Novel NDUFA12 variants are associated with isolated complex I defect and variable clinical manifestation.

Isolated biochemical deficiency of mitochondrial complex I is the most frequent signature amongst mitochondrial diseases and is associated with a wide variety of clinical symptoms. Leigh syndrome represents the most frequent neuroradiological finding in patients with complex I defect and >80 monogenic causes have been involved in the disease. In this report, we describe 7 patients from four unrelated families harbouring novel NDUFA12 variants, 6 of them presenting with Leigh syndrome. Molecular genetic characterization was performed using next generation sequencing combined with the Sanger method. Biochemical and protein studies were achieved by enzymatic activities, blue native gel electrophoresis and Western blotting. All patients displayed novel homozygous mutations in the NDUFA12 gene leading to the virtual absence of the corresponding protein. Surprisingly, despite in none of the analyzed patients NDUFA12 protein was detected, they present a different onset and clinical course of the disease. Our report expands the array of genetic alterations in NDUFA12 and underlines phenotype variability associated with NDUFA12 defect. This article is protected by copyright. All rights reserved

Selective blockade of interferon-α and -β reveals their non-redundant functions in a mouse model of West Nile virus infection

Although type I interferons (IFNs) were first described almost 60 years ago, the ability to monitor and modulate the functional activities of the individual IFN subtypes that comprise this family has been hindered by a lack of reagents. The major type I IFNs, IFN-β and the multiple subtypes of IFN-α, are expressed widely and induce their effects on cells by interacting with a shared heterodimeric receptor (IFNAR). In the mouse, the physiologic actions of IFN-α and IFN-β have been defined using polyclonal anti-type I IFN sera, by targeting IFNAR using monoclonal antibodies or knockout mice, or using Ifnb-/- mice. However, the corresponding analysis of IFN-α has been difficult because of its polygenic nature. Herein, we describe two monoclonal antibodies (mAbs) that differentially neutralize murine IFN-β or multiple subtypes of murine IFN-α. Using these mAbs, we distinguish specific contributions of IFN-β versus IFN-α in restricting viral pathogenesis and identify IFN-α as the key mediator of the antiviral response in mice infected with West Nile virus. This study thus suggests the utility of these new reagents in dissecting the antiviral and immunomodulatory roles of IFN-β versus IFN-α in murine models of infection, immunity, and autoimmunity

A remarkable synergistic effect at the transcriptomic level in peach fruits doubly infected by Prunus necrotic ringspot virus and Peach latent mosaic viroid

[EN] Background: Microarray profiling is a powerful technique to investigate expression changes of large amounts of genes in response to specific environmental conditions. The majority of the studies investigating gene expression changes in virus-infected plants are limited to interactions between a virus and a model host plant, which usually is Arabidopsis thaliana or Nicotiana benthamiana. In the present work, we performed microarray profiling to explore changes in the expression profile of field-grown Prunus persica (peach) originating from Chile upon single and double infection with Prunus necrotic ringspot virus (PNRSV) and Peach latent mosaic viroid (PLMVd), worldwide natural pathogens of peach trees. Results: Upon single PLMVd or PNRSV infection, the number of statistically significant gene expression changes was relatively low. By contrast, doubly-infected fruits presented a high number of differentially regulated genes. Among these, down-regulated genes were prevalent. Functional categorization of the gene expression changes upon double PLMVd and PNRSV infection revealed protein modification and degradation as the functional category with the highest percentage of repressed genes whereas induced genes encoded mainly proteins related to phosphate, C-compound and carbohydrate metabolism and also protein modification. Overrepresentation analysis upon double infection with PLMVd and PNRSV revealed specific functional categories over- and underrepresented among the repressed genes indicating active counter-defense mechanisms of the pathogens during infection. Conclusions: Our results identify a novel synergistic effect of PLMVd and PNRSV on the transcriptome of peach fruits. We demonstrate that mixed infections, which occur frequently in field conditions, result in a more complex transcriptional response than that observed in single infections. Thus, our data demonstrate for the first time that the simultaneous infection of a viroid and a plant virus synergistically affect the host transcriptome in infected peach fruits. These field studies can help to fully understand plant-pathogen interactions and to develop appropriate crop protection strategies.We thank Drs M.A. Perez-Amador y J. Gadea for helping in the result analysis. This work was supported by grant BIO2011-25018 from the Spanish granting agency Direccion General de Investigacion Cientifica for the transcriptomic analyses and from the grant 2009CL0020 from the bilateral project INIA-Chile/CSIC-Spain for the phytosanitary evaluation. MC Herranz was the recipient of a contract from the Juan de la Cierva program of the Ministerio de Educacion y Ciencia of Spain.Herranz Gordo, MDC.; Niehl, A.; Rosales, M.; Fiore, N.; Zamorano, A.; Granell Richart, A.; Pallás Benet, V. (2013). 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Redução das internações por condições sensíveis à atenção primária no Brasil entre 1998-2009

