Duplicated membrane estrogen receptors in the European sea bass (Dicentrarchus labrax): Phylogeny, expression and regulation throughout the reproductive cycle

The numerous estrogen functions reported across vertebrates have been classically explained by their binding to specific transcription factors, the nuclear estrogen receptors (ERs). Rapid non-genomic estrogenic responses have also been recently identified in vertebrates including fish, which can be mediated by membrane receptors such as the G protein-coupled estrogen receptor (Gper). In this study, two genes for Gper, namely gpera and gperb, were identified in the genome of a teleost fish, the European sea bass. Phylogenetic analysis indicated they were most likely retained after the 3R teleost-specific whole genome duplication and raises questions about their function in male and female sea bass. Gpera expression was mainly restricted to brain and pituitary in both sexes while gperb had a widespread tissue distribution with higher expression levels in gill filaments, kidney and head kidney. Both receptors were detected in the hypothalamus and pituitary of both sexes and significant changes in gpers expression were observed throughout the annual reproductive season. In female pituitaries, gpera showed an overall increase in expression throughout the reproductive season while gperb levels remained constant. In the hypothalamus, gpera had a higher expression during vitellogenesis and decreased in fish entering the ovary maturation and ovulation stage, while gperb expression increased at the final atresia stage. In males, gpers expression was constant in the hypothalamus and pituitary throughout the reproductive cycle apart from the mid- to late testicular development stage transition when a significant up-regulation of gpera occurred in the pituitary. The differential sex, seasonal and subtype-specific expression patterns detected for the two novel gper genes in sea bass suggests they may have acquired different and/or complementary roles in mediating estrogens actions in fish, namely on the neuroendocrine control of reproduction.info:eu-repo/semantics/publishedVersio

Control of puberty in farmed fish

91 p., il., y bibliografía. Geir Lasse Taranger [et al.]Puberty comprises the transition from an immature juvenile to a mature adult state of the reproductive system, i.e. the individual becomes capable of reproducing sexually for the first time, which implies functional competence of the brain-pituitary-gonad (BPG) axis. Early puberty is a major problem in many farmed fish species due to negative effects on growth performance, flesh composition, external appearance, behaviour, health, welfare and survival, as well as possible genetic impact on wild populations. Late puberty can also be a problem for broodstock management in some species, while some species completely fail to enter puberty under farming conditions. Age and size at puberty varies between and within species and strains, and are modulated by genetic and environmental factors. Puberty onset is controlled by activation of the BPG axis, and a range of internal and external factors are hypothesized to stimulate and/or modulate this activation such as growth, adiposity, feed intake, photoperiod, temperature and social factors. For example, there is a positive correlation between rapid growth and early puberty in fish. Age at puberty can be controlled by selective breeding or control of photoperiod, feeding or temperature. Monosex stocks can exploit sex dimorphic growth patterns and sterility can be achieved by triploidisation. However, all these techniques have limitations under commercial farming conditions. Further knowledge is needed on both basic and applied aspects of puberty control to refine existing methods and to develop new methods that are efficient in terms of production and acceptable in terms of fish welfare and sustainability.Peer reviewe

Efectos de la restricción calórica sobre el inicio de la pubertad y la calidad del esperma en la lubina europea (Dicentrarchus labrax)

Ponencia presentada en el XIII Congreso Nacional de Acuicultura celebrado en Barcelona del 21 al 24 de noviembre de 2011.This study reports the effects induced by a long fasting protocol on the reproductive performance of male sea bass during the first reproductive season. Two different treatments of food deprivation were carried out from July to March, one feed 1/4 and another feed 1/8 of the ration given to the control group (1/4C, 1/8C and C). Both restricted feed regimes resulted in a deep impact over the weight, length and growth rate indexes. Also, the fat visceral index decreased dramatically in November in both feed restricted groups (1/4C and 1/8C). Interestingly, both restricted and controls had similar gonadosomatic index values in November (IGS= 0.4-0.7%). Moreover, the histological analysis revealed the presence of a high number of death cell bodies in testis of those animals kept under both restricted feed regimes. Furthermore, we evaluated the sperm quality along the reproductive season (December-March) and it was shown that a long-term fasting affects sperm quality parameters of pubertal male sea bass such as, density (nº spz cells/ml) and quantity (ml/kg wt), although no differences were observed in motility (µm/seg). Additionally, no statically differences in 11KT plasma levels were observed among experimental groups. Our study evidences that a shortage on energy store is not enough to abolish partially or totally the puberty onset of prepubertal male sea bass.Proyecto Europeo LIFECYCLE (FP7-222719-1) y Generalitat Valenciana (PROMETEO/2010/003). S.E. disfrutó de una beca JAE-Predoc CSIC y M.S. disfrutó de una beca CIHEAM.Peer Reviewe

Neurones à kisspeptine et oestrogènes. Etude chez le poisson zèbre et le loup de mer. Kisspeptin neurones and their relationships with estrogens. Study in two fish species the zebrafish and the sea bass.

