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Abstract Groupers (Epinephelidae and Serranidae) have attracted special attention to fish farming, and their species offer good opportunities for successful hybridizations. Cytogenetic data allow a better understanding of the role of karyotypic diversification in the acquisition of post-zygotic reproductive isolation (RI). Thus, chromosomal analyses were performed on E. striatus (Caribbean Sea), E. coioides and E. tauvina (Indo-Pacific Region), using standard procedures and mapping of six repetitive DNA classes by the in situ hybridization. The three species have 2n=48 chromosomes. The karyotypes of E. coioides and E. striatus are composed only of acrocentric chromosomes (FN=48), while E. tauvina has 8 submetacentric chromosomes (FN=56). Heterochromatin has a preferential centromeric distribution, and the microsatellite repeats are dispersed throughout the chromosomes of all species. The 18S and 5S rDNA sites are unique but show a colocalization arrangement in E. tauvina and E. striatus. The chromosomal organization suggests that the three species still maintain a significant amount of syntenic regions. The range of the karyotype divergence and the RI levels showed low, but goes turn proportionally greater in relation to the divergence time between the parental species. The slow acquisition of postzygotic RI is consistent with the high karyotype homogeneity presented by Epinephelidae family.

Antipsychotics may prolong or retain telomere length, affect mitochondrial function, and then affect the metabolism of nerve cells. To validate the hypothesis that antipsychotics can prolong telomere length after oxidative stress injury, leukocytes from healthy volunteers were extracted using Ficoll-Histopaque density gradient. The mononuclear cells layer was resuspended in cell culture medium. Oxidative stress was induced with hydrogen peroxide in cultured leukocytes. Four days later, leukocytes were treated with aripiprazole, haloperidol or clozapine for 7 days. Real-time PCR revealed that treatments with aripiprazole and haloperidol increased the telomere length by 23% and 20% in peripheral blood mononuclear cells after acute oxidative stress injury. These results suggest that haloperidol and aripiprazole can reduce the damage to telomeres induced by oxidative stress. The experiment procedure was approved by the Ethics Committee of Faculty of Medicine of the University of São Paulo (FMUSP/CAAE approval No. 52622616.8.0000.0065).

In this study, we obtained a lipidomic profile of plasma samples from drug-naïve patients with schizophrenia (SZ) and bipolar disorder (BD) in comparison to healthy controls. The sample cohort consisted of 30 BD and 30 SZ patients and 30 control individuals. An untargeted lipidomics strategy using liquid chromatography coupled with high-resolution mass spectrometry was employed to obtain the lipid profiles. Data were preprocessed, then univariate (t-test) and multivariate (principal component analysis and orthogonal partial least squares discriminant analysis) statistical tools were applied to select differential lipids, which were putatively identified. Afterward, multivariate receiver operating characteristic tests were performed, and metabolic pathway networks were constructed, considering the differential lipids. Our results demonstrate alterations in distinct lipid pathways, especially in glycerophospholipids, sphingolipids and glycerolipids, between SZ and BD patients. The results obtained in this study may serve as a basis for differential diagnosis, which is crucial for effective treatment and improving the quality of life of patients with psychotic disorders.

Objective: To assess the influence of migration on the psychopathological presentation of individuals at ultra-high risk for psychosis (UHR) in São Paulo, Brazil. Methods: This study is part of the Subclinical Symptoms and Prodromal Psychosis (SSAPP) project, a cohort study in São Paulo, Brazil, designed to follow individuals at UHR. After screening with the Prodromal Questionnaire (PQ) and a clinical interview, the Global Assessment of Functioning (GAF) was administered, a neuropsychological assessment was performed, sociodemographic and migration data were obtained. We then analyzed UHR individuals who had migration data to see if migration had any effect on their cognition and psychopathology. Chi-square tests were used for categorical variables, and Student’s t test or analysis of variance (ANOVA) were used for nonparametric and parametric distributions, respectively. Results: The sample was composed of 42 at-risk subjects, of whom 5 had a migration history in the past two generations. Those with migration history showed significantly more formal thought disturbances (p = 0.012) and sleeping problems (p = 0.033) compared to those without. Conclusions: Our data reinforce migration as a risk factor for psychosis in developing countries as well, and highlights the importance of studying the specific effect of this factor in UHR psychopathology.

