Mutations in the intellectual disability gene Ube2a cause neuronal dysfunction and impair parkin-dependent mitophagy.

The prevalence of intellectual disability is around 3%; however, the etiology of the disease remains unclear in most cases. We identified a series of patients with X-linked intellectual disability presenting mutations in the Rad6a (Ube2a) gene, which encodes for an E2 ubiquitin-conjugating enzyme. Drosophila deficient for dRad6 display defective synaptic function as a consequence of mitochondrial failure. Similarly, mouse mRad6a (Ube2a) knockout and patient-derived hRad6a (Ube2a) mutant cells show defective mitochondria. Using in vitro and in vivo ubiquitination assays, we show that RAD6A acts as an E2 ubiquitin-conjugating enzyme that, in combination with an E3 ubiquitin ligase such as Parkin, ubiquitinates mitochondrial proteins to facilitate the clearance of dysfunctional mitochondria in cells. Hence, we identify RAD6A as a regulator of Parkin-dependent mitophagy and establish a critical role for RAD6A in maintaining neuronal function.

Immune response in hamsters immunised with a recombinant fragment of LigA from Leptospira interrogans, associated with carrier molecules.

Immunisation with the C-terminal region of leptospiral immunoglobulin-like A protein (LigANI) has shown promising results against leptospirosis. We evaluated the humoral immune response and protection induced by LigANI associated with carboxyl multi-walled carbon nanotubes (COOH-MWCNTs), CpG oligodeoxynucleotides (CpG ODNs), or Alhydrogel. Animals immunised with CpG ODNs were unable to develop a humoral immune response, whereas immunisation with LigANI and COOH-MWCNTs produced a high level of IgG antibodies, similar to that with LigANI and Alhydrogel, but it was not protective. The use of carbon nanotubes as an adjuvant in subunit vaccines against leptospirosis is a novel approach for improving specific IgG production.

Interval regression model adequacy checking and its application to estimate school dropout in Brazilian municipality educational scenario.

Interval-valued data have been commonly encountered in practice, and Symbolic Data Analysis provides a solution to the statistical treatment of these data. Regression analysis for interval-valued symbolic data is a topic that has been widely investigated in the literature of symbolic data analysis, and several models from different paradigms have been proposed. There are basic regression assumptions, and it is essential to validate them. This paper introduces an approach to check interval regression model adequacy based on residual analysis. Concepts of ordinary and standardized interval residual are presented, and graphical analysis of these residuals is also proposed. To show the usefulness of the proposed approach, an application for estimating school dropout in the scenario of Brazilian municipalities is performed. We observed some outliers from the interval residuals analysis, and interval robust regression models are more suitable for estimating school dropout.

The promoter of filamentation (POF1) protein from Saccharomyces cerevisiae is an ATPase involved in the protein quality control process.

BACKGROUND: The gene YCL047C, which has been renamed promoter of filamentation gene (POF1), has recently been described as a cell component involved in yeast filamentous growth. The objective of this work is to understand the molecular and biological function of this gene. RESULTS: Here, we report that the protein encoded by the POF1 gene, Pof1p, is an ATPase that may be part of the Saccharomyces cerevisiae protein quality control pathway. According to the results, Δpof1 cells showed increased sensitivity to hydrogen peroxide, tert-butyl hydroperoxide, heat shock and protein unfolding agents, such as dithiothreitol and tunicamycin. Besides, the overexpression of POF1 suppressed the sensitivity of Δpct1, a strain that lacks a gene that encodes a phosphocholine cytidylyltransferase, to heat shock. In vitro analysis showed, however, that the purified Pof1p enzyme had no cytidylyltransferase activity but does have ATPase activity, with catalytic efficiency comparable to other ATPases involved in endoplasmic reticulum-associated degradation of proteins (ERAD). Supporting these findings, co-immunoprecipitation experiments showed a physical interaction between Pof1p and Ubc7p (an ubiquitin conjugating enzyme) in vivo. CONCLUSIONS: Taken together, the results strongly suggest that the biological function of Pof1p is related to the regulation of protein degradation.

