Роль нейтрофилов в патогенезе ишемического инсульта

Background. Immune responses and inflammation play an important role in the pathogenesis of ischemic stroke.Aim. To analyze the involvement of neutrophils in the pathogenesis of ischemic stroke.Results. Data on the contribution of neutrophil granulocytes to the development of local sterile inflammation and secondary brain injury in acute ischemic stroke were summarized. Mechanisms of neutrophil influence on thrombosis, neutrophil extracellular trap formation (NETosis), protease release, and direct interaction with platelets with subsequent formation of platelet-leukocyte aggregates were discussed. Available information on the effectiveness of reperfusion therapy and an association of changes in neutrophil activity with development of infectious complications of stroke were presented. In addition, research data were presented on the contribution of neutrophils to atherogenesis, which is one of the most important etiological factors in ischemic stroke. The review showed that the contribution of neutrophils to the pathogenesis of ischemic stroke is associated with implementation of their secretory, regulatory, and phagocytic functions, as well as with NETosis.Conclusion. It was shown that neutrophils are involved in the pathogenesis of ischemic stroke and modulate a response to treatment.Актуальность. Иммунные реакции и воспалительный процесс играют важную роль в патогенезе ишемического инсульта.Цель. На основании научных публикаций проанализировать вовлеченность нейтрофилов в патогенез ишемического инсульта.Результаты. Обобщены данные о вкладе нейтрофильных гранулоцитов в развитие локального асептического воспаления и вторичного повреждения мозга при остром инсульте. Обсуждены механизмы влияния нейтрофилов на процесс тромбообразования, образование нейтрофильных внеклеточных ловушек (нетоз), высвобождение протеаз и прямое взаимодействие с тромбоцитами с образованием лейкоцитарно-тромбоцитарных агрегатов. Приведены имеющиеся сведения об эффективности реперфузионной терапии, а также ассоциации изменений активности нейтрофилов с развитием инфекционных осложнений инсульта. Представлены данные исследований о вкладе нейтрофилов в атерогенез, являющийся одним из важнейших этиологических факторов ишемического инсульта. Показано, что участие нейтрофилов в патогенезе ишемического инсульта связано с реализацией их секреторных, регуляторных, фагоцитарных функций и с нетозом.Заключение. Установлено, что нейтрофилы принимают активное участие в патогенезе ишемического инсульта и модулируют ответ на лечение

Recycling-Oriented Design of the Al-Zn-Mg-Ca Alloys

Presented at the 1st International Electronic Conference on Metallurgy and Metals, 22 February–7 March 2021; Available online: https://iec2m.sciforum.net/.Approaches to the design of recycling-tolerant Al-Zn-Mg alloys were formulated to be achieved via combined Ca, Fe, and Si, and appropriate solidification conditions and heat treatment. A CalPhaD calculation and experimental study were employed for analysis of the Al-8%Zn-3%Mg alloy doped with 1–2%Ca, 0.5%Fe, and 0.5%Si. The Al-8%Zn-3%Mg-1%Ca-0.5%Fe-0.5%Si (AlZnMg1CaFeSi) alloy was preliminarily found to be promising since it showed a high equilibrium solidus, and an as-cast structure including curved phases (Al), Al3Fe, Al2CaSi2, Al10CaFe2, and (Al, Zn)4Ca; favouring a further spheroidization response during a two-step annealing at 450 °C, 3 h + 520 °C, 3 h. Furthermore, the alloy showed an excellent age-hardening response (195 HV, T6), which did not yield the values of the base alloy and outperformed the values of the other experimental counterparts. Regarding feasibility, 80% reduction hot rolling was successfully conducted, as well as a brief comparison with commercial 6063 impurity-tolerant alloys. As it showed qualitatively similar structural patterns and Fe and Si alloying opportunities, the AlZnMg1CaFeSi alloy may serve as a sustainable basis for the further development of high-strength aluminum alloys tailored for manufacture from scrap materials.Russian Science Foundation, Project No. 20-79-10373

Difficulties in diagnosis and treatment of adult-onset Still's disease concurrent with pericardial effusion as a leading clinical manifestation

The paper considers a case of adult-onset Still's disease that occurred as acute pericarditis, two-spike hectic fever, and neutrophilic leukocytosis in a young man. It was difficult to establish a correct diagnosis because there were no characteristic clinical symptoms of Still's disease, such as salmon colored rash, arthralgia, and sore throat. The diagnosis of adult-onset Still's disease was verified on the basis of the classification criteria described by M. Yamaguchi et al. The special feature of the clinical case was the development of steroid resistance and the effective use of a combination of the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, given intravenously dropwise once every four weeks) and methotrexate (15 mg/week orally). During this treatment, a sustained clinical and laboratory response was achieved, which could reduce the dose of glucocorticoids to the maintaining one