Bee pollination is crucial for ecosystem maintenance and crop production. The ubiquity of bee pollinators in agricultural landscapes frequently results in their exposure to agrochemicals, which has been associated with their decline. Stingless bees are wild pollinators restricted to the Pantropical region, and like honey bees, are suffering colony losses. However, stingless bees and honey bees do not show the same behaviors, therefore, methods used for risk assessment of honey bees cannot be utilized on stingless bees. Herein, we describe protocols to standardize methods that allow for the exploration of lethal and sublethal effects of agrochemicals via acute and chronic exposure of stingless bees. The in vitro rearing used for chronic exposure from the egg to the adult stage proved to be effective in obtaining relevant screenings. In addition, we performed a meta‐analysis and summarized the results of toxicological studies conducted with the protocols described. The meta-analyses indicated a reduction in survival under acute and chronic exposures to agrochemicals, and revealed that our protocols for toxicological assessments did not have publication bias for either acute or chronic exposure. These findings proved that these standardized protocols are reliable for toxicological research on stingless bee.

Representatives of the order Labriformes show karyotypes of extreme conservatism together with others with high chromosomal diversification. However, the cytological characterization of epigenetic modifications remains unknown for the majority of the species. In the family Labridae, the most abundant fishes on tropical reefs, the genomes of the genus Bodianus Bloch, 1790 have been characterized by the occurrence of a peculiar chromosomal region, here denominated BOD. This region is exceptionally decondensed, heterochromatic, argentophilic, GC-neutral and, in contrast to classical secondary constrictions, shows no signals of hybridization with 18S rDNA probes. In order to characterize the BOD region, the methylation pattern, the distribution of Alu and Tol2 retrotransposons and of 18S and 5S rDNA sites, respectively, were analyzed by Fluorescence In Situ Hybridization (FISH) on metaphase chromosomes of two Bodianus species, B. insularis Gomon & Lubbock, 1980 and B. pulchellus (Poey, 1860). Immunolocalization of the 5-methylcytosine revealed hypermethylated chromosomal regions, dispersed along the entire length of the chromosomes of both species, while the BOD regions exhibited a hypomethylated pattern. Hypomethylation of the BOD region is associated with the precise co-location of Tol2 and Alu elements, suggesting their active participation in the regulatory epigenetic process. This evidence underscores a probable differential methylation action during the cell cycle, as well as the role of Tol2/Alu elements in functional processes of fish genomes.

Cadmium is considered a potentially toxic element, since it doesn't perform any biological function and is highly cumulative. This element is usually found in environmental samples in very low concentrations. For this reason, there is a necessity to develop methods that allow sufficiently low detection limits. From this perspective, a simple, sensitive, selective and low cost methodology was developed for the determination of Cd by F AAS. The system involves the on-line pre concentration of cadmium onto a commercial polystyrene divinil benzene (PSDV) resin modified with phenylfluorone (PF). The experimental conditions (both chemical and physical) were optimized to achieve highest sensitivity. The modified resin had high chemical and physical resistance, and could be reused for 300 cycles without compromising the system's sensitivity. The obtained enrichment factor was around 8 times and accuracy, calculated as relative standard deviation (RSD), of 5.5% for cadmium concentration of 40 µg L-1. The limits of detection and quantification obtained were 0.15 and 0.49 µg L-1, respectively. This methodology proved to be applicable for samples of river waters, in which matrix interferences were not observed. In these samples recovery tests were conducted in order to evaluate the accuracy of the method, and these results varied between 89 and 118%.

