Estimation of Genetic Effects and Genotype-Phenotype Maps

Determining the genetic architecture of complex traits is a necessary step to understand phenotypic changes in natural, experimental and domestic populations. However, this is still a major challenge for modern genetics, since the estimation of genetic effects tends to be complicated by genetic interactions, which lead to changes in the effect of allelic substitutions depending on the genetic background. Recent progress in statistical tools aiming to describe and quantify genetic effects meaningfully improves the efficiency and the availability of genotype-to-phenotype mapping methods. In this contribution, we facilitate the practical use of the recently published ‘NOIA’ quantitative framework by providing an implementation of linear and multilinear regressions, change of reference operation and genotype-to-phenotype mapping in a package (‘noia’) for the software R, and we discuss theoretical and practical benefits evolutionary and quantitative geneticists may find in using proper modeling strategies to quantify the effects of genes

Orthogonal Decomposition of the Genetic Variance for Epistatic Traits Under Linkage Disequilibrium—Applications to the Analysis of Bateson-Dobzhansky-Müller Incompatibilities and Sign Epistasis

The one-century-old theory of orthogonal genetic variance decomposition originated the field of quantitative genetics and has kept on being improved ever since. Recently, serious concerns about the possibility of attaining a satisfactory implementation of genetic variance decomposition with linkage disequilibrium (LD) and epistasis have been raised. In this paper we dissipate such doubts by completing the classical theory of variance decomposition into additive, dominance and epistasis components with LD. We apply that theory to the analysis of the genotype-to-phenotype maps of two cases of particular evolutionary interest—Bateson-Dobzhansky-Müller incompatibilities and sign epistasis. For the first case we show how negative LD and reduction of heterozygotes may contribute to maintain genetic variability after secondary contact. For the second case we show that LD transforms the set of frequencies leading to an evolutionary plateau into a ridge. Our theoretical developments reassuringly reflect the complexity LD conveys to genetic systems throughout novel properties—as compared with systems under linkage equilibrium. We argue that such particularities might have actually contributed to cause confusion about the feasibility of developing this methodology. In any case, the theory we provide in this paper enables new perspectives in both evolutionary and quantitative genetics studies

Evidencias do cambio climático na hidrografía e a dinámica das rías e da plataforma galega

16 páginas, 9 figuras, 3 tablas[EN] This study is focused on multidecadal-scale variations of the hydrographic and hydrodynamic features of Rías and shelf waters off Galicia. Water masses take, through their thermohaline characteristics, a footprint of the climatic variability, mainly caused by changes either in the hydrological budget (precipitation, evaporation, runoff), in heat exchange and wind stress. In this study we focus in the evidences of change in the surface and sub-surface water mass characteristics. Regarding surface water masses, a significant warming during the last 45 years has been noticed, at a rate of 0.17 ºC/ decade. This warming was especially intense from the 1970’s, 0.27 ºC/decade. The tendency is opposite in subsurface waters, but it only takes into account data from the last 15 years. Regarding hydrodynamics, because of its strong influence in the renewal time of the Rías and consequently in their living resources, a study of decadal changes in the estuarine circulation of the Rías de Vigo and Arousa has been made. Results showed a progressive decay in the estuarine circulation, which causes an increase of renewal times. On the other hand, indirect evidence of a possible deceleration of the winter Iberian Poleward Current (IPC) are reported. This slow down is partially caused by a decrease in the meridional (N-S) temperature gradient off the Iberian coast. Nevertheless, the fall of the meridional gradient is not clear because it has been inferred from surface waters. On the contrary, IPC seems to be intensified by the increasing southerly autumn winds, although it appears weakened by the decreasing southerly winter winds. Thus, the overall effect of the CIP is still uncertain. Finally, a study of sea level and wave changes on the Galician coast has been made. An increase of (2-2.5 cm/ decade) in the sea level as well as a decrease in the wave height (3 cm/decade) has been reported, but in this last topic results are not significant[GA] Este estudo centrarase en determinar as variacións que ocorren a escalas multidecadais nas características hidrográficas e hidrodinámicas das augas das rías e da plataforma fronte a Galicia. As masas de auga reciben a través das súas características termohalinas unha pegada das alteracións climáticas, principalmente a causa de cambios no balance hidrolóxico (precipitación, evaporación, achegas continentais), do intercambio de calor e da acción do vento. Neste estudo analizaremos as evidencias de cambio nas características das masas de auga superficiais e subsuperficiais. Nas primeiras detectouse quentamento de xeito significativo nos últimos 45 anos a unha taxa media de 0,17 ºC por década, especialmente intenso desde hai 30 anos, 0,27 ºC por década. Nas augas subsuperficiais a tendencia é a inversa, aínda que só se conta con datos dos últimos 15 anos. En canto á hidrodinámica, e pola súa forte implicación nos tempos de renovación da ría e, polo tanto, nos recursos mariños que viven nela, fíxose un estudo sobre os cambios na circulación estuárica das rías de Vigo e Arousa nas últimas décadas. Os resultados amosan un descenso paulatino a longa escala temporal da circulación que causa un aumento dos tempos de renovación. Por outra banda, achéganse evidencias indirectas dunha posible ralentización da corrente invernal cara ao Polo (CIP) causada por un descenso no gradiente meridional (N-S) de temperatura fronte ás costas ibéricas. Non obstante, o descenso do gradiente meridional non está claro, pois induciuse só a partir de datos superficiais. Ademais, a propia CIP amosa estar intensificada pola maior intensidade dos ventos sur no outono e debilitada polo descenso dos ventos do sur no inverno, polo que o efecto global na CIP é aínda incerto. Por último, faise un estudo dos cambios do nivel do mar e da ondada nas costas galegas que amosa un aumento daquel (2-2,5 cm/década) e un descenso desta (3 cm/década), aínda que no caso da ondada os resultados non son concluíntesPeer reviewe

