SEARCH · Search PubMed

Results for “Serine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2022

Genetic variants in ALDH1L1 and GLDC influence the serine-to-glycine ratio in Hispanic children.

BACKGROUND: Glycine is a proteogenic amino acid that is required for numerous metabolic pathways, including purine, creatine, heme, and glutathione biosynthesis. Glycine formation from serine, catalyzed by serine hydroxy methyltransferase, is the major source of this amino acid in humans. Our previous studies in a mouse model have shown a crucial role for the 10-formyltetrahydrofolate dehydrogenase enzyme in serine-to-glycine conversion. OBJECTIVES: We sought to determine the genomic influence on the serine-glycine ratio in 803 Hispanic children from 319 families of the Viva La Familia cohort. METHODS: We performed a genome-wide association analysis for plasma serine, glycine, and the serine-glycine ratio in Sequential Oligogenic Linkage Analysis Routines while accounting for relationships among family members. RESULTS: All 3 parameters were significantly heritable (h2 = 0.22-0.78; P < 0.004). The strongest associations for the serine-glycine ratio were with single nucleotide polymorphisms (SNPs) in aldehyde dehydrogenase 1 family member L1 (ALDH1L1) and glycine decarboxylase (GLDC) and for glycine with GLDC (P < 3.5 × 10-8; effect sizes, 0.03-0.07). No significant associations were found for serine. We also conducted a targeted genetic analysis with ALDH1L1 exonic SNPs and found significant associations between the serine-glycine ratio and rs2886059 (β = 0.68; SE, 0.25; P = 0.006) and rs3796191 (β = 0.25; SE, 0.08; P = 0.003) and between glycine and rs3796191 (β = -0.08; SE, 0.02; P = 0.0004). These exonic SNPs were further associated with metabolic disease risk factors, mainly adiposity measures (P < 0.006). Significant genetic and phenotypic correlations were found for glycine and the serine-glycine ratio with metabolic disease risk factors, including adiposity, insulin sensitivity, and inflammation-related phenotypes [estimate of genetic correlation = -0.37 to 0.35 (P < 0.03); estimate of phenotypic correlation = -0.19 to 0.13 (P < 0.006)]. The significant genetic correlations indicate shared genetic effects among glycine, the serine-glycine ratio, and adiposity and insulin sensitivity phenotypes. CONCLUSIONS: Our study suggests that ALDH1L1 and GLDC SNPs influence the serine-to-glycine ratio and metabolic disease risk.

Child↗

PubMed2026

Serine: From Metabolic Intermediate to Signaling Entity.

Serine, a nonessential amino acid classically defined as a precursor for protein synthesis and one-carbon metabolism, is increasingly recognized as a signaling metabolite that links the cellular metabolic status to regulatory decision-making. Intracellular serine availability is shaped by nutrient conditions, glycolytic flux, and activity of the serine synthesis pathway, and these fluctuations are sensed to elicit coordinated metabolic and signaling responses. This review discusses mechanisms by which serine modulates cell growth and stress responses, with particular emphasis on its interaction with central nutrient-sensing pathways, including mTORC1 and the integrated stress response. In parallel, serine-driven one-carbon metabolism is examined for its role in supporting nucleotide biosynthesis, methylation reactions, and redox homeostasis through folate-dependent pathways and NADPH generation, thereby coupling anabolic processes to the maintenance of redox balance and genome integrity. In addition to intracellular functions, serine contributes to intercellular signaling. Conversion of l-serine to d-serine mediates neuromodulatory activity via N-methyl-d-aspartate receptors, while serine availability also influences immune cell function, inflammatory signaling, and host-microbe interactions. Dysregulation of serine metabolism and signaling is further considered in the context of disease states, including cancer, neurodegeneration, and metabolic disorders. Together, these observations support a framework in which serine functions as an information-bearing metabolic signal that coordinates the biosynthetic capacity with cellular adaptation and intercellular communication.

