Vaccinia virus (VV) is a cytocidal virus that causes major changes in host cell

Overall, evidence suggests an association between chronic occupational exposure to OP pesticides and neuropsychological effects. However, there is no consensus about the specific cognitive skills affected.

An insulin-like signaling pathway regulates development and lifespan in Caenorhabditis elegans. Genetic screens that identified many components of the C. elegans insulin pathway did not identify homologs of insulin receptor substrates or the phosphoinositide 3-kinase (PI3K) adaptor/regulatory subunit, which are both required for signaling by mammalian insulin/insulinlike growth factor I pathways. The C. elegans genome contains one homolog of each protein. The C. elegans versions of insulin receptor substrate (IST-1) and PI3K p50/p55 (AAP-1) share moderate sequence similarity with their vertebrate and Drosophila counterparts. Genetic experiments show that ist-1 and aap-1 potentiate C. elegans insulin-like signaling, although they are not required for signaling in the pathway under most conditions. Worms lacking AAP-1 activity because of the mutation aap-1(m889) constitutively arrest development at the dauer larval stage when raised at high temperatures. aap-1 mutants also live longer than wild-type animals, a phenotype observed in other C. elegans mutants with defects in DAF-2 signaling. Interestingly, IST-1 appears to be required for signaling through a pathway that may act in parallel to AGE-1/PI3K.An insulin-like signaling pathway controls development and lifespan in Caenorhabditis elegans (1-3). Genetic studies have shown that the C. elegans insulin-like pathway utilizes many of the same components as the human insulin and insulin-like growth factor (IGF-I) 1 pathways. C. elegans insulin-like signaling requires the genes daf-2, encoding an insulin/IGF-I receptor-like protein, age-1, a homolog of vertebrate p110 catalytic subunits of phosphoinositide 3-kinase (PI3K), akt-1 and akt-2, encoding AKT/protein kinase B-like proteins activated by the phospholipid products of PI3K, and pdk-1, encoding a PDK-1-like kinase also required for AKT/protein kinase B activation (1, 4 -6). In both worms and vertebrates, insulin-like signaling antagonizes forkhead transcription factors DAF-16 in the worm and FKHR, FKHRL1, and AFX in vertebrates (7-11). Loss-of-function mutations in daf-2, age-1, akt-1, or pdk-1 cause constitutive developmental arrest at the dauer larval stage, a long-lived stress-resistant non-reproductive larval form specialized to survive in hostile environments. Weak mutations in these genes allow normal reproductive development but significantly extend adult lifespan (2, 12, 13). daf-16 activity is required for dauer arrest and long lifespan as daf-16 mutations suppress these phenotypes in daf-2 and age-1 mutants (2, 12, 14 -17).In vertebrates and Drosophila, insulin-like signaling utilizes adaptor proteins that link activated growth factor receptors to intracellular signaling pathways (18 -20). Ligand binding activates the tyrosine kinase activity of the insulin and IGF-I receptors, resulting in the phosphorylation of the insulin receptor substrate (IRS). Phosphotyrosines on IRS act as binding sites for downstream targets of growth factor receptors such as PI3K and Ras/MAPK pathways. Biochemical and geneti...

In animal cells, cytokinesis occurs by constriction of an actomyosin ring. In fission yeast cells, ring constriction is triggered by the septum initiation network (SIN), an SPB-associated GTPase-regulated kinase cascade that coordinates exit from mitosis with cytokinesis. We have identified a novel protein, Etd1p, required to trigger actomyosin ring constriction in fission yeasts. This protein is localised at the cell tips during interphase. In mitosis, it relocates to the medial cortex region and, coincident with cytokinesis, it assembles into the actomyosin ring by association to Cdc15p. Relocation of Etd1p from the plasma membrane to the medial ring is triggered by SIN signalling and, reciprocally, relocation of the Sid2p-Mob1p kinase complex from the SPB to the division site, a late step in the execution of the SIN, requires Etd1p. These results suggest that Etd1p coordinates the mitotic activation of SIN with the initiation of actomyosin ring constriction. Etd1p peaks during cytokinesis and is degraded by the ubiquitin-dependent 26S-proteasome pathway at the end of septation, providing a mechanism to couple inactivation of SIN to completion of cytokinesis.