Предопухолевая патология молочных желез в различных этнических популяциях населения Крыма

Серед жіночого населення АРК виявлені популяції із украй високою захворюваністю РМЖ (армянки - 114,25); з високою захворюваністю (слов’янки - 65,21); а також з відносно низькою захворюваністю (кримські татарки - 41,99 на 100 тис. відповідного жіночого населення; р < 0,001). Порівняльний аналіз поширеності доброякісної патології в 531 пацієнтки (399 слов’янок, 69 татарок, 63 армянки) показав, що вірогідно найбільш частими захворюваннями у вірменській популяції з високою захворюваністю РМЖ є кисты молочних залоз (Р=0,033) і вузлова форма фиброзно-кистозной хвороби (Р=0,040), які, очевидно, можна відносити до предраковой патології.In Crimean woman there are populations with very high Breast Cancer incidence (Armenians - 114,25); with high incidence (Slavs - 65,21); and with lowest incidence (Tatars - 41,99 in 100 000 woman populations; р < 0,001). In 531 patients (399 Slavs, 69 Tatars, 63 Armenians) more freqwently was diagnosed Breast Cysts (Р=0,033) and Nodular Fibrocystic disease (Р=0,040) in Armenian ethnic group with very high Breast Cancer incidence. Breast Cysts and Nodular Fibrocystic disease only are precancerous diseases of the Breast

Структурные изменения в системе гемостаза у больных меланомой кожи на ранней стадии ее развития

Мета дослідження – оцінка показників системи гемостазу у 27 хворих на меланому шкіри. Виявлено подовження активованого часткового тромбопластинового часу, подовження часткового тромбопластинового часу, подовження часу рекальцифікації, зниження рівня антитромбіну III, підвищення рівня розчинних фібрін-мономерних комплексів. Таким чином, мають місце серйозні структурні зміни системного гемостазу - гіпокоагуляція і гіперфібриноліз. Діагностика та корекція цих змін допоможе поліпшити клінічний перебіг і прогноз захворювання.A research aim is an estimation of indexes of the system of hemostasis at 27 patients by the melanoma of skin. Lengthening of the activated partial tromboplastin time, lengthening of partial tromboplastin time, lengthening of time of recalcification, decline of level of antithrombin of III, increase of level of soluble fibrinmonomers complexes is educed. Thus, the serious structural changes in the system of hemostasis - incoagulability and hyperfibrinolysis take place. Diagnostics and correction of these changes will help to improve a clinical flow and prognosis of disease

Liver and Adipose Expression Associated SNPs Are Enriched for Association to Type 2 Diabetes

Genome-wide association studies (GWAS) have demonstrated the ability to identify the strongest causal common variants in complex human diseases. However, to date, the massive data generated from GWAS have not been maximally explored to identify true associations that fail to meet the stringent level of association required to achieve genome-wide significance. Genetics of gene expression (GGE) studies have shown promise towards identifying DNA variations associated with disease and providing a path to functionally characterize findings from GWAS. Here, we present the first empiric study to systematically characterize the set of single nucleotide polymorphisms associated with expression (eSNPs) in liver, subcutaneous fat, and omental fat tissues, demonstrating these eSNPs are significantly more enriched for SNPs that associate with type 2 diabetes (T2D) in three large-scale GWAS than a matched set of randomly selected SNPs. This enrichment for T2D association increases as we restrict to eSNPs that correspond to genes comprising gene networks constructed from adipose gene expression data isolated from a mouse population segregating a T2D phenotype. Finally, by restricting to eSNPs corresponding to genes comprising an adipose subnetwork strongly predicted as causal for T2D, we dramatically increased the enrichment for SNPs associated with T2D and were able to identify a functionally related set of diabetes susceptibility genes. We identified and validated malic enzyme 1 (Me1) as a key regulator of this T2D subnetwork in mouse and provided support for the association of this gene to T2D in humans. This integration of eSNPs and networks provides a novel approach to identify disease susceptibility networks rather than the single SNPs or genes traditionally identified through GWAS, thereby extracting additional value from the wealth of data currently being generated by GWAS

Teixobactin kills bacteria by a two-pronged attack on the cell envelope

Antibiotics that use novel mechanisms are needed to combat antimicrobial resistance1–3. Teixobactin4 represents a new class of antibiotics with a unique chemical scaffold and lack of detectable resistance. Teixobactin targets lipid II, a precursor of peptidoglycan5. Here we unravel the mechanism of teixobactin at the atomic level using a combination of solid-state NMR, microscopy, in vivo assays and molecular dynamics simulations. The unique enduracididine C-terminal headgroup of teixobactin specifically binds to the pyrophosphate-sugar moiety of lipid II, whereas the N terminus coordinates the pyrophosphate of another lipid II molecule. This configuration favours the formation of a β-sheet of teixobactins bound to the target, creating a supramolecular fibrillar structure. Specific binding to the conserved pyrophosphate-sugar moiety accounts for the lack of resistance to teixobactin4. The supramolecular structure compromises membrane integrity. Atomic force microscopy and molecular dynamics simulations show that the supramolecular structure displaces phospholipids, thinning the membrane. The long hydrophobic tails of lipid II concentrated within the supramolecular structure apparently contribute to membrane disruption. Teixobactin hijacks lipid II to help destroy the membrane. Known membrane-acting antibiotics also damage human cells, producing undesirable side effects. Teixobactin damages only membranes that contain lipid II, which is absent in eukaryotes, elegantly resolving the toxicity problem. The two-pronged action against cell wall synthesis and cytoplasmic membrane produces a highly effective compound targeting the bacterial cell envelope. Structural knowledge of the mechanism of teixobactin will enable the rational design of improved drug candidates

