117 research outputs found

    Corruption in the Middle East and the Limits of Conventional Approaches

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    Die Unzufriedenheit mit der verbreiteten Korruption war 2011/2012 eine wesentliche Ursache fĂŒr die arabischen Unruhen und weitere AufstĂ€nde weltweit. Der Fall Jordanien zeigt allerdings, dass konventionelle AnsĂ€tze zur BekĂ€mpfung von Korruption nicht ausreichen. Eine angemessene Strategie gegen Korruption muss diese als ein Problem der Verteilungsgerechtigkeit und nicht des Strafrechts verstehen. Wie in allen anderen arabischen Staaten ist die Unzufriedenheit in der Bevölkerung ĂŒber die offensichtliche Korruption auch in Jordanien betrĂ€chtlich. Allerdings wird im Allgemeinen nicht ĂŒber FĂ€lle von Bestechung und Erpressung geklagt, die weniger hĂ€ufig vorkommen, sondern ĂŒber lokale Praktiken politischer Patronage und BegĂŒnstigung, die unter dem Begriff "Wasta" zusammengefasst werden. "Wasta" wurde bislang als Form der Korruption und strafrechtliches Problem angesehen, weshalb Versuche zur EindĂ€mmung ĂŒberwiegend ineffizient blieben: "Wasta"-Praktiken werden in der Regel nicht mit RechtsverstĂ¶ĂŸen verbunden, sondern bewegen sich innerhalb formal legaler Verfahren. Konventionelle AnsĂ€tze zur BekĂ€mpfung von Korruption, die sich an rechtsstaatlichen GrundsĂ€tzen und Transparenz orientieren, sind deshalb nicht zielfĂŒhrend. Demokratisierung allein ist ebenfalls ungeeignet, das Problem „Wasta” zu lösen. In der parlamentarischen Praxis macht "Wasta" den Großteil der AktivitĂ€ten aller Parlamentsmitglieder aus. Diese werden deshalb als persönliche Dienstleister fĂŒr ihre Wahlbezirke und nicht als Mitglieder einer gesetzgebenden Körperschaft wahrgenommen. Gleichzeitig hĂ€lt die Bevölkerung das Parlament fĂŒr eine zutiefst korrupte Institution. "Wasta" wird problematisch, wenn diese Praxis zu einem ungleichen Zugang der BĂŒrger zu öffentlichen Ressourcen fĂŒhrt. Statt sich nur auf politische und administrative Reformen zu konzentrieren, muss der Fokus der BekĂ€mpfung auf den (Wieder-)Aufbau wohlfahrtsstaatlicher Strukturen gelegt werden, zu denen alle BĂŒrger gleichermaßen Zugang haben

    The Epstein-Barr Virus Glycoprotein gp150 Forms an Immune-Evasive Glycan Shield at the Surface of Infected Cells

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    Cell-mediated immunity plays a key role in host control of viral infection. This is exemplified by life-threatening reactivations of e.g. herpesviruses in individuals with impaired T-cell and/or iNKT cell responses. To allow lifelong persistence and virus production in the face of primed immunity, herpesviruses exploit immune evasion strategies. These include a reduction in viral antigen expression during latency and a number of escape mechanisms that target antigen presentation pathways. Given the plethora of foreign antigens expressed in virus-producing cells, herpesviruses are conceivably most vulnerable to elimination by cell-mediated immunity during the replicative phase of infection. Here, we show that a prototypic herpesvirus, Epstein-Barr virus (EBV), encodes a novel, broadly acting immunoevasin, gp150, that is expressed during the late phase of viral replication. In particular, EBV gp150 inhibits antigen presentation by HLA class I, HLA class II, and the non-classical, lipid-presenting CD1d molecules. The mechanism of gp150-mediated T-cell escape does not depend on degradation of the antigen-presenting molecules nor does it require gp150’s cytoplasmic tail. Through its abundant glycosylation, gp150 creates a shield that impedes surface presentation of antigen. This is an unprecedented immune evasion mechanism for herpesviruses. In view of its likely broader target range, gp150 could additionally have an impact beyond escape of T cell activation. Importantly, B cells infected with a gp150-null mutant EBV displayed rescued levels of surface antigen presentation by HLA class I, HLA class II, and CD1d, supporting an important role for iNKT cells next to classical T cells in fighting EBV infection. At the same time, our results indicate that EBV gp150 prolongs the timespan for producing viral offspring at the most vulnerable stage of the viral life cycle