Using zebrafish embryo bioassays combined with high-resolution mass spectrometry screening to assess ecotoxicological water bodies quality status: A case study in Panama rivers

Several studies show that many water bodies in developing countries are increasingly affected by anthropogenic pressure, such as agricultural activities, domestic and industrial wastewater. However, data is scarce in several of such countries, including Panama. Thus, in this work, the ecotoxicological status of selected rivers in Panama with distinct input sources were evaluated using the zebrafish (Danio rerio) embryo bioassays combined with a liquid chromatography-high resolution mass spectrometry screening of contaminants of emerging concern (CECs), using a library of over 3200 chemicals. A total of 68 CECs, including pharmaceuticals and metabolites, pesticides and several industrial chemicals, could be tentatively identified. Additionally, the zebrafish embryo bioassays showed a significant increase (p < 0.05) in embryo mortality/abnormalities when incubated with water samples from two rivers, Matasnillo and Curundú (47.5% and 32%, respectively). Importantly, a positive correlation between ecotoxicological endpoints and some of the detected CECs was observed. The findings demonstrate that both rivers are under strong anthropogenic pressure, and therefore, management actions are urgently needed to decrease their level of contamination. Overall, this study further supports the use of the zebrafish embryo bioassay as a fast, high throughput approach for screening the toxicity of water samples, and highlights the advantages of combining ecotoxicological assays with high-resolution mass spectrometry to an expedite assessment of the ecotoxicological status of water bodies.This work was supported by the Portuguese Foundation for Science and Technology (FCT) (PTDC|CTA-AMB|31554|2017; UIDB/04423/2020; UIDP/04423/2020), the Spanish Agencia Estatal de Investigación (ref. CTM2017-84763-C3-2-R), the Galician Council of Culture, Education and Universities (ref. ED431C2017/36 and Verónica Castro predoctoral contract, ref. ED481A-2017/156), co-funded by the European Regional Development Fund (ERDF/FEDER).2023-02-02S

Venous thromboembolism in heart transplant recipients: Incidence, recurrence and predisposing factors

