Associations of BCL-2 (RS17759659), CTLA-4 (RS231775), APO-1/FAS (RS2234767) genes polymorphisms with activity of proliferation and apoptosis in thyroid tissue of patients with nodular forms of goiter combined with autoimmune thyroiditis and thyroid adenoma

The study of apoptosis and proliferative activity in the thyroid gland (TG) tissue of patients with nodular goiter and autoimmune thyroiditis (NGAIT) and thyroid adenoma (TA) is based on the expression/density of Fas/FasL, BCL-2, p53, and Ki-67 markers assessment depending on the genetic polymorphisms of BCL-2 (rs17759659), CTLA-4 (rs231775) and APO-1/Fas (rs2234767) genes.Several mechanisms of thyroid cells' programmed killing are activated in NGAIT and TA with domination of Fas-induced apoptosis, which strongly associates with the BCL-2 gene's (rs17759659) promoter (F=25.33; p<0.001) and almost six fold weaker associates with the CTLA-4 gene's (rs231775) promoter (F=4.23, p=0.017). Factors that decrease the likelihood of NGAIT and TA regardless of the CTLA-4 (rs231775) and APO-1/Fas (rs2234767) genes' genotypes are the high Ki-67 density and reduction of cells containing p53 or BCL-2 proteins (OR=0.07-0.17; 95% CI OR: 0.03-0.36; p<0.001, and OR=0.08-0.11; 95% CI OR: 0.02-0.31; p<0.001, re­spectively). High expression of surface Fas and FasL in lymphoid infiltration and de­struction of thyroid cells (stronger in GG-genotype carriers of the BCL-2 gene by 18.54% (pAA=0.043) and 36.18% (pAG=0.018), respectively) indicates the initiation of the external pathway of apoptosis through the caspase mechanism (effector caspase- 8)

Dynamics of spin correlations in the spin-1/2 isotropic XY chain in a transverse field

Dynamic xx spin pair correlation functions for the isotropic spin-1/2 XY chain are calculated numerically for long open chains in the presence of a transverse magnetic field at finite temperature. As an application we discuss the temperature dependence of the spin-spin relaxation time in PrCl_3.Comment: 2 pages, latex, 2 figures, abstract of the paper presented at Ampere Summer School ``Applications of Magnetic Resonance in Novel Materials'' Nafplion, Greece, 3-9 September, 2000, partially published in J. Phys. A: Math. Gen. 33, 3063 (2000

Поліморфізм генів apo-1 / fas, ctla-4 та bcl-2 у пацієнтів, оперованих із приводу вузлової патології щитоподібної залози

