Chromosome Res. 2025 Apr 4;33(1):5. doi: 10.1007/s10577-025-09764-4.

ABSTRACT

DNA topoisomerase II beta (TOP2B) is required for correct execution of certain developmental transcriptional programs and for signal-induced transcriptional activation, including transcriptional activation by nuclear hormone ligands such as retinoic acid. In addition, TOP2B is enriched at genomic locations occupied by CCCTC-Binding factor (CTCF) and cohesin (RAD21). suggesting a role in chromosome looping and/or establishing or maintaining aspects of chromosome 3D structure. This led us to investigate the effect of TOP2B inactivation on patterns of intra- and inter- chromosomal interaction that reflect the 3D architecture of the genome. Using the retinoic acid responsive SH-SY5Y neuroblastoma cell line model, we had previously demonstrated many gene expression changes upon retinoic acid treatment and upon deletion of TOP2B. We report here that these expression changes in TOP2B null versus WT cells are accompanied by surprisingly subtle changes in local chromosome organization. However, we do observe quantitative changes in chromosome organization on a megabase scale. First, lack of TOP2B did affect compartment strength changes that occur upon ATRA treatment. Second, we observe an excess of very long-range interactions, reminiscent of interactions seen in mitotic cells, suggesting the possibility that in the absence of TOP2B some mitotic interactions are retained. Third, we see quantitative changes in centromere-telomere interactions, again indicating global changes at the megabase and chromosome level. These data support the surprising conclusion that TOP2B has only a minor role in chromosome dynamics and organization.

PMID:40183884 | DOI:10.1007/s10577-025-09764-4

Immunology. 2025 Apr 4. doi: 10.1111/imm.13923. Online ahead of print.

ABSTRACT

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD) and irritable bowel syndrome (IBS) are distinct gastrointestinal disorders. Mycobacterium avium subspecies paratuberculosis (MAP) is implicated in IBD pathogenesis, while the roles of human endogenous retroviruses (HERVs) are under investigation. We aimed (a) to investigate whether the levels of humoral response to MAP-3865c, HERV-K envelope and HERV-W envelope against the epitopes in IBD/IBS patients; (b) to determine the frequency of micronuclei in IBD patients and (c) to evaluate the possible correlation between genomic damage and humoral response. This study investigates antibody titres against MAP 3865c, HERV-K env and HERV-W env in plasma from 102 IBD, 20 IBS patients and 92 healthy controls (HCs). Micronuclei (MNi) frequency in IBD patients is assessed, correlating with humoral responses and patient genotype profiles. IBD patients exhibited elevated antibody responses to MAP 3865c, with those carrying the GA genotype for TNF-α showing higher anti-MAP 3865c IgG levels. A significant positive correlation was observed between MNi frequency and the humoral response against MAP 3865c in IBD patients. Higher antibody responses to HERV-K env were detected in both IBD and IBS patients compared to HCs, with significant positive correlations found between MAP 3865c and HERV-K env peptide responses in IBD patients. HERV-W env antibody levels were higher in IBS patients than in HCs. Our findings highlight the association between UC and CD and immune responses targeting MAP and HERV-Kenv. Specific genetic profiles may exacerbate inflammation, potentially amplifying genetic damage observed in IBD patients, as indicated by MNi frequencies.

PMID:40183428 | DOI:10.1111/imm.13923

Front Genet. 2025 Mar 20;16:1440364. doi: 10.3389/fgene.2025.1440364. eCollection 2025.

ABSTRACT

BACKGROUND: Coronary heart disease (CHD) represents a substantial global burden in terms of morbidity and mortality. Understanding the causal relationships between serum metabolites and CHD can provide a crucial understanding of disease mechanisms and potential therapeutic targets.

METHODS: We conducted a Mendelian randomization (MR) approach to explore the potential causal associations between serum metabolites and CHD risk. The primary analysis employed the inverse variance weighted (IVW) method, supplemented by additional analyses, including MR-Egger, weighted median, weighted mode, and sample mode. To bolster the robustness and reliability of our findings, we performed sensitivity analyses, which included evaluating, horizontal pleiotropy and leave-one-out analysis. Additionally, pathway enrichment analysis was conducted.

