Monkey hybrid stem cells develop cellular features of Huntington's disease

Background  

Pluripotent stem cells that are capable of differentiating into different cell types and develop robust hallmark cellular features are useful tools for clarifying the impact of developmental events on neurodegenerative diseases such as Huntington's disease. Additionally, a Huntington's cell model that develops robust pathological features of Huntington's disease would be valuable for drug discovery research.     

Stability and Change in Estuarine Biofilm Bacterial Community Diversity

Biofouling communities contribute significantly to aquatic ecosystem productivity and biogeochemical cycling. Our knowledge of the distribution, composition, and activities of these microbially dominated communities is limited compared to other components of estuarine ecosystems. This study investigated the temporal stability and change of the dominant phylogenetic groups of the domain Bacteria in estuarine biofilm communities. Glass slides were deployed monthly over 1 year for 7-day incubations during peak tidal periods in East Sabine Bay, Fla. Community profiling was achieved by using 16S rRNA genes and terminal restriction fragment length polymorphism (T-RFLP) of 16S rRNA genes in combination with ribotyping, cloning, and sequencing to evaluate diversity and to identify dominant microorganisms. Bacterial community profiles from biofilms grown near the benthos showed distinct periods of constancy within winter and summer sampling periods. Similar periods of stability were also seen in T-RFLP patterns from floating biofilms. Alternating dominance of phylogenetic groups between seasons appeared to be associated with seasonal changes in temperature, nutrient availability, and light. The community structure appeared to be stable during these periods despite changes in salinity and in dissolved oxygen.     

DANGER, a novel regulatory protein of inositol 1,4,5-trisphosphate-receptor activity

We report the cloning and characterization of DANGER, a novel protein which physiologically binds to inositol 1,4,5-trisphosphate receptors (IP(3)R). DANGER is a membrane-associated protein predicted to contain a partial MAB-21 domain. It is expressed in a wide variety of neuronal cell lineages where it localizes to membranes in the cell periphery together with IP(3)R. DANGER interacts with IP(3)R in vitro and co-immunoprecipitates with IP(3)R from cellular preparations. DANGER robustly enhances Ca(2+)-mediated inhibition of IP(3) RCa(2+) release without affecting IP(3) binding in microsomal assays and inhibits gating in single-channel recordings of IP(3)R. DANGER appears to allosterically modulate the sensitivity of IP(3) RtoCa(2+) inhibition, which likely alters IP(3)R-mediated Ca(2+) dynamics in cells where DANGER and IP(3)R are co-expressed.     

Nitric oxide-GAPDH-Siah: a novel cell death cascade

1. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extremely abundant glycolytic enzyme, and exemplifies the class of proteins with multiple, seemingly unrelated functions. Recent studies indicate that it is a major intracellular messenger mediating apoptotic cell death. This paper reviews the GAPDH cell death cascade and discusses its clinical relevance. 2. A wide range of apoptotic stimuli activate NO formation, which S-nitrosylates GAPDH. The S-nitrosylation abolishes catalytic activity and confers upon GAPDH the ability to bind to Siah, an E3-ubiquitin-ligase, which translocates GAPDH to the nucleus. In the nucleus, GAPDH stabilizes the rapidly turning over Siah, enabling it to degrade selected target proteins and affect apoptosis. 3. The cytotoxicity of mutant Huntingtin (mHtt) requires nuclear translocation which appears to be mediated via a ternary complex of GAPDH-Siah-mHtt. The neuroprotective actions of the monoamine oxidase inhibitor R-(-)-deprenyl (deprenyl) reflect blockade of GAPDH-Siah binding. Thus, novel cytoprotective therapies may emerge from agents that prevent GAPDH-Siah binding.     

The genome of Rhizobium leguminosarum has recognizable core and accessory components

Background

Rhizobium leguminosarum is an α-proteobacterial N₂-fixing symbiont of legumes that has been the subject of more than a thousand publications. Genes for the symbiotic interaction with plants are well studied, but the adaptations that allow survival and growth in the soil environment are poorly understood. We have sequenced the genome of R. leguminosarum biovar viciae strain 3841.

Results

The 7.75 Mb genome comprises a circular chromosome and six circular plasmids, with 61% G+C overall. All three rRNA operons and 52 tRNA genes are on the chromosome; essential protein-encoding genes are largely chromosomal, but most functional classes occur on plasmids as well. Of the 7,263 protein-encoding genes, 2,056 had orthologs in each of three related genomes (Agrobacterium tumefaciens, Sinorhizobium meliloti, and Mesorhizobium loti), and these genes were over-represented in the chromosome and had above average G+C. Most supported the rRNA-based phylogeny, confirming A. tumefaciens to be the closest among these relatives, but 347 genes were incompatible with this phylogeny; these were scattered throughout the genome but were over-represented on the plasmids. An unexpectedly large number of genes were shared by all three rhizobia but were missing from A. tumefaciens.

Conclusion

Overall, the genome can be considered to have two main components: a 'core', which is higher in G+C, is mostly chromosomal, is shared with related organisms, and has a consistent phylogeny; and an 'accessory' component, which is sporadic in distribution, lower in G+C, and located on the plasmids and chromosomal islands. The accessory genome has a different nucleotide composition from the core despite a long history of coexistence.     

Gene therapy: can neural stem cells deliver?

Neural stem cells are a self-renewing population that generates the neurons and glia of the developing brain. They can be isolated, proliferated, genetically manipulated and differentiated in vitro and reintroduced into a developing, adult or pathologically altered CNS. Neural stem cells have been considered for use in cell replacement therapies in various neurodegenerative diseases, and an unexpected and potentially valuable characteristic of these cells has recently been revealed--they are highly migratory and seem to be attracted to areas of brain pathology such as ischaemic and neoplastic lesions. Here, we speculate on the ways in which neural stem cells might be exploited as delivery vehicles for gene therapy in the CNS.     

Proteome chips for whole-organism assays

Over the past 5 years, protein-chip technology has emerged as a useful tool for the study of many kinds of protein interactions and biochemical activities. The construction of Saccharomyces cerevisiae whole-proteome arrays has enabled further studies of such interactions in a proteome-wide context. Here, we explore some of the recent advances that have been made at the '-omic' level using protein microarrays.     

Dopamine receptor excess and mouse madness

The dopamine hypothesis of schizophrenia is based on evidence that the major antipsychotic drugs act by blocking dopamine D2 receptors and that dopamine-releasing drugs worsen symptoms. In this issue of Neuron, Kellendonk et al. report an elegant conditional transgenic mouse overexpressing dopamine D2 receptors selectively in the striatum. Strikingly, these animals display selective cognitive impairment typically associated with frontal cortical defects and abnormal dopamine markers in the prefrontal cortex, suggesting that striatal dopamine receptors can influence cortical dopamine function.