Tau Phosphorylation, Aggregation, and Cell Toxicity

Protein aggregation takes place in many neurodegenerative disorders. However, there is a controversy about the possible toxicity of these protein aggregates. In this review, this controversy is discussed, focussing on the tau aggregation that takes place in those disorders known as tauopathies

High genetic variability of HIV-1 in female sex workers from Argentina

<p>Abstract</p> <p>Background</p> <p>A cross-sectional study on 625 Female Sex Workers (FSWs) was conducted between 2000 and 2002 in 6 cities in Argentina. This study describes the genetic diversity and the resistance profile of the HIV-infected subjects.</p> <p>Results</p> <p>Seventeen samples from HIV positive FSWs were genotyped by <it>env </it>HMA, showing the presence of 9 subtype F, 6 subtype B and 2 subtype C. Sequence analysis of the protease/RT region on 16 of these showed that 10 were BF recombinants, three were subtype B, two were subtype C, and one sample presented a dual infection with subtype B and a BF recombinant. Full-length genomes of five of the protease/RT BF recombinants were also sequenced, showing that three of them were CRF12_BF. One FSW had a dual HIV-1 infection with subtype B and a BF recombinant. The B sections of the BF recombinant clustered closely with the pure B sequence isolated from the same patient. Major resistance mutations to antiretroviral drugs were found in 3 of 16 (18.8%) strains.</p> <p>Conclusion</p> <p>The genetic diversity of HIV strains among FSWs in Argentina was extensive; about three-quarters of the samples were infected with diverse BF recombinants, near twenty percent had primary ART resistance and one sample presented a dual infection. Heterosexual transmission of genetically diverse, drug resistant strains among FSWs and their clients represents an important and underestimated threat, in Argentina.</p

Gene discovery in Triatoma infestans

Background: Triatoma infestans is the most relevant vector of Chagas disease in the southern cone of South America. Since its genome has not yet been studied, sequencing of Expressed Sequence Tags ( ESTs) is one of the most powerful tools for efficiently identifying large numbers of expressed genes in this insect vector. Results: In this work, we generated 826 ESTs, resulting in an increase of 47% in the number of ESTs available for T. infestans. These ESTs were assembled in 471 unique sequences, 151 of which represent 136 new genes for the Reduviidae family. Conclusions: Among the putative new genes for the Reduviidae family, we identified and described an interesting subset of genes involved in development and reproduction, which constitute potential targets for insecticide development

S-adenosylmethionine regulates MAT1A and MAT2A gene expression in cultured rat hepatocytes: a new role for S-adenosylmethionine in the maintenance of the differentiated status of the liver

Methionine metabolism starts with the formation of S-adenosylmethionine (AdoMet), the most important biological methyl donor. This reaction is catalyzed by methionine adenosyltransferase (MAT). MAT is the product of two different genes: MAT1A, which is expressed only in the adult liver, and MAT2A, which is widely distributed, expressed in the fetal liver, and replaces MAT1A in hepatocarcinoma. In the liver, preservation of high expression of MAT1A and low expression of MAT2A is critical for the maintenance of a functional and differentiated organ. Here we describe that in cultured rat hepatocytes MAT1A expression progressively decreased, as described for other liver-specific genes, and MAT2A expression was induced. We find that this switch in gene expression was prevented by adding AdoMet to the culture medium. We also show that in cultured hepatocytes with decreased MAT1A expression AdoMet addition markedly increased MAT1A transcription in a dose-dependent fashion. This effect of AdoMet was mimicked by methionine, and blocked by 3-deazaadenosine and L-ethionine, but not D-ethionine, indicating that the effect was specific and mediated probably by a methylation reaction. These findings identify AdoMet as a key molecule that differentially regulates MAT1A and MAT2A expression and helps to maintain the differentiated status of the hepatocyte

