractInterest in forensic RNA analysis has increased over the last years. RNA molecules present in forensic samples can accurately be quantified via quantitative PCR (qPCR), however, due to the limited number of markers that can be assayed simultaneously per reaction, qPCR is less suitable for applications requiring gene expression quantification of large marker sets. Few years ago, massively parallel targeted RNA-sequencing (targRNAseq) allowing to simultaneously and accurately quantify several hundreds of markers has been added to the forensic genetic tool set. However, typical targRNAseq protocols include a multiplex-PCR-step to amplify selected targets which potentially introduces bias and limits accurate gene expression quantification.Unique Molecular Indices (UMIs) have been invented to overcome this limitation and have been implemented in protocols from some vendors.In this study, we compared two targeted RNAseq protocols assaying expression of a set of 121 forensically relevant mRNA biomarkers: The Ion Ampliseq targeted RNA sequencing panel (Thermo Fisher Scientific), which employs a multiplex-PCR without the use of UMIs, and the QIAseq targeted RNA panel (QIAGEN), which uses UMIs prior to multiplex amplification.Both protocols were tested on replicated samples and dilution series and compared with respect to sensitivity and accuracy of gene expression quantification.The UMI-based protocol exhibited decreased sensitivity in comparison to the non-UMI-based alternative, however, making use of UMI technology greatly improved gene expression quantification accuracy. We thus recommend the use of UMI-based protocols for targeted RNA sequencing for applications requiring accurate gene expression quantification.
Large interspecific and intraspecific variation in seed longevity in storage
Authors: Klepka Lea , Liepelt Sascha , Bucharova Anna 
Published: January 2025

ABSTRACTPremiseConservation seed banks are an essential tool for plant ex-situ conservation. However, seeds stored for long periods of time slowly deteriorate and lose viability. While seed longevity is known to vary between species, the extent of variability within species and the factors driving it remain unclear.MethodsWe focused on both inter- and intraspecific variability in seed longevity and its determinants. We studied 41 common grassland species and 188 seed accessions from across Europe. We exposed the seeds to artificial ageing conditions (60% RH, 45°C) and estimated the seed longevity (p50), defined as the time required for viability to decline to 50% of the initial viability. We then tested the relationships between seed longevity and both species- and origin-specific factors.ResultsVariability in seed longevity was only slightly greater between species than within species, with species identity explaining 51.9% of the total variation in seed longevity among seed accessions, leaving 48.1% of the variation within species. In interspecific species comparison, seed viability was predicted only by initial seed viability, but unrelated to species-specific seed mass or seed chemical composition. Within species, seed longevity increased with the initial viability of the seed accession and mean annual temperature at the accession origin, but was unrelated to seed mass or precipitation in the origin, and the residual variance was substantial.ConclusionOur findings highlight that seed longevity on the level of individual seed accessions remains challenging to predict.
Role of Age in Mediating the Association Between the Vaginal Microbiota and Preterm Birth
Authors: Xie Yun , Wang Qi , Li Dan , Jia Fengan , Chang Fan , Zhang Zhen , Sun Yanmei , Wang Shiwei 
Published: January 2025

AbstractThe vaginal microbiota plays a crucial role in vaginal health and pregnancy outcomes. However, the influence of maternal characteristics, especially age, on the relationship between the vaginal microbiota and preterm birth is poorly understood. This study quantifies the effects of race, maternal age, and gestational age on vaginal microbiota composition. Our results demonstrate stronger associations between preterm birth and a less optimal vaginal microbiota in White and Asian women compared to Black or African American women. The microbiota difference between preterm and term births was more pronounced in older reproductive-age women, withLactobacillusspecies increasing with age only in term births. Additionally, lower alpha diversity was observed in term pregnancies compared to preterm during both early and late pregnancy, particularly in women aged above 25 years. These findings highlight the mediating role of age in the relationship between the vaginal microbiota and preterm birth.
Single-Cell Multimodal Profiling Reveals a Novel CD26+Fibroblast Subpopulation in Atherosclerosis
Authors: Bashore Alexander C. , Coronel Johana , Xue Chenyi , Zhu Lucie Y. , Reilly Muredach P. 
Published: January 2025