Supported by EU Project LIFECYCLE (FP7-222719-1) to OK and SZ, NEMO project to OK and ACOM/2010/086-GV. SE was supported by a JAE-Predoc (CSIC, Spain).Peer Reviewe

Comparative expression analysis in mature gonads, liver and brain of turbot (Scophthalmus maximus) by cDNA-AFLPS

Turbot is one of the most important farmed fish in Europe. This species exhibits a considerable sexual dimorphism in growth and sexual maturity that makes the all-female production recommended for turbot farming. Our knowledge about the genetic basis of sex determination and the molecular regulation of gonad differentiation in this species is still limited. Our goal was to identify and compare gene expression and functions between testes and ovaries in adults in order to ascertain the relationship between the genes that could be involved in the gonad differentiation or related to the sex determination system. The identification of differentially expressed sex related genes is an initial step towards understanding the molecular mechanisms of gonad differentiation. For this, we carried out a transcriptome analysis based on cDNA-AFLP technique which allowed us to obtain an initial frame on sex-specific gene expression that will facilitate further analysis especially along the critical gonad differentiating period. With the aim of widening the study on sex-biased gene expression we reproduced the same experiments in two somatic tissues: liver and brain. We have selected the liver because it is the most analyzed one regarding sexual dimorphic gene expression and due to its importance in steroid hormones metabolism and the brain because the functional relationship between brain and gonad is documented. We found slight but important differences between sexes which deserve further investigationThis research work was financially supported by the Xunta of Galicia (07MMA004200PR) to A. Viñas. X. Taboada was supported by a fellowship from the European Social Fund and Consellería de Educación e Ordenación Universitaria- Xunta de Galicia (Spain)S

Molecular evolution of aphids and their primary (buchnera sp.) and secondary endosymbionts: implications for the role of symbiosis in insect evolution

Aphids maintain an obligate, endosymbiotic association with Buchnera sp., a bacterium closely related to Escherichia coli. Bacteria are housed in specialized cells of organ-like structures called bacteriomes in the hemocoel of the aphid and are maternally transmitted. Phylogenetic studies have shown that the association had a single origin, dated about 200-250 million years ago, and that host and endosymbiont lineages have evolved in parallel since then. However, the pattern of deepest branching within the aphid family remains unsolved, which thereby hampers an appraisal of, for example, the role played by horizontal gene transfer in the early evolution of Buchnera. The main role of Buchnera in this association is the biosynthesis and provisioning of essential amino acids to its aphid host. Physiological and metabolic studies have recently substantiated such nutritional role. In addition, genetic studies of Buchnera from several aphids have shown additional modifications, such as strong genome reduction, high A+T content compared to free-living bacteria, differential evolutionary rates, a relative increase in the number of non-synonymous substitutions, and gene amplification mediated by plasmids. Symbiosis is an active process in insect evolution as revealed by the intermediate values of the previous characteristics showed by secondary symbionts compared to free-living bacteria and Buchnera.The authors thank the Servicio Central de Soporte a la Investigación Científica (Universitat de València) for bioinformatics and sequencing facilities. The work has been supported by grants GV-3216/95 from Generalitat Valenciana (Spain), BFM2000-1383 from MEC (Spain) and FEDER 2FD1997-1006 (Spain).Peer reviewe

Gonadotropin actions in European sea bass: endocrine roles and biotechnological applications

