Surgical treatment of transposition of great arteries with ventricular septal defect and left ventricular outflow tract obstruction: midterm results.

Our purpose was to evaluate our single-center experience with the treatment of transposition of the great arteries (TGA) with ventricular septal defect (VSD) and left ventricular outflow tract obstruction (LVOTO). Between 1992 and 2009, 42 patients were operated on. Twenty-three patients underwent the Rastelli operation, 8 patients underwent arterial switch operation (ASO) with associated LVOTO procedures, 4 patients underwent the réparation à l'étage ventriculaire (REV) procedure, 3 patients underwent the Bex/Nikaidoh (BN) procedure, and the Fontan operation was performed in 4 patients. The median age at final operation was 20.7 months (range, 0.3-234). The overall survival rate was 97% (1 early death), with a median follow-up of 8.2 years. There were no differences in survival among the surgical groups. Event-free survival was 100%, 84%, 59%, and 24% at 1, 5, 10, and 15 years of follow-up, respectively, with it being worse in the Rastelli group (P < .0348). The last echocardiography showed good function of the systemic ventricle in all patients; LVOTO pressure gradient greater than 30 mm Hg was observed in 2 patients (5%), and right ventricular outflow tract obstruction (RVOTO) pressure gradient >30 mm Hg was observed in 12 patients (31%). All patients are in sinus rhythm, and 74% of them are without medication. All surgical approaches are safe and show excellent midterm functional outcome. ASO is the best option if the LVOTO is resectable. Intraventricular rerouting (Rastelli or REV) is the method of choice in the majority of patients, but Rastelli has a significant reintervention rate. The BN operation has the potential to minimize utilization of the Fontan operation, which was used in the past if the intracardiac anatomy was unfavorable.

A root-expressed magnesium transporter of the MRS2/MGT gene family in Arabidopsis thaliana allows for growth in low-Mg2+ environments.

The MRS2/MGT gene family in Arabidopsis thaliana belongs to the superfamily of CorA-MRS2-ALR-type membrane proteins. Proteins of this type are characterized by a GMN tripeptide motif (Gly-Met-Asn) at the end of the first of two C-terminal transmembrane domains and have been characterized as magnesium transporters. Using the recently established mag-fura-2 system allowing direct measurement of Mg(2+) uptake into mitochondria of Saccharomyces cerevisiae, we find that all members of the Arabidopsis family complement the corresponding yeast mrs2 mutant. Highly different patterns of tissue-specific expression were observed for the MRS2/MGT family members in planta. Six of them are expressed in root tissues, indicating a possible involvement in plant magnesium supply and distribution after uptake from the soil substrate. Homozygous T-DNA insertion knockout lines were obtained for four members of the MRS2/MGT gene family. A strong, magnesium-dependent phenotype of growth retardation was found for mrs2-7 when Mg(2+) concentrations were lowered to 50 microM in hydroponic cultures. Ectopic overexpression of MRS2-7 from the cauliflower mosaic virus 35S promoter results in complementation and increased biomass accumulation. Green fluorescent protein reporter gene fusions indicate a location of MRS2-7 in the endomembrane system. Hence, contrary to what is frequently found in analyses of plant gene families, a single gene family member knockout results in a strong, environmentally dependent phenotype.

Illumination is necessary and sufficient to induce histone acetylation independent of transcriptional activity at the C4-specific phosphoenolpyruvate carboxylase promoter in maize.

Expression of the C4-specific phosphoenolpyruvate carboxylase (C4-PEPC) gene in maize (Zea mays) is regulated in a tissue-specific manner, but affected by light and nutrient availability. We manipulated these stimuli in a combinatorial manner and analyzed concomitant changes in histone acetylation of the nucleosomes associated with the C4-PEPC gene in relation to transcriptional activity and steady-state mRNA levels. Whereas the transition from the lowest activity to an intermediate activity was observed in the absence of histone acetylation, the light-induced boost to full activity was associated with strong enhancement of the acetylation of both histones H3 and H4 limited to the gene region. Once activated by light, prolonged darkness was necessary to reduce both transcription and, in parallel, histone acetylation. Unexpectedly, histone acetylation was also induced in bundle sheath cells, although the transcriptional activity did not respond to illumination in this tissue. Furthermore, we were able to down-regulate the promoter by nitrogen depletion in the light without any decrease in the hyperacetylation of histone H4. When plants kept in prolonged darkness were nitrogen depleted and then exposed to light, transcription was not induced, but the promoter chromatin became hyperacetylated. We suggest a model where inhibition of a histone deacetylase in the light triggers H4 hyperacetylation at the C4-PEPC gene promoter regardless of the transcriptional activity of the gene. Our data indicate that an understanding of the interplay between histone modification and transcription requires analysis of signal integration on promoters in vivo.

Transport of magnesium and other divalent cations: evolution of the 2-TM-GxN proteins in the MIT superfamily.

In bacteria, magnesium uptake is mainly mediated by the well-characterized CorA type of membrane proteins. In recent years, functional homologues have been characterized in the inner mitochondrial membrane of yeast and mammals (the MRS2/LPE10 type), in the plasma membrane of yeast (the ALR/MNR type) and, as an extended family of proteins, in the model plant Arabidopsis thaliana. Despite generally low sequence similarity, individual proteins can functionally complement each other over large phylogenetic distances. All these proteins are characterized by a universally conserved Gly-Met-Asn (GMN) motif at the end of the first of two conserved transmembrane domains near the C-terminus. Mutations of the GMN motif are known to abolish Mg(2+) transport, but the naturally occurring variants GVN and GIN may be associated with the transport of other divalent cations, such as zinc and cadmium, respectively. We refer to this whole class of proteins as the 2-TM-GxN type. The functional membrane channel is thought to be formed by oligomers containing four or five subunits. The wealth of sequence data now available allows us to explore the evolutionary diversification of the basic 2-TM-GxN model within the so-called metal ion transporter (MIT) superfamily. Here we report phylogenetic analyses on more than 360 homologous protein sequences derived from genomic sequences from representatives of all three domains of life. Independent gene duplications have occurred in fungi, plants and proteobacteria at different phylogenetic depths. Moreover, there is ample evidence for several instances of horizontal gene transfer of members of the 2-TM-GxN superfamily in Eubacteria and Archaea. Only single genes of the MRS2 type have been identified in vertebrate genomes. In contrast, 15 members are found in the model plant Arabidopsis thaliana, which appear to have arisen by at least four independent founder events before the diversification of flowering plants. Phylogenetic clade assignment seems to correlate with alterations in the highly conserved sequence around the GMN motif. This presumably forms an integral part of the pore surface, and changes in its structure may result in altered transport capacities for different divalent cations.