Search Results (1,792)

Human remains detection (HRD) dogs are vital tools in forensic science and disaster response, but their training is limited by the restricted availability of human material. Synthetic odorants such as Sigma Pseudo™ formulations provide safer, standardized alternatives, yet current products reproduce only a fraction of the volatile organic compound (VOC) profile of decomposition. In particular, sulfur-containing volatiles, which are highly odor-active and consistently present in human remains, are often missing, reducing biological fidelity. Here, we integrate analytical chemistry with canine olfactory genetics and molecular biology to explain these limitations. Dogs possess one of the largest olfactory receptor (OR) repertoires among mammals, with high allelic diversity and specialized trace amine-associated receptors (TAARs) tuned to cadaveric amines. Together with olfactory binding proteins (OBPs) and ciliary signal transduction cascades, these molecular mechanisms highlight why incomplete VOC mixtures may fail to activate the full receptor network required for reliable odor imprinting. We propose the “sulfur gap hypothesis” and suggest hybrid training strategies combining improved synthetics with ethically sourced biological samples to enhance HRD dog performance. Full article

Transcription factors (TFs) are important gene transcription regulators involved in myriad functions such as development, metabolism, and stress response. TFs are found in all eukaryotes, with many families of TFs unique to plants and algae. Algae are of interest due to a wide range of novel metabolites, of which TFs play an important role in regulating their biosynthesis. In particular, the red algae (phylum Rhodophyta) are a source of several important metabolites that are a current focus of further research. However, to date, investigations of TF families in rhodophytes have been limited due to the relative lack of genomic resources available and the small number of in silico analyses of their TFs. In this study, we used genomic and transcriptomic data to identify rhodophyte TFs. We found that the general proportion of TFs in rhodophytes was overall consistent with previous research. However, for the first time in the rhodophyte class Florideophyceae, we report the presence of a putative TF within the trihelix TF (TTF) family, which are light-sensitive TFs associated with growth and stress response. In particular, we demonstrate evidence suggesting the presence of putative TTFs in three Asparagopsis taxiformis genomes, as well as in several other florideophyte assemblies. This was supported by analyses including Neighbour-Joining phylogeny, protein structure prediction, and motif analysis. In summary, this research reported the repertoire of TFs in rhodophyte algae across a much greater range than previously reported and identified putative TTFs in several algae from the class Florideophyceae. This opens an avenue for further research into the evolution of various TFs in early plants, as well as key regulatory factors in rhodophyte metabolism, though future research, such as functional characterisation, will be required to confirm these findings. Full article

Renalase, a flavin adenine dinucleotide (FAD)-dependent enzyme/hormone, has emerged as a molecule of significant interest in cardiovascular medicine since its discovery nearly two decades ago. Initially proposed as a catecholamine-degrading enzyme crucial for blood pressure regulation, its functional repertoire has expanded to include potential α-NAD(P)H oxidase/anomerase activity and roles as a signalling cytokine. This review synthesises the current understanding of renalase, encompassing its fundamental biology, intricate gene regulation by transcriptional factors, microRNAs, and physiological stimuli, and its implications in cardiovascular health and disease. A central focus is the critical appraisal of circulating renalase as a clinical biomarker. We critically evaluate findings from preclinical animal and cellular models related to atherosclerosis, heart failure, and blood pressure control. Furthermore, this review examines the extensive literature on RNLS gene polymorphisms and their associations with human cardiovascular phenotypes, alongside the complex and often context-dependent data regarding circulating renalase levels as a potential clinical biomarker in conditions such as hypertension, coronary artery disease, atrial fibrillation, and heart failure. While renalase shows context-specific promise, its multifaceted biology and the current methodological disparities limit its immediate clinical application. This review concludes by outlining a clear path forward, emphasising the need for standardised research and mechanistic studies to unlock the true diagnostic and therapeutic potential of renalase in CVD. Full article