OBJETIVO: Descrever a tendência de hospitalizações por condições sensíveis à atenção primária entre 1998 e 2009 no Brasil. MÉTODOS: Estudo ecológico de séries temporais com dados secundários referentes às internações hospitalares por condições sensíveis à atenção primária no Sistema Único de Saúde. Os dados foram obtidos do Sistema de Informações Hospitalares. As taxas de internações por 10.000 habitantes foram padronizadas por faixa etária e sexo, considerando a população brasileira masculina recenseada em 2000 como padrão. A análise de tendência da série histórica foi realizada por regressão linear generalizada pelo método de Prais-Winsten. RESULTADOS: Houve redução média anual de internações por condições sensíveis à atenção primária de 3,7% entre homens (IC95% -2,3;-5,1) e mulheres (IC95% -2,5;-5,6) entre 1998 e 2009. A tendência variou em cada unidade federativa, porém em nenhuma houve aumento das internações. No sexo masculino e feminino as maiores reduções foram observadas nas internações por úlceras gastrintestinais (-11,7% ao ano e -12,1%, respectivamente), condições evitáveis (-8,8% e -8,9%) e doenças das vias aéreas inferiores (-8,0% e -8,1%). Angina (homens), infecção no rim e trato urinário (homens e mulheres) e condições relacionadas ao pré-natal e parto (mulheres) apresentaram aumento nas internações. Os três grupos de doenças que mais ocasionaram internações foram gastrenterites infecciosas e complicações, internações por insuficiência cardíaca e asma. CONCLUSÕES: Houve redução substancial nas internações por condições sensíveis à atenção primária no Brasil entre 1998 e 2009, porém algumas doenças apresentaram estabilidade ou acréscimo, exigindo atenção do setor saúde.OBJECTIVE: To describe the trends in hospitalizations for ambulatory care sensitive conditions between 1998 and 2009 in Brazil. METHODS: The ecological time series study used secondary data on hospitalizations for ACSC in the Sistema Único de Saúde (SUS, National Unified Health System). Data were obtained from the Hospital Information System. Hospital admission rates per 10,000 inhabitants were standardized by age range and gender, using the 2000 census male Brazilian population as standard. Trend analysis of the historic series was performed through generalized linear regression using the Prais-Winsten method. RESULTS: Between 1998 and 2009, there was an average annual reduction in admissions for ambulatory care sensitive conditions of 3.7% in men (95%CI -2.3;-5.1) and women (95%CI -2.5; -5.6). The trend varied in each state, although no increase in admissions was observed in any state. In both men and women, the highest reductions were observed in hospitalizations for gastrointestinal ulcers (-11.7% a year and -12.1%, respectively), avoidable conditions (-8.8% and -8.9%) and lower respiratory diseases (-8.0% and -8.1%). Hospitalization increased only for angina (men), kidney infections and urinary tract infections (men and women) and conditions related to prenatal care and delivery (women). The three groups of illness which led to the most admissions were infectious gastroenteritis and its complications, cardiac insufficiency and asthma. CONCLUSIONS: Between 1998 and 2009, there was a substantial reduction in admissions for ambulatory care sensitive conditions in Brazil, although some illnesses presented stability or even an increase, which calls for attention from the health sector.OBJETIVO: Describir la tendencia de hospitalizaciones por condiciones susceptibles a atención primaria entre 1998 y 2009 en Brasil. MÉTODOS: Estudio ecológico de series temporales con datos secundarios relacionados con las Internaciones Hospitalarias por condiciones susceptibles a atención primaria en el Sistema Único de Salud de Brasil. Los datos fueron obtenidos del Sistema de Informaciones Hospitalarias. Las tasas de internaciones por 10.000 habitantes fueron estandarizadas por grupo etario y sexo, considerando la población brasileña masculina recensada en 2000 como patrón. El análisis de tendencia de la serie histórica fue realizado por regresión linear generalizado por el método de Prais-Winsten. RESULTADOS: Hubo reducción en el promedio anual de internaciones por condiciones susceptibles a atención primaria de 3,7% entre hombres (IC95% -2,3;-5,1) y mujeres (IC95% -2,5;-5,6) entre 1998 y 2009. La tendencia varió en cada unidad federativa, sin embargo, en ninguna hubo aumento de las internaciones. En el sexo masculino y femenino las mayores reducciones fueron observadas en las internaciones por úlceras gastrointestinales (-11,7% al año y -12,1%, respectivamente), condiciones evitables (-8,8% y -8,9%) y enfermedades de las vías aéreas inferiores (-8,0% y -8,1%). Angina (hombres), infección en el riñón y tracto urinario (hombres y mujeres) y condiciones relacionados al prenatal y parto (mujeres) presentaron aumento en las internaciones. Los tres grupos de enfermedades que más ocasionaron internaciones fueron gastroenteritis infecciosas y complicaciones, internaciones por insuficiencia cardíaca y asma. CONCLUSIONES: Hubo reducción sustancial en las internaciones por condiciones susceptibles a atención primaria en Brasil entre 1998 y 2009, sin embargo, algunas enfermedades presentaron estabilidad o aumento, exigiendo atención del sector salud