Abstract Schizophrenia is an illness that affects 26 million people worldwide. However, conventional antipsychotics present side effects and toxicity, highlighting the need for new antipsychotics. We aimed to evaluate the cytotoxicity of haloperidol (HAL), clozapine (CLO), and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells. The neutral red uptake assay and the MTT assay were performed to evaluate cell viability and mitochondrial activity, morphological changes were assessed, and intracellular reactive oxygen species (ROS) detection was performed. HAL and CLO (0.1 μM) showed a decrease in cell viability in the neutral red uptake assay and in the MTT assay. In addition, cell detachment, content decrease, rounding and cell death were also observed at 0.1 μM for both antipsychotics. An increase in ROS was observed for HAL (0.001, 0.01 and 1 μM) and CLO (0.01 and 1 μM). PT-31 did not alter cell viability in any of the assays, although it increased ROS at 0.01 and 1 μM. HAL and CLO present cytotoxicity at 0.1 μM, possibly through apoptosis and necrosis. In contrast, PT-31 does not present cytotoxicity to NIH-3T3 cells. Further studies must be performed for a better understanding of these mechanisms and the potential risk of conventional antipsychotics. 2 worldwide However toxicity HAL, , (HAL) CLO, (CLO) PT31, PT31 PT 31, 31 NIH3T3 NIHT NIH 3T3 T NIH-3T cells activity assessed (ROS 01 0 (0. addition detachment 0. 0.001, 0001 001 (0.001 0.0 (0.0 . PT-3 assays necrosis contrast (HAL (CLO PT3 3 NIH3T 3T (0 0.001 000 00 (0.00 PT- ( 0.00

ABSTRACT Dengue virus, the etiological agent of dengue fever (DF) occurs in four genetically distinct serotypes (DENV1-4), being transmitted by female Aedes mosquitoes. DF incidence is increasing in Brazil, following vector dispersal, proliferation and DENV serotypes introduction, co-circulation and substitution. Medium- and small-sized cities in Sao Paulo State, such as Marilia (Midwest region), have been affected by huge epidemics. To understand the evolution of DENV epidemics in medium-sized cities, in this study a historical data on DENV incidence (2000-2015) in Marilia, was evaluated. Previous studies disclosed regional and specific DF outcomes associated with 2007 outbreak in that city, when co-circulating DENV1 and DENV3 presented different hematological profiles. In this study, characteristics of 2007 DENV epidemics were compared to the epidemiological, hematological and demographic outlines of the major outbreak of DENV1 in Marilia in 2015. DENV1 genetic diversity was assessed through capsid and pre-membrane junction encoding gene (CprM) sequencing. The results revealed circulation of DENV1 serotype from 2007 to 2015, with epidemics occurring every three-years until 2013 and then, increasing yearly. There were significant differences in hematological profiles of DENV1 patients between 2015 and 2007. CprM showed DENV1 genetic variability in 2015, contrasting with the unique sequence pattern in 2007. These results reinforce the regional and temporal characteristics of DENV epidemics that need local public health research to improve care for people and to limit the spread of new serotypes/genotypes to uninfected areas.

O objetivo deste estudo foi investigar o sistema de reprodução de uma população fragmentada da espécie arbórea dióica, Myracrodruon urundeuva Allemão, utilizando cinco locos microssatélites e os modelos mistos de reprodução e de cruzamentos correlacionados. O estudo foi conduzido na Estação Ecológica de Paulo de Faria (436 ha), onde a população ocupa uma área aproximada de 142 ha. Foram amostradas 514 progênies de polinização aberta coletadas de 30 árvores matrizes da população. A estimativa da taxa de cruzamento multilocus confirma que a espécie é dióica (t m = 1,0). Baixos níveis de cruzamentos entre parentes foram detectados na população (1 - t s = 0,020). A estimativa da correlação de paternidade (r p(m)) indicou que as progênies são compostas por misturas de meios-irmãos e irmãos-completos, embora este último ocorra em menor proporção (média de 0,148). O coeficiente de coancestria dentro das progênies (Θ = 0,147) foi maior e o tamanho efetivo de variância (Ne(v) = 2,98) foi menor do que o esperado em progênies de populações panmíticas (Θ = 0,125, Ne(v) = 4, respectivamente). Em termos de conservação genética, os resultados indicam que para se obterem lotes de sementes com tamanho efetivo de referência de 150, é necessário coletar sementes de pelo menos 50 árvores matrizes.

