Mitochondrial dysfunction mediates neuronal cell response to DMMB photodynamic therapy

Photodynamic therapy (PDT) is a process in which a photosensitizer (PS) is exposed to specific wavelengths and generates reactive oxygen species (ROS) which act within nanometers. The low invasive nature and directed cytotoxicity of this approach render it attractive to the treatment of different conditions, including the ones that affect the central nervous system (CNS). The effect of PDT on healthy neurons is one main concern over its use in the CNS, since neuronal-like cells were shown to be particularly sensitive to certain PSs. Among available PSs, 1,9-dimethyl-methylene blue (DMMB) stands out as being resistant to reduction to its inactive leuco form and by being able to produce high levels of singlet‑oxygen. In this study, we aimed to investigate DMMB photodamage mechanisms in the hippocampal cell line HT22. Our results demonstrate that DMMB-PDT decrease in cell viability was linked with an increase in cell death and overall ROS production. Besides, it resulted in a significant increase in mitochondrial ROS production and decreased mitochondria membrane potential. Furthermore, DMMB-PDT significantly increased the presence of acidic autolysosomes, which was accompanied by an increase in ATG1 and ATG8 homologue GaBarap1 expression, and decreased DRAM1 expression. Taken together our results indicated that mitochondrial and autophagic dysfunction underlie DMMB-PDT cytotoxicity in neuronal cells.</p

Is the expansion of sugarcane over pasturelands a sustainable strategy for Brazil's bioenergy industry?

The authors gratefully thank the São Paulo Research Foundation (FAPESP) (grants # 2014/08632-9 # 2015/14122-6, # 2013/17581-6, # 2014/16612-8 and 2018/09845-7) for the scholarship granted while this research was carried out, and CNPq (grants # 402992/2013-0 and # 311661/2014-9) for the financial support of the present research. Anonymous reviewers are also thanked for their valuable criticisms and comments, which led to substantial improvements of this manuscript.Peer reviewedPostprintPostprin

Desempenho preliminar de novos genótipos de aveia e trigo na Depressão Ccentral do RS

More than two hundred oat and wheat advanced-lines selected in 1983 were grown in field experiments at Guaíba, RS, Brazil, in 1984. The objective was to quantify, grain yield, 100 grain weight, hectoliter weight, biological yield, heading time, and plant stature. The results were significant for all traits, indicating that selection was efficient in oats; on the other hand, only one wheat-line showed superiority to the best check-variety.Mais de 200 linhagens avançadas de aveia (Avena sativa L.) e trigo (Triticum aestivum L.), selecionadas em 1983, foram avaliadas em dois experimentos, conduzidos em Guaíba, RS, durante o ano de 1984. O objetivo foi testar rendimento de grãos, peso do hectolitro e de 100 grãos, rendimento biológico, ciclo de desenvolvimento e estatura de planta. Os resultados foram significativos para todas as variáveis, indicando que a seleção tem sido eficiente na aveia; por outro lado, em trigo, somente uma linhagem mostrou superioridade em rendimento de grãos sobre a melhor cultivar-padrão

Imprinted Gene Expression and Function of the Dopa Decarboxylase Gene in the Developing Heart

Dopa decarboxylase (DDC) synthesizes serotonin in the developing mouse heart where it is encoded by Ddc_exon1a, a tissue-specific paternally expressed imprinted gene. Ddc_exon1a shares an imprinting control region (ICR) with the imprinted, maternally expressed (outside of the central nervous system) Grb10 gene on mouse chromosome 11, but little else is known about the tissue-specific imprinted expression of Ddc_exon1a. Fluorescent immunostaining localizes DDC to the developing myocardium in the pre-natal mouse heart, in a region susceptible to abnormal development and implicated in congenital heart defects in human. Ddc_exon1a and Grb10 are not co-expressed in heart nor in brain where Grb10 is also paternally expressed, despite sharing an ICR, indicating they are mechanistically linked by their shared ICR but not by Grb10 gene expression. Evidence from a Ddc_exon1a gene knockout mouse model suggests that it mediates the growth of the developing myocardium and a thinning of the myocardium is observed in a small number of mutant mice examined, with changes in gene expression detected by microarray analysis. Comparative studies in the human developing heart reveal a paternal expression bias with polymorphic imprinting patterns between individual human hearts at DDC_EXON1a, a finding consistent with other imprinted genes in human

Comparative Study of rK39 Leishmania Antigen for Serodiagnosis of Visceral Leishmaniasis: Systematic Review with Meta-Analysis

Visceral Leishmaniasis (VL) is a neglected tropical disease for which serodiagnostic tests are available, but not yet widely implemented in rural areas. The rK39 recombinant protein is derived from a kinesin-like protein of parasites belonging to the Leishmania donovani complex, and has been used in the last two decades for the serodiagnosis of VL. We present here a systematic review and meta-analysis of studies evaluating serologic assays (rK39 strip-test, rK39 ELISA, Direct Agglutination Test [DAT], Indirect Immunofluorescence test [IFAT] and ELISA with a promastigote antigen preparation [p-ELISA]) to diagnose VL to determine the accuracy of rK39 antigen in comparison to the use of other antigen preparations. Fourteen papers fulfilled the inclusion and exclusion selection criteria. The summarized sensitivity for the rK39-ELISA was 92% followed by IFAT 88% and p-ELISA 87%. The summarized specificity for the three diagnostic tests was 81%, 90%, and 77%. Studies comparing the rK39 strip test with DAT found a similar sensitivity (94%) and specificity (89%). However, the rK39 strip test was more specific than the IFAT and p-ELISA. In conclusion, we found the rK39 protein used either in a strip test or in an ELISA is a good choice for the serodiagnosis of VL

Fortalecer as atividades de informação e vigilância epidemiológica é essencial e urgente para reduzir a força de transmissão do SARS-CoV-2

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