Alstonine as an Antipsychotic: Effects on Brain Amines and Metabolic Changes

Managing schizophrenia has never been a trivial matter. Furthermore, while classical antipsychotics induce extrapyramidal side effects and hyperprolactinaemia, atypical antipsychotics lead to diabetes, hyperlipidaemia, and weight gain. Moreover, even with newer drugs, a sizable proportion of patients do not show significant improvement. Alstonine is an indole alkaloid identified as the major component of a plant-based remedy used in Nigeria to treat the mentally ill. Alstonine presents a clear antipsychotic profile in rodents, apparently with differential effects in distinct dopaminergic pathways. The aim of this study was to complement the antipsychotic profile of alstonine, verifying its effects on brain amines in mouse frontal cortex and striatum. Additionally, we examined if alstonine induces some hormonal and metabolic changes common to antipsychotics. HPLC data reveal that alstonine increases serotonergic transmission and increases intraneuronal dopamine catabolism. In relation to possible side effects, preliminary data suggest that alstonine does not affect prolactin levels, does not induce gains in body weight, but prevents the expected fasting-induced decrease in glucose levels. Overall, this study reinforces the proposal that alstonine is a potential innovative antipsychotic, and that a comprehensive understanding of its neurochemical basis may open new avenues to developing newer antipsychotic medications.

Genetic parameters for pre-weaning traits in Braunvieh cattle

The objective of this study was to estimate genetic parameters for pre-weaning traits of Braunvieh cattle raised under tropical conditions in Brazil. The weight and weight gain parameters were birth weight (BW, N = 9955), weight at 120 days of age (W120, N = 5901), weaning weight at 205 days (WW, N = 6970), weight gain from birth to 205 days (GAIN205, N = 6013), weight gain from birth to 120 days (GAIN120, N = 5135), and weight gain from 120 to 205 days (GAIN85, N = 4482). Variance components were estimated using the animal model with the MTDFREML software. The relationship matrix included 35,188 animals; phenotypic measures were available for 18,688. Direct and maternal heritability increased from birth to weaning, with estimates of 0.23 +/- 0.037, 0.25 +/- 0.050, 0.41 +/- 0.059 for direct heritability for BW, W120 and WW, respectively, 0.08 +/- 0.012, 0.15 +/- 0.032, 0.22 +/- 0.036 for maternal genetic effects, and 0.18, 0.14 and 0.16 for total heritability estimates. For pre-weaning gains, estimates of heritability were 0.36 +/- 0.059, 0.30 +/- 0.059, 0.12 +/- 0.035 for direct genetic effects of the traits GAIN205, GAIN120 and GAIN85, respectively, 0.23 +/- 0.038, 0.17 +/- 0.037, 0.03 +/- 0.029 for estimates of maternal heritability, and 0.12, 0.13, 0.16 for total heritability, respectively. Genetic correlations between weights were greater between measures taken at shorter intervals. This information can be used to optimize the design of programs for genetic improvement of Braunvieh cattle raised under tropical conditions.

Genetic parameters for postweaning traits in Braunvieh cattle

Genetic parameters for traits related to postweaning growth in Braunvieh cattle, reared under tropical and sub-tropical conditions in Brazil, were studied. Weight traits were weight at 365 days of age (W365, N = 4055), at 450 days (W450, N = 3453), and at 550 days (W550, N = 1946), while weight gains were gain from weaning to 365 days of age (WGW365, N = 3060), from weaning to 450 days (WGW450, N = 2764), from weaning to 550 days (WGW550, N = 1531), from 365 to 550 days of age (WG365550, N = 1528), from 365 to 450 days (WG365450, N = 2401), and from 450 to 550 days (WG450550, N = 1563). A full animal model was used for estimating the variance components, using the MTDFREML software. The dataset contained 18,688 animals with phenotypic measures and 35,188 animals in the relationship matrix. Heritability estimates for postweaning weights decreased with age. For W365, W450 and W550, respectively, the direct heritability estimates were 0.29 +/- 0.061, 0.25 +/- 0.057, 0.16 +/- 0.060, maternal heritability was 0.20 +/- 0.035, 0.18 +/- 0.035, 0.13 +/- 0.052, and total heritability was 0.30, 0.35, 0.26. In this breed, maternal influence was found to be important up to 550 days of age. The greater genetic correlations between weights were observed for weights measured at shorter intervals. A large environmental effect was observed for weight gain between weaning and 550 days; this effect was greater for the gains between 365 and 550 days.