RESULTS: We identified 15 known and 11 unknown metabolites with potential associations to CHD. Among the known, six displayed protective effects, while nine were identified as risk factors. Notably, many of these metabolites are closely related to mitochondrial function, which was further supported by pathways and enrichment analysis. Using multiple statistical models to ensure robust results, we unveiled a significant association between hexadecanedioate, a palmitoyl lipid metabolized in mitochondria, and a ∼18% reduced risk of CHD (OR = 0.82, 95%CI: 0.72-0.93).

CONCLUSION: MR analysis revealed 6 protective molecules, 9 hazardous metabolites associated with CHD. Many of these known metabolites are closely link to mitochondrial function, suggesting a critical role of mitochondria in CHD development. In particular, hexadecanedioate, an essential component for mitochondrial energy production, was inversely associated with CHD risk. This suggests that mitochondrial function, and specifically the role of hexadecanedioate, may be pivotal in the development and progression of CHD.

PMID:40182922 | PMC:PMC11965349 | DOI:10.3389/fgene.2025.1440364

Patterns (N Y). 2025 Feb 25;6(3):101184. doi: 10.1016/j.patter.2025.101184. eCollection 2025 Mar 14.

ABSTRACT

Immunotherapies, including checkpoint blockade and chimeric antigen receptor T cell (CAR-T) therapy, have revolutionized cancer treatment; however, many patients remain unresponsive to these treatments or relapse following treatment. CRISPR screenings have been used to identify novel single gene targets that can enhance immunotherapy effectiveness, but the identification of combinational targets remains a challenge. Here, we introduce a computational approach that uses sgRNA set enrichment analysis to identify cancer-intrinsic paralog pairs for enhancing immunotherapy using genome-wide screens. We have further developed an ensemble learning model that uses an XGBoost classifier and incorporates features to predict paralog gene pairs that influence immunotherapy efficacy. We experimentally validated the functional significance of these predicted paralog pairs using CRISPR double knockout (DKO). These data and analyses collectively provide a sensitive approach to identifying previously undetected paralog gene pairs that can significantly affect cancer immunotherapy response, even when individual genes within the pair have limited effect.

PMID:40182179 | PMC:PMC11963098 | DOI:10.1016/j.patter.2025.101184

F1000Res. 2025 Jan 6;14:37. doi: 10.12688/f1000research.160371.1. eCollection 2025.

ABSTRACT

TAF15 (TATA-box binding protein-associated factor 15) is a member of the FET protein family, known for their roles in transcriptional regulation and RNA metabolism. Here we have characterized five TAF15 commercial antibodies for western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.

PMID:40182019 | PMC:PMC11966097 | DOI:10.12688/f1000research.160371.1

BMC Oral Health. 2025 Apr 3;25(1):476. doi: 10.1186/s12903-025-05847-0.

ABSTRACT

BACKGROUND: Spleen-stomach damp-heat syndrome is one of the most common syndrome types in periodontitis from traditional Chinese medicine theory. However, its pathological mechanism is still uncertain. Tissue metabolism is driven by microbes in the host and its microenvironment. Hostmicrobe-metabolism is an interacting and closely related complex. Lipid metabolomics can find lipid metabolites in disease or healthy state, which is beneficial to explore the metabolic process and change mechanism of lipids that may be involved in organisms in healthy or disease state from the perspective of systems biology.

METHODS: In this study, 10 patients in the periodontitis group (CP), 10 patients in the periodontitis with spleen-stomach dampness-heat syndrome group (SP) and 10 patients in the healthy group (H) were recruited for participation, whose unstimulated saliva was collected. The differential metabolites between the groups were detected by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and screened out based on the variable importance in projection (VIP) combined with the P-value and fold change (FC) value of univariate analysis. Finally, KEEG pathway enrichment analysis was performed on these differential metabolites.

