RESUMO
Nation-wide surveillance of transmissible spongiform encephalopathies including Creutzfeldt-Jakob disease, is performed by the Australian National Creutzfeldt-Jakob Disease Registry, based at the University of Melbourne. Surveillance has been undertaken since 1993. Over this dynamic period in transmissible spongiform encephalopathy research and understanding, the unit has evolved and adapted to changes in surveillance practices and requirements, the emergence of new disease subtypes, improvements in diagnostic capabilities and the overall heightened awareness and understanding of Creutzfeldt-Jakob disease and other transmissible spongiform encephalopathies in the health care setting. In 2013, routine surveillance continued and this brief report provides an update of the surveillance data collected by the Australian National Creutzfeldt-Jakob Disease Registry prospectively from 1993 to December 2013, and retrospectively to 1970. The report highlights the recent multi-national collaborative study published that has verified the correlation between surveillance intensity and reported disease incidence.
Assuntos
Síndrome de Creutzfeldt-Jakob/epidemiologia , Doenças Priônicas/epidemiologia , Sistema de Registros , Proteínas 14-3-3/líquido cefalorraquidiano , Idoso , Austrália/epidemiologia , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/mortalidade , Notificação de Doenças/estatística & dados numéricos , Monitoramento Epidemiológico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doenças Priônicas/líquido cefalorraquidiano , Doenças Priônicas/diagnóstico , Doenças Priônicas/mortalidade , Estudos Prospectivos , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver and key therapeutic target for human cancers. Current therapies targeting HER2 are primarily based on overexpression of the wild-type form of HER2. However, kinase domain mutations have been identified that can increase the activity of HER2 even when expressed at basal levels. Using purified enzymes, we confirmed the hyperactivity of two HER2 mutants (D769Y and P780insGSP). To identify small molecule inhibitors against these cancer-associated variants, we used a combined approach consisting of biochemical testing, similarity-based searching, and in silico modeling. These approaches resulted in the identification of a candidate molecule that inhibits mutant forms of HER2 in vitro and in cell-based assays. Our structural model predicts that the compound takes advantage of water-mediated interactions in the HER2 kinase binding pocket.
Assuntos
Neoplasias , Receptor ErbB-2 , Humanos , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Ligação Proteica , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Linhagem Celular TumoralRESUMO
The influence of the growth of psychrotrophic bacteria in raw milk on the acceptability and resultant shelf life of ultra-high temperature (UHT) processed skim milk was investigated. Five batches of raw milk with different psychrotrophic counts were UHT processed in a commercial dairy plant. The processed milk of each batch was divided into three lots which were stored for 139 d at 20, 30, and 40°C, respectively. Changes in the extent of proteolysis, lipolysis, and sensory attributes of the five batches of UHT milk stored at the various temperatures were determined at fixed intervals of storage. The psychrotrophic counts in the raw milk were strongly correlated with the extent of proteolysis (r = 0.9476) but not with the extent of lipolysis (r = 0.18) in the stored UHT milk. Correlations between the extent of proteolysis and bitterness scores in the stored UHT milk were high at 30°C (r = 0.916) and at 40°C (r = 0.896) but not at 20°C (r = -0.233). Correlations between the extent of lipolysis and rancidity scores were not significant in the stored UHT milk. It appeared that the proteinases played a more important role in the loss of taste and acceptability of the UHT skim milk than did the lipases. This investigation suggested that storage time and storage temperature had a greater influence on the sensory acceptance and resultant shelf life of the UHT skim milk than the psychrotrophic count of the raw milk.