Serine↗

PubMed2023

Serine-threonine phosphoregulation by PknB and Stp contributes to quiescence and antibiotic tolerance in Staphylococcus aureus.

Staphylococcus aureus can cause infections that are often chronic and difficult to treat, even when the bacteria are not antibiotic resistant because most antibiotics act only on metabolically active cells. Subpopulations of persister cells are metabolically quiescent, a state associated with delayed growth, reduced protein synthesis, and increased tolerance to antibiotics. Serine-threonine kinases and phosphatases similar to those found in eukaryotes can fine-tune essential bacterial cellular processes, such as metabolism and stress signaling. We found that acid stress-mimicking conditions that S. aureus experiences in host tissues delayed growth, globally altered the serine and threonine phosphoproteome, and increased threonine phosphorylation of the activation loop of the serine-threonine protein kinase B (PknB). The deletion of stp, which encodes the only annotated functional serine-threonine phosphatase in S. aureus, increased the growth delay and phenotypic heterogeneity under different stress challenges, including growth in acidic conditions, the intracellular milieu of human cells, and abscesses in mice. This growth delay was associated with reduced protein translation and intracellular ATP concentrations and increased antibiotic tolerance. Using phosphopeptide enrichment and mass spectrometry-based proteomics, we identified targets of serine-threonine phosphorylation that may regulate bacterial growth and metabolism. Together, our findings highlight the importance of phosphoregulation in mediating bacterial quiescence and antibiotic tolerance and suggest that targeting PknB or Stp might offer a future therapeutic strategy to prevent persister formation during S. aureus infections.

Animals↗

PubMed2025

Hatching of whipworm eggs induced by bacterial contact is serine-protease dependent.

Whipworms (Trichuris spp) are ubiquitous parasites of humans and domestic and wild mammals that cause chronic disease, considerably impacting human and animal health. Egg hatching is a critical phase in the whipworm life cycle that marks the initiation of infection, with newly hatched larvae rapidly migrating to and invading host intestinal epithelial cells. Hatching is triggered by the host microbiota; however, the physical and chemical interactions between bacteria and whipworm eggs, as well as the bacterial and larval responses that result in the disintegration of the polar plug and larval eclosion, are not completely understood. Here, we examined hatching in the murine whipworm, Trichuris muris, and investigated the role of specific bacterial and larval structures and molecules in this process. Using scanning and transmission electron microscopy, we characterised the physical interactions of both fimbriated (Escherichia coli, Salmonella typhimurium and Pseudomonas aeruginosa) and non-fimbriated (Staphylococcus aureus) bacteria with the egg polar plugs during the induction/initiation stage, and visualised the effects of structural changes in the polar plugs, leading to larval eclosion. Further, we found that protease inhibitors blocked whipworm hatching induced by both fimbriated and non-fimbriated bacteria in a dose-dependent manner, suggesting the partial involvement of bacterial enzymes in this process. In addition, we identified the minimal egg developmental timing required for whipworm hatching, and transcriptomic analysis of T. muris eggs through embryonation revealed the specific upregulation of serine proteases (S01A family) in fully embryonated eggs containing 'hatch-ready' L1 larvae. Finally, we demonstrated that inhibition of serine proteases with the serine-protease inhibitor Pefabloc ablated T. muris egg hatching induced by bacteria. Collectively, our findings unravel the temporal and physicochemical bacterial-egg interactions leading to whipworm hatching and indicate serine proteases of both bacterial and larval origin mediate these processes.

Animals↗

PubMed2026

Reduced platelet formation associated with serine metabolic dysregulation in integrin αIIbβ3-deficient megakaryocytes.

