Biology subjects

Santos, Y.

Publications and source records attributed to Santos, Y..

4 recordsLinked to original sources

bioRxiv2026

Characterization of the IGH locus and tissue specific immunoglobulin repertoires in turbot (Scophthalmus maximus).

Turbot (Scophthalmus maximus) is an important aquaculture species, but the genomic organization and expressed diversity of its antibody repertoire remain incompletely characterized. In this study, we annotated the immunoglobulin heavy chain (IGH) locus using the haplotype resolved fScoMax1.1 genome assembly, and we used this as a reference to profile the expressed turbot IgM, IgD and IgT repertoires in skin and spleen. The primary IGH locus was located on chromosome 19, spanned approximately 72 kb, and contained 25 IGHV genes, including 24 functional genes and one pseudogene, together with three IGHD, seven IGHJ and three IGHC genes corresponding to IgT, IgM and IgD. Comparison with the alternate fScoMax1.1 haplotype and a second turbot genome assembly showed conserved IGHD, IGHJ and IGHC content, whereas IGHV gene number differed among assemblies. High throughput 5RACE repertoire sequencing revealed isotype and tissue associated differences in expressed IGH diversity. IgM represented the dominant productive repertoire in both skin and spleen and showed the highest clonotypic diversity, particularly in spleen. IgD displayed an intermediate profile, whereas IgT was more enriched in skin and exhibited the strongest clonal restriction. IGHV subgroup usage was dominated by IGHV3 in IgM and IgD, whereas IgT showed a distinct profile characterized by preferential use of IGHV4, especially in skin. Gene level analysis further showed broad IGHV-IGHJ pairing in IgM and IgD, with preferential use IGHJ3 segment, while IgT sequences paired exclusively with IGHJT. Clonotype sharing between skin and spleen was isotype dependent, being strongest for IgT, intermediate for IgM, and negligible for IgD, suggesting that clonal expansion did not necessarily predict inter tissue trafficking. Together, these results provide a curated genomic and expressed repertoire framework for turbot IGH genes and reveal isotype specific organization of antibody diversity, with IgT displaying a particular repertoire pattern.

immunology↗

bioRxiv2026

Platelet Molecular Maturation Links Platelet Aging and the Platelet Storage Lesion

Human platelets change over their 7-10 day lifespan, yet the molecular mechanisms underlying platelet aging remain poorly defined. Using two independent RNA sequencing datasets of fluorescence-activated cell sorted young and old human platelets, we developed a unified transcriptomic model to characterize RNA metabolism across the platelet lifespan, which we termed platelet molecular maturation. This was applied to RNA sequencing data from room-temperature stored platelets (up to 7 days) and cold-stored platelets (7, 14, or 21 days). We identified highly concordant aging signatures, including 6,015 shared expressed genes and 2,008 shared differentially expressed genes (DEGs) with strongly correlated fold changes, demonstrating a conserved platelet aging program. Nucleotide-level analyses revealed preferential 3'-directed degradation among downregulated transcripts during endogenous platelet aging and room-temperature storage, supporting an organized RNA decay process that was correlated with platelet function changes. Room-temperature storage recapitulated platelet molecular maturation, showing concordance with aging-related gene expression changes and enrichment of downregulated gene sets. In contrast, cold-storage significantly attenuated platelet molecular maturation and 3'-directed degradation. A total of 669 genes were consistently differentially expressed between room-temperature and cold-stored platelets, while no DEGs were detected during cold-storage, indicating transcriptional stability. Platelet transcript stability in cold-storage correlated with preserved platelet hemostatic function. These findings establish platelet molecular maturation as a conserved, functionally relevant model linking endogenous platelet aging to platelet storage lesions and providing mechanistic insight into preserved platelet hemostatic function in cold-storage. This atlas of platelet RNA metabolism supports biomarker discovery and strategies to improve storage. KEY POINTSO_LIBy integrating multiple high-quality RNA sequencing datasets with novel analytic approaches tailored to the biology of anucleate platelets, we show that platelet aging is not a passive process of transcript decay, but follows a structured and reproducible molecular trajectory both endogenously and in storage, which we term platelet molecular maturation. C_LIO_LIStorage temperature emerged as a dominant modifier of this trajectory, with cold-storage markedly slowing RNA metabolic kinetics and preserving transcripts associated with younger, more hemostatically competent platelets. C_LIO_LITogether, these findings provide mechanistic insight into the platelet storage lesion and identify transcriptomic features that may serve as biomarkers or therapeutic targets to extend platelet shelf life. C_LI

genomics↗

bioRxiv2022

Longitudinal comparison of the developing gut virome in infants and their mothers

The virome of the human gut and its development in early life are poorly understood. Here we performed viral metagenomic sequencing on stool samples from a multiethnic, socioeconomically diverse cohort of 53 infants collected longitudinally over their first 3 years of life and their mothers to investigate and compare their viromes. The asymptomatic infant virome consisted of bacteriophages, dietary/environmental viruses, and human pathogenic viruses, in contrast to the material virome, in which sequence reads from human pathogenic viruses were absent or present at extremely low levels. Picornaviruses and phages in the family Microviridae (microviruses) dominated the infant virome, while microviruses and tomato mosaic virus dominated the maternal virome. As the infants aged, the human pathogenic and dietary/environmental virus components remained distinct from the materal virome, while the phage component evolved to become more similar. However, the composition of the evolving infant virome was not determined by the mother and was still maturing to the adult virome at three years of age. ImportanceThe development of the human gut virome in early childhood is poorly understood. Here we use viral metagenomic sequencing in a cohort of 53 infants to the characterize their gut viromes and compare them to their mothers.. This study finds that the infant virome consists of phages and human pathogenic viruses in asymptomatic individuals and is still maturing into the adult virome at three years of age.

microbiology↗

bioRxiv2022

The salivary, metal-binding peptide histatin-5 buffers extracellular copper availability

Antimicrobial peptides (AMPs) are key components of diverse host innate immune systems. The family of human salivary AMPs known as histatins bind Zn and Cu. Fluctuations in Zn and Cu availability play significant roles in the host innate immune response (so-called "nutritional immunity"). Thus, we hypothesised that histatins contribute to nutritional immunity by influencing host Zn and/or Cu availability. We posited that histatins limit Zn availability (promote bacterial Zn starvation) and/or raise Cu availability (promote bacterial Cu poisoning). To test this hypothesis, we examined the interactions between histatin-5 (Hst5) and Group A Streptococcus (GAS), which colonises the human oropharynx. Our results showed that Hst5 does not strongly influence Zn availability. Hst5 did not induce expression of Zn-responsive genes in GAS, nor did it suppress growth of mutant strains that are impaired in Zn transport. Biochemical examination of purified peptides confirmed that Hst5 binds Zn only weakly. By contrast, Hst5 bound Cu tightly and it strongly influenced Cu availability. However, Hst5 did not promote Cu toxicity. Instead, Hst5 suppressed expression of Cu-inducible genes, stopped intracellular accumulation of Cu, and rescued growth of a {Delta}copA mutant strain that is impaired in Cu efflux. We thus proposed a new role for salivary histatins as major Cu buffers in saliva that contribute to microbial homeostasis in the oral cavity and oropharynx by reducing the potential negative effects of Cu exposure (e.g. from food) to microbes. Our results raise broad questions regarding the physiological roles of diverse metal-binding AMPs and the management of host metal availability during host-microbe interactions.

microbiology↗