Acid sphingomyelinase is required for efficient phago-lysosomal fusion

Die saure Sphingomyelinase (ASMase) hydrolysiert Sphingomyelin, einen wichtigen Bestandteil des äußeren Blattes von Biomembranen. Die ASMase ist in Endosomen, Phagosomes und Lysosomen und damit in den Kompartimenten, die für die antimikrobielle Aktivität von Makrophagen am wichtigsten sind, präsent. Im Gegensatz zu Makrophagen aus Wildtyp-Mäusen können ASMase-defiziente (ASMase-/-) Makrophagen das intrazelluläre Wachstum von Listeria monocytogenes (L. monocytogenes) nicht unterbinden. In ASMase-/- Makrophagen entkommen phagozytierte L. monocytogenes aus dem Phagosom, rekrutieren Aktin und vermehren sich massiv im Zytosol, obwohl die Aktivität der oxidativen bakteriziden Effektormechanismen normal ist. Die Analyse der Kinetik der phagosomalen Reifung zeigte, dass Phagosomen, die entweder lebende L. monocytogenes, hitzegetöte L. monocytogenes (HKLM) oder die avirulenten (delta)hly- oder (delta)prfA-Mutanten von L. monocytogenes enthalten, in ASMase-/- Makrophagen nicht zu bakteriziden Phagolysosomen reifen. L. monocytogenes-enthaltende Phagosomen blieben in ASMase-/- Makrophagen positiv für die spät-endosomalen Marker M6PR und Rab7 und akquirierten signifikant weniger Lamp1. Weiterhin, wurden HKLM-enthaltende Phagosomen in ASMase-/- Makrophagen signifikant schlechter angesäuert. Der Transfer von Flüssigphasenmarkern aus Lysosomen in HKLM-enthaltende Phagosomen war in ASMase-/- Makrophagen signifikant gestört, was auf eine gestörte phago-lysosomale Fusion hinweist. Weiterhin acquirierten L. monocytogenes-enthaltende Phagosomen in ASMase-/- Makrophagen signifikant weniger Cathepsin D, B und L, was zu einer signifikant verringerten proteolytischen Aktivität führte. Zusammenfassend deuten diese Daten darauf hin, dass die ASMase notwendig für die Fusion von späten Phagosomen mit Lysosomen und damit für die Generierung von bakteriziden Phagolysosomen ist

The Benefits And Challenges Of Integrating Self-Assessed Grading Into A 7th Grade Math Classroom

This project documents one teacher’s exploration of self-assessment as a strategy for teaching and learning in middle school math, addressing the research question, “What are the benefits and challenges of integrating self-assessed grading into a 7th grade pre-algebra curriculum?” It explores research relevant to the idea of self-assessment in middle school, focusing on constructivism, self-regulated learning and self-efficacy. It also includes a review of research about the implementation of self-assessment strategies. The author concludes with a curriculum aimed at helping teachers implement self-assessment in their own classrooms. The centerpiece of the curriculum is an outline of a structure and materials that can be used for self-assessment on daily work in math class. It also includes general tools that can be used for year-round self-assessment and multi-day units that can be used to give students extended practice with self-assessment

Ecological segregation of burrowing petrels (Procellariidae) at Marion Island

1. Eight burrowing petrel species were found nesting within the area studied in north-eastern Marion Island during April 1979 to May 1980. These were Salvin's Prion Pachyptila vittata salvini, Blue Petrel Halobaena caerulea, Greatwinged Petrel Pterodroma macroptera, Kerguelen Petrel Pterodroma brevirostris, Softplumaged Petrel Pterodroma mollis, Whitechinned Petrel Procellaria aequinoctialis, Grey Petrel Procellaria cinerea and South Georgian Divingpetrel Pelecanoides georgicus. Eighty-one percent of burrows found belonged to Salvin's Prions. 2. The nest site preferences of Salvin's Prion, Blue Petrel, Greatwinged Petrel, Kerguelen Petrel, Softplumaged Petrel and Whitechinned Petrel were investigated. These species had individual preferences with respect to soil depth, soil moisture content, slope angle or slope aspect. 3. The Kerguelen breeding biologies and diets of Greatwinged Petrels, Petrels and Softplumaged Petrels were studied. The species bred at different times of the year with non-overlapping chick-rearing periods. Incubation periods were similar but, relative to adult size, Kerguelen Petrel chicks grew fastest. All three species took mainly cephalopods although Kerguelen Petrels took the most crustaceans and fish. 4. Subantarctic Skuas Catharacta antarctica were important predators of petrels. They preyed upon whatever petrel species were most abundant in an area, although large petrels (Whitechinned Petrel) and those breeding in winter (Greatwinged Petrel) were seldom taken. 5. Similar petrel species had the bulk of their breeding populations spread over different habitats thus reducing any competition for nest space. At the same time, staggered timing of breeding, and particularly the non-overlapping chick-rearing periods of the three Pterodroma petrels, helped to minimize competition for food

Current Advancements of and Future Developments for Fourth Party Logistics in a Digital Future

This paper aims to analyze the potential future of the 4PL concept based on expert opinions with special regard to the influence of digitalization coming with a disruptive trans-formation of supply chains. Service arrangements, provider capabilities and benefits resulting from a 4PL partnership are compared in current and future configurations. The research follows an explorative mixed methods approach with semi structured interviews followed by an expert panel. This builds a basis for an online survey questionnaire to inquire on important future aspects for the 4PL concept by a sample of respondents from multinational companies. Our results show a clear trend away from simply organizing transportation and logistics activities towards the provision of an IT platform as well as further value-added service activities such as planning, analytics and monitoring. Along with this, IT capabilities appear to be an important differentiator for 4PL providers in the future. Moreover, relationships between 4PL providers and their clients become closer and more strategic, which leads to a customer valuing not only direct cost reductions but rather improvements resulting from optimized operations through superior analysis and planning functions

Astrophysical and cosmological constraints to neutrino properties

The astrophysical and cosmological constraints on neutrino properties (masses, lifetimes, numbers of flavors, etc.) are reviewed. The freeze out of neutrinos in the early Universe are discussed and then the cosmological limits on masses for stable neutrinos are derived. The freeze out argument coupled with observational limits is then used to constrain decaying neutrinos as well. The limits to neutrino properties which follow from SN1987A are then reviewed. The constraint from the big bang nucleosynthesis on the number of neutrino flavors is also considered. Astrophysical constraints on neutrino-mixing as well as future observations of relevance to neutrino physics are briefly discussed