RESULTS: A total of 1131 metabolites were detected in saliva in this study. 497 metabolites were significantly up-regulated in periodontitis, mainly plasma-membrane-associated lipids, unsaturated fatty acids and oxidized lipids. Compared with the healthy group, the lipid metabolism pathways of periodontitis with or without spleen-stomach dampness-heat syndrome group were mainly characterized by significant enrichment of glycerophospholipid metabolism and unsaturated fatty acid metabolism such as arachidonic acid metabolism.

CONCLUSION: Compared with periodontally healthy patients, periodontitis with or without spleen-stomach dampness-heat syndrome can cause changes in lipid metabolism in saliva samples of patients. These metabolites are mainly plasma membrane lipids, unsaturated fatty acids and oxidized lipids quality. These lipids may be potential biomarkers of periodontitis. The downstream metabolites of unsaturated fatty acids in the saliva samples of patients with periodontitis and spleen-stomach dampness-heat syndrome were abnormal, and the oxidized lipid (±)5-HETE was significantly abnormal. We speculate that this may be related to the increased state of oxidative stress in saliva samples in disease states.

PMID:40181453 | DOI:10.1186/s12903-025-05847-0

Neurobiol Dis. 2025 Apr 1:106888. doi: 10.1016/j.nbd.2025.106888. Online ahead of print.

ABSTRACT

Epilepsy is a severe common neurological disease affecting all ages. Epilepsy with onset before the age of 5 years, designated early-onset epilepsy (EOE), is of special importance. According to previous studies, genetic factors contribute significantly to the pathogenesis of EOE that remains unclear and must be explored. So, a list of 229 well-selected EOE-associated genes expressed in the brain was created for the investigation of genetic factors and molecular mechanisms involved in its pathogenesis. Enrichment analysis showed that among significant pathways were nicotine addiction, GABAergic synapse, synaptic vesicle cycle, regulation of membrane potential, cholinergic synapse, dopaminergic synapse, and morphine addiction. Performing an integrated analysis as well as protein-protein interaction network-based approaches with the use of GO, KEGG, ClueGO, cytoHubba and 3 network metrics, 12 hub genes were identified, seven of which, CDKL5, GABRA1, KCNQ2, KCNQ3, SCN1A, SCN8A and STXBP1, were identified as key genes (via Venn diagram analysis). These key genes are mostly enriched in SNARE interactions in vesicular transport, regulation of membrane potential and synaptic vesicle exocytosis. Clustering analysis of the PPI network via MCODE showed significant functional modules, indicating also other pathways such as N-Glycan biosynthesis and protein N-linked glycosylation, retrograde endocannabinoid signaling, mTOR signaling and aminoacyl-tRNA biosynthesis. Drug-gene interaction analysis identified a number of drugs as potential medications for EOE, among which the non-FDA approved drugs azetukalner (under clinical development), indiplon and ICA-105665 and the FDA approved drugs retigabine, ganaxolone and methohexital.

PMID:40180227 | DOI:10.1016/j.nbd.2025.106888

Mol Cell Proteomics. 2025 Apr 1:100960. doi: 10.1016/j.mcpro.2025.100960. Online ahead of print.

ABSTRACT

Nsun5 assumes a pivotal role in the regulation of RNA methylation, and its deficiency has been linked to the advancement of hepatocellular carcinoma, gliomas, tetralogy of Fallot, cognitive deficits in Williams-Beuren syndrome (WBS), and brain development. This underscores Nsun5's significant involvement in the nervous system. In this study, we present evidence of Nsun5's influence on the structure of the primary somatosensory cortex. Through comprehensive multi-omics analyses, we unveil a spectrum of systematically altered genes and proteins, collectively engaged in the orchestration of translation, neurotransmitter metabolism, nerve conduction, synaptic transmission, and other functions. Notably, there are discernible changes in molecules associated with pain sensation, strongly indicating that Nsun5 deficiency undermines pain-related behavior. This study establishes a clear link between Nsun5 deficiency and transcriptional and proteomic changes, as well as neurotransmitter expression within the primary somatosensory cortex, and uncovers its novel role in impaired pain perception.

