Extracellular alpha-synuclein: Sensors, receptors, and responses

Synucleinopathies are a group of progressive neurodegenerative diseases known for the accumulation of insoluble aggregates containing the protein alpha-synuclein (aSyn). Recently, it has been assumed that pathology spreads in the brain during disease progression, implying that, at some point in the process, aSyn may exist outside of cells. In this context, extracellular-aSyn (e-aSyn) might transduce signals to the inside of the cells it interacts with, and/or be internalized by different types of cells through the extracellular matrix. Both negatively charged lipids and membrane receptors have been hypothesized as modulators of the loss of cellular homeostasis and cytotoxicity, and of the internalization of e-aSyn. Internalized e-aSyn causes the disruption of multiple cellular processes such as the autophagy lysosomal pathway (ALP), mitochondrial function, endoplasmic reticulum (ER)-stress, UPR activation, or vesicular transport. These processes happen not only in neurons but also in glial cells, activating inflammatory or anti-inflammatory pathways that can affect both neuronal function and survival, thereby affecting disease progression. In this review, we explore possible effects e-aSyn, all the way from the extracellular matrix to the nucleus. In particular, we highlight the glial-neuronal relationship as this is particularly relevant in the context of the spreading of aSyn pathology in synucleinopathies

Características industriais do maracujá (Passiflora edulis var. flavicarpa) e maturação do fruto

Some physical and chemical characteristics during the growth and ripening of the yellow passion fruit (Passiflora edulis var. flavicarpa Deg.) cultivated at the Federal Rural University of Rio de Janeiro (Km 47, Rio de Janeiro) have been evaluated. Fruits of different ages obtained from flowers tagged on the day of anthesis were submitted to several analysis (weight, juice yield, soluble and total solids, total acidity, sugars and vitamin C). Results show that quality of the fruits is satisfactory and that the maximum levels of fresh weight and soluble solids occurred 10 to 15 days before fruit fall. Due to this fact the usual manner of daily picking of fallen fruits should be avoided.Com a finalidade de se avaliar as características industriais dos frutos de maracujá amarelo (Passiflora edulis var. flavicarpa Deg.) produzidos no Estado do Rio de janeiro, foi conduzida na Universidade Federal Rural do Rio de Janeiro uma investigação na qual foram coletados frutos, semanalmente, a partir da data de abertura das flores, sendo neles avaliadas as seguintes características: peso médio de frutos, rendimento em suco, acidez titulável, teor de sólidos solúveis, açúcares redutores e totais, vitamina C total e desenvolvimento de coloração e princípios aromáticos. O processo de desenvolvimento e maturação do fruto durou, nas condições locais, aproximadamente 70 dias. O peso médio dos frutos cresceu até o 53.° dia, caindo em seguida. As curvas representativas da evolução dos teores de sólidos solúveis, acidez, vitamina C total, açúcares redutores e totais também apresentaram ramos descendentes no final da maturação. O índice de pH foi mantido relativamente estável, oscilando entre 3,15 e 2,67. O rendimento em suco, durante todo o processo, apresentou acréscimos. Aos 33 dias após a antese, o suco já mostrava coloração satisfatória, mas o aroma característico somente foi notado na amostra colhida no 53.° dia. Pelos dados obtidos e analisados, concluiu-se que são satisfatórias, sob o ponto-de-vista industrial, as características dos frutos produzidos no local em pauta; observou-se que os frutos colhidos segundo a técnica usual (com epiderme totalmente amarela) já mostram indícios de perda de qualidade, talvez devido a um incipiente processo de senescência. Admite-se que seja viável a obtenção de melhores rendimentos e diminuição de freqüência de colheitas uma vez conhecido o aspecto de frutos em final de maturação

Development of a portfolio of learning for postgraduate family medicine training in South Africa: a Delphi study

<p>Abstract</p> <p>Background</p> <p>Within the 52 health districts in South Africa, the family physician is seen as the clinical leader within a multi-professional district health team. Family physicians must be competent to meet 90% of the health needs of the communities in their districts. The eight university departments of Family Medicine have identified five unit standards, broken down into 85 training outcomes, for postgraduate training. The family medicine registrar must prove at the end of training that all the required training outcomes have been attained. District health managers must be assured that the family physician is competent to deliver the expected service. The Colleges of Medicine of South Africa (CMSA) require a portfolio to be submitted as part of the uniform assessment of all registrars applying to write the national fellowship examinations. This study aimed to achieve a consensus on the contents and principles of the first national portfolio for use in family medicine training in South Africa.</p> <p>Methods</p> <p>A workshop held at the WONCA Africa Regional Conference in 2009 explored the purpose and broad contents of the portfolio. The 85 training outcomes, ideas from the WONCA workshop, the literature, and existing portfolios in the various universities were used to develop a questionnaire that was tested for content validity by a panel of 31 experts in family medicine in South Africa, via the Delphi technique in four rounds. Eighty five content items (national learning outcomes) and 27 principles were tested. Consensus was defined as 70% agreement. For those items that the panel thought should be included, they were also asked how to provide evidence for the specific item in the portfolio, and how to assess that evidence.</p> <p>Results</p> <p>Consensus was reached on 61 of the 85 national learning outcomes. The panel recommended that 50 be assessed by the portfolio and 11 should not be. No consensus could be reached on the remaining 24 outcomes and these were also omitted from the portfolio. The panel recommended that various types of evidence be included in the portfolio. The panel supported 26 of the 27 principles, but could not reach consensus on whether the portfolio should reflect on the relationship between the supervisor and registrar.</p> <p>Conclusion</p> <p>A portfolio was developed and distributed to the eight departments of Family Medicine in South Africa, and the CMSA, to be further tested in implementation.</p