Kalanchoe pinnata, commonly known as the “miracle plant” or “life plant”, is a succulent species traditionally used for various health conditions. Recent research investigations have intensified interest in this species due to its diverse repertoire of bioactive constituents, including flavonoids, alkaloids, triterpenes, and glycosides. These compounds have been associated with multiple therapeutic effects, notably antioxidant, anti-inflammatory, and antidiabetic activities. Although several studies have highlighted the positive effects of the extracts of K. pinnata on key factors contributing to the pathophysiology and complications of diabetes mellitus, a systematic overview focusing on the use of these extracts and their bioactive constituents in the management of the disease is lacking. This literature review summarizes the phytochemical composition, traditional uses, and recent scientific data supporting the antidiabetic potential of K. pinnata, with a particular focus on its effects on glycemic control, as well as inflammatory and oxidative homeostasis, toxicity, safety, and potential clinical implications. The phytochemical constituents discussed include quercetin, kaempferol, apigenin, epigallocatechin gallate (EGCG), avicularin, and bufadienolides, along with a presentation of representative structures. The review also covers the potential mechanisms of action in diabetes mellitus. The survey of available literature highlights the effects of K. pinnata on indices of diabetes mellitus, including enhancing insulin sensitivity, mitigating oxidative stress and inflammation, lowering blood glucose levels, and the potential adverse effects. These results point to the promising prospect for K. pinnata use in the management of diabetes mellitus and its associated complications, while underscoring the need for more rigorous investigations, including well-controlled clinical trials. Full article

Background/Objectives: Biofilms are key in spreading antibiotic resistance in various ecosystems. This study employed comparative genomics to examine the resistance and adaptability mechanisms of the Vibrio parahaemolyticus strain Vaw-5, isolated from a seafood market biofilm. Methods: A comparative examination of Vaw-5 and 32 publicly available V. parahaemolyticus genomes identified a distinct set of genetic resistance characteristics. Results: Unlike clinical strains, Vaw-5 lacks acquired antimicrobial resistance genes like the blaCARB and qnr variations. Instead, its resistance potential is based on chromosomal alterations, efflux pump systems (vmeAB, vcmD), and a unique repertoire of 16 strain-specific transposons, including Tn5501 and Tn5393, which are well-known vectors for antibiotic resistance gene (ARG) mobilization. Although not multidrug-resistant, Vaw-5 possesses unique genomic islands that share negligible homology with those of clinical strains, enriched with gene clusters for environmental adaptation, such as exopolysaccharide production and a fully functional Type VI Secretion System. Vaw-5 carries a distinctive plasmid with the resistance gene aac(2${}^{\prime }$)-Ia. Conclusions: Biofilm adaptation promotes structural integrity, inherent processes, and resistance above standard ARG acquisition. This study focuses on how biofilm communities in the food chain can operate as covert incubators for mobilizable resistance determinants, emphasizing the significance of ecological monitoring within a One Health paradigm to reduce possible public health hazards. Full article

Background: Most immunologically “cold” tumors do not respond durably to checkpoint blockade because tumor antigen (TA) release and presentation are insufficient to prime effective T-cell immunity. While prior work demonstrated synergy between cisplatin and a TLR7/8/9 agonist (CR108) in 4T1 tumors, the underlying mechanism—particularly whether chemotherapy functions as a broad antigen-releasing agent enabling TLR-driven immune amplification—remained undefined. Methods: Using murine models of breast (4T1), melanoma (B16-F10), and colorectal cancer (CT26), we tested multiple chemotherapeutic classes combined with CR108. We quantified intratumoral and systemic soluble TAs, antigen presentation and cross-priming by antigen-presenting cells, tumor-infiltrating lymphocytes, and cytokine production by flow cytometry/ICS. T-cell receptor β (TCRβ) repertoire dynamics in tumor-draining lymph nodes were profiled to assess amplitude and breadth. Tumor microenvironment remodeling was analyzed, and public datasets (e.g., TCGA basal-like breast cancer) were interrogated for expression of genes linked to TA generation/processing and peptide loading. Results: Using cisplatin + CR108 in 4T1 as a benchmark, we demonstrate that diverse chemotherapies—especially platinum agents—broadly increase the repertoire of soluble tumor antigens available for immune recognition. Across regimens, chemotherapy combined with CR108 increased T-cell recognition of candidate TAs and enhanced IFN-γ⁺ CD8⁺ responses, with platinum agents producing the largest expansions in soluble TAs. TCRβ sequencing revealed increased clonal amplitude without loss of repertoire breadth, indicating focused yet diverse antitumor T-cell expansion. Notably, therapeutic efficacy was not predicted by canonical damage-associated molecular pattern (DAMP) signatures but instead correlated with antigen availability and processing capacity. In human basal-like breast cancer, higher expression of genes involved in TA generation and antigen processing/presentation correlated with improved survival. Conclusions: Our findings establish an antigen-centric mechanism underlying chemo–TLR agonist synergy: chemotherapy liberates a broadened repertoire of tumor antigens, which CR108 then leverages via innate immune activation to drive potent, T-cell-mediated antitumor immunity. This framework for rational selection of chemotherapy partners for TLR7/8/9 agonism and support clinical evaluation to convert “cold” tumors into immunologically responsive disease. Full article

