Clathrin- and caveolin-1–independent endocytosis: entry of simian virus 40 into cells devoid of caveolae

Simian Virus 40 (SV40) has been shown to enter host cells by caveolar endocytosis followed by transport via caveosomes to the endoplasmic reticulum (ER). Using a caveolin-1 (cav-1)–deficient cell line (human hepatoma 7) and embryonic fibroblasts from a cav-1 knockout mouse, we found that in the absence of caveolae, but also in wild-type embryonic fibroblasts, the virus exploits an alternative, cav-1–independent pathway. Internalization was rapid (t1/2 = 20 min) and cholesterol and tyrosine kinase dependent but independent of clathrin, dynamin II, and ARF6. The viruses were internalized in small, tight-fitting vesicles and transported to membrane-bounded, pH-neutral organelles similar to caveosomes but devoid of cav-1 and -2. The viruses were next transferred by microtubule-dependent vesicular transport to the ER, a step that was required for infectivity. Our results revealed the existence of a virus-activated endocytic pathway from the plasma membrane to the ER that involves neither clathrin nor caveolae and that can be activated also in the presence of cav-1

The AP-1-BATF and -BATF3 module is essential for growth, survival and TH17/ILC3 skewing of anaplastic large cell lymphoma.

Transcription factor AP-1 is constitutively activated and IRF4 drives growth and survival in ALK+ and ALK- anaplastic large cell lymphoma (ALCL). Here we demonstrate high-level BATF and BATF3 expression in ALCL. Both BATFs bind classical AP-1 motifs and interact with in ALCL deregulated AP-1 factors. Together with IRF4, they co-occupy AP-1-IRF composite elements, differentiating ALCL from non-ALCL. Gene-specific inactivation of BATFs, or global AP-1 inhibition results in ALCL growth retardation and/or cell death in vitro and in vivo. Furthermore, the AP-1-BATF module establishes TH17/group 3 innate lymphoid cells (ILC3)-associated gene expression in ALCL cells, including marker genes such as AHR, IL17F, IL22, IL26, IL23R and RORγt. Elevated IL-17A and IL-17F levels were detected in a subset of children and adolescents with ALK+ ALCL. Furthermore, a comprehensive analysis of primary lymphoma data confirms TH17-, and in particular ILC3-skewing in ALCL compared with PTCL. Finally, pharmacological inhibition of RORC as single treatment leads to cell death in ALCL cell lines and, in combination with the ALK inhibitor crizotinib, enforces death induction in ALK+ ALCL. Our data highlight the crucial role of AP-1/BATFs in ALCL and lead to the concept that some ALCL might originate from ILC3

Verfügbare Wasserressourcen in der Emscherregion für eine aktive Kühlung durch Böden während Trockenperioden

Abschlussarbeit zur Erlangung des akademischen Grades Master of Science an der RWTH Aachen, Lehr- und Forschungsgebiet Abfallwirtschaft. Grünflächen können durch die Verdunstung von Wasser eine kühlende Wirkung auf ihre Umgebung haben. In trockenen Sommern steht oft nicht ausreichend Wasser für eine optimale Kühlleistung der Flächen zu Verfügung. Klimamodellierungen prognostizieren eine Häufung dieser Sommer. Der Wasserbedarf, der für die Kühlleistung von Grünflächen bedeutend ist, wird zukünftig steigen. An drei Parkanlagen in der Stadt Bottrop wurden der Bedarf sowie die verfügbaren Wasserressourcen für eine Optimierung der Kühlleistung in extrem trockenen Sommern ermittelt und gegenübergestellt. Aus den Ergebnissen konnten Handlungsoptionen für eine zukünftige Umsetzung zur Verbesserung des Stadtklimas abgeleitet werden

Mental illness and migration stress : an analytical study of a comparative groups of German immigrants and Canadian-born patients, hospitalized at the Crease Clinic of Psychological Medicine, Essondale, British Columbia, 1953-1958

