Soluble and membrane-bound interleukin (IL)-15 Rα/IL-15 complexes mediate proliferation of high-avidity central memory CD8 T cells for adoptive immunotherapy of cancer and infections.

The lack of persistence of infused T cells is a principal limitation of adoptive immunotherapy in man. Interleukin (IL)-15 can sustain memory T cell expansion when presented in complex with IL-15Rα (15Rα/15). We developed a novel in-vitro system for generation of stable 15Rα/15 complexes.

Retinol as a cofactor for PKCδ-mediated impairment of insulin sensitivity in a mouse model of diet-induced obesity.

We previously defined that the mitochondria-localized PKCδ signaling complex stimulates the conversion of pyruvate to acetyl-coenzyme A by the pyruvate dehydrogenase complex. We demonstrated in vitro and ex vivo that retinol supplementation enhances ATP synthesis in the presence of the PKCδ signalosome. Here, we tested in vivo if a persistent oversupply of retinol would further impair glucose metabolism in a mouse model of diet-induced insulin resistance.

Cholesteryl ester diffusion, location and self-association constraints determine CETP activity with discoidal HDL: excimer probe study.

The transfer of cholesteryl ester by recombinant cholesteryl ester transfer protein (CETP) between reconstituted discoidal high-density lipoprotein (rHDL) was studied. Particles contained apolipoprotein A-I, unsaturated POPC or saturated DPPC and cholesteryl ester as cholesteryl 1-pyrenedecanoate (CPD) or cholesteryl laurate (CL) in donor and acceptor rHDL, respectively. Probe dynamics fulfilled the quenching sphere-of-action model.

Two protein kinase C isoforms, δ and ε, regulate energy homeostasis in mitochondria by transmitting opposing signals to the pyruvate dehydrogenase complex.

Energy production in mitochondria is a multistep process that requires coordination of several subsystems. While reversible phosphorylation is emerging as the principal tool, it is still unclear how this signal network senses the workloads of processes as different as fuel procurement, catabolism in the Krebs cycle, and stepwise oxidation of reducing equivalents in the electron transfer chain. We previously proposed that mitochondria use oxidized cytochrome c in concert with retinol to activate protein kinase Cδ, thereby linking a prominent kinase network to the redox balance of the ETC.

Insights into the molecular mechanisms of the anti-atherogenic actions of flavonoids in normal and obese mice.

Obesity is a major and independent risk factor for cardiovascular disease and it is strongly associated with the development of dyslipidemia, insulin resistance and type 2 diabetes. Flavonoids, a diverse group of polyphenol compounds of plant origin widely distributed in human diet, have been reported to have numerous health benefits, although the mechanisms underlying these effects have remained obscure. We analyzed the effects of chronic dietary supplementation with flavonoids extracted from cranberry (FLS) in normal and obese C57/BL6 mice compared to mice maintained on the same diets lacking FLS.

Composition, structure and substrate properties of reconstituted discoidal HDL with apolipoprotein A-I and cholesteryl ester.

To investigate the influence of lipid unsaturation and neutral lipid on the maturation of high density lipoproteins, the discoidal complexes of apoA-I, phosphatidylcholine and cholesteryl ester (CE) were prepared. Saturated dipalmitoylphosphatidylcholine (DPPC) and unsaturated palmitoyllinoleoylphosphatidylcholine (PLPC), palmitoyloleoylphosphatidylcholine (POPC), and fluorescent probe cholesteryl 1-pyrenedecanoate (CPD) that forms in a diffusion- and concentration-dependent manner short-lived dimer of unexcited and excited molecules (excimer) were used. The apoA-I/DPPC/CPD complexes were heterogeneous by size, composition and probe location.

Serum retinol-binding protein 4 (RBP4) and retinol in a cohort of borderline obese women with and without gestational diabetes.

Objectives: To evaluate whether serum RBP4 correlates with gestational diabetes mellitus (GDM) in a cohort of borderline obese (BMI>30) pregnant women.

