Environmental chemicals change extracellular lipidome of mature human white adipocytes.

Certain environmental chemicals affect the body's energy balance and are known as metabolism disrupting chemicals (MDCs). MDCs have been implicated in the development of metabolic diseases, such as obesity and type 2 diabetes. In contrast to their well-known impact on developing adipocytes, MDC effects leading to altered energy balance and development of insulin resistance in mature white adipocytes, constituents of adult adipose tissue, are largely unclear.

Insulin Directly Regulates the Circadian Clock in Adipose Tissue.

Adipose tissue (AT) is a key metabolic organ which functions are rhythmically regulated by an endogenous circadian clock. Feeding is a "zeitgeber" aligning the clock in AT with the external time, but mechanisms of this regulation remain largely unclear. We tested the hypothesis that postprandial changes of the hormone insulin directly entrain circadian clocks in AT and investigated a transcriptional-dependent mechanism of this regulation.

Quantification of Intracellular Accumulation and Retention of Lysosomotropic Macrocyclic Compounds by High-Throughput Imaging of Lysosomal Changes.

Many marketed pharmaceuticals reach extremely high tissue concentrations due to accumulation in lysosomes (lysosomotropism). Quantitative prediction of intracellular concentrations of accumulating drugs is challenging, especially for macrocyclic compounds that mainly do not fit in current in silico models. We tested a unique library of 47 compounds (containing 39 macrocycles) specifically designed to cover the entire range of accumulation intensities observed with pharmaceuticals so far.

Lysosomotropic cationic amphiphilic drugs inhibit adipocyte differentiation in 3T3-L1K cells via accumulation in cells and phospholipid membranes, and inhibition of autophagy.

Some cationic amphiphilic drugs (CADs) have been individually reported to interfere with the differentiation of immune system cells, such as macrophages and dendritic cells. To investigate the possible generic nature of this process, in this study we aimed to see whether these drugs are capable of interfering with the differentiation of adipocytes. Further, we investigated whether this feature might be connected to the lysosomotropic character of these drugs, and their disturbance of intracellular membrane trafficking rather than to the individual pharmacologic properties of each drug.

Cellular accumulation and lipid binding of perfluorinated alkylated substances (PFASs) - A comparison with lysosomotropic drugs.

Many chemicals accumulate in organisms through a variety of different mechanisms. Cationic amphiphilic drugs (CADs) accumulate in lysosomes and bind to membranes causing phospholipidosis, whereas many lipophilic chemicals target adipose tissue. Perfluoroalkyl substances (PFASs) are widely used as surfactants, but many of them are highly bioaccumulating and persistent in the environment, making them notorious environmental toxicants.

HEALTH STATUS OF PREGNANT WOMEN.

The article covers the study into the structure of extragenital pathology in pregnantwomen based on the data obtained at the antenatal clinic of the perinatal center of the State Organization of the Ministry of Health of the Sakha Republic (Yakutia) National Center of Medicine - Republican Hospital No. 1 in 2013. The presence of extragenital pathology in pregnant women is a major factor in the high risk of maternal mortality.

[Monitoring of health of young students of northern territories residing in conditions of ecological trouble].

In recent years, in sanitary science the interest in issues of young people has dramatically increased, that has been actualized by the necessity of a new objective assessment of the role of the youth in modern sanitary-ecological, sociocultural and economic processes. In this regard, a special interest is aroused by young students, the health of whom is determined largely by the condition of the habitat. So far complex assessment ofriskfactors in urbanized areas, prioritization of impacts, the establishment ofpriority impacts, the detection of informative territorial environmentally dependent indices ofpopulation health are presented to be important tasks in the solution of the regional challenges.

Glyoxylate, a new marker metabolite of type 2 diabetes.

Type 2 diabetes (T2D) is characterized by a variety of metabolic impairments that are closely linked to nonenzymatic glycation reactions of proteins and peptides resulting in advanced glycation end-products (AGEs). Reactive aldehydes derived from sugars play an important role in the generation of AGEs. Using metabolite profiling to characterize human plasma from diabetic versus nondiabetic subjects we observed in a recent study that the reactive aldehyde glyoxylate was increased before high levels of plasma glucose, typical for a diabetic condition, could be measured.

