Toll-like receptors (TLRs) play a fundamental role in the recognition of bacteria and viruses. TLR3 is activated by viral dsRNA and polyinosinic-polycytidylic acid (poly(I:C)), a synthetic mimetic of viral RNA. We show that NK cells, known for their capacity to eliminate virally infected cells, express TLR3 and up-regulate TLR3 mRNA upon poly(I:C) stimulation. Treatment of highly purified NK cells with poly(I:C) significantly augments NK cell-mediated cytotoxicity. Poly(I:C) stimulation also leads to up-regulation of activation marker CD69 on NK cells. Furthermore, NK cells respond to poly(I:C) by producing proinflammatory cytokines like IL-6 and IL-8, as well as the antiviral cytokine IFN-γ. The induction of cytokine production by NK cells was preceded by activation of NF-κB. We conclude that the ability of NK cells to directly recognize and respond to viral products is important in mounting effective antiviral responses.

In the wild-type brain, the Drosophila classic cadherin DE-cadherin is expressed globally by postembryonic neuroblasts and their lineages ("secondary lineages"), as well as glial cells. To address the role of DE-cadherin in the larval brain, we took advantage of the dominant-negative DE-cad(ex) construct, the expression of which was directed to neurons, glial cells, or both. Global expression of DE-cad(ex) driven by a heat pulse during the early second instar resulted in a severe phenotype that included deficits in neural proliferation. Neuroblasts appeared in approximately normal numbers but had highly reduced mitotic activity. When the DE-cad(ex) construct was driven by the glial-specific driver gcm-Gal4, the effect of DE-cad(ex) on neuroblast proliferation could be replicated, which indicates that DE-cadherin acts in glial cells to promote proliferation of neuroblasts. Expression of DE-cad(ex) in neurons, cortex glia, or both results in abnormalities in cortex layering and in trajectories of secondary axons. In the wild-type brain, neuroblasts and neurons generated at different time points are arranged concentrically around the neuropile, with the DE-cadherin-positive neuroblasts and young secondary neurons at the surface, followed by older secondary neurons and primary neurons. Axons of secondary lineages follow a straight radial course toward the neuropile. Processes of glial cells located in the cortex form a scaffold, called trophospongium, that enwraps neuroblasts and neurons. Expression of DE-cad(ex) in neurons, cortex glia, or both disrupted the regular placement of neuroblasts and secondary neurons and resulted in abnormal trajectories of cell body fiber tracts. We conclude that DE-cadherin plays a pivotal role in larval brain proliferation, brain cortex morphogenesis, and axon growth.

DNA microarrays were used to measure the time course of gene expression during skeletal muscle damage and regeneration in mice following femoral artery ligation (FAL). We found 1,289 known sequences were differentially expressed between the FAL and control groups. Gene expression peaked on day 3, and the functional cluster "inflammation" contained the greatest number of genes. Muscle function was depressed for 3 days postligation, but returned to normal by day 7. Decreased muscle function was accompanied by reduced expression of genes involved in mitochondrial energy production, muscle contraction, and calcium handling. The induction of MyoD on day 1 denoted the beginning of muscle regeneration and was followed by the reemergence of the embryonic forms of muscle contractile proteins, which peaked at day 7. Transcriptional analysis indicated that the ischemic skeletal muscle may transition through a functional adaptation stage with recovery of contractile force prior to full regeneration. Several members of the insulin-like growth factor axis were coordinately induced in a time frame consistent with their playing a role in the regenerative process.

The Drosophila E-cadherin homolog, DE-cadherin, is expressed postembryonically by brain neuroblasts and their lineages of neurons ("secondary lineages"). DE-cadherin appears in neuroblasts as soon as they can be identified by their increase in size and then remains expressed uninterruptedly throughout larval life. DE-cadherin remains transiently expressed in the cell bodies and axons of neurons produced by neuroblast proliferation. In general, axons of neurons belonging to one lineage form tight bundles. The trajectories of these bundles are correlated with the location of the neuronal lineages to which they belong. Thus, axon bundles of lineages that are neighbors in the cortex travel parallel to each other and reach the neuropile at similar positions. It is, therefore, possible to assign coherent groups of neuroblasts and their lineages to the individual neuropile compartments and long axon tracts introduced in the accompanying articles (Nassif et al. [2003] J Comp Neurol 455:417-434; Younossi-Hartenstein et al. [2003] J Comp Neurol 455:435-450). In this study, we have reconstructed the pattern of secondary lineages and their projection in relationship to the compartments and Fasciclin II-positive long axon tracts. Based on topology and axonal trajectory, the lineages of the central brain can be subdivided into 11 groups that can be followed throughout successive larval stages. The map of larval lineages and their axonal projection will be important for future studies on postembryonic neurogenesis in Drosophila. It also lays a groundwork for investigating the role of DE-cadherin in larval brain development.

ACE inhibition after MI inhibits cardiac hypertrophy, preserves cardiac function, and attenuates changes in myocardial gene expression. Gene expression profiling reveals, however, that some elements of the pathophysiology may be unaffected by the treatment and be targets for new therapies.