[Prenatal care protocol: actions and the easy and difficult aspects dealt by Family Health Strategy nurses]. / Protocolo na assistência pré-natal: ações, facilidades e dificuldades dos enfermeiros da Estratégia de Saúde da Família.

The objective of this study was to learn the perception that nurses have about the protocol of their attributions in prenatal care, identifying the health actions they develop, as well as the easy and difficult aspects in using the referred protocol. This qualitative study was developed with Family Health Strategy nurses in Divinópolis, Minas Gerais. The data survey was performed through interviews with five nurses. The data was submitted to thematic content analysis. Results showed the need for investments in professional qualification for women's health care in the pregnancy-postpartum cycle, as well as to create and implement protocols that promote a better interaction between the medical and nursing work.

Confinement of Dyes inside Boron Nitride Nanotubes: Photostable and Shifted Fluorescence down to the Near Infrared.

Fluorescence is ubiquitous in life science and used in many fields of research ranging from ecology to medicine. Among the most common fluorogenic compounds, dyes are being exploited in bioimaging for their outstanding optical properties from UV down to the near IR (NIR). However, dye molecules are often toxic to living organisms and photodegradable, which limits the time window for in vivo experiments. Here, it is demonstrated that organic dye molecules are passivated and photostable when they are encapsulated inside a boron nitride nanotube (dyes@BNNT). The results show that the BNNTs drive an aggregation of the encapsulated dyes, which induces a redshifted fluorescence from visible to NIR-II. The fluorescence remains strong and stable, exempt of bleaching and blinking, over a time scale longer than that of free dyes by more than 104 . This passivation also reduces the toxicity of the dyes and induces exceptional chemical robustness, even in harsh conditions. These properties are highlighted in bioimaging where the dyes@BNNT nanohybrids are used as fluorescent nanoprobes for in vivo monitoring of Daphnia Pulex microorganisms and for diffusion tracking on human hepatoblastoma cells with two-photon imaging.

Nanotechnology for Combating Microbial Contamination of Water

El agua es una necesidad universal que ha sido reportada por las Naciones Unidas (ONU) y la Organización Mundial de la Salud (OMS) como una prioridad. Existe una necesidad apremiante de acceso gratuito al agua potable para las poblaciones de los países en desarrollo. Además, las fuentes de agua de los países desarrollados también requieren atención debido a la presencia de un alto nivel de contaminantes emergentes. Por lo tanto, la nanotecnología parece ser una herramienta poderosa que podría usarse como sensores, filtros, superficies antibacterianas y nanoantimicrobianos. En esta revisión, hemos discutido la aplicación de las nanopartículas y los nanocompuestos para el tratamiento de aguas y aguas residuales. Además, el impacto de las nanopartículas libres como contaminantes emergentes en las plantas de tratamiento de agua, así como en las aguas subterráneas, merece más estudios.

The water is a universal need that has been reported by the United Nations (UN) and World Health Organization (WHO) as a priority. There is a pressing need for free access to drinking water for populations from developing countries. Furthermore, the water sources of developed countries also require attention due to the presence of a high level of emergent contaminants. Therefore, nanotechnology appears to be a powerful tool that could be used as sensors, filters, antibacterial surfaces, and nanoantimicrobials. In this review, we have discussed the application of nanoparticles and nanocomposites for water and wastewater treatment. Moreover, the impact of free-nanoparticles as emergent contaminants in water treatment plants as well as groundwater warrants further studies.