PMID:40180179 | DOI:10.1016/j.mcpro.2025.100960

Biotechnol Adv. 2025 Apr 1:108574. doi: 10.1016/j.biotechadv.2025.108574. Online ahead of print.

ABSTRACT

Human settlements on the Moon, crewed missions to Mars and space tourism will become a reality in the next few decades. Human presence in space, especially for extended periods of time, will therefore steeply increase. However, despite more than 60 years of spaceflight, the mechanisms underlying the effects of the space environment on human physiology are still not fully understood. Animals, ranging in complexity from flies to monkeys, have played a pioneering role in understanding the (patho)physiological outcome of critical environmental factors in space, in particular altered gravity and cosmic radiation. The use of animals in biomedical research is increasingly being criticized because of ethical reasons and limited human relevance. Driven by the 3Rs concept, calling for replacement, reduction and refinement of animal experimentation, major efforts have been focused in the past decades on the development of alternative methods that fully bypass animal testing or so-called new approach methodologies. These new approach methodologies range from simple monolayer cultures of individual primary or stem cells all up to bioprinted 3D organoids and microfluidic chips that recapitulate the complex cellular architecture of organs. Other approaches applied in life sciences in space research contribute to the reduction of animal experimentation. These include methods to mimic space conditions on Earth, such as microgravity and radiation simulators, as well as tools to support the processing, analysis or application of testing results obtained in life sciences in space research, including systems biology, live-cell, high-content and real-time analysis, high-throughput analysis, artificial intelligence and digital twins. The present paper provides an in-depth overview of such methods to replace or reduce animal testing in life sciences in space research.

PMID:40180136 | DOI:10.1016/j.biotechadv.2025.108574

Int J Biol Macromol. 2025 Apr 1:142469. doi: 10.1016/j.ijbiomac.2025.142469. Online ahead of print.

ABSTRACT

Pancreatic cancer (PC) is one of the deadliest cancers, characterized by a poor prognosis. Currently, there are no screening programs for the early detection of PC, and existing diagnostic methods are primarily limited to high-risk individuals. Biomarkers such as CA19-9 have not significantly improved early diagnosis, making the identification of new potential biomarkers crucial for routine clinical practice. Among the candidate biomarkers, miRNAs have been most extensively studied due to their role in regulating gene expression (either as oncomiRs or tumor suppressor miRNAs) and their potential for minimally invasive analysis through liquid biopsy techniques. This review aims to summarize the current literature on blood-circulating miRNAs and their diagnostic value in PC detection, considering the context of CA19-9 and benign pancreatic diseases. The data from the collected studies were curated through both statistical and bioinformatics analyses to identify the most promising miRNAs with optimal diagnostic accuracy for PC detection and to assess their role in the molecular processes leading to tumor development.

PMID:40180095 | DOI:10.1016/j.ijbiomac.2025.142469

Med. 2025 Mar 27:100642. doi: 10.1016/j.medj.2025.100642. Online ahead of print.

ABSTRACT

BACKGROUND: Adverse drug events (ADEs) are the fourth leading cause of death in the US and cost billions of dollars annually in increased healthcare costs. However, few machine-readable databases of ADEs exist, limiting our capacity to study drug safety on a broader, systematic scale. Recent advances in natural language processing methods, such as BERT models, present an opportunity to accurately extract relevant information from unstructured biomedical text.

METHODS: We fine-tune a PubMedBERT model to extract ADE terms from text in FDA Structured Product Labels for prescription drugs. Here, we present OnSIDES (on-label side effects resource), a compiled, machine-friendly database of drug-ADE pairs generated with this method. We further utilize this method to extract pediatric-specific ADEs, serious ADEs from labels' "Boxed Warnings" section, and ADEs from drug labels of other major nations-the UK, the European Union, and Japan-to build a complementary OnSIDES-INTL database. To present OnSIDES' potential applications, we leverage the database to predict novel drug targets and indications, analyze enrichment of ADEs across drug classes, and predict novel ADEs from chemical compound structures.

