Generation and Analysis of Interaction Energy Maps of p-Substituted Benzoic Acid [(5-Nitro-thiophen-2-yl)-methylene]-Hydrazides Active against MRSA

In this preliminary study eighteen p-substituted benzoic acid [(5-nitro-thiophen-2-yl)-methylene]-hydrazides with antimicrobial activity were evaluated against multidrug-resistant Staphylococcus aureus, correlating the three-dimensional characteristics of the ligands with their respective bioactivities. The computer programs Sybyl and CORINA were used, respectively, for the design and three-dimensional conversion of the ligands. Molecular interaction fields were calculated using GRID program. Calculations using Volsurf resulted in a statistically consistent model with 48 structural descriptors showing that hydrophobicity is a fundamental property in the analyzed biological response.

Binding of Dengue Virus Partitcles and Dengue Proteins onto Solid Surfaces

The interaction between dengue virus particles (DENV), sedimentation hemagglutinin particles (SHA), dengue virus envelope protein (Eprot), and solid surfaces was investigated by means of ellipsometry and atomic force microscopy (AFM). The surfaces chosen are bare Si/SiO(2) wafers and Si/SiO(2) wafers covered with concanavalin A (ConA), jacalin (Jac), polystyrene (PS), or poly(styrene sulfonate) (PSS) films. Adsorption experiments at pH 7.2 and pH 3 onto all surfaces revealed that (i) adsorption of DENV particles took place only onto ConA under pH 7.2, because of specific recognition between glycans on DENV surface and ConA binding site; (ii) DENV particles did not attach to any of the surfaces at pH 3, suggesting the presence of positive charges on DENV surface at this pH, which repel the positively charged lectin surfaces; (iii) SHA particles are positively charged at pH 7.2 and pH 3 because they adhered to negatively charged surfaces at pH 7.2 and repelled positively charged layers at pH 3; and (iv) SHA particles carry polar groups on the surface because they attached to silanol surfaces at pH 3 and avoided hydrophobic PS films at pH 3 and pH 7.2. The adsorption behavior of Eprot at pH 7.2 revealed affinity for ConA > Jac > PSS > PS approximate to bare Si/SiO(2) layers. These findings indicate that selectivity of the Eprot adsorption is higher when it is part of virus structure than when it is free in solution. The correlation between surface energy values determined by means of contact angle measurements and DENV, SHA, or Eprot adsorption behavior was used to understand the intermolecular forces at the interfaces. A direct correlation was not found because the contributions from surface energy were probably surpassed by specific contributions.

Mapping the Intramolecular Vibrational Energy Flow in Proteins Reveals Functionally Important Residues

Unveiling the mechanisms of energy relaxation in biomolecules is key to our understanding of protein stability, allostery, intramolecular signaling, and long-lasting quantum coherence phenomena at ambient temperatures. Yet, the relationship between the pathways of energy transfer and the functional role of the residues involved remains largely unknown. Here, we develop a simulation method of mapping out residues that are highly efficient in relaxing an initially localized excess vibrational energy and perform site-directed mutagenesis functional assays to assess the relevance of these residues to protein function. We use the ligand binding domains of thyroid hormone receptor (TR) subtypes as a test case and find that conserved arginines, which are critical to TR transactivation function, are the most effective heat diffusers across the protein structure. These results suggest a hitherto unsuspected connection between a residue`s ability to mediate intramolecular vibrational energy redistribution and its functional relevance.

Flexibility and inhibitor binding in Cdc25 phosphatases

Cdc25 phosphatases involved in cell cycle checkpoints are now active targets for the development of anti-cancer therapies. Rational drug design would certainly benefit from detailed structural information for Cdc25s. However, only apo- or sulfate-bound crystal structures of the Cdc25 catalytic domain have been described so far. Together with previously available crystalographic data, results from molecular dynamics simulations, bioinformatic analysis, and computer-generated conformational ensembles shown here indicate that the last 30-40 residues in the C-terminus of Cdc25B are partially unfolded or disordered in solution. The effect of C-terminal flexibility upon binding of two potent small molecule inhibitors to Cdc25B is then analyzed by using three structural models with variable levels of flexibility, including an equilibrium distributed ensemble of Cdc25B backbone conformations. The three Cdc25B structural models are used in combination with flexible docking, clustering, and calculation of binding free energies by the linear interaction energy approximation to construct and validate Cdc25B-inhibitor complexes. Two binding sites are identified on top and beside the Cdc25B active site. The diversity of interaction modes found increases with receptor flexibility. Backbone flexibility allows the formation of transient cavities or compact hydrophobic units on the surface of the stable, folded protein core that are unexposed or unavailable for ligand binding in rigid and densely packed crystal structures. The present results may help to speculate on the mechanisms of small molecule complexation to partially unfolded or locally disordered proteins.

