Extracellular vesicles from neural progenitor cells promote functional recovery after stroke in mice with pharmacological inhibition of neurogenesis.

Neural progenitor cells (NPCs) of the subventricular zone proliferate in response to ischemic stroke in the adult mouse brain. Newly generated cells have been considered to influence recovery following a stroke. However, the mechanism underlying such protection is a matter of active study since it has been thought that proliferating NPCs mediate their protective effects by secreting soluble factors that promote recovery rather than neuronal replacement in the ischemic penumbra.

Targeted gene delivery by new folate-polycationic amphiphilic cyclodextrin-DNA nanocomplexes in vitro and in vivo.

Aim: Development and evaluation of a new targeted gene delivery system by first preforming self-assembled nanocomplexes from a polycationic amphiphilic cyclodextrin (paCD) and pDNA and then decorating the surface of the nanoparticles with folic acid (FA).

Experimental Section: The cyclodextrin derivative (T2) is a tetradecacationic structure incorporating 14 primary amino groups and 7 thioureido groups at the primary face of a cyclomaltoheptaose (β-CD) core and 14 hexanoyl chains at the secondary face.

Results And Conclusions: T2 complexed and protected pDNA (luciferase-encoding plasmid DNA, pCMVLuc) and efficiently mediated transfection in vitro and in vivo with no associated toxicity.

Paralogous ALT1 and ALT2 retention and diversification have generated catalytically active and inactive aminotransferases in Saccharomyces cerevisiae.

Background: Gene duplication and the subsequent divergence of paralogous pairs play a central role in the evolution of novel gene functions. S. cerevisiae possesses two paralogous genes (ALT1/ALT2) which presumably encode alanine aminotransferases.

Polycationic amphiphilic cyclodextrin-based nanoparticles for therapeutic gene delivery.

Aim: In this study, a set of polycationic amphiphilic cyclodextrins featuring self-assembling capabilities in the presence of nucleic acids have been evaluated as therapeutic gene vectors for in vivo purposes.

Materials & Methods: A tetradecacationic structure incorporating 14 primary amino groups and 7 thioureido groups in the primary face of the cyclooligosaccharide core and 14 hexanoyl chains in the secondary face was judged to be optimal for therapeutic gene delivery.

Results & Conclusion: This compound efficiently mediated serum-resistant transfection in HeLa and HepG2 cells, comparing favorably with branched poly(ethyleneimine), with a low associated toxicity.

Saccharomyces cerevisiae Bat1 and Bat2 aminotransferases have functionally diverged from the ancestral-like Kluyveromyces lactis orthologous enzyme.

Background: Gene duplication is a key evolutionary mechanism providing material for the generation of genes with new or modified functions. The fate of duplicated gene copies has been amply discussed and several models have been put forward to account for duplicate conservation. The specialization model considers that duplication of a bifunctional ancestral gene could result in the preservation of both copies through subfunctionalization, resulting in the distribution of the two ancestral functions between the gene duplicates.

Gln3-Gcn4 hybrid transcriptional activator determines catabolic and biosynthetic gene expression in the yeast Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae is able to sense the availability and quality of nitrogen sources and the intrinsic variation of amino acid disponibility for protein synthesis. When this yeast is provided with secondary nitrogen sources, transcription of genes encoding enzymes involved in their catabolism is elicited through the action of Gln3, which constitutes the main activator of the Nitrogen Catabolite Repression network (NCR). Activation of genes encoding enzymes involved in the amino acid biosynthetic pathways is achieved through the action of the GCN4-encoded transcriptional modulator whose transcriptional activation is induced at the translational level by limitation for any amino acid.

Effect of alphas1-casein ( CSN1S1) genotype on milk CSN1S1 content in Malagueña and Murciano-Granadina goats.

There is substantial evidence showing that the polymorphism of the goat alphas1-casein (CSN1S1) gene has a major effect on milk protein, casein and fat content as well as on cheese yield. However, its influence on the synthesis rate of CSN1S1 has been less studied, with measurements only available in French breeds. In this article, we have measured milk CSN1S1 content in 89 Malagueña and 138 Murciano-Granadina goats with 305 and 460 phenotypic registers, respectively.

[Leprosy: control of household contacts in the municipality of Londrina-PR for a ten-year period].

