The cinnamyl alcohol dehydrogenase gene family in Populus: phylogeny, organization, and expression

Background  

Lignin is a phenolic heteropolymer in secondary cell walls that plays a major role in the development of plants and their defense against pathogens. The biosynthesis of monolignols, which represent the main component of lignin involves many enzymes. The cinnamyl alcohol dehydrogenase (CAD) is a key enzyme in lignin biosynthesis as it catalyzes the final step in the synthesis of monolignols. The CAD gene family has been studied in Arabidopsis thaliana, Oryza sativa and partially in Populus. This is the first comprehensive study on the CAD gene family in woody plants including genome organization, gene structure, phylogeny across land plant lineages, and expression profiling in Populus.     

Anti-tubercular activity of ruthenium (II) complexes with polypyridines

A series of nine polypyridyl-ruthenium (II) complexes (N-ligands = 2,2'-bipyridines; 2,2'-6',2'-terpyridines, di-alkyloxy-2,2'-6,2-bipyridine-3,3'-di-carboxylates), were tested against Mycobacterium tuberculosis (MBT). The complex (11) showed remarkable activity against MBT as compared to other complexes, (1-10). The aquo ligand of complex (11), as opposed to other chloro and acetonitrile derivatives, appears to play a key role in the antitubercular potency of this new class of metal-based compounds.     

Red Wine Polyphenols Prevent Metabolic and Cardiovascular Alterations Associated with Obesity in Zucker Fatty Rats (Fa/Fa)

Background

Obesity is associated with increased risks for development of cardiovascular diseases. Epidemiological studies report an inverse association between dietary flavonoid consumption and mortality from cardiovascular diseases. We studied the potential beneficial effects of dietary supplementation of red wine polyphenol extract, Provinols™, on obesity-associated alterations with respect to metabolic disturbances and cardiovascular functions in Zucker fatty (ZF) rats.

Methodology/Principal Findings

ZF rats or their lean littermates received normal diet or supplemented with Provinols™ for 8 weeks. Provinols™ improved glucose metabolism by reducing plasma glucose and fructosamine in ZF rats. Moreover, it reduced circulating triglycerides and total cholesterol as well as LDL-cholesterol in ZF rats. Echocardiography measurements demonstrated that Provinols™ improved cardiac performance as evidenced by an increase in left ventricular fractional shortening and cardiac output associated with decreased peripheral arterial resistances in ZF rats. Regarding vascular function, Provinols™ corrected endothelial dysfunction in aortas from ZF rats by improving endothelium-dependent relaxation in response to acetylcholine (Ach). Provinols™ enhanced NO bioavailability resulting from increased nitric oxide (NO) production through enhanced endothelial NO-synthase (eNOS) activity and reduced superoxide anion release via decreased expression of NADPH oxidase membrane sub-unit, Nox-1. In small mesenteric arteries, although Provinols™ did not affect the endothelium-dependent response to Ach; it enhanced the endothelial-derived hyperpolarizing factor component of the response.

Conclusions/Significance

Use of red wine polyphenols may be a potential mechanism for prevention of cardiovascular and metabolic alterations associated with obesity.     

Comparative and phylogenomic analyses of cinnamoyl-CoA reductase and cinnamoyl-CoA-reductase-like gene family in land plants

The biosynthesis of monolignols, the main components of lignin, involves many intermediates and enzymes. The cinnamoyl-CoA reductase (CCR) enzyme catalyzes the conversion of cinnamoyl-CoAs to cinnamaldehydes, i.e. the first specific step in lignin synthesis. The CCR and CCR-like gene family was studied partially in several plant species. This is a comprehensive study of the CCR and CCR-like gene family including genome organization, gene structure, phylogeny across land plant species, and, expression profiling in Populus. Analysis of amino acid motifs enabled the identification of sequence variations in the CCR catalytic site and annotates CCR and CCR-like genes. CCR and CCR-like genes were distributed in three major phylogenetic classes of which one includes the bona fide CCR genes. The other two classes include CCR and CCR-like, of which several genes present a high similarity to cinnamyl alcohol dehydrogenase, or dihydroflavonol reductase (DFR) genes. All CCR, CCR-like, and DFR classes were deeply rooted in the phylogeny of land plants suggesting that their evolution preceded the evolution of lycophytes. Over two thirds of CCR and CCR-like Populus genes were physically distributed on duplicated regions. This suggests that these duplication/retention processes contributed significantly to the size of the CCR and CCR-like gene family. The Populus CCR and CCR-like genes showed six expression patterns in the tissues studied with a preferential expression of PoptrCCR12 in xylem. The other genes present divergent expression profiles with some preferentially expressed in leaves, bark, or both. Several CCR and CCR-like genes were induced or repressed under various abiotic stresses suggesting that their duplication was followed by the evolution of divergent expression profiles and divergence of functions.     

