Prothymosin α fragmentation in apoptosis

AbstractWe observed fragmentation of an essential proliferation-related human nuclear protein prothymosin α in the course of apoptosis induced by various stimuli. Prothymosin α cleavage occurred at the DDVD99 motif. In vitro, prothymosin α could be cleaved at D99 by caspase-3 and -7. Caspase hydrolysis disrupted the nuclear localization signal of prothymosin α and abrogated the ability of the truncated protein to accumulate inside the nucleus. Prothymosin α fragmentation may therefore be proposed to disable intranuclear proliferation-related function of prothymosin α in two ways: by cleaving off a short peptide containing important determinants, and by preventing active nuclear uptake of the truncated protein

Arabidopsis thaliana phytaspase: identification and peculiar properties

Phytaspases are plant cell death-related proteases of the subtilisin-like protease family that possess an unusual aspartate cleavage specificity. Although phytaspase activity is widespread in plants, phytaspase of Arabidopsis thaliana (L.) Heynh. has escaped detection and identification thus far. Here, we show that a single gene (At4 g10540) out of 56 A. thaliana subtilisin-like protease genes encodes a phytaspase. The recombinant phytaspase was overproduced in Nicotiana benthamiana Domin leaves, isolated, and its substrate specificity and properties were characterised. At pH 5.5, at physiological mildly acidic reaction conditions, the Arabidopsis phytaspase was shown to be strictly Asp-specific. The strongly preferred cleavage motifs of the enzyme out of a panel of synthetic peptide substrates were YVAD and IETD, while the VEID-based substrate preferred by the tobacco and rice phytaspases was almost completely resistant to hydrolysis. At neutral pH, however, the Arabidopsis phytaspase could hydrolyse peptide substrates after two additional amino acid residues, His and Phe, in addition to Asp. This observation may indicate that the repertoire of Arabidopsis phytaspase targets could possibly be regulated by the conditions of the cellular environment. Similar to tobacco and rice phytaspases, the Arabidopsis enzyme was shown to accumulate in the apoplast of epidermal leaf cells. However, in stomatal cells Arabidopsis phytaspase was observed inside the cells, possibly co-localising with vacuole. Our study thus demonstrates that the Arabidopsis phytaspase possesses both important similarities with and distinctions from the already known phytaspases, and is likely to be the most divergent member of the phytaspase family

РЕНАЛЬНАЯ ДЕНЕРВАЦИЯ: ОБЗОР

The review describes an up-to-date status and development prospects of a minimally invasive method of arterial hypertension treatment, the renal denervation.Представлен обзор литературы, описывающий современное состояние вопроса и перспективы развития малоинвазивного направления в лечении резистентной к терапии артериальной гипертензии – ренальной денервации

From structure to function – a family portrait of plant subtilases

Subtilases (SBTs) are serine peptidases that are found in all three domains of life. As compared with homologs in other Eucarya, plant SBTs are more closely related to archaeal and bacterial SBTs, with which they share many biochemical and structural features. However, in the course of evolution, functional diversification led to the acquisition of novel, plant-specific functions, resulting in the present-day complexity of the plant SBT family. SBTs are much more numerous in plants than in any other organism, and include enzymes involved in general proteolysis as well as highly specific processing proteases. Most SBTs are targeted to the cell wall, where they contribute to the control of growth and development by regulating the properties of the cell wall and the activity of extracellular signaling molecules. Plant SBTs affect all stages of the life cycle as they contribute to embryogenesis, seed development and germination, cuticle formation and epidermal patterning, vascular development, programmed cell death, organ abscission, senescence, and plant responses to their biotic and abiotic environments. In this article we provide a comprehensive picture of SBT structure and function in plants.Instituto de Fisiología Vegeta

Клиническая эффективность криобаллонной изоляции легочных вен у пациентов с фибрилляцией предсердий