FINDINGS: We achieve an F1 score of 0.90, AUROC of 0.92, and AUPR of 0.95 at extracting ADEs from the labels' "Adverse Reactions" section. OnSIDES contains over 3.6 million drug-ADE pairs for 3,233 unique drug ingredient combinations extracted from 47,211 labels.

CONCLUSIONS: OnSIDES can be used as a comprehensive resource to study and enhance drug safety.

FUNDING: R35GM131905 to N.P.T.; T32GM145440 to H.Y.C.; and T15LM007079 to U.G., M.Z., and K.L.B.

PMID:40179876 | DOI:10.1016/j.medj.2025.100642

Eur J Obstet Gynecol Reprod Biol. 2025 Mar 30;310:113947. doi: 10.1016/j.ejogrb.2025.113947. Online ahead of print.

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder; however, the current guidelines do not adequately address the metabolic aspect. By gathering patients' perspectives, this survey investigates potential issues with the current diagnostic process to identify key points that need addressing in the future.

METHOD: A survey comprising of 49 multiple-choice question was distributed to members of the Italian PCOS community NoiPCOS, including topics such as demographics, PCOS diagnosis experience, symptom management, quality of life, and access to information about PCOS.

RESULTS: 769 women aged 18-40 responded to the survey. 72.2% of responders were employed and perceived their socio-economic status as "good". PCOS diagnosis was primarily obtained in adolescence (35.1%) or late adolescence (33.6 %), with the most common symptoms being polycystic ovaries (85.8%), irregular menses (80.4%), and hirsutism (64.1%). Moreover, PCOS symptoms were seen to severely impact the mental health for 64.7% of responders. Treatments prescribed for PCOS were diet (49.5%), exercise (46.9%), metformin (27.6%), hormonal contraception (26.4%), and myo-inositol and D-chiro-inositol (25.2%). When accessing information about PCOS, women often relied on unofficial sources (i.e. internet sources) rather guidance from their physician.

CONCLUSION: Findings of this survey highlight that a thorough update of PCOS diagnostic criteria is required, which should consider the endocrine and metabolic aspects of the syndrome. Such revision should enable a more accurate, precise diagnosis that translates to effective therapy. Finally, any reconsideration of the PCOS guidelines should increase the perceived reliability by patients of medical care, reducing the communication gap between specialists and patients.

PMID:40179473 | DOI:10.1016/j.ejogrb.2025.113947

J Am Soc Mass Spectrom. 2025 Apr 3. doi: 10.1021/jasms.4c00467. Online ahead of print.

ABSTRACT

Targeted quantification metabolomics provides dynamic insights across various domains within the life sciences. Nevertheless, maintaining high-quality data obtained through liquid chromatography-mass spectrometry presents ongoing challenges. It is essential to develop normalization methods to correct for unwanted variations in metabolomic profiling such as batch effects and analytical drift. In this study, we assessed the normalization efficacy of Norm ISWSVR in targeted quantification metabolomics by comparing it with IS normalization and SERRF normalization. Consequently, Norm ISWSVR demonstrated exceptional efficacy in mitigating batch effects and reducing the relative standard deviation of quality control samples, in addition to correcting signal drift. Following normalization with Norm ISWSVR, the number of metabolites suitable for quantification increased with high precision. Collectively, Norm ISWSVR proves to be a robust and reliable method for enhancing data quality in targeted metabolomics, establishing itself as a promising approach for metabolomics research.

PMID:40179246 | DOI:10.1021/jasms.4c00467

Science. 2025 Apr 4;388(6742):52-59. doi: 10.1126/science.ads7951. Epub 2025 Apr 3.

