bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of the Histone Deacetylase Inhibitor Valproic Acid in Combination with Fear Memory Retrieval before Exposure Therapy for Spider Phobia: A Randomized Controlled Trial
Authors: Schicktanz Nathalie S. , Dechent Frieder , Huber Carlo Andreas , Zimmer Anja , Iseli Galya Clara , Howald Jeanne , Schenker Maya Thalia , Gräff Johannes , Lang Undine , de Quervain Dominique JF , Bentz Dorothée 
Published: January 2025

AbstractReturn of fear after successful exposure therapy for phobia is a common clinical challenge. A previous study on mice demonstrated that the persistent attenuation of remote fear memories can be achieved by combining histone deacetylase inhibitors (HDACis) with fear-memory retrieval prior to extinction training. To evaluate the translational potential of this approach, we conducted a randomized, double-blind placebo-controlled trial. Forty-eight individuals with DSM-IV spider phobia received either HDACi valproic acid (VPA, 500 mg) or a placebo prior to the retrieval of fear memory followed by exposure therapy in virtual reality. No significant group difference was found in terms of behavioral change on the behavioral approach test at 3 months follow-up and baseline (primary outcome). However, the VPA group displayed significantly reduced fear in two self-report questionnaires related to spider phobia (Fear of Spider Questionnaire; Spider Phobia Beliefs Questionnaire) as compared to the placebo group. No group differences were observed for psychophysiological indicators of fear. The favorable impact of a single administration of VPA in combination with fear-memory retrieval prior to exposure therapy suggests that it might be an effective way to enhance symptom improvement at the subjective level in the treatment of phobias. Further studies need to investigate the conditions under which an improvement on the physiological and behavioral levels can be achieved as well.
Sugar-mediated control ofATG101modulates carbon deficiency-induced autophagy in Arabidopsis
Authors: Boycheva Woltering Svetlana , Tanigawa Mirai , Bläske Tobias , Isono Erika 
Published: January 2025

AbstractAutophagy is a major eukaryotic degradation and recycling pathway, which eliminates damaged cellular components and provides energy and building blocks especially under adverse environmental conditions. While the core autophagy machinery has been extensively studied, autophagy initiation and regulation remain less understood. In this study, we show that genes encoding the core autophagy initiation complex,ATG1,ATG11,ATG13, andATG101, are transcriptionally regulated by sugars. To analyze the expression of these genes, we took advantage ofArabidopsis thalianaaccessions, which display strong variations in their responses to darkness-induced fixed carbon deprivation. One of the components of the initiation complex,ATG101, has multiple sugar-related elements, and was repressed by sugar. Moreover,ATG101was induced stronger upon starvation in carbon starvation-resistant accessions when compared to carbon starvation-sensitive accessions. We identified three single nucleotide polymorphisms in the genomic region ofATG101which are associated with the carbon-starvation phenotype. Further analyses through complementation of theatg101mutant with different variants ofATG101demonstrated that the single nucleotide polymorphism alleles contribute differently toATG101expression regulation, response to sugar, and phenotype recovery. Taken together, our data suggest that modulation ofATG101by sugar is part of a multi-layered mechanism regulating the sensitivity to carbon starvation in Arabidopsis.
Ameliorative Effects ofBrideliaferrugineaExtracts on Cadmium Chloride-Induced Reproductive Hormone Imbalance, Oxidative Stress, Hepatorenal Damage, Hematological Disorders, and Acute Toxicity in Wistar Rats
Authors: Adewuyi Hassan Abdulsalam , Shekari Abednego , Adio Sakariyau Waheed , Oluwatoyin Adebimpe Hameedah , Fagbohun Rokibat Omowunmi , Owoeye Emmanuel Abiodun , Korie George Chibuike , Nasiru Monsurat Ololade , Olusegun Timothy God-Giveth , Ishola Ayomide Babatunde , Gidado Medina Ojuolape 
Published: January 2025

