Exploring the multifactorial nature of autism through computational systems biology: Calcium and the Rho GTPase RAC1 under the spotlight

Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication accompanied with repetitive behavioral patterns and unusual stereotyped interests. Autism is considered a highly heterogeneous disorder with diverse putative causes and associated factors giving rise to variable ranges of symptomatology. Incidence seems to be increasing with time, while the underlying pathophysiological mechanisms remain virtually uncharacterized (or unknown). By systematic review of the literature and a systems biology approach, our aims were to examine the multifactorial nature of autism with its broad range of severity, to ascertain the predominant biological processes, cellular components, and molecular functions integral to the disorder, and finally, to elucidate the most central contributions (genetic and/or environmental) in silico. With this goal, we developed an integrative network model for gene-environment interactions (GENVI model) where calcium (Ca2+) was shown to be its most relevant node. Moreover, considering the present data from our systems biology approach together with the results from the differential gene expression analysis of cerebellar samples from autistic patients, we believe that RAC1, in particular, and the RHO family of GTPases, in general, could play a critical role in the neuropathological events associated with autism. © 2013 Springer Science+Business Media New York.

Predominant Rab-GTPase amplicons contributing to oral squamous cell carcinoma progression to metastasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A novel voltage step-down/up ZCS-PWM Zeta converter

This paper presents an analysis of a novel pulse-width-modulated (PWM) voltage step-down/up Zeta converter, featuring zero-current-switching (ZCS) at the active switches. The applications in de to de and ac to de (rectifier) operation modes are used as examples to illustrate the performance of this new ZCS-PWM Zeta converter. Regarding to the new ZCS-PWM Zeta rectifier proposed, it should be noticed that the average-current mode control is used in order to obtain a structure with high power-factor (HPF) and low total harmonic distortion (THD) at the input current.Two active switches (main and auxiliary transistors), two diodes, two small resonant inductors and one small resonant capacitor compose the novel ZCS-PWM soft-commutation cell, used in these new ZCS-PWM Zeta converters. In this cell, the turn-on of the active switches occurs in zero-current (ZC) and their turn-off in zero-current and zero-voltage (ZCZV). For the diodes, their turn-on process occurs in zero-voltage (ZV) and their reverse-recovery effects over the active switches are negligible. These characteristics make this cell suitable for Insulated-Gate Bipolar Transistors (IGBTs) applications.The main advantages of these new Zeta converters, generated from the new soft-commutation cell proposed, are possibility of obtaining isolation (through their accumulation inductors), and high efficiency, at wide load range. In addition, for the rectifier application, a high power factor and low THD in the input current ran be obtained, in agreement with LEC 1000-3-2 standards.The principle of operation, the theoretical analysis and a design example for the new de to de Zeta converter operating in voltage step-down mode are presented. Experimental results are obtained from a test unit with 500W output power, 110V(dc) output voltage, 220V(dc) input voltage, operating at 50kHz switching frequency. The efficiency measured at rated toad is equal to 97.3%for this new Zeta converter.Finally, the new Zeta rectifier is analyzed, and experimental results from a test unit rated at 500W output power, 110V(dc) output voltage, 220V(rms) input voltage, and operating at 50kHz switching frequency, are presented. The measured efficiency is equal to 96.95%, the power-factor is equal to 0.98, and the input current THD is equal to 19.07%, for this new rectifier operating at rated load.

High power factor dimmable electronic ballast for multiple tubular fluorescent lamps

This paper presents a dimmable electronic ballast designed for multiple fluorescent lamps applications. A ZCS-PWM Boost rectifier and a classical resonant Full-Bridge inverter compose this new electronic ballast, providing conditions for the obtaining of high input power-factor, and soft-switching processes for all semiconductor devices employed in the structure. The instantaneous average input current control technique is employed in the Boost rectifier. Concerning the Full-Bridge inverter, it is controlled by the imposition of phase-shift in the current processed through the sets of resonant filters + lamps, according to an adaptation in a specially designed control IC, called IR2159. Experimental results are presented in order to validate the analyses developed in this paper.

