Endoribonuclease L (RNase L) Regulates the Myogenic and Adipogenic Potential of Myogenic Cells

Skeletal muscle maintenance and repair involve several finely coordinated steps in which pluripotent stem cells are activated, proliferate, exit the cell cycle and differentiate. This process is accompanied by activation of hundreds of muscle-specific genes and repression of genes associated with cell proliferation or pluripotency. Mechanisms controlling myogenesis are precisely coordinated and regulated in time to allow the sequence of activation/inactivation of genes expression. Muscular differentiation is the result of the interplay between several processes such as transcriptional induction, transcriptional repression and mRNA stability. mRNA stability is now recognized as an essential mechanism of control of gene expression. For instance, we previously showed that the endoribonuclease L (RNase L) and its inhibitor (RLI) regulates MyoD mRNA stability and consequently muscle differentiation

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

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

Alzheimer Demenz in verschiedenen Wohn- und Betreuungsformen : Konsequenzen für die psychosoziale Arbeit

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The Molecular Assembly of Amyloid Aβ Controls Its Neurotoxicity and Binding to Cellular Proteins

Accumulation of β-sheet-rich peptide (Aβ) is strongly associated with Alzheimer's disease, characterized by reduction in synapse density, structural alterations of dendritic spines, modification of synaptic protein expression, loss of long-term potentiation and neuronal cell death. Aβ species are potent neurotoxins, however the molecular mechanism responsible for Aβ toxicity is still unknown. Numerous mechanisms of toxicity were proposed, although there is no agreement about their relative importance in disease pathogenesis. Here, the toxicity of Aβ 1–40 and Aβ 1–42 monomers, oligomers or fibrils, was evaluated using the N2a cell line. A structure-function relationship between peptide aggregation state and toxic properties was established. Moreover, we demonstrated that Aβ toxic species cross the plasma membrane, accumulate in cells and bind to a variety of internal proteins, especially on the cytoskeleton and in the endoplasmatic reticulum (ER). Based on these data we suggest that numerous proteins act as Aβ receptors in N2a cells, triggering a multi factorial toxicity

Systematic Analysis of Cis-Elements in Unstable mRNAs Demonstrates that CUGBP1 Is a Key Regulator of mRNA Decay in Muscle Cells

BACKGROUND: Dramatic changes in gene expression occur in response to extracellular stimuli and during differentiation. Although transcriptional effects are important, alterations in mRNA decay also play a major role in achieving rapid and massive changes in mRNA abundance. Moreover, just as transcription factor activity varies between different cell types, the factors influencing mRNA decay are also cell-type specific. PRINCIPAL FINDINGS: We have established the rates of decay for over 7000 transcripts expressed in mouse C2C12 myoblasts. We found that GU-rich (GRE) and AU-rich (ARE) elements are over-represented in the 3'UTRs of short-lived mRNAs and that these mRNAs tend to encode factors involved in cell cycle and transcription regulation. Stabilizing elements were also identified. By comparing mRNA decay rates in C2C12 cells with those previously measured for pluripotent and differentiating embryonic stem (ES) cells, we identified several groups of transcripts that exhibit cell-type specific decay rates. Further, whereas in C2C12 cells the impact of GREs on mRNA decay appears to be greater than that of AREs, AREs are more significant in ES cells, supporting the idea that cis elements make a cell-specific contribution to mRNA stability. GREs are recognized by CUGBP1, an RNA-binding protein and instability factor whose function is affected in several neuromuscular diseases. We therefore utilized RNA immunoprecipitation followed by microarray (RIP-Chip) to identify CUGBP1-associated transcripts. These mRNAs also showed dramatic enrichment of GREs in their 3'UTRs and encode proteins linked with cell cycle, and intracellular transport. Interestingly several CUGBP1 substrate mRNAs, including those encoding the myogenic transcription factors Myod1 and Myog, are also bound by the stabilizing factor HuR in C2C12 cells. Finally, we show that several CUGBP1-associated mRNAs containing 3'UTR GREs, including Myod1, are stabilized in cells depleted of CUGBP1, consistent with the role of CUGBP1 as a destabilizing factor. CONCLUSIONS: Taken together, our results systematically establish cis-acting determinants of mRNA decay rates in C2C12 myoblast cells and demonstrate that CUGBP1 associates with GREs to regulate decay of a wide range of mRNAs including several that are critical for muscle development