Aim. To estimate the clinical success of cryoballoon pulmonary vein isolation (PVI).Methods. 230 patients (males: 49.6%, mean age 57 (53; 62) with symptomatic paroxysmal and persistent atrial fibrillation (AF) resistant to antiarrhythmic therapy were included in a single-center prospective study. The patients were randomized into 2 groups to undergo either cryoballoon ablation (n = 122) or radiofrequency (RF) (n = 108) ablation. Both groups were comparable in baseline parameters. The follow-up period was 12 months. Clinical outcomes were estimated with the use of a three-stage scale. The rates of cardiovascular rehospitalizations, direct-current cardioversions and repeated ablations during were estimated within the follow-up. The quality of life (QoL) in the cryoablation group was measured using the AFEQT scale.Results. 77% (n = 94) of patients in the cryoballoon ablation group and 71.3% (n = 77) of patients in the RF group (р = 0.71) demonstrated reported the optimal clinical effects. Both groups, cryo ablation and RF ablation, had similar rates of cardiovascular hospitalizations (23.8 vs 28.7%, OR 0.8, 95% CI 0.4–1.4; р = 0.39), direct-current cardioversions (12.3 vs 17.6%, OR 0.7, 95% CI 0.3–1.4; р = 0.26) and repeated ablations (9.8–11.1%, OR 0.9, 95% CI 0.4–2.0; р = 0.75). The patients treated with cryoballoon as opposed to RF ablation had significantly more successful usage of “pill-in-pocket” strategy – 14.8 vs 6.5% (OR 2.5, 95% CI 1.01–6.2; р = 0.04). Significant improvements of the QoL parameters with strong size effect have been found in the cryoablation group, i.e. global score (GS) increased by 8.9±6.9 (95% CI 6.6–10.1; dCohen 1.2; р<0.001), symptoms (S) – by 8.3±7.9 (95% CI 4.2–8.8; dCohen 1.5; р<0.001), daily activities (DA) – by 10.0±6.9 (95% CI = 6.4–10.6; dCohen 0.9; р<0.001), treatment concerns (TC) – by 5.5±6.0 (95% CI 6.3–9.2; dCohen 1.2; р<0.001) and treatment satisfaction (TS) – by 5.5±6.0 (95% CI 5.4–9.8; dCohen 0.9; р<0.001).Conclusion. The both catheter-based technologies had comparable clinical success. Cryoablation was characterized by improvement in all QoL parameters based on the AFEQT score.Цель. Оценить клиническую эффективность криобаллонной изоляции легочных вен (ЛВ).Материалы и методы. В проспективное исследование было включено 230 пациентов (49,6% мужчин, средний возраст 57 (53; 62 лет)) с пароксизмальной и персистирующей фибрилляцией предсердий (ФП), резистентной к антиаритмической терапии. Пациенты были случайным образом распределены в группы криобаллонной (n = 122) и радиочастотной (РЧ) (n = 108) изоляции ЛВ. По основным клиническим характеристикам группы не различались. Период наблюдения составил 12 месяцев. Для оценки клинического эффекта применялась трехступенчатая шкала. Также оценивалась частота госпитализаций по поводу сердечно-сосудистых заболеваний, кардиоверсий и реаблаций. Дополнительно в группе криоаблации была изучена динамика показателей качества жизни с применением шкалы AFEQT.Результаты. Оптимальный клинический эффект был выявлен в 77% (94) случаев в группе криоаблации и 71,3% (77) – в группе РЧА (р = 0,71). Между группами не выявлено различий в отношении частоты госпитализаций по поводу ССЗ – 23,8 против 28,7% (ОШ = 0,8, 95% ДИ = 0,4–1,4; р = 0,39), кардиоверсий – 12,3 vs 17,6% (ОШ = 0,7, 95% ДИ = 0,3–1,4; р = 0,26) и повторных аблаций – 9,8– 11,1% (ОШ = 0,9, 95% ДИ = 0,4–2,0; р = 0,75). В группе криоаблации частота эффективного применения стратегии «таблетка в кармане» была выше: 14,8 (n = 18) против 6,5% (ОШ = 2,5, 95% ДИ = 1,01–6,2; p = 0,04). В группе криоаблации была выявлена значимая положительная динамика всех показателей качества жизни с выраженной величиной эффекта – суммарный показатель (GS) увеличился на 8,9±6,9 (95% ДИ 6,6–10,1; dCohen 1,2; р<0,001), симптомности (S) – на 8,3±7,9 (95% ДИ 4,2–8,8; dCohen 1,5; р<0,001), ежедневной активности (DA) – на 10,0±6,9 (95% ДИ 6,4–10,6; dCohen 0,9; р<0,001), обеспокоенности (TC) – на 5,5±6,0 (95% ДИ 6,3–9,2; dCohen 1,2; р<0,001) и удовлетворенности (TS) лечением – на 5,5±6,0 (95% ДИ 5,4–9,8; dCohen 0,9; р<0,001).Заключение. Клиническая эффективность криобаллонной и радиочастотной изоляции ЛВ сопоставима. Криоаблация характеризуется значимым улучшением всех показателей качества жизни на основании данных шкалы AFEQT

