VEGF receptors on PC12 cells mediate transient activation of ERK1/2 and Akt: comparison of nerve growth factor and vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) and endostatin are angiogenic and anti-angiogenic molecules, respectively, that have been implicated in neurogenesis and neuronal survival. Using alkaline phosphatase fusion proteins, we show that the PC12 neuronal cell line contains cell membrane receptors for VEGF but not for endostatin and the collagen XV endostatin homologue. Immunocytochemistry confirmed that proliferating and differentiated PC12 cells express VEGF receptors 1, 2 and neuropilin-1. While no functional effects of VEGF on PC12 cell proliferation and differentiation could be observed, a slight VEGF-induced reduction of caspase-3 activity in differentiated apoptotic PC12 cells was paralleled by transient activation of ERK1/2 and Akt. In direct comparison, nerve growth factor proved to be a strikingly more potent neuroprotective agent than VEGF

The Object of Criminal Appropriation of Authorship (Plagiarism)

In the article a personal non-property right to authorship is argued to be a supplementary direct object of a crime, specified in Art. 146, Part 1 of the Criminal Code of the Russian Federation. It does not allow to provide proper defense of rights of a person by the Criminal Code of the Russian Federation. Thus, the provisions of Art. 146, Part 1 of the Criminal Code of the Russian Federation require revising.В статье обосновывается, что личное неимущественное право авторства является дополнительным непосредственным объектом преступления, предусмотренного ч. 1 ст. 146 Уголовного кодекса РФ. Это не позволяет обеспечить полноценную уголовно-правовую охрану прав личности, и, следовательно, диспозиция указанной нормы требует изменения

O некоторых квалифицирующих признаках присвоения авторства (плагиата)

The author proves that it is not reasonable to introduce plagiarism concerning two or more people or plagiarism causing an extra large damage as an aggravating element of the crime in the contents of art. 146 of the RF Criminal Code. An introduction of the aggravating element – the appropriation of the authorship in relation to two or more people in art. 146 of the RF Criminal Code– doesn’t always show the number of broken rights and degree of their diminishing, and consequently it can’t serve as a true criterion of the higher social danger degree. The social danger degree of the appropriation of the authorship is connected with the number of broken rights, the ways and/or degree of their violation, and not with the number of victims. The introduction of the aggravating element – plagiarism causing extra large damage in art. 146 of the RF Criminal Code – means: the extra large damage after the appropriation of the authorship consists in the property damage not in the moral harm. But it is impossible to assess the exact amount of the property damage as it usually consists of loss of profitВ статье обосновывается нецелесообразность введения в содержание ст. 146 УК РФ таких квалифицирующих признаков плагиата, как присвоение авторства в отношении двух и более лиц, присвоение авторства с причинением особо крупного ущерба. Введение квалифицирующего признака – присвоение авторства в отношении двух и более лиц – в ст. 146 УК РФ не всегда отражает число нарушенных прав и степень их умаления, а потому не может считаться бесспорным критерием, свидетельствующим о повышенной общественной опасности деяния. Поэтому общественную опасность присвоения авторства следует связывать не с числом лиц, в отношении которых совершено преступление, а с числом нарушенных прав, а также способом и/или масштабом их нарушения. Введение квалифицирующего признака – присвоение авторства с причинением особо крупного ущерба – в ст. 146 УК РФ значит, что под особо крупным должен пониматься только материальный ущерб. Однако размер имущественного ущерба, выражающегося прежде всего в упущенной выгоде, не поддается точному исчислени

The Object of Criminal Appropriation of Authorship (Plagiarism)