AbstractBackgroundCadmium chloride is a toxic heavy metal that can cause oxidative stress, damage to organs, and disrupt hormonal balance.Brideliaferrugineais a plant with antioxidant and free radical-scavenging properties. The aim of this study was to investigate the protective effects ofBrideliaferrugineaextract against cadmium chloride-induced toxicity in rats.MethodsThis study used a randomized controlled design, with 36 rats divided into 6 groups. The rats were treated with cadmium chloride,Brideliaferrugineaextract, or a combination of both. The study employed various assay methods, including acute toxicity test, reproductive hormone marker assays, oxidative stress marker assays, hepatic marker assays, and hematological parameter assays.Main findingsThe results showed that cadmium chloride induced significant acute toxicity, as evidenced by 33.33% mortality rate and significant body weight loss (-15.67 ± 3.33 g), whereas co-treatment with BFE (100 and 200 mg/kg) reduced mortality to 0% and reversed body weight loss to a gain of 10.00 ± 2.50g and 20.00 ± 2.50g, respectively. CdCl2 group had significantly lower testosterone, LH, and FSH levels compared to the control group (p < 0.05), significantly higher MDA levels and lower SOD and CAT levels compared to the control group (p < 0.05).significantly higherALT, AST, and ALP levels compared to the control group (p < 0.05), and significantly lower Hb, PCV, WBC, and RBC levels compared to the control group (p < 0.05) respectively. Co-administration ofBrideliaferrugineaextract with CdCl2 significantly improved reproductive hormone markers, reduced MDA levels and improved SOD and CAT levels in a dose-dependent manner (p < 0.05). Additionally, ALT, AST, and ALP levels were significantly reduced in a dose-dependent manner (p < 0.05), hematological parameters significantly improved in Hb, PCV, WBC, and RBC levels in a dose-dependent manner (p < 0.05). The highest dose of Brideliaferruginea extract (200 mg/kg) showed the most significant improvement in all parameters (p < 0.01).ImplicationsThis study suggests thatBrideliaferrugineaextract may be a useful therapeutic agent against heavy metal toxicity. The findings have implications for the development of novel treatments for heavy metal poisoning and highlight the potential of Brideliaferruginea extract as a natural remedy for heavy metal toxicity.
CSMA: an ImageJ Plugin for the Analysis of Wound Healing Assays
Authors: Pham Tri T. , Sagymbayeva Amina , Elebessov Timur , Onzhanova Zhadyra , Molnár Ferdinand 
Published: January 2025

ABSTRACTAccurate quantification of wound closure in cell migration assays is crucial yet challenging. Still, existing methods often underperform due to omitting cell detection within the wound area, resulting in biased outcomes. To overcome this limitation, we developed the CSMA plugin for ImageJ. CSMA utilizes advanced image processing techniques, including contrast enhancement, edge detection, and morphological operations, to precisely identify and quantify cells in the wound region. The plugin offers user-friendly features and adjustable parameters to accommodate different imaging conditions, ensuring robust performance across diverse experimental setups. Validation against conventional tools confirms CSMA’s superior ability to delineate wound boundaries and provide accurate estimations of area and width at every time point. As applied to SW480-ADH colon cancer cells treated with various compounds, CSMA proves valuable in biomedical research. It represents a significant advancement in wound healing assay analysis, providing researchers with a simple and reliable tool for studying cell migration dynamics with enhanced precision and reproducibility. CSMA is available as an ImageJ plugin and source code athttps://github.com/AminaSagymbayeva/CSMA_WoundHealing.
The 3D affinities of the OT-I TCR to foreign and self-antigens predict their 2D affinities and reveal imperfect antigen discrimination
Authors: Huhn Anna , Kutuzov Mikhail A. , Maclean Keir , Uhl Lion F. K. , Mahale Jagdish M. , Gerard Audrey , van der Merwe P. Anton , Dushek Omer 
Published: January 2025