    New function of the myostatin/activin type I receptor (ALK4) as a mediator of muscle atrophy and muscle regeneration

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    Skeletal muscle fibrosis and impaired muscle regeneration are major contributors to muscle wasting in Duchenne muscular dystrophy (DMD). Muscle growth is negatively regulated by myostatin (MSTN) and activins. Blockage of these pathways may improve muscle quality and function in DMD. Antisense oligonucleotides (AONs) were designed specifically to block the function of ALK4, a key receptor for the MSTN/activin pathway in skeletal muscle. AON-induced exon skipping resulted in specific Alk4 down-regulation, inhibition of MSTN activity, and increased myoblast differentiation in vitro Unexpectedly, a marked decrease in muscle mass (10%) was found after Alk4 AON treatment in mdx mice. In line with in vitro results, muscle regeneration was stimulated, and muscle fiber size decreased markedly. Notably, when Alk4 was down-regulated in adult wild-type mice, muscle mass decreased even more. RNAseq analysis revealed dysregulated metabolic functions and signs of muscle atrophy. We conclude that ALK4 inhibition increases myogenesis but also regulates the tight balance of protein synthesis and degradation. Therefore, caution must be used when developing therapies that interfere with MSTN/activin pathways

    Do Biofilm Formation and Interactions with Human Cells Explain the Clinical Success of Acinetobacter baumannii?

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    BACKGROUND: The dramatic increase in antibiotic resistance and the recent manifestation in war trauma patients underscore the threat of Acinetobacter baumannii as a nosocomial pathogen. Despite numerous reports documenting its epidemicity, little is known about the pathogenicity of A. baumannii. The aim of this study was to obtain insight into the factors that might explain the clinical success of A. baumannii. METHODOLOGY/PRINCIPAL FINDINGS: We compared biofilm formation, adherence to and inflammatory cytokine induction by human cells for a large panel of well-described strains of A. baumannii and compared these features to that of other, clinically less relevant Acinetobacter species. Results revealed that biofilm formation and adherence to airway epithelial cells varied widely within the various species, but did not differ among the species. However, airway epithelial cells and cultured human macrophages produced significantly less inflammatory cytokines upon exposure to A. baumannii strains than to strains of A. junii, a species infrequently causing infection. CONCLUSION/SIGNIFICANCE: The induction of a weak inflammatory response may provide a clue to the persistence of A. baumannii in patients

    Radioactive Holmium Acetylacetonate Microspheres for Interstitial Microbrachytherapy: An In Vitro and In Vivo Stability Study

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    Purpose The clinical application of holmium acetylacetonate microspheres (HoAcAcMS) for the intratumoral radionuclide treatment of solid malignancies requires a thorough understanding of their stability. Therefore, an in vitro and an in vivo stability study with HoAcAcMS was conducted. Methods HoAcAcMS, before and after neutron irradiation, were incubated in a phosphate buffer at 37°C for 6 months. The in vitro release of holmium in this buffer after 6 months was 0.5%. Elemental analysis, scanning electron microscopy, infrared spectroscopy and time of flight secondary ion mass spectrometry were performed on the HoAcAcMS. Results After 4 days in buffer the acetylacetonate ligands were replaced by phosphate, without altering the particle size and surface morphology. HoAcAcMS before and after neutron irradiation were administered intratumorally in VX2 tumor-bearing rabbits. No holmium was detected in the faeces, urine, femur and blood. Histological examination of the tumor revealed clusters of intact microspheres amidst necrotic tissue after 30 days. Conclusion HoAcAcMS are stable both in vitro and in vivo and are suitable for intratumoral radionuclide treatment.Radiation, Radionuclides and ReactorsApplied Science
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