Lentiviral vectors mediate efficient and stable gene transfer in adult neural stem cells in vivo.

Modulation of adult neurogenesis may offer new therapeutic strategies for various brain disorders. In the adult mammalian brain the subventricular zone (SVZ) of the lateral ventricle is a region of continuous neurogenesis. Lentiviral vectors stably integrate into dividing and nondividing cells, in contrast to retroviral vectors, which integrate only into dividing cells.

Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum.

Recent studies have revealed that the adult mammalian brain has the capacity to regenerate some neurons after various insults. However, the precise mechanism of insult-induced neurogenesis has not been demonstrated. In the normal brain, GFAP-expressing cells in the subventricular zone (SVZ) of the lateral ventricles include a neurogenic cell population that gives rise to olfactory bulb neurons only.

4'-phosphopantetheine and coenzyme A biosynthesis in plants.

Coenzyme A is required for many synthetic and degradative reactions in intermediary metabolism and is the principal acyl carrier in prokaryotic and eukaryotic cells. Coenzyme A is synthesized in five steps from pantothenate, and recently the CoaA biosynthetic genes in bacteria and human have all been identified and characterized. Coenzyme A biosynthesis in plants is not fully understood, and to date only the AtHAL3a (AtCoaC) gene of Arabidopsis thaliana has been cloned and identified as 4'-phosphopantothenoylcysteine (PPC) decarboxylase (Kupke, T.

Crystal structure of the plant PPC decarboxylase AtHAL3a complexed with an ene-thiol reaction intermediate.

The Arabidopsis thaliana protein AtHAL3a decarboxylates 4'-phosphopantothenoylcysteine to 4'-phosphopantetheine, a step in coenzyme A biosynthesis. Surprisingly, this decarboxylation reaction is carried out as an FMN-dependent redox reaction. In the first half-reaction, the side-chain of the cysteine residue of 4'-phosphopantothenoylcysteine is oxidised and the thioaldehyde intermediate decarboxylates spontaneously to the 4'-phosphopantothenoyl-aminoethenethiol intermediate.

Molecular characterization of the Arabidopsis thaliana flavoprotein AtHAL3a reveals the general reaction mechanism of 4'-phosphopantothenoylcysteine decarboxylases.

The Arabidopsis thaliana flavoprotein AtHAL3a, which is linked to plant growth and salt and osmotic tolerance, catalyzes the decarboxylation of 4'-phosphopantothenoylcysteine to 4'-phosphopantetheine, a key step in coenzyme A biosynthesis. AtHAL3a is similar in sequence and structure to the LanD enzymes EpiD and MrsD, which catalyze the oxidative decarboxylation of peptidylcysteines. Therefore, we hypothesized that the decarboxylation of 4'-phosphopantothenoylcysteine also occurs via an oxidatively decarboxylated intermediate containing an aminoenethiol group.

Arabidopsis thaliana flavoprotein AtHAL3a catalyzes the decarboxylation of 4'-Phosphopantothenoylcysteine to 4'-phosphopantetheine, a key step in coenzyme A biosynthesis.

The Arabidopsis thaliana flavoprotein AtHAL3a is related to plant growth and salt and osmotic tolerance. AtHAL3a shows sequence homology to the bacterial flavoproteins EpiD and Dfp. EpiD, Dfp, and AtHAL3a are members of the homo-oligomeric flavin-containing Cys decarboxylase (HFCD) protein family.