Vrije Universiteit Brussel

About: Vrije Universiteit Brussel is a education organization based out in Brussels, Belgium. It is known for research contribution in the topics: Population & Context (language use). The organization has 14295 authors who have published 38258 publications receiving 1203970 citations. The organization is also known as: VUB.

A homologue of the Parkinson's disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover.

Abstract: Mutations in LRRK2 are a common cause of genetic Parkinson's disease (PD). LRRK2 is a multi-domain Roco protein, harbouring kinase and GTPase activity. In analogy with a bacterial homologue, LRRK2 was proposed to act as a GTPase activated by dimerization (GAD), while recent reports suggest LRRK2 to exist under a monomeric and dimeric form in vivo. It is however unknown how LRRK2 oligomerization is regulated. Here, we show that oligomerization of a homologous bacterial Roco protein depends on the nucleotide load. The protein is mainly dimeric in the nucleotide-free and GDP-bound states, while it forms monomers upon GTP binding, leading to a monomer-dimer cycle during GTP hydrolysis. An analogue of a PD-associated mutation stabilizes the dimer and decreases the GTPase activity. This work thus provides insights into the conformational cycle of Roco proteins and suggests a link between oligomerization and disease-associated mutations in LRRK2.

Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages

Abstract: Alternatively activated macrophages (aaMphi) display molecular and biological characteristics that differ from those of classically activated macrophages (caMphi). Recently, we described an experimental model of murine trypanosomosis in which the early stage of infection of mice with a Trypanosoma brucei brucei variant is characterized by the development of caMphi, whereas in the late and chronic stages of infection, aaMphi develop. In the present study, we used suppression subtractive hybridization (SSH) to identify genes that are expressed differentially in aaMphi versus caMphi elicited during infection with this T. b. brucei variant. We show that FIZZ1 and Ym1 are induced strongly in in vivo- and in vitro-elicited aaMphi as compared with caMphi. Furthermore, we demonstrate that the in vivo induction of FIZZ1 and Ym1 in macrophages depends on IL-4 and that in vitro, IFN-gamma antagonizes the effect of IL-4 on the expression of FIZZ1 and Ym1. Collectively, these results open perspectives for new insights into the functional properties of aaMphi and establish FIZZ1 and Ym1 as markers for aaMphi.

A typology of compound weather and climate events

Abstract: Compound weather and climate events describe combinations of multiple climate drivers and/or hazards that contribute to societal or environmental risk. Although many climate-related disasters are caused by compound events, the understanding, analysis, quantification and prediction of such events is still in its infancy. In this Review, we propose a typology of compound events and suggest analytical and modelling approaches to aid in their investigation. We organize the highly diverse compound event types according to four themes: preconditioned, where a weather-driven or climate-driven precondition aggravates the impacts of a hazard; multivariate, where multiple drivers and/or hazards lead to an impact; temporally compounding, where a succession of hazards leads to an impact; and spatially compounding, where hazards in multiple connected locations cause an aggregated impact. Through structuring compound events and their respective analysis tools, the typology offers an opportunity for deeper insight into their mechanisms and impacts, benefiting the development of effective adaptation strategies. However, the complex nature of compound events results in some cases inevitably fitting into more than one class, necessitating soft boundaries within the typology. Future work must homogenize the available analytical approaches into a robust toolset for compound-event analysis under present and future climate conditions. Research on compound events has increased vastly in the last several years, yet, a typology was absent. This Review proposes a comprehensive classification scheme, incorporating compound events that are preconditioned, multivariate, temporally compounding and spatially compounding events.

Identification of heavy-flavour jets with the CMS detector in pp collisions at 13 TeV

Abstract: Many measurements and searches for physics beyond the standard model at the LHC rely on the efficient identification of heavy-flavour jets, i.e. jets originating from bottom or charm quarks. In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented. Heavy-flavour jet identification algorithms have been improved compared to those used previously at centre-of-mass energies of 7 and 8 TeV. For jets with transverse momenta in the range expected in simulated events, these new developments result in an efficiency of 68% for the correct identification of a b jet for a probability of 1% of misidentifying a light-flavour jet. The improvement in relative efficiency at this misidentification probability is about 15%, compared to previous CMS algorithms. In addition, for the first time algorithms have been developed to identify jets containing two b hadrons in Lorentz-boosted event topologies, as well as to tag c jets. The large data sample recorded in 2016 at a centre-of-mass energy of 13 TeV has also allowed the development of new methods to measure the efficiency and misidentification probability of heavy-flavour jet identification algorithms. The b jet identification efficiency is measured with a precision of a few per cent at moderate jet transverse momenta (between 30 and 300 GeV) and about 5% at the highest jet transverse momenta (between 500 and 1000 GeV).