Investigation of inventory accounting principles in term of tax legislation and accounting standards: Comparison of Turkey and Afghanistan

Günümüzde küreselleşmenin etkisini; ekonomi, siyasi ve teknoloji gibi her alanda görebilmek mümkündür. Küreselleşme ile birlikte ülkelerarası sermaye hareketlerinin de serbestleşmesi, ülkelerarası bilgiye ihtiyacı arttırmış, kullanıcılar için belirli bir raporlama ve muhasebe sistemine ihtiyaç duyulmuştur. Bu durum sonucunda ilgililer için doğru, anlamlı, anlaşılabilir ve ihtiyaç duydukları bilgileri karşılamak amacı ile çeşitli muhasebe standartları ve muhasebe ilkeleri düzenlenmiştir. Bu çalışmanın amacı, stokların muhasebeleştirilme esaslarını; Türk Vergi Usul Kanunu (VUK), Afganistan Gelir Vergisi Kanunu (AGVK), Stoklar Standardı (TMS-2) ile Türkiye'de uygulanmakta olan Tekdüzen Muhasebe Sistemi çerçevesinde incelemek ve stoklar ile ilgili düzenlemeler hakkında bilgi vermek olarak belirlenmiştir. Bu amaç doğrultusunda, çalışmada öncelikle stokların değerleme ilkeleri açıklanmış, daha sonra ise stoklarla ilgili özellik arz eden durumlar her üç düzenleme açısından incelenmiştir. Son olarak stokların muhasebeleştirme sürecinde yer alan yöntem ve uygulamalar karşılaştırılmak suretiyle farklılıklar ile benzerlikler incelenmiştir. Anahtar Kelimeler: Stoklar, TMS-2, Vergi Usul Kanunu, Afganistan Gelir Vergisi Kanunu.Nowadays it is easy to see the impacts of globalization in the world economics, politics and technologies. With the globalization and liberalization movement of capitals the need for information and a specific reporting and accounting system has increased. In order to provide accurate, meaningful and understandable information, various accounting standards and accounting principles have been arranged. The aim of this study is to investigate the principles of inventory accounting according to Turkey tax legislation, Afghanistan tax law, International accounting standards, uniform accounting system and giving information about these regulations. This study examined, first the valuation principles of inventories. Secondly the situations that are related to inventories were reviewed in terms of all mentioned regulations and finally, the difference analysis has been made by comparing the methods and applications in the accounting process of the inventories in all three regulations. Keywords: Inventories, TAS-2, Turkey Tax Procedure Law, Afghanistan Income Tax Law

[RNase L, a crucial mediator of innate immunity and other cell functions.]

5 pagesInternational audienceThe 2-5A/RNase L pathway is one of the first cellular defences against viruses. RNase L is an unusual endoribonuclease which activity is strictly regulated by its binding to a small oligonucleotide, 2-5A. 2-5A itself is very unusual, consisting of a series of 5'- triphosphorylated oligoadenylates with 2'-5' bonds. But RNase L activity is not limited to viral RNA cleavage. RNase L plays a central role in innate immunity, apoptosis, cell growth and differentiation by regulating cellular RNA stability and expression. Default in its activity leads to increased susceptibility to virus infections and to tumor development. RNase L gene has been identified as HPC1 (Hereditary Prostate Cancer 1) gene. Study of RNase L variant R462Q in etiology of prostate cancer has led to the identification of the novel human retrovirus closely related to xenotropic murine leukemia viruses (MuLVs) and named XMRV

La RNase L, un acteur essentiel de la réponse cellulaire antivirale

La RNase L, une endoribonuclease activée lors d’une infection virale, est l’effecteur enzymatique d’une voie de dégradation des ARN simple brin. Son activité n’est pas limitée à la dégradation des ARN viraux. Elle joue un rôle majeur dans l’immunité innée, l’apoptose et la différenciation en régulant aussi l’expression et la stabilité d’ARN cellulaires. La dérégulation de son activité est impliquée dans la susceptibilité à l’infection virale et le développement tumoral. Le gène RNase L a été identifié comme HPC1 (hereditary prostate cancer 1), l’un des gènes de susceptibilité au cancer de la prostate. L’étude de son rôle dans ce cancer a permis l’identification d’un nouveau rétrovirus humain, le xenotropic murine leukaemia related virus (XMRV) qui est un virus proche des rétrovirus leucémiques murins (MuLV)