Multiple trait and random regression models using linear splines for genetic evaluation of multiple breed populations.

This study aimed to verify if random regression models using linear splines (RRMLS) are suitable for identifying genetic parameters in multiple-breed populations and also to investigate whether an interaction exists between the breeding value (BV) of sires and their progeny breed group. Ten populations were simulated by crossing 2 breeds with distinct genetic variance and nonzero segregation variance. To obtain the genetic parameters, 2 models were used: a multiple-trait model (MULT), in which the trait was considered distinct when evaluated in each group (1/2P1 + 1/2P2, 5/8P1 + 3/8P2, and 3/4P1 + 1/4P2), and a RRMLS with the spline polynomial knots adjusted to these same groups. The genetic parameters estimated through MULT and RRMLS did not differ from the simulated values. The correlations between BV (simulated and estimated) of animals were high and varied from 0.74 to 0.76, which indicates the efficiency of using MULT and RRMLS for predicting BV. Using field data, the traits age at first calving (AFC), first lactation length (LL), and 305-d milk yield (MY-305) from a multiple-breed population of Holstein-Gyr cattle were analyzed. The BV of animals were modeled through RRMLS with 3, 5, and 7 knots, distributed in accordance with the fraction of Holstein breed in each progeny breed group. It was verified that RRMLS with 7 knots for adjusting mean trajectories and genetic effects, with homogeneous residual variance, best fit AFC and LL. For MY-305, the best fit for mean trajectory and genetic effects was the RRMLS with 5 knots and with homogeneous residual variance. The posterior means of heritability varied from 0.21 to 0.48, 0.21 to 0.38, and 0.10 to 0.33 for AFC, LL, and MY-305, respectively. Estimates from genetic parameters obtained by using RRMLS with field data showed that this model is a useful tool for genetic evaluations of populations formed by a great number of breed groups. An interaction occurred between the BV of sires and their progeny breed group, and the genetic parameters for AFC, LL, and MY-305 traits from a multiple-breed population depend on breed composition of the progeny from which the evaluations are based.

Potential of Casiopeínas® Copper Complexes and Antituberculosis Drug Combination against Mycobacterium tuberculosis.

New compounds with antituberculosis activity and their combination with classic drugs have been evaluated to determine possible interactions and antagonism. The aim of this study was to evaluate the in vitro activity of Casiopeínas® copper-based compounds (CasIIIia, CasIIIEa, and CasIIgly) alone and combined with isoniazid (INH), rifampicin, or ethambutol (EMB) against resistant and susceptible Mycobacterium tuberculosis. Seventeen clinical M. tuberculosis isolates (5 multi-drug resistant and 2 resistant to INH and/or EMB) were subjected to determination of the minimal inhibitory concentration (MIC) by the resazurin microtiter assay and combination assessment by the resazurin drug combination microtiter assay. The Casiopeínas® alone showed a remarkable effect against resistant isolates with MIC values from 0.78 to 12.50 µg/ml. Furthermore, a synergistic effect mainly with EMB is shown for both resistant and susceptible clinical isolates. Casiopeínas® are promising candidates for future investigation into the development of antituberculosis drugs, being one of the first examples of essential metal-based drugs used in this field.

P2X7 receptor activation downmodulates Na(+)-dependent high-affinity GABA and glutamate transport into rat brain cortex synaptosomes.

Sodium-dependent high-affinity amino-acid transporters play crucial roles in terminating synaptic transmission in the central nervous system (CNS). However, there is lack of information about the mechanisms underlying the regulation of amino-acid transport by fast-acting neuromodulators, like ATP. Here, we investigated whether activation of the ATP-sensitive P2X7 receptor modulates Na(+)-dependent high-affinity γ-aminobutyric acid (GABA) and glutamate uptake into nerve terminals (synaptosomes) of the rat cerebral cortex. Radiolabeled neurotransmitter accumulation was evaluated by liquid scintillation spectrometry. The cell-permeant sodium-selective fluorescent indicator, SBFI-AM, was used to estimate Na(+) influx across plasma membrane. 2'(3')-O-(4-benzoylbenzoyl)ATP (BzATP, 3-300 µM), a prototypic P2X7 receptor agonist, concentration-dependently decreased [(3)H]GABA (14%) and [(14)C]glutamate (24%) uptake; BzATP decreased transport maximum velocity (Vmax) without affecting the Michaelis constant (Km) values. The selective P2X7 receptor antagonist, A-438079 (3 µM), prevented inhibition of [(3)H]GABA and [(14)C]glutamate uptake by BzATP (100 µM). The inhibitory effect of BzATP coincided with its ability to increase intracellular Na(+) and was mimicked by Na(+) ionophores, like gramicidin and monensin. Increases in intracellular Na(+) (with veratridine or ouabain) or substitution of extracellular Na(+) by N-methyl-D-glucamine (NMDG)(+) all decreased [(3)H]GABA and [(14)C]glutamate uptake and attenuated BzATP effects. Uptake inhibition by BzATP (100 µM) was also attenuated by calmidazolium, which selectively inhibits Na(+) currents through the P2X7 receptor pore. In conclusion, disruption of the Na(+) gradient by P2X7 receptor activation downmodulates high-affinity GABA and glutamate uptake into rat cortical synaptosomes. Interference with amino-acid transport efficacy may constitute a novel target for therapeutic management of cortical excitability.

[Comparison of body fat using anthropometry bioelectrical impedance and DEXA in elderly women]. / Comparação da gordura corporal de mulheres idosas segundo antropometria, bioimpedância e DEXA.

Verify correspondence and compare percentage body fat (%BF) estimates by skinfold thickness (SKT), bioelectrical impedance analysis (BIA) and DEXA. Twenty voluntaries women (aged 62-79 yr) were assessed. The body fat was estimated using two different equations of SKT(Jackson (19); Durning and Womersley, (20)), BIA using two-predictions formulas (23) and DEXA. To compare mean values of %BF was used analysis of variance for repeated measures (ANOVA--Bonferroni), the correlation of the inter-method was verified by Pearson correlation coefficients (r), and correspondence between prediction formulas was tested by using the approach by Bland and Altman (25). The %BF assessed by BIA (23) shown poor correlation (r < 0.5) with two SKT equations. The %BF ranged from 31.5 +/- 5.5 to 41.2 +/- 6.1 (mean +/- SD) for Jackson (19) e DEXA, respectively. The analysis of variance shown no significant differences (p > 0.05) between methods and/or equations by BIA (RJL-CompCorp) vs. DC-Jackson (19). There were observed significant differences (p < 0.001) between all comparisons. The correspondence between RJL-CompCorp vs. Deurenberg (23) was good and the same was observed for DEXA vs. Durning and Womersley (20). Although the methods and/or equations used in this study have been commonly utilized to estimate BF in elderly subjects, they neither must be used as a standard method. Each method has limitations and the comparison can be useful for interpretation of results.