AbstractBackgroundAtherosclerosis involves complex interactions between lipids, immune cells, vascular smooth muscle cells (VSMCs), and fibroblasts within the arterial wall. While significant advances in single-cell technologies have shed light on the roles of immune cells and VSMCs in plaque development, fibroblasts remain underexplored, leaving critical gaps in understanding their contributions to disease progression and plaque stability. Comprehensive characterization of fibroblast phenotypes in atherosclerosis is essential to unravel their diverse functions and to distinguish between subsets that may play protective versus pathogenic roles in the disease process.MethodsHere, we utilized CITE-seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) to comprehensively profile fibroblast diversity in a mouse model of atherosclerosis. Mice were fed an atherogenic diet for 0, 8, 19, and 26 weeks, representing distinct stages of disease progression, enabling a detailed phenotypic characterization of fibroblasts throughout the course of atherosclerosis development.ResultsWe identified four distinct fibroblast subpopulations, including a myofibroblast population closely resembling VSMC-derived chondromyocytes. The proportions of these fibroblast subsets exhibited a modest decline as atherosclerosis progressed. Through multimodal analysis, we identified CD26 as a highly expressed and specific marker for one of these fibroblast subpopulations, distinguishing it from other subsets. Using a combination of flow cytometry and immunohistochemistry, we demonstrated that CD26+fibroblasts predominantly reside in the adventitia of healthy arteries. During atherosclerosis progression, these cells expand into the intima and primarily localize within the fibrous cap of the lesion.ConclusionsOur multi-omic analysis highlights the phenotypic diversity and dynamic changes of fibroblasts during atherosclerosis progression. Among these, CD26+ fibroblasts emerge as a distinct subpopulation that expands within atherosclerotic lesions and may play a critical role in promoting plaque stability through their migration into the fibrous cap.
ArtSymbioCyc, a metabolic network database collection dedicated to arthropod symbioses: a case study, the tripartite cooperation inSipha maydis
Authors: Baa-Puyoulet Patrice , Gerlin Léo , Parisot Nicolas , Peignier Sergio , Renoz François , Calevro Federica , Charles Hubert 
Published: January 2025

AbstractMost arthropods live in close association with bacteria. The genomes of associated partners have co-evolved creating situations of interdependence that are complex to decipher despite the availability of their complete sequences. We developed ArtSymbioCyc, a metabolism-oriented database collection gathering genomic resources for arthropods and their associated bacteria. ArtSymbioCyc uses the powerful tools of the BioCyc community to produce high quality annotations and to analyze and compare metabolic networks on a genome-wide scale. We used ArtSymbioCyc to study the case of the tripartite symbiosis of the cereal aphidSipha maydisfocusing on amino acid and vitamin metabolisms, as these compounds are known to be important in this strictly phloemophagous insect. We showed how the metabolic pathways of the insect host and its two obligate bacterial associates are interdependent and specialized in the exploitation of Poaceae phloem, for example for the biosynthesis of sulfur-containing amino acids and most vitamins. This demonstrates that ArtSymbioCyc does not only reveal the individual metabolic capacities of each partner and their respective contributions to the holobiont they constitute, but also allows to predict the essential inputs that must come from host nutrition.IMPORTANCEEvolution has driven the emergence of complex arthropod-microbe symbiotic systems, whose metabolic integration is difficult to unravel. With its user-friendly interface, ArtSymbioCyc (https://artsymbiocyc.cycadsys.org) eases and speeds up the analysis of metabolic networks by enabling precise inference of compound exchanges between associated partners, and helps unveil the adaptive potential of arthropods in contexts such as conservation or agricultural control.
A cross-species multimodal database of gene expression in cardiac hypertrophy
Authors: Sandmann Christoph , Lanzer Jan D , Stein Frank , Malovrh Ellen , Rüdinger Nicholas , Frey Norbert , Saez-Rodriguez Julio , Völkers Mirko 
Published: January 2025

SummaryChanges in gene expression determine the pathophysiological response of the heart during increased workload and biomechanical stress.1,2Understanding the complex gene expression regulation during physiological and pathological stress provides insight into mechanisms that mediate the transition from cardiac hypertrophy to heart failure. We curated and generated a multi-omics database of cardiac hypertrophy and heart failure and exemplified its usage by evaluating the regulation of UCK2, a gene that belongs to a conserved cardiomyocyte hypertrophy gene expression signature with unknown function in heart disease. To provide the community with simple access to the database, we developed CHEERIO (Cardiac HypErtrophy gEne expRessIOn Database), a free and easy-to-use interactive web application to explore rodent and human gene expression during early, late, physiological and pathological cardiac hypertrophy, as well as heart failure at transcriptome, translatome, proteome, bulk and single-cell resolution. CHEERIO is freely available athttps://voelkerslab.shinyapps.io/CHEERIO/.