Glanzmann thrombasthenia (GT) is characterized by absent platelet aggregation in response to all agonists except ristocetin and is caused by recessive inactivating variants in ITGA2B or ITGB3. Although patients with GT typically are described as having normal platelet counts, autosomal dominant activating variants in ITGA2B or ITGB3 cause macrothrombocytopenia. Interestingly, in our cohort of 16 patients with GT, 8 consistently exhibited platelet counts at the lower end of the normal range. We studied the role of integrin αIIbβ3 in platelet formation using megakaryocytes (MKs) derived from genetically modified immortalized MK cell lines (imMKCLs), focusing on 2 modifications of ITGB3: ITGB3-/- (inactivating) and ITGB3WT/D673_E713del (activating). In static differentiation cultures, ITGB3-/- and ITGB3WT/D673_E713del imMKCLs exhibited normal MK differentiation but reduced proplatelet formation. Platelet production was also impaired in a 3-dimensional silk-based bone marrow system and in shaking cultures, confirming a quantitative role for ITGB3 in platelet production independent of the type of variant. Although thrombin receptor activating protein-activated, in vitro-generated platelets lacking αIIbβ3 failed to bind the activation-dependent PAC-1 antibody, ITGB3WT/D673_E713del platelets bound PAC-1 before activation, mimicking the patient's phenotype. Transcriptome profiling and metabolomic analyses of integrin αIIbβ3-deficient MKs revealed impaired serine metabolism and downregulation of SLC3A2 (CD98hc), an amino acid transporter chaperon known to interact with the β3 subunit. Flow cytometry confirmed decreased CD98hc in mutant MKs, whereas reexpression of wild-type ITGB3 in ITGB3-/- MKs restored αIIbβ3 and CD98hc expression, normalized proplatelet formation, and enhanced serine uptake. These results uncover a previously unrecognized role of integrin αIIbβ3 in coupling serine metabolism to platelet biogenesis.

Humans↗

PubMed2026

Small serine recombinases are markers for antiphage defense system discovery.

Renewed interest in phage therapy has highlighted a need to understand how bacteria subvert phage infection through antiphage defense systems. Traditionally, strategies to identify antiphage defense systems lack throughput or have limitations for bacterial species where antiphage defense systems are understudied. Herein, we developed a bioinformatic pipeline that uses a small serine recombinase to identify known and unknown antiphage defense systems. Using this approach to query reference genomes and metagenomes, we show that small serine recombinase genes are genetically linked to antiphage defense systems and serve as bait for finding these systems across diverse bacterial phyla. Using co-transcription predictions and statistical analysis of protein domain abundances, we experimentally validated our bioinformatic approach by discovering that KAP P-loop NTPases are fused to putative antiphage domains and reinforce prokaryotic Schlafen proteins as a new class of antiphage defense. Our work shows that small serine recombinases are a reliable genetic marker for the discovery of antiphage defenses across diverse bacterial phyla.

Bacteriophages↗

PubMed2026

Upregulation of Endogenous Serine Proteinases by SVMPs Contributes to Muscle Damage Induced by Bothrops atrox Venom.

In Brazil, approximately 25,000 snakebites occur annually, with Bothrops atrox responsible for most cases. Local morbidity is high, driven primarily by snake venom metalloproteases (SVMPs). The major SVMPs in B. atrox venom, Atroxlysin-Ia (ATXL) and Batroxrhagin (BATX), efficiently hydrolyze extracellular matrix proteins, inducing rapid hemorrhage and dermonecrosis. Thus, we characterized the composition of the exudate produced after SVMPs injection into the mice gastrocnemius muscle using proteomics. Muscle damage was evaluated by histological analysis. The composition of the exudate was analyzed by mass spectrometry. The SVMPs induced disorganization of muscle fibers and inflammatory cell migration. However, ATXL-induced a significantly higher neutrophil influx compared to BATX, likely triggered by an increase in CXCL16, suggesting a superior inflammatory capacity. In summary, despite being metalloproteases, these toxins exhibit distinct pathological profiles: ATXL is predominantly inflammatory, while BATX is more hemorrhagic. Interestingly, while endogenous serine proteinase levels were similar in both exudates, BATX showed significantly higher levels of proteinase inhibitors. Furthermore, identification of peptide bond cleavage sites revealed a pattern consistent with trypsin-like serine proteinases. These findings suggest that SVMPs not only damage tissue directly but also associate with the activation of host endogenous proteinases, which may contribute to the complex pathology of B. atrox envenomation, although direct causation remains to be established.

