Improved estimation of inbreeding and kinship in pigs using optimized SNP panels

BACKGROUND: Traditional breeding programs consider an average pairwise kinship between sibs. Based on pedigree information, the relationship matrix is used for genetic evaluations disregarding variation due to Mendelian sampling. Therefore, inbreeding and kinship coefficients are either over or underestimated resulting in reduction of accuracy of genetic evaluations and genetic progress. Single nucleotide polymorphism (SNPs) can be used to estimate pairwise kinship and individual inbreeding more accurately. The aim of this study was to optimize the selection of markers and determine the required number of SNPs for estimation of kinship and inbreeding. RESULTS: A total of 1,565 animals from three commercial pig populations were analyzed for 28,740 SNPs from the PorcineSNP60 Beadchip. Mean genomic inbreeding was higher than pedigree-based estimates in lines 2 and 3, but lower in line 1. As expected, a larger variation of genomic kinship estimates was observed for half and full sibs than for pedigree-based kinship reflecting Mendelian sampling. Genomic kinship between father-offspring pairs was lower (0.23) than the estimate based on pedigree (0.26). Bootstrap analyses using six reduced SNP panels (n = 500, 1000, 1500, 2000, 2500 and 3000) showed that 2,000 SNPs were able to reproduce the results very close to those obtained using the full set of unlinked markers (n = 7,984-10,235) with high correlations (inbreeding r > 0.82 and kinship r > 0.96) and low variation between different sets with the same number of SNPs. CONCLUSIONS: Variation of kinship between sibs due to Mendelian sampling is better captured using genomic information than the pedigree-based method. Therefore, the reduced sets of SNPs could generate more accurate kinship coefficients between sibs than the pedigree-based method. Variation of genomic kinship of father-offspring pairs is recommended as a parameter to determine accuracy of the method rather than correlation with pedigree-based estimates. Inbreeding and kinship coefficients can be estimated with high accuracy using ≥2,000 unlinked SNPs within all three commercial pig lines evaluated. However, a larger number of SNPs might be necessary in other populations or across lines

Evidence for a role of nitric oxide in hindlimb vasodilation induced by hypothalamic stimulation in anesthetized rats

Electrical stimulation of the hypothalamus produces cardiovascular adjustments consisting of hypertension, tachycardia, visceral vasoconstriction and hindlimb vasodilation. Previous studies have demonstrated that hindlimb vasodilation is due a reduction of sympathetic vasoconstrictor tone and to activation of beta2-adrenergic receptors by catecholamine release. However, the existence of a yet unidentified vasodilator mechanism has also been proposed. Recent studies have suggested that nitric oxide (NO) may be involved. The aim of the present study was to investigate the role of NO in the hindquarter vasodilation in response to hypothalamic stimulation. In pentobarbital-anesthetized rats hypothalamic stimulation (100 Hz, 150µA, 6 s) produced hypertension, tachycardia, hindquarter vasodilation and mesenteric vasoconstriction. Alpha-adrenoceptor blockade with phentolamine (1.5 mg/kg, iv) plus bilateral adrenalectomy did not modify hypertension, tachycardia or mesenteric vasoconstriction induced by hypothalamic stimulation. Hindquarter vasodilation was strongly reduced but not abolished. The remaining vasodilation was completely abolished after iv injection of the NOS inhibitor L-NAME (20 mg/kg, iv). To properly evaluate the role of the mechanism of NO in hindquarter vasodilation, in a second group of animals L-NAME was administered before alpha-adrenoceptor blockade plus adrenalectomy. L-NAME treatment strongly reduced hindquarter vasodilation in magnitude and duration. These results suggest that NO is involved in the hindquarter vasodilation produced by hypothalamic stimulation.Em animais anestesiados a EE do hipotálamo produz um padrão de ajustes cardiovasculares caracterizado por hipertensão arterial, taquicardia, vasodilatação muscular e vasoconstrição mesentérica, entretanto, os mecanismos periféricos envolvidos nestes ajustes cardiovasculares ainda não foram completamente esclarecidos. O presente estudo teve como objetivo caracterizar os mecanismos periféricos responsáveis pela redistribuição de fluxo sanguíneo produzidas pela EE do hipotálamo. Os resultados obtidos demonstraram que 1) em ratos anestesiados a EE do hipotálamo produziu hipertensão arterial, taquicardia, vasoconstrição no leito mesentérico e acentuada vasodilatação dos membros posteriores; 2) a combinação do bloqueio farmacológico de receptores alfa1 e alfa2 adrenérgicos com fentolamina mais adrenalectomia bilateral reduziu a vasoconstrição mesentérica e a vasodilatação dos membros posteriores. Nestes animais o bloqueio da síntese de NO com L-NAME provocou nova redução significante da vasodilatação dos membros posteriores; 3) a administração de L-NAME, previamente o bloqueio farmacológico com fentolamina mais adrenalectomia bilateral, reduziu as respostas de vasoconstrição mesentérica e de vasodilatação dos membros posteriores. Estes resultados sugerem a existência de pelo menos três possíveis mecanismos responsáveis pela vasodilatação dos membros posteriores induzida pela EE do hipotálamo: 1) ativação de receptores beta-adrenérgicos por catecolaminas liberadas pela medula adrenal; 2) redução do tono vasoconstritor simpático e 3) um terceiro mecanismo que utiliza NO como mediador.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)UNIFESP-EPM Departamento de FisiologiaUNIFESP, EPM, Depto. de FisiologiaSciEL

