Evidence by interaction : a new role of caspase-2

Caspase-2 is the best conserved member of the caspase family. Although being known to mediate cell death following DNA damage, many studies have implicated that this protease regulates a variety of cellular processes. Despite this, few well-defined and mechanistically explained functions of caspase-2 has been described. In an attempt to shed light on this enigma, we performed a yeast two-hybrid screen, searching for interaction partners of caspase-2 which could explain many of the reported observations. From the screen two hits stood out, relating to the proteins RFXANK and FAN. In the first study we investigated the relationship between caspase-2 and RFXANK, a protein known for regulating expression of MHC class II genes. The interaction between the two proteins was confirmed to take place primarily in the cytoplasm of cells. Caspase-2 was able to bind to a construct resembling the four ankyrin repeats of RFXANK, indicating that this is the region important for the interaction. Cells lacking caspase-2 contained higher total levels of MHC II, thereby suggesting that caspase-2 suppresses normal expression of the complex. Surprisingly, antigen-presenting cells from caspase-2-/- mice did not display any differences in surface distribution of the MHC II, indicating that the transport of MHC II from the cell interior to the exterior was somehow impaired. In the second study, we were interested in the understanding of the relationship between caspase-2 and FAN. Like in the first study, the interaction between the two proteins was confirmed by methodologies separated from yeast two-hybrid. FAN is a protein which has been reported to regulate a wide range of processes. We, therefore, systematically evaluated how a lack of caspase-2 would affect cells, while comparing to what is known about FAN-deficiency. Interestingly, we found that loss of caspase-2 caused the same outcomes as has been described for cells which have lost FAN. Notably, the ability to secrete IL-6 was greatly impaired in caspase-2-deficient cells, when comparing with relevant controls. Furthermore, enzyme-deficient cells took longer time to repopulate cell-free areas, indicating hampered cell motility. Although FAN is known to also regulate ceramide production, we did not observe any differences in sphingolipid contents when removing caspase-2. We did, however, observe that caspase-2-deficient cells contained abnormally enlarged vesicular/lysosomal structures, similar to what has been described following loss of FAN. In the third study we investigated the potential involvement of caspase-2 in the cell death process induced by Gemtuzumab ozogamicin (GO; Mylotarg®). This was based on the fact that GO causes DNA damage, a cause known to activate the proapoptotic function of caspase-2. We found that inhibition or removal of caspase-2 protected AML cells from GO-induced apoptosis. Strikingly, caspase-2 appeared to be involved in the processing of BID, but not the activation of BAX following treatment with GO. This may imply that the protease acts in parallel with GO, mainly by increasing the effect of the drug rather than being vital for the drug toxicity. Taken together we describe novel interaction partners to caspase-2 and highlight how the protease may regulate processes which are not necessarily tied with apoptosis

Learning Entrepreneurship with Serious Games - A Classroom Approach

The use of educational games for pedagogical practice can provide new conceptions of teaching-learning in an interactive environment stimulating the acquisition of new knowledge. The so-called serious games are focused on the goal of transmitting educational content or training to the user. In the context of entrepreneurship, serious games appear to have greater importance due to the multidisciplinary of the knowledge needed. Therefore, we propose the adoption of the Entrexplorer game in the context of a university classroom. The game is a cloud-based serious game about the theme of entrepreneurship where users can access learning contents that will assist them in the acquisition of entrepreneurial skills. The organization of the game in eight levels with six additional floors let students learn the different dimensions of an entrepreneurship project while progressing during the gameplay.Comment: 6 page

ICE‐ARC airborne campaign 2015 - Data collection and processing report

The British Antarctic Survey (BAS) and the Danish National Space Institute (DTU Space) coordinated an airborne campaign in the period April 13‐24, 2015 as part of ICE‐ARC project (Ice, Climate, Economics – Arctic Researchon Change). The ICE‐ARC programme is funded by the EU 7th framework programme running from 2014 to2017. Coincident laser/radar measurements over sea ice were collected in the Fram Strait, north of Svalbard and north of Station Nord. The laser measurements give information on sea ice freeboard and ridges/leads distribution, while the CryoSat‐type 13 GHz radar altimeter (ASIRAS) gives information on radar penetration into the snow. The measurements north of Greenland and Svalbard are partially a continuation of time series of sea ice changes by various airborne campaigns since 1998. Two overflights of the validation site near RV Lance were conducted on April 19 and 24, including short parallellines (mow‐the‐lawn) near the ship, and longer lines aligned with EM soundings obtained by helicopter. These data, together with NASA’s Operation IceBridge overflight of RV Lance on March 19, gives a uniquecombination of in situ measurements with airborne sensors to obtain information of snow and sea iceproperties for validation of CryoSat‐2 sea ice thickness and sea surface height.For the airborne campaign, a BAS Twin Otter (VP‐FAZ) was equipped with a laser scanner, the Airborne Synthetic Interferometer Radar System (ASIRAS), and an airborne meteorology system (MASIN) to map the sea ice and ice sheet topography together with atmospheric properties. The operations were coordinated with the Norwegian Young Sea ICE cruise (N‐ICE) organized by Norwegian Polar Institute (NPI) where observations of sea ice properties were based out of the research vessel Lance.This report is part of ICE‐ARC deliverable 1.62, and describes the data collection and the data processing carried out by DTU Space for this airborne campaign 2015 with focus on the laser and radar altimetry measurements

Rates of lobar atrophy in asymptomatic MAPT mutation carriers.

IntroductionThe aim of this study was to investigate the rates of lobar atrophy in the asymptomatic microtubule-associated protein tau (MAPT) mutation carriers.MethodsMAPT mutation carriers (n = 14; 10 asymptomatic, 4 converters from asymptomatic to symptomatic) and noncarriers (n = 13) underwent structural magnetic resonance imaging and were followed annually with a median of 9.2 years. Longitudinal changes in lobar atrophy were analyzed using the tensor-based morphometry with symmetric normalization algorithm.ResultsThe rate of temporal lobe atrophy in asymptomatic MAPT mutation carriers was faster than that in noncarriers. Although the greatest rate of atrophy was observed in the temporal lobe in converters, they also had increased atrophy rates in the frontal and parietal lobes compared to noncarriers.DiscussionAccelerated decline in temporal lobe volume occurs in asymptomatic MAPT mutation carriers followed by the frontal and parietal lobe in those who have become symptomatic. The findings have implications for monitoring the progression of neurodegeneration during clinical trials in asymptomatic MAPT mutation carriers

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Candida auris‒Associated Hospitalizations, United States, 2017–2022

Using a large US hospital database, we describe 192 Candida auris‒associated hospitalizations during 2017–2022, including 38 (20%) C. auris bloodstream infections. Hospitalizations involved extensive concurrent conditions and healthcare use; estimated crude mortality rate was 34%. These findings underscore the continued need for public health surveillance and C. auris containment efforts