Effect of repeated disinfections by microwave energy on the physical and mechanical properties of denture base acrylic resins

The present study evaluated the effect of repeated simulated microwave disinfection on physical and mechanical properties of Clássico, Onda-Cryl and QC-20 denture base acrylic resins. Aluminum patterns were included in metallic or plastic flasks with dental stone following the traditional packing method. The powder/liquid mixing ratio was established according to the manufacturer's instructions. After water-bath polymerization at 74ºC for 9 h, boiling water for 20 min or microwave energy at 900 W for 10 min, the specimens were deflasked after flask cooling and finished. Each specimen was immersed in 150 mL of distilled water and underwent 5 disinfection cycles in a microwave oven set at 650 W for 3 min. Non-disinfected and disinfected specimens were subjected to the following tets: Knoop hardness test was performed with 25 g load for 10 s, impact strength test was done using the Charpy system with 40 kpcm, and 3-point bending test (flexural strength) was performed at a crosshead speed of 0.5 mm/min until fracture. Data were analyzed statistically by ANOVA and Tukey's test (α= 0.05%). Repeated simulated microwave disinfections decreased the Knoop hardness of Clássico and Onda-Cryl resins and had no effect on the impact strength of QC-20. The flexural strength was similar for all tested resins.

Effects of dietary energy and nitrogen supplements on rumen fermentation and protozoa population in buffalo and zebu cattle

The effects were assessed of two energy sources in concentrate (ground grain corn vs. citrus pulp) and two nitrogen sources (soybean meal vs. urea) on rumen metabolism in four buffaloes and four zebu cattle (Nellore) with rumen cannula and fed in a 4 × 4 Latin square design with feeds containing 60% sugar cane. Energy supplements had no effect on the rumen ammonia concentration in cattle, but ground grain corn promoted higher ammonia level than citrus pulp in buffalo. Urea produced higher ammonia level than soybean meal in both animal species. On average, the buffaloes maintained a lower rumen ammonia concentration (11.7 mg/dL) than the cattle (14.5 mg/dL). Buffaloes had lower production of acetic acid than cattle (58.7 vs. 61.6 mol/100 mol) and higher of propionic acid (27.4 vs. 23.6 mol/100 mol). There was no difference in the butyric acid production between the buffaloes (13.6 mol/100 mol) and cattle (14.8 mol/100 mol) and neither in the total volatile fatty acids concentration (82.5 vs. 83.6 mM, respectively). The energy or nitrogen sources had no effect on rumen protozoa count in either animal species. The zebu cattle had higher rumen protozoa population (8.8 × 10(5)/mL) than the buffaloes (6.1 × 10(5)/mL). The rumen protozoa population differed between the animal species, except for Dasytricha and Charonina. The buffaloes had a lower Entodinium population than the cattle (61.0 vs 84.9%, respectively) and a greater percentage of species belonging to the Diplodiniinae subfamily than the cattle (28.6 vs. 1.4%, respectively). In cattle, ground corn is a better energy source than citrus pulp for use by Entodinium and Diplodiniinae. In the buffaloes, the Entodinium are favored by urea and Diplodiniinae species by soybean meal.