Falta de periodicidade na realização do exame citopatológico do colo uterino: motivações das mulheres / Lack of periodicity in realization the cytological examination of the cervix: motivations of women / Falta de periodicidad en la realización del examen citopatológico de cuello uterino: motivos de las mujeres

Nas últimas décadas vem diminuindo o número de mulheres que nunca fizeram o exame citopatológico do colo do útero. No entanto, aperiodicidade preconizada do exame ainda não é seguida, resultando em baixas coberturas e persistência dessa causa de morbimortalidade. Oobjetivo deste trabalho foi conhecer as motivações de mulheres que não realizam de forma periódica o exame. Realizou-se estudo qualitativocom 14 dessas mulheres atendidas na atenção primária à saúde de Divinópolis, Minas Gerais, Brasil. Os dados foram coletados por meio deentrevistas semiestruturadas e analisados pelo conteúdo, modalidade temática. Os resultados mostram que as motivações estão relacionadas asentimentos, pouca informação, sobrecarga do cotidiano, dificuldades na relação profissional-usuária e barreiras institucionais. Assim, revela-se anecessidade dos gestores se preocuparem com a capacitação dos profissionais que desenvolvem essa atividade, com a reorientação dos serviçosde saúde, proporcionando às usuárias conhecimento e sensibilização para atuarem como corresponsáveis da sua saúde.

The number of women who have never had a Pap smear (of the cervix) has decreased in recent decades. However, the recommended frequencyof screening is still not followed, resulting in low coverage and persistence of this cause of morbidity and mortality. The aim of this study was tounderstand the motivations of women who do not perform the test regularly. This is a qualitative study with 14 women seen in a primary healthcare unit in Divinópolis, Minas Gerais, Brazil. Data were collected through semi-structured interviews and analyzed using thematic content analysis.The results show that motivations are related to feelings, little information, daily life issues, difficulties in the relationship between professionals andwomen, and institutional barriers. Thus, managers need to worry about the training of professionals responsible for this activity. There should be areorientation of health services to be more supportive of health promotion, providing women with the necessary knowledge and awareness to beco-responsible for their health.

En las últimas décadas ha disminuido el número de mujeres que no realizan el examen citopatológico de cuello uterino. Sin embargo, no lo efectúancon la frecuencia recomendada lo cual resulta en baja cobertura y su persistencia causa morbilidad y mortalidad. El objetivo de este estudio fuecomprender por qué las mujeres que no realizan el examen regularmente. Se llevó a cabo un estudio cualitativo con 14 mujeres tratadas en laatención primaria de Divinópolis, Minas Gerais, Brasil. Los datos fueron recogidos a través de entrevistas semiestructuradas y analizados segúnsu contenido temático. Los resultados muestran que los motivos están relacionados con sentimientos, poca información, sobrecarga cotidiana,dificultades en la relación profesional-usuaria y trabas institucionales. Se pone de manifiesto la necesidad de que los administradores se preocupenpor la capacitación de los profesionales involucrados en esta tarea. Los servicios de salud deben ser reorientados para que las usuarias adquieranconocimiento y conciencia y compartan la responsabilidad de su salud.

Cuidado à mulher com transtorno mental / Health condition of women with mental disorder / Condiciones de salud de mujeres con trastorno mental

Pesquisa exploratória com abordagem quantitativa realizada em um Centro de Atenção Psicossocial III de Divinópolis, Minas Gerais, Brasil, com o objetivo de avaliar os aspectos reprodutivo, ginecológico e sexual de mulheres portadoras de transtorno mental. Participaram do estudo 39 mulheres com transtorno mental em tratamento no Centro de Atenção Psicossocial. Os dados foram coletados no período de Outubro a Dezembro de 2012. Para coleta de dados utilizou-se entrevistas semi estruturadas e verificação da pressão arterial, glicemia capilar, peso e altura. Os resultados apontam níveis normais de pressão arterial e de glicemia capilar pós-prandial, alteração do índice de massa corporal, presença de fluxo menstrual, nuliparidade, sexarca na adolescência, menarca precoce e ausência de sintomatologia climatérica e história de aborto entre as mulheres com transtornos mentais. A atenção integral à saúde da mulher implica cuidado além das demandas e necessidades do campo da saúde mental.