Extreme Bowen-York initial data

The Bowen-York family of spinning black hole initial data depends essentially on one, positive, free parameter. The extreme limit corresponds to making this parameter equal to zero. This choice represents a singular limit for the constraint equations. We prove that in this limit a new solution of the constraint equations is obtained. These initial data have similar properties to the extreme Kerr and Reissner-Nordstrom black hole initial data. In particular, in this limit one of the asymptotic ends changes from asymptotically flat to cylindrical. The existence proof is constructive, we actually show that a sequence of Bowen-York data converges to the extreme solution.Comment: 21 page

L-methionine availability regulates expression of the methionine adenosyltransferase 2A gene in human hepatocarcinoma cells: role of S-adenosylmethionine

In mammals, methionine adenosyltransferase (MAT), the enzyme responsible for S-adenosylmethionine (AdoMet) synthesis, is encoded by two genes, MAT1A and MAT2A. In liver, MAT1A expression is associated with high AdoMet levels and a differentiated phenotype, whereas MAT2A expression is associated with lower AdoMet levels and a dedifferentiated phenotype. In the current study, we examined regulation of MAT2A gene expression by l-methionine availability using HepG2 cells. In l-methionine-deficient cells, MAT2A gene expression is rapidly induced, and methionine adenosyltransferase activity is increased. Restoration of l-methionine rapidly down-regulates MAT2A mRNA levels; for this effect, l-methionine needs to be converted into AdoMet. This novel action of AdoMet is not mediated through a methyl transfer reaction. MAT2A gene expression was also regulated by 5'-methylthioadenosine, but this was dependent on 5'-methylthioadenosine conversion to methionine through the salvage pathway. The transcription rate of the MAT2A gene remained unchanged during l-methionine starvation; however, its mRNA half-life was significantly increased (from 100 min to more than 3 h). The effect of l-methionine withdrawal on MAT2A mRNA stabilization requires both gene transcription and protein synthesis. We conclude that MAT2A gene expression is modulated as an adaptive response of the cell to l-methionine availability through its conversion to AdoMet

Un caso de síndrome de mano ajena fronto-calloso

Setenes Jornades de Foment de la Investigació de la FCHS (Any 2001-2002)Diferentes estudios teóricos (Feinberg, y cols., 1992; Baynes y cols. 1997; Doody y Jankovic 1992) han mostrado que el síndrome de la mano ajena (Brion y Jedynak 1972) puede tener dos manifestaciones que son: mano ajena con afectación callosa y mano ajena de afectación fronto-callosa. Este estudio presenta el caso de una mujer de 63 años relacionado con este último síndrome. Ingresada por torpeza en miembros inferiores, alteración del habla, hemiparesia derecha y cefalea. Las técnicas de neuroimagen mostraron signos indirectos de infarto en la arteria cerebral anterior izquierda que afectaban al área motora suplementaria y el cuerpo calloso. Las pruebas neuropsicológicas evaluaron funciones de atención, lenguaje, memoria, gnosias, praxias y funciones ejecutivas. Los resultados de las pruebas indicaron déficits en distintas funciones cognitivas superiores entre las que destacaba el síndrome de utilización compulsiva de objetos. Para profundizar en el análisis de este síndrome se planteó un estudio Resonancia Magnética Funcional del que se desprende que el área premotora contralateral es la responsable de los movimientos de la mano ajena

Transformed but not normal hepatocytes express UCP2

Uncoupling protein 2 (UCP2) expression in liver is restricted to non-parenchymal cells. By means of differential display screening between normal rat liver and H4IIE hepatoma cells we have isolated a cDNA clone encompassing part of UCP2 cDNA. Northern blot analysis revealed that UCP2 is expressed in some hepatocarcinoma cell lines, while it is absent in adult hepatocytes. UCP2 mRNA in H4IIE cells was downregulated when cells were cultured for 36 h in 0.1% serum and its expression was restored upon addition of 10% serum or phorbol esters. Hypomethylation of UCP2 was observed in transformed UCP2 expressing cells. Our results indicate that UCP2 is expressed in some hepatocarcinoma cell lines and that serum components may participate in maintaining elevated UCP2 levels