d=3 random field behavior near percolation

The highly diluted antiferromagnet Mn(0.35)Zn(0.65)F2 has been investigated by neutron scattering for H>0. A low-temperature (T<11K), low-field (H<1T) pseudophase transition boundary separates a partially antiferromagnetically ordered phase from the paramagnetic one. For 1<H<7T at low temperatures, a region of antiferromagnetic order is field induced but is not enclosed within a transition boundary.Comment: 9 pages, 4 figure

Food intake regulation during pregnancy and lactation in mice with reduced activity of the melanocortin system

Hypothalamic melanortin receptor (MCR) activation inhibits appetite. Neuropeptide Y (NPY) and Agouti Related Protein (AgRP) are coexpressed in some hypothalamic neurons and stimulate feeding, NPY via inhibition of MCR-expressing neurons, and AgRP via MCR4 antagonism. Mutation yellow at the mouse agouti locus (Ау) evokes MCR blockage and stimulates appetite in nulliparous females. The role of MCRs in food intake regulation during pregnancy and lactation is unclear. In this study we measured hypothalamic AgRP and NPY mRNA levels in virgin and mated C57Bl a/a (control) and Ау/a females on days 7, 13, 18 of pregnancy, 10, 21 of lactation, and after offspring separation, AgRP immunoreactivity in virgin and lactating females, and correlated gene expression with food intake (FI). Virgin Ау/a compared to a/a females had higher FI and lower AgRP expression. Pregnant Ау/a and a/a mice showed different patterns of food intake and neuropeptide expressions. NPY mRNA levels increased during pregnancy only in a/a mice, while AgRP mRNA levels increased in both genotypes being lower in Ау/a then in a/a mice. In lactating Ау/a and a/a mice, AgRP expression and NPY mRNA level were similar. AgRP expression was higher in lactating then in virgin Ау/a mice. The results obtained demonstrate that in nonbreeding female mice, MCR blockage is associated with AgRP expression inhibition which vanishes in lactation. In lactation, hyperphagia is independent of MCR blockage. In pregnancy, food intake regulation involves MCR signaling and activation of NPY and AgRP expression

Sex differences in the expression of lipid oxidation and glucose uptake genes in muscles of fasted mice

Fasting has become increasingly popular for treatment and prevention of obesity. Sex differences in the mechanisms of adaptation to fasting may contribute to choosing a therapeutic strategy for correction of metabolic disorders. Hepatokine fibroblast growth factor 21 (FGF21) is involved in the adaptation to fasting. Muscles are assumed to be the main energy-consuming tissue in the body, as muscle metabolism plays an important role in the adaptation to nutritional deficit. However, there is still little information on sex differences in muscle and FGF21 physiological response to fasting. Our aim was to find out whether there were sex differences in hormonal regulation and the expression of genes controlling glucose and lipid metabolism in skeletal muscles in response to fasting. We estimated the effect of 24-hour fasting on the expression of genes involved in lipid (Ucp3, Cpt1) and carbohydrate (Slc2a4) metabolism in muscles and evaluated changes in body weight and blood plasma levels of glucose, insulin, free fatty acids (FFA), adiponectin, and FGF21 in male and female C57BL/6J mice. None of the genes studied (Ucp3, Cpt1 and Slc2a4) showed sex-related changes at mRNA levels in control groups, but females exposed to fasting demonstrated a significant increase in the expression of all genes as compared to control. Fasting significantly decreased body weight and glucose blood plasma levels in animals of both sexes but exerted no effect on the levels of insulin or FFA. The adiponectin and FGF21 levels were increased in response to fasting, the increase in females being significant. We were first to show sex dimorphism in muscle gene expression and FGF21 blood level in response to fasting. In females, the greater increase in FGF21 and adiponectin blood levels was positively associated with the greater upregulation of lipid oxidation and glucose uptake gene expression

Impact of sex on the adaptation of adult mice to long consumption of sweet-fat diet

In rodents, the most adequate model of human diet-induced obesity is obesity caused by the consumption of a sweet-fat diet (SFD), which causes more pronounced adiposity in females than in males. The aim of this work was to determine the sex-associated effect of SFD on the expression of genes related to carbohydrate-lipid metabolism in adult mice. For 10 weeks, male and female С57Bl mice were fed a standard laboratory chow (Control group) or a diet, which consisted of laboratory chow supplemented with sweet cookies, sunflower seeds and lard (SFD group). Weights of body, liver and fat depots, blood concentrations of hormones and metabolites, liver fat, and mRNA levels of genes involved in regulation of energy metabolism in the liver, perigonadal and subcutaneous white adipose tissue (pgWAT, scWAT) and brown adipose tissue (BAT) were measured. SFD increased body weight and insulin resistance in mice of both sexes. Female mice that consumed SFD (SFD females) had a greater increase in adiposity than SFD males. SFD females showed a decreased expression of genes related to lipogenesis (Lpl) and glucose metabolism (G6pc, Pklr) in liver, as well as lipogenesis (Lpl, Slca4) and lipolysis (Lipe) in pgWAT, suggesting reduced energy expenditure. In contrast, SFD males showed increased lean mass gain, plasma insulin and FGF21 levels, expressions of Cpt1α gene in pgWAT and scWAT and Pklr gene in liver, suggesting enhanced lipid and glucose oxidation in these organs. Thus, in mice, there are sex-dependent differences in adaptation to SFD at the transcriptional level, which can help to explain higher adiposity in females under SFD consumtion

