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The Rap family of small GTPases is implicated in the mechanisms of synaptic plasticity, particularly synaptic depression. Here we studied the role of Rap in neuronal morphogenesis and synaptic transmission in cultured neurons. Constitutively active Rap2 expressed in hippocampal pyramidal neurons caused decreased length and complexity of both axonal and(More)
How does chronic activity modulation lead to global remodeling of proteins at synapses and synaptic scaling? Here we report that guanylate kinase-associated protein (GKAP; also known as SAPAP), a scaffolding molecule linking NMDA receptor-PSD-95 to Shank-Homer complexes, acts in these processes. Overexcitation removes GKAP from synapses via the(More)
Studies in anesthetized animals have advanced the theory that there is an important neurogenic component to the hypertension caused by pharmacological inhibition of nitric oxide, but studies in conscious animals have produced conflicting evidence for and against this theory. To try to reconcile the seemingly contradictory data, we hypothesized that the(More)
Activation of a metabolically generated reflex in exercising skeletal muscle (muscle metaboreflex) in humans is known to trigger increases in sympathetic nerve activity (SNA) to resting skeletal muscles. In seven healthy human subjects, to determine whether this reflex mechanism also increases SNA to the exercising muscles, we recorded muscle SNA with(More)
Metabolic products of skeletal muscle contraction activate metaboreceptor muscle afferents that reflexively increase sympathetic nerve activity (SNA) targeted to both resting and exercising skeletal muscle. To determine effects of the increased sympathetic vasoconstrictor drive on muscle oxygenation, we measured changes in tissue oxygen stores and(More)
Carcinosarcomas of the prostate gland are exceedingly rare, and previous reports exist on only seven of these neoplasms. The authors studied two such tumors, which occurred in 63- and 69-year-old patients. One of them had osseous metastases develop, which were treated unsuccessfully by irradiation and diethylstilbestrol therapy. The other patient is free of(More)
Regulation of innate inflammatory responses against the enteric microbiota is essential for the maintenance of intestinal homeostasis. Key participants in innate defenses are macrophages. In these studies, the basic leucine zipper protein, NFIL3, is identified as a regulatory transcription factor in macrophages, controlling IL-12 p40 production induced by(More)
Studies of whole limb blood flow have shown that static handgrip elicits a vasodilatation in the resting forearm and vasoconstriction in the resting leg. We asked if these responses occur in the skeletal muscle vascular bed, and if so, what is the relative contribution of local metabolic versus other mechanisms to these vascular responses. Blood flow(More)
BACKGROUND & AIMS Propofol is under evaluation as a sedative for endoscopic procedures. We compared nurse-administered propofol to midazolam plus fentanyl for outpatient colonoscopy. METHODS One hundred outpatients undergoing colonoscopy were randomized to receive propofol or midazolam plus fentanyl, administered by a registered nurse and supervised only(More)
BACKGROUND While others have described gene expression patterns in humans with inflammatory bowel diseases and animals with chemically induced colitis, a genome-wide comparison of gene expression in genetically susceptible animals that develop spontaneous colitis has not been reported. METHODS We used microarray technology to compare gene expression(More)