Promjene u metabolizmu lijekova i lipoproteina u radnika profesionalno eksponiranih DDT-ju i lindanu

In twenty-six men occupationally exposed mainly to lindane and DDT antipyrine had a significantly shorter plasma half-life than in 33 control subjects. Twenty-two men exposed mainly to lindane and DDT in their occupation and 19 healthy male persons were studied with regard to their fasting serum lipid levels and to the amounts of lipids in the three ultracentrifugally separated lipoprotein families, VLDL, LDL and HDL. Eight of the exposed subjects and none of the controls had hyper-HDL (a)-lipoproteinemia. Plasma levels of Iiridane, p,p\u27-DDE and p,p\u27-DDT were determined with a new gas chromatographic method in fourty-two spraymen exposed to lindane and in twenty-three nursery workers with a low and intermittent exposure to DDT. Controls were eleven and twenty-one respectively. The plasma lindane levels of the exposed groups differed significantly (p < 0.001) from the non-exposed ones. The plasma DDE and DDT values of the exposed persons did not differ from controls with only low dietary exposure to DDT. No changes in the clinical state of health could be recorded in any of the examined groups.U 26 ljudi eksponiranih pretežno lindanu i DDT-ju vrijeme zadržavanja polovične količine antipirina u plazmi bilo je znatno kraće nego u 33 kontrolne osobe. Skupini od 22 muškarca profesionalno izloženoj lindanu i DDT-ju i kontrolnoj skupini od 19 zdravih osoba mjerena je razina serumskih lipida u gladovanju i količina lipida u tri lipoproteinske grupacije odijeljene ultracentrifugom. U osmorice od eksponiranih ispitanika nađena je hiper-HDL (a)-lipoproteinemija, a ni u jednog od kontrolnih. Razine lindana, P,P\u27-DDE i P,P\u27-DDT u plazmi mjerene su novom kromatografskom metodom u 42 prskača eksponirana lindanu i u 23 radnika u rasadniku, izložena povremeno malim dozama DDT-ja. Kontrolnih ispitanika bilo je 11, odnosno 21. Razina lindana u plazmi eksponiranih grupa razlikovala se signifikantno (P < 0,001) od one u neeksponiranih. Vrijednosti DDE i DDT-ja u plazmi izloženih osoba nisu se razlikovale od onih u kontrolnoj skupini. Nisu nađene nikakve kliničke promjene zdravstvenog stanja u bilo kojoj od istraživanih grupa

Response to mass selection when the genotype by environment interaction is modelled as a linear reaction norm

A breeding goal accounting for the effects of genotype by environment interaction (G × E) has to define not only traits but also the environment in which those traits are to be improved. The aim of this study was to predict the selection response in the coefficients of a linear reaction norm, and response in average phenotypic value in any environment, when mass selection is applied to a trait where G × E is modelled as a linear reaction norm. The optimum environment in which to test the selection candidates for a given breeding objective was derived. Optimisation of the selection environment can be used as a means to either maximise genetic progress in a certain response environment, to keep the change in environmental sensitivity at a desired rate, or to reduce the proportion of animals performing below an acceptance level. The results showed that the optimum selection environment is not always equal to the environment in which the response is to be realised, but depends on the degree of G × E (determined by the ratio of variances in slope and level of a linear reaction norm), the correlation between level and slope, and the heritability of the trait

Model for fitting longitudinal traits subject to threshold response applied to genetic evaluation for heat tolerance

A semi-parametric non-linear longitudinal hierarchical model is presented. The model assumes that individual variation exists both in the degree of the linear change of performance (slope) beyond a particular threshold of the independent variable scale and in the magnitude of the threshold itself; these individual variations are attributed to genetic and environmental components. During implementation via a Bayesian MCMC approach, threshold levels were sampled using a Metropolis step because their fully conditional posterior distributions do not have a closed form. The model was tested by simulation following designs similar to previous studies on genetics of heat stress. Posterior means of parameters of interest, under all simulation scenarios, were close to their true values with the latter always being included in the uncertain regions, indicating an absence of bias. The proposed models provide flexible tools for studying genotype by environmental interaction as well as for fitting other longitudinal traits subject to abrupt changes in the performance at particular points on the independent variable scale

