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- Toll-like receptor evolution: does temperature matter?Publication . Sousa, Carmen; Fernandes, Stefan A.; Cardoso, João; Wang, Ying; Zhai, Wanying; Guerreiro, Pedro; Chen, Liangbiao; Canario, A.V.M.; Power, DeborahToll-like receptors (TLRs) recognize conserved pathogen-associated molecular patterns (PAMPs) and are an ancient and well-conserved group of pattern recognition receptors (PRRs). The isolation of the Antarctic continent and its unique teleost fish and microbiota prompted the present investigation into Tlr evolution. Gene homologues of tlr members in teleosts from temperate regions were present in the genome of Antarctic Nototheniidae and the non-Antarctic sister lineage Bovichtidae. Overall, in Nototheniidae apart from D. mawsoni, no major tlr gene family expansion or contraction occurred. Instead, lineage and species-specific changes in the ectodomain and LRR of Tlrs occurred, particularly in the Tlr11 superfamily that is well represented in fish. Positive selective pressure and associated sequence modifications in the TLR ectodomain and within the leucine-rich repeats (LRR), important for pathogen recognition, occurred in Tlr5, Tlr8, Tlr13, Tlr21, Tlr22, and Tlr23 presumably associated with the unique Antarctic microbiota. Exposure to lipopolysaccharide (Escherichia coli O111:B4) Gram negative bacteria did not modify tlr gene expression in N. rossii head-kidney or anterior intestine, although increased water temperature (+4 degrees C) had a significant effect.
- Transcriptomic down-regulation of immune system components in barrier and hematopoietic tissues after lipopolysaccharide injection in antarctic notothenia coriicepsPublication . Sousa, Carmen; Power, Deborah; Guerreiro, Pedro M; Louro, Bruno; Chen, Liangbiao; Canario, AdelinoThe environmental conditions and isolation in the Antarctic have driven the evolution of a unique biodiversity at a macro to microorganism scale. Here, we investigated the possible adaptation of the teleost Notothenia coriiceps immune system to the cold environment and unique microbial community of the Southern Ocean. The fish immune system was stimulated through an intraperitoneal injection of lipopolysaccharide (LPS 0111:B4 from E. coli) and the tissue transcriptomic response and plasma biochemistry were analyzed 7 days later and compared to a sham injected control. Gene transcription in the head-kidney, intestine and skin was significantly modified by LPS, although tissues showed different responsiveness, with the duodenum most modified and the skin the least modified. The most modified processes in head-kidney, duodenum and skin were related to cell metabolism (up-regulated) and the immune system (comprising 30% of differentially expressed genes). The immune processes identified were mostly down-regulated, particularly interleukins and pattern recognition receptors (PRRs), nucleotide-binding oligomerization domain-like receptors and mannose receptors, unlike the toll-like receptors response commonly described in other teleost fish. The modified transcriptional response was not mirrored by a modified systemic response, as the circulating levels of enzymes of innate immunity, lysozyme and antiproteases, were not significantly different from the untreated and sham control fish. In conclusion, while the N. coriiceps immune system shares many features with other teleosts there are also some specificities. Further studies should better characterize the PRRs and their role in Antarctic teleosts, as well as the importance of the LPS source and its consequences for immune activation in teleosts.
- Responsiveness of pituitary to galanin throughout the reproductive cycle of male European sea bass (Dicentrarchus labrax)Publication . Pinto, P.; Velez, Zélia; Sousa, Carmen; Santos, Soraia; Andrade, André; Alvarado, M. V.; Felip, A.; Zanuy, S.; Canario, A.V.M.The neuropeptide galanin (Gal) is a putative factor regulating puberty onset and reproduction through its actions on the pituitary. The present study investigated the pituitary responsiveness to galanin and the patterns of galanin receptors (Galrs) expression throughout the reproductive cycle of two years old male European sea bass (Dicentrarchus labrax), an important aquaculture species. Quantitative analysis of pituitary and hypothalamus transcript expression of four galr subtypes revealed differential regulation according to the testicular developmental stage, with an overall decrease in expression from the immature stage to the mid-recrudescence stage. Incubation of pituitary cells with mammalian 1-29 Gal peptide induced significant changes in cAMP concentration, with sensitivities that varied according to the testicular development stages. Furthermore 1-29 Gal was able to stimulate both follicle stimulating hormone (Fsh) and luteinizing hormone (Lh) release from pituitary cell suspensions. The magnitude of the effects and effective concentrations varied according to reproductive stage, with generalized induction of Fsh and Lh release in animals sampled in January (full spermiation). The differential expression of galrs in pituitary and hypothalamus across the reproductive season, together with the differential effects of Gal on gonadotropins release in vitro strongly suggests the involvement of the galaninergic system in the regulation the hypothalamus-pituitary-gonad axis of male sea bass. This is to our knowledge the first clear evidence for the involvement of galanin in the regulation of reproduction in non-mammalian vertebrates. (C) 2017 Elsevier Inc. All rights reserved.