Animals↗

PubMed2026

The Staphylococcus aureus serine protease-like protein B is a potent allergen in a murine asthma model.

BACKGROUND: Asthma is associated with Staphylococcus aureus colonization. Two hypotheses were proposed to explain this phenomenon: (1) the allergic environment in asthma favors S. aureus colonization and (2) S. aureus colonization creates a pro-allergic environment. Since several S. aureus virulence factors, such as the serine protease-like protein (Spl) B, elicit a type 2 biased immune response, we asked whether the pathogen itself can cause asthma. OBJECTIVE: Test the ability of recombinant SplB of S. aureus to sensitize mice and induce allergic airway inflammation (AAI). METHODS: Mice were treated with repeated intratracheal inoculations of either catalytically active SplB or an inactive mutant. AAI was assessed by evaluating airway hypersensitivity, immune cell infiltration, cytokines, mucus production, fibrosis, and specific serum IgE. We compared the outcome between wild-type and gene-deficient C57BL/6J mice, including recombination-activating gene knockout mice (Rag2-/-), interleukin-33 knockout mice (Il33-/-), and protease-activated receptor 2 knockout mice (F2rl1-/-). RESULTS: Intratracheal exposure to SplB sensitized the mice and caused eosinophilic airway inflammation and hyperresponsiveness. The development of asthma required both the proteolytic activity of SplB and a functional adaptive immune system. The soluble protease sensor IL-33 was necessary for eosinophil tissue invasion, whereas the membrane-bound protease sensor PAR2 was not. CONCLUSION: The serine protease SplB of S. aureus is a potent allergen. Based on this finding we propose a third mechanism to explain the relationship between S. aureus colonization and asthma: S. aureus can release allergens, such as SplB, that sensitize individuals and lead to the development of asthma.

Allergy↗

PubMed2022

Chemical acylation of an acquired serine suppresses oncogenic signaling of K-Ras(G12S).

Drugs that directly impede the function of driver oncogenes offer exceptional efficacy and a therapeutic window. The recently approved mutant selective small-molecule cysteine-reactive covalent inhibitor of the G12C mutant of K-Ras, sotorasib, provides a case in point. KRAS is the most frequently mutated proto-oncogene in human cancer, yet despite success targeting the G12C allele, targeted therapy for other hotspot mutants of KRAS has not been described. Here we report the discovery of small molecules that covalently target a G12S somatic mutation in K-Ras and suppress its oncogenic signaling. We show that these molecules are active in cells expressing K-Ras(G12S) but spare the wild-type protein. Our results provide a path to targeting a second somatic mutation in the oncogene KRAS by overcoming the weak nucleophilicity of an acquired serine residue. The chemistry we describe may serve as a basis for the selective targeting of other unactivated serines.

Humans↗

PubMed2026

Adipocyte-derived CRAMP-neutrophil serine protease interaction axis regulates innate cutaneous defense against Staphylococcus aureus.

Dermal adipocytes have emerged as active participants in cutaneous host defense. In parallel, adipocyte hypertrophy and hyperplasia-driven obesity has become a global public health priority and is strongly associated with increased risk and severity of bacterial infections. Here, we established and optimized two complementary S. aureus infection models-epidermal and subcutaneous-and in combination with diet-induced (HFD) and genetic (ob/ob) obesity, to systematically evaluate cathelin-related antimicrobial peptide (CRAMP) expression in adipocytes and its crosstalk with neutrophils. Obese mice displayed impaired cutaneous defense despite marked thickening of the fat layer, characterized by attenuated induction of adipocyte CRAMP and reduced local antibacterial activity. In vitro, CRAMP followed a biphasic pattern during adipocyte differentiation-upregulated at early stages but diminished with advanced maturation and lipid accumulation. Mechanistically, neutrophils processed adipocyte-derived CRAMP via serine proteases to generate shorter peptides with enhanced antibacterial activity. Collectively, these findings identify a CRAMP-neutrophil (serine protease) interaction axis as a key amplifier of cutaneous innate immunity and provide mechanistic insight into obesity-associated susceptibility to skin infection, suggesting potential avenues for targeted intervention.