[Abstract] Background. A high frequency of venous thromboembolism (VTE) has been observed after lung, kidney, and liver transplantation. However, data about the incidence of this complication among heart transplant (HT) recipients are lacking. Methods. We analyzed the incidence, recurrence, and predisposing factors of VTE in a single-center cohort of 635 patients who underwent HT from April 1991 to April 2013. Deep venous thrombosis (DVT) and pulmonary embolism (PE) were considered as VTE episodes. Results. During a median post-transplant follow-up of 8.4 years, 62 VTE episodes occurred in 54 patients (8.5%). Incidence rates of VTE, DVT, and PE were, respectively, 12.7 (95% confidence interval [CI], 9.7–16.3), 8.4 (95% CI, 6.0–11.4), and 7.0 (95% CI 4.8–9.7) episodes per 1,000 patient-years. Incidence rates of VTE during the first post-transplant year and beyond were, respectively, 45.1 (95% CI, 28.9–67.1) and 8.7 (95% CI 6.2–11.2) episodes per 1,000 patient-years. The incidence rate of VTE recurrence after a first VTE episode was 30.5 (95% CI, 13.2–60.2) episodes per 1,000 patient-years. By means of multivariable Cox regression, chronic renal dysfunction, older age, obesity, and the use of mammalian target of rapamycin inhibitors were identified as independent risk factors for VTE among HT recipients. Conclusions. VTE is a frequent complication after HT, mainly during the first post-operative year. In view of a high recurrence rate, long-term anti-coagulation should be considered in HT recipients who experience a first VTE episode

Transcriptomic data on the transgenerational exposure of the keystone amphipod Gammarus locusta to simvastatin

The use of transcriptomics data brings new insights and works as a powerful tool to explore the molecular mode of action (MoA) of transgenerational inheritance effects of contaminants of emerging concern. Therefore, in this dataset, we present the transcriptomic data of the transgenerational effects of environmentally relevant simvastatin levels, one of the most prescribed human pharmaceuticals, in the keystone amphipod species Gammarus locusta. In summary, G. locusta juveniles were maintained under simvastatin exposure up to adulthood (exposed group - F0E) and the offspring of F0E were transferred to control water for the three subsequent generations (transgenerational group - F1T, F2T and F3T). To gain insights into the biological functions and canonical pathways transgenerationally disrupted by simvastatin, a G. locusta de novo transcriptome assembly was produced and the transcriptomic profiles of three individual G. locusta females, per group, over the four generations (F0 to F3) - solvent control groups (F0.C, F1.C, F2.C and F3.C), F0 320 ng/L simvastatin exposed group (F0.320E) and F1 to F3 320 transgenerational group (F1.320T; F2.320T and F3.320T) - were analyzed. Briefly, Illumina HiSeq™ 2500 platform was used to perform RNA sequencing, and due to the unavailability of G. locusta genome, the RNA-seq datasets were assembled de novo using Trinity and annotated with Trinotate software. After assembly and post-processing steps, 106093 transcripts with N50 of 2371 bp and mean sequence length of 1343.98 bp was produced. BUSCO analyses showed a transcriptome with gene completeness of 97.5 % Arthropoda library profile. The Bowtie2, RSEM and edgeR tools were used for the differential gene expression (DEGs) analyses that allowed the identification of a high quantity of genes differentially expressed in all generations. Finally, to identify the main metabolic pathways affected by the transgenerational effects of SIM across all generations, the DGEs genes were blasted onto KEGG pathways database using the KAAS webserver. The data furnished in this article allows a better molecular understanding of the transgenerational effects produced by simvastatin in the keystone amphipod G. locusta and has major implications for hazard and risk assessment of pharmaceuticals and other emerging contaminants. This article is related to the research article entitled “Transgenerational inheritance of chemical-induced signature: a case study with simvastatinThis article was developed under the Transobesogen project - Trans-phyletic obesogenic responses: from epigenetic modules to transgenerational environmental impacts (reference PTDC/CTA-AMB/31544/2017 - NORTE-01-0145-FEDER-031544), cofunded by Portugal 2020, the European Union through the ERDF and by the Portuguese Foundation for Science and Technology – FCT. This article was also supported by FCT through national funds (UIDB/04423/2020; UIDP/04423/2020), by the Spanish Agencia Estatal de Investigación (CTM2017-84763-C3-2-R) and by the Galician Council of Culture, Education and Universities (ED431C2017/36), cofounded by ERDF. A PhD grant awarded to Susana Barros acknowledges the doctoral grant attributed by FCT with reference PD/BD/143090/2018S