Interleukin-33 drives activation of alveolar macrophages and airway inflammation in a mouse model of acute exacerbation of chronic asthma.

We investigated the role of interleukin-33 (IL-33) in airway inflammation in an experimental model of an acute exacerbation of chronic asthma, which reproduces many of the features of the human disease. Systemically sensitized female BALB/c mice were challenged with a low mass concentration of aerosolized ovalbumin for 4 weeks to induce chronic asthmatic inflammation and then received a single moderate-level challenge to trigger acute airway inflammation simulating an asthmatic exacerbation. The inflammatory response and expression of cytokines and activation markers by alveolar macrophages (AM) were assessed, as was the effect of pretreatment with a neutralizing antibody to IL-33.

[Spin-lattice relaxation of water protons in plant and animal cells].

NMR-spin echo method has been used to study spin-lattice relaxation time of protons T1 in plant and animal cells - muscle tissue of fish, the cells of which unlike plant cells have no developed system of vacuoles, plastids and a solid cell wall. According to the values of T1 time a new NMR parameter K, a coefficient of relaxation effectiveness of a cell structure, has been calculated. This parameter can be used for quantitative characterization of the influence of different cell structures, the tissue water interact with, for a time of spin-lattice relaxation of water protons.

Insulin up-regulates natriuretic peptide clearance receptor expression in the subcutaneous fat depot in obese subjects: a missing link between CVD risk and obesity?

Context: Natriuretic peptides (NP) regulate cardiovascular homeostasis and have multiple metabolic properties. Decreased levels of NP or "natriuretic handicap" are signs of insulin resistance such as central obesity. Increased expression of NP clearance receptor (NPRC) in sc adipose tissue (SAT) was observed in insulin-resistant subjects.

Metabolomic linkage reveals functional interaction between glucose-dependent insulinotropic polypeptide and ghrelin in humans.

The gastric peptide ghrelin promotes energy storage, appetite, and food intake. Nutrient intake strongly suppresses circulating ghrelin via molecular mechanisms possibly involving insulin and gastrointestinal hormones. On the basis of the growing evidence that glucose-dependent insulinotropic polypeptide (GIP) is involved in the control of fuel metabolism, we hypothesized that GIP and/or insulin, directly or via changes in plasma metabolites, might affect circulating ghrelin.

The complexity of gene expression dynamics revealed by permutation entropy.

Background: High complexity is considered a hallmark of living systems. Here we investigate the complexity of temporal gene expression patterns using the concept of Permutation Entropy (PE) first introduced in dynamical systems theory. The analysis of gene expression data has so far focused primarily on the identification of differentially expressed genes, or on the elucidation of pathway and regulatory relationships.

A contribution to identification of novel regulators of plant response to sulfur deficiency: characteristics of a tobacco gene UP9C, its protein product and the effects of UP9C silencing.

Extensive changes in plant transcriptome and metabolome have been observed by numerous research groups after transferring plants from optimal conditions to sulfur (S) deficiency. Despite intensive studies and recent important achievements, like identification of SLIM1/EIL3 as a major transcriptional regulator of the response to S-deficiency, many questions concerning other elements of the regulatory network remain unanswered. Investigations of genes with expression regulated by S-deficiency stress encoding proteins of unknown function might help to clarify these problems.

Sequence-structure relationships in RNA loops: establishing the basis for loop homology modeling.

The specific function of RNA molecules frequently resides in their seemingly unstructured loop regions. We performed a systematic analysis of RNA loops extracted from experimentally determined three-dimensional structures of RNA molecules. A comprehensive loop-structure data set was created and organized into distinct clusters based on structural and sequence similarity.

Stability of metabolic correlations under changing environmental conditions in Escherichia coli--a systems approach.

Background: Biological systems adapt to changing environments by reorganizing their cellular and physiological program with metabolites representing one important response level. Different stresses lead to both conserved and specific responses on the metabolite level which should be reflected in the underlying metabolic network.