This research aimed to evaluate the reproductive, gynecological, sexual and clinical aspects of women with mental disorders. This is an exploratory research with quantitative approach performed in a Psychosocial Care Center, Type III, in Divinópolis, Minas Gerais, Brazil, with 39 women with mental disorders. Data collection took place from October to December 2012, through used semi-structured interviews and checked blood pressure, blood glucose, weight and height. The results revealed normal levels of blood pressure and postprandial blood glucose, change in body mass index, presence of menstrual flow, nulliparity, first sexual intercourse in adolescence, early menarche, and lack of climacteric symptoms and history of abortion. Comprehensive health care for women involves more than the demands and needs of the mental health field.

El objetivo fue evaluar aspectos reproductivos, ginecológicos y sexuales de mujeres con trastornos mentales. Investigación exploratoria, cuantitativa, realizada en Centro de Atención Psicosocial III de Divinópolis (Minas Gerais, Brasil), con 39 mujeres con trastornos mentales. La recolección de datos se llevó a cabo de octubre a diciembre de 2012, a través de entrevistas semiestructuradas y verificación de la presión arterial, glucemia, peso y altura. Los resultados señalaron niveles normales de presión arterial y glucemia postprandial, cambio en el índice de masa corporal, presencia de flujo menstrual, nuliparidad, primera relación sexual en la adolescencia, menarquia precoz y falta de síntomas climatéricos e historia de aborto. La atención integral a la salud de la mujer implica cuidados que ultrapasan las demandas y necesidades del campo de la salud mental.

Ecomapa e Apgar Familiar na atenção à família com portador de transtorno mental / Ecomap and family APGAR in family care for patients with psychiatric disorders

Este estudo objetiva conhecer as redes sociais e vínculos estabelecidos por seis famílias com portadores de transtorno psiquiátrico. Trata-se de uma pesquisa qualitativa realizada, em seis famílias do município de Divinópolis (Minas Gerais). Para coleta de dados, foram utilizados o Apgar Familiar e o Ecomapa realizados durante as visitas domiciliares. Nas famílias que apresentam insatisfação familiar, identificam-se vínculos conflituosos com o serviço de saúde mental e frágeis com a família extensa. O conhecimento dos vínculos e as redes de apoio social são estratégias facilitadoras e ampliadoras das ações de Saúde Mental na Atenção Básica.

This study aimed to understand the social networks and linkages established by six families having members with psychiatric disorder. It is a qualitative study conducted with six families in the municipality of Divinópolis (Minas Gerais). Family APGAR and Ecomap done during home visits were used for data collection. In the families that have family dissatisfaction, conflicting linkages with the mental health service and fragile ones with the extended family are identified. Knowledge of the linkages and the social support networks are strategies that facilitate and amplify the actions of Mental Health in Primary Care.

Protocolo na assistência pré-natal: ações, facilidades e dificuldades dos enfermeiros da Estratégia de Saúde da Família / Prenatal care protocol: actions and the easy and difficult aspects dealt by Family Health Strategy nurses / Protocolo de atención prenatal: acciones, facilidades y dificultades de los enfermeros de la Estrategia de Salud de la Familia

Este estudo teve como objetivo conhecer a percepção dos enfermeiros acerca do uso do protocolo de suas atribuições na assistência pré-natal, identificando as ações de saúde desenvolvidas por esses profissionais, assim como os pontos facilitadores e dificultadores no uso do referido protocolo. Trata-se de um estudo qualitativo, desenvolvido junto aos enfermeiros da Estratégia de Saúde da Família do município de Divinópolis, Minas Gerais. Para o levantamento dos dados, foram realizadas entrevistas com cinco enfermeiros. Os dados foram analisados pelo conteúdo, na modalidade temática. Os resultados demonstraram a necessidade de investimentos na formação de pessoal qualificado para o atendimento à mulher no ciclo gravídico-puerperal, assim como a criação e a incorporação de protocolos que promovam uma melhor interação do trabalho médico e de enfermagem.