Population parameters in Brazilian Thoroughbred

The information in this study has been provided by the Brazilian Association of Racehorse Breeders [Associação do Brasileira dos Criadores do Cavalo de Corrida (ABCCC)]. It can be found in the files on the CD-ROM developed by the ABCCC in 1999. A total of 5008 finishing time records related to 2545 winning horses that ran in the classical calendar on Brazilian hippodromes during 25 years (197498) were analysed. There were a total of 9949 horses on the relationship matrix. The variance components were estimated using the multiple-trait derivate-free restricted maximum likelihood (MTDFREML) program, for an animal model. Generation intervals were higher in the maternal side (10.91 years) than in the paternal one (10.41 years). The estimates for genetic permanent environmental and phenotypic variances and heritability were 0.291, 0.161, 3.486 and 0.08, respectively. The phenotypic standard deviation for time in races was 1.86729 s. Genetic time trend on Thoroughbred races in Brazil was small and could be accelerated if selection considered the trait time effectively. With respect to the animal's country of birth, the results show that there has been an intense participation of foreign animals in breeding Brazilian Thoroughbreds.

Proteomic profiling of the molecular targets of interactions of the mastoparan peptide Protopolybia MP-III at the level of endosomal membranes from rat mast cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Corallus caninus (Serpentes, Boidae): a new host for Ophiotaenia sp. (Cestoda, Proteocephalidae)

Relata-se a ocorrência de Ophiotaenia sp. (Cestoda, Proteocephalidae) parasitando Corallus caninus (Serpentes, Boidae). A serpente foi recebida no Parque Zoológico de Goiânia, Goiás, proveniente de apreensão pelo RAN/IBAMA em tráfico de animais silvestres. O animal estava apático, com disecdise e desidratação. Após alguns dias, morreu no cativeiro. A necropsia revelou a presença de um cestódeo no intestino que foi fixado em AFA após compressão, corado em carmim e analisado em sistema de análise de imagens. Os aspectos morfológicos indicaram ser uma espécie do gênero Ophiotaenia, mas não foi possível sua identificação. Este é o primeiro relato sobre a ocorrência de um cestódeo do gênero Ophiotaenia parasitando C. caninus.

AN IMPROVED ELECTROPHORETIC METHOD FOR THE DETERMINATION OF SERUM MILK PROTEIN VARIANTS IN GYR-HOLSTEIN COWS

Milk serum proteins such as alpha-lactalbumin (ALA) and beta-lactoglobulin (BLG) present biochemical polymorphism which is under the control of codominant autosomal alleles. In the present report, we propose modifications of traditional electrophoretic techniques such as increasing the running gel concentration from 5 to 10% and the addition of 5 M urea to the stacking gel, which permitted the detection of two variants (A and B) at the ALA and BLG loci. About 8 mul of milk serum (6 mg/ml protein) and 10 pl of total fresh milk were applied. Bovine serum albumin (BSA) and immunolactoglobulins (ILG) could also be discriminated. Total fresh milk was as useful as the purified serum milk proteins for the discrimination of ALA and BLG serum milk protein polymorphism by alkaline vertical slab polyacrylamide gel electrophoresis. However, BSA and ILG ran with caseins, which prevented their characterization in this system.