Validation of the Deardorff model for estimating energy balance components for a sugarcane crop

The quantification of the available energy in the environment is important because it determines photosynthesis, evapotranspiration and, therefore, the final yield of crops. Instruments for measuring the energy balance are costly and indirect estimation alternatives are desirable. This study assessed the Deardorff's model performance during a cycle of a sugarcane crop in Piracicaba, State of São Paulo, Brazil, in comparison to the aerodynamic method. This mechanistic model simulates the energy fluxes (sensible, latent heat and net radiation) at three levels (atmosphere, canopy and soil) using only air temperature, relative humidity and wind speed measured at a reference level above the canopy, crop leaf area index, and some pre-calibrated parameters (canopy albedo, soil emissivity, atmospheric transmissivity and hydrological characteristics of the soil). The analysis was made for different time scales, insolation conditions and seasons (spring, summer and autumn). Analyzing all data of 15 minute intervals, the model presented good performance for net radiation simulation in different insolations and seasons. The latent heat flux in the atmosphere and the sensible heat flux in the atmosphere did not present differences in comparison to data from the aerodynamic method during the autumn. The sensible heat flux in the soil was poorly simulated by the model due to the poor performance of the soil water balance method. The Deardorff's model improved in general the flux simulations in comparison to the aerodynamic method when more insolation was available in the environment.

Hormônio do crescimento e exercício físico: considerações atuais

Embora o hormônio do crescimento (GH) seja um dos hormônios mais estudados, vários de seus aspectos fisiológicos ainda não estão integralmente esclarecidos, incluindo sua relação com o exercício físico. Estudos mais recentes têm aumentado o conhecimento a respeito dos mecanismos de ação do GH, podendo ser divididos em: 1) ações diretas, mediadas pela rede de sinalizações intracelulares, desencadeadas pela ligação do GH ao seu receptor na membrana plasmática; e 2) ações indiretas, mediadas principalmente pela regulação da síntese dos fatores de crescimento semelhantes à insulina (IGF). Tem sido demonstrado que o exercício físico é um potente estimulador da liberação do GH. A magnitude deste aumento sofre influência de diversos fatores, em especial, da intensidade e do volume do exercício, além do estado de treinamento. Atletas, normalmente, apresentam menor liberação de GH induzida pelo exercício que indivíduos sedentários ou pouco treinados. Evidências experimentais demonstram que o GH: 1) favorece a mobilização de ácidos graxos livres do tecido adiposo para geração de energia; 2) aumenta a capacidade de oxidação de gordura e 3) aumenta o gasto energético.

Synthesis, screening for antiacetylcholinesterase activity and binding mode prediction of a new series of [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters

A series of nine new [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters (phosphate-carbamate compounds) was obtained through the reaction of (4,4,4-trifluoro-3-hydroxybut-1-yl)-carbamic acid ethyl esters with phosphorus oxychloride followed by the addition of alcohols. The products were characterized by ¹H, 13C, 31P, and 19F NMR spectroscopy, GC-MS, and elemental analysis. All the synthesized compounds were screened for acetylcholinesterase (AChE) inhibitory activity using the Ellman method. All compounds containing phosphate and carbamate pharmacophores in their structures showed enzyme inhibition, being the compound bearing the diethoxy phosphate group (2b) the most active compound. Molecular modeling studies were performed to investigate the detailed interactions between AChE active site and small-molecule inhibitor candidates, providing valuable structural insights into AChE inhibition.

Comparison of some theoretical models for fittings of the temperature dependence of the fundamental energy gap in GaAs

In this work we report on a comparison of some theoretical models usually used to fit the dependence on temperature of the fundamental energy gap of semiconductor materials. We used in our investigations the theoretical models of Viña, Pässler-p and Pässler-ρ to fit several sets of experimental data, available in the literature for the energy gap of GaAs in the temperature range from 12 to 974 K. Performing several fittings for different values of the upper limit of the analyzed temperature range (Tmax), we were able to follow in a systematic way the evolution of the fitting parameters up to the limit of high temperatures and make a comparison between the zero-point values obtained from the different models by extrapolating the linear dependence of the gaps at high T to T = 0 K and that determined by the dependence of the gap on isotope mass. Using experimental data measured by absorption spectroscopy, we observed the non-linear behavior of Eg(T) of GaAs for T > ΘD.

