RESUMO
BACKGROUND: Retroviruses encode a very limited number of proteins and therefore must exploit a wide variety of host proteins for completion of their lifecycle. METHODS: We performed an insertional mutagenesis screen to identify novel cellular regulators of retroviral replication. RESULTS: This approach identified the ATP-dependent chromatin remodeler, chromodomain helicase DNA-binding protein 2 (CHD2), as well as the highly related CHD1 protein, as positive regulators of both MLV and HIV-1 replication in rodent and human cells. RNAi knockdown of either CHD2 or the related CHD1 protein, in human cells resulted in a block to infection by HIV-1, specifically at the level of transcription. CONCLUSIONS: These results demonstrate that CHD1 and CHD2 can act as positive regulators of HIV-1 gene expression.
Assuntos
DNA Helicases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Viral da Expressão Gênica , Infecções por HIV/enzimologia , HIV-1/genética , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/metabolismo , Humanos , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
Adolescence is a vulnerable developmental phase marked by physical, psychological, and social changes that rapidly expose young people to a wide range of new stressors. When differentiating between bipolar disorder and teenage "acting out," a careful history is important. Adolescent bipolar disorder is a psychiatric illness characterized by fluctuating episodes of mood elevation and depression that is frequently neither recognized nor formally diagnosed. Adolescents with bipolar disorder often manifest a more nonepisodic, chronic course with continuous rapid-cycling patterns than do adults. Pharmacologic treatment of adolescent bipolar disorder is difficult and often requires combination therapy to address comorbidities like attention-deficit/hyperactivity disorder and anxiety disorder. Adjuncts to pharmacologic treatment of bipolar disorder can be beneficial. Psychosocial treatments include family education, enhanced parenting techniques, stress management, and the development of effective coping strategies.
RESUMO
The parasitic protozoan Trypanosoma brucei contains two type III phosphatidylinositol 4-kinases (alpha and beta). We have cloned the gene encoding the T. brucei type III phosphatidylinositol 4-kinase beta (TbPI4KIII-beta), expressed the protein in COS-7 cells, and confirmed that the protein catalyzes the phosphorylation of phosphatidylinositol. Depletion of TbPI4KIII-beta in procyclic T. brucei by RNA interference (RNAi) resulted in inhibition of cell growth and a distorted cellular morphology. RNAi cells had a distorted Golgi apparatus, and lysosomal and flagellar pocket proteins were mislocalized. Ultrastructural analysis revealed the internal accumulation of a heterogeneous population of vesicles, abnormal positioning of organelles, and a loss of cell polarity. Scanning electron microcopy revealed a twisted phenotype, and dividing cells often exhibited a detached daughter flagellum and lacked a cleavage furrow. Cell cycle analysis confirmed that cells depleted of TbPI4KIII-beta have a postmitotic cytokinesis block that occurs after a single round of mitosis, suggestive of a specific cell cycle block. In summary, TbPI4KIII-beta is an essential protein in procyclic T. brucei, required for maintenance of Golgi structure, protein trafficking, normal cellular shape, and cytokinesis.