The aim of the work: to analyze the frequency of polymorphic variants of genes BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1/ Fas (rs2234767) in patients, operated on nodular thyroid pathology with regard to its form (NGAIT, TA- thyroid adenoma).Materials and Methods. An analysis of the frequency of polymorphic variants of genes BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1/Fas (rs2234767) in 125 patients, operated on nodular thyroid pathology with regard to its form (NGAIT, TA) was conducted. Also, we examined 25 healthy donors. The study of polymorphism of genes was carried out by the method of polymerase chain reac­tion in real time.Results and Discussion. Mutation of BCL-2 gene (rs17759659) and CTLA-4 (rs231775) in the homozygous state among patients, operated on nodular thyroid pathology occurs with a frequency 3.2–4.0 % no reliable difference between patients with thyroid pathology and healthy. Mutation of the gene APO-1/Fas (rs2234767) in the homozygous state among surveyed patients was not met at all.Цель работы: провести анализ частоты полиморфных вариантов генов BCL-2 ( rs17759659), CTLA-4 ( rs231775), APO-1/Fas (rs2234767) у пациентов, оперированных по поводу узловой патологии щитовидной железы (ЩЖ) с учетом ее вида (узловой зоб на фоне аутоиммунного тиреоидита, аденома щитовидной железы.Материалы и методы. Проведен анализ частоты полиморфных вариантов генов BCL-2 ( rs17759659), CTLA-4 (rs231775), APO-1/Fas (rs2234767) у 125 пациентов, оперированных по поводу узловой патологии щитовидной железы с учетом ее вида (узловой зоб на фоне аутоиммунного тиреоидита, аденома щитовидной железы). Также обследовано 25 практически здоровых доноров. Исследование полиморфизма генов проводили методом полимеразной цепной реакции в режиме реального времени.Результаты исследований и их обсуждение. Мутация генов BCL-2 ( rs17759659) и CTLA-4 ( rs231775) в гомозиготном состоянии среди пациентов, оперированных по поводу узловой патологии щитовидной железы, встречается с частотой 3,2– 4,0 % без достоверной разницы между больными на патологию щитовидной железы и здоровыми. Мутация гена APO-1/Fas (rs2234767) в гомозиготном состоянии среди обследованных не встречалась вообще.Мета роботи: провести аналіз частоти поліморфних варіантів генів BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1/Fas (rs2234767) у хворих, оперованих із приводу вузлової патології щитоподібної залози із урахуванням її виду вузловий зоб на фоні автоімунного тиреоїдиту, аденома щитоподібної залози. Матеріали і методи. Проведено аналіз частоти поліморфних варіантів генів BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1/Fas (rs2234767) у 125 хворих, оперованих з приводу вузлової патології щитоподібної залози із урахуванням її виду – вузлового зоба на фоні автоімунного тиреоїдиту, аденома щитоподібної залози. Також обстежено 25 практично здорових донорів. Дослідження поліморфізму генів проводили методом полімеразної ланцюгової реакції в режимі реального часу.Результати досліджень та їх обговорення. Мутація генів BCL-2 (rs17759659) та CTLA-4 (rs231775) у гомозиготному стані у хворих, оперованих з приводу вузлової патології щитоподібної залози, зустрічається із частотою 3,2–4,0 % без вірогідної різниці між хворими на патологію щитоподібної залози та здоровими. Мутація гена APO-1/Fas (rs2234767) у гомозиготному стані серед обстежених не траплялася взагалі

Effective transcription factor binding site prediction using a combination of optimization, a genetic algorithm and discriminant analysis to capture distant interactions

<p>Abstract</p> <p>Background</p> <p>Reliable transcription factor binding site (TFBS) prediction methods are essential for computer annotation of large amount of genome sequence data. However, current methods to predict TFBSs are hampered by the high false-positive rates that occur when only sequence conservation at the core binding-sites is considered.</p> <p>Results</p> <p>To improve this situation, we have quantified the performance of several Position Weight Matrix (PWM) algorithms, using exhaustive approaches to find their optimal length and position. We applied these approaches to bio-medically important TFBSs involved in the regulation of cell growth and proliferation as well as in inflammatory, immune, and antiviral responses (NF-κB, ISGF3, IRF1, STAT1), obesity and lipid metabolism (PPAR, SREBP, HNF4), regulation of the steroidogenic (SF-1) and cell cycle (E2F) genes expression. We have also gained extra specificity using a method, entitled SiteGA, which takes into account structural interactions within TFBS core and flanking regions, using a genetic algorithm (GA) with a discriminant function of locally positioned dinucleotide (LPD) frequencies.</p> <p>To ensure a higher confidence in our approach, we applied resampling-jackknife and bootstrap tests for the comparison, it appears that, optimized PWM and SiteGA have shown similar recognition performances. Then we applied SiteGA and optimized PWMs (both separately and together) to sequences in the Eukaryotic Promoter Database (EPD). The resulting SiteGA recognition models can now be used to search sequences for BSs using the web tool, SiteGA.</p> <p>Analysis of dependencies between close and distant LPDs revealed by SiteGA models has shown that the most significant correlations are between close LPDs, and are generally located in the core (footprint) region. A greater number of less significant correlations are mainly between distant LPDs, which spanned both core and flanking regions. When SiteGA and optimized PWM models were applied together, this substantially reduced false positives at least at higher stringencies.</p> <p>Conclusion</p> <p>Based on this analysis, SiteGA adds substantial specificity even to optimized PWMs and may be considered for large-scale genome analysis. It adds to the range of techniques available for TFBS prediction, and EPD analysis has led to a list of genes which appear to be regulated by the above TFs.</p

