РЕГИОНАЛЬНАЯ СПРАВЕДЛИВОСТЬ И НАЦИОНАЛЬНОЕ ЕДИНСТВО

In regions of Russia who lag behind the national average both in pay and in economic development, the problem of raising living standards should be solved through a nation-wide program which would be believed by peoples of Russia regardless of ethnicity. It should include creation of jobs, leveling of wages, abolition of fees for education and for a significant portion of health services, reducing utility tariffs and prices for public transportation, introduction of an income-based progressive taxation system, improving law enforcement activities, etc. Considerable attention is paid to the analysis of macroeconomic indicators of Russian economy in recent years.В регионах РФ, отстающих и в оплате труда, и в экономическом развитии от средних показателей по стране, проблему повышения благосостояния трудящихся необходимо решать на основе общегосударственной программы, в которую поверят жители России независимо от национальной принадлежности. Она должна предусматривать создание рабочих мест, выравнивание уровня заработной платы, отмену платы за образование и за значительную часть медицинских услуг, снижение тарифов ЖКХ и цен на проезд в транспорте, введение системы налогообложения в зависимости от доходов, повышение эффективности правоохранительных органов и многое другое. Значительное внимание уделено анализу макроэкономических показателей развития экономики России в последние годы

Novel insights into iron metabolism by integrating deletome and transcriptome analysis in an iron deficiency model of the yeast Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Iron-deficiency anemia is the most prevalent form of anemia world-wide. The yeast <it>Saccharomyces cerevisiae </it>has been used as a model of cellular iron deficiency, in part because many of its cellular pathways are conserved. To better understand how cells respond to changes in iron availability, we profiled the yeast genome with a parallel analysis of homozygous deletion mutants to identify essential components and cellular processes required for optimal growth under iron-limited conditions. To complement this analysis, we compared those genes identified as important for fitness to those that were differentially-expressed in the same conditions. The resulting analysis provides a global perspective on the cellular processes involved in iron metabolism.</p> <p>Results</p> <p>Using functional profiling, we identified several genes known to be involved in high affinity iron uptake, in addition to novel genes that may play a role in iron metabolism. Our results provide support for the primary involvement in iron homeostasis of vacuolar and endosomal compartments, as well as vesicular transport to and from these compartments. We also observed an unexpected importance of the peroxisome for growth in iron-limited media. Although these components were essential for growth in low-iron conditions, most of them were not differentially-expressed. Genes with altered expression in iron deficiency were mainly associated with iron uptake and transport mechanisms, with little overlap with those that were functionally required. To better understand this relationship, we used expression-profiling of selected mutants that exhibited slow growth in iron-deficient conditions, and as a result, obtained additional insight into the roles of <it>CTI6</it>, <it>DAP1</it>, <it>MRS4 </it>and <it>YHR045W </it>in iron metabolism.</p> <p>Conclusion</p> <p>Comparison between functional and gene expression data in iron deficiency highlighted the complementary utility of these two approaches to identify important functional components. This should be taken into consideration when designing and analyzing data from these type of studies. We used this and other published data to develop a molecular interaction network of iron metabolism in yeast.</p

Persistent changes in spinal cord gene expression after recovery from inflammatory hyperalgesia: A preliminary study on pain memory

<p>Abstract</p> <p>Background</p> <p>Previous studies found that rats subjected to carrageenan injection develop hyperalgesia, and despite complete recovery in several days, they continue to have an enhanced hyperalgesic response to a new noxious challenge for more than 28d. The study's aim was to identify candidate genes that have a role in the formation of the long-term hyperalgesia-related imprint in the spinal cord. This objective was undertaken with the understanding that the long-lasting imprint of acute pain in the central nervous system may contribute to the transition of acute pain to chronicity.</p> <p>Results</p> <p>To analyze changes in gene expression when carrageenan-induced hyperalgesia has disappeared but propensity for the enhanced hyperalgesic response is still present, we determined the gene expression profile using oligo microarray in the lumbar part of the spinal cord in three groups of rats: 28d after carrageenan injection, 24h after injection (the peak of inflammation), and with no injection (control group). Out of 17,000 annotated genes, 356 were found to be differentially expressed compared with the control group at 28d, and 329 at 24h after carrageenan injection (both groups at p < 0.01). Among differentially expressed genes, 67 (39 in 28d group) were identified as being part of pain-related pathways, altered in different models of pain, or interacting with proteins involved in pain-related pathways. Using gene ontology (GO) classification, we have identified 3 functional classes deserving attention for possible association with pain memory: They are related to cell-to-cell interaction, synaptogenesis, and neurogenesis.</p> <p>Conclusion</p> <p>Despite recovery from inflammatory hyperalgesia, persistent changes in spinal cord gene expression may underlie the propensity for the enhanced hyperalgesic response. We suggest that lasting changes in expression of genes involved in the formation of new synapses and neurogenesis may contribute to the transition of acute pain to chronicity.</p

Genome-Wide Functional Profiling Reveals Genes Required for Tolerance to Benzene Metabolites in Yeast

Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ), catechol (CAT) and 1,2,4-benzenetriol (BT), in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(P)H:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease

REGIONAL JUSTICE AND NATIONAL UNITY

In regions of Russia who lag behind the national average both in pay and in economic development, the problem of raising living standards should be solved through a nation-wide program which would be believed by peoples of Russia regardless of ethnicity. It should include creation of jobs, leveling of wages, abolition of fees for education and for a significant portion of health services, reducing utility tariffs and prices for public transportation, introduction of an income-based progressive taxation system, improving law enforcement activities, etc. Considerable attention is paid to the analysis of macroeconomic indicators of Russian economy in recent years

Novel insights into iron metabolism by integrating deletome and transcriptome analysis in an iron deficiency model of the yeast Saccharomyces cerevisiae.