The Stockholm Paradigm, a multilevel framework for studying coevolutionary interactions, it is a promising method for obtaining a globally relevant understanding of the emergence of present and past host–parasite and insect–plant interactions. This research aimed to expand the application of the Paradigm to virus–host interactions, considering that viruses are being subjected to the same evolutionary forces as any other living organism. By applying different data science techniques, we described and discussed capacity and opportunity traits for Influenza A H1N1 strains, and how they might influence the pathogen’s host repertoire evolution, and thus ranked different strains according to their emergence risk in the human population. We hope to contribute to the application of different methods for understanding disease emergence, and consequently to the development of new public health strategies for preventing (re)emerging diseases. Full article

This study advances Spanish Heritage Language (SHL) pedagogy by investigating the integration of Critically Oriented Sociolinguistic Topics (COST) into the heritage language curriculum. Thirteen self-identified SHL students from three courses (Intermediate, Advanced I, and Advanced II) at two universities in the Washington, D.C. metro area participated in semi-structured Zoom interviews exploring their motivations for enrolling in an SHL class, their perceptions of Spanish, and the impact of COST. Analysis identified recurring themes about underlying language ideologies and enrollment motivations, such as improving academic Spanish and grammar, career preparation, and connecting with course topics. Dominant ideologies, including essentialist, standard language, deficit, and commodification, were evident in students’ perceptions of Spanish and Latinx communities in the U.S. and abroad. Findings showed that students developed critical awareness of language variation that supported validation of their HL practices and the emergence of student agency. Some students moved from reproducing to contesting deficit and standard ideologies, asserting legitimacy for their own bilingual repertoires. These findings underscore the need for integrating COST in SHL courses to promote student agency, foster positive attitudes, and strengthen students’ linguistic confidence. Full article

Antinuclear antibodies, especially anti-DNA antibodies, are known to be a hallmark of systemic lupus erythematosus (SLE) and represent a diverse pool of autoantibodies with different origins, antigenic properties, and physicochemical features. Antibodies with catalytic properties have been found among the antibody repertoire in SLE, but the specific features and clinical associations of such antibodies have not been sufficiently studied. This study showed that chromatographically purified IgG from the serum of SLE patients effectively hydrolyzed DNA and DNA-associated proteins such as histones and high-mobility group box 1 (HMGB1) compared to healthy individuals. Remarkably, the level of hydrolysis of DNA and DNA-associated proteins was closely correlated. At the same time, these antibodies did not hydrolyze the control protein, tumor necrosis factor-α (TNFα), which does not possess DNA-binding properties. IgG DNase activity levels varied significantly, so patients were divided into high- and low-activity subgroups using the DBSCAN algorithm, with the difference between median values being greater than 49 times. The subgroup with high IgG DNase activity was characterized by an increase in anti-DNA antibodies (p < 0.04) than the subgroup with low activity, which had a shorter duration of the disease (p = 0.03) and was more often characterized by a subacute rather than a non-chronic course of the disease (p = 0.048). High catalase-like activity of IgG was also detected in SLE. Thus, the antibody pool in SLE contains not only high-affinity antinuclear autoantibodies but also catalytic antibodies capable of hydrolyzing DNA and DNA-associated proteins. These findings expand our understanding of the heterogeneity of the repertoire of catalytic autoantibodies among SLE patients. Full article