AbstractT cells use the T cell antigen receptor (TCR) to discriminate between higher-affinity foreign and lower-affinity self peptide-MHC (pMHC) antigens. The OT-I mouse TCR is widely used to study anti-gen discrimination utilising many pMHCs, including foreign and self antigens. Previous studies sug-gested that OT-I T cells achieve near-perfect discrimination between higher and lower affinity antigens. Moreover, these 3D affinities measured in solution did not correlate with the 2D membrane affinities, suggesting a complex relationship between 3D and 2D affinities. In contrast, other TCRs have shown imperfect antigen discrimination and strong correlations between 3D and 2D affinities. To resolve these discrepancies, we extended a protocol for measuring ultra-low TCR/pMHC affinities to accurately de-termine the 3D affinities of the OT-I TCR binding 19 pMHC complexes. These revised 3D affinities now strongly correlate with the 2D affinities, and accurately predict functional responses. Importantly, we now find that the OT-I TCR exhibits enhanced yet imperfect antigen discrimination, similar to other TCRs, allowing it to detect abnormally high levels of low-affinity self-antigens. Finally, we show that discrimination is highest with low-affinity pMHC ligands, a finding predicted by the kinetic-proofreading model of antigen discrimination. This work underscores the ability of T cells to effectively gauge prox-ies for 3D affinity within the 2D cell-cell interface, with significant implications for the mechanisms underlying antigen discrimination.Lay abstractT cells protect the body from infection by distinguishing between foreign and self molecules. They do this using a specialized receptor called the T cell receptor (TCR), which senses differences in how strongly it binds to foreign versus self molecules. Scientists have used a mouse TCR called OT-I to understand this process, concluding that OT-I T cells exhibit near perfect discrimination between foreign and self antigens based on a sharp affinity threshold. However, conflicting results from experiments on other TCRs hinted at a more complicated picture. In this study, we used an improved method to accurately measure OT-I TCR binding affinity to 19 peptides, including foreign and self antigens. In contrast to previous results and like other TCRs, we found that OT-I T cells display enhanced but im-perfect discrimination, enabling them to be activated by high levels of self antigen. The new data also revealed that the ability of T cells to discriminate antigens is particularly high at low affinities. These findings reconcile apparent discrepancies between the OT-I TCR and other TCRs, and have implications for understanding diseases where T cells often respond to self antigen, such as autoimmunity and cancer.Graphical abstract
FaRIF at the Core of Strawberry Fruit Ripening: Deciphering its Targets and Interaction Networks
Authors: Martín-Pizarro Carmen , Franco-Zorrilla José M. , Perotti María Florencia , Lozano-Durán Rosa , Qin Guozheng , Posé David 
Published: January 2025

ABSTRACTRipening Inducing Factor (RIF) is a key NAC transcription factor regulating strawberry fruit ripening. Previous studies usingRIF-RNAi and overexpression lines inFragaria × ananassaand CRISPR knock-out lines inF. vescahave established the role of RIF in controlling ABA biosynthesis and signaling, cell wall remodeling, and secondary metabolism.In this study, we deciphered FaRIF’s transcriptional regulatory network by combining ChIP-seq-based identification of its direct targets with an analysis ofFaRIF-RNAi transcriptome data. These analyses revealed FaRIF’s direct role in multiple aspects of strawberry fruit ripening, including the regulation of ripening-related transcription factors, phytohormone content and signaling, primary and secondary metabolism, and cell wall degradation. Additionally, using the TurboID-based proximity labeling approach, we have identified FaRIF interactors, including proteins involved in mRNA and protein homeostasis, as well as several NAC transcription factors. Among these, FaNAC034 was found to synergistically enhance FaRIF’s transcriptional activity.This integrative analysis, combining transcriptome analysis,in vivoChIP-seq, and proximity labeling, broadens our knowledge of FaRIF-mediated transcriptional networks and interaction partners, providing valuable insights into the molecular mechanisms underlying strawberry fruit ripening regulation by this transcription factor.
Mechanisms of dexamethasone-induced bone toxicity in developing bone: a single-cell perspective
Authors: Warmink Kelly , Lijnzaad Philip , Vermaat Tristan C.W. , Jansen Lisa , van Gend Marloes C.C. , Zhang Baojie , Balwierz Aleksandra , Proost Natalie , van de Ven Marieke , Merks Johannes H.M. , Margaritis Thanasis , Janda Claudia Y. 
Published: January 2025

