207 research outputs found

    RNAse L and genome expression during early period of the rat liver regeneration

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    Partial hepatectomy (PHE) stimulates an intact part of the liver to exchange the existing «quiescence» program for the proliferative one. Several changes between 0.5 and 3 h after PHE are considered as manifestations of the abolishment of «quiescence» program: a temporal decrease of either UNA synthesis or accumulation of the newly formed RNA; a restricted variability of RNA transcripts; a partial retention of newly synthesized RNA within the nuclei thereby providing less RNA for the cytoplasm; previously obtained data about transient dissociation of ribosomes from endoplasmic reticulum. An involvement of the 2',5'-oligo(A)synthetase–RNAse L system in the process is suggested by up- and down-regulation of 2',5'-oligo(A)synthetase activity in the cytoplasm and in the nucleus, respectively, and by up-regulation of RNAse L content in regenerating liver. The production of IFN α/β, an inducer of the 2',5'-oligo(A)synthetase–RNAse L system, is also increased during transition period. A specific role of sinusoidal cells, the main producers of IFN α/β m the liver, in the abolishment of the old program is strongly suggested.Внаслідок часткової гепатектомії (ЧГЕ) в клітинах печінки відбувається зміна програми їхньої життєдіяльності, а саме: перехід від проліферативно неактивного до проліферативно активного стану. Декілька змін, що відбуваються між 0,5 і З год після ЧГЕ, розглядаються як прояв активного усунення існуючої до операції програми: тимчасове зниження синтезу та накопичення новоутвореної РНК; обмежена варіабельність РНК-транскриптів; затримка частини новоутвореної РНК в ядрі і відповідно менше надходження її в цитоплазму; раніше отримані нами відомості про тимчасову дисоціацію рибосом з ендоплазматичного ретикулуму. Зроблено припущення стосов­но участі в цих процесах системи 2'5'-оліго(А)синтетаза–РНКаза L. Підставою для цього послужили дані щодо підви­щення і зниження активності 2 '5' -оліго(А)синтетази від­повідно в цитоплазмі і ядрі, а також щодо зростання концен­трації РНКази L у регенеруючій печінці. Продукування IFN α/β, який індукує систему 2'5'-оліго(А)синтетаза–РНКаза L, також підвищується протягом перехідного періоду. Наведені дані узгоджуються з гіпотезою щодо специфічної ролі синусоїдальних клітин печінки в переході від стану спокою до поділу, оскільки саме синусоїдальні клітини є основними продуцента­ми IFN α/β.В результате частичной гепатэктомии (ЧГЭ) в клетках печени происходит изменение их жизнедеятельности, а имен­но: переход от пролиферативно неактивного к пролиферативно активному состоянию. Несколько изменений, происходящих между 0,5 и 3 ч после ЧГЭ, рассматриваются как проявление активного устранения существующей до операции программы: временное снижение синтеза и накопления новообразованной РНК; ограниченная вариабельность РНК-транскриптов; за­ держка части новообразованной РНК в ядре и соответственно меньшее ее поступление в цитоплазму; ранее полученные нами данные о временной диссоциации робосом из эндоплазматического ретикулума. Выдвинуто предположение об участии в этих процессах системы 2'5'-олиго(А)синтетаза–РНКаза L. Основанием для этого послужили данные о повышении и снижении активности 2'5'-олиго(А)синтетазы соответст­венно в цитоплазме и ядре, а также о возрастании концент­рации РНКазы L в регенерирующей печени. Образование IFN α/β, индуцирующего систему 2'5'-олиго(А)синтетаза–РНКа­за L, также повышается на протяжении переходного периода. Приведенные данные согласуются с гипотезой о специфической роли синусоидальных клеток печени в ее переходе от состояния покоя к делению, поскольку именно синусоидальные клетки являются основными продуцентами IFN α/β

    Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats

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    Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully understood. In this study, we investigated the effect of EPO on glucose metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of rats fed with a high-fat diet (HFD) improved fasting glucose levels and glucose tolerance, without altering total body weight or retroperitoneal fat mass. Concomitantly, EPO partially rescued insulin-stimulated AKT activation, reduced markers of oxidative stress, and restored heat-shock protein 72 expression in soleus muscles from HFD-fed rats. Incubation of skeletal muscle cell cultures with EPO failed to induce AKT phosphorylation and had no effect on glucose uptake or glycogen synthesis. We found that the EPO receptor gene was expressed in myotubes, but was undetectable in soleus. Together, our results indicate that EPO treatment improves glucose tolerance but does not directly activate the phosphorylation of AKT in muscle cells. We propose that the reduced systemic inflammation or oxidative stress that we observed after treatment with EPO could contribute to the improvement of whole-body glucose metabolism.Corinne Caillaud, Mie Mechta, Heidi Ainge, Andreas N Madsen, Patricia Ruell, Emilie Mas, Catherine Bisbal, Jacques Mercier, Stephen Twigg, Trevor A Mori, David Simar and Romain Barrè

    Aspects of the gaming industry in particular view of pathological gambling and the protection of players in Austria

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    Die Abschaffung des „kleinen Glückspiels“ in der Wiener Bundeshauptstadt zur Bekämpfung der damit verbundenen negativen Aspekte wie beispielsweise die Spielabhängigkeit und deren Folgen für den Spieler,aber auch für die Familien-angehörigen, gibt Anlass für die vorliegende Arbeit. Die Spielabhängigkeit in Österreich, die gesetzlichen Schutzmaßnahmen und ausgewählte Beispiele von der Industrie erbrachten Gegenmaßnahmen sollen in dieser Arbeit erörtert und auf deren Wirksamkeit untersucht werden

    The media use of diaspora in a conflict situation : A case study of Venezuelans in Finland

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    Many Venezuelan emigrants have an emotional connection and/or they have family members and friends in the country of origin, and that is why they seek to find reliable information on the conflict situation in Venezuela. Therefore, they keep in touch with family members, read mainstream news and use different social media platforms. Thus, what kind of impact the conflict has on the media use and how events reported in the media are interpreted is investigated in this study of Venezuelan diaspora in Finland by using social media ethnography. There are internal and external factors behind the media use. External factors come from societies of the host and origin countries. Internal factors rise from family connections and identity construction concerning personal national identity or political activism.Peer reviewe

    RNase L Mediated Protection from Virus Induced Demyelination

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    IFN-α/β plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-α/β dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-α/β pathway through RNA degradation intermediates. Infection of RNase L deficient (RL−/−) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-α/β expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL−/− mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-α/β mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination

    Activation of mGluR5 Induces Rapid and Long-Lasting Protein Kinase D Phosphorylation in Hippocampal Neurons

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    Metabotropic glutamate receptors (mGluRs), including mGluR5, play a central role in regulating the strength and plasticity of synaptic connections in the brain. However, the signaling pathways that connect mGluRs to their downstream effectors are not yet fully understood. Here, we report that stimulation of mGluR5 in hippocampal cultures and slices results in phosphorylation of protein kinase D (PKD) at the autophosphorylation site Ser-916. This phosphorylation event occurs within 30 s of stimulation, persists for at least 24 h, and is dependent on activation of phospholipase C and protein kinase C. Our data suggest that activation of PKD may represent a novel signaling pathway linking mGluR5 to its downstream targets. These findings have important implications for the study of the molecular mechanisms underlying mGluR-dependent synaptic plasticity.Howard Hughes Medical InstituteFRAXA Research FoundationNational Institute of Mental Health (U.S.)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.

    Broad-Spectrum Antiviral Therapeutics

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    Currently there are relatively few antiviral therapeutics, and most which do exist are highly pathogen-specific or have other disadvantages. We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells. We have created DRACOs and shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. We have also demonstrated that DRACOs can rescue mice challenged with H1N1 influenza. DRACOs have the potential to be effective therapeutics or prophylactics for numerous clinical and priority viruses, due to the broad-spectrum sensitivity of the dsRNA detection domain, the potent activity of the apoptosis induction domain, and the novel direct linkage between the two which viruses have never encountered.National Institute of Allergy and Infectious Diseases (U.S.) (grant AI057159)New England Regional Center of Excellence for Biodefense and Emerging Infectious DiseasesUnited States. Dept. of Defense (Director of Defense Research & Engineering)United States. Defense Threat Reduction AgencyUnited States. Defense Advanced Research Projects Agenc
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