T cell receptor (TCR) profiling using next-generation sequencing (NGS) enables high-throughput, in-depth analysis of repertoire diversity, offering numerous clinical applications. We developed a DNA-based strategy to analyse the TCRβ-chain using NGS and established reference values for T cell repertoire characteristics in 74 healthy donors, including 44 adults, 20 paediatrics, and 10 cord blood units (CBUs). Additionally, four paediatric patients with combined immunodeficiency (CID) or severe CID (SCID) due to deleterious mutations in recombination activating genes (RAG) were analysed. The developed strategy demonstrated high specificity, reproducibility, and sensitivity, and all functional variable and joining genes were detected with minimal PCR bias. All donors had a Gaussian-like distribution of complementary-determining region 3 length, with lower presence of non-templated nucleotides and higher proportion of non-functional clonotypes in CBUs. Both CBUs and paediatrics showed greater convergence and TCRβ diversity was significantly lower in adults and donors with cytomegalovirus-positive serostatus. Finally, an analysis of paediatric patients with RAG-SCID/CID showed significantly shorter CDR3 region length and lower repertoire diversity compared to healthy paediatrics. In summary, we developed a reliable and feasible TCRβ sequencing strategy for application in the clinical setting, and established reference values that could assist in the diagnosis and monitoring of pathological conditions affecting the T cell repertoire. Full article

Polyhydroxyalkanoate (PHA) bioplastics are produced from wastewater as a carbon recovery strategy. However, the tuneable characteristics of PHAs and wastewater biorefinery potential have not been comprehensively reviewed. The aim of this study is to review the main challenges and strategies for carbon recovery from wastewater feedstocks via PHA production, assessing potential target biopolymer applications. Diverse PHA-accumulating prokaryotes metabolize organic pollutants present in wastewater through different metabolic pathways, determining the biopolymer characteristics. The synthesis of PHAs using mixed microbial cultures with wastewater feedstocks derived from municipal, agro-industrial, food processing, lignocellulosic biomass processing and biofuel production activities are described. Acidogenic fermentation of wastewater feedstocks and mixed microbial culture enrichment are key steps in order to enhance PHA productivity and determine biopolymer properties towards customized bioplastics for specific applications. Biorefinery of PHA copolymers and extracellular polysaccharides (EPSs), including alginate-like polysaccharides, are alternatives to enhance the value-chain of carbon recovery from wastewater. PHAs and EPSs exhibit a wide repertoire of applications with distinct safety control requirements; hence, coupling biopolymer production demonstrations with target applications is crucial to move towards full-scale applications. This study discusses the relationship between the metabolic basis of PHA synthesis and composition, wastewater type, and target applications, describing the potential to maximize carbon resource valorisation. Full article

Lignocellulosic agricultural residues represent a rich source of potential feedstock for biorefinery applications, but their valorization remains challenging. The white-rot fungus Irpex lacteus J2 exhibited a promising degradation effect, but its molecular mechanisms of lignocellulose degradation remained largely uncharacterized. Here, we performed high-quality whole-genome sequencing and untargeted metabolomic profiling of I. lacteus J2 during the degradation of corn straw as the sole carbon source. The assembled I. lacteus J2 genome contained 14,647 protein-coding genes, revealing a rich genetic repertoire for biomass degradation and secondary metabolite synthesis. Comparative genomics showed high synteny (mean amino acid sequence identity 92.28%) with I. lacteus Irplac1. Untargeted metabolomic analysis unveiled a dynamic metabolic landscape during corn straw fermentation. Dominant metabolite classes included organic acids and derivatives (27.32%) and lipids and lipid-like molecules (25.40%), as well as heterocyclic compounds (20.41%). KEGG pathway-enrichment analysis highlighted significant activation of core metabolic pathways, with prominent enrichment in global metabolism (160 metabolites), amino acid metabolism (99 metabolites), carbohydrate metabolism (24 metabolites), and lipid metabolism (19 metabolites). Fermentation profiles at 3 and 15 days demonstrated substantial metabolic reprogramming, with up to 210 upregulated and 166 downregulated metabolites. Correlation analyses further revealed complex metabolic interdependencies and potential regulatory roles of key compounds. These integrated multi-omics insights significantly expand our understanding of the genetic basis and metabolic versatility, enabling I. lacteus J2 to efficiently utilize lignocellulose. Our findings position I. lacteus J2 as a robust model strain and provide a valuable foundation for developing advanced fungus-based strategies for sustainable bioprocessing and valorization of agricultural residues. Full article

