Von Kommanivanh Interview

2010 interview with Loatian born/Chicago based painter Von Kommanivahn by John Plucienni

Impaired Nuclear Export of Polyglutamine-Expanded Androgen Receptor in Spinal and Bulbar Muscular Atrophy.

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by polyglutamine (polyQ) expansion in the androgen receptor (AR). Prior studies have highlighted the importance of AR nuclear localization in SBMA pathogenesis; therefore, in this study, we sought to determine the role of AR nuclear export in the pathological manifestations of SBMA. We demonstrate here that the nuclear export of polyQ-expanded AR is impaired, even prior to the formation of intranuclear inclusions of aggregated AR. Additionally, we find that promoting AR export with an exogenous nuclear export signal substantially reduces its aggregation and blocks hormone-induced toxicity. Moreover, we show that these protective effects are conferred by destabilization of the mutant protein due to an increase in proteasomal degradation of the cytoplasmic AR. Despite a growing body of evidence that global disruption of nucleo/cytoplasmic transport occurs in ALS and HD, our data suggest that no such global disruption occurs in models of SBMA; rather, AR-specific mechanisms, including reduced phosphorylation at Serine 650, are likely responsible for the impaired nuclear export of polyQ-expanded AR

DNA Mismatch Repair and its Role in Huntington\u27s Disease

DNA mismatch repair (MMR) is a highly conserved genome stabilizing pathway that corrects DNA replication errors, limits chromosomal rearrangements, and mediates the cellular response to many types of DNA damage. Counterintuitively, MMR is also involved in the generation of mutations, as evidenced by its role in causing somatic triplet repeat expansion in Huntington\u27s disease (HD) and other neurodegenerative disorders. In this review, we discuss the current state of mechanistic knowledge of MMR and review the roles of key enzymes in this pathway. We also present the evidence for mutagenic function of MMR in CAG repeat expansion and consider mechanistic hypotheses that have been proposed. Understanding the role of MMR in CAG expansion may shed light on potential avenues for therapeutic intervention in HD

Social determinants of health and the Brazilian Family Health Care Program in the city of Sao Paulo, Southeastern Brazil

OBJETIVO Analisar a situação do trabalho com determinantes sociais da saúde no âmbito do Programa Saúde da Família. MÉTODOS Estudo de caso com métodos mistos de pesquisa, ancorados em estratégia sequencial explanatória, com 171 gerentes das unidades do Programa Saúde da Família em São Paulo, SP, em 2005/2006. Questionários autopreenchíveis foram aplicados. Entrevistas semiestruturadas e grupos focais foram realizados com amostra intencional de profissionais envolvidos no trabalho com determinantes sociais da saúde. Os dados quantitativos foram analisados por análise descritiva, análise de correspondência múltipla, análise de agrupamento e testes de correlação entre variáveis. Os dados qualitativos foram apurados por análise de conteúdo e a criação de categorias temáticas. RESULTADOS Apesar da concentração de atividades direcionadas ao cuidado com a doença, o Programa Saúde da Família realizou atividades relacionadas à determinação social da saúde, contemplando todas as formas de abordagem da promoção da saúde (biológico, comportamental, psicológico, social e estrutural) e os principais determinantes sociais da saúde descritos na literatura. Houve diferença significativa quanto à abrangência dos determinantes trabalhados nas unidades em relação às diferentes regiões do município. Constatou-se fragilidade das iniciativas e a sua desconexão com a estrutura programática do Programa Saúde da Família. CONCLUSÕES A quantidade e variedade de atividades com determinantes sociais da saúde realizadas no Programa Saúde da Família mostram potencial para trabalhar a determinação social da saúde. Mas a fluidez de objetivo e o caráter extraordinário das atividades descritas questionam sua sustentabilidade como parte integral da atual estrutura organizacional do programa.OBJETIVO Analizar la situación del trabajo con determinantes sociales de la salud en el ámbito del Programa Salud de la Familia. MÉTODOS Estudio de caso con métodos mixtos de investigación, anclados en estrategia secuencial explicativa, con 171 gerentes de las unidades del Programa Salud de la Familia en Sao Paulo, SP, en 2005/2006. Cuestionarios auto-llenables fueron aplicados. Entrevistas semi-estructuradas y grupos focales fueron realizados con muestra intencional de profesionales involucrados en el trabajo con determinantes sociales de la salud. Los datos cuantitativos fueron analizados a través de análisis descriptivo, análisis de correspondencia múltiple, análisis de agrupamiento y pruebas de correlación entre variables. Los datos cualitativos fueron analizados a través de análisis de contenido y con la creación de categorías temáticas. RESULTADOS A pesar de la concentración de actividades dirigidas al cuidado de la enfermedad, el Programa de Salud de la Familia realizó actividades relacionadas con la determinación de la salud, contemplando todas las formas de abordaje de la promoción de la salud (biológico, conductual, psicológico, social y estructural) y los principales determinantes sociales de la salud descritos en la literatura. Hubo diferencia significativa con relación a la amplitud de los determinantes trabajados en las unidades con respecto a las diferentes regiones del municipio. Se verificó fragilidad de las iniciativas y su desconexión con la estructura programática del Programa Salud de la Familia. CONCLUSIONES La cantidad y variedad de actividades con determinantes sociales de la salud realizadas en el Programa Salud de la Familia muestran potencial para trabajar la determinación social de la salud. Sin embargo, la fluidez del objetivo y el carácter extraordinario de las actividades descritas cuestionan su sustentabilidad como parte integral de la actual estructura organizativa del programa.OBJECTIVE To analyze the current status of the interventions related to social determinants of health conducted in the context of the brazilian family health program. METHODS A case study using a mixed method approach based on a sequential explanatory strategy with 171 unit managers in the Family Health Care Program in the municipality of Sao Paulo, SP, Southeastern Brazil, in 2005/2006. Self-administered questionnaires were applied and semi-structured interviews and focus groups were conducted with a purposive sample of professionals involved in initiatives related to social determinants of health. Quantitative data were analyzed using descriptive statistics, multiple correspondence analysis, cluster analysis and correlation tests. Qualitative data were analyzed through content analysis and the creation of thematic categories. RESULTS Despite the concentration of activities directed at disease care, the Family Health Care Program carries out various activities related to the social determination of health, encompassing the entire spectrum of health promotion approaches (biological, behavioral, psychological, social and structural) and all major social determinants of health described in the literature. There was a significant difference related to the scope of the determinants being worked on in the units according to the area of the city. The description of the activities revealed the fragility of the initiatives and a disconnection with the organizational structure of the Family Health Care Program. CONCLUSIONS The quantity and variety of initiatives related to social determinants of health attests to the program’s potential to deal with the social determination of health. On the other hand, the fluidity of objectives and the ‘out of the ordinary/extraordinary’ characterization of the described initiatives raises concern about its sustainability as an integral part of the program’s current operational model