Blood glucose responses in humans mirror lactate responses for individual anaerobic threshold and for lactate minimum in track tests

The equilibrium point between blood lactate production and removal (La-min(-)) and the individual anaerobic threshold (IAT) protocols have been used to evaluate exercise. During progressive exercise, blood lactate [La-](b), catecholamine and cortisol concentrations, show exponential increases at upper anaerobic threshold intensities. Since these hormones enhance blood glucose concentrations [Glc](b), this study investigated the [Glc] and [La-](b) responses during incremental tests and the possibility of considering the individual glucose threshold (IGT) and glucose minimum;(Glc(min)) in addition to IAT and La-min(-) in evaluating exercise. A group of 15 male endurance runners ran in four tests on the track 3000 m run (v(3km)); IAT and IGT- 8 x 800 m runs at velocities between 84% and 102% of v(3km); La-min(-) and Glc(min) - after lactic acidosis induced by a 500-m sprint, the subjects ran 8 x 800 m at intensities between 87% and 97% of v(3km); endurance test (ET)- 30 min at the velocity of IAT. Capillary blood (25 mu l) was collected for [La-](b) and [Glc](b) measurements. The TAT and IGT were determined by [La-](b) and [Glc](b) kinetics during the second test. The La-min(-) and Glc(min) were determined considering the lowest [La-] and [Glc](b) during the third test. No differences were observed (P < 0.05) and high correlations were obtained between the velocities at IAT [283 (SD 19) and IGT 281 (SD 21)m. min(-1); r = 0.096; P < 0.001] and between La,, [285 (SD 21)] and Glc(min) [287 (SD 20) m. min(-1) = 0.77; P < 0.05]. During ET, the [La-](b) reached 5.0 (SD 1.1) and 5.3 (SD 1.0) mmol 1(-1) at 20 and 30 min, respectively (P > 0.05). We concluded that for these subjects it was possible to evaluate the aerobic capacity by IGT and Glc(min), as well as by IAT and La-min(-).

Partial characterization of the polluting load of swine wastewater treated with an integrated biodigestion system

The stabilization of swine wastewaters from swine confined housing by the combination of a upflow anaerobic sludge blanket (UASB) reactor and waste stabilization ponds is a viable alternative to minimize the environmental impact caused by inadequate disposal of swine wastewaters. In the present study, the polluting load of pre-decanted swine wastewater treated with a series of two 0.705 m(3) UASB reactors and then in parallel in aerated and non-aerated stabilization tanks was investigated from January to July, 2000. Physicochemical and microbiological analyses were made adopting standard methods (Standard Methods for Examination of Water and Wastewater, 19th ed., American Public Health Association, Washington, DC, 1995). COD values decreased as the wastewater ran through the integrated biodigestion system dropping from about 3492 +/- 511-4094 mg l(-1) +/- 481 to 124 +/- 52-490 mg l(-1) +/- 230, while nitrate and nitrite levels increased in stabilization tanks, ranging respectively from 4 +/- 0 to 20 mg l(-1) +/- 3 and 3 +/- 1 to 11 mg l(-1) +/- 24. Although the removal of Escherichia coli was more than 97% +/- 6, the effluents of the treatment system still contained unacceptable levels of E. coli (1.6 x 10(3)-1.2 x 10(6) 100 ml(-1)) according to WHO guidelines for use of wastewater in agriculture and aquaculture. These results indicate the necessity of changes on operational characteristics of the treatment system such as an increase of the hydraulic retention time in UASB reactors or in stabilization tanks. (C) 2003 Published by Elsevier Ltd.

Influence of the solution pH on the morphological, structural and electrical properties of Bi3.50La0.50Ti3O12 thin films obtained by the polymeric precursor method

Lanthanum-doped Bi4Ti3O12 thin films (BLT) were deposited on Pt/Ti/SiO2/Si substrates using a polymeric precursor solution. The spin-coated films were specular, crack-free and crystalline after annealing at 700 degrees C for 2 h. Crystallinity and morphological evaluation were examined by X ray diffraction (YRD) and atomic force microscopy (AFM). The stability of the formed complex is of extreme importance for the formation of the perovskite phase. Films obtained from acid pH solution present elongated grains around 200 ran in size, whereas films obtained from basic solution present a dense microstructure with spherical grains (100 nm). The dielectric and ferroelectric properties of the BLT films are strongly affected by the solution pH. The hysteresis loops are fully saturated with a remnant polarization and coercive voltage of P-r=20.2 mu C/cm(2) and V-c = 1.35 V and P-r= 15 mu C/cm(2) and V-c = 1.69 V for the films obtained from basic and acid solutions, respectively. (C) 2005 Elsevier B.V. All rights reserved.