Proteolysis-targeting chimeras (PROTACs) are a transformative therapeutic modality that co-opts the ubiquitin-proteasome system for selective protein degradation. To date, the development of PROTACs has been overwhelmingly dominated by the recruitment of four canonical E3 ligases: CRBN, VHL, MDM2, and IAP. This limited repertoire represents a critical bottleneck, restricting the scope of degradable proteins and potential therapeutic applications. Addressing this challenge, recent years have witnessed a surge in the successful recruitment of novel E3 ligases. This review provides a dedicated and comprehensive summary of this progress, focusing exclusively on the emerging E3 ligases and their cognate ligands reported for PROTAC technology outside of the well-established quartet. We detail their discovery and strategic application, highlighting how this rapidly expanding toolbox promises to overcome existing limitations and unlock the full potential of targeted protein degradation. Full article

Colibacillosis, caused by avian pathogenic Escherichia coli (APEC), represents a major threat to poultry production, leading to significant mortality and economic losses. This study aimed to characterize an APEC strain, HPVN24, isolated from diarrheic chickens at a farm in Hai Phong, Vietnam. The strain was investigated through phenotypic assays, antibiotic susceptibility profiling, and whole-genome sequencing using the Illumina platform. HPVN24 exhibited β-hemolytic activity and resistance to trimethoprim, ampicillin, and ciprofloxacin. Whole-genome analysis identified the strain as serotype O78:H9 and sequence type ST23, with a genome size of 5.05 Mb and a GC content of 50.57%. Genome annotation revealed a wide repertoire of genes involved in metabolism, secretion systems, virulence, and biofilm formation. Virulence-associated genes included those related to adhesion, iron acquisition, hemolysin production, and stress response. Analysis predicted multidrug resistance to 18 antibiotic classes, with particularly strong resistance to fluoroquinolones. Phylogenetic comparison demonstrated that HPVN24 clustered closely with O78:H9 strains isolated from poultry in other regions, suggesting potential transmission across populations. These findings indicate that HPVN24 is a multidrug-resistant and highly virulent APEC strain linked to colibacillosis outbreaks in Vietnam and highlight the need for ongoing surveillance, judicious antibiotic usage, and alternative strategies to ensure poultry health and food safety. Full article

Extracellular vesicles (EVs) are rapidly gaining recognition as critical mediators of inter-cellular communication during viral infections. To contribute to fill the gap in knowledge regarding the role of EVs in adenovirus infection, we used human adenovirus type 4 of species Mastadenovirus exoticum (HAdV-E4), a prevalent respiratory and ocular pathogen, and characterized the cargo and biological properties of EVs released by HAdV-E4-infected A549 lung epithelial cells at a pre-lytic stage of infection. Using immunocapture-based isolation and multi-omics approaches, we found that infection profoundly alters the EV uploaded proteome and small non-coding RNA repertoire. Mass spectrometry identified 268 proteins unique to EVs purified from infected cells (AdV-EVs), with enrichment in pathways supporting vesicle trafficking and viral protein translation, and importantly also a few virus-encoded proteins. A small RNA transcriptome analysis showed differential uploading in AdV-EVs of various small non-coding RNAs, including snoRNAs, as well as the presence of virus associated RNAs I and II. Notably, AdV-EVs contained viral genomic DNA and could initiate productive infection upon delivery to naïve cells in the absence of detectable viral particles. Our data suggest that EVs released during the HAdV-E4 infection may serve as vehicles for non-lytic viral dissemination and highlight their possible role in intra-host dissemination Full article