Ionic liquids at electrified interfaces

Until recently, “room-temperature” (<100–150 °C) liquid-state electrochemistry was mostly electrochemistry of diluted electrolytes(1)–(4) where dissolved salt ions were surrounded by a considerable amount of solvent molecules. Highly concentrated liquid electrolytes were mostly considered in the narrow (albeit important) niche of high-temperature electrochemistry of molten inorganic salts(5-9) and in the even narrower niche of “first-generation” room temperature ionic liquids, RTILs (such as chloro-aluminates and alkylammonium nitrates).(10-14) The situation has changed dramatically in the 2000s after the discovery of new moisture- and temperature-stable RTILs.(15, 16) These days, the “later generation” RTILs attracted wide attention within the electrochemical community.(17-31) Indeed, RTILs, as a class of compounds, possess a unique combination of properties (high charge density, electrochemical stability, low/negligible volatility, tunable polarity, etc.) that make them very attractive substances from fundamental and application points of view.(32-38) Most importantly, they can mix with each other in “cocktails” of one’s choice to acquire the desired properties (e.g., wider temperature range of the liquid phase(39, 40)) and can serve as almost “universal” solvents.(37, 41, 42) It is worth noting here one of the advantages of RTILs as compared to their high-temperature molten salt (HTMS)(43) “sister-systems”.(44) In RTILs the dissolved molecules are not imbedded in a harsh high temperature environment which could be destructive for many classes of fragile (organic) molecules

Teixobactin kills bacteria by a two-pronged attack on the cell envelope

Antibiotics that use novel mechanisms are needed to combat antimicrobial resistance1–3. Teixobactin4 represents a new class of antibiotics with a unique chemical scaffold and lack of detectable resistance. Teixobactin targets lipid II, a precursor of peptidoglycan5. Here we unravel the mechanism of teixobactin at the atomic level using a combination of solid-state NMR, microscopy, in vivo assays and molecular dynamics simulations. The unique enduracididine C-terminal headgroup of teixobactin specifically binds to the pyrophosphate-sugar moiety of lipid II, whereas the N terminus coordinates the pyrophosphate of another lipid II molecule. This configuration favours the formation of a β-sheet of teixobactins bound to the target, creating a supramolecular fibrillar structure. Specific binding to the conserved pyrophosphate-sugar moiety accounts for the lack of resistance to teixobactin4. The supramolecular structure compromises membrane integrity. Atomic force microscopy and molecular dynamics simulations show that the supramolecular structure displaces phospholipids, thinning the membrane. The long hydrophobic tails of lipid II concentrated within the supramolecular structure apparently contribute to membrane disruption. Teixobactin hijacks lipid II to help destroy the membrane. Known membrane-acting antibiotics also damage human cells, producing undesirable side effects. Teixobactin damages only membranes that contain lipid II, which is absent in eukaryotes, elegantly resolving the toxicity problem. The two-pronged action against cell wall synthesis and cytoplasmic membrane produces a highly effective compound targeting the bacterial cell envelope. Structural knowledge of the mechanism of teixobactin will enable the rational design of improved drug candidates

Teixobactin kills bacteria by a two-pronged attack on the cell envelope

Antibiotics that use novel mechanisms are needed to combat antimicrobial resistance1–3. Teixobactin4 represents a new class of antibiotics with a unique chemical scaffold and lack of detectable resistance. Teixobactin targets lipid II, a precursor of peptidoglycan5. Here we unravel the mechanism of teixobactin at the atomic level using a combination of solid-state NMR, microscopy, in vivo assays and molecular dynamics simulations. The unique enduracididine C-terminal headgroup of teixobactin specifically binds to the pyrophosphate-sugar moiety of lipid II, whereas the N terminus coordinates the pyrophosphate of another lipid II molecule. This configuration favours the formation of a β-sheet of teixobactins bound to the target, creating a supramolecular fibrillar structure. Specific binding to the conserved pyrophosphate-sugar moiety accounts for the lack of resistance to teixobactin4. The supramolecular structure compromises membrane integrity. Atomic force microscopy and molecular dynamics simulations show that the supramolecular structure displaces phospholipids, thinning the membrane. The long hydrophobic tails of lipid II concentrated within the supramolecular structure apparently contribute to membrane disruption. Teixobactin hijacks lipid II to help destroy the membrane. Known membrane-acting antibiotics also damage human cells, producing undesirable side effects. Teixobactin damages only membranes that contain lipid II, which is absent in eukaryotes, elegantly resolving the toxicity problem. The two-pronged action against cell wall synthesis and cytoplasmic membrane produces a highly effective compound targeting the bacterial cell envelope. Structural knowledge of the mechanism of teixobactin will enable the rational design of improved drug candidates