Sialyl Lewis x expression in canine malignant mammary tumours: correlation with clinicopathological features and E-Cadherin expression

<p>Abstract</p> <p>Background</p> <p>Sialyl Lewis x (sLe^x) antigen is a carbohydrate antigen that is considered not only a marker for cancer but also implicated functionally in the malignant behaviour of cancer cells. Overexpression of sLe^xis associated with enhanced progression and metastases of many types of cancer including those of the mammary gland. Canine mammary tumours can invade and give rise to metastases via either lymphatic or blood vessels.</p> <p>E-Cadherin is specifically involved in epithelial cell-to-cell adhesion. In cancer, E-Cadherin underexpression is one of the alterations that characterizes the invasive phenotype and is considered an invasion/tumour suppressor gene. Partial or complete loss of E-Cadherin expression correlates with poor prognosis in canine malignant mammary cancer.</p> <p>The aim of this study was to analyse the sLe^xexpression in canine malignant mammary tumours and to evaluate if the presence of sLe^xcorrelates with the expression of E-Cadherin and with clinicopathological features.</p> <p>Methods</p> <p>Fifty-three cases of canine mammary carcinomas were analysed immunohistochemically using monoclonal antibodies against sLe^x(IgM) and E-Cadherin (IgG). The clinicopathological data were then assessed to determine whether there was a correlation with sLe^xtumour expression. Double labelled immunofluorescence staining was performed to analyse the combined expression of sLe^xand E-Cadherin.</p> <p>Results</p> <p>sLe^xexpression was consistently demonstrated in all cases of canine mammary carcinomas with different levels of expression. We found a significant relationship between the levels of sLe^xexpression and the presence of lymph node metastases. We also demonstrated that when E-Cadherin expression was increased sLe^xwas reduced and vice-versa. The combined analysis of both adhesion molecules revealed an inverse relationship.</p> <p>Conclusion</p> <p>In the present study we demonstrate the importance of sLe^xin the malignant phenotype of canine malignant mammary tumours. Our results support the use of sLe^xas a prognostic tumour marker in canine mammary carcinomas. Furthermore, we showed that sLe^xand E-Cadherin expression were inversely correlated. Future studies are warranted to clarify the molecular mechanism underlying the relation between sLe^xand E-Cadherin in canine mammary carcinoma cells which represents an important comparative model to woman breast cancer.</p

Genomic selection for crossbred performance accounting for breed-specific effects

International audienceAbstractBackgroundBreed-specific effects are observed when the same allele of a given genetic marker has a different effect depending on its breed origin, which results in different allele substitution effects across breeds. In such a case, single-breed breeding values may not be the most accurate predictors of crossbred performance. Our aim was to estimate the contribution of alleles from each parental breed to the genetic variance of traits that are measured in crossbred offspring, and to compare the prediction accuracies of estimated direct genomic values (DGV) from a traditional genomic selection model (GS) that are trained on purebred or crossbred data, with accuracies of DGV from a model that accounts for breed-specific effects (BS), trained on purebred or crossbred data. The final dataset was composed of 924 Large White, 924 Landrace and 924 two-way cross (F1) genotyped and phenotyped animals. The traits evaluated were litter size (LS) and gestation length (GL) in pigs.ResultsThe genetic correlation between purebred and crossbred performance was higher than 0.88 for both LS and GL. For both traits, the additive genetic variance was larger for alleles inherited from the Large White breed compared to alleles inherited from the Landrace breed (0.74 and 0.56 for LS, and 0.42 and 0.40 for GL, respectively). The highest prediction accuracies of crossbred performance were obtained when training was done on crossbred data. For LS, prediction accuracies were the same for GS and BS DGV (0.23), while for GL, prediction accuracy for BS DGV was similar to the accuracy of GS DGV (0.53 and 0.52, respectively).ConclusionsIn this study, training on crossbred data resulted in higher prediction accuracy than training on purebred data and evidence of breed-specific effects for LS and GL was demonstrated. However, when training was done on crossbred data, both GS and BS models resulted in similar prediction accuracies. In future studies, traits with a lower genetic correlation between purebred and crossbred performance should be included to further assess the value of the BS model in genomic predictions

