THE PRESENT-DAY CLIMATE OF EASTERN EUROPE AS VIEWED IN THE CONTEXT OF ATMOSPHERIC CIRCULATION CHANGE

Climate change over the territory of the Atlantic-European sector during the recent decades is studied with reference to changes in the large-scale atmospheric circulation. The classification of synoptic patterns (from the class of most probably to the class of least probable fields) is given for winter and summer for the last three decades, starting from 1974-1983. The synoptic pattern of the most probable class of field sea-level pressure shows high pressure over Europe in 1974-2005, which from decade to decade occupies more and more territory in summer and winter. The high temporal stability of predominant synoptic patterns is responsible for long-lived events of extreme warm and dry weather in winter and in summer for heat waves and droughts. The synoptic patterns corresponding to such dangerous weather conditions as extreme cold, strong precipitation, glaze ice, strong winds, hail etc. are discussed as well

Investigation of the composition of the Luna 16 lunar sample

The concentrations of aluminum, manganese, sodium, chromium, iron, cobalt, and 12 rare earth elements were determined by neutron activation analysis using slow neutrons. Oxygen and silicon were determined using a fast neutron generator. Mossbauer spectroscopy was used to investigate iron compounds in Luna 16 regolith samples from the upper part of the core

Innovative activity and methods for innovative ideas evaluation

It is vitally important for a country to ensure stability and provide constant growth of economy in contemporary world. The key factor of economic growth is innovative activity which leads to scientific and technological progress. This article describes the main role of innovative activity and idea selecting process in enhancing competitiveness of a company. It is difficult to choose among the big range of ideas the right one under the conditions of resource limits. In this way the article gives several methods for evaluating ideas. Such methods are extremely useful for governance, technoparks, commercialization offices and companies with innovative activity

Innovative activity and methods for innovative ideas evaluation

It is vitally important for a country to ensure stability and provide constant growth of economy in contemporary world. The key factor of economic growth is innovative activity which leads to scientific and technological progress. This article describes the main role of innovative activity and idea selecting process in enhancing competitiveness of a company. It is difficult to choose among the big range of ideas the right one under the conditions of resource limits. In this way the article gives several methods for evaluating ideas. Such methods are extremely useful for governance, technoparks, commercialization offices and companies with innovative activity

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81

Human gestational N‐methyl‐d‐aspartate receptor autoantibodies impair neonatal murine brain function

Objective: Maternal autoantibodies are a risk factor for impaired brain development in offspring. Antibodies (ABs) against the NR1 (GluN1) subunit of the N-methyl-d-aspartate receptor (NMDAR) are among the most frequently diagnosed anti-neuronal surface ABs, yet little is known about effects on fetal development during pregnancy. Methods: We established a murine model of in utero exposure to human recombinant NR1 and isotype-matched nonreactive control ABs. Pregnant C57BL/6J mice were intraperitoneally injected on embryonic days 13 and 17 each with 240μg of human monoclonal ABs. Offspring were investigated for acute and chronic effects on NMDAR function, brain development, and behavior. Results: Transferred NR1 ABs enriched in the fetus and bound to synaptic structures in the fetal brain. Density of NMDAR was considerably reduced (up to -49.2%) and electrophysiological properties were altered, reflected by decreased amplitudes of spontaneous excitatory postsynaptic currents in young neonates (-34.4%). NR1 AB-treated animals displayed increased early postnatal mortality (+27.2%), impaired neurodevelopmental reflexes, altered blood pH, and reduced bodyweight. During adolescence and adulthood, animals showed hyperactivity (+27.8% median activity over 14 days), lower anxiety, and impaired sensorimotor gating. NR1 ABs caused long-lasting neuropathological effects also in aged mice (10 months), such as reduced volumes of cerebellum, midbrain, and brainstem. Interpretation: The data collectively support a model in which asymptomatic mothers can harbor low-level pathogenic human NR1 ABs that are diaplacentally transferred, causing neurotoxic effects on neonatal development. Thus, AB-mediated network changes may represent a potentially treatable neurodevelopmental congenital brain disorder contributing to lifelong neuropsychiatric morbidity in affected children

