THDP17 Decreases Ammonia Production through Glutaminase Inhibition. A New Drug for Hepatic Encephalopathy Therapy

Ammonia production is implicated in the pathogenesis of hepatic encephalopathy (HE), being intestinal glutaminase activity the main source for ammonia. Management of ammonia formation can be effective in HE treatment by lowering intestinal ammonia production. The use of glutaminase inhibitors represents one way to achieve this goal. In this work, we have performed a search for specific inhibitors that could decrease glutaminase activity by screening two different groups of compounds: i) a group integrated by a diverse, highly pure small molecule compounds derived from thiourea ranging from 200 to 800 Daltons; and ii) a group integrated by commonly use compounds in the treatment of HE. Results shown that THDP-17 (10 µM), a thiourea derivate product, could inhibit the intestinal glutaminase activity (57.4±6.7%). Inhibitory effect was tissue dependent, ranging from 40±5.5% to 80±7.8% in an uncompetitive manner, showing V_max and K_m values of 384.62 µmol min⁻¹, 13.62 mM with THDP-17 10 µM, respectively. This compound also decreased the glutaminase activity in Caco-2 cell cultures, showing a reduction of ammonia and glutamate production, compared to control cultures. Therefore, the THDP-17 compound could be a good candidate for HE management, by lowering ammonia production.     

A study on the minimum number of loci required for genetic evaluation using a finite locus model

For a finite locus model, Markov chain Monte Carlo (MCMC) methods can be used to estimate the conditional mean of genotypic values given phenotypes, which is also known as the best predictor (BP). When computationally feasible, this type of genetic prediction provides an elegant solution to the problem of genetic evaluation under non-additive inheritance, especially for crossbred data. Successful application of MCMC methods for genetic evaluation using finite locus models depends, among other factors, on the number of loci assumed in the model. The effect of the assumed number of loci on evaluations obtained by BP was investigated using data simulated with about 100 loci. For several small pedigrees, genetic evaluations obtained by best linear prediction (BLP) were compared to genetic evaluations obtained by BP. For BLP evaluation, used here as the standard of comparison, only the first and second moments of the joint distribution of the genotypic and phenotypic values must be known. These moments were calculated from the gene frequencies and genotypic effects used in the simulation model. BP evaluation requires the complete distribution to be known. For each model used for BP evaluation, the gene frequencies and genotypic effects, which completely specify the required distribution, were derived such that the genotypic mean, the additive variance, and the dominance variance were the same as in the simulation model. For lowly heritable traits, evaluations obtained by BP under models with up to three loci closely matched the evaluations obtained by BLP for both purebred and crossbred data. For highly heritable traits, models with up to six loci were needed to match the evaluations obtained by BLP.     

Phytoplankton Growth and Microzooplankton Grazing in the Subtropical Northeast Atlantic

Dilution experiments were performed to estimate phytoplankton growth and microzooplankton grazing rates during two Lagrangian surveys in inner and eastern locations of the Eastern North Atlantic Subtropical Gyre province (NAST-E). Our design included two phytoplankton size fractions (0.2–5 µm and >5 µm) and five depths, allowing us to characterize differences in growth and grazing rates between size fractions and depths, as well as to estimate vertically integrated measurements. Phytoplankton growth rates were high (0.11–1.60 d⁻¹), especially in the case of the large fraction. Grazing rates were also high (0.15–1.29 d⁻¹), suggesting high turnover rates within the phytoplankton community. The integrated balances between phytoplankton growth and grazing losses were close to zero, although deviations were detected at several depths. Also, O₂ supersaturation was observed up to 110 m depth during both Lagrangian surveys. These results add up to increased evidence indicating an autotrophic metabolic balance in oceanic subtropical gyres.     

Phospholipid and fatty acid changes produced by cholecalciferol on intestinal mitochondrial membranes

Cholecalciferol administration to vitamin D-deficient chicks produces, 24 h after treatment, a specific increase of the phosphatidylcholine content in the intestinal mitochondrial inner membrane plus matrix fraction without changes in its proportion in the outer membrane. The ratio of unsaturated/saturated fatty acids in the outer membrane phosphatidylcholine was increased by that treatment. The inner membrane plus matrix presents a decrease of 16:1 in phosphatidylethanolamine and 18:0 in the phosphatidylcholine fraction. Cardiolipin shows the largest change in the ratio of unsaturated/saturated fatty acids predominantly by an increase in the linoleic acid. The present data suggest that phosphatidylcholine and fatty acids modifications in both mitochondrial subfractions caused by vitamin D3 might have some role in the intestinal mitochondrial Ca transport.     

First record of anomalous otoliths of Menticirrhus americanus in the South Atlantic

Sagitta otoliths are usually formed of calcium carbonate polymorphs as aragonite. The objective of this study was to verify which carbonate polymorph is predominant in the sagitta otolith of Menticirrhus americanus and check whether this pattern remains in otoliths with morphological alterations. Otoliths of M. americanus were obtained from five sites on the southeast‐south coast of Brazil (São Sebastião (SS) 23°45′S–45°24′O, n = 29; Cananéia‐Iguape Estuarine Complex (CI) 25°02′S–47°54′O, n = 30; Paranaguá Estuarine Complex (PEC) 25°28′S–48°20′O, n = 35; Itapoá (IT) 26°07′S–48°36′O, n = 31; Laguna (LA) 28°28′S–48°46′O, n = 13). The characterization of carbonate polymorphs of otoliths was performed through Raman spectroscopy, a photonic and non‐destructive technique that analyzes molecular vibrations induced by laser. We analyzed 138 pairs of M. americanus otoliths, of which eight otoliths from different pairs presented morphological alterations (SS n = 1, CEP n = 5, IT n = 1, LA n = 1). The Raman spectra show that normal otoliths, that is, without morphological alterations, presented only aragonite in their structure. Among the otoliths that presented morphological alterations, the Raman spectra allowed to identify in six otoliths the deposition of aragonite and in only two otoliths the deposition of vaterite (one specimen of the PEC and one of SS).     

Symmetry and asymmetry in fingerprints of three genera of South American monkeys in relation to morphological evolutionary problems

Fingerprints of South American monkeys of the genera Alouatta, Ateles and Cebus were studied. Dermatoglyphics were analysed in relation to pattern intensities; the distribution of symmetric and asymmetric designs was also determined. Results have been related to some aspects of the contribution of dermatoglyphics to the study of Primate morphological evolution.