Убивство з милосердя?

Березовська Н. Л. Убивство з милосердя? / Н. Л. Березовська // Актуальні проблеми держави і права: зб. наук.пр. /редкол.: С. В. Ківалов (голов. ред.), В. М. Дрьомін (заст. голов. ред.), Ю. П. Аленін [та ін.]; МОН України, НУ ОЮА. – Одеса: Юрид. л-ра, 2013. – Вип. 70. - С. 250-256.У статті аналізується законодавство України, наводяться погляди на проблему вбивства ненароджених дітей за бажанням матері, пропонуються шляхи захисту життя з моменту зачаття

Міжнародне співробітництво у сфері покарання неповнолітніх

Березовська Н. Л. Міжнародне співробітництво у сфері покарання неповнолітніх / Н. Л. Березовська // Актуальні проблеми держави і права : збірник наук. праць. Вип. 64 / НУ «ОЮА» , редкол. С. В. Ківалов (голов. ред.) та ін., відп. за вип. В. М. Дрьомін. – Одеса : Юрид. л-ра, 2012. – С. 559-567.В статті проведений загальний аналіз міжнародно-правового законодавства щодо покарання с неповнолітніх. Співвідносяться положення діючого кримінального законодавства та міжнародно-правових актів щодо покарання неповнолітніх

Каральні властивості громадських робіт

Березовська Н. Л. Каральні властивості громадських робіт / Н. Л. Березовська // Актуальні проблеми держави і права : зб. наук. пр. / редкол.: С. В. Ківалов (голов. ред.), Ю. М. Оборотов (заст. голов. ред.), Л. Р. Біла (відп. секр.) [та ін.] ; ОНЮА. – Одеса : Юрид. л-ра, 2005. – Вип. 25. – С. 444-448

ВПЛИВ КОНЦЕНТРАЦІЇ ДРІЖДЖОВИХ КЛІТИН НА ЗБРОДЖУВАННЯ ВИСОКОГУСТИННОГО ПИВНОГО СУСЛА

The effect of the concentration of yeast cells on fermentation rate and the degree of beer fermentation involving lager brewing yeast strain Saflager W–34/70 was studied. physical and chemical characteristics of the young beer obtained with studied concentrations of yeasts were determined. It was found that the fermentation rate of wort with the yeast pitching rate of 22,5–50 million cells per 1 cm3 differed slightly and was higher than with the pitching rate of 15 and 7,5 million cells in 1 cm3, which increased the delay of fermentation. With the increasing of yeast cells concentrations in the wort at the start of fermentation from 7,5 to 15 million cells in 1 cm3, content of ethanol in young beer and its degree of fermentation were increased slightly. Pitching rate of 22,5 million cells per 1 cm3 stimulated the formation of the maximum quantity of ethanol and achieving the maximum degree of fermentation. When the yeast concentration increased to 30 and 50 million cells in 1 cm3these parameters were slightly lower. At all investigated pitching rates of yeast, exept 7,5 million cells per 1 cm3, the content of vicinal diketones was in the normal range for young beer before the maturation stage. It was established that to achive the fermentation of 16 % beer wort with adequate fermentation rate and to get the young beer with relevant physico–chemical parameters, the optimal pitching rate is 22,5 million cells per 1 cm3of wort.Исследовано влияние концентрации дрожжевых клеток на скорость брожения и степень сбраживания пива с участием низового штамма пивных дрожжей Saflager W–34/70. Определены физико–химические показатели молодого пива, полученного при исследуемых концентрациях дрожжей.Выявлено, что при внесении 22,5–50 млн. клеток на 1 см3 скорость брожения сусла отличалась незначительно и была выше, чем при нормах внесения дрожжей 15 и 75 млн. клеток на 1 см3, при которых увеличивалась продолжительность задержки брожения. При увеличении концентрации дрожжей от 7,5 до 15 млн. клеток в 1 см3 содержание этанола в молодом пиве и степень его сбраживания увеличивались незначительно. При норме внесения 22,5 млн. клеток на 1 см3 наблюдали образование максимального количества этанола и достижение максимального степени сбраживания. При повышении концентрации до 30 и 50 млн. клеток в 1 см3 эти показатели были незначительно ниже. При всех исследуемых нормах внесения дрожжей, кроме 7,5 млн. клеток на 1 см3, содержание вицинальных дикетонов было в пределах нормы для пива перед стадией дображивания и созревания.Установлено, что для сбраживания 16%–го пивного сусла с адекватной скоростью и получения молодого пива с соответствующими физико–химическим показателям оптимальная норма внесения дрожжей составляет 22,5 млн. клеток на 1 см3 сусла.Досліджено вплив концентрації дріжджових клітин на швидкість бродіння та ступінь зброджування пива за участю низового штаму пивних дріжджів Saflager W–34/70. Визначено фізико–хімічні показники молодого пива, отриманого при досліджуваних концентраціях дріжджів. Виявлено, що при внесенні 22,5–50 млн. клітин на 1 см3 швидкість бродіння сусла відрізнялась незначно та була вищою, ніж при нормах внесення дріжджів 15 і 7,5 млн. клітин на 1 см3, за яких збільшувалась тривалість затримки бродіння. При збільшенні концентрації дріжджів від 7,5 до 15 млн. клітин в 1 см3 вміст етанолу в молодому пиві та ступінь його зброджування збільшувались несуттєво. При нормі внесення 22,5 млн. клітин на 1 см3 спостерігали утворення максимальної кількості етанолу та досягнення максимального значення ступеня зброджування. При підвищенні концентрації до 30 і 50 млн. клітин в 1 см3 ці показники були незначно нижчими. При всіх досліджуваних нормах внесення дріжджів, крім 7,5 млн. клітин на 1 см3, вміст віцинальних дікетонів був в межах норми для пива перед стадією доброджування та дозрівання. Встановлено, що для зброджування 16 %–го пивного сусла з адекватною швидкістю та отримання молодого пива з відповідними фізико–хімічними показниками оптимальна норма внесення дріжджів становить 22,5 млн. клітин на 1 см3 сусла. &nbsp