The objective of this study was to learn the perception that nurses have about the protocol of their attributions in prenatal care, identifying the health actions they develop, as well as the easy and difficult aspects in using the referred protocol. This qualitative study was developed with Family Health Strategy nurses in Divinópolis, Minas Gerais. The data survey was performed through interviews with five nurses. The data was submitted to thematic content analysis. Results showed the need for investments in professional qualification for women's health care in the pregnancy-postpartum cycle, as well as to create and implement protocols that promote a better interaction between the medical and nursing work.

Este estudio tuvo como objetivo conocer la percepción de los enfermeros acerca del uso del protocolo de sus atribuciones en la atención prenatal, identificando las acciones de salud desarrolladas por estos profesionales, así como los puntos que facilitan o dificultan el uso del referido protocolo. Se trata de n estudio cualitativo, desarrollado junto a los enfermeros de la estrategia de salud de la familia del municipio de Divinópolis-MG. Para la recolección de datos se realizaron entrevistas con cinco enfermeros. Los datos fueron sometidos a análisis de contenido, en la modalidad temática. Los resultados demuestran la necesidad de inversiones en la formación de personal calificado para la atención de la mujer en el ciclo gravídico-puerperal, así como la creación e incorporación de protocolos que promuevan una mejor interacción del trabajo médico y de enfermería.

UBE2A, which encodes a ubiquitin-conjugating enzyme, is mutated in a novel X-linked mental retardation syndrome.

We report a mutation of UBE2A/HR6A, which encodes a ubiquitin-conjugating enzyme (E2), a member of the ubiquitin proteasome pathway, as the cause of a novel X-linked mental retardation (XLMR) syndrome that affects three males in a two-generation family. A single-nucleotide substitution, c.382C-->T in UBE2A, led to a premature UAG stop codon (Q128X). As a consequence, the predicted polypeptide lacks the 25 C-terminal amino acid residues. The importance of this terminal sequence for UBE2 function is inferred by its conservation in vertebrates and in Drosophila. UBE2A mutations do not appear to significantly contribute to XLMR, since no UBE2A mutations were identified in 15 families with nonsyndromic and 4 families with syndromic idiopathic XLMR previously mapped to intervals encompassing this gene. This is the first description of a mutation in a ubiquitin-conjugating enzyme gene as the cause of a human disease.

The promoter of filamentation (POF1) protein from Saccharomyces cerevisiae is an ATPase involved in the protein quality control process

The gene YCL047C, which has been renamed promoter of filamentation gene (POF1), has recentlybeen described as a cell component involved in yeast filamentous growth. The objective of this work is tounderstand the molecular and biological function of this gene.Here, we report that the protein encoded by the POF1 gene, Pof1p, is an ATPase that may be part of theSaccharomyces cerevisiae protein quality control pathway. According to the results, Äpof1 cells showed increasedsensitivity to hydrogen peroxide, tert-butyl hydroperoxide, heat shock and protein unfolding agents, such asdithiothreitol and tunicamycin. Besides, the overexpression of POF1 suppressed the sensitivity of Äpct1, a strain thatlacks a gene that encodes a phosphocholine cytidylyltransferase, to heat shock. In vitro analysis showed, however,that the purified Pof1p enzyme had no cytidylyltransferase activity but does have ATPase activity, with catalyticefficiency comparable to other ATPases involved in endoplasmic reticulum-associated degradation of proteins(ERAD). Supporting these findings, co-immunoprecipitation experiments showed a physical interaction betweenPof1p and Ubc7p (an ubiquitin conjugating enzyme) in vivo.Taken together, the results strongly suggest that the biological function of Pof1p is related to the regulation of protein degradation.