The endoglycosidase EndoS and the protease IdeS from the human pathogen Streptococcus pyogenes are immunomodulating enzymes hydrolyzing human IgG. IdeS cleaves IgG in the lower hinge region, while EndoS hydrolyzes the conserved N-linked glycan in the Fc region. Both enzymes are remarkably specific for human IgG that after hydrolysis loses most of its effector functions, such as binding to leukocyt

Mycobacteria are a major human health problem globally. Regarding tuberculosis the situation is worsened by the poor efficacy of current vaccine regimens and by emergence of drug-resistant strains (Manjelievskaia J et al, Trans R Soc Trop Med Hyg 110: 110, 2016; Pereira et al., Lancet Infect Dis 12:300–306, 2012; http://www.who.int/tb/publications/global_report/en/) undermining both disease-preven

The sterile worker castes found in the colonies of social insects are often cited as archetypal examples of altruism in nature. The challenge is to explain why losing the ability to mate has evolved as a superior strategy for transmitting genes into future generations. We propose that two conditions are necessary for the evolution of sterility: completely overlapping generations and monogamy. A re

The HOPS tethering complex facilitates autophagosome-lysosome fusion by binding to Syx17 (Syntaxin 17), the autophagosomal SNARE. Here we show that loss of the core HOPS complex subunit Vps16A enhances autophagosome formation and slows down Drosophila development. Mechanistically, Tor kinase is less active in Vps16A mutants likely due to impaired endocytic and biosynthetic transport to the lysosom

Homotypic fusion and vacuole protein sorting (HOPS) is a tethering complex required for trafficking to the vacuole/lysosome in yeast. Specific interaction of HOPS with certain SNARE (soluble NSF attachment protein receptor) proteins ensures the fusion of appropriate vesicles. HOPS function is less well characterized in metazoans. We show that all six HOPS subunits (Vps11 [vacuolar protein sorting

Phagophore-derived autophagosomes deliver cytoplasmic material to lysosomes for degradation and reuse. Autophagy mediated by the incompletely characterized actions of Atg proteins is involved in numerous physiological and pathological settings including stress resistance, immunity, aging, cancer, and neurodegenerative diseases. Here we characterized Atg17/FIP200, the Drosophila ortholog of mammali

The Atg2-Atg18 complex acts in parallel to Atg8 and regulates Atg9 recycling from phagophore assembly site (PAS) during autophagy in yeast. Here we show that in Drosophila, both Atg9 and Atg18 are required for Atg8a puncta formation, unlike Atg2. Selective autophagic degradation of ubiquitinated proteins is mediated by Ref(2)P/p62. The transmembrane protein Atg9 accumulates on refractory to Sigma

Autophagy, a lysosomal self-degradation and recycling pathway, plays dual roles in tumorigenesis. Autophagy deficiency predisposes to cancer, at least in part, through accumulation of the selective autophagy cargo p62, leading to activation of antioxidant responses and tumor formation. While cell growth and autophagy are inversely regulated in most cells, elevated levels of autophagy are observed

The causes and consequences of the financial crises in the Nordic countries in the early are examined and lessons from this episode are extracted. The focus is on the boom–bust episode in Finland, Norway and Sweden as these three economies went into a deep recession. The lessons from the Scandinavian experience are organised under three headings: (i) how to liberalise without causing a boom–bust c

Partially Premixed Combustion (PPC) is a promising combustion concept for future IC engines. However, controllability of PPC is still a challenge and needs more investigation. The scope of the present study is to investigate the ignition sensitivity of PPC to the injection timing at different injection pressures. To better understand this, high-speed shadowgraphy is used to visualize fuel injectio

We point out that official forecasts of output dynamics are crucial to the assessment of cyclically adjusted budget balances, and provide evidence that in some euro-area countries biased forecasts have played a thus far neglected role in generating excessive deficits. We suggest that the forecast bias may be politically motivated, and that forecasts produced by an independent authority would be be