Genetics of Ascites Resistance and Tolerance in Chicken: A Random Regression Approach

Resistance and tolerance are two complementary mechanisms to reduce the detrimental effects of parasites, pathogens, and production diseases on host performance. Using body weight and ascites data on domesticated chicken Gallus gallus domesticus, we demonstrate the use of random regression animal model and covariance functions to estimate genetic parameters for ascites resistance and tolerance and illustrate the way individual variation in resistance and tolerance induce both genotype re-ranking and changes in variation of host performance along increasing ascites severity. Tolerance to ascites displayed significant genetic variance, with the estimated breeding values of tolerance slope ranging from strongly negative (very sensitive genotype) to weakly negative (less sensitive). Resistance to ascites had heritability of 0.34. Both traits are hence expected to respond to selection. The two complementary defense strategies, tolerance and resistance, were genetically independent. Ascites induced changes to the correlations between ascites resistance and body weight, with the genetic correlations being weak when birds were ascites-free but moderately negative when both healthy and affected birds were present. This likely results because ascites reduces growth, and thus high ascites incidence is genetically related to low adult body weight. Although ascites induced elevated phenotypic and genetic variances in body weight of affected birds, heritability displayed negligible changes across healthy and affected birds. Ascites induced moderate genotype re-ranking in body weight, with the genetic correlation of healthy birds with mildly affected birds being unity but with severely affected birds 0.45. This study demonstrates a novel approach for exploring genetics of defense traits and their impact on genotype-by-environment interactions

Genotype by environment interaction for 450-day weight of Nelore cattle analyzed by reaction norm models

Genotype by environment interactions (GEI) have attracted increasing attention in tropical breeding programs because of the variety of production systems involved. In this work, we assessed GEI in 450-day adjusted weight (W450) Nelore cattle from 366 Brazilian herds by comparing traditional univariate single-environment model analysis (UM) and random regression first order reaction norm models for six environmental variables: standard deviations of herd-year (RRMw) and herd-year-season-management (RRMw-m) groups for mean W450, standard deviations of herd-year (RRMg) and herd-year-season-management (RRMg-m) groups adjusted for 365-450 days weight gain (G450) averages, and two iterative algorithms using herd-year-season-management group solution estimates from a first RRMw-m and RRMg-m analysis (RRMITw-m and RRMITg-m, respectively). The RRM results showed similar tendencies in the variance components and heritability estimates along environmental gradient. Some of the variation among RRM estimates may have been related to the precision of the predictor and to correlations between environmental variables and the likely components of the weight trait. GEI, which was assessed by estimating the genetic correlation surfaces, had values < 0.5 between extreme environments in all models. Regression analyses showed that the correlation between the expected progeny differences for UM and the corresponding differences estimated by RRM was higher in intermediate and favorable environments than in unfavorable environments (p < 0.0001)

Vanadyl complexes with dansyl-labelled dipicolinic acid ligands: synthesis, phosphatase inhibition activity and cellular uptake studies

Vanadium complexes have been previously utilised as potent inhibitors of cysteine based phosphatases (CBPs). Herein, we present the synthesis and characterisation of two new fluorescently labelled vanadyl complexes (14 and 15) with bridged di-picolinic acid ligand. These compounds differ significantly from previous vanadyl complexes with phosphatase inhibition properties in that the metal-chelating part is a single tetradentate unit, which should afford greater stability and scope for synthetic elaboration then the earlier complexes. These new complexes inhibit a selection of cysteine based phosphatases (CBPs) in the nM range with some selectivity. Fluorescence spectroscopic studies (including fluorescence anisotropy) were carried out to demonstrate that the complexes are not simply acting as vanadyl delivery vehicles but they interact with the proteins. Finally, we present preliminary fluorescence microscopy studies to demonstrate that the complexes are cell permeable and localise throughout the cytoplasm of NIH3T3 cells