Protein O-GlcNAcylation regulates Drosophila growth through the insulin signaling pathway

Modification of nuclear and cytosolic proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) is ubiquitous in cells. The in vivo function of the protein O-GlcNAcylation, however, is not well understood. Here, we manipulated the cellular O-GlcNAcylation level in Drosophila and found that it promotes developmental growth by enhancing insulin signaling. This increase in growth is due mainly to cell growth and not to cell proliferation. Our data suggest that the increase in the insulin signaling activity is mediated, at least in part, through O-GlcNAcylation of Akt. These results indicate that O-GlcNAcylation is one of the crucial mechanisms involved in control of insulin signaling during Drosophila development.     

Enniatin,ein neues,gegen Mykobakterien wirksames Antibiotikum

Summary From the mycelium ofFusarium orthoceras App. et Wr. var.enniatinum n. v. we have isolated in crystalline form a new antibiotic substance called Enniatin. The chemical and biological characteristics of this substance are described. Enniatin is especially activein vitro against several mycobacteria.

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Ausgeführt mit einem Beitrag aus den Arbeitsbeschaffungskrediten des Eidg. Militärdepartements.     

Novel role of PKR in inflammasome activation and HMGB1 release

The inflammasome regulates the release of caspase activation-dependent cytokines, including interleukin (IL)-1β, IL-18 and high-mobility group box 1 (HMGB1). By studying HMGB1 release mechanisms, here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation. PKR inactivation by genetic deletion or pharmacological inhibition severely impaired inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminium, rotenone, live Escherichia coli, anthrax lethal toxin, DNA transfection and Salmonella typhimurium infection. PKR deficiency significantly inhibited the secretion of IL-1β, IL-18 and HMGB1 in E. coli-induced peritonitis. PKR physically interacts with several inflammasome components, including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLRP1, NLR family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. PKR autophosphorylation in a cell-free system with recombinant NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC, also known as PYCARD) and pro-caspase-1 reconstitutes inflammasome activity. These results show a crucial role for PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation.     

Improved method for extraction of mycobacterial DNA from blood

Conclusions In attempting to improve the sensitivity of MAV PCR for blood, we have evaluated a new DNA extraction method exploiting the high resistance of mycobacteria to chemical and physical agents. Our experiments indicate that pretreatment of the blood sample using proteolysis and a detergent partially eliminates contaminating human DNA (up to 40%) and may contribute to removing inhibitors. Although the method produces a crude DNA preparation, inclusion of a chloroform extraction step combined with the above mentioned pretreatment makes further purification unnecessary.     

Institutionalizing Insider Action Research Initiatives in Organizations: The Role of Learning Mechanisms

Managers face increasing pressure to find ways to surface, utilize and integrate bits and pieces of relevant knowledge that reside within and outside the organizational boundaries to address emerging challenges. Grappling with this issue and based on a longitudinal study with a biopharma company, this paper offers the notion that insider action research coupled with the design and management of learning mechanism tapestry can enhance continuous organizational learning and improvement. The institutionalization of the learning mechanism tapestry provided new capability that enhanced the organization’s agility as well as a way to stabilize insider action research role and practices.