In the article a personal non-property right to authorship is argued to be a supplementary direct object of a crime, specified in Art. 146, Part 1 of the Criminal Code of the Russian Federation. It does not allow to provide proper defense of rights of a person by the Criminal Code of the Russian Federation. Thus, the provisions of Art. 146, Part 1 of the Criminal Code of the Russian Federation require revising.В статье обосновывается, что личное неимущественное право авторства является дополнительным непосредственным объектом преступления, предусмотренного ч. 1 ст. 146 Уголовного кодекса РФ. Это не позволяет обеспечить полноценную уголовно-правовую охрану прав личности, и, следовательно, диспозиция указанной нормы требует изменения

O некоторых квалифицирующих признаках присвоения авторства (плагиата)

The author proves that it is not reasonable to introduce plagiarism concerning two or more people or plagiarism causing an extra large damage as an aggravating element of the crime in the contents of art. 146 of the RF Criminal Code. An introduction of the aggravating element – the appropriation of the authorship in relation to two or more people in art. 146 of the RF Criminal Code– doesn’t always show the number of broken rights and degree of their diminishing, and consequently it can’t serve as a true criterion of the higher social danger degree. The social danger degree of the appropriation of the authorship is connected with the number of broken rights, the ways and/or degree of their violation, and not with the number of victims. The introduction of the aggravating element – plagiarism causing extra large damage in art. 146 of the RF Criminal Code – means: the extra large damage after the appropriation of the authorship consists in the property damage not in the moral harm. But it is impossible to assess the exact amount of the property damage as it usually consists of loss of profitВ статье обосновывается нецелесообразность введения в содержание ст. 146 УК РФ таких квалифицирующих признаков плагиата, как присвоение авторства в отношении двух и более лиц, присвоение авторства с причинением особо крупного ущерба. Введение квалифицирующего признака – присвоение авторства в отношении двух и более лиц – в ст. 146 УК РФ не всегда отражает число нарушенных прав и степень их умаления, а потому не может считаться бесспорным критерием, свидетельствующим о повышенной общественной опасности деяния. Поэтому общественную опасность присвоения авторства следует связывать не с числом лиц, в отношении которых совершено преступление, а с числом нарушенных прав, а также способом и/или масштабом их нарушения. Введение квалифицирующего признака – присвоение авторства с причинением особо крупного ущерба – в ст. 146 УК РФ значит, что под особо крупным должен пониматься только материальный ущерб. Однако размер имущественного ущерба, выражающегося прежде всего в упущенной выгоде, не поддается точному исчислени

α-Tocopherol at Nanomolar Concentration Protects PC12 Cells from Hydrogen Peroxide-Induced Death and Modulates Protein Kinase Activities

The aim of this work was to compare protective and anti-apoptotic effects of α-tocopherol at nanomolar and micromolar concentrations against 0.2 mM H2O2-induced toxicity in the PC12 neuronal cell line and to reveal protein kinases that contribute to α-tocopherol protective action. The protection by 100 nM α-tocopherol against H2O2-induced PC12 cell death was pronounced if the time of pre-incubation with α-tocopherol was 3–18 h. For the first time, the protective effect of α-tocopherol was shown to depend on its concentration in the nanomolar range (1 nM < 10 nM < 100 nM), if the pre-incubation time was 18 h. Nanomolar and micromolar α-tocopherol decreased the number of PC12 cells in late apoptosis induced by H2O2 to the same extent if pre-incubation time was 18 h. Immunoblotting data showed that α-tocopherol markedly diminished the time of maximal activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and protein kinase B (Akt)-induced in PC12 cells by H2O2. Inhibitors of MEK 1/2, PI 3-kinase and protein kinase C (PKC) diminished the protective effect of α-tocopherol against H2O2-initiated toxicity if the pre-incubation time was long. The modulation of ERK 1/2, Akt and PKC activities appears to participate in the protection by α-tocopherol against H2O2-induced death of PC12 cells. The data obtained suggest that inhibition by α-tocopherol in late stage ERK 1/2 and Akt activation induced by H2O2 in PC12 cells makes contribution to its protective effect, while total inhibition of these enzymes is not protective

α-Tocopherol at Nanomolar Concentration Protects Cortical Neurons against Oxidative Stress