High-energy events and short-term changes in superficial beach sediments

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Diet quality index adjusted for energy requirements in adults

This study aimed to develop a diet quality index (DQI-a) adjusted for energy requirement. Dietary intake of adults was assessed using 24-hour food recall. The DQI was developed for scores evenly distributed across ten items characterizing different aspects of diet: food groups, nutrients, and variety. The components categorized under the food groups from the Dietary Guide for Brazilians were adjusted according to the estimated energy requirements of the population studied. Index consistency and correlation with nutrients of the diet was analyzed by Cronbach's alpha. A total of 737 individuals were assessed and energy requirements ranged from 1,800 to 2,500kcal among women and 2,500 to 3,400kcal in men. The food group with greatest variation in total portions was cereals and tubers. Cronbach's alpha of the DQI-a was 0.643 and the index correlated with most of the nutrients. The DQI-a can be considered a valuable instrument for assessing diet quality of the Brazilian population.

Sources of variation of energy and nutrient intake among adolescents in São Paulo, Brazil

The aim of the current study was to describe the sources of variation of energy and nutrient intake and to calculate the number of repetitions of diet measurements to estimate usual intake in adolescents from São Paulo, Brazil. Data was collected using 24-hour dietary recalls (24hR) in 273 adolescents between 2007 and 2008. Individuals completed a repeat 24hR around two months later. The sources of variation were estimated using the random effect model. Variance ratios (within-person to between-person variance ratio) and the number of repetitions of 24hR to estimate usual intake were calculated. The principal source of variation was due to within-person variance. The contribution of day of week and month of year was less than 8%. Variations ranged from 1.15 for calcium to 7.31 for vitamin E. The number of 24hR repeats required to estimate usual intake varied according to nutrient and gender, numbering 15 for males and 8 for females.

Effect of an energy-deficient diet on populations of ciliate protozoans in bovine rumen

Ten young rumen-cannulated crossbred steers were randomly divided into two groups: a control group (C; n=4), which was fed a balanced diet for daily weight gain of 900g; and a pronounced energy-deprived group (PED; n=6), receiving 30% less of the required energy for maintenance. After 140 days of these alimentary regimes, rumen fluid and urine samples were collected for biochemical and functional tests, before feeding and at 1, 3, 6, and 9 hours after feeding. The energy-deprivation diet caused a significant reduction in the number of Entodinium, Eodinium, Isotricha, Dasytricha, Eremoplastron, Eudiplodinium, Metadinium, Charonina, Ostracodinium, and Epidinium protozoa. There was no effect of the time of sampling in both groups on the total number of ciliates in rumen fluid. A higher number of protozoan forms in binary division were recorded in the control group, at the 6th and 9th hours after feeding (P<0.019). There was a high positive correlation between the total count of protozoans in rumen fluid and glucose fermentation, ammonia, and urinary allantoin excretion index; and a negative correlation between the total count of protozoa and metilene blue reduction, and a medium correlation between the total count of protozoa and total volatile fatty acids concentration. The determination of the protozoa populations does not imply in the use of complex and hard-to-execute techniques, although it is time consuming and needs practice. This exam particularly helps in clinical expected diagnosis.

Apparent digestibility of diets with different concentrations of lysine and energy in piglets with different body weights and post-weaning age

The effects of body weight or age and dietary digestible lysine and metabolizable energy on apparent digestibility of energy and dry matter were evaluated in piglets after weaning. The animals were weaned at 21 days of age and distributed in two groups: 8.68 ± 0.76 kg at 28 days of age (weaned 7 days earlier); and 12.73 ± 0.99 kg at 35 days of age (weaned 14 days earlier). The pigs were allotted in digestibility cages in a completely randomized block design with the following factorial arrangements: 2 × 4 composed of two weight categories and four levels of digestible lysine (1.222; 1.305; 1.390 and 1.497%); and 2 × 3 composed of two weight categories and three levels of metabolizable energy (3,510; 3,700 and 3,830 kcal/kg rations). Digestible lysine was evaluated in six replications and metabolizable energy in eight replications and each animal constituted an experimental unit. Piglets with higher body weight and age were more efficient in nitrogen retention and energetic balance, compared to lighter and younger piglets, particularly those given lower concentration of lysine in the diet. The energy increase favored nitrogen retention by the heavier and older piglets. However, coefficients of dry matter and energy apparent digestibility did not differ among weight categories. Older and heavier piglets were more efficient in nitrogen retention, although this efficacy depended on concentration of the energy in the diet. This better use of protein and energy suggest differences on nutritional requirements.