Mitochondrial death protein Nix is induced in cardiac hypertrophy and triggers apoptotic cardiomyopathy

Loss of cardiomyocytes through programmed cell death is a key event in the development of heart failure, but the inciting molecular mechanisms are largely unknown. We used microarray analysis to identify a genetic program for myocardial apoptosis in Gq-mediated and pressure-overload cardiac hypertrophy. A critical component of this apoptotic program was Nix/Bnip3L. Nix localized to mitochondria and caused release of cytochrome c, activation of caspase-3 and apoptotic cell death, when expressed in HEK293 fibroblasts. A previously undescribed truncated Nix isoform, termed sNix, was not targeted to mitochondria but heterodimerized with Nix and protected against Nix-mediated apoptosis. Forced in vivo myocardial expression of Nix resulted in apoptotic cardiomyopathy and rapid death. Conversely, sNix protected against apoptotic peripartum cardiomyopathy in G(alpha)q-overexpressors. Thus, Nix/Bnip3L is upregulated in myocardial hypertrophy, and is both necessary and sufficient for Gq-mediated apoptosis of cardiomyocytes and resulting hypertrophy decompensation.     

Bacterial interactions with the autophagic pathway

Bacteria have evolved a variety of mechanisms to invade eukaryotic cells and survive intracellularly. Once inside, bacterial pathogens often modulate their phagosome to establish an intracellular niche for survival and replication. A subset of intracellular pathogens, including Brucella abortus, Legionella pneumophila and Porphyromonas gingivalis, are diverted from the endosomal pathway to the auto-phagic pathway. Once within the autophagosome, each in some way presumably modifies this compartment to establish an environment necessary for its survival. Transit into autophagosomes represents an avenue by which to escape host defences. In this review, we examine the biochemical and morphological evidence for the survival of some bacterial pathogens by replicating within an autophagosome-like compartment.     

Beta 1-adrenergic receptor polymorphisms confer differential function and predisposition to heart failure

Catecholamines stimulate cardiac contractility through beta(1)-adrenergic receptors (beta(1)-ARs), which in humans are polymorphic at amino acid residue 389 (Arg/Gly). We used cardiac-targeted transgenesis in a mouse model to delineate mechanisms accounting for the association of Arg389 with human heart failure phenotypes. Hearts from young Arg389 mice had enhanced receptor function and contractility compared with Gly389 hearts. Older Arg389 mice displayed a phenotypic switch, with decreased beta-agonist signaling to adenylyl cyclase and decreased cardiac contractility compared with Gly 389 hearts. Arg389 hearts had abnormal expression of fetal and hypertrophy genes and calcium-cycling proteins, decreased adenylyl cyclase and G alpha(s) expression, and fibrosis with heart failure This phenotype was recapitulated in homozygous, end-stage, failing human hearts. In addition, hemodynamic responses to beta-receptor blockade were greater in Arg389 mice, and homozygosity for Arg389 was associated with improvement in ventricular function during carvedilol treatment in heart failure patients. Thus the human Arg389 variant predisposes to heart failure by instigating hyperactive signaling programs leading to depressed receptor coupling and ventricular dysfunction, and influences the therapeutic response to beta-receptor blockade.     

Linear polyethylenimine as a tool for comparative studies of antisense and short double-stranded RNA oligonucleotides

Despite the recently enlarged field of available RNA knock-down technologies, e.g., antisense oligonucleotides (ASOs) and duplexes of synthetic 21 nucleotides RNAs (siRNAs), no versatile transfection reagent has been reported to deliver different nucleic acids formats at high rates of efficiency. We have evaluated the versatility and efficacy of linear PEI in transfecting and properly delivering a broad panel of nucleic acids such as short oligonucleotides and double-stranded RNA into cells in culture.     

20-Hydroxyecdysone-induced differentiation and apoptosis in the Drosophila cell line, l(2)mbn

20-Hydroxyecdysone has an inhibitory effect on the proliferation of l(2)mbn cells, causes vacuolization and fragmentation of cells, and promotes a strong phagocytotic activity. From several lines of evidence, it can be concluded that 20-hydroxyecdysone induces apoptosis. Long-term video observations following the fate of individual cells, scanning and transmission electron microscopy reveal the typical characteristics of apoptosis: sequestration of small cellular protuberances or larger parts of the cell with nuclear fragments (apoptotic bodies), chromatin condensation, condensation and vesiculation of cytoplasm, whereas the mitochondria retain their normal appearance. The induction of apoptosis by 20-hydroxyecdysone was confirmed by the TUNEL reaction and quantitatively determined by a method based on this reaction. Onset of apoptosis precedes phagocytotic activity. JH III alone has no clear-cut effect on l(2)mbn cells. In double treatments, the inhibitory effect of 20-hydroxyecdysone on cell proliferation is significantly reduced by the addition of JH III. Whether or not JH III also reduces apoptotic activity is not yet clear. It is shown that the l(2)mbn cell line is an advantageous model system for the exploration of steroid-induced apoptosis.     

A taxonomic study of Salix section Longifoliae (Salicaceae)

Salix section Longifoliae occurs from Alaska to Guatemala and from the Atlantic to the Pacific. Nine taxa are here accepted as five species with one of the species including two subspecies and four varieties. the holotype of Salix taxifolia Humb., Bonpl. & Kunth represents the same taxon as the lectotype of Salix microphylla Schltdl. & Cham. Material recently called S. taxifolia is given a new name. Salix exilifolia Dorn. The name Salix fluviatilis Nutt is considered to be synonymous with S. melanopsis Nutt. One new variety is described and two new combinations are made under Salix exigua Nutt.     

A web server to locate periodicities in a sequence

Summary : FT is a tool written in C++, which implements the Fourier analysis method to locate periodicities in aminoacid or DNA sequences. It is provided for free public use on a WWW server with a Java interface. Availability : The server address is http://o2.db. uoa.gr/FT Contact : shamodr@atlas.uoa.gr      

The comparative antimalarial properties of weak base and neutral synthetic ozonides

Thirty-three N-acyl 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. For these ozonides, weak base functional groups were not required for high antimalarial potency against Plasmodium falciparum in vitro, but were necessary for high antimalarial efficacy in Plasmodium berghei-infected mice. A wide range of Log P/D_{pH 7.4} values were tolerated, although more lipophilic ozonides tended to be less metabolically stable.     

Early‐Season Headspace Volatiles from Apple and Their Effect on the Apple Blossom Weevil Anthonomus pomorum

Apple volatiles emitted at early phenological stages are little investigated, although they may influence behavior of early‐season pests. The apple blossom weevil Anthonomus pomorum is a herbivore pest of orchards in Europe. It colonizes apple trees in early season and oviposits into developing flower buds, often leading to economic damage. Using in situ radial diffusive sampling and thermal desorption, followed by GC/MS analysis, headspace volatiles from apple twigs with flower buds at three early phenological tree stages were identified and quantified. The volatile blend consisted of 13 compounds for the first, and increased to 15 compounds for the third phenological stage sampled. These blends included benzenoids, terpenes, and derivatives of fatty acids. A recombined synthetic blend served as the odor source in a still‐air dual‐choice olfactometer bioassay, in which individual male and female weevils were tested. Results from this behavioral test document an attraction of both sexes to odors of their host plant, suggesting that apple volatiles emitted in early season serve as olfactory cues for host location of A. pomorum in the field.