Sex differences of molecular mechanisms of insulin sensitivity in young and adult C57BL/6J mice

Reduced insulin sensitivity plays an important role in the pathogenesis of type II diabetes. There are sex differences in the development of metabolic disorders. The aim of this work was to investigate the insulin signal transduction gene expression in mice of different sex and age. Male and female C57BL/6J mice were used in our studies. Gene expression was assayed by RT-PCR. It was shown that insulin sensitivity in females was higher than in males regardless of age because the level of glucose in blood plasma of females does not differ from that in males, whereas female insulin levels were lower than male insulin levels. Female glucose tolerance increased with age, and glucose tolerance was higher in females than in males at the age of 30 weeks. It was shown that sex and age affect the expressions of insulin signal transduction genes. It was shown that there are sex differences in the levels of mRNA Pik3cd in the liver, in the levels of mRNA Irs1 in the muscle, in the levels of mRNA Irs1 and Slc2a4 in adipose tissue at the age of 10 weeks, and there are sex differences in the levels of mRNA Irs2 and Pik3cd in the liver, in the levels mRNA Pik3cd and Slc2a4 in the muscle, in the levels mRNA Insr and Pik3cd in adipose tissue at the age of 30 weeks. In young animals, the expression of the genes was higher in females than in males in all tissues. In adult animals, the expression of the genes in the liver was higher in females than in males, the expression of the genes in muscle and adipose tissues were lower in females than in males. In males, the levels of mRNA Insr in the liver and muscles and mRNA Pik3cd in adipose tissue decreased with age, and the level of mRNA Pik3cd in muscles  increased with age. In females, the levels of mRNA Irs1 in muscle and mRNA Pik3cd and Slc2a4 in adipose tissue decreased with age. Thus the molecular basis of sex differences and age-related changes in insulin sensitivity may be a change in expressions of insulin signal transduction genes in the target tissues

Artificial Epitope-Based Immunogens in HIV-Vaccine Design

One of the promising approaches for designing HIV vaccines is construction of synthetic polyepitope HIV-1 immunogen using a wide range of conservative T- and B-cell epitopes of the main virus antigens. In theory this approach helps cope with HIV-1 antigenic variability, focuses immune responses on protective determinants and enables to exclude from the vaccine compound adverse regions of viral proteins that can induce autoantibodies or antibodies enhancing infectivity of virus. The paper presents the experience of our team in development of artificial polyepitope HIV-1 immunogens, which can induce both a humoral response, and responses of cytotoxic (CD8 + CTL) and helpers (CD4 + Th) T-cells. The design of HIV-immunogens has been done using our original software, TEpredict and PolyCTLDesigner. We describe development of the candidate HIV-1/AIDS vaccine – CombiHIVvac, which included two artificial polyepitope immunogens TBI and TCI for stimulating humoral and cellular responses. The results of the specific activity and safety of CombiHIVvac vaccine, obtained during preclinical and clinical trials, are presented

Mutation yellow in agouti loci prevents age-related increase of skeletal muscle genes regulating free fatty acids oxidation

The lethal yellow mutation in agouti loci (Ay mutation) reduces the activity of melanocortin (MC) receptors and causes hyperphagia, obesity and type two diabetes mellitus in aging mice (Ay mice). It is unknown if changes in distinct elements of the metabolic system such as white adipose tissue (WAT) and brown adipose tissue (BAT), and skeletal muscle will manifest before the development of obesity. The aim of this work was to measure the relative gene expression of key proteins that regulate carbohydrate-lipid metabolism in WAT, BAT and skeletal muscle in Ay mice before the development of obesity. C57Bl/6J mice bearing a dominant autosomal mutation Ay (Ay /a mice) and mice of the standard genotype (a/a mice, control) have been studied in three age groups: 10, 15 and 30 weeks. The relative mRNA level of genes was measured by real-time PCR in skeletal muscles (uncoupling protein 3 (Ucp3) and carnitine palmitoyl transferase 1b (Cpt1b) (free fatty acids oxidation), solute carrier family 2 (facilitated glucose transporter), member 4 (Slc2a4) (glucose uptake)), in WAT lipoprotein lipase (Lpl) (triglyceride deposition), hormone-sensitive lipase (Lipe) (lipid mobilization), and Slc2a4 (glucose uptake)), and in BAT: uncoupling protein 1 (Ucp1) (energy expenditure). The expression of Cpt1b was reduced in young Ay mice (10 weeks), there was no transient peak of transcription of Cpt1b, Ucp3 in skeletal muscle tissue and Lipe, Slc2a4 in WAT in early adult Ay mice (15 weeks), which was noted in а/а mice. Reduction of the transcriptional activity of the studied genes in skeletal muscle and white adipose tissue can initiate the development of melanocortin obesity in Ay mice

Magnetoresistive study of antiferromagnetic--weak ferromagnetic transition in single-crystal La2_{2}CuO4+δ_{4+\delta}

The resistive measurements were made to study the magnetic field-induced antiferromagnetic (AF) - weak ferromagnetic (WF) transition in La$_2$CuO$_4$ single-crystal. The magnetic field (DC or pulsed) was applied normally to the CuO$_2$ layers. The transition manifested itself in a drastic decrease of the resistance in critical fields of ~5-7 T. The study is the first to display the effect of the AF -WF transition on the conductivity of the La$_2$CuO$_4$ single-crystal in the parallel - to - CuO$_2$ layers direction. The results provide support for the 3-dimensional nature of the hopping conduction of this layered oxide.Comment: 8 pages, 7 figures, RevTe