Role of LAG-3 in Regulatory T Cells

AbstractRegulatory T cells (Tregs) limit autoimmunity but also attenuate the magnitude of antipathogen and antitumor immunity. Understanding the mechanism of Treg function and therapeutic manipulation of Tregs in vivo requires identification of Treg-selective receptors. A comparative analysis of gene expression arrays from antigen-specific CD4+ T cells differentiating to either an effector/memory or a regulatory phenotype revealed Treg-selective expression of LAG-3, a CD4-related molecule that binds MHC class II. Antibodies to LAG-3 inhibit suppression by induced Tregs both in vitro and in vivo. Natural CD4+CD25+ Tregs express LAG-3 upon activation, which is significantly enhanced in the presence of effector cells, whereas CD4+CD25+ Tregs from LAG-3−/− mice exhibit reduced regulatory activity. Lastly, ectopic expression of LAG-3 on CD4+ T cells significantly reduces their proliferative capacity and confers on them suppressor activity toward effector T cells. We propose that LAG-3 marks regulatory T cell populations and contributes to their suppressor activity

Observation of narrow baryon resonance decaying into pKs0pK^0_s in pA-interactions at 70GeV/c70 GeV/c with SVD-2 setup

SVD-2 experiment data have been analyzed to search for an exotic baryon state, the $\Theta^+$-baryon, in a $pK^0_s$ decay mode at $70 GeV/c$ on IHEP accelerator. The reaction $pA \to pK^0_s+X$ with a limited multiplicity was used in the analysis. The $pK^0_s$ invariant mass spectrum shows a resonant structure with $M=1526\pm3(stat.)\pm 3(syst.) MeV/c^2$ and $\Gamma < 24 MeV/c^2$. The statistical significance of this peak was estimated to be of $5.6 \sigma$. The mass and width of the resonance is compatible with the recently reported $\Theta^+$- baryon with positive strangeness which was predicted as an exotic pentaquark ($uudd\bar{s}$) baryon state. The total cross section for $\Theta^+$ production in pN-interactions for $X_F\ge 0$ was estimated to be $(30\div120) \mu b$ and no essential deviation from A-dependence for inelastic events $(\sim A^{0.7})$ was found.Comment: 8 pages, 7 figures, To be submitted to Yadernaya Fizika. v3-v5 - Some references added, minor typos correcte

Малоинвазивные методы временной декомпрессии ободочной кишки при обтурационной толстокишечной непроходимости: обзор литературы

Colorectal cancer is one of the most common oncological diseases. In 40–60% of cases, patients with colorectal cancer enter general surgical hospitals with complications. Obstructive colonic obstruction is the most common complication of colorectal cancer. The radical operation against the background of colonic obstruction is associated with a high postoperative lethality, ranging from 5% to 34%. To improve the results of surgical treatment of patients with colorectal cancer complicated by obturation colonic obstruction, various minimally invasive methods of temporary decompression have been proposed, followed by radical surgery, which signifcantly reduce the risk of complications and mortality. Колоректальный рак является одним из наиболее распространенных онкологических заболеваний. В 40–60% случаев больные колоректальным раком поступают в общехирургические стационары с осложненными формами. Обтурационная толстокишечная непроходимость является наиболее часто встречающимся осложнением рака ободочной кишки. Выполнение радикальных операций на фоне кишечной непроходимости сопряжено с высокой послеоперационной летальностью, составляющей от 5% до 34%. Для улучшения результатов хирургического лечения больных колоректальным раком, осложненным обтурационной толстокишечной непроходимостью, предложены различные малоинвазивные методы временной декомпрессии кишечника с последующим радикальным хирургическим вмешательством, которые значительно снижают риск развития осложнений и летальности

Authoritarian Neoliberalism and Democratic Backsliding in Turkey: Beyond the Narratives of Progress

Unpacking the core themes that are discussed in this collection, this article both offers a research agenda to re-analyse Turkey’s ‘authoritarian turn’ and mounts a methodological challenge to the conceptual frameworks that reinforce a strict analytical separation between the ‘economic’ and the ‘political’ factors. The paper problematises the temporal break in scholarly analyses of the AKP period and rejects the argument that the party’s methods of governance have shifted from an earlier ‘democratic’ model – defined by ‘hegemony’ – to an emergent ‘authoritarian’ one. In contrast, by retracing the mechanisms of the state-led reproduction of neoliberalism since 2003, the paper demonstrates that the party’s earlier ‘hegemonic’ activities were also shaped by authoritarian tendencies which manifested at various levels of governance