ABSTRACT

Most phenotype-associated genetic variants map to noncoding regulatory regions of the human genome, but their mechanisms remain elusive in most cases. We developed a highly efficient strategy, Perturb-multiome, to simultaneously profile chromatin accessibility and gene expression in single cells with CRISPR-mediated perturbation of master transcription factors (TFs). We examined the connection between TFs, accessible regions, and gene expression across the genome throughout hematopoietic differentiation. We discovered that variants within TF-sensitive accessible chromatin regions in erythroid differentiation, although representing <0.3% of the genome, show a ~100-fold enrichment for blood cell phenotype heritability, which is substantially higher than that for other accessible chromatin regions. Our approach facilitates large-scale mechanistic understanding of phenotype-associated genetic variants by connecting key cis-regulatory elements and their target genes within gene regulatory networks.

PMID:40179192 | DOI:10.1126/science.ads7951

J Agric Food Chem. 2025 Apr 3. doi: 10.1021/acs.jafc.5c00568. Online ahead of print.

ABSTRACT

Natural acylsucrose, often found in the glandular trichomes of Solanaceae plants, has potential applications in many industries, including food, cosmetics, and pharmaceuticals. In this study, we engineered an Escherichia coli strain to complete the biosynthesis of acylsucroses through whole-cell transformation. Using acylsucrose acyltransferases and CoA ligases, acylsucroses, including monoacylsucrose S1:5 ("S" represents an acylsucrose backbone, the number before the colon indicates the number of acyl chains, and the number after the colon indicates the sum of carbons in all acyl chains), diacylsucrose S2:10, triacylsucrose S3:14, and triacylsucrose S3:15 were synthesized from the substrate sucrose and short branched-chain fatty acids by the engineered E. coli EcoSE07, of which S3:15 was the primary product. Several strategies were applied to improve acylsucrose production, including codon optimization, constitutive promoter replacement, and serial resting cell assays. The use of fed-batch fermentation with an engineered E. coli strain of EcoSE22 containing a constitutive promoter further improved the production of acylsucroses. Serial resting cell assays with an optical density of 50 at 600 nm significantly increased the production of acylsucroses S3:15 and S2:10. These findings will facilitate the synthesis of natural acylsucroses through whole-cell transformations and provide the potential for future industrial applications.

PMID:40179051 | DOI:10.1021/acs.jafc.5c00568

Semin Immunopathol. 2025 Apr 3;47(1):24. doi: 10.1007/s00281-025-01047-8.

ABSTRACT

Galectin-1 (Gal-1), a member of the β-galactoside-binding soluble lectin family, is a double-edged sword in immunity. On one hand, it plays a crucial role in regulating diverse immune cell functions, including the apoptosis of activated T cells. These processes are key in resolving inflammation and preventing autoimmune diseases. On the other hand, Gal-1 has significant implications in cancer, where tumor cells and the tumor microenvironment (TME) (e.g., tumor-associated fibroblasts, myeloid-derived suppressor cells) secrete Gal-1 to evade immune surveillance and promote cancer cell growth. Within the TME, Gal-1 enhances the differentiation of tolerogenic dendritic cells, induces the apoptosis of effector T cells, and enhances the proliferation of regulatory T cells, collectively facilitating tumor immune escape. Therefore, targeting Gal-1 holds the potential to boost anti-tumor immunity and improve the efficacy of cancer immunotherapy. This review provides insights into the intricate role of Gal-1 in immune cell regulation, with an emphasis on T cells, and elucidates how tumors exploit Gal-1 for immune evasion and growth. Furthermore, we discuss the potential of Gal-1 as a therapeutic target to augment current immunotherapies across various cancer types.

PMID:40178639 | DOI:10.1007/s00281-025-01047-8

Plant Dis. 2025 Apr 3. doi: 10.1094/PDIS-02-25-0251-PDN. Online ahead of print.