The aim of the present work is to study the mechanism of the α-tocopherol (α-T) protective action at nanomolar and micromolar concentrations against H2O2-induced brain cortical neuron death. The mechanism of α-T action on neurons at its nanomolar concentrations characteristic for brain extracellular space has not been practically studied yet. Preincubation with nanomolar and micromolar α-T for 18 h was found to increase the viability of cortical neurons exposed to H2O2; α-T effect was concentration-dependent in the nanomolar range. However, preincubation with nanomolar α-T for 30 min was not effective. Nanomolar and micromolar α-T decreased the reactive oxygen species accumulation induced in cortical neurons by the prooxidant. Using immunoblotting it was shown that preincubation with α-T at nanomolar and micromolar concentrations for 18 h prevented Akt inactivation and decreased PKCδ activation induced in cortical neurons by H2O2. α-T prevented the ERK1/2 sustained activation during 24 h caused by H2O2. α-T at nanomolar and micromolar concentrations prevented a great increase of the proapoptotic to antiapoptotic proteins (Bax/Bcl-2) ratio, elicited by neuron exposure to H2O2. The similar neuron protection mechanism by nanomolar and micromolar α-T suggests that a “more is better” approach to patients’ supplementation with vitamin E or α-T is not reasonable

Isotopes & Geochemistry: Tools For Geothermal Reservoir Characterization (Kamchatka Examples)

The thermal, hydrogeological, and chemical processes affecting Kamchatka geothermal reservoirs were studied by using isotope and geochemistry data: (1) The Geysers Valley hydrothermal reservoirs; (2) The Paratunsky low temperature reservoirs; (3) The North-Koryaksky hydrothermal system; (4) The Mutnovsky high temperature geothermal reservoir; (5) The Pauzhetsky geothermal reservoir. In most cases water isotope in combination with Cl- transient data are found to be useful tool to estimate reservoirs natural and disturbed by exploitation recharge conditions, isotopes of carbon-13 (in CO2) data are pointed either active magmatic recharge took place, while SiO2 and Na-K geothermometers shows opposite time transient trends (Paratunsky, Geysers Valley) suggest that it is necessary to use more complicated geochemical systems of water/mineral equilibria

The Protective Effect of Insulin on Rat Cortical Neurons in Oxidative Stress and Its Dependence on the Modulation of Akt, GSK-3beta, ERK1/2, and AMPK Activities

Insulin is a promising drug for the treatment of diseases associated with brain damage. However, the mechanism of its neuroprotective action is far from being understood. Our aim was to study the insulin-induced protection of cortical neurons in oxidative stress and its mechanism. Immunoblotting, flow cytometry, colorimetric, and fluorometric techniques were used. The insulin neuroprotection was shown to depend on insulin concentration in the nanomolar range. Insulin decreased the reactive oxygen species formation in neurons. The insulin-induced modulation of various protein kinase activities was studied at eight time-points after neuronal exposure to prooxidant (hydrogen peroxide). In prooxidant-exposed neurons, insulin increased the phosphorylation of GSK-3beta at Ser9 (thus inactivating it), which resulted from Akt activation. Insulin activated ERK1/2 in neurons 5&ndash;30 min after cell exposure to prooxidant. Hydrogen peroxide markedly activated AMPK, while it was for the first time shown that insulin inhibited it in neurons at periods of the most pronounced activation by prooxidant. Insulin normalized Bax/Bcl-2 ratio and mitochondrial membrane potential in neurons in oxidative stress. The inhibitors of the PI3K/Akt and MEK1/2/ERK1/2 signaling pathways and the AMPK activator reduced the neuroprotective effect of insulin. Thus, the protective action of insulin on cortical neurons in oxidative stress appear to be realized to a large extent through activation of Akt and ERK1/2, GSK-3beta inactivation, and inhibition of AMPK activity increased by neuronal exposure to prooxidant