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Neuronal differentiation involves Rac and Cdc42 GTPases. alpha-Chimaerin, a Rac/Cdc42 regulator, occurs as alpha1- and alternatively spliced Src homology 2 (SH2) domain-containing alpha2-isoforms. alpha2-chimaerin mRNA was highly expressed in the rat embryonic nervous system, especially in early postmitotic neurons. alpha1-chimaerin mRNA was undetectable(More)
Neurite outgrowth is influenced by positive and negative signals that include the semaphorins, an important family of axonal outgrowth inhibitors. Here we report that the Rac GTPase activating protein (GAP)alpha2-chimaerin is involved in Semaphorin 3A (Sema 3A) signaling. In dorsal root ganglion neurons, Sema 3A-induced growth cone collapse was inhibited by(More)
In the developing forebrain, neuronal polarization is a stepwise and initially reversible process that underlies correct migration and axon specification. Many aspects of cytoskeletal changes that accompany polarization are currently molecularly undefined and thus poorly understood. Here we reveal that the p21-activated kinase (Pak1) is essential for the(More)
The normal formation and function of the mammalian cerebral cortex depend on the positioning of its neurones, which occurs in a highly organized, layer-specific manner. The correct morphology and movement of neurones rely on synchronized regulation of their actin filaments and microtubules. The p21-activated kinase (Pak1), a key cytoskeletal regulator,(More)
The formation and directional guidance of neurites involves dynamic regulation of Rho family GTPases. Rac and Cdc42 promote neurite outgrowth, whereas Rho activation causes neurite retraction. Here we describe a role for collapsin response mediator protein (Crmp-2), a neuronal protein implicated in axonal outgrowth and a component of the semaphorin 3A(More)
AIMS The objective of the study was to evaluate the pharmacokinetics (and how they are affected by food), CNS pharmacodynamics and the adverse event profile of brivaracetam after single increasing doses. METHODS Healthy males (n = 27, divided into three alternating panels of nine subjects) received two different single oral doses of brivaracetam (10-1400(More)
www.nature.com/naturebiotechnology • OCTOBER 2002 • VOLUME 20 • nature biotechnology The latest biotechnology boom is over, and now it is time for the fall. And here is the evidence: fifty-six percent of the 471 companies within the broad biotechnology/drug industry sector finished their most recent financial quarter with less cash in hand than they had(More)
Brivaracetam is a novel high-affinity SV2A ligand currently in clinical development for epilepsy. The objective was to characterize its disposition in patients with renal impairment. A single oral dose of 200 mg brivaracetam was administered to 9 patients with severe renal impairment not requiring dialysis (creatinine clearance <15 mL/min, n = 6; 15-29(More)
The correct morphology and migration of neurons, which is essential for the normal development of the nervous system, is enabled by the regulation of their cytoskeletal elements. We reveal that Neurabin-I, a neuronal-specific F-actin-binding protein, has an essential function in the developing forebrain. We show that gain and loss of Neurabin-I expression(More)
Diabetic foot and pressure ulcers are chronic wounds by definition. They share similar pathogeneses; i.e., a combination of increased pressure and decreased angiogenic response. Neuropathy, trauma, and deformity also often contribute to development of both types of ulcers. Early intervention and proper treatment should result in complete healing of(More)