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Louro, B.

Publications and source records attributed to Louro, B..

3 recordsLinked to original sources

Harnessing the immune system to treat bone loss: The immunomodulatory and osteoprotective effects of the microalga Skeletonema costatum

The emerging field of osteoimmunology provides compelling evidence for the pivotal role of the immune system in the development of bone erosive pathologies such as osteoporosis. However, no immunomodulatory drug has yet been integrated into the therapeutic management of bone loss. Recently, driven by the demand for next-generation treatments for these conditions, natural compounds are gaining renewed attention as promising candidates for drug discovery. In this study, we explored the anti-osteoclastogenic effects of an emerging extract from the marine microalga Skeletonema costatum. Using a zebrafish model of bone regeneration, we demonstrated the extracts ability to inhibit the recruitment of osteoclast progenitors and block their differentiation into mature osteoclasts in vivo. Bulk RNA sequencing of early-stage fin blastemas revealed the downregulation of genes involved in inflammation, T-cell activation, and antigen presentation, suggesting that the extract exerts its effects primarily through immunomodulatory mechanisms. To further assess its therapeutic potential, we tested the extract in a medaka model of RANKL-induced osteoporosis and on a murine macrophage cell line. The extract effectively prevented bone loss in fish and inhibited osteoclastic differentiation in murine macrophages in vitro. Collectively, our findings provide mechanistic insights into a novel, therapeutically relevant natural extract, offering proof of concept for its osteoprotective potential through immune system modulation. SignificanceRecent findings in the field of osteoimmunology reveal the potential of targeting immune cells to regulate bone homeostasis. However, this approach has yet to be applied to therapies for bone erosive conditions. This study explores the potential of an immunomodulatory strategy using an emerging natural extract, which prevent osteoclast differentiation by modulating inflammation, T-cell activation, and macrophage fate determination in zebrafish and medaka models of bone regeneration and osteoporosis. The extract also inhibits osteoclastic differentiation in a murine macrophage line, suggesting its translatability to mammalian systems. By focusing on immune pathways, this research provides a proof of concept for developing immunomodulatory treatments for osteoporosis and similar conditions, addressing a critical need in bone health management.

immunology↗

Inversions Dominate Evolution in the Highly Admixed European Sardine (Sardina pilchardus)

Inversions can play key roles in the genetic architecture of adaptation, but the scale of their effects across different species remains poorly understood. Here, we use whole- genome sequencing to investigate the influence of inversions on the population genomics of the r-selected European sardine (Sardina pilchardus). Allele frequency differences from millions of SNPs across 34 populations spanning the species range were analyzed. Genomic scans identified several extreme outlier regions overlapping chromosome-scale inversions, collectively representing over half the genome. Our findings suggest these inversions are associated with locally adapted life history strategies. First, SNPs within outlier regions containing inversions exhibited striking allele frequency differences between Atlantic and Mediterranean sardines, which differ in key adaptive life history traits. In the Atlantic, inversion allele frequencies varied latitudinally, while in the Mediterranean, they shifted longitudinally, aligning with temperature and oceanographic features that influence sardine life history strategies. Moreover, adjacent populations in contrasting environments displayed pronounced allele frequency differences in inversions. These spatial patterns of allele frequencies sharply contrasted with those based on neutral loci, indicating they are driven by selection. After rigorously filtering SNPs affected by selection and inversions, sardine populations showed high admixture across their range but significant population structure and isolation by distance, especially in the Mediterranean. This study demonstrates that inversions can shape genome-wide patterns of genetic diversity and population structure in highly admixed r-selected marine species. These findings also offer crucial insights for stock delimitation and management of this commercially valuable species in the face of climate change.

genomics↗

A haplotype-resolved draft genome of the European sardine (Sardina pilchardus)

BackgroundThe European sardine (Sardina pilchardus Walbaum, 1792) has a high cultural and economic importance throughout its distribution. Monitoring studies of sardine populations report an alarming decrease in stocks due to overfishing and environmental change, which has resulted in historically low captures along the Iberian Atlantic coast. Consequently, there is an urgent need to better understand the causal factors of this continuing decrease in the sardine stock. Important biological and ecological features such as levels of population diversity, structure, and migratory patterns can be addressed with the development and use of genomics resources.\n\nFindingsThe sardine genome of a single female individual was sequenced using Illumina HiSeq X Ten 10X Genomics linked-reads generating 113.8 Gb of data. Three draft genomes were assembled: two haploid genomes with a total size of 935 Mbp (N50 103Kb) each, and a consensus genome with a total size of 950 Mbp (N50 97Kb). The genome completeness assessment captured 84% of Actinopterygii Benchmarking Universal Single-Copy Orthologs. To obtain a more complete analysis, the transcriptomes of eleven tissues were sequenced and used to aid the functional annotation of the genome, resulting in 40 777 genes predicted. Variant calling on nearly half of the haplotype genome resulted in the identification of more than 2.3 million phased SNPs with heterozygous loci.\n\nConclusionsA draft genome was obtained with the 10X Genomics linked-reads technology, despite a high level of sequence repeats and heterozygosity that are expected genome characteristics of a wild sardine. The reference sardine genome and respective variant data are a cornerstone resource of ongoing population genomics studies to be integrated into future sardine stock assessment modelling to better manage this valuable resource.

genomics↗