Strengths and weaknesses of EST-based prediction of tissue-specific alternative splicing

BACKGROUND: Alternative splicing contributes significantly to the complexity of the human transcriptome and proteome. Computational prediction of alternative splice isoforms are usually based on EST sequences that also allow to approximate the expression pattern of the related transcripts. However, the limited number of tissues represented in the EST data as well as the different cDNA construction protocols may influence the predictive capacity of ESTs to unravel tissue-specifically expressed transcripts. METHODS: We predict tissue and tumor specific splice isoforms based on the genomic mapping (SpliceNest) of the EST consensus sequences and library annotation provided in the GeneNest database. We further ascertain the potentially rare tissue specific transcripts as the ones represented only by ESTs derived from normalized libraries. A subset of the predicted tissue and tumor specific isoforms are then validated via RT-PCR experiments over a spectrum of 40 tissue types. RESULTS: Our strategy revealed 427 genes with at least one tissue specific transcript as well as 1120 genes showing tumor specific isoforms. While our experimental evaluation of computationally predicted tissue-specific isoforms revealed a high success rate in confirming the expression of these isoforms in the respective tissue, the strategy frequently failed to detect the expected restricted expression pattern. The analysis of putative lowly expressed transcripts using normalized cDNA libraries suggests that our ability to detect tissue-specific isoforms strongly depends on the expression level of the respective transcript as well as on the sensitivity of the experimental methods. Especially splice isoforms predicted to be disease-specific tend to represent transcripts that are expressed in a set of healthy tissues rather than novel isoforms. CONCLUSIONS: We propose to combine the computational prediction of alternative splice isoforms with experimental validation for efficient delineation of an accurate set of tissue-specific transcripts

Ouabain Stimulates a Na+/K+-ATPase-Mediated SFK-Activated Signalling Pathway That Regulates Tight Junction Function in the Mouse Blastocyst

The Na+/K+-ATPase plays a pivotal role during preimplantation development; it establishes a trans-epithelial ionic gradient that facilitates the formation of the fluid-filled blastocyst cavity, crucial for implantation and successful pregnancy. The Na+/K+-ATPase is also implicated in regulating tight junctions and cardiotonic steroid (CTS)-induced signal transduction via SRC. We investigated the expression of SRC family kinase (SFK) members, Src and Yes, during preimplantation development and determined whether SFK activity is required for blastocyst formation. Embryos were collected following super-ovulation of CD1 or MF1 female mice. RT-PCR was used to detect SFK mRNAs encoding Src and Yes throughout preimplantation development. SRC and YES protein were localized throughout preimplantation development. Treatment of mouse morulae with the SFK inhibitors PP2 and SU6656 for 18 hours resulted in a reversible blockade of progression to the blastocyst stage. Blastocysts treated with 10−3 M ouabain for 2 or 10 minutes and immediately immunostained for phosphorylation at SRC tyr418 displayed reduced phosphorylation while in contrast blastocysts treated with 10−4 M displayed increased tyr418 fluorescence. SFK inhibition increased and SFK activation reduced trophectoderm tight junction permeability in blastocysts. The results demonstrate that SFKs are expressed during preimplantation development and that SFK activity is required for blastocyst formation and is an important mediator of trophectoderm tight junction permeability

Проблемы выбора стратегии скрининга рака молочной железы у женщин старших возрастных групп

The article describes modern view on early breast cancer diagnosis in elderly women. The emphasis was made on controversies and problems of breast cancer mammography screening in women older than 75 years. As a result of Moscow breast cancer statistics analysis the authors made a conclusion that breast cancer mammographic screening could be performed in women 75 years or older. Final decision of inclusion or exclusion needs to be accepted individually in each case, and should be made regarding individual comorbidity of patients. В статье отражен современный взгляд на различные варианты проведения скрининга рака молочной железы (РМЖ) у пожилых женщин. Особое внимание уделено сложностям и противоречиям в определении возрастных рамок к проведению маммографического скрининга РМЖ, существующим в научной литературе. На основании анализа статистических данных по г. Москве авторами сделаны выводы о возможности проведения маммо-графического скрининга РМЖ у женщин в возрасте 75 лет и старше при условии индивидуального подхода к включению в программу скрининга РМЖ с учетом коморбидности. 

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

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