Design And Methods: Serum RBP4 and retinol were measured in pregnant women with (n=12) and without (n=10) GDM.

Results: RBP4, retinol and RBP4:retinol molar ratio were not different between the groups and were not associated with markers of insulin resistance.

Hepatic retinol secretion and storage are altered by dietary CLA: common and distinct actions of CLA c9,t11 and t10,c12 isomers.

Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid obtained from ruminant products. Previous studies in rats and pigs showed that a dietary equimolar mixture of c9,t11 and t10,c12 CLA isomers induces changes in serum and tissue levels of retinoids (vitamin A derivatives). However, the mechanism(s) responsible for these actions remain(s) unexplored.

Allosteric control of the RNA polymerase by the elongation factor RfaH.

Efficient transcription of long polycistronic operons in bacteria frequently relies on accessory proteins but their molecular mechanisms remain obscure. RfaH is a cellular elongation factor that acts as a polarity suppressor by increasing RNA polymerase (RNAP) processivity. In this work, we provide evidence that RfaH acts by reducing transcriptional pausing at certain positions rather than by accelerating RNAP at all sites.

Comparative functional analysis of human medium-chain dehydrogenases, short-chain dehydrogenases/reductases and aldo-keto reductases with retinoids.

Retinoic acid biosynthesis in vertebrates occurs in two consecutive steps: the oxidation of retinol to retinaldehyde followed by the oxidation of retinaldehyde to retinoic acid. Enzymes of the MDR (medium-chain dehydrogenase/reductase), SDR (short-chain dehydrogenase/reductase) and AKR (aldo-keto reductase) superfamilies have been reported to catalyse the conversion between retinol and retinaldehyde. Estimation of the relative contribution of enzymes of each type was difficult since kinetics were performed with different methodologies, but SDRs would supposedly play a major role because of their low K(m) values, and because they were found to be active with retinol bound to CRBPI (cellular retinol binding protein type I).

DNA diversity of human populations from Eastern Europe and Siberia studied by multilocus DNA fingerprinting.

We used DNA fingerprinting with M13 phage DNA as a probe to estimate the degree of genomic variability and genetic relationships in a heterogeneous group of 13 populations from Eastern Europe and Siberia. The popultaions belong to three language families: Indo-European (Slavonic: Russians, Byelorussians), Uralic (Finno-Ugric: Maris, Mordvinians, Udmurts), and Altaic (Turkic: Bashkirs, Tatars, Chuvashes, Yakuts). Multivariate statistical analyses were used (multidimensional scaling, cluster, and multiple correspondence analyses), and coefficients of gene differentiation ( Gst') were evaluated.

[Differentiation of closely related and distant human populations by multilocus DNA fingerprinting].

Using multilocus DNA fingerprinting with phage M13 DNA as a probe, we have investigated a heterogeneous group of four human populations from Eastern Europe and Northeastern Asia. These populations belong to two language families: Indo-European (Eastern Slavonic branch: Russians, Belarussians) and Altaian (Turkic branch: Yakuts). The experimental results were treated by different statistical techniques: cluster analysis, multidimensional scaling, and multiple correspondence analysis.

[Genetic and demographic structure of the yakut population: reproduction indices].

Genetic and demographic information for the Yakut population living in the Republic of Sakha (Yakutia) is presented. The mean number of children per woman constituted 4.605.

[Multiloci DNA fingerprinting in population studies: primary analysis of blot-hybridization results].

The principles of primary treatment of blot-hybridization patterns obtained by means of multilocus DNA fingerprinting method are suggested. Final results, represented as a matrix of fragment sizes, are characterized by sufficiently high fidelity and reproducibility.

[Methodologic aspects of genomic fingerprinting in population studies].

Use of DNA fingerprinting in population studies is complicated by a number of methodical problems caused by the necessity to work with a large amount of experimental data and insufficient reproducibility of the results. In this work, possible approaches to overcome methodical difficulties faced by the authors during elaboration of the experimental technique are discussed.