Catálogo de publicaciones - revistas

<jats:p>The firing rate responses of neurons in the primary visual cortex grow with stimulus contrast, the variation in the luminance of an image relative to the mean luminance. These responses, however, are reduced after a cell is exposed for prolonged periods to high-contrast visual stimuli. This phenomenon, known as contrast adaptation, occurs in the cortex and is not present at earlier stages of visual processing. To investigate the cellular mechanisms underlying cortical adaptation, intracellular recordings were performed in the visual cortex of cats, and the effects of prolonged visual stimulation were studied. Surprisingly, contrast adaptation barely affected the stimulus-driven modulations in the membrane potential of cortical cells. Moreover, it did not produce sizable changes in membrane resistance. The major effect of adaptation, evident both in the presence and in the absence of a visual stimulus, was a tonic hyperpolarization. Adaptation affects a class of synaptic inputs, most likely excitatory in nature, that exert a tonic influence on cortical cells.</jats:p>

<jats:p>Timely deactivation of kinase cascades is crucial to the normal control of cell signaling and is partly accomplished by protein phosphatase 2A (PP2A). The catalytic (α) subunit of the serine-threonine kinase casein kinase 2 (CK2) bound to PP2A in vitro and in mitogen-starved cells; binding required the integrity of a sequence motif common to CK2α and SV40 small t antigen. Overexpression of CK2α resulted in deactivation of mitogen-activated protein kinase kinase (MEK) and suppression of cell growth. Moreover, CK2α inhibited the transforming activity of oncogenic Ras, but not that of constitutively activated MEK. Thus, CK2α may regulate the deactivation of the mitogen-activated protein kinase pathway.</jats:p>

<jats:p>A new class of protein tyrosine kinase inhibitors was identified that is based on an oxindole core (indolinones). Two compounds from this class inhibited the kinase activity of fibroblast growth factor receptor 1 (FGFR1) and showed differential specificity toward other receptor tyrosine kinases. Crystal structures of the tyrosine kinase domain of FGFR1 in complex with the two compounds were determined. The oxindole occupies the site in which the adenine of adenosine triphosphate binds, whereas the moieties that extend from the oxindole contact residues in the hinge region between the two kinase lobes. The more specific inhibitor of FGFR1 induces a conformational change in the nucleotide-binding loop. This structural information will facilitate the design of new inhibitors for use in the treatment of cancer and other diseases in which cell signaling by tyrosine kinases plays a crucial role in disease pathogenesis.</jats:p>

<jats:p>In lymphoid tissue, where human immunodeficiency virus–type 1 (HIV-1) is produced and stored, three-drug treatment with viral protease and reverse transcriptase inhibitors markedly reduced viral burden. This was shown by in situ hybridization and computerized quantitative analysis of serial tonsil biopsies from previously untreated adults. The frequency of productive mononuclear cells (MNCs) initially diminished with a half-life of about 1 day. Surprisingly, the amount of HIV-1 RNA in virus trapped on follicular dendritic cells (FDCs) decreased almost as quickly. After 24 weeks, MNCs with very few copies of HIV-1 RNA per cell were still detectable, as was proviral DNA; however, the amount of FDC-associated virus decreased by ≥3.4 log units. Thus, 6 months of potent therapy controlled active replication and cleared &gt;99.9 percent of virus from the secondary lymphoid tissue reservoir.</jats:p>