Karyotypic evolution trends in Rhamdia quelen (Siluriformes, Heptapteridae) with considerations about the origin and differentiation of its supernumerary chromosomes

Among catfish species of the genus Rhamdia reported for the Brazilian territory, R. quelen is the most widespread, being found in nearly all hydrographic basins of Brazil. Nowadays, R. quelen is a synonym for at least 47 other species in this genus, its taxonomic status still being controversial. The available cytogenetic reports show a wide variation in the karyotypic macrostructure, with the frequent presence of supernumerary chromosomes. The remarkable cytogenetic variability associated with taxonomic issues in this species indicates that R. quelen is actually a species complex. In order to carry out a wide comparative cytogenetic study in R. quelen from southern and southeastern Brazil and examine a species complex, we analyzed the chromosomes of 14 populations from the main hydrographic basins of these two regions. Using classic and molecular cytogenetic techniques, we found seven distinct karyotypic formulae, all bearing 2n = 58 chromosomes. Supernumerary chromosomes were present in most of the populations; their number, size and C-banding pattern allowed us to differentiate populations with similar karyotypic compositions. We examined patterns of chromosomal evolution as well as the probable mechanisms involved in the origin and morphological differentiation of their supernumerary chromosomes.

Leishmania-Specific Surface Antigens Show Sub-Genus Sequence Variation and Immune Recognition

Background: A family of hydrophilic acylated surface (HASP) proteins, containing extensive and variant amino acid repeats, is expressed at the plasma membrane in infective extracellular (metacyclic) and intracellular (amastigote) stages of Old World Leishmania species. While HASPs are antigenic in the host and can induce protective immune responses, the biological functions of these Leishmania-specific proteins remain unresolved. Previous genome analysis has suggested that parasites of the sub-genus Leishmania (Viannia) have lost HASP genes from their genomes. Methods/Principal Findings: We have used molecular and cellular methods to analyse HASP expression in New World Leishmania mexicana complex species and show that, unlike in L. major, these proteins are expressed predominantly following differentiation into amastigotes within macrophages. Further genome analysis has revealed that the L. (Viannia) species, L. (V.) braziliensis, does express HASP-like proteins of low amino acid similarity but with similar biochemical characteristics, from genes present on a region of chromosome 23 that is syntenic with the HASP/SHERP locus in Old World Leishmania species and the L. (L.) mexicana complex. A related gene is also present in Leptomonas seymouri and this may represent the ancestral copy of these Leishmania-genus specific sequences. The L. braziliensis HASP-like proteins (named the orthologous (o) HASPs) are predominantly expressed on the plasma membrane in amastigotes and are recognised by immune sera taken from 4 out of 6 leishmaniasis patients tested in an endemic region of Brazil. Analysis of the repetitive domains of the oHASPs has shown considerable genetic variation in parasite isolates taken from the same patients, suggesting that antigenic change may play a role in immune recognition of this protein family. Conclusions/Significance: These findings confirm that antigenic hydrophilic acylated proteins are expressed from genes in the same chromosomal region in species across the genus Leishmania. These proteins are surface-exposed on amastigotes (although L. (L.) major parasites also express HASPB on the metacyclic plasma membrane). The central repetitive domains of the HASPs are highly variant in their amino acid sequences, both within and between species, consistent with a role in immune recognition in the host.