Effect of exercise mode on the blood lactate removal during recovery of high-intensity exercise

The aim of this study was to determine the effect of exercise mode on the blood lactate removal during recovery of high-intensity exercise. Nine male individuals performed the following tests in order to determine the blood lactate removal: Running - 2x200 m, the subjects ran at their maximum capacity, and rested 2 min between each bout. Swimming - 2x50 m, the subjects swam at their maximum capacity, and rested 2 min between each bout. Each test was realized on different days with three recovery modes: passive (sitting down), swimming, or running. Recovery exercise intensity was corresponding to the aerobic threshold. All recovery activities lasted 30 min. The two forms of active recovery were initiated 2 min after the end of high-intensity exercise and lasted 15 min, and were followed by 13 min of seated rest. After 1,7, 12,17, and 30 min of the end of high-intensity exercise, blood samples (25 mu l) were collected in order to determine the blood lactate concentration. By linear regression, between the logarithm of lactate concentration and its respective time of recovery, the half-time of blood lactate removal (t1/2) was determined. Time of high-intensity exercise and the lactate concentration obtained in the 1(st) min of recovery were not different between running and swimming. Passive recovery (PR) following running (R-PR=25.5+/-4.3 min) showed a t1/2 significantly higher than PR after swimming (S-PR=18.6+/-4.3 min). The t1/2 of the sequences running-running (R-R=13.0 min), running-swimming (R-S=12.9+/-3.8 min), swimming-swimming (S-S=13.2+/-2.8 min), and swimming-running (S-R=12.9+/-3.8 min) were significantly lower than the t1/2 of the R-PR and S-PR. There was no difference between the t1/2 of the sequences R-R R-S, and S-S. on the other hand the sequence S-R showed a t1/2 significantly lower than the sequences S-S and R-R. It was concluded that the two forms of active recovery determine an increase in the blood lactate removal, regardless of the mode of high-intensity exercise performed previously. Active recovery performed by the muscle groups that were not previously fatigued, can improve the blood lactate removal.

Genetic Algorithms (Binary and Real Codes) for the Optimisation of a Fermentation Process for Butanol Production

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Geographic distribution and morphological variation in Mimon bennettii (Chiroptera, Phyllostomidae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Plant glandular trichomes mediate protective mutualism in a spider-plant system

1. Although several species of Peucetia (Oxyopidae) live strictly in association with plants bearing glandular trichomes worldwide, to date little is known about whether these associations are mutualistic.2. In this study we manipulated the presence of Peucetia flava on the glandular plant Rhynchanthera dichotoma in the rainy and post-rain season, to test the strength of its effects on leaf, bud, and flower damage and plant reproductive output. In addition, we ran independent field experiments to examine whether these sticky structures improve spider fidelity to plants.3. Peucetia suppressed some species of foliar phytophages, but not others. Although spiders have reduced levels of leaf herbivory, this phenomenon was temporally conditional, i.e. occurred only in the post-rain but not in the rainy season. Floral herbivory was also reduced in the presence of spiders, but these predators did not affect plant fitness components.4. Plants that had their glandular trichomes removed retained fewer insects than those bearing such structures. Spiders remained longer on plants with glandular trichomes than on plants in which these structures had been removed. Isotopic analyses showed that spiders that fed on live and dead labelled flies adhered to the glandular hairs in similar proportions.5. Spiders incurred no costs to the plants, but can potentially increase individual plant fitness by reducing damage to reproductive tissues. Temporal conditionality probably occurred because plant productivity exceeded herbivore consumption, thus dampening top-down effects. Specialisation to live on glandular plants may have favoured scavenging behaviour in Peucetia, possibly an adaptation to periods of food scarcity.