Геномные технологии в пульмонологии: роль микроРНК в развитии бронхиальной астмы и хронической обструктивной болезни легких

MicroRNAs (miRNAs) are small noncoding RNA molecules that affect gene expression and thus take part in the epigenetic regulation of almost all physiological and pathological processes. About 1,800 human miRNAs have been discovered to date; however, biological functions and protein targets for the majority remain to be unknown. Within the respiratory system, miRNAs contribute to the lung growth and lifelong maintenance of pulmonary homeostasis. Recently, the leading role of miRNAs in pathogenesis of various pulmonary diseases has been found, including asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Due to a significant progress in studying interactions between genes and their products and environmental factors, a great role of epigenetic variability, which is gene expression change not related to DNA damage, but could be inherited consistently, became apparent. There are three levels of epigenetic regulation corresponding to three main mechanisms: genomic (DNA methylation), proteomic (histone modification) and transcriptomic (regulation through RNA, primarily miRNA). Extending our knowledge on a role of miRNAs for the respiratory system could open new therapeutic targets and diagnostic markers for respiratory diseases, particularly asthma and COPD.МикроРНК – это малые некодирующие молекулы РНК, которые влияют на экспрессию генов и таким образом участвуют в эпигенетической регуляции практически всех физиологических и патологических процессов. Примерно 1 800 микроРНК человека на сегодняшний день открыты, однако биологическая функция и белки-мишени для большинства из них остаются неизвестными. В рамках дыхательной системы микроРНК необходимы для развития легких и поддержания легочного гомеостаза на протяжении всей жизни. В последние годы была открыта главнейшая роль микроРНК в патогенезе различных заболеваний, в т. ч. бронхиальной астмы (БА), хронической обструктивной болезни легких (ХОБЛ) и рака легкого. Благодаря значительному прогрессу в изучении взаимодействий между генами и их продуктами с факторами окружающей среды стала очевидной огромная роль эпигенетической изменчивости – изменений экспрессии генов, не связанных с нарушением структуры ДНК, однако способных устойчиво передаваться в ряду поколений. Существуют 3 уровня эпигенетической регуляции и соответственно – 3 ее основных механизма: геномный (метилирование ДНК), протеомный (модификация гистонов) и транскриптомный (регуляция посредством РНК, в первую очередь микроРНК). Успехи в понимании роли микроРНК в дыхательной системе помогут пролить свет на новые перспективы в поиске терапевтических мишеней и диагностических маркеров для заболеваний респираторной системы, в частности БА и ХОБЛ

Results of Monitoring over and Biological Properties of <I>Vibrio cholerae</I> Isolated from Ambient Environment Objects in the Khabarovsk Territory

genotype and a unique MLVA profile. The results of the monitoring indicated that there were optimal for V. cholerae accumulation in surface water reservoirs conditions and it was necessary to enhance measures for cholera prophylaxis in the post-flood period

Фармакогенетические и эпигенетические особенности синдрома перекреста бронхиальной астмы и хронической обструктивной болезни легких

Recently, investigation of asthma-COPD overlap syndrome (ACOS) is an actual topic due to difficulties in diagnosis and treatment. The aim of our study was to investigate HDAC2, PI3K-δ, GR-α, and GR-β relative expressions in order to found markers of steroid sensitivity in ACOS patients. Methods. We examined 31 ACOS patients and 32 control patients. Blood levels of HDAC2, PI3K-δ, GR-α, and GR-β mRNAs were measured by the real-time polymerase chain reaction. Results. Reduced expressions of HDAC2 and GR-α, as well as increased expressions of PI3K-δ and GR-β could result in lower steroid sensitivity and more severe ACOS course. Conclusion. Investigation of pharmacogenetic and epigenetic mechanisms of steroid sensitivity in patients with ACOS could predict the efficacy of steroids and personalize the choice of the targeted treatment. Изучение сочетания бронхиальной астмы (БА) и хронической обструктивной болезни легких (ХОБЛ) – синдрома перекреста (ПС) – на сегодняшний день актуально в связи с имеющимися трудностями диагностики и лечения данного состояния. Большой интерес представляет возможность прогнозирования эффективности терапии у больных с ПС. Актуальным и перспективным является изучение фармакогенетических и эпигенетических маркеров у пациентов указанной категории. Целью данного исследования явилась оценка относительной экспрессии HDAC2, PI3K-δ и изоформ глюкокортикостероидных (ГКС)-рецепторов (ГР) – ГР-α и ГР-δ – для создания маркерного профиля стероидочувствительности у больных с ПС. Материалы и методы. Обследованы лица (n = 31) с установленным сочетанием БА и ХОБЛ (ПС) в фазу обострения, курящие или с профессиональными вредностями в анамнезе, получавшие лечение внутривенными ГКС. Контрольную группу составили некурящие лица (n = 32) без хронических заболеваний дыхательной системы в анамнезе и отягощенного аллергического анамнеза. Уровни мРНК HDAC2, PI3K-δ и изоформ ГР-α и ГР-β в крови определялись методом полимеразной цепной реакции в реальном времени. Результаты. Выявлено, что снижение экспрессии HDAC2 и ГР-#a, а также повышение экспрессии PI3K-δ и ГР-β может привести к снижению стероидочувствительности и более тяжелому течению ПС. Заключение. При изучении фармакогенетических и эпигенетических механизмов стероидочувствительности у больных ПС возможно не только уточнение прогноза эффективности терапии ГКС, но и осуществление персонализированного подхода при назначении прецизионный (таргетной) терапии. 