CHARACTERIZATION OF EXPONENTIAL DIVERGENCE OF THE KALMAN FILTER FOR TIME-VARYING SYSTEMS

This paper studies semistability of the recursive Kalman filter in the context of linear time-varying (LTV), possibly nondetectable systems with incorrect noise information. Semistability is a key property, as it ensures that the actual estimation error does not diverge exponentially. We explore structural properties of the filter to obtain a necessary and sufficient condition for the filter to be semistable. The condition does not involve limiting gains nor the solution of Riccati equations, as they can be difficult to obtain numerically and may not exist. We also compare semistability with the notions of stability and stability w.r.t. the initial error covariance, and we show that semistability in a sense makes no distinction between persistent and nonpersistent incorrect noise models, as opposed to stability. In the linear time invariant scenario we obtain algebraic, easy to test conditions for semistability and stability, which complement results available in the context of detectable systems. Illustrative examples are included.

Retinoic Acid-Treated Pluripotent Stem Cells Undergoing Neurogenesis Present Increased Aneuploidy and Micronuclei Formation

The existence of loss and gain of chromosomes, known as aneuploidy, has been previously described within the central nervous system. During development, at least one-third of neural progenitor cells (NPCs) are aneuploid. Notably, aneuploid NPCs may survive and functionally integrate into the mature neural circuitry. Given the unanswered significance of this phenomenon, we tested the hypothesis that neural differentiation induced by all-trans retinoic acid (RA) in pluripotent stem cells is accompanied by increased levels of aneuploidy, as previously described for cortical NPCs in vivo. In this work we used embryonal carcinoma (EC) cells, embryonic stem (ES) cells and induced pluripotent stem (iPS) cells undergoing differentiation into NPCs. Ploidy analysis revealed a 2-fold increase in the rate of aneuploidy, with the prevalence of chromosome loss in RA primed stem cells when compared to naive cells. In an attempt to understand the basis of neurogenic aneuploidy, micronuclei formation and survivin expression was assessed in pluripotent stem cells exposed to RA. RA increased micronuclei occurrence by almost 2-fold while decreased survivin expression by 50%, indicating possible mechanisms by which stem cells lose their chromosomes during neural differentiation. DNA fragmentation analysis demonstrated no increase in apoptosis on embryoid bodies treated with RA, indicating that cell death is not the mandatory fate of aneuploid NPCs derived from pluripotent cells. In order to exclude that the increase in aneuploidy was a spurious consequence of RA treatment, not related to neurogenesis, mouse embryonic fibroblasts were treated with RA under the same conditions and no alterations in chromosome gain or loss were observed. These findings indicate a correlation amongst neural differentiation, aneuploidy, micronuclei formation and survivin downregulation in pluripotent stem cells exposed to RA, providing evidence that somatically generated chromosomal variation accompanies neurogenesis in vitro.

Disparity between Multilocus Enzyme Electrophoresis, Microsatellite Markers and Pulsed-Field Gel Electrophoresis in epidemiological tracking of Candida albicans

Various molecular systems are available for epidemiological, genetic, evolutionary, taxonomic and systematic studies of innumerable fungal infections, especially those caused by the opportunistic pathogen C. albicans. A total of 75 independent oral isolates were selected in order to compare Multilocus Enzyme Electrophoresis (MLEE), Electrophoretic Karyotyping (EK) and Microsatellite Markers (Simple Sequence Repeats - SSRs), in their abilities to differentiate and group C. albicans isolates (discriminatory power), and also, to evaluate the concordance and similarity of the groups of strains determined by cluster analysis for each fingerprinting method. Isoenzyme typing was performed using eleven enzyme systems: Adh, Sdh, M1p, Mdh, Idh, Gdh, G6pdh, Asd, Cat, Po, and Lap (data previously published). The EK method consisted of chromosomal DNA separation by pulsed-field gel electrophoresis using a CHEF system. The microsatellite markers were investigated by PCR using three polymorphic loci: EF3, CDC3, and HIS3. Dendrograms were generated by the SAHN method and UPGMA algorithm based on similarity matrices (S(SM)). The discriminatory power of the three methods was over 95%, however a paired analysis among them showed a parity of 19.7-22.4% in the identification of strains. Weak correlation was also observed among the genetic similarity matrices (S(SM)(MLEE) x S(SM)(EK) x S(SM)(SSRs)). Clustering analyses showed a mean of 9 +/- 12.4 isolates per cluster (3.8 +/- 8 isolates/taxon) for MLEE, 6.2 +/- 4.9 isolates per cluster (4 +/- 4.5 isolates/taxon) for SSRs, and 4.1 +/- 2.3 isolates per cluster (2.6 +/- 2.3 isolates/taxon) for EK. A total of 45 (13%), 39(11.2%), 5 (1.4%) and 3 (0.9%) clusters pairs from 347 showed similarity (Si) of 0.1-10%, 10.1-20%, 20.1-30% and 30.1-40%, respectively. Clinical and molecular epidemiological correlation involving the opportunistic pathogen C. albicans may be attributed dependently of each method of genotyping (i.e., MLEE, EK, and SSRs) supplemented with similarity and grouping analysis. Therefore, the use of genotyping systems that give results which offer minimum disparity, or the combination of the results of these systems, can provide greater security and consistency in the determination of strains and their genetic relationships. (C) 2010 Elsevier B.V. All rights reserved.