ABSTRACT

In July 2024, a pooled leaf sample (D760/24) was collected from several plants of three watermelon cultivars (Citrullus lanatus cvs. Crimson Sweet, Asahi Miyako Hybrid F1 and Top Gun) grown in an open field (approx. 0.5ha) in Dombrava, Slovenia. The plants which were included in the pooled sample showed virus-like symptoms, such as leaf mosaic, wilting and necrosis (eXtra Supplementary material Fig. S1). The disease incidence was estimated at 10%. DNA and RNA were extracted following Mehle et al. (2013) and RNeasy Plant Mini Kit (Qiagen, Germany) protocols, respectively. The sample was tested positive by reverse-transcription (RT)-PCR for watermelon crinkle leaf-associated virus 1 (WCLaV-1) and WCLaV-2 ( Hernandez et al. 2021) and negative for other viruses (details on viruses tested and primers used are available in eXtra Table S1). The obtained amplicons of expected sizes of WCLaV-1 and WCLaV-2 movement protein (MP) and RNA-dependent RNA polymerase (RdRp) genes (eXtra Fig S2) were then subjected to Sanger sequencing (Eurofins Genomics, Germany) and BLAST analysis. The MP (PQ570004, PQ570006) and the RdRp (PQ570005, PQ570007) sequences exhibited 100% identity with multiple accessions of WCLaV-1, such as PP792977 and PP792976, and WCLaV-2, such as LC636073 and LC636074. Illumina high-throughput sequencing (HTS, Novogene, Germany, NovaSeq X Plus, PE150) identified WCLaV-1 (PV012703-04) and WCLaV-2 (PV012705-06) reads, along with cucumis melo amalgavirus 1 (CmAV1, PV012707) and solanum nigrum ilarvirus 1 reads (insufficient reads to reconstruct genome segments, it may originate from pollen contamination of nearby infected plants in the field (Rivarez et al. 2023)). HTS data were analyzed in CLC Genomics Workbench v. 24 (Qiagen, USA) using the pipeline by (Pecman et al. 2022). Consensus genome sequences were reconstructed by iterative read mapping to the most similar reference sequence of the virus obtained from NCBI GenBank. To check for WCLaVs in watermelon seeds sold in Slovenia, we tested five seed samples from Sugar Baby, Crimstar F1, and Crimson Sweet (three lots) by RT-PCR. We also tested four leaf samples from plants grown from these seeds at 3-5 true leaves stage. Both viruses were found in all seed and leaf extracts. However, mechanical inoculations with the sap of two samples (plants grown from infected seed sample and sample D760/24) on several commonly used indicator plants including Chenopodium quinoa, Capsicum annuum, Nicotiana clevelandii, Nicotiana glutinosa, Nicotiana benthamiana, Nicotiana tabacum cv. White Burley, Nicotiana rustica, Datura stramonium, Cucurbita pepo cv. Bianca di Trieste, and Cucurbita maxima did not result in their infection. Retrospective analyses of our HTS data of two watermelon and 84 other cucurbits samples from previous years showed WCLaV-1 and WCLaV-2 reads in two pooled samples (containing equal amount of RNA of each sample): one from 2018 and another from 2019. RT-PCR confirmed the presence of WCLaVs only in watermelons. The pool from 2018 was sequenced at GATC (Germany, NovaSeq 6000 S2, PE 150) and from 2019 in-house using Oxford Nanopore Technologies (UK, MinION Mk1B device, SQK-PCS108, R9 flow cell). All HTS reads are deposited in the NCBI Short Reads Archive (PRJNA1202089). This is the first report of WCLaV-1 and WCLaV-2 in Slovenia and Europe, the two viruses which were included to the Alert list of the European and Mediterranean Plant Protection Organization, due to limited knowledge about their epidemiology (EPPO 2023). Further research is necessary to determine the incidence of these viruses in Europe, elucidate their epidemiology, symptoms association and their potential impact on the production of watermelons in the region.

PMID:40178537 | DOI:10.1094/PDIS-02-25-0251-PDN

Plant Cell. 2025 Apr 3:koaf059. doi: 10.1093/plcell/koaf059. Online ahead of print.

