Novel cytoprotective mechanism of anti-parkinsonian drug deprenyl: PI3K and Nrf2-derived induction of antioxidative proteins

Neuroprotection has received considerable attention as a strategy for the treatment of Parkinson's disease (PD). Deprenyl (Selegiline) is a promising candidate for neuroprotection; however, its cytoprotective mechanism has not been fully clarified. Here, we report a novel cytoprotective mechanism of deprenyl involving PI3K and Nrf2-mediated induction of oxidative stress-related proteins. Deprenyl increased the expression of HO-1, PrxI, TrxI, TrxRxI, gammaGCS, and p62/A170 in SH-SY5Y cells. Deprenyl also induced the nuclear accumulation of Nrf2 and increased the binding activity of Nrf2 to the enhancer region of human genomic HO-1. The Nrf2-mediated induction of antioxidative molecules was controlled by PI3K. Indeed, furthermore, neurotrophin receptor TrkB was identified as an upstream signal for PI3K-Nrf2 activation by deprenyl. These results suggest that the cytoprotective effect of deprenyl is, in part, dependent on Nrf2-mediated induction of antioxidative proteins, suggesting that activation of the PI3K-Nrf2 system may be a useful therapeutic strategy for PD.     

Molecular characterization of the obligate endosymbiont "Caedibacter macronucleorum"Fokin and Görtz, 1993 and of its host Paramecium duboscqui strain Ku4-8

ABSTRACT. Bacterial endosymbionts of protozoa were often described as new species by protozoologists mainly on the basis of few morphological characters and partly by host specificity. Many of these species have never been validated by prokaryotic microbiologists whose taxonomic rules are quite different from those of protozoologists, who use the Zoological Code of Nomenclature. “Caedibacter macronucleorum” Fokin and Görtz 1993 , an endosymbiont of Paramecium duboscqui, belongs to this category. Here we provide the molecular characterization of this organism and of its host P. duboscqui strain Ku4‐8. Bacterial 16S rRNA gene sequence analysis proved that “C. macronucleorum” belongs to the Alphaproteobacteria. It is closely related to Caedibacter caryophilus but not to Caedibacter taeniospiralis, which belongs to the Gammaproteobacteria. “Caedibacter macronucleorum” and C. caryophilus 16S rRNA genes show a similarity value of 99%. This high 16S rRNA sequence similarity and the lack of a specific oligonucleotide probe for distinguishing the two endosymbionts do not allow validating “C. macronucleorum” as a provisional taxon (Candidatus). Nevertheless, “C. macronucleorum” and C. caryophilus can be easily discriminated on the basis of a highly variable stretch of nucleotides that interrupts the 16S rRNA genes of both organisms.     

Advances in Arachis genomics for peanut improvement

Peanut genomics is very challenging due to its inherent problem of genetic architecture. Blockage of gene flow from diploid wild relatives to the tetraploid; cultivated peanut, recent polyploidization combined with self pollination, and the narrow genetic base of the primary genepool have resulted in low genetic diversity that has remained a major bottleneck for genetic improvement of peanut. Harnessing the rich source of wild relatives has been negligible due to differences in ploidy level as well as genetic drag and undesirable alleles for low yield. Lack of appropriate genomic resources has severely hampered molecular breeding activities, and this crop remains among the less-studied crops. The last five years, however, have witnessed accelerated development of genomic resources such as development of molecular markers, genetic and physical maps, generation of expressed sequenced tags (ESTs), development of mutant resources, and functional genomics platforms that facilitate the identification of QTLs and discovery of genes associated with tolerance/resistance to abiotic and biotic stresses and agronomic traits. Molecular breeding has been initiated for several traits for development of superior genotypes. The genome or at least gene space sequence is expected to be available in near future and this will further accelerate use of biotechnological approaches for peanut improvement.     

FTIR spectro-imaging of collagens for characterization and grading of gliomas

Collagens are a family of at least 30 protein types organized as networks. They constitute the main support material of cells under the form of extracellular matrix as well as for membranes in vessels, organs, and tissue compartments. Collagen network abnormalities are at the origin of many diseases, including myopathies and fibroses. The characterization of collagens remains an analytical challenge due to the insolubility of these molecules and the difficulty encountered in isolating given types without altering their structure or in maintaining network organization, which is critical to diagnosing related pathologies. We have proposed using a vibrational spectroscopy based imaging technique, namely Fourier-transform infrared (FTIR) imaging, for a spatially-resolved analysis of secondary structure of different collagen types in complex samples, and more specifically for characterizing gliomas. With newly developed spectral data treatments and chemometrics using secondary structure parameters of collagen proteins, FTIR imaging is now able to distinguish between several types. On this basis, gliomas have been investigated as specific collagen-rich tissues developing in a non-collagenous environment, providing high specificity to this FTIR imaging utilization. Here, we review the recent advances in this imaging approach for understanding glioma development, with FTIR imaging now being proposed as a molecular histopathology tool for clinicians.     

Conservation genetics of South American aquatic mammals: an overview of gene diversity,population structure,phylogeography, non‐invasive methods and forensics

• 1 Most aquatic mammals have high dispersal potential, and there are often severe conservation concerns related to their legal or illegal harvesting. Therefore, economic, social and forensic factors often arise in decisions relating to their population management. Molecular markers are essential tools in modern conservation genetics, revealing previously unknown aspects of aquatic mammal behaviour, natural history, population structure and demography. Molecular markers also have been used to define management units, to recognize taxonomic units, to conduct forensic analyses and to control illegal wildlife trade, providing valuable information for decision‐making in wildlife conservation and management.
• 2 We review studies published in peer‐reviewed journals between 1993 and 2010, in which genetic approaches have been applied to conservation‐related issues involving natural populations of 25 species of aquatic mammals in South America. These studies cover just 34% of the 70 aquatic mammal species recorded in South America.
• 3 Most of the studies are related to population structure, phylogeography, gene flow and dispersal movements. In addition, recent findings relate to evolutionarily significant units, management units, forensics and conservation policy.
• 4 Finally, we look to the future and, based on numbers of studies and conservation concerns, suggest which species, geographic areas and genetic studies should be prioritized. Moreover, we discuss constraints on research and suggest collaborative works that would provide critical information towards the effective conservation and management of aquatic mammals in South America.

     

Copy number variations of 11 macronuclear chromosomes and their gene expression in Oxytricha trifallax

Genome-wide methylation studies frequently lack adequate controls to estimate proportions of background reads in the resulting datasets. To generate appropriate control pools, we developed technique termed nMETR (non-methylated tag recovery) based on digestion of genomic DNA with methylation-sensitive restriction enzyme, ligation of adapter oligonucleotide and PCR amplification of non-methylated sites associated with genomic repetitive elements. The protocol takes only two working days to generate amplicons for deep sequencing. We applied nMETR for human DNA using BspFNI enzyme and retrotransposon Alu-specific primers. 454-sequencing enabled identification of 1113 nMETR tag sites, of them ~65% were parts of CpG islands. Representation of reads inversely correlated with methylation levels, thus confirming nMETR fidelity. We created software that eliminates background reads and enables to map and annotate individual tags on human genome. nMETR tags may serve as the controls for large-scale epigenetic studies and for identifying unmethylated transposable elements located close to genomic CpG islands.