Animals↗

PubMed2025

HLA-B Serine 116 Confers Protection Against Severe COVID-19 in a Cohort From Rio de Janeiro, Brazil.

COVID-19 is a respiratory disease caused by SARS-CoV-2, in which severe outcomes are primarily driven by an exacerbated immune response. The HLA region has been extensively investigated in COVID-19 due to its central role in the immune response, although genetic associations vary across populations. Here, the association of HLA genetic variability with COVID-19 severe respiratory outcomes was investigated in an admixed population from Rio de Janeiro, Brazil. Results of a comparative study between mild and severe COVID-19 cases involving 306 individuals have suggested risk associations with severe COVID-19 for the HLA-DPB1*13:01 allele (OR = 3.42, 95% CI = 1.05-11.16, p = 0.041) and the HLA-B*39 allele group (OR = 3.26, 95% CI = 1.16-9.13, p = 0.024), although statistical significance was lost after FDR adjustment for multiple comparisons (adjusted p > 0.05). Amino acid analyses showed that a serine at position 116 of HLA-B conferred protection against severe COVID-19 (OR = 0.4774, 95% CI = 0.28-0.81, p = 0.006, adjusted p = 0.031). In silico analysis using the NetMHCpan tool predicted that this residue, located in the HLA-B peptide-binding groove, has enhanced binding affinity to immunodominant SARS-CoV-2 epitopes, suggesting a functional mechanism underlying the observed protection. The association of single nucleotide variants at the HLA region was also investigated, and no statistically significant association was found. Results obtained in the present study underscore the importance of HLA in COVID-19 severity, likely mediated by its influence on viral peptide presentation, and advance our understanding of the genetic underpinnings of severe disease in admixed populations.

Humans↗

PubMed2026

Functional divergence of two soybean cytosolic serine hydroxymethyltransferases in development and defense against soybean cyst nematode.

Serine hydroxymethyltransferase (SHMT) is an enzyme essential for one-carbon metabolism. In higher plants, multiple SHMT genes code for isoforms that function in the cytosol, nucleus, mitochondria, and chloroplasts. The soybean genome contains two cytosolic SHMTs, GmSHMT05 and GmSHMT08, sharing high sequence identity and similar expression throughout soybean development. In certain soybean genotypes, two amino acid substitutions negatively impact GmSHMT08's ability to bind to tetrahydrofolate (THF), leading to a gain-of-function in resistance to the soybean cyst nematode (SCN). Whether this perturbation to the enzyme has other functional consequences for soybean growth and development remains unknown. Here, we investigated the roles of cytosolic GmSHMTs in soybean growth and development. We determined that the 3D structure and folate-binding affinity of GmSHMT05 are highly similar to the version of GmSHMT08 found in susceptible soybeans. We further measured phenotypic traits of two ethyl methanesulfonate-derived Gmshmt08 mutant plants in an SCN-resistant soybean background. Aboveground soybean growth and development were similar, except the Gmshmt08 mutant plants showed a significant increase in pods/plant in field phenotyping trials. Belowground analyses revealed a significant increase in lateral root and total root length in mutant plants, and CRISPR-Cas9 editing demonstrated an essential role of cytosolic SHMTs in root growth. Taken together, our results indicate that GmSHMT05 sustains overall soybean growth and development in the absence of GmSHMT08; however, GmSHMT08's gain-of-function in SCN resistance negatively influences pod and root growth, highlighting a potential trade-off between soybean defense and development that may impact yield when breeding with GmSHMT08 to develop SCN-resistant varieties.