Biofuels and Sustainable Energy Development in Brazil

Through the assessment of three decades of the Alcohol Program in Brazil, the paper shows that adequate public policies regarding biomass production can deliver direct benefits like energy security improvement, foreign exchange savings, and local employment generation, reduced urban air pollution and avoided CO(2) emissions. Moreover, the paper shows that Brazilian produced ethanol has faced economies of scale, technical progress and productivity gains and is no longer dependent on subsidies to be competitive. The paper also examines the potential in Brazil for fostering other biofuels, namely biodiesel obtained from vegetable oils, as well as their implications on sustainable energy development. (C) 2011 Elsevier Ltd. All rights reserved.

Elderly online: Effects of a digital inclusion program in cognitive performance

There is little empirical data about the impact of digital inclusion on cognition among older adults. This paper aimed at investigating the effects of a digital inclusion program in the cognitive performance of older individuals who participated in a computer learning workshop named ""Idosos On-Line`` (Elderly Online). Forty-two aged individuals participated in the research study: 22 completed the computer training workshop and 20 constituted the control group. All subjects answered a sociodemographic questionnaire and completed the Addenbrooke`s cognitive examination, revised (ACE-R), which examines five cognitive domains: orientation and attention, memory, verbal fluency, language, and visuo-spatial skills. It was noted that the experimental group`s cognitive performance significantly improved after the program, particularly in the language and memory domains, when compared to the control group. These findings suggest that the acquisition of new knowledge and the use of a new tool, that makes it possible to access the Internet, may bring gains to cognition. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Kallikrein-Kinin System Mediated Inflammation in Alzheimer`s Disease In Vivo

The Kallikrein-Kinin System (KKS) has been associated to inflammatory and immunogenic responses in the peripheral and central nervous system by the activation of two receptors, namely B1 receptor and B2 receptor. The B1 receptor is absent or under-expressed in physiological conditions, being up-regulated during tissue injury or in the presence of cytokines. The B2 receptor is constitutive and mediates most of the biological effects of kinins. Some authors suggest a link between the KKS and the neuroinflammation in Alzheimer`s disease (AD). We have recently described an increase in bradykinin (BK) in the cerebrospinal fluid and in densities of B1 and B2 receptors in brain areas related to memory, after chronic infusion of amyloid-beta (A beta) peptide in rats, which was accompanied by memory disruption and neuronal loss. Mice lacking B1 or B2 receptors presented reduced cognitive deficits related to the learning process, after acute intracerebroventricular (i.c.v). administration of A. Nevertheless, our group showed an early disruption of cognitive function by i.c.v. chronic infusion of A beta after a learned task, in the knock-out B2 mice. This suggests a neuroprotective role for B2 receptors. In knock-out B1 mice the memory disruption was absent, implying the participation of this receptor in neurodegenerative processes. The acute or chronic infusion of A beta can lead to different responses of the brain tissue. In this way, the proper involvement of KKS on neuroinflammation in AD probably depends on the amount of A beta injected. Though, BK applied to neurons can exert inflammatory effects, whereas in glial cells, BK can have a potential protective role for neurons, by inhibiting proinflammatory cytokines. This review discusses this duality concerning the KKS and neuroinflammation in AD in vivo.