Comunicación presentada en el 10th International Symposium on Reproductive Physiology of Fish, celebrado en Olhao, Portugal, del 25 al 30 de mayo de 2014The follicle stimulating hormone (Fsh) and the luteinizing hormone (Lh) are central endocrine regulators of gonad function in vertebrates. These gonadotropins act by binding and activating their specific receptors that are located in certain cell types of the gonads. In fish, the differential roles of these hormones are being progressively elucidated with the development of different tools for their study. In the case of European sea bass Dicentrarchus labrax, the isolation of the genes coding for the gonadotropin subunits and receptors allowed in first instance for expression studies. Later, to overcome the limitation of native hormones, recombinant dimeric gonadotropins have been generated, which show different functional characteristics depending on the cell system and DNA construct. In addition, single gonadotropin beta-subunits have been produced and used as antigens for antibody production. This last approach has allowed the development of detection methods for native gonadotropins being the European sea bass one of the few species where both gonadotropins can be detected in their native form. The generation of antibodies has also allowed for their cellular localization and co-localization with other factors, helping to a better understanding of their function. By administration of the recombinant gonadotropins to gonad tissues cultured in vitro we have studied their effects on steroidogenesis, the activated intracellular pathways and their target genes. Their administration in vivo has also been tested both for basic studies and as a biotechnological approach. In this frame, it is known from different studies in mammals that exogenous administration of native hormones in cases of deficiency, including assisted reproduction, can be unsatisfactory due to their rapid clearance from circulation or limited availability. Other than the production of recombinant hormones gene-based therapies by using somatic gene transfer are offered as an alternative. Such an approach has been tested in sea bass for gonadotropin delivery in vivo. The hormones produced by the injected genes were functional and have allowed for different studies on gonadotropin action in spermatogenesis. All together, the use of gene therapy for hormone replacement in fish is a real alternative to the production of recombinant gonadotropins for in vivo use, due to the low cost of production and the high persistence of the injected DNA, and has a broad range of potential applications such as its use in out-of-season breeding programs or reproductive dysfunctions in fish species.Supported by MINECO (AGL2011-28890) and GV (ACOMP/2013/085).Peer Reviewe

Post-transplant lymphomas: a 20-year epidemiologic, clinical and pathologic study in a single center

Background and objectives: to study the incidence, clinical presentation, pathologic features and outcome of post-transplant lymphomas (PTL) during the past 20 years. Design and methods: we undertook a descriptive study of all biopsy-proven cases of PTL diagnosed in our hospital from 1979 through 1999. The average annual incidence rate of PTL was analyzed at 5-year intervals from 1979 to 1999. Risk ratios were estimated by comparing the incidence of PTL among transplanted patients with that of lymphoma observed in the general population of the region. Survival analysis was performed at the univariate level using the Kaplan Meier technique and at the multivariate level by Cox hazard models. Results: seventeen of 1,860 transplanted patients developed a PTL (0.9%). The risk of PTL was calculated to be almost 8-fold higher than the risk of lymphoma in the general population. The risk was highest among those who had received a heart transplant (RR=35.6). The mean time between transplant and the diagnosis of PTL was 31 +/- 29 months. Of all PTL, 88% were of B-cell origin and 53% of the cases tested were Epstein-Barr virus (EBV)-positive. The median survival was 24 months. The majority of patients with allograft involvement died within the 2 months following diagnosis (hazard ratio 5.3; 95% CI 1.4-20.7). Interpretation and conclusions: organ transplantation is a major risk factor for the development of lymphoma, a disease with a particularly bad prognosis when it develops at the site of the allograft. Early diagnosis and more specific treatment may improve PTL survival

ICO-ICS Praxis para el tratamiento médico y con irradiación del cáncer de orofaringe, hipofaringe, laringe y nasofaringe

Tractament mèdic; Tractament amb irradiació; Càncer de cap i coll; Carcinoma de nasofaringeTratamiento médico; Tratamiento con irradiación; Cáncer de cabeza y cuello; Carcinoma de nasofaringeMedical treatment; Irradiation treatment; Head and neck cancer; Nasopharyngeal carcinomaL’anomenat càncer de cap i coll engloba un grup de tumors malignes localitzats en diverses zones de les vies aerodigestives superiors: sins paranasals, nasofaringe, orofaringe (amígdala, paladar tou, base de la llengua), hipofaringe, laringe, cavitat oral (mucosa oral, geniva, paladar dur, llengua i terra de la boca) i glàndules salivals. L'objectiu d'aquest document és - Desenvolupar, difondre, implementar i avaluar resultats de la ICO-ICSPraxi per al tractament del càncer d’orofaringe, hipofaringe, laringe i nasofaringe. - Disminuir la variabilitat terapèutica entre els pacients tractats en els diversos centres d’aquesta institució. - Implementar els resultats de la terapèutica en els pacients amb càncer de càvum, orofaringe, hipofaringe o laringe tractats d’acord amb les recomanacions d’aquesta guia

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response