This study deals with that minority segment of the German immigration population which, as evidenced by hospitalization for mental illness, has failed to make a satisfactory adjustment in Canada. Heavy environmental demands of a new country, or personal and social inadequacies, or a combination of both factors, have been held responsible for such failures. This exploratory study seeks to throw light on either interpretation. It examines clinical information, and suggests ways of analyzing case histories so that environmental and personal factors contributing to mental illness, can be more closely investigated. For the purpose of intensive study, ten case records of German immigrants were carefully selected, and were compared with those of twenty Canadian-born patients chosen on the same basis of elimination. The material available was analyzed, and classified with a view to underlining the correlating or diverging factors in the functioning of both groups. The extracted findings led to an assessment scheme in the areas of economic and work capacities, social and personal factors, applicable to individual patients and to comparable groups. A rating scale was designed which could become a measuring tool for present or future functional capacities. In spite of the small numbers used and of the analytical limitations, this attempt resulted in some well-marked similarities and deviations. To supplement this method, two composite examples of patients, reflecting causative influences in the social diagnosis, are presented. The outstanding result of this study is the emergence of similarities rather than differences between the German and Canadian patient groups. This suggests that the impact of immigration stress cannot be solely responsible for mental illness in the German group. Migration to a completely unfamiliar country, it is assumed, renders certain dormant inadequacies, for example in social relations, more prominent than a pattern of mobility or instability in one's native country would do. However, in both groups there is also the indication of low-grade functioning in economic, social and personal areas, and evidence that personal, as well as precipitating situational forces, could be accountable for mental illness in both. This experimental study strongly suggests the need for further research in this field along the same lines. However, some social work implications can be, and have been drawn from the study.Arts, Faculty ofSocial Work, School ofGraduat

Methane excess production in oxygen-rich polar water and a model of cellular conditions for this paradox

Summer sea ice cover in the Arctic Ocean has undergone a reduction in the last decade exposing the sea surface to unforeseen environmental changes. Melting sea ice increases water stratification and induces nutrient limitation, which is also known to play a crucial role in methane formation in oxygenated surface water. We report on an excess of methane in the marginal ice zone in the western Fram Strait. Our study is based on measurements of oxygen, methane, DMSP, nitrate and phosphate concentrations as well as on phytoplankton composition and light transmission, conducted along the 79°N oceanographic transect from Svalbard to the Northwest Water Polynya region off Greenland. Between the eastern Fram Strait, where Atlantic water enters from the south and the western Fram Strait, where Polar water enters from the north, different nutrient limitations occurred and consequently different bloom conditions were established. Ongoing sea ice melting enhances the environmental differences and initiates regenerated production in the western Fram Strait. In a unique biogeochemical feedback process, methane production occurs despite an oxygen excess. We postulate that DMSP (dimethylsulfoniopropionate) released from sea ice may serve as a precursor for methane formation. Thus, feedback effects on cycling pathways of methane are likely and could constitute an additional component in biogeochemical cycling in a seasonal ice-free Arctic Ocean. The metabolic activity (respiration) of unicellular organisms explains the presence of anaerobic conditions in the cellular environment. Therefore we present a theoretical model which explains the maintenance of anaerobic conditions for methane formation inside bacterial cells, despite enhanced oxygen concentrations in the environment

Waterside convection and stratification control methane spreading in supersaturated Arctic fjords (Spitsbergen)

Seasonally ice covered in the past, the fjords in West Spitsbergen turn into being perennially ice free in the present. This feedback to Arctic amplification of global warming changes gas fluxes at the atmosphere-ocean interface. Furthermore, in this Polar region, coupled feedbacks likely enhance Arctic amplification of global warming as numerous gas seepages provide evidence for active gas emissions at the sediment-water interface. We present a time series (2015–2017) of dissolved methane concentrations combined with hydrographic data in Adventfjorden and Tempelfjorden, two sub-fjords of Isfjorden located at the west coast of Spitsbergen. While both sub-fjords remained permanently supersaturated, we detected pronounced temporal and spatial variations in the methane excess level. Our study revealed that seasonal water transformations were key to seasonally changing methane pathways including potential sea-air flux (efflux). We suggest that a cascade of feedback processes, seasonally triggered by waterside convection and stratification, adjusts the amount of methane released and transported within fjord water. When sea ice was missing, strong winter cooling affected the methane supersaturation in contrary directions: first a drop and then a strong increase. In early winter, convective mixing favoured efflux, which reduced the supersaturation. Later in winter, the thermal convection resulted in a continuous overturning of the water column. When the thermal convection reached the bottom, sediment resuspension by turbulence increased, which in turn encouraged enhanced methane release. Subsequently transported along vertical isopycnals, methane from the bottom water reached the water-atmosphere interface. These coupled events created a steady state, simultaneously maintaining supersaturation and efflux. During the warm season, the fjord water became stratified and methane transport occurred mainly laterally in the bottom water. The seasonally changing hydrographic conditions strongly triggered the methane spreading in both sub-fjords and point to a switch between the atmosphere and ocean as main sinks in winter and summer, respectively. Upcoming variations in seasonality, i.e. warmer/cooler summer compared to colder/warmer winter will influence these pathways and the final fate of methane discharged into Arctic fjords