1-C folate metabolism↗

PubMed2025

A novel regulation on the developmental checkpoint protein Sda that controls sporulation and biofilm formation in Bacillus subtilis.

UNLABELLED: Biofilm formation by Bacillus subtilis is triggered by an unusually simple environmental sensing mechanism. Certain serine codons, the four TCN codons (N for A, T, C, or G), in the gene for the biofilm repressor SinR caused lowered SinR translation and subsequent biofilm induction during transition from exponential to stationary growth. Global ribosome profiling showed that ribosomes pause when translating the four UCN (U for T on the mRNA) serine codons on mRNA, but not the two AGC/AGU serine codons. We proposed a serine codon hierarchy (AGC/AGT vs TCN) in that genes enriched in the TCN serine codons may experience reduced translation efficiency when serine is limited. In this study, we designed an algorithm to score all protein-coding genes in B. subtilis NCIB3610 based on the serine codon hierarchy. We generated a short list of 50 genes that could be subject to regulation by this novel mechanism. We further investigated one such gene from the list, sda, which encodes a developmental checkpoint protein regulating both sporulation and biofilm formation. We showed that synonymously switching the TCN serine codons to AGC in sda led to delayed biofilm formation and sporulation. This engineered strain also outgrew strains with other synonymously substituted sda alleles (TCN) in competition assays for biofilm formation and sporulation. Finally, we showed that the AGC serine codon substitutions in sda elevated the Sda protein levels. This serine codon hierarchy-based novel signaling mechanism could be exploited by bacteria in adapting to stationary phase and regulating important biological processes. IMPORTANCE: Genome-wide ribosome profiling in Bacillus subtilis shows that under serine limitation, ribosomes pause on the four TCN (N for A, C, G, and T), but not AGC/AGT serine codons, during translation at a global scale. This serine codon hierarchy (AGC/T vs TCN) differentially influences the translation efficiency of genes enriched in certain serine codons. In this study, we designed an algorithm to score all 4,000+ genes in the B. subtilis genome and generated a list of 50 genes that could be subject to this novel serine codon hierarchy-mediated regulation. We further investigated one such gene, sda, encoding a developmental checkpoint protein. We show that sda and cell developments controlled by Sda are also regulated by this novel mechanism.

Bacillus subtilis↗

PubMed2026

The tumor suppressor NDRG2 recruits protein phosphatase 2A to suppress STAT5 phosphorylation in adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell malignancy with a poor prognosis that is caused by human T-cell leukemia virus type 1 infection. We previously demonstrated that N-myc downstream-regulated gene 2 (NDRG2) is significantly downregulated in ATL, resulting in aberrant activation of the signal transduction pathways through the dissociation of serine/threonine protein phosphatase 2A. To identify potential targets of NDRG2, we performed comprehensive mass spectrometry of differentially phosphorylated peptides in ATL cells with overexpression of NDRG2 using a TiO2-based enrichment method. Kyoto Encyclopedia of Genes and Genomes and gene ontology analysis revealed that the downregulated phosphopeptides correlated with signaling pathways, T-cell differentiation, and proliferation. Our results identified signal transducer and activator of transcription 5B as a novel NDRG2-regulated protein that is dephosphorylated at serine 193 and tyrosine 699. Although enforced expression of NDRG2 in ATL cell lines does not change the phosphorylation of Janus kinase 3, an upstream regulator of STAT5, phosphorylated STAT5 at tyrosine and serine is significantly suppressed by the direct binding to STAT5 with NDRG2 leading to the inhibition of STAT5 downstream gene expression. Furthermore, NDRG2 binds to STAT5B with alanine replacement of Y699 (Y699A), but only weakly associates with S193A, suggesting that NDRG2 is directly involved in serine phosphorylation through the recruitment of serine/threonine protein phosphatase 2A to STAT5. Because S193 A remarkably induces reduced phosphorylation of Y699 and subsequent transcriptional activity, the induction of serine phosphorylation through the loss of NDRG2 expression is dispensable for STAT5 tyrosine phosphorylation and activity. Since the loss of NDRG2 expression is essential factor to maintenance of ATL cells by STAT5 activity through phosphorylation of serine and tyrosine, targeting STAT5 becomes a feasible and effective strategy in NDRG2-deficient ATL.