The present paper demonstrates the application of functional GGA hybrids, with long-range corrections, for the calculation of the electronic properties of artemisinin and two of its derivatives - artemether e artesunate. Due to the relatively large amount of data obtained, the statistical method of Principal Component Analysis was employed. The functionals of the WB97 family are observed to be the most appropriate for the determining of reactivity indexes, which are the principal descriptors that, probably, are associated with the antimalarial and anticancer properties of this group of molecules. In addition, it was also observed that all the functionals obtained satisfactorily describe the geometric properties of the studied.

Background: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-based morphometry (VBM) study was carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertain which (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity. Methods: We gathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) from four previous morphometric MRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General Linear Model Analysis of Co-variance (ANCOVA), always including total GM volume, scan protocol, age and gender as nuisance variables. Finally, correlation analyses were performed between the aforementioned clinical moderators and regional and global brain volumes. Results: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume-corrected (SVC) analyses (p

Background: Pediatric overweight is associated with higher incidences of musculoskeletal pain and injuries. It is still not known exactly what causes these problems. The purpose of this study was to compare overweight children with their non-overweight counterparts with respect to the leg axis and joint mobility.Methods: In all, 46 overweight children (girls: age: 8y. 9m. 1y. 2m., BMI-Percentile: 97.7 3.0; boys: age: 9y. 6m. 1y. 4m., BMI-Percentile: 98.2 2.5 (mean value standard deviation)) were compared with 42 non-overweight children (girls: age: 9 y. 3 mo. 1 y. 3 mo., BMI-Percentile: 26.9 20.8; boys: age: 9 y. 4 mo. 1 y. 2 mo., BMI-Percentile: 41.32 27.6). The passive range of joint motion in the lower extremity was assessed. Knee alignment was determined by digital photographs. Injury and pain history were recorded.Results: Overweight children showed deficits in the range of motion of the hip and the knee joints. Overweight girls had significantly higher knee valgus angles than non-overweight girls. In overweight children, ankle sprain (13/46) was the most common injury compared with six of 42 non-overweight children.Conclusions: Overweight children showed joint mobility restrictions and increased knee valgus angles when compared with non-overweight ones. These factors could influence the risk of sustaining injuries at the lower extremities. Prevention programs need to be established already in childhood.KEY WORDS: Paediatric Overweight, Paediatric Obesity, Leg Axis, Range of Motion, Injury

Freshwater prawns of the genus Macrobrachium are one of the important components of circumtropical marine, estuarine, and freshwater environments. They have been extensively exploited for human consumption for many years. More than 250 species reflect the evolutionary success of this highly diversified group, with a complex and challenging taxonomy due to morphological variations and vast geographical distribution. Although genetic approaches have been used to clarify phylogenetic and taxonomic aspects of Macrobrachium species, cytogenetic information is still very scarce and mostly focused on chromosome number and morphology. Here, we present chromosome data for three species from the Neotropical region, M. carcinus, M. acanthurus, and M. amazonicum, and one species from the Oriental region, M. rosenbergii. Using conventional cytogenetic approaches and chromosome mapping of repetitive DNAs by fluorescence in situ hybridization (FISH), we identified numerical diversification of the diploid set, within and between both zoogeographic regions. These included M. acanthurus and M. amazonicum sharing diploid chromosomes of 98, while M. carcinus has 94, and M. rosenbergii has 118 chromosomes. Argentophilic sites are also variable in number, but they occur in a much higher number than 18S rDNA, representing two to 10 sites within the study species. Microsatellites repeat motifs are also abundant in the chromosomes, with a co-localization and uniform distribution along the chromosome arms, but completely absent in the AT-rich centromeric regions. As a whole, our study suggests that the 2n divergence was followed by a considerable rDNA diversification. The abundance of the exceptional amount of microsatellite sequences in the chromosomes also suggests that they are essential components of the Macrobrachium genome and, therefore, maintained as a shared feature by the species, the reason for which is yet unknown.