Preliminary Assessment of the Chemical Stability of Dried Extracts from Guazuma ulmifolia Lam. (Sterculiaceae)

We report the results of a preliminary estimation of the stability of the dried extract from bark of Guazuma ulmifolia Lam. (“Mutamba”), with and without added colloidal silicon dioxide (CSD). The physical and chemical properties and the compatibility of CSD in the extract were evaluated for 21 days of storage under stress conditions of temperature (45 ± 2°C) and humidity (75 ± 5%). Thermogravimetry (TG) was supplemented using selective high-performance liquid chromatography (HPLC) for determination of stability of the characteristic constituents (chemical markers), namely, procyanidin B2 (PB2) and epicatechin (EP). The results showed that PB2 is an appropriate compound to be used as a chemical marker in the quality control of dried extracts of G. ulmifolia. The stress study showed that there was no significant difference between the two formulations. However, considering the TG data and the high temperatures involved, the results suggest that CSD increases the stability of the dried extract of G. ulmifolia

Counting BPS states on the Enriques Calabi-Yau

We study topological string amplitudes for the FHSV model using various techniques. This model has a type II realization involving a Calabi-Yau threefold with Enriques fibres, which we call the Enriques Calabi-Yau. By applying heterotic/type IIA duality, we compute the topological amplitudes in the fibre to all genera. It turns out that there are two different ways to do the computation that lead to topological couplings with different BPS content. One of them leads to the standard D0-D2 counting amplitudes, and from the other one we obtain information about bound states of D0-D4-D2 branes on the Enriques fibre. We also study the model using mirror symmetry and the holomorphic anomaly equations. We verify in this way the heterotic results for the D0-D2 generating functional for low genera and find closed expressions for the topological amplitudes on the total space in terms of modular forms, and up to genus four. This model turns out to be much simpler than the generic B-model and might be exactly solvable.Comment: 62 pages, v3: some results at genus 3 corrected, more typos correcte

Safflower oil: an integrated assessment of phytochemistry, antiulcerogenic activity, and rodent and environmental toxicity

Gastric ulcers are a significant medical problem and the development of complications lead to significant mortality rates worldwide. In Brazil, Carthamus tinctorius L., Asteraceae, seeds essential oil, the safflower oil, is currently used as a thermogenic compound and as treatment for problems related to the cardiovascular system. In this study, by Raman spectroscopy, it was shown that oleic and linoleic acids are the compounds present in higher concentrations in the safflower oil. We demonstrated that safflower oil (750 mg/kg, p.o.) decrease the ulcerogenic lesions in mice after the administration of hydrochloric acid-ethanol. The gastric ulcers induced by non-steroidal anti-inflammatory drug (NSAID) in mice treated with cholinomimetics were treated with four different doses of safflower oil, of which, the dose of 187.5 mg/kg (p.o.) showed significant antiulcerogenic properties (**p < 0.01). Moreover, the safflower oil at doses of 187.5 mg/kg (i.d.) increased the pH levels, gastric volume (**p < 0.01) and gastric mucus production (***p < 0.001), and decreased the total gastric acid secretion (***p < 0.001). The acute toxicity tests showed that safflower oil (5.000 mg/kg, p.o.) had no effect on mortality or any other physiological parameter. Ecotoxicological tests performed using Daphnia similis showed an EC50 at 223.17 mg/l, and therefore safflower oil can be considered “non-toxic” based on the directive 93/67/EEC on risk assessment for new notified substances by European legislation. These results indicate that the antiulcer activity of Safflower oil may be due to cytoprotective effects, which serve as support for new scientific studies related to this pathology.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Santa Cecília Programa de Pós-graduação em Sustentabilidade de Ecossistemas Costeiros e Marinhos Laboratório de Pesquisa em Produtos NaturaisUniversidade Estadual de Campinas Departamento de Fisiologia e Biofísica Laboratório de Produtos NaturaisUniversidade Santa Cecília Laboratório de EcotoxicologiaUniversidade Federal de São Paulo (UNIFESP) Instituto do MarUniversidade Camilo Castelo Branco Instituto de Engenharia BiomédicaUNIFESP, Instituto do MarFAPESP: 2009/01788-5SciEL

Optimization of cutoff parameters using DFT periodic calculations for (110) rutile and (101) anatase TiO2 surfaces

