FOX-2 Dependent Splicing of Ataxin-2 Transcript Is Affected by Ataxin-1 Overexpression

Alternative splicing is a fundamental posttranscriptional mechanism for controlling gene expression, and splicing defects have been linked to various human disorders. The splicing factor FOX-2 is part of a main protein interaction hub in a network related to human inherited ataxias, however, its impact remains to be elucidated. Here, we focused on the reported interaction between FOX-2 and ataxin-1, the disease-causing protein in spinocerebellar ataxia type 1. In this line, we further evaluated this interaction by yeast-2-hybrid analyses and co-immunoprecipitation experiments in mammalian cells. Interestingly, we discovered that FOX-2 localization and splicing activity is affected in the presence of nuclear ataxin-1 inclusions. Moreover, we observed that FOX-2 directly interacts with ataxin-2, a protein modulating spinocerebellar ataxia type 1 pathogenesis. Finally, we provide evidence that splicing of pre-mRNA of ataxin-2 depends on FOX-2 activity, since reduction of FOX-2 levels led to increased skipping of exon 18 in ataxin-2 transcripts. Most striking, we observed that ataxin-1 overexpression has an effect on this splicing event as well. Thus, our results demonstrate that FOX-2 is involved in splicing of ataxin-2 transcripts and that this splicing event is altered by overexpression of ataxin-1

Avaliação da perviedade precoce das fístulas arteriovenosas para hemodiálise Evaluation of early patency of the arteriovenous fistulas for hemodialysis

CONTEXTO: A insuficiência renal crônica é uma doença de alta prevalência e morbidade, o que determina queda da qualidade de vida. Pacientes em hemodiálise necessitam de um acesso vascular que permita a conexão da circulação do paciente ao circuito externo de hemodiálise. Dentre os acessos disponíveis, as fístulas arteriovenosas (FAV) são as que mais se aproximam do acesso ideal. OBJETIVO: Avaliar a perviedade precoce das FAV, identificando os fatores relacionados ao insucesso destas. MÉTODOS: Foram acompanhados todos os pacientes submetidos à confecção das FAV no Hospital do Servidor Público Municipal de São Paulo, no período de agosto de 2008 a janeiro de 2009, avaliando-se a perviedade destas no 1º, 10º e 30º pós-operatório. Foram realizadas 31 FAV no período, apresentando-se média de idade de 63,06 anos, sendo 18 pacientes do sexo masculino e 13 do feminino. RESULTADOS: Vinte e seis FAV foram distais, todas radiocefálicas; quatro foram proximais, das quais duas braquiocefálicas e duas braquiobasílicas superficializadas; uma FAV confeccionada com alça de politetrafluoretileno (PTFE) fêmoro-femoral esquerda. A taxa de perviedade no primeiro mês foi de 71% dos casos. O uso de cateteres venosos centrais apresentou-se como fator de risco para oclusão da FAV (p=0,01). As FAV continuam sendo o acesso vascular para hemodiálise mais aceito e mais seguro. A indicação precoce para confecção das FAV é de fundamental importância, evitando-se, assim, o uso de cateteres e suas complicações. CONCLUSÕES: A perviedade precoce encontrada neste estudo é semelhante à da literatura, e o uso prévio de cateteres é o fator de risco mais significativo para oclusão precoce desta.<br>BACKGROUND: Chronic renal failure is a disease of high prevalence and high morbidity, which impairs the patients' quality of life. Patients on hemodialysis need a vascular access for connection with the hemodialysis equipment. Arteriovenous fistulas (AVF) are the best option for this purpose. OBJECTIVE: To evaluate the early patency of AVFs and to identify the causes of their failure. METHODS: All patients AVF underwent operations for dialysis from August, 2008 to January, 2009. The AVF patency was evaluated on the 1st, 10th and 30th postoperative days. Thirty-one operations for AVF were performed in our hospital in the period; 18 patients were males and the mean age was 63.03 years. RESULTS: Twenty-six AVF were distal, all radial-cephalic; four were proximal, out of which two were brachiocephalic and two were brachiobasilic; one AVF was a femoral-femoral loop PTFE graft. The patency rate in the first month was of 71%. The use of central venous catheters was a risk factor for AVF occlusion (p=0.01). AVF remains the most accepted and safe vascular access. Early performance of the AVF is very important to avoid the complications resulting from long-term use of central venous catheters. CONCLUSIONS: Data regarding early patency found in this study were similar to those found in literature, and the use of central venous catheters before performing AVF is an important risk factor for occlusion