The parasitic protozoan Trypanosoma brucei contains two type III phosphatidylinositol 4-kinases (␣ and ). We have cloned the gene encoding the T. brucei type III phosphatidylinositol 4-kinase  (TbPI4KIII-), expressed the protein in COS-7 cells, and confirmed that the protein catalyzes the phosphorylation of phosphatidylinositol. Depletion of TbPI4KIII- 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- have a postmitotic cytokinesis block that occurs after a single round of mitosis, suggestive of a specific cell cycle block. In summary, TbPI4KIII- is an essential protein in procyclic T. brucei, required for maintenance of Golgi structure, protein trafficking, normal cellular shape, and cytokinesis.
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.
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