Under standard conditions, cultured ventral spinal neurons cluster AMPA- but not NMDA-type glutamate receptors at excitatory synapses on their dendritic shafts in spite of abundant expression of the ubiquitous NMDA receptor subunit NR1. We demonstrate here that the NMDA receptor subunits NR2A and NR2B are not routinely expressed in cultured spinal neurons and that transfection with NR2A or NR2B...

In Escherichia coli, there are 32 open reading frames (ORFs) that are assumed to be response regulator genes of two-component signal transduction systems on the basis of sequence similarities. We cloned all of these 32 ORFs into a multicopy expression vector and investigated whether or not they confer drug resistance via control of drug resistance determinants. Fifteen of these ORFs, i.e., baeR...

We report a family with an undiagnosed X linked condition. The grandmother, two of her three daughters, and one of her grand-daughters have a slowly progressive proximal weakness, brisk reflexes, poor bladder function, static reduced night vision, and IgG2 deficiency. The diagnosis of the three living symptomatic females was "hereditary spastic paraplegia plus". They have lost five male childre...

Mitochondrial encephalopathies (MEs) are characterized by an extreme clinical heterogeneity since they can involve different systems and manifest at distinct ages with variable course. Many affected individuals display a cluster of clinical features that fall into discrete syndromes among syndromic pictures, epilepsy is relevant in myoclonic epilepsy with ragged-red fibers (MERRF), mitochondria...

We designed and engineered mitochondrially targeted obligate heterodimeric zinc finger nucleases (mtZFNs) for site-specific elimination of pathogenic human mitochondrial DNA (mtDNA). We used mtZFNs to target and cleave mtDNA harbouring the m.8993T>G point mutation associated with neuropathy, ataxia, retinitis pigmentosa (NARP) and the "common deletion" (CD), a 4977-bp repeat-flanked deletion as...

We used engineered zinc finger peptides (ZFPs) to bind selectively to predetermined sequences in human mtDNA. Surprisingly, we found that engineered ZFPs cannot be reliably routed to mitochondria by using only conventional mitochondrial targeting sequences. We here show that addition of a nuclear export signal allows zinc finger chimeric enzymes to be imported into human mitochondria. The selec...

Several lines of evidence implicate BDNF in the pathogenesis of stress-induced depression and the delayed efficacy of antidepressant drugs. Antidepressant-induced upregulation of BDNF signaling is thought to promote adaptive neuronal plasticity through effects on gene expression, but the effector genes downstream of BDNF has not been identified. Local infusion of BDNF into the dentate gyrus ind...