Polysaccharide-derived mesoporous materials (Starbon®) for sustainable separation of complex mixtures

The recovery and separation of high value and low volume extractives are a considerable challenge for the commercial realisation of zero-waste biorefineries. Using solid-phase extractions (SPE) based on sustainable sorbents is a promising method to enable efficient, green and selective separation of these complex extractive mixtures. Mesoporous carbonaceous solids derived from renewable polysaccharides are ideal stationary phases due to their tuneable functionality and surface structure. In this study, the structure-separation relationships of thirteen polysaccharide-derived mesoporous materials and two modified types as sorbents for ten naturally-occurring bioactive phenolic compounds were investigated. For the first time, a comprehensive statistical analysis of the key molecular and surface properties influencing the recovery of these species was carried out. The obtained results show the possibility of developing tailored materials for purification, separation or extraction, depending on the molecular composition of the analyte. The wide versatility and application span of these polysaccharide-derived mesoporous materials offer new sustainable and inexpensive alternatives to traditional silica-based stationary phases

We’re All Cultural Historians Now: Revolutions In Understanding Archaeological Theory And Scientific Dating

Radiocarbon dating has had profound implications for archaeological understanding. These have been identified as various “revolutions,” with the latest—Bayesian chronological statistical analyses of large datasets—hailed as a “revolution in understanding.” This paper argues that the full implications of radiocarbon (14C) data and interpretation on archaeological theory have yet to be recognized, and it suggests that responses in Britain to earlier revolutions in archaeological understanding offer salutary lessons for contemporary archaeological practice. This paper draws on the work of David Clarke and Colin Renfrew to emphasize the importance of critical considerations of the relationships between archaeological theory and scientific method, and to emphasize that seemingly neutral aspects of archaeological thought are highly laden interpretatively, and have significant implications for the kinds of archaeology that we write

DnaN clamp zones provide a platform for spatiotemporal coupling of mismatch detection to DNA replication

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96373/1/mmi12115-sup-0001-si.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96373/2/mmi12115.pd

Single-molecule visualization reveals the damage search mechanism for the human NER protein XPC-RAD23B

DNA repair is critical for maintaining genomic integrity. Finding DNA lesions initiates the entire repair process. In human nucleotide excision repair (NER), XPC-RAD23B recognizes DNA lesions and recruits downstream factors. Although previous studies revealed the molecular features of damage identification by the yeast orthologs Rad4-Rad23, the dynamic mechanisms by which human XPC-RAD23B recognizes DNA defects have remained elusive. Here, we directly visualized the motion of XPC-RAD23B on undamaged and lesion-containing DNA using high-throughput single-molecule imaging. We observed three types of one-dimensional motion of XPC-RAD23B along DNA: diffusive, immobile and constrained. We found that consecutive AT-tracks led to increase in proteins with constrained motion. The diffusion coefficient dramatically increased according to ionic strength, suggesting that XPC-RAD23B diffuses along DNA via hopping, allowing XPC-RAD23B to bypass protein obstacles during the search for DNA damage. We also examined how XPC-RAD23B identifies cyclobutane pyrimidine dimers (CPDs) during diffusion. XPC-RAD23B makes futile attempts to bind to CPDs, consistent with low CPD recognition efficiency. Moreover, XPC-RAD23B binds CPDs in biphasic states, stable for lesion recognition and transient for lesion interrogation. Taken together, our results provide new insight into how XPC-RAD23B searches for DNA lesions in billions of base pairs in human genome