Humans↗

PubMed2026

MARK1 suppresses infectious bursal disease virus replication via phosphorylating VP3.

Infectious bursal disease virus (IBDV) of the Birnaviridae family is a non-envelope, double-stranded RNA virus that encodes a VP3 protein with multiple functions, which controls viral genome replication, IFN-β production, and virus traffic in infected cells. Posttranslational modifications (PTMs), such as ubiquitination, of VP3 have been demonstrated for affecting its function and stability. To clarify the mechanism by which VP3 is regulated in IBDV infected cells, we focused on the phosphorylation of VP3. Mass spectrometry analysis identified that microtubule-affinity regulating kinases 1 (MARK1) was a kinase interacting protein of VP3. Inhibitory function of MARK1 in affecting viral replication was validated. We describe the phosphorylation event at the serine 130 (S130) and serine 163 (S163) residues of VP3 mediated by MARK1 via mass spectrometry analysis. Alanine replacement of the phosphorylation sites in VP3 significantly enhanced its RNA-binding activity. Additionally, the mutation of two serine residues led to remarkably improved in its polymerase-enhancing function. We then incorporated the two mutations to rescue recombinant IBDV. Viral growth curve analysis revealed that replication of mutant IBDV was significantly enhanced relative to wild type (WT) virus. In conclusion, we found that VP3 functions are specifically regulated by MARK1 mediated phosphorylation at S130 and S163 and that this regulation suppresses IBDV replication ultimately.

Infectious bursal disease virus↗

PubMed2026

Functional mapping of the Trypanosoma cruzi serinome by fluorophosphonate activity-based protein profiling.

Serine hydrolases (SHs) constitute one of the largest enzyme superfamilies in eukaryotes, yet their roles in Trypanosoma cruzi, the causative agent of Chagas disease, remain largely uncharacterized. Here, we report an activity-based chemoproteomic map of the T. cruzi epimastigote serinome by combining genome-informed in silico curation with whole-cell activity-based protein profiling (ABPP) using a panel of cell-permeable fluorophosphonate (FP)-alkyne probes. Whole-cell labelling followed by label-free quantitative proteomics (LFQ-MS) identified 37 enriched SH-like proteins, including 35 with conserved or partially conserved catalytic triad/dyad features, spanning lipases, peptidases, esterases, and previously uncharacterized hydrolases. The 35 SHs represent approximately 63% of the 56 predicted SHs retained after catalytic-site curation. Domain architecture analysis revealed broad structural diversity, while orthologue-based localization data suggested association with multiple subcellular compartments, including glycosomal, mitochondrial, and endosomal localizations. Gene Ontology enrichment highlighted lipid metabolic and catabolic processes as dominant functional themes, and protein-protein interaction network analysis supported functional connectivity among the captured enzymes. Several identified SHs, including oligopeptidase B, prolyl oligopeptidase Tc80, serine carboxypeptidase CPB1, and phospholipase A1 (PLA1) have previously been characterized in trypanosomatids, with roles linked to parasite virulence or host-pathogen interactions. Together, these findings establish a fluorophosphonate-based chemoproteomic resource for the kinetoplastid community and prioritize probe-accessible active T. cruzi SHs for future functional validation and antiparasitic inhibitor discovery.

Activity-based protein profiling↗

PubMed2025

Amino acid profiles, aging, and sex hormone interactions in the elderly Iranian population: a metabolomics study.

