Gene Expression and Immunohistochemistry in Adipose Tissue of HIV Type 1-Infected Patients with Nucleoside Analogue Reverse-Transcriptase Inhibitor-Associated Lipoatrophy

BackgroundLong-term use of both zidovudine (AZT) and stavudine (d4T) is associated with lipoatrophy, but it occurs possibly through different mechanisms MethodsSurgical biopsy specimens of subcutaneous adipose tissue were obtained from 18 human immunodeficiency virus type 1 (HIV-1)-infected lipoatrophic patients (the LA+ group) who were treated with either zidovudine (the AZT+LA+ group; n=10) or stavudine (the d4T+LA+ group; n=8) and from 10 nonlipoatrophic HIV-1-infected patients (the LA− group) who received antiretroviral therapy. Mitochondrial DNA (mtDNA) copy numbers, gene expression, and immunohistochemistry data were analyzed ResultsmtDNA copy numbers were significantly reduced in the LA+ group, compared with the LA− group, and in the d4T+LA+ group, compared with the AZT+LA+ group. The ratio of mtDNA-encoded cytochrome COX3 to nuclear DNA-encoded COX4 expression was significantly lower in the LA+ group than in the LA− group. Compared with the LA− group, the LA+ group had significantly lower expression of genes involved in adipogenesis (SREBP1cand CEBPB) lipid (fatty acid synthase), and glucose (GLUT4) metabolism. Expression of genes involved in mitochondrial biogenesis (PGC1B) apoptosis (FAS) inflammation (IL1B) oxidative stress (PCNA and SOD1) and lamin B was significantly higher in the LA+ group than in the LA− group. The d4T+LA+ group had significantly lower expression of genes involved in mitochondrial biogenesis (POLG1) energy metabolism (the COX3/COX4 ratio), adipogenesis (SREBP1c and CEBPA) perilipin, and hexokinase than did the AZT+LA+ group. There were 7-fold more macrophages in adipose tissue specimens obtained from patients in the LA+ group, compared with the LA− group ConclusionsLipoatrophy is characterized by mtDNA depletion, inflammation, and signs of apoptosis. Changes were more profound in the d4T+LA+ group than in the AZT+LA+ grou

A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes: The EPIC-InterAct case-cohort study.

BACKGROUND: Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated. METHODS AND FINDINGS: We measured plasma phospholipid fatty acids by gas chromatography in 27,296 adults, including 12,132 incident cases of T2D, over the follow-up period between baseline (1991-1998) and 31 December 2007 in 8 European countries in EPIC-InterAct, a nested case-cohort study. The first principal component derived by principal component analysis of 27 individual fatty acids (mole percentage) was the main exposure (subsequently called the fatty acid pattern score [FA-pattern score]). The FA-pattern score was partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated fatty acids and low concentrations of γ-linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids, and it explained 16.1% of the overall variability of the 27 fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifth of the score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19-0.29) adjusted for potential confounders and 0.37 (95% CI 0.27-0.50) further adjusted for metabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and was positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p < 0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding. CONCLUSIONS: A combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors

Келейные книги патриарха Никона в Ферапонтовом монастыре

The first reconstruction of patriarch Nikon’s library in exile, in the Ferapontov Monastery, on the basis of materials of the “case” of patriarch Nikon. The composition of the Nikon’s Cell Book collection has allowed to reveal the influence of separate books and some works on the content of Nikon correspondence with his contemporaries, and also one of the reasons of the disgraced patriarch conflicts with the northern monasteries authorities.На основе документов «дела» патриарха Никона впервые реконструируется его библиотека в ссылке, в Ферапонтовом монастыре. Состав келейного книжного собрания владыки позволил выявить влияние отдельных книг и некоторых сочинений на содержание переписки Никона с современниками, а также одну из причин конфликтов опального патриарха с властями северных монастырей

STRUCTURE FEATURES OF THE SODIUM-GERMANATE GLASSES DOPED WITH YTTERBIUM ERBIUM RETRIEVED FROM RAMAN SPECTROSCOPY

Subject of Research.The paper deals with study of Raman spectra and luminescence spectra in the visible region of the sodium-germanate glass: 49 GeO2 – 13 Na2O – 27 Yb2O3 – 11 La2O3 - 0,25 Er2O3 and presents research results. In addition, this glass is doped with 5 mol% of the following components MgO, BaO, Al2O3, PbO, Nb2O5, TiO2, SiO2, P2O5 in order to study the effect of these additives on the structure of the glassy matrix and the anti-Stokes luminescence spectra of erbium ions. Method. Raman scatteringspectra were recorded by Renishaw inVia Raman Microscope. Excitation source is a helium neon laser (λ= 633 nm) with power equal to 50Wt. Anti-Stokes luminescence of erbium ions was registered in spectral region of 450–750 nm at room temperature (excitation laser wavelength is 975 nm, power is 1Wt). Main Results. It was shown that the structure of the initial glass does not change with the introduction of niobium as Nb2O5 in any coordination plays a role of network forming, building a single mixed grid with tetrahedrons [GeO4]. Introduction of the second glass former P2O5 leads to loosening germanate structure due to the appearance of the phosphate sublattice. This leads to a redistribution of the relative intensity of up-conversion luminescence bands with maxima at 540 and 670 nm compared with the initial glass. Introduction of additives PbO, MgO, Al2O3, TiO2 results in a multicenter structure. In case of titanium oxide addition it leads to a change in the relative intensities of the erbium luminescence