A promyelocytic leukemia protein-thrombospondin 2 axis and the risk of relapse in neuroblastoma

Purpose. Neuroblastoma is a childhood malignancy originating from the sympathetic nervous system with a complex biology, prone to metastasize and relapse. High-risk, metastatic cases are explained in part by amplification or mutation of oncogenes such as MYCN and ALK and loss of tumour suppressor genes in chromosome band 1p. However, it is fundamental to identify other pathways responsible for the large portion of neuroblastomas with no obvious molecular alterations. Experimental design. Neuroblastoma cell lines were used for assessment of tumour growth in vivo and in vitro. Protein expression in tissues and cells was assessed using immunofluorescence and immunohistochemistry. The association of PML expression with neuroblastoma outcome and relapse was calculated using log-rank and Mann-Whitney tests, respectively. Gene expression was assessed using chip microarrays. Results: PML is detected in the developing and adult sympathetic nervous system, whereas it is not expressed or low in metastatic neuroblastoma tumours. Reduced PML expression in patients with low-risk cancers - i.e. localized and negative for the MYCN protooncogene - is strongly associated with tumour recurrence. PML-I, but not PML-IV, isoform suppresses angiogenesis via upregulation of thrombospondin-2 (TSP-2), a key inhibitor of angiogenesis. Finally, PML-I and TSP-2 expression inversely correlates with tumour angiogenesis and recurrence in localized neuroblastomas. Dvorkina et al. A promyelocytic leukaemia protein-thrombospondin 2 axis and the risk of relapse in neuroblastoma 3 Conclusions: Our work reveals a novel PML-I-TSP2 axis for regulation of angiogenesis and cancer relapse, which could be used to identify patients with low-risk, localized tumours that might benefit from chemotherapy

CHEMICAL STUDY OF SNOW OF VLADIVOSTOK CITY AND RUSSKY ISLAND

In the paper thefirst results of mass and spectrometer research of snow cover of the largest city in the Far East - Vladivostok (mainland and Island Russky), dropped-out on the November 19 2012, are presented. To exclude secondary pollution by anthropogenous aerosols we used the top layer (5-10 cm) of just dropped-out snow placed in the 3-liter sterile containers. In a couple of hours, when snow in containers thawed, 10 ml of liquid were gained from each sample and were analyzed on a mass spectrometer of high resolution with inductive-connected plasma (MS-ICP) Element XR (Thermo Scientific). Measurements were carried out with use of a technique of TsV3.18.05-2005 Fr.1.31.2005.01714. Tests were selected in 20 points: 16 points - Vladivostok, 3 points - Island Russky (DVFU campus, the bridge, the settlement) and a comparison point - the bay Hero in the southwest of Peter the Great Bay. For the first time application of the most highly sensitive chemical method for an applied ecological task is shown today. Distribution of Pb, Cr, Mn, Fe, Co, Ni, Cu and Zn in areas of Vladivostok different by anthropogenous loading and on Russian Island is revealed. In districts of Vladivostok with high transport loading high contents of metals (Mn, Cu, Zn) which source is motor transport (exhaustgases, autopaint, catalysts) are fixed also. Tests from districts of the Academic Town have traces of influence of the sea coast (halite and potassium-containing minerals) and railroad tracks (a microparticle of iron and its oxides) that strongly pollutes environment iron because of continuous movement of trains. In the tests taken on the Eagle hill, the highest point of Vladivostok, high concentrations of Mn (the highest concentration from all tests) and Cu (the third concentration from all tests) are recorded. This point of selection is in the downtown and, apparently, isn't ecologically clear. It should be noted that height above sea level in an urban environment isn't in sufficient condition for ecological safety. Russian Island is a pure zone with low background contents of heavy metals. The raised maintenance of Cu, Ni and Zn in snow cover of the bay Hero is shown