Clonotype and repertoire changes drive the functional improvement of HIV-specific CD8 T cell populations under conditions of limited antigenic stimulation

Persistent exposure to cognate Ag leads to the functional impairment and exhaustion of HIV-specific CD8 T cells. Ag withdrawal, attributable either to antiretroviral treatment or the emergence of epitope escape mutations, causes HIV-specific CD8 T cell responses to wane over time. However, this process does not continue to extinction, and residual CD8 T cells likely play an important role in the control of HIV replication. In this study, we conducted a longitudinal analysis of clonality, phenotype, and function to define the characteristics of HIV-specific CD8 T cell populations that persist under conditions of limited antigenic stimulation. Ag decay was associated with dynamic changes in the TCR repertoire, increased expression of CD45RA and CD127, decreased expression of programmed death-1, and the emergence of polyfunctional HIV-specific CD8 T cells. High-definition analysis of individual clonotypes revealed that the Ag loss-induced gain of function within HIV-specific CD8 T cell populations could be attributed to two nonexclusive mechanisms: 1) functional improvement of persisting clonotypes; and 2) recruitment of particular clonotypes endowed with superior functional capabilities.     

Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA

Replication of human cytomegalovirus (CMV) requires the expression of the viral mitochondria-localized inhibitor of apoptosis (vMIA). vMIA inhibits apoptosis by recruiting Bax to mitochondria, resulting in its neutralization. We show that vMIA decreases cell size, reduces actin polymerization, and induces cell rounding. As compared with vMIA-expressing CMV, vMIA-deficient CMV, which replicates in fibroblasts expressing the adenoviral apoptosis suppressor E1B19K, induces less cytopathic effects. These vMIA effects can be separated from its cell death-inhibitory function because vMIA modulates cellular morphology in Bax-deficient cells. Expression of vMIA coincided with a reduction in the cellular adenosine triphosphate (ATP) level. vMIA selectively inhibited one component of the ATP synthasome, namely, the mitochondrial phosphate carrier. Exposure of cells to inhibitors of oxidative phosphorylation produced similar effects, such as an ATP level reduced by 30%, smaller cell size, and deficient actin polymerization. Similarly, knockdown of the phosphate carrier reduced cell size. Our data suggest that the cytopathic effect of CMV can be explained by vMIA effects on mitochondrial bioenergetics.     

The decreased susceptibility of Bcr/Abl targets to NK cell-mediated lysis in response to imatinib mesylate involves modulation of NKG2D ligands, GM1 expression, and synapse formation

Chronic myeloid leukemia is a clonal multilineage myeloproliferative disease of stem cell origin characterized by the presence of the Bcr/Abl oncoprotein, a constitutively active tyrosine kinase. In previous studies, we have provided evidence that Bcr/Abl overexpression in leukemic cells increased their susceptibility to NK-mediated lysis by different mechanisms. In the present study, using UT-7/9 cells, a high level Bcr/Abl transfectant of UT-7 cells, we show that the treatment of Bcr/Abl target by imatinib mesylate (IM), a specific Abl tyrosine kinase inhibitor, hampers the formation of the NK/target immunological synapse. The main effect of IM involves an induction of surface GM1 ganglioside on Bcr/Abl transfectants that prevents the redistribution of MHC-related Ag molecules in lipid rafts upon interaction with NK cells. IM also affects cell surface glycosylation of targets, as assessed by binding of specific lectins resulting in the subsequent modulation of their binding to lectin type NK receptor, particularly NKG2D. In addition, we demonstrate that the tyrosine kinase activity repression results in a decrease of MHC-related Ags-A/B and UL-16-binding protein expression on Bcr/Abl transfectants UT-7/9. We show that NKG2D controls the NK-mediated lysis of UT-7/9 cells, and IM treatment inhibits this activating pathway. Taken together, our results show that the high expression of Bcr/Abl in leukemic cells controls the expression of NKG2D receptor ligands and membrane GM1 via a tyrosine kinase-dependent mechanism and that the modulation of these molecules by IM interferes with NK cell recognition and cytolysis of the transfectants.