This paper is based on the last talk of the summer school. The intention of the talk was not to repeat any highlights of the school, rather to place the energy issue in a wider frame of global issues like global warming and the global responses to this threat. Therefore, I tried to compile —where possible— new data which inform the audience on the present stage of the energy transition toward carbon-free technologies and some expected future trends. The largest hopes for a successful transformation are connected to renewable energy forms. This field is discussed here mostly from a system point of view whereas I resort heavily to examples from Germany. The most obvious reason is that I am familiar with the German development and have access to the most relevant data. On the other hand, the German experience is of importance for other highly industrialised economies and its development affects other countries because of its central location.

Objective:To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT) Val158Met and dopamine receptor 3 (DRD3) Ser9Gly.Methods:Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs) using age, sex, and years of education as covariates compared cognitive performance for the proposed genotypes in patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype combinations on cognitive performance.Results:For executive functioning, COMT Val/Val patients performed in a similar range as controls (30.70-33.26 vs. 35.53-35.67), but as COMT Met allele frequency increased, executive functioning worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184 vs. 27.388-31.824). Scores of carriers of this COMT/DRD3 combination significantly differed from all DRD3 Gly/Gly combinations (p < 0.05), from COMT Val/Met DRD3 Ser/Gly (p = 0.02), and from COMT Val/Val DRD3 Ser/Ser (p = 0.01) in patients. It also differed significantly from all control scores (p < 0.001).Conclusion:Combined genetic polymorphisms related to dopamine neurotransmission might influence executive function in schizophrenia. Looking at the effects of multiple genes on a single disease trait (epistasis) provides a comprehensive and more reliable way to determine genetic effects on endophenotypes.

The Epinephelidae form a group of species of high biological and economical interests. It´s phylogeographic patterns are not well known especially the distributed populations in the western region of the Atlantic Ocean. Among the representatives is a small species called Cephalopholis fulva, Coney, which presents a wide geographical distribution, polychromia, hermaphroditism and is quickly becoming a large target for the exploration of commercial fishing. The genetic and historical demography were obtained through the partial sequence analysis of Control Region from six locations on the coastline of Brazil from the northeast coast to the southwest coast, including the oceanic islands of Rocas Atoll and Fernando de Noronha Archipelago. The analyzed samples revealed a high genetic variability and a strong gene flow among the sampled locations. Additionally, the genetic data revealed that population expansions probably occurred due to the changes in the sea levels that occurred during the Pleistocene. The large population connectivity found in Coney constitutes relevant conditions for their biological conservation.

Mechanisms of accumulation based on typical centromeric drive or of chromosomes carrying pericentric inversions are adjusted to the general karyotype differentiation in the principal Actinopterygii orders. Here, we show that meiotic drive in fish is also supported by preferential establishment of sex chromosome systems and B chromosomes in orders with predominantly bi-brachial chromosomes. The mosaic of trends acting at an infra-familiar level in fish could be explained as the interaction of the directional process of meiotic drive as background, modulated on a smaller scale by adaptive factors or specific karyotypic properties of each group, as proposed for the orthoselection model.

This study presents the proposal of dynamic cognitive networks (DCN), and also the evolution of Cognitive Maps and Fuzzy Cognitive Maps. Fuzzy Cognitive Maps (FCM) can be applied in several areas of knowledge; however, it presents some restrictions in dynamic systems. Due to these restrictions, some architectures proposals are based on FCM and also classical proposals for cognitive models based on these concepts are available in the literature. Dynamic Cognitive Networks is one of these approaches. Hence, this study presents an original proposal with background for the construction of DCN and applications in process control and autonomous navigation.