BackgroundIron-deficiency anemia is the most prevalent form of anemia world-wide. The yeast Saccharomyces cerevisiae has been used as a model of cellular iron deficiency, in part because many of its cellular pathways are conserved. To better understand how cells respond to changes in iron availability, we profiled the yeast genome with a parallel analysis of homozygous deletion mutants to identify essential components and cellular processes required for optimal growth under iron-limited conditions. To complement this analysis, we compared those genes identified as important for fitness to those that were differentially-expressed in the same conditions. The resulting analysis provides a global perspective on the cellular processes involved in iron metabolism.ResultsUsing functional profiling, we identified several genes known to be involved in high affinity iron uptake, in addition to novel genes that may play a role in iron metabolism. Our results provide support for the primary involvement in iron homeostasis of vacuolar and endosomal compartments, as well as vesicular transport to and from these compartments. We also observed an unexpected importance of the peroxisome for growth in iron-limited media. Although these components were essential for growth in low-iron conditions, most of them were not differentially-expressed. Genes with altered expression in iron deficiency were mainly associated with iron uptake and transport mechanisms, with little overlap with those that were functionally required. To better understand this relationship, we used expression-profiling of selected mutants that exhibited slow growth in iron-deficient conditions, and as a result, obtained additional insight into the roles of CTI6, DAP1, MRS4 and YHR045W in iron metabolism.ConclusionComparison between functional and gene expression data in iron deficiency highlighted the complementary utility of these two approaches to identify important functional components. This should be taken into consideration when designing and analyzing data from these type of studies. We used this and other published data to develop a molecular interaction network of iron metabolism in yeast

Gene Transcription, Metabolite and Lipid Profiling in Eco-Indicator Daphnia magna Indicate Diverse Mechanisms of Toxicity by Legacy and Emerging Flame-Retardants

The use of chemical flame-retardants (FR) in consumer products has steadily increased over the last 30 years. Toxicity data exist for legacy FRs such as pentabromodiphenyl ether (pentaBDE), but less is known about effects of new formulations. To address this issue, the toxicity of seven FR chemicals and formulations was assessed on the freshwater crustacean Daphnia magna. Acute 48-h nominal LC50 values for penta- and octabromodiphenyl ether (pentaBDE, octaBDE), Firemaster 550 (FM550), Firemaster BZ-54 (BZ54), bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), triphenyl phosphate (TPhP), and nonbrominated BEH-TEBP analog bis(2-ethylhexyl) phthalate (BEHP) ranged from 0.058 mg/L (pentaBDE) to 3.96 mg/L (octaBDE). mRNA expression, 1H NMR-based metabolomic and lipidomic profiling at 1/10 LC50 revealed distinct patterns of molecular response for each exposure, suggesting pentaPBDE affects transcription and translation, octaBDE and BEH-TEBP affect glycosphingolipid biosynthesis and BZ54 affects Wnt and Hedgehog signal pathways as well as glycosaminoglycan degradation. Brominated components of FM550 (i.e., BZ54) were significantly higher in Daphnia after 48 h following 1/10 LC50 exposure. FM550 elicited significant mRNA changes at five concentrations across a range from 1/106 LC50 to 1/2 LC50. Analyses suggest FM550 impairs nutrient utilization or uptake in Daphnia

Silver Nanowire Exposure Results in Internalization and Toxicity to Daphnia magna

Nanowires (NWs), high-aspect-ratio nanomaterials, are increasingly used in technological materials and consumer products and may have toxicological characteristics distinct from nanoparticles. We carried out a comprehensive evaluation of the physicochemical stability of four silver nanowires (AgNWs) of two sizes and coatings and their toxicity to Daphnia magna. Inorganic aluminum-doped silica coatings were less effective than organic poly(vinyl pyrrolidone) coatings at preventing silver oxidation or Ag⁺ release and underwent a significant morphological transformation within 1 h following addition to low ionic strength Daphnia growth media. All AgNWs were highly toxic to D. magna but less toxic than ionic silver. Toxicity varied as a function of AgNW dimension, coating, and solution chemistry. Ag⁺ release in the media could not account for observed AgNW toxicity. Single-particle inductively coupled plasma mass spectrometry distinguished and quantified dissolved and nanoparticulate silver in microliter-scale volumes of Daphnia magna hemolymph with a limit of detection of approximately 10 ppb. The silver levels within the hemolymph of Daphnia exposed to both Ag⁺ and AgNW met or exceeded the initial concentration in the growth medium, indicating effective accumulation during filter feeding. Silver-rich particles were the predominant form of silver in hemolymph following exposure to both AgNWs and Ag⁺. Scanning electron microscopy imaging of dried hemolymph found both AgNWs and silver precipitates that were not present in the AgNW stock or the growth medium. Both organic and inorganic coatings on the AgNW were transformed during ingestion or absorption. Pathway, gene ontology, and clustering analyses of gene expression response indicated effects of AgNWs distinct from ionic silver on Daphnia magna