Substrate docking to γ-secretase allows access of γ-secretase modulators to an allosteric site

γ-Secretase generates the peptides of Alzheimer's disease, Aβ40 and Aβ42, by cleaving the amyloid precursor protein within its transmembrane domain. γ-Secretase also cleaves numerous other substrates, raising concerns about γ-secretase inhibitor off-target effects. Another important class of drugs, γ-secretase modulators, alter the cleavage site of γ-secretase on amyloid precursor protein, changing the Aβ42/Aβ40 ratio, and are thus a promising therapeutic approach for Alzheimer's disease. However, the target for γ-secretase modulators is uncertain, with some data suggesting that they function on γ-secretase, whereas others support their binding to the amyloid precursor. In this paper we address this controversy by using a fluorescence resonance energy transfer-based assay to examine whether γ-secretase modulators alter Presenilin-1/γ-secretase conformation in intact cells in the absence of its natural substrates such as amyloid precursor protein and Notch. We report that the γ-secretase allosteric site is located within the γ-secretase complex, but substrate docking is needed for γ-secretase modulators to access this site

Forced Notch Signaling Inhibits Commissural Axon Outgrowth in the Developing Chick Central Nerve System

BACKGROUND: A collection of in vitro evidence has demonstrated that Notch signaling plays a key role in the growth of neurites in differentiated neurons. However, the effects of Notch signaling on axon outgrowth in an in vivo condition remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the neural tubes of HH10-11 chick embryos were in ovo electroporated with various Notch transgenes of activating or inhibiting Notch signaling, and then their effects on commissural axon outgrowth across the floor plate midline in the chick developing central nerve system were investigated. Our results showed that forced expression of Notch intracellular domain, constitutively active form of RBPJ, or full-length Hes1 in the rostral hindbrain, diencephalon and spinal cord at stage HH10-11 significantly inhibited commissural axon outgrowth. On the other hand, inhibition of Notch signaling by ectopically expressing a dominant-negative form of RBPJ promoted commissural axonal growth along the circumferential axis. Further results revealed that these Notch signaling-mediated axon outgrowth defects may be not due to the alteration of axon guidance since commissural axon marker TAG1 was present in the axons in floor plate midline, and also not result from the changes in cell fate determination of commissural neurons since the expression of postmitotic neuron marker Tuj1 and specific commissural markers TAG1 and Pax7 was unchanged. CONCLUSIONS/SIGNIFICANCE: We first used an in vivo system to provide evidence that forced Notch signaling negatively regulates commissural axon outgrowth

Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma

Background: The enhancer of zeste homolog 2 (EZH2) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC). Methods: EZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical assessment of EZH2 expression, nuclear staining quantity was evaluated using a semiquantitative score. The effect of EZH2 expression on cancer specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses. Results: During follow-up, 147 patients (28%) had died of their disease, median follow-up of patients still alive was 6.0 years (range 0 - 16.1 years). EZH2 nuclear staining was present in tumor cores of 411 (79%) patients. A multivariate Cox regression analysis revealed that high nuclear EZH2 expression was an independent predictor of poor CSS (>25-50% vs. 0%: HR 2.72, p = 0.025) in patients suffering from non-metastatic RCC. Apart from high nuclear EZH2 expression, tumor stage and Fuhrman's grading emerged as significant prognostic markers. In metastatic disease, nuclear EZH2 expression and histopathological subtype were independent predictive parameters of poor CSS (EZH2: 1-5%: HR 2.63, p = 0.043, >5-25%: HR 3.35, p = 0.013, >25%-50%: HR 4.92, p = 0.003, all compared to 0%: HR 0.36, p = 0.025, respectively). Conclusions: This study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC

Rho GTPases as therapeutic targets in Alzheimer’s disease

The progress we have made in understanding Alzheimer’s disease (AD) pathogenesis has led to the identification of several novel pathways and potential therapeutic targets. Rho GTPases have been implicated as critical components in AD pathogenesis, but their various functions and interactions make understanding their complex signaling challenging to study. Recent advancements in both the field of AD and Rho GTPase drug development provide novel tools for the elucidation of Rho GTPases as a viable target for AD. Herein, we summarize the fluctuating activity of Rho GTPases in various stages of AD pathogenesis and in several in vitro and in vivo AD models. We also review the current pharmacological tools such as NSAIDs, RhoA/ROCK, Rac1, and Cdc42 inhibitors used to target Rho GTPases and their use in AD-related studies. Finally, we summarize the behavioral modifications following Rho GTPase modulation in several AD mouse models. As key regulators of several AD-related signals, Rho GTPases have been studied as targets in AD. However, a consensus has yet to be reached regarding the stage at which targeting Rho GTPases would be the most beneficial. The studies discussed herein emphasize the critical role of Rho GTPases and the benefits of their modulation in AD

The Role of Presenilin and its Interacting Proteins in the Biogenesis of Alzheimer’s Beta Amyloid

The biogenesis and accumulation of the beta amyloid protein (Aβ) is a key event in the cascade of oxidative and inflammatory processes that characterises Alzheimer’s disease. The presenilins and its interacting proteins play a pivotal role in the generation of Aβ from the amyloid precursor protein (APP). In particular, three proteins (nicastrin, aph-1 and pen-2) interact with presenilins to form a large multi-subunit enzymatic complex (γ-secretase) that cleaves APP to generate Aβ. Reconstitution studies in yeast and insect cells have provided strong evidence that these four proteins are the major components of the γ-secretase enzyme. Current research is directed at elucidating the roles that each of these protein play in the function of this enzyme. In addition, a number of presenilin interacting proteins that are not components of γ-secretase play important roles in modulating Aβ production. This review will discuss the components of the γ-secretase complex and the role of presenilin interacting proteins on γ-secretase activity

The structure and function of Alzheimer's gamma secretase enzyme complex

The production and accumulation of the beta amyloid protein (Aβ) is a key event in the cascade of oxidative and inflammatory processes that characterizes Alzheimer’s disease (AD). A multi-subunit enzyme complex, referred to as gamma (γ) secretase, plays a pivotal role in the generation of Aβ from its parent molecule, the amyloid precursor protein (APP). Four core components (presenilin, nicastrin, aph-1, and pen-2) interact in a high-molecular-weight complex to perform intramembrane proteolysis on a number of membrane-bound proteins, including APP and Notch. Inhibitors and modulators of this enzyme have been assessed for their therapeutic benefit in AD. However, although these agents reduce Aβ levels, the majority have been shown to have severe side effects in pre-clinical animal studies, most likely due to the enzymes role in processing other proteins involved in normal cellular function. Current research is directed at understanding this enzyme and, in particular, at elucidating the roles that each of the core proteins plays in its function. In addition, a number of interacting proteins that are not components of γ-secretase also appear to play important roles in modulating enzyme activity. This review will discuss the structural and functional complexity of the γ-secretase enzyme and the effects of inhibiting its activity