Fluorescent Advanced Glycation End Products and Their Soluble Receptor: The Birth of New Plasmatic Biomarkers for Risk Stratification of Acute Coronary Syndrome

Objective: Advanced glycation end products (AGEs) have pathophysiological implications in cardiovascular diseases. The aim of our study was to evaluate the prognostic value of fluorescent AGEs and its soluble receptor (sRAGE) in the context of acute coronary syndrome (ACS), both in-hospital phase and follow-up period. Methods: A prospective clinical study was performed in patients with debut's ACS. The endpoints were the development of cardiac events (cardiac deaths, re-infarction and new-onset heart failure) during in-hospital phase and follow-up period (366 days, inter-quartile range: 273-519 days). 215 consecutive ACS patients admitted to the coronary care unit (62.7±13.0 years, 24.2% female) were included. 47.4% had a diagnosis of ST segment elevation myocardial infarction. AGEs and sRAGE were analysed by fluorescence spectroscopy and competitive ELISA, respectively. Risk scores (GRACE, TIMI, PURSUIT) were calculated retrospectively using prospective data. The complexity of coronary artery disease was evaluated by SYNTAX score. Results: The mean fluorescent AGEs and sRAGE levels were 57.7±45.1 AU and 1045.4±850.0 pg/mL, respectively. 19 patients presented cardiac events during in-hospital phase and 29 during the follow-up. In-hospital cardiac events were significantly associated with higher sRAGE levels (p = 0.001), but not long-term cardiac events (p = 0.365). Regarding fluorescent AGE the opposite happened. After multivariate analysis correcting by gender, left ventricular ejection fraction, glucose levels, haemoglobin, GRACE and SYNTAX scores, sRAGE was significantly associated with in-hospital prognosis, whereas fluorescent AGEs was significantly associated with long-term prognosis. Conclusions: We conclude that elevated values of sRAGE are associated with worse in-hospital prognosis, whereas high fluorescent AGE levels are associated with more follow-up events

Transgenerational inheritance of chemical-induced signature: A case study with simvastatin

The hypothesis that exposure to certain environmental chemicals during early life stages may disrupt reproduction across multiple non-exposed generations has significant implications for understanding disease etiology and adverse outcomes. We demonstrate here reproductive multi and transgenerational effects, at environmentally relevant levels, of one of the most prescribed human pharmaceuticals, simvastatin, in a keystone species, the amphipod Gammarus locusta. The transgenerational findings has major implications for hazard and risk assessment of pharmaceuticals and other contaminants of emerging concern given that transgenerational effects of environmental chemicals are not addressed in current hazard and risk assessment schemes. Considering that the mevalonate synthesis, one of the key metabolic pathways targeted by simvastatin, is highly conserved among metazoans, these results may also shed light on the potential transgenerational effects of simvastatin on other animals, including humans.This research was funded by COMPETE 2020, Portugal 2020, the European Union through the ERDF and the Portuguese Foundation for Science and Technology – FCT (Transobesogen project – Trans-phyletic obesogenic responses: from epigenetic modules to transgenerational environmental impacts, reference: PTDC/CTA-AMB/31544/2017 – NORTE-01-0145-FEDER-031544). This research was also supported by the National Funds through FCT under the projects (UIDB/04423/2020; UIDP/04423/2020), by the Spanish Agencia Estatal de Investigación (CTM2017-84763-C3-2-R), and by the Galician Council of Culture, Education and Universities (ED431C2017/36), cofounded by ERDF. A PhD grant awarded to Susana Barros (PD/BD/143090/2018) was funded by the FCTS

Effects of ispaghula husk and guar gum on postprandial glucose and insulin concentrations in healthy subjects

P. 235-243The aim of this study was to evaluate, under the same experimental conditions and in the same subjects, the effects of ispaghula husk and guar gum on postprandial glucose and insulin concentrations in healthy female subjects(ten healthy female volunteers aged 30 ± 48 y with normal body mass indices).S