O uso do TiO2 como catalisador na conversão de Compostos Orgânicos Voláteis em substâncias menos tóxicas é uma importante aplicação para a melhoria da qualidade de vida do ser humano. Nesse trabalho, foram estudadas as superfícies (110) rutilo e (101) anatase do TiO2. Estas superfícies foram utilizadas para estudos de adsorção de moléculas de benzeno, tolueno, etilbenzeno, o-xileno, m-xileno e p-xileno (BTEX). A Teoria do Funcional de Densidade (DFT) com condições de contorno periódicas e conjunto de funções de base de ondas planas e o funcional de troca e correlação PW91 foram usados. Os resultados mostraram que o uso de 300 eV e 3x3x3 para a energia de corte das ondas planas e a malha de pontos k, respectivamente, foram considerados apropriados para os cálculos da adsorção do BTEX. As supercélulas com quatro camadas (3x2) para a superfície (110) do TiO2 rutilo e (3x1) para a superfície (101) do TiO2 anatase foram usadas para a modelagem da superfície. _______________________________________________________________________________________________ ABSTRACTTiO2 used as a catalyst in the conversion of Volatile Organic Compounds into less toxic substances is an important application for improving the quality of human life. In this work, TiO2 (110) rutile and (101) anatase surfaces were studied. These surfaces were used for benzene, toluene, ethylbenzene, o-xylene, m-xylene and p-xylene (BTEX) molecules adsorption studies. The Density Functional Theory (DFT) with periodic boundary conditions and plane wave basis set with the PW91 exchange-correlation functional were used. The results showed that 300 eV for the cutoff energy of the plane waves and 3x3x3 k points mesh were appropriate for the BTEX adsorption calculation. A supercell with four layers (3x2) for the (110) rutile TiO2, and (3x1) for the (101) anatase TiO2 were considered for the surface modeling

Environmental and cultivar variability in composition, content and biological activity of phenolic acids and alkylresorcinols of winter wheat grains from a multi-site field trial across Europe

Different factors such as the genotype, environmental conditions, temperature stress, solar radiation and others can influence the phytochemical status of plants. The concentration of phenolic acids and alkylresorciols (ARs) as well as their chemical composition and biological activity have been determined in twelve winter wheat cultivars grown at eight European locations. This was the first winter wheat multi-location field trial of the European Consortium for Open Field Experimentation (ECOFE). Extracts from grain were analyzed using a UPLC-PDA-ESI-MS system (phenolic acids), UPLC-PDA-MS/MS (alkylresorcinols) and TLC-DPPH• test with ImageJ program (antiradical activity). The phenolic acid profile consisted of five hydroxybenzoic acid and four hydroxycinnamic acid derivatives, among which ferulic and sinapic acids were predominated. The ARs profile consisted of nine AR derivatives, among which 5-n-heneicosylresorcinol (C21:0) and 5-n-nonadecanylresorcinol (C19:0) were predominated. Our study showed significant differences in phenolic acids and AR content between wheat cultivars, as well as between locations. We observed a positive correlation between the biological activity of extracts and the total amount of phenolic acids and ARs. Two cultivars, Chambo and Julius (average of all sites) and samples from the Spanish site (average of all cultivars) showed the highest content and composition of nutritional substances.info:eu-repo/semantics/publishedVersio

Stereological assessment of sexual dimorphism in the rat liver reveals differences in hepatocytes and Kupffer cells but not hepatic stellate cells

There is long‐standing evidence that male and female rat livers differ in enzyme activity. More recently, differences in gene expression profiling have also been found to exist; however, it is still unclear whether there is morphological expression of male/female differences in the normal liver. Such differences could help to explain features seen at the pathological level, such as the greater regenerative potential generally attributed to the female liver. In this paper, hepatocytes (HEP), Kupffer cells (KC) and hepatic stellate cells (HSC) of male and female rats were examined to investigate hypothesised differences in number, volume and spatial co‐localisation of these cell types. Immunohistochemistry and design‐based stereology were used to estimate total numbers, numbers per gram and mean cell volumes. The position of HSC within lobules (periportal vs. centrilobular) and their spatial proximity to KC was also assessed. In addition, flow cytometry was used to investigate the liver ploidy. In the case of HEP and KC, differences in the measured cell parameters were observed between male and female specimens; however, no such differences were detected for HSC. Female samples contained a higher number of HEP per gram, with more binucleate cells. The HEP nuclei were smaller in females, which was coincident with more abundant diploid particles in these animals. The female liver also had a greater number of KC per gram, with a lower percentage of KC in the vicinity of HSC compared with males. In this study, we document hitherto unknown morphological sexual dimorphism in the rat liver, namely in HEP and KC. These differences may account for the higher regenerative potential of the female liver and lend weight to the argument for considering the rat liver as a sexually dimorphic organ