ABSTRACT

The significance of research conducted on Arabidopsis thaliana cannot be overstated. This focus issue showcases how insights from Arabidopsis have opened new areas of biology and directly advanced our understanding of crops. Here, experts intimately involved in bridging between Arabidopsis and crops share their perspectives on the challenges and opportunities for translation. First, we examine the translatability of genetic modules from Arabidopsis into maize, emphasizing the need to publish well-executed translational experiments, regardless of outcome. Second, we highlight the landmark success of HB4, the first GM wheat cultivar on the market, whose abiotic tolerance is borne from direct translation and based on strategies first outlined in Arabidopsis. Third, we discuss the decades-long journey to engineer oilseed crops capable of producing omega-3 fish oils, with Arabidopsis serving as a critical intermediary. Fourth, we explore how direct translation of starch synthesizing proteins characterised in Arabidopsis helped uncover novel mechanisms and functions in crops, with potential valuable applications. Finally, we illustrate how shared molecular factors between Arabidopsis and barley exhibit distinct molecular wiring as exemplified in cuticular and stomatal development. Together, these vignettes underscore the pivotal role of Arabidopsis as a foundational model plant while highlighting the challenges of translating discoveries into field-ready, commercial cultivars with enhanced knowledge-based traits.

PMID:40178150 | DOI:10.1093/plcell/koaf059

Bioinform Adv. 2025 Mar 20;5(1):vbaf044. doi: 10.1093/bioadv/vbaf044. eCollection 2025.

ABSTRACT

SUMMARY: Modern biological research critically depends on public databases. The introduction and propagation of errors within and across databases can lead to wasted resources as scientists are led astray by bad data or have to conduct expensive validation experiments. The emergence of generative artificial intelligence systems threatens to compound this problem owing to the ease with which massive volumes of synthetic data can be generated. We provide an overview of several key issues that occur within the biological data ecosystem and make several recommendations aimed at reducing data errors and their propagation. We specifically highlight the critical importance of improved educational programs aimed at biologists and life scientists that emphasize best practices in data engineering. We also argue for increased theoretical and empirical research on data provenance, error propagation, and on understanding the impact of errors on analytic pipelines. Furthermore, we recommend enhanced funding for the stewardship and maintenance of public biological databases.

AVAILABILITY AND IMPLEMENTATION: Not applicable.

PMID:40177265 | PMC:PMC11964588 | DOI:10.1093/bioadv/vbaf044

Bioact Mater. 2025 Mar 19;49:437-455. doi: 10.1016/j.bioactmat.2025.02.008. eCollection 2025 Jul.

ABSTRACT

Peptide metabolites are emerging biomolecules with numerous possibilities in biomaterial-based regenerative medicine due to their inherent bioactivities. These small, naturally occurring compounds are intermediates or byproducts of larger proteins and peptides, and they can have profound effects, such as antiviral therapeutics, proangiogenic agents, and regenerative medicinal applications. This study is among the first to focus on using thymosin β4 protein-derived metabolites to pioneer novel applications for peptide metabolites in biomaterials. This study found that the novel peptide metabolite acetyl-thymosin β4 (amino acid 1-17) (Ac-Tβ1-17) exhibited significant protease inhibition activity against SARS-CoV-2, surpassing its precursor protein. Additionally, Ac-Tβ1-17 demonstrated beneficial effects, such as cell proliferation, wound healing, and scavenging of reactive oxygen species (ROS) in human umbilical vein endothelial cells (HUVEC). Integrating Ac-Tβ1-17 into a peptide-based scaffold facilitated cell growth and angiogenesis inside the scaffold and through gradual release into the surrounding environment. The Ac-Tβ1-17 peptide treatment induced significant biochemical responses in HUVEC, increasing Akt, ERK, PI3K, MEK, and Bcl-2 gene expression and proangiogenic proteins. Ac-Tβ1-17 peptide treatment showed similar results in ex vivo by enhancing mouse fetal metatarsal growth and angiogenesis. These findings highlight the potential of natural protein metabolites to generate biologically active peptides, offering a novel strategy for enhancing biomaterial compatibility. This approach holds promise for developing therapeutic biomaterials using peptide metabolites, presenting exciting prospects for future research and applications.

PMID:40177110 | PMC:PMC11964602 | DOI:10.1016/j.bioactmat.2025.02.008