Morfologia de machos e fêmeas de Euglossa annectans Dresler 1982 (Hymenoptera, Apidae, Euglossini).

Foram coletados dados de morfometria de machos e fêmeas de Euglossa annectans em condições de laboratório, de um grupo de células separado artificialmente, a partir de um ninho alojado espontaneamente em caixa racional de abelhas sem ferrão

Identification and functional validation of FDA-approved positive and negative modulators of the mitochondrial calcium uniporter

The mitochondrial calcium uniporter (MCU), the highly selective channel responsible for mitochondrial Ca2+ entry, plays important roles in physiology and pathology. However, only few pharmacological compounds directly and selectively modulate its activity. Here, we perform high-throughput screening on a US Food and Drug Administration (FDA)-approved drug library comprising 1,600 compounds to identify molecules modulating mitochondrial Ca2+ uptake. We find amorolfine and benzethonium to be positive and negative MCU modulators, respectively. In agreement with the positive effect of MCU in muscle trophism, amorolfine increases muscle size, and MCU silencing is sufficient to blunt amorolfine-induced hypertrophy. Conversely, in the triple-negative breast cancer cell line MDA-MB-231, benzethonium delays cell growth and migration in an MCU-dependent manner and protects from ceramide-induced apoptosis, in line with the role of mitochondrial Ca2+ uptake in cancer progression. Overall, we identify amorolfine and benzethonium as effective MCU-targeting drugs applicable to a wide array of experimental and disease conditions

Longevidade e tamanho de ninho gregário de Euglossa annectans em área urbana.

Observações em um ninho gregário foram feitas em um jardim de casa de bairro arborizado da cidade de São Paulo instalado em caixa de madeira para ninhos de abelhas sem ferrão a 1.8Om de altura e distante 0.70cm de outro ninho em muro. No verão de 2003, o ninho com pelo menos 27 abelhas se distribuía em duas gavetas com 108 células na parte inferior, junto da entrada, e 31 na parte superior

PW06-05 The predictive role of anxiety disorders on depressive phenomenology during post-partum period

Aims:To investigate the predictive role of any specific (DSM-IV) Anxiety Disorders (AD) on depressive symptoms and Major or Minor Depressive Disorder (MDD, mDD) during early postpartum period.Method:Women (at the 12th-15th gestational week, N=1066) were recruited in the framework of the Program 'Perinatal Depression - Research & Screening Unit (PND-ReScU)". Depressive symptoms were assessed by the Edinburgh Postnatal Depression Scale (EPDS), and Axis-I disorders (AD, MDD, mDD) were diagnosed with the Structured Clinical Interview for Axis-I Disorders (SCID-I).Results:Any current AD at baseline (3rd month of pregnancy) was detected in 231 (21.7%). Having at least one current AD, was associated with a greater likelihood of having MDD or mDD during the early postpartum period, even after the adjustment for the confounding factor of having a lifetime history of MDD (RR=3.86 95%CI 1.58-9.42).In particular, women affected by Obsessive Compulsive Disorder (N=17; 1.6%) or Panic Disorder (N=43; 4%) had at higher risk to develop depressive symptoms (EPDS≥13) during the postpartum period than women without these AD (RR=6.9 and 6.7 respectively). As for the risk of developing PPD, the strongest association was found for women with Panic Disorder (RR=7.6 95% CI 2.62-22.0).Conclusions:AD are associated with a greater likelihood to develop depressive symptoms and MDD or mDD during the early postpartum period. Women with current PD have the strongest risk to develop both MDD or mDD and depressive symptoms during early postpartum period compared to other anxiety disorders

Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich's ataxia.