Проявление патогномоничных признаков при моделировании сахарного диабета стрептозотоцином у мышей BALB/c

Relevance. Diabetes mellitus is a widespread, socially significant disease. In this regard, it is important to obtain an experimental model that precedes subsequent experiments on pharmacological screening and/or study of the mechanism of action of antidiabetic agents.The aim of this work was a comparative assessment of the manifestation of hyperglycemia, DNA damage, and morphology of internal organs in BALB/c mice in the modeling of diabetes mellitus by a single administration of streptozotocin at a dose of 200 mg/kg and its fractional, five-day administration at a rate of 40 mg/kg per day.Methods. Streptozotocin was used as an inducer of diabetes. The drug was administered to mice once at a dose of 200 mg/kg or 5 times daily at a dose of 40 mg/kg. We monitored hyperglycemia, DNA damage in the cells of the brain, liver, kidneys, pancreas and testes, and also assessed the microscopic picture of individual internal organs, including the pancreas.Results. In both variants of the experiment, the reproduction of pathognomonic signs of diabetes mellitus is traced. They are somewhat more clearly seen in the variant of the experiment with a fractional, five-day administration of streptozotocin in single doses of 40 mg/kg.Актуальность. Сахарный диабет является широко распространённым, социально-значимым заболеванием. В связи с этим важно получить экспериментальную модель, предваряющую последующие эксперименты по фармакологическому скринингу и/или изучению механизма действия антидиабетических средств.Целью настоящей работы явилась сравнительная оценка проявления гипергликемии, повреждений ДНК и морфологии внутренних органов у мышей BALB/c при моделировании сахарного диабета однократным введением стрептозотоцина в дозе 200 мг/кг и его дробным, пятидневным введением из расчёта 40 мг/кг в сутки.Методы. В качестве индуктора диабета применяли стрептозотоцин. Препарат вводили мышам однократно в дозе 200 мг/кг или 5-кратно ежедневно в дозе 40 мг/кг. Осуществляли контроль гипергликемии, повреждённости ДНК в клетках мозга, печени, почек, поджелудочной железы и семенников, а также оценивали микроскопическую картину отдельных внутренних органов, включая поджелудочную железу.Результаты. В обоих вариантах эксперимента прослеживается воспроизведение патогномонических признаков сахарного диабета. Несколько более отчётливо они прослеживаются в варианте эксперимента с дробным, пятидневном введением стрептозотоцина в разовых дозах 40 мг/кг

CLU blocks HDACI-mediated killing of neuroblastoma

Clusterin is a ubiquitously expressed glycoprotein with multiple binding partners including IL-6, Ku70, and Bax. Clusterin blocks apoptosis by binding to activated Bax and sequestering it in the cytoplasm, thereby preventing Bax from entering mitochondria, releasing cytochrome c, and triggering apoptosis. Because increased clusterin expression correlates with aggressive behavior in tumors, clusterin inhibition might be beneficial in cancer treatment. Our recent findings indicated that, in neuroblastoma cells, cytoplasmic Bax also binds to Ku70; when Ku70 is acetylated, Bax is released and can initiate cell death. Therefore, increasing Ku70 acetylation, such as by using histone deacetylase inhibitors, may be therapeutically useful in promoting cell death in neuroblastoma tumors. Since clusterin, Bax, and Ku70 form a complex, it seemed likely that clusterin would mediate its anti-apoptotic effects by inhibiting Ku70 acetylation and blocking Bax release. Our results, however, demonstrate that while clusterin level does indeed determine the sensitivity of neuroblastoma cells to histone deacetylase inhibitor-induced cell death, it does so without affecting histone deacetylase-inhibitor-induced Ku70 acetylation. Our results suggest that in neuroblastoma, clusterin exerts its anti-apoptotic effects downstream of Ku70 acetylation, likely by directly blocking Bax activation