BACKGROUND: Aging and sex hormones significantly influences on metabolic profiles, particularly in individuals aged 50 year and older. This study aimed to investigate the associations between serum metabolites, aging, and sex hormone levels among elderly individuals in Bushehr, Iran - a coastal region characterized by a unique lifestyle, dietary patterns, and environmental conditions, such as high seafood consumption and exposure to marine climate, which may collectively influence metabolic profiles and hormone levels in the aging population. METHODS: This cross-sectional study analyzed data from the Bushehr Elderly Health Program, which included 2001 participants (1143 women and 858 men) aged over 50 years old from Bushehr, Iran. Serum levels of 20 amino acids were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the results were analyzed based on gender, age, menopause status, menopause age, and serum levels of sex hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol (E2). Statistical analyses were performed using SPSS version 25.0 and R version 4.0.3, with a focus on gender differences and the correlation between aging, sex hormones, and metabolite profiles. RESULTS: Among the 2001 participants, mean ages were 61.57 ± 7.6 years for women and 62.92 ± 8.4 years for men. Men had higher serum levels of glutamic acid, leucine, methionine, phenylalanine, tyrosine, valine, citrulline, ornithine, proline, threonine, histidine, lysine, tryptophan, asparagine, and glutamine, while women had higher levels of glycine and serine. Aging was associated with notable changes in amino acid levels, such as increased citrulline and decreased threonine in women, and similar trends in men with a pronounced decrease in alanine. In men, low testosterone levels were linked to reduced concentration of alanine, methionine, phenylalanine, tyrosine, citrulline, glycine ornithine, serine, lysine, asparagine, and glutamine. Postmenopausal women showed a significant decrease in threonine levels. DISCUSSION: The findings highlight the complex interplay between aging, sex hormones, and metabolic changes. Gender-specific differences in amino acid profiles suggest that sex hormones play a pivotal role in modulating metabolism, which may influence susceptibility to metabolic disorders. These insights could inform the development of targeted interventions tailored to the specific needs of aging populations. Future research should investigate the underlying mechanisms linking sex hormones to metabolic pathways and assess their potential for improving health outcomes in older adults.

Aging↗

PubMed2026

One-carbon metabolism and chemotherapy-induced toxicities in patients with stage II-III colorectal cancer: a prospective cohort study.

BACKGROUND: One-carbon metabolism (OCM) is a target of the chemotherapeutic agent capecitabine. OBJECTIVES: We investigated OCM biomarker concentrations in relation to capecitabine-induced toxicities in patients with stage II-III colorectal cancer. METHODS: Within a prospective cohort, 297 patients receiving adjuvant capecitabine-based chemotherapy were included. Pretreatment plasma concentrations of the OCM biomarkers folate, vitamin B2, vitamin B6, vitamin B12, total homocysteine, methionine, serine, and glycine were determined. We also investigated whether associations differed according to methylenetetrahydrofolate reductase (MTHFR) C677T genotypes. Chemotherapy-induced toxicities were defined as toxicity-induced modifications of capecitabine treatment. To allow for inspection of shapes of the associations, restricted cubic splines and Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and sex. RESULTS: In total, 156 (53%) patients experienced toxicity-induced modifications of capecitabine treatment. Folate was not associated with toxicities in the overall population. Higher folate concentrations were associated with a lower risk of toxicities in patients with MTHFR C677T CT/TT genotype (HRperdoubling: 0.75; 95% CI: 0.57, 0.98) but not in patients with CC genotype (HRperdoubling: 1.17; 95% CI: 0.84, 1.63). Higher concentrations of vitamin B2 were associated with a lower risk of toxicities (HRperdoubling: 0.81; 95% CI: 0.67, 0.99), whereas higher glycine concentrations were associated with a higher risk of toxicities (HRperdoubling: 1.87; 95% CI: 1.18, 2.94). The association between vitamin B6 and vitamin B12 and toxicities appeared nonlinear. Homocysteine, methionine, and serine were not associated with toxicities. CONCLUSIONS: Future studies investigating whether nutrition-guided optimization of OCM biomarkers will result in improved treatment tolerance are warranted.

Humans↗