Inherited deficiency in the mitochondrial protein frataxin (FXN) causes the rare disease Friedreich's ataxia (FA), for which there is no successful treatment. We identified a redox deficiency in FA cells and used this to model the disease. We screened a 1600-compound library to identify existing drugs, which could be of therapeutic benefit. We identified the topical anesthetic dyclonine as protective. Dyclonine increased FXN transcript and FXN protein dose-dependently in FA cells and brains of animal models. Dyclonine also rescued FXN-dependent enzyme deficiencies in the iron-sulfur enzymes, aconitase and succinate dehydrogenase. Dyclonine induces the Nrf2 [nuclear factor (erythroid-derived 2)-like 2] transcription factor, which we show binds an upstream response element in the FXN locus. Additionally, dyclonine also inhibited the activity of histone methyltransferase G9a, known to methylate histone H3K9 to silence FA chromatin. Chronic dosing in a FA mouse model prevented a performance decline in balance beam studies. A human clinical proof-of-concept study was completed in eight FA patients dosed twice daily using a 1% dyclonine rinse for 1 week. Six of the eight patients showed an increase in buccal cell FXN levels, and fold induction was significantly correlated with disease severity. Dyclonine represents a novel therapeutic strategy that can potentially be repurposed for the treatment of FA

The Influence of Shc Proteins on Life Span in Mice

The signaling molecule p66Shc is often described as a longevity protein. This conclusion is based on a single life span study that used a small number of mice. The purpose of the present studies was to measure life span in a sufficient number of mice to determine if longevity is altered in mice with decreased Shc levels (ShcKO). Studies were completed at UC Davis and the European Institute of Oncology (EIO). At UC Davis, male C57BL/6J WT and ShcKO mice were fed 5% or 40% calorie-restricted (CR) diets. In the 5% CR group, there was no difference in survival curves between genotypes. There was also no difference between genotypes in prevalence of neoplasms or other measures of end-of-life pathology. At 40% calorie restriction group, 70th percentile survival was increased in ShcKO, while there were no differences between genotypes in median or subsequent life span measures. At EIO, there was no increase in life span in ShcKO male or female mice on C57BL/6J , 129Sv, or hybrid C57BL/6J -129Sv backgrounds. These studies indicate that p66Shc is not a longevity protein. However, additional studies are needed to determine the extent to which Shc proteins may influence the onset and severity of specific age-related diseases

Antimalarial Activity of Potential Inhibitors of Plasmodium falciparum Lactate Dehydrogenase Enzyme Selected by Docking Studies

The Plasmodium falciparum lactate dehydrogenase enzyme (PfLDH) has been considered as a potential molecular target for antimalarials due to this parasite's dependence on glycolysis for energy production. Because the LDH enzymes found in P. vivax, P. malariae and P. ovale (pLDH) all exhibit ∼90% identity to PfLDH, it would be desirable to have new anti-pLDH drugs, particularly ones that are effective against P. falciparum, the most virulent species of human malaria. Our present work used docking studies to select potential inhibitors of pLDH, which were then tested for antimalarial activity against P. falciparum in vitro and P. berghei malaria in mice. A virtual screening in DrugBank for analogs of NADH (an essential cofactor to pLDH) and computational studies were undertaken, and the potential binding of the selected compounds to the PfLDH active site was analyzed using Molegro Virtual Docker software. Fifty compounds were selected based on their similarity to NADH. The compounds with the best binding energies (itraconazole, atorvastatin and posaconazole) were tested against P. falciparum chloroquine-resistant blood parasites. All three compounds proved to be active in two immunoenzymatic assays performed in parallel using monoclonals specific to PfLDH or a histidine rich protein (HRP2). The IC50 values for each drug in both tests were similar, were lowest for posaconazole (<5 µM) and were 40- and 100-fold less active than chloroquine. The compounds reduced P. berghei parasitemia in treated mice, in comparison to untreated controls; itraconazole was the least active compound. The results of these activity trials confirmed that molecular docking studies are an important strategy for discovering new antimalarial drugs. This approach is more practical and less expensive than discovering novel compounds that require studies on human toxicology, since these compounds are already commercially available and thus approved for human use