Objective: To critically review and evaluate existing knowledge on the conceptual limits and clinical usefulness of the diagnosis of mild cognitive impairment (MCI) and the neuropsychological assessment and short- and long-term prognosis thereof. Methods: We conducted a systematic search of the PubMed and Web of Science electronic databases, limited to articles published in English between 1999 and 2012. Based on the search terms mild cognitive impairment or MCI and epidemiology or diagnosis, we retrieved 1,698 articles, of which 248 were critically eligible (cross-sectional and longitudinal studies); the abstracts of the remaining 1,450 articles were also reviewed. Results: A critical review on the MCI construct is provided, including conceptual and diagnostic aspects; epidemiological relevance; clinical assessment; prognosis; and outcome. The distinct definitions of cognitive impairment, MCI included, yield clinically heterogeneous groups of individuals. Those who will eventually progress to dementia may present with symptoms consistent with the definition of MCI; conversely, individuals with MCI may remain stable or return to normal cognitive function. Conclusion: On clinical grounds, the cross-sectional diagnosis of MCI has limited prognostic relevance. The characterization of persistent and/or progressive cognitive deficits over time is a better approach for identification of cases at the pre-dementia stages, particularly if these cognitive abnormalities are consistent with the natural history of incipient Alzheimer's disease.

In this study, we investigated the associations between single-nucleotide polymorphisms in GAB2 (rs2373115), GSK3B (rs6438552) and SORL1 (rs641120) and Alzheimer's disease (AD), both alone and in combination with the APOE*4 allele.

BACKGROUND:Major depressive disorder (MDD) is a highly prevalent, heterogeneous and systemic medical condition. Treatment options are limited, and recent studies have suggested that physical exercise can play an important role in the therapeutics of MDD. The aim of this study was to evaluate the antidepressant efficacy of adjunctive aerobic activity in association with pharmacotherapy (selective serotonin reuptake inhibitor) in symptomatic MDD as well as its association with physiological biomarkers. METHODS:In this randomized, single-blind, add-on, controlled clinical trial, 57 patients (18-55 years of age) were followed-up for 28 days. All patients were drug-free, had been diagnosed with symptomatic MDD and received flexible dose of sertraline during the trial. Patients were randomized to either a 4-week program (4x/week) of add-on aerobic exercise (exercise group, N = 29) or no activity (control group, N = 28). Depression severity was assessed using the Hamilton Rating Scale for Depression (HAM-D) as the primary outcome. At baseline and endpoint, all patients underwent a comprehensive metabolic/cardiopulmonary exercise testing-including determination of maximal oxygen uptake (VO2max), VO2 at the second ventilatory threshold (VO2-VT2), and oxygen pulse (O2 pulse). RESULTS:Depression scores significantly decreased in both groups after intervention. Importantly, patients in the aerobic exercise group required lower sertraline dose compared to the control group (sertraline monotherapy). The VO2max and O2 pulse parameters increased over time only in the exercise group and remained unchanged in the control group. CONCLUSIONS:The present findings suggest that a 4-week training of aerobic exercise significantly improves functional capacity in patients with MDD and may be associated with antidepressant efficacy. This approach may also decrease the need for higher doses of antidepressants to achieve response. Further studies in unmedicated and treatment-resistant MDD patients are needed in order to confirm the utility of short-term aerobic exercise as an alternative therapeutic approach in MDD. TRIAL REGISTRATION:ClinicalTrials.gov NCT02427789.