The tomato subtilase family includes several cell death-related proteinases with caspase specificity

Phytaspases are Asp-specific subtilisin-like plant proteases that have been likened to animal caspases with respect to their regulatory function in programmed cell death (PCD). We identified twelve putative phytaspase genes in tomato that differed widely in expression level and tissue-specific expression patterns. Most phytaspase genes are tandemly arranged on tomato chromosomes one, four, and eight, and many belong to taxon-specific clades, e.g. the P69 clade in the nightshade family, suggesting that these genes evolved by gene duplication after speciation. Five tomato phytaspases (SlPhyts) were expressed in N. benthamiana and purified to homogeneity. Substrate specificity was analyzed in a proteomics assay and with a panel of fluorogenic peptide substrates. Similar to animal caspases, SlPhyts recognized an extended sequence motif including Asp at the cleavage site. Clear differences in cleavage site preference were observed implying different substrates in vivo and, consequently, different physiological functions. A caspase-like function in PCD was confirmed for five of the seven tested phytaspases. Cell death was triggered by ectopic expression of SlPhyts 2, 3, 4, 5, 6 in tomato leaves by agro-infiltration, as well as in stably transformed transgenic tomato plants. SlPhyts 3, 4, and 5 were found to contribute to cell death under oxidative stress conditions

The tomato subtilase family includes several cell death-related proteinases with caspase specificity

Phytaspases are Asp-specific subtilisin-like plant proteases that have been likened to animal caspases with respect to their regulatory function in programmed cell death (PCD). We identified twelve putative phytaspase genes in tomato that differed widely in expression level and tissue-specific expression patterns. Most phytaspase genes are tandemly arranged on tomato chromosomes one, four, and eight, and many belong to taxon-specific clades, e.g. the P69 clade in the nightshade family, suggesting that these genes evolved by gene duplication after speciation. Five tomato phytaspases (SlPhyts) were expressed in N. benthamiana and purified to homogeneity. Substrate specificity was analyzed in a proteomics assay and with a panel of fluorogenic peptide substrates. Similar to animal caspases, SlPhyts recognized an extended sequence motif including Asp at the cleavage site. Clear differences in cleavage site preference were observed implying different substrates in vivo and, consequently, different physiological functions. A caspase-like function in PCD was confirmed for five of the seven tested phytaspases. Cell death was triggered by ectopic expression of SlPhyts 2, 3, 4, 5, 6 in tomato leaves by agro-infiltration, as well as in stably transformed transgenic tomato plants. SlPhyts 3, 4, and 5 were found to contribute to cell death under oxidative stress conditions

ПОДХОДЫ К ВЕДЕНИЮ БОЛЬНЫХ С ВЫСОКИМ РИСКОМ ВНЕЗАПНОЙ СМЕРТИ С НАДЖЕЛУДОЧКОВЫМИ ТАХИАРИТМИЯМИ: ОБЗОР РЕКОМЕНДАЦИЙ

Patients with Wolff-Parkinson-White syndrome (WPW), neonates, and patients with major structural cardiac pathology who suffer from supraventricular tachycardia are at higher risk of sudden cardiac death. The review article accumulates evidence-based knowledge provided in the recent guidelines and expert consensus on the prevention of sudden cardiac death in adults and children with different SVT types. The review provides current data on the risk of sudden cardiac death in patients with supraventricular tachycardia, possible pathogenetic patterns of sudden cardiac death in this patient population, current guidelines on catheter ablation for supraventricular tachycardia to prevent sudden cardiac death in adults and children.Группа пациентов с наличием суправентрикулярных тахикардий (СВТ) и высоким риском внезапной смерти объединяет больных с синдромом Вольфа-Паркинсона-Уайта (WPW), новорожденных с СВТ и пациентов с СВТ и выраженной структурной патологией сердца. Обзорная статья включает основные положения всех действующих в настоящий момент рекомендательных документов и экспертных консенсусов, касающихся подходов к профилактике внезапной сердечной смерти при различных видах СВТ у взрослых и детей. В обзоре описываются современные данные о риске внезапной сердечной смерти у пациентов, страдающих наджелудочковыми тахикардиями, возможные варианты патогенеза внезапной сердечной смерти у данной категории пациентов, действующей в настоящее время рекомендации по катетерной аблации суправентрикулярных тахикардий для профилактики внезапной сердечной смерти у взрослых и детей