- LPS modulates the expression of iron-related immune genes in two Antarctic notothenoidsPublication . Martínez, Danixa Pamela; Sousa, Carmen; Oyarzún, Ricardo; Pontigo, Juan Pablo; Canario, Adelino; Power, Deborah; Vargas-Chacoff, Luis; Guerreiro, PedroThe non-specific immunity can induce iron deprivation as a defense mechanism against potential bacterial pathogens, but little information is available as to its role in Antarctic fish. In this study the response of iron metabolism related genes was evaluated in liver and head kidney of the Antarctic notothenoids Notothenia coriiceps and Notothenia rossii 7 days after lipopolysaccharide (LPS) injection. Average plasma Fe2+ concentration was unaffected by treatment in any of the species. The gene expression response to LPS varied between tissues and species, being stronger in N. coriiceps and more prominent in the head kidney than liver. The reaction to LPS was marked by increased individual variability in most genes analyzed, even when the change in expression was not statistically significant, suggesting different individual sensitivity and coping responses in these wild fish. We found that iron related genes had an attenuated and homogenous response to LPS but there was no detectable relationship between plasma Fe2+ and gene expression. However, overall in both tissues and species LPS exposure set a multilevel response that concur to promote intracellular accumulation of iron, an indication that Antarctic Notothenoids use innate nutritional immunity as a resistance mechanism against pathogens.
- Differential tissue immune stimulation through immersion in bacterial and viral agonists in the Antarctic Notothenia rossiiPublication . Sousa, Carmen; Peng, Maoxiao; Guerreiro, Pedro; Cardoso, João; Chen, Liangbiao; Canario, Adelino; Power, DeborahThe genome evolution of Antarctic notothenioids has been modulated by their extreme environment over millennia and more recently by human -caused constraints such as overfishing and climate change. Here we investigated the characteristics of the immune system in Notothenia rossii and how it responds to 8 h immersion in viral (Poly I:C, polyinosinic: polycytidylic acid) and bacterial (LPS, lipopolysaccharide) proxies. Blood plasma antiprotease activity and haematocrit were reduced in Poly I:C-treated fish only, while plasma protein, lysozyme activity and cortisol were unchanged with both treatments. The skin and duodenum transcriptomes responded strongly to the treatments, unlike the liver and spleen which had a mild response. Furthermore, the skin transcriptome responded most to the bacterial proxy (cell adhesion, metabolism and immune response processes) and the duodenum (metabolism, response to stress, regulation of intracellular signal transduction, and immune system responses) to the viral proxy. The differential tissue response to the two proxy challenges is indicative of immune specialisation of the duodenum and the skin towards pathogens. NOD -like and C -type lectin receptors may be central in recognising LPS and Poly I:C. Other antimicrobial compounds such as iron and seleniumrelated genes are essential defence mechanisms to protect the host from sepsis. In conclusion, our study revealed a specific response of two immune barrier tissue, the skin and duodenum, in Notothenia rossii when exposed to pathogen proxies by immersion, and this may represent an adaptation to pathogen infective strategies.