The aims of this study were to investigate the mating system of a fragmented population of the dioecious tropical tree Myracrodruon urundeuva Allemão, using five microsatellite loci and the mixed mating and correlated mating models. The study was conducted in the Estação Ecológica de Paulo de Farias (436 ha), where the population occupies about 142 ha. The mating system was estimated using 514 open-pollinated offspring, collected from 30 seed-trees. Estimates of the multilocus outcrossing rate confirm that the species is dioecious (t m = 1.0). Low levels of mating among relatives were detected in the population (1 - t s = 0.020). The estimate of paternity correlation (r p(m)) indicated that offsprings were composed of mixtures of half-sibs and full-sibs, with the latter occurring at a low frequency (average of 0.148). The estimated coancestry coefficient within families (Θ = 0.147) was larger and the effective population size (Ne(v)) was lower (Ne(v) = 2.98) than expected in progenies from panmictic populations (Θ = 0.125, Ne(v) = 4, respectively). In terms of conservation, the results indicate that to retain an effective population size of 150, is necessary to collect seeds from at least 50 seed-trees.

O objetivo deste trabalho foi investigar a diversidade, a estrutura genética e o tamanho efetivo, retido em um banco de germoplasma, de duas populações de Myracrodruon urundeuva Fr. All. (aroeira), procedentes de Aramina-SP e Selvíria-MS. As populações foram avaliadas a partir da amostragem de 25 progênies de polinização aberta de cada população. De cada progênie, 17 a 20 indivíduos foram amostrados e genotipados para oito locos microssatélites. Os maiores valores para o número total de alelos (At), número médio de alelos por loco (A), número efetivo de alelos (Ae), heterozigosidade observada (H0) e esperada (He) foram detectados na população Selvíria (At = 105, A = 13,13, Ae = 3,98, H0 = 0,669 e He = 0,749), enquanto Aramina teve At = 94, A = 13,75, Ae = 3,10, H 0 = 0,535 e He = 0,678. A diferenciação nas frequências alélicas das duas populações, com relação ao pólen cruzado (0,159) e do óvulo (0,235), indica que cerca de 84% e 77%, respectivamente, da diversidade genética está dentro das populações. O coeficiente médio de coancestria foi maior (Selvíria Θ = 0,165, Aramina Θ = 0,169) e o tamanho efetivo médio das progênies (Selvíria Ne(v) = 3,04, Aramina Ne(v) = 2,69) foi menor do que o esperado em progênies de populações panmíticas (Θ = 0,125, Ne(v) = 4). O tamanho efetivo total retido no banco ex situ foi estimado em 67,5 na população Selvíria e 71,1 na população Aramina, valores menores do que o requerido (Ne = 150) para a conservação de populações em curto prazo. Entretanto, as duas populações apresentaram alta diversidade genética, o que as qualifica para serem utilizadas em programas de conservação e melhoramento genético da espécie, desde que seja aumentado o tamanho efetivo populacional conservado ex situ.

The objective of this study was to investigate genetic diversity, genetic structure and effective size retained in a germplasm bank formed by two populations of Myracrodruon urundeuva Fr. All. (aroeira) from Aramina-SP and Selvíria-MS. The populations were evaluated from the sample of 25 open-pollinated progenies of each population. From each progeny, 17 to 20 individuals were sampled and genotyped for eight microsatellite loci. The greatest values for the total number of alleles (At), average number of alleles per locus (Ae), effective number of alleles per locus (A), observed heterozygosity (H0) and expected heterozygosity (He) were detected in Selvíria population (At=105, A=13.13, Ae =3.98, H0) =0.669 and He =0.749) in comparison to Aramina (At =94, A =13.75, Ae =3.10, H0=0.535 and He =0.678). The differentiation in allele frequencies between the two populations for the outcross-pollen (0.159) and ovules (0.235), indicate that about 84% and 77% of genetic diversity was within populations. The average coancestry coefficient was higher (Selvíria Θ =0.165, Aramina Θ =0.169) and the average effective population size within progenies (Selvíria Ne(v) =3.04, Aramina Ne(v) =2.69) was lower than expected in progenies of panmitic populations (Θ=0.125, Ne(v) =4). The total effective population size retained in the ex situ bank was estimated in 67.5 in Selvíria population and 71.1 in Aramina population, which values lower than the required (Ne =150) for short terms population conservation. However, the two populations showed high genetic diversity, which qualifies them for use in conservation and breeding programs of the species, provided the ex situ conserved population effective size is increased.