Role of morphogenic proteins of the WNT signaling pathway in coronary artery disease

In recent years, researchers’ attention has been directed to the WNT signaling pathway study, which regulates embryogenesis processes and is involved in pathological condition development. The role of morphogenic proteins of WNT signaling pathway in the cardiovascular pathology genesis is practically not clear. The research aim was a comprehensive study of the main proteins of WNT signaling pathway (β-catenin, sclerostin, GSK-3α, GSK-3β, WIF-1 and DVL-1) in the blood serum of 353 patients with coronary artery disease acute forms who were treated at the Orel regional vascular center from 2019 to 2021, and 50 healthy individuals. A comprehensive analysis included an assessment of clinical, laboratory and instrumental parameters in the framework of current clinical guidelines, as well as an immunological examination to determine the morphogenic proteins of WNT signaling by enzyme immunoassay. The results showed a wide variability in the values of morphogenic proteins of WNT signaling pathway in the patient’s blood serum. The levels of β-catenin, WIF-1 and DVL-1 significantly exceeded those obtained in healthy individuals, while the concentrations of sclerostin and GSK-3β did not differ significantly from them. The level of GSK-3α of patients was twice lower than in healthy individuals. The highest sclerostin concentrations were found in patients with existing calcification of the aortic valve leaflets and aortic walls. Acute coronary syndrome unfavorable course was observed in patients with both extremely high and extremely low WIF-1 levels. Significant correlations were established between the level of morphogenic proteins of WNT signaling pathway and lipid metabolism, as well as myocardial remodeling. The obtained data on changes in the protein production of WNT signaling pathway allow us to expand our understanding of the molecular aspects of the immunopathogenesis of myocardial remodeling in coronary artery disease, increase the predictive potential for cardiovascular disease diagnosis and determine the vector for further development of cardioimmunology determination

ROLE OF GSK-3 IN Wnt/β-CATENIN SIGNALING PATHWAY IN OBESITY

The complexity of the adipogenesis mechanism results from the impact of multiple cues, among which an important place is held by the components of the Wnt signaling pathway. The search for potential markers of the development of diseases related to obesity aroused an interest in the study of GSK-3 (glycogen synthase kinase), β-catenin. GSK-3β is an intracellular serine / threonine kinase found in the cytoplasm, nucleus, mitochondria, synthesized in all body tissues and involved in regulating metabolic processes, cell proliferation, apoptosis etc. The first of the discovered functions of GSK-3β was the regulation of glycogen synthesis. Active GSK-3β phosphorylates and thereby inhibits glycogen synthase. As a result of the insulin binding to the cell receptor via inositol-3-phosphate, protein kinase B (Akt1) is activated, which, in turn, phosphorylates and inhibits GSK-3β. In addition, GSK-3β is involved in the regulating glucose metabolism. The most important function of GSK-3β is the inhibition of the β-catenin protein. In a resting cell, GSK-3β in complex with the APC and Axin proteins binds and phosphorylates the β-catenin transcription factor, which leads to its ubiquitination and degradation. When Wnt proteins act on the cell, the Dvl protein is activated, which, by binding to GSK-3β, releases β-catenin, preventing its degradation, however, the role of GSK3α/β in the adipocyte inflammatory response has not yet been fully investigated, therefore it seems promising to study the role of GSK-3 in the Wnt/β-catenin signaling pathway in obesityThe aim of the study was to assess the activity of the components of the Wnt signaling pathway in obese patients by measuring the serum level of GSK-3 and β-catenin. There were enrolled 32 patients with progressive forms of I-III degree obesity in the absence of diabetes mellitus. The concentration of serum GSK-3α, GSK-3β, and β-catenin was measured by enzyme-linked immunoassay. Data are presented as absolute and relative (%) number of patients; arithmetic mean; medians, 1 and 3 quartiles – Ме (Q0.25-Q0.75). Obese patients contained a 7.5-fold increased serum level of GSK-3α (785 (371-1317.5) pg/ml) compared to healthy individuals 105 (102.5-110) pg/ml, (p < 0.001), paralleled with increased amount of GSK-3β, which level in obese patients was 295 (190-695) pg/ml, which is by 18.3% higher than those in healthy individuals 241 (218.75-287.5) pg/ml, p = 0.111. Amount of GSK-3 depending on the degree of obesity tended to increase, most often coupled to decreased β-catenin level which is consistent with the literature data and can be considered as a prognostic criterion for the course of pathological processes in obesity

Early stages of the evolution of chernozems under forest vegetation (Belgorod Oblast)

We studied automorphic forest-steppe Luvic and Haplic Chernozems (Siltic/Clayic, Pachic) of the southern part of the Central Russian Upland (Belgorod region), which were covered with broadleaved forest vegetation at different times (from 25 to 75 years ago). The studies were carried out on an overgrowing fallow and the adjacent maple-ash shelterbelt and on an area of growth of a natural oak forest towards the virgin meadow stepp

Новые области применения компьютерной томографии сердца в диагностике ишемии миокарда

MSCT is known for its extremely high diagnostic accuracy in coronary artery stenosis detection and quantification. However, there are still questions about physiological assessment of myocardial ischemia, since the degree of arterial stenosis and clinical outcomes do not always correlate. It is also noted that the exclusive use of functional non-invasive tests to assess the grade of stenosis can lead to false-negative results and worsen the long-term prognosis of cardiovascular events. Thus, the combined use of anatomical and functional tests can improve the prognosis in coronary heart disease patient. MSCT coronary angiography, combined with stress perfusion and/or CT derived fractional flow reserve, could be used as an all-in-one approach. This review describes new applications of cardiac MSCT.КТ-коронарография показала высокую диагностическую точность в диагностике ишемической болезни сердца (ИБС) и стенозов венечных артерий. Тем не менее остаются вопросы функциональной оценки ишемии миокарда, так как степень стеноза артерий и клинические исходы не всегда коррелируют, а оценка гемодинамической значимости стенозов коронарных артерий остается сложной. Отмечено, что исключительное проведение функциональных неинвазивных тестов для оценки возможных стенозов может приводить к ложноотрицательным результатам и, как следствие, ухудшать долгосрочный прогноз вероятности кардиоваскулярных событий. Таким образом, сочетанное применение анатомической и функциональной оценки венечных артерий может улучшить прогноз пациентов с ИБС. В качестве единого (“всё-в-одном”) метода обследования может выступать КТ-коронарография н, дополненная стресс-перфузией и/или измерением фракционного резерва кровотока.Данный обзор представляет собой описание новых методов диагностики ишемии миокарда при проведении КТ коронарных сосудов при стабильной ИБС и перспективы их применения

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model