- Galanin isoforms by alternative splicing: structure, expression, and immunohistochemical location in the gonads of European sea bassPublication . Martins, Rute; Sousa, Carmen; Andrade, André; Molés, Gregorio; Zanuy, Silvia; Gómez, Ana; Canario, Adelino; Pinto, PatríciaGalanin (Gal) is a neuropeptide with multiple functions that is widely expressed in the central and peripheral nervous systems of vertebrates. Anatomical and functional evidence suggests a possible role in regulating reproduction in fishes. To test this possibility, we have isolated and characterized two gal alternative transcripts in European sea bass (Dicentrarchus labrax) that encode two prepropeptides, respectively of 29 (gal_MT853221) and 53 (gal_MT853222) amino acids. The two gal transcripts are highly expressed in brain, pituitary and gonads, and appear to be differentially regulated in males and females. In males, gal_MT853222 in the hypothalamus and gal_MT853221 in the pituitary were downregulated with the progression of spermatogenesis (stages I-III). Both transcripts are downregulated in testicles of 1-year (precocious) and 2-year spermiating males compared to immature fish of the same age. Gal peptides and receptors are expressed throughout ovarian development in the hypothalamic-pituitary-gonadal (HPG) axis of females. In the testis, immunoreactive Gal-29 and Gal-53 peptides were detected in blood vessels and Leydig cells during the spermatogenesis stages I-III but Gal immunostaining was barely undetected in more advanced stages. In the ovary, both peptides localized in interstitial cells and blood vessels and in theca cells surrounding the maturing oocytes. The immunolocalization of galanin in Leydig and theca cells suggests a possible role in steroid production regulation. The different pattern of gal expression and Gal localization in the testis and ovary may suggest the possibility that androgens and estrogens may also regulate Gal gene transcription and translation. Altogether, this study showed evidence for the possible involvement of locally produced Gal in gametogenesis and that its production is differentially regulated in male and female gonads.
- Colocalised genetic associations reveal alternative splicing variants as candidate causal links for breast cancer risk in 10 LociPublication . Duarte, André; Carrasqueiro, Beatriz; Vieira de Sousa, Cármen Sofia; Gonçalves de Gouveia Maia Xavier, Joana; Maia, Ana-TeresaSimple Summary Hundreds of common genetic variants have been linked to breast cancer, but their exact mechanisms of action remain unclear. Understanding these mechanisms could lead to better prevention strategies and improved survival rates. Our study focused on how these variants influence splicing-a process by which a gene's coding elements are rearranged to produce different proteins. By analysing data from healthy breast tissue, we identified 43 variants within twelve genes associated with both alternative splicing and breast cancer risk. We then used advanced computational tools and existing experimental data to explore the biological significance of these findings.Abstract Genome-wide association studies (GWASs) have revealed numerous loci associated with breast cancer risk, yet the precise causal variants, their impact on molecular mechanisms, and the affected genes often remain elusive. We hypothesised that specific variants exert their influence by affecting cis-regulatory alternative splice elements. An analysis of splicing quantitative trait loci (sQTL) in healthy breast tissue from female individuals identified multiple variants linked to alterations in splicing ratios. Through colocalisation analysis, we pinpointed 43 variants within twelve genes that serve as candidate causal links between sQTL and GWAS findings. In silico splice analysis highlighted a potential mechanism for three genes-FDPS, SGCE, and MRPL11-where variants in proximity to or on the splice site modulate usage, resulting in alternative splice transcripts. Further in vitro/vivo studies are imperative to fully understand how these identified changes contribute to breast oncogenesis. Moreover, investigating their potential as biomarkers for breast cancer risk could enhance screening strategies and early detection methods for breast cancer.
- Potential biomarkers of metal toxicity in deep-sea invertebrates – a critical review of the omics dataPublication . Vieira de Sousa, Cármen Sofia; Sun, Jin; Mestre, NéliaDeep-sea mining (DSM) activities are expected to release potentially toxic metal mixtures through the generation of sediment plumes to the marine environment. This may disrupt the normal functioning of biological mechanisms, adversely affecting deep-sea invertebrate organisms. It is thus essential to understand the ecotoxicological effects from these toxic elements in deep-sea organisms and the omics approaches applied to ecotoxicology are seen as promising tools. Here, we provide an overview of the principal biological modifications identified in deep-sea invertebrates when exposed to metals and critically evaluate the current knowledge and discuss which potential biomarkers may be useful after metal exposure. Most of the 50 omics studies on deep-sea invertebrates revised are comparative transcriptomes (n = 41). Forty-three potential biomarker candidates are highlighted from immune system, 46 from cellular metabolism and 29 from oxidative stress. The processes mostly affected by metal toxicity in deep-sea invertebrates are related to innate immune defense; sulfur, chitin, and catabolic metabolism; antioxidation; and detoxification. We acknowledge the current limitations and future perspectives for their uses and emphasize the need to invest in further ecotoxicological studies using the omics approaches.