Alzheimer disease is the most common cause of dementia among the elderly, accounting for ~60-70% of all cases of dementia. The neuropathological hallmarks of Alzheimer disease are senile plaques (mainly containing p-amyloid peptide derived from amyloid precursor protein) and neurofibrillary tangles (containing hyperphosphorylated Tau protein), along with neuronal loss. At present there is no effective treatment for Alzheimer disease. Given the prevalence and poor prognosis of the disease, the development of animal models has been a research priority to understand pathogenic mechanisms and to test therapeutic strategies. Most cases of Alzheimer disease occur sporadically in people over 65 years old, and are not genetically inherited. Roughly 5% of patients with Alzheimer disease have familial Alzheimer disease-that is, related to a genetic predisposition, including mutations in the amyloid precursor protein, presenilin 1, and presenilin 2 genes. The discovery of genes for familial Alzheimer disease has allowed transgenic models to be generated through the overexpression of the amyloid precursor protein and/or presenilins harboring one or several mutations found in familial Alzheimer disease. Although none of these models fully replicates the human disease, they have provided valuable insights into disease mechanisms as well as opportunities to test therapeutic approaches. This review describes the main transgenic mouse models of Alzheimer disease which have been adopted in Alzheimer disease research, and discusses the insights into Alzheimer disease pathogenesis from studies in such models. In summary, the Alzheimer disease mouse models have been the key to understanding the roles of soluble b-amyloid oligomers in disease pathogenesis, as well as of the relationship between p-amyloid and Tau pathologies.

OBJECTIVE: To identify predictors of the progression from pre-dementia stages of cognitive impairment in Alzheimer's disease is relevant to clinical management and to substantiate the decision of prescribing antidementia drugs. METHOD: Longitudinal study of a cohort of elderly adults with amnestic mild cognitive impairment and healthy controls, carried out to estimate the risk and characterize predictors of the progression to Alzheimer's disease. RESULTS: Patients with amnestic mild cognitive impairment had a higher risk to develop Alzheimer's disease during follow-up (odds ratio = 4.5, CI95% [1.3-13.6], p = 0.010). At baseline, older age, lower scores on memory tests and presence of the APOE*4 allele predicted the progression from amnestic mild cognitive impairment to Alzheimer's disease. In a sub sample of amnestic mild cognitive impairment patients, those who progressed to Alzheimer's disease had lower cerebrospinal fluid concentrations of amyloid-beta peptide (Aβ42, p = 0.020) and higher concentrations of total TAU (p = 0.030) and phosphorylated TAU (p = 0.010), as compared to non-converters. DISCUSSION: This is the first Brazilian study to report cerebrospinal fluid biomarkers in the prediction of the conversion from MCI to Alzheimer's disease. Our data are in accordance with those reported in other settings. The measurement of cerebrospinal fluid total-TAU, phospho-TAU and Aβ42 may help identify patients with mild cognitive impairment at higher risk for developing Alzheimer's disease.OBJETIVO: A identificação de preditores da conversão para a doença de Alzheimer em pacientes com comprometimento cognitivo leve é relevante para o manejo clínico e para decidir sobre a prescrição de drogas antidemência. MÉTODO: Estudo longitudinal em coorte de indivíduos idosos com comprometimento cognitivo leve amnéstico e controles saudáveis; estimativa do risco da progressão para doença de Alzheimer nos dois grupos; determinação das variáveis preditivas desse desfecho. RESULTADOS: Pacientes com comprometimento cognitivo leve amnéstico apresentaram maior risco de desenvolver doença de Alzheimer ao longo do seguimento (odds ratio = 4,5, CI95% [1,3-13,6], p = 0,012). Na avaliação inicial, idade mais avançada, escores mais baixos nos testes cognitivos e do alelo APOE*4 foram preditores da conversão do comprometimento cognitivo leve amnéstico para doença de Alzheimer. Em uma subamostra de pacientes com comprometimento cognitivo leve amnéstico, aqueles que progrediram para doença de Alzheimer tinham concentrações liquóricas mais baixas do peptídeo beta-amilóide (Aβ42, p = 0,020) e mais altas da proteína TAU total (p = 0,030) e TAU fosforilada (p = 0,010) do que os pacientes que não progrediram para doença de Alzheimer. DISCUSSÃO: Este é o primeiro estudo brasileiro com biomarcadores liquóricos a relatar preditores da conversão comprometimento cognitivo leve-doença de Alzheimer. Nossos dados biológicos (aumento de TAU total e fosfo-TAU; redução de Aβ42), e podem auxiliar na identificação dos pacientes com comprometimento cognitivo leve com maior risco de evolução para demência.