University of Luxembourg

About: University of Luxembourg is a education organization based out in Luxembourg, Luxembourg. It is known for research contribution in the topics: Population & European union. The organization has 4744 authors who have published 22175 publications receiving 381824 citations.

Broad RNA Interference–Mediated Antiviral Immunity and Virus-Specific Inducible Responses in Drosophila

Abstract: The fruit fly Drosophila melanogaster is a good model to unravel the molecular mechanisms of innate immunity and has led to some important discoveries about the sensing and signaling of microbial infections. The response of Drosophila to virus infections remains poorly characterized and appears to involve two facets. On the one hand, RNA interference involves the recognition and processing of dsRNA into small interfering RNAs by the host RNase Dicer-2 (Dcr-2), whereas, on the other hand, an inducible response controlled by the evolutionarily conserved JAK-STAT pathway contributes to the antiviral host defense. To clarify the contribution of the small interfering RNA and JAK-STAT pathways to the control of viral infections, we have compared the resistance of flies wild-type and mutant for Dcr-2 or the JAK kinase Hopscotch to infections by seven RNA or DNA viruses belonging to different families. Our results reveal a unique susceptibility of hop mutant flies to infection by Drosophila C virus and cricket paralysis virus, two members of the Dicistroviridae family, which contrasts with the susceptibility of Dcr-2 mutant flies to many viruses, including the DNA virus invertebrate iridescent virus 6. Genome-wide microarray analysis confirmed that different sets of genes were induced following infection by Drosophila C virus or by two unrelated RNA viruses, Flock House virus and Sindbis virus. Overall, our data reveal that RNA interference is an efficient antiviral mechanism, operating against a large range of viruses, including a DNA virus. By contrast, the antiviral contribution of the JAK-STAT pathway appears to be virus specific.

BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation

Abstract: The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis. Further to its role in the tricarboxylic acid cycle, αKG is an essential cofactor for αKG-dependent dioxygenases such as Egl-9 family hypoxia inducible factor 1 (EGLN1) and the ten-eleven translocation (TET) family of DNA demethylases. Knockdown of BCAT1 in leukaemia cells caused accumulation of αKG, leading to EGLN1-mediated HIF1α protein degradation. This resulted in a growth and survival defect and abrogated leukaemia-initiating potential. By contrast, overexpression of BCAT1 in leukaemia cells decreased intracellular αKG levels and caused DNA hypermethylation through altered TET activity. AML with high levels of BCAT1 (BCAT1high) displayed a DNA hypermethylation phenotype similar to cases carrying a mutant isocitrate dehydrogenase (IDHmut), in which TET2 is inhibited by the oncometabolite 2-hydroxyglutarate. High levels of BCAT1 strongly correlate with shorter overall survival in IDHWTTET2WT, but not IDHmut or TET2mut AML. Gene sets characteristic for IDHmut AML were enriched in samples from patients with an IDHWTTET2WTBCAT1high status. BCAT1high AML showed robust enrichment for leukaemia stem-cell signatures, and paired sample analysis showed a significant increase in BCAT1 levels upon disease relapse. In summary, by limiting intracellular αKG, BCAT1 links BCAA catabolism to HIF1α stability and regulation of the epigenomic landscape, mimicking the effects of IDH mutations. Our results suggest the BCAA-BCAT1-αKG pathway as a therapeutic target to compromise leukaemia stem-cell function in patients with IDHWTTET2WT AML.

Foundations of attack-defense trees

Abstract: We introduce and give formal definitions of attack-defense trees. We argue that these trees are a simple, yet powerful tool to analyze complex security and privacy problems. Our formalization is generic in the sense that it supports different semantical approaches. We present several semantics for attack-defense trees along with usage scenarios, and we show how to evaluate attributes.

On Optimal Scheduling in Duty-Cycled Industrial IoT Applications Using IEEE802.15.4e TSCH

Abstract: As exposed in a recent report by General Electric, an industrial Internet of Things (IoT) is emerging as a commercially viable embodiment of the IoT where physical sensors gather data readings from the field and deliver the traffic to the Internet. The collected real-time big data, in turn, allow the optimizing of entire industry verticals with enormous return of investments. Although opportunities are ample, it comes along with serious engineering design challenges as industrial applications have stringent requirements on delay, lifetime and standards-compliance. To this end, we advocate the use of an IEEE/IETF standardized IoT architecture along with a recently introduced data-centric scheduling algorithm known as traffic aware scheduling algorithm (TASA). Applying graph theoretical tools to the multi-channel, time-synchronized, and duty-cycled nature of TASA, we rigorously derive optimality and bounds on the minimum number of needed active slots (impacting end-to-end delays) and the network duty-cycle (impacting lifetime). We demonstrate the enormous superiority of TASA over traditional IEEE802.15.4/ZigBee approaches in terms of energy efficiency. The outcome of this paper is currently to lay foundations of the recently formed IETF standardization group 6TSCH with the aim to significantly improve IoT data flows over IEEE802.15.4e TSCH and IETF 6LoWPAN/ROLL enabled technologies.