AbstractGlucocorticoids, such as dexamethasone, are essential for treating severe childhood conditions, including cancer, organ transplantation, and inflammatory disorders. However, their long-term use can impair bone development, posing risks to pediatric bone health, which is vital for lifelong skeletal integrity. A mechanistic insight on how glucocorticoids negatively impact bone could improve decision-making in patient care to improve the quality of life for pediatric cancer patients and survivors. In this study, we aimed to elucidate the molecular mechanisms underlying dexamethasone-induced bone toxicity in developing bones using single-cell transcriptomics. We treated skeletally immature C57BL/6JRj mice with dexamethasone for 28 days, and assessed the bone architecture with micro-computed tomography, and characterized bone and bone marrow cells from the femurs using single-cell RNA sequencing. Our findings revealed a marked reduction in osteoblast and chondrocyte cell populations and impaired function of pre-osteoblasts. Additionally, dexamethasone adversely affected B cell subsets, significantly depleting early B cell progenitors while allowing some further developed immature B cells to persist. These cellular changes were accompanied by reduced longitudinal bone growth, compromised bone architecture, and increased bone fragility at the highest doses of dexamethasone. Interestingly, unlike observations in adults, dexamethasone did not enhance osteoclast activity in our model. Overall, our study suggests that the adverse effects of dexamethasone on bone development are primarily due to its impact on osteoblastic, chondroblastic and B cell lineages, disrupting the critical signaling crosstalk between the cells necessary for bone development and hematopoiesis.Layman summaryGlucocorticoids, like dexamethasone, are vital for treating severe childhood illnesses but can harm bone development when used long-term. This study investigated how dexamethasone affects bone health in young mice. Using advanced techniques, we found that dexamethasone reduced key bone-building cells (osteoblasts and chondrocytes) and weakened their function. It also disrupted immune cell development in the bone marrow, especially early B cells. These changes led to weaker, more fragile bones without increasing bone breakdown, unlike in adults. The findings highlight the need to carefully balance treatment benefits and risks for children to protect their bone health and overall well-being.
2D, or not 2D? Investigating Vertical Signal Integrity of Tissue Slices
Authors: Tiesmeyer Sebastian , Müller-Bötticher Niklas , Malt Alexander , Long Brian , Marco-Salas Sergio , Kiessling Paul , Horn Paul , Guillot Adrien , Kuemmerle Louis B , Ma Leyao , Tacke Frank , Theis Fabian , Kuppe Christoph , Nillson Mats , Eils Roland , Ishaque Naveed 
Published: January 2025

AbstractImaging-based spatially resolved transcriptomics can localise transcripts within cells in 3D. Cell segmentation precedes assignment of transcripts to cells and annotation of cell function. However, cell segmentation is usually performed in 2D, thus unable to deal with spatial doublets arising from overlapping cells, resulting in segmented cells containing transcripts originating from multiple cell-types. Here we present a computational tool called ovrlpy that identifies overlapping cells, tissue folds and inaccurate cell-segmentation.
A fast numerical integration scheme for clonal expansion processes on graphs
Authors: Paterson Chay , Gao Miaomiao , Hellier Joshua , Luebeck Georg , Wedge David , Bozic Ivana 
Published: January 2025

AbstractCompound birth-death processes are widely used to model the age-incidence curves of many cancers [1]. There are efficient schemes for directly computing the relevant probability distributions in the context of linear multi-stage clonal expansion (MSCE) models [2]. However, these schemes have not been generalised to models on arbitrary graphs, forcing the use of either full stochastic simulations or mean-field approximations, which can become inaccurate at late times or old ages [3, 4]. Here, we present a numerical integration scheme for directly computing survival probabilities of a first-order birth-death process on an arbitrary directed graph, without the use of stochastic simulations. As a concrete application, we show that this new numerical method can be used to infer the parameters of an example graphical model from simulated data.
Clustering Digestive Tract Tumors Using Transcriptomic and Mutation Data
Authors: Tally Dwayne G. , Bombina Polina , Reed Jake , Kinne Jeffrey , Abruzzo Lynne V. , Coombes Kevin R. , Abrams Zachary B. 
Published: January 2025

AbstractDigestive tract cancers, like most other cancers, are usually categorized based on cell or tissue of origin. Molecular clustering based on the transcriptome often produces the same classification. We developed a new method, Newmanization, to reduce underlying tissue signals from transcriptomic analysis. To test our method, we downloaded data on 1635 samples of digestive tract cancers from The Cancer Genome Atlas. The available data includes transcriptomic data, by RNA-Seq, as well as binary mutation allele frequency data by whole exome sequencing. We compared, using silhouette widths and visualization by dimension reduction plots, the effectiveness of Newmanized transcriptome and mutation data to separate digestive tract cancers. The Newmanized transcriptome clusters have clearer separation and larger average silhouette widths. Feature analysis of each cluster for Newmanized transcriptomic data and mutation data revealed that clusters determined with Newmanized data contained more mRNAs present at higher frequencies than clusters defined by mutation data. This suggests that the Newmanized method holds great potential for advancing personalized transcriptomic medicine.
Condensate screening identifies YM155 as β-catenin condensate inhibitor in colorectal cancer
Authors: Manzato Caterina , Sirati Nafiseh , Knol Bronwen A. , Kuiken Hendrik J. , Morris Ben , Fleming Cassio , Beijersbergen Roderick L. , Schuijers Jurian 
Published: January 2025