Methodology/principal Findings: Starting from experimental data obtained by a GC-MS based high-throughput metabolic profiling technology we here develop an approach that: (1) extracts network representations from metabolic condition-dependent data by using pairwise correlations, (2) determines the sets of stable and condition-dependent correlations based on a combination of statistical significance and homogeneity tests, and (3) can identify metabolites related to the stress response, which goes beyond simple observations about the changes of metabolic concentrations.

[Evaluating fluorine effects in children of Irkutsk area].

The authors studied connection between exposure to fluorine compounds and fluorides excretion. Average fluorine content of urine and hair samples of children exceeds the reference values. Ambient air and soil pollution with fluorine was proved to be an important health risk factor for urban children in Irkutsk region.

The influence of genetic variations in HHEX gene on insulin metabolism in the German MESYBEPO cohort.

Background: In the present study, we aimed to validate the type 2 diabetes (T2DM) susceptibility alleles identified in the first genome-wide association study in the hematopoietically expressed homeobox protein (HHEX) gene region (rs1111875 and rs7923837). Furthermore, we investigated quantitative metabolic risk phenotypes of these two variants for association with three key components of the insulin metabolism: insulin secretion, insulin sensitivity and insulin degradation.

Methods: Two HHEX polymorphisms were genotyped in 1026 subjects from the German MESYBEPO cohort.

Reconfiguration of the achene and receptacle metabolic networks during strawberry fruit development.

The anatomy of strawberry (Fragaria x ananassa) fruit, in which the achene is found on the outer part of the fruit, makes it an excellent species for studying the regulation of fruit development. It can provide a model for the cross talk between primary and secondary metabolism, whose role is of pivotal importance in the process. By combining gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry with the aim of addressing the metabolic regulation underlying fruit seed development, we simultaneously analyzed the composition of primary and secondary metabolites, separately, in achene and receptacle during fruit ripening of strawberry cultivar Herut.

Metabolomics integrated with transcriptomics: assessing systems response to sulfur-deficiency stress.

Sulfur-containing amino acids, cysteine and methionine synthesized in plants are essential for human and animal nutrition. That is why understanding of how inorganic sulfur is taken up by plants and built into the organic molecules in the process of sulfur assimilation is important. As complex biological systems, plants subsist as integrated molecular, organelle, cell, tissue and organ entities, being in permanent synergistic coordination.

Gene expression profiling of the different stages of Arabidopsis thaliana trichome development on the single cell level.

Leaf hairs (trichomes) of Arabidopsis thaliana are a model system for studying cell development, differentiation and cell cycle regulation. To exploit this model system with ultimate spatial resolution we applied single cell sampling, thus avoiding the averaging effect induced by complex tissue mixtures. In particular, we analysed gene expression profiles of two selected stages of the developing trichome: trichome initial cells and mature trichomes, as well as pavement cells.

[Development of measures to health maintenance in the programs of the socioeconomic developments of areas].

The paper deals with the information provision and use of mathematical statistical and mathematical economic methods in the substantiation of measures provided by the socioeconomic development programs. The development of a package of human health maintenance measures may involve 2 stages: (1) analysis of long-term data on the man-caused pollution of environmental objects, socioeconomic conditions, and the medicodemographic situation; (2) medium-range forecast of indicators. Testing the proposed approaches applied in Irkutsk has ascertained that the investment area development causes a steady-state decrease in morbidity rates in all population groups and a reduction in disorders-caused economic damages.

On the processing of metabolic information through metabolite-gene communication networks: an approach for modelling causality.

Gene-metabolite correlation networks of three independent biological systems were interrogated using an approach to define, and subsequently model, causality. The major goal of this work was to analyse how information from those metabolites, that displayed a rapid response to perturbation of the biological system, is processed through the response network to provide signal-specific adaptation of metabolism. For this purpose, comparison of network topologies was carried out on three different groups of system elements: transcription factors, other genes and metabolites, with special emphasis placed on those features which are possible sites of metabolic regulation or response propagation.

Network visualization and network analysis.

Network analysis of living systems is an essential component of contemporary systems biology. It is targeted at assemblance of mutual dependences between interacting systems elements into an integrated view of whole-system functioning. In the following chapter we describe the existing classification of what is referred to as biological networks and show how complex interdependencies in biological systems can be represented in a simpler form of network graphs.