The purpose of this descriptive study is to analyze variables related to leprosy patients' household contacts who received treatment in Londrina-PR-Brazil for a ten-year period. The data analysis was based on the health service's records and from a system of infectious disease. Out of 1055 leprosy's patients, it was recorded 3394 contacts with an average of 3,2.

Specialization of the paralogue LYS21 determines lysine biosynthesis under respiratory metabolism in Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, the first committed step of the lysine biosynthetic pathway is catalysed by two homocitrate synthases encoded by LYS20 and LYS21. We undertook a study of the duplicate homocitrate synthases to analyse whether their retention and presumable specialization have affected the efficiency of lysine biosynthesis in yeast. Our results show that during growth on ethanol, homocitrate is mainly synthesized through Lys21p, while under fermentative metabolism, Lys20p and Lys21p play redundant roles.

Gcn5p contributes to the bidirectional character of the UGA3-GLT1 yeast promoter.

Analysis of the UGA3-GLT1 bidirectional promoter has indicated that its transcriptional activation is determined by the combined action of Gcn4p and Gln3p, and that its bidirectional character is influenced by chromatin organization, through the action of an Abf1p binding site and a polydAdTtract. Results presented in this paper show that lack of Gcn5p impairs histone acetylation and nucleosomal organization of the UGA3-GLT1 promoter, resulting in an asymmetrical transcriptional activation response of UGA3 and GLT1. The phenotype displayed by a double mutant impaired in GCN5 and in the Abf1p binding site indicates that the combined action of these two elements determines the bidirectional capacity of the UGA3-GLT1 intergenic region.

The UGA3-GLT1 intergenic region constitutes a promoter whose bidirectional nature is determined by chromatin organization in Saccharomyces cerevisiae.

Transcription of an important number of divergent genes of Saccharomyces cerevisiae is controlled by intergenic regions, which constitute factual bidirectional promoters. However, few of such promoters have been characterized in detail. The analysis of the UGA3-GLT1 intergenic region has provided an interesting model to study the joint action of two global transcriptional activators that had been considered to act independently.

Swi/SNF-GCN5-dependent chromatin remodelling determines induced expression of GDH3, one of the paralogous genes responsible for ammonium assimilation and glutamate biosynthesis in Saccharomyces cerevisiae.

It is accepted that Saccharomyces cerevisiae genome arose from complete duplication of eight ancestral chromosomes; functionally normal ploidy was recovered because of the massive loss of 90% of duplicated genes. There is evidence that indicates that part of this selective conservation of gene pairs is compelling to yeast facultative metabolism. As an example, the duplicated NADP-glutamate dehydrogenase pathway has been maintained because of the differential expression of the paralogous GDH1 and GDH3 genes, and the biochemical specialization of the enzymes they encode.

Salt-dependent expression of ammonium assimilation genes in the halotolerant yeast, Debaryomyces hansenii.

Debaryomyces hansenii is adapted to grow in saline environments, accumulating high intracellular Na(+) concentrations. Determination of the DhGDH1-encoded NADP-glutamate dehydrogenase enzymatic activity showed that it increased in a saline environment. Thus, it was proposed that, in order to overcome Na(+) inhibition of enzyme activity, this organism possessed salt-dependent mechanisms which resulted in increased activity of enzymes pertaining to the central metabolic pathways.

Gcn4 negatively regulates expression of genes subjected to nitrogen catabolite repression.

It has been considered that three key elements participate in nitrogen catabolite repression (NCR) of Saccharomyces cerevisiae: the GLN3 and GAT1/NIL1-encoded transcriptional activators and their negative regulator Ure2. The fact that expression of various NCR-sensitive genes is not derepressed in the absence of Ure2 has led to the proposition that there must exist a protein with a similar function to that of Ure2. The results presented in this paper show that various NCR-sensitive genes are derepressed through GLN3-mediated transcriptional activation in a gcn4Delta mutant.

Pathways for glutamate biosynthesis in the yeast Kluyveromyces lactis.

Purified glutamate synthase (GOGAT) from Kluyveromyces lactis was characterized as a high-molecular-mass polypeptide, a distinction shared with previously described GOGATs from other eukaryotic micro-organisms. Using degenerate deoxyoligonucleotides, designed from conserved regions of the alfalfa, maize and Escherichia coli GOGAT genes, a 300 bp PCR fragment from the K. lactis GOGAT gene KIGLT1 was obtained.