ABSTRACTβ-catenin is a transcriptional cofactor crucial in forming biomolecular condensates that drive WNT target gene transcription. Its pathological accumulation in the nucleus is a critical step in WNT-driven cancers, such as colorectal cancer. Disrupting β-catenin condensates is a promising cancer treatment strategy, but no clinical applications currently exist. In this study, we developed a Nanobody Enabled Condensate Observation (NECO) screening platform to identify small molecules that modulate β-catenin condensates. The platform revealed compounds that either enhanced or reduced β-catenin transcriptional condensates. Among them, YM155 (sepantronium bromide) was identified as an inhibitor, disrupting essential weak interactions for condensate formation. This disruption effectively inhibits the proliferation of WNT-driven colorectal cancer organoids. These findings show that the NECO platform can identify small molecules that target β-catenin condensates and suggest YM155 as a potential anti-cancer agent for colorectal cancer.
It takes two: Aberrant repair and low-grade inflammation characterizes bronchiolitis obliterans syndrome after lung transplantation in serum proteomic analysis
Authors: van der Ploeg Eline A. , Faiz Alen , Teitsma Greta J. , Brotons Alejandro Sánchez , Govorukhina Natalia , Sand Jannie M.B. , Leeming Diana J. , Melgert Barbro N. , Horvatovich Peter , Burgess Janette K. , Tji Gan C. 
Published: January 2025

AbstractAimThe obstructive phenotype of chronic lung allograft dysfunction, bronchiolitis obliterans syndrome (BOS), is diagnosed after lung transplantation (LTx) when irreversible airway obstruction is already present. This study aimed to investigate the fibrotic response and inflammation signals in serum of BOS patients.MethodsLTx patients transplanted at the University Medical Center Groningen between 2004 and 2017 were screened. Nineteen patients with BOS were selected and matched to 19 non-BOS patients. Only patients for whom lung function and longitudinal serum samples post-LTx were available were included. Enzyme-linked immunosorbent assays were performed for neoepitopes of collagen types I, III, and VI and osteoprotegerin (OPG) in serum. Additionally, serum samples were analyzed by label free liquid chromatography with tandem mass spectrometry proteomics analysis.ResultsCollagen neoepitopes did not differ significantly between BOS and non-BOS patients at any timepoint. OPG was significantly higher in non-BOS compared to BOS six months before BOS onset (p<0.04). In proteomics analysis, proteins indicating cell repair and proliferation, namely human type II keratin-6 and centromere protein F (both FDR<0.1), were significantly lower three months before BOS onset in BOS compared to non-BOS patients. C-reactive protein (FDR<0.05) and SERPINA3 (FDR<0.05) amongst others, were higher in end-stage BOS compared to non-BOS patients.ConclusionDifferences in expression of proteins that reflect the complex interplay between fibrosis and inflammation in BOS were identified. These proteins should be investigated and validated in larger cohorts and may aid in expanding knowledge about the development of BOS.
Comparative analysis ofXenopusmesonephric transcriptomics: Conservation of the developmental lineage of nephron stages
Authors: Corkins Mark E. , Romero-Mora Adrian , Achieng MaryAnne A. , Lindström Nils O. , Miller Rachel K. 
Published: January 2025

AbstractThe mammalian kidney develops in three sequential stages referred to as the pronephros, mesonephros, and metanephros, each developing from the preceding form. All three phases of kidney development utilize epithelized tubules called nephrons, which function to take in filtrate from the blood or coelom and selectively reabsorb solutes the organism needs, leaving waste products to be excreted as urine. The pronephros are heavily studied in aquatic organisms such as zebrafish and Xenopus, as they develop quickly and are functional. The metanephros is a preferred mammalian kidney model, as it best recapitulates human disease. However, very little is known about the mesonephric stage of kidney development in any organism. The pronephros extend to form the mesonephric duct, which ultimately develops into the Wolffian duct in male amniotes. Meanwhile, in organisms that lay their eggs in aquatic environments, the mesonephric kidney is the final form that is generated. Therefore, further understanding of the development and physiology of these kidneys will provide insight into the urogenital system as well as its evolutionary conservation. To gain a better understanding of its structure and cell types, we analyzed the developing mesonephros by in situ and single-cell mRNA sequencing of cells the that make up the developing mesonephros. By comparing these data to those published for theXenopuspronephros and mammalian metanephros, we were able to evaluate nephron conservation between the three kidney stages.