Expression of genes related to muscle plasticity after strength and power training regimens

The purpose of our study was to compare the effects of 8-week progressive strength and power training regimens on strength gains and muscle plasticity [muscle fiber hypertrophy and phenotype shift, mammalian target of rapamycin (mTOR), regulatory-associated protein of mTOR (RAPTOR), rapamycin-insensitive companion of m-TOR (RICTOR), calcineurin and calcipressin gene expression]. Twenty-nine physically active subjects were divided into three groups: strength training (ST), power training (PT) and control (C). Squat 1 RM and muscle biopsies were obtained before and after the training period. Strength increased similarly for both ST and PT groups (P < 0.001). Fiber types I, IIa and IIb presented hypertrophy main time effect (P < 0.05). Only type IIb percentage decreased from pre- to post-test (main time effect, P < 0.05). mTOR and RICTOR mRNA expression increased similarly from pre- to post-test (P < 0.01). RAPTOR increased after training for both groups (P < 0.0001), but to a greater extent in the ST (P < 0.001) than in the PT group. 4EBP-1 decreased after training when the ST and PT groups were pooled (P < 0.05). Calcineurin levels did not change after training, while calcipressin increased similarly from pre- to post-test (P < 0.01). In conclusion, our data indicate that these training regimens produce similar performance improvements; however, there was a trend toward greater hypertrophy-related gene expression and muscle fiber hypertrophy in the ST group.

Effects of strength training and vascular occlusion

The purpose of our study was to determine if vascular Occlusion produced an additive effect on muscle hypertrophy and strength performance with high strength training loads. Sixteen physically active men were divided into two groups: high-intensity (HI = 6 RM) and moderate-intensity training (MI = 12 RM). An occlusion cuff was attached to the proximal end of the right thigh, so that blood flow was reduced during the exercise. The left leg served as a control, thus was trained without vascular occlusion. Knee extension 1 RM and quadriceps cross-sectional area (MRI) were evaluated pre- and post-8 weeks of training. We only found a main time effect for both strength gains and quadriceps hypertrophy (p < 0.001). Therefore, we conclude that vascular occlusion in combination with high-intensity strength training does not augment muscle strength or hypertrophy when compared to high-intensity strength training alone.

Effect of eight weeks of strength training on fatigue resistance in men and women

The purpose of the present study was to compare the effects of eight weeks of strength training on fatigue resistance in men and women. Thirty-three men and twenty-three women performed eight weeks of strength training in three weekly sessions. Subjects performed four sets using 80% of 1-RM tests on bench press, squat and arm curl. Fatigue index (FI) was used for analysis of decline in motor performance along the sets. The sum of the number of repetitions accomplished in the four sets in each exercise was used to indicate the fatigue resistance. Anova or Ancova two-way ( time x gender) was employed for statistical analysis ( P < 0.05). Eight weeks of strength training increased significantly 1-RM strength, fatigue resistance and total number of repetitions in both genders. FI decreased significantly in both genders after training ( men = 50% vs. women = Time x gender interaction was observed in the total number of repetitions in squat ( P = 0.04) and arm curl exercises, regarding gains to women ( P = 0.01). In conclusion, eight weeks of ST improved strength, FR, FI and total number of repetitions performed. However, women obtained greater adaptations than men.

Control system design for flexible rotors supported by actively lubricated bearings

This article presents a methodology for calculating the gains of an output feedback controller for active vibration control of flexible rotors. The methodology is based on modal reduction. The proportional and derivative gains are obtained by adjusting the first two damping factors of the system and keeping the lengths of the two eigenvalues constant in the real-imaginary plane. The methodology is applied to an industrial gas compressor supported by active tilting-pad journal bearings. The unbalance response functions and mode shapes of the flexible rotor with and without active control are presented, showing significative improvement in damping reserve with the control. The importance of sensor location is emphasized, on the basis of the energy necessary to operate the active system over the entire frequency range studied. The best results are obtained by a decentralized controller, observing displacement and velocity of the shaft at the bearing positions.