Dijet Resonance Search with Weak Supervision Using root S=13 TeV pp Collisions in the ATLAS Detector

This Letter describes a search for narrowly resonant new physics using a machine-learning anomaly detection procedure that does not rely on signal simulations for developing the analysis selection. Weakly supervised learning is used to train classifiers directly on data to enhance potential signals. The targeted topology is dijet events and the features used for machine learning are the masses of the two jets. The resulting analysis is essentially a three-dimensional search A → BC, for mA ∼ OðTeVÞ, mB; mC ∼ Oð100 GeVÞ and B, C are reconstructed as large-radius jets, without paying a penalty associated with a large trials factor in the scan of the masses of the two jets. The full run 2 ffiffi s p ¼ 13 TeV pp collision dataset of 139 fb−1 recorded by the ATLAS detector at the Large Hadron Collider is used for the search. There is no significant evidence of a localized excess in the dijet invariant mass spectrum between 1.8 and 8.2 TeV. Cross-section limits for narrow-width A, B, and C particles vary with mA, mB, and mC. For example, when mA ¼ 3 TeV and mB ≳ 200 GeV, a production cross section between 1 and 5 fb is excluded at 95% confidence level, depending on mC. For certain masses, these limits are up to 10 times more sensitive than those obtained by the inclusive dijet search. These results are complementary to the dedicated searches for the case that B and C are standard model boson

Measurement of the energy asymmetry in t(t)over-barj production at 13 TeV with the ATLAS experiment and interpretation in the SMEFT framework

A measurement of the energy asymmetry in jet-associated top-quark pair production is presented using $$139\,{\mathrm {fb}}^{-1}$$ 139 fb - 1 of data collected by the ATLAS detector at the Large Hadron Collider during pp collisions at $$\sqrt{s}=13\,\text {TeV}$$ s = 13 TeV . The observable measures the different probability of top and antitop quarks to have the higher energy as a function of the jet scattering angle with respect to the beam axis. The energy asymmetry is measured in the semileptonic $$t{\bar{t}}$$ t t ¯ decay channel, and the hadronically decaying top quark must have transverse momentum above $$350\,\text {GeV}$$ 350 GeV . The results are corrected for detector effects to particle level in three bins of the scattering angle of the associated jet. The measurement agrees with the SM prediction at next-to-leading-order accuracy in quantum chromodynamics in all three bins. In the bin with the largest expected asymmetry, where the jet is emitted perpendicular to the beam, the energy asymmetry is measured to be $$-0.043\pm 0.020$$ - 0.043 ± 0.020 , in agreement with the SM prediction of $$-0.037\pm 0.003$$ - 0.037 ± 0.003 . Interpreting this result in the framework of the Standard Model effective field theory (SMEFT), it is shown that the energy asymmetry is sensitive to the top-quark chirality in four-quark operators and is therefore a valuable new observable in global SMEFT fits

Search for bottom-squark pair production in pp collision events at √s=13 TeV with hadronically decaying τ-leptons, b-jets, and missing transverse momentum using the ATLAS detector

A search for pair production of bottom squarks in events with hadronically decaying τ -leptons, b -tagged jets, and large missing transverse momentum is presented. The analyzed dataset is based on proton-proton collisions at √ s = 13     TeV delivered by the Large Hadron Collider and recorded by the ATLAS detector from 2015 to 2018, and corresponds to an integrated luminosity of 139     fb − 1 . The observed data are compatible with the expected Standard Model background. Results are interpreted in a simplified model where each bottom squark is assumed to decay into the second-lightest neutralino ˜ χ 0 2 and a bottom quark, with ˜ χ 0 2 decaying into a Higgs boson and the lightest neutralino ˜ χ 0 1 . The search focuses on final states where at least one Higgs boson decays into a pair of hadronically decaying τ -leptons. This allows the acceptance and thus the sensitivity to be significantly improved relative to the previous results at low masses of the ˜ χ 0 2 , where bottom-squark masses up to 850 GeV are excluded at the 95% confidence level, assuming a mass difference of 130 GeV between ˜ χ 0 2 and ˜ χ 0 1 . Model-independent upper limits are also set on the cross section of processes beyond the Standard Model

Measurement of the tt¯tt¯ production cross section in pp collisions at √s=13 TeV with the ATLAS detector

A measurement of four-top-quark production using proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the ATLAS detector at the Large Hadron Collider corresponding to an integrated luminosity of 139 fb−1 is presented. Events are selected if they contain a single lepton (electron or muon) or an opposite-sign lepton pair, in association with multiple jets. The events are categorised according to the number of jets and how likely these are to contain b-hadrons. A multivariate technique is then used to discriminate between signal and background events. The measured four-top-quark production cross section is found to be 26+17−15 fb, with a corresponding observed (expected) significance of 1.9 (1.0) standard deviations over the background-only hypothesis. The result is combined with the previous measurement performed by the ATLAS Collaboration in the multilepton final state. The combined four-top-quark production cross section is measured to be 24+7−6 fb, with a corresponding observed (expected) signal significance of 4.7 (2.6) standard deviations over the background-only predictions. It is consistent within 2.0 standard deviations with the Standard Model expectation of 12.0 ± 2.4 fb