Université libre de Bruxelles

About: Université libre de Bruxelles is a education organization based out in Brussels, Belgium. It is known for research contribution in the topics: Population & Breast cancer. The organization has 24974 authors who have published 56969 publications receiving 2084303 citations. The organization is also known as: ULB.

Robustness of circadian rhythms with respect to molecular noise

Abstract: We use a core molecular model capable of generating circadian rhythms to assess the robustness of circadian oscillations with respect to molecular noise. The model is based on the negative feedback exerted by a regulatory protein on the expression of its gene. Such a negative regulatory mechanism underlies circadian oscillations of the PER protein in Drosophila and of the FRQ protein in Neurospora. The model incorporates gene transcription into mRNA, translation of mRNA into protein, reversible phosphorylation leading to degradation of the regulatory protein, transport of the latter into the nucleus, and repression of gene expression by the nuclear form of the protein. To assess the effect of molecular noise, we perform stochastic simulations after decomposing the deterministic model into elementary reaction steps. The oscillations predicted by the stochastic simulations agree with those obtained with the deterministic version of the model. We show that robust circadian oscillations can occur already with a limited number of mRNA and protein molecules, in the range of tens and hundreds, respectively. Entrainment by light/dark cycles and cooperativity in repression enhance the robustness of circadian oscillations with respect to molecular noise.

Cost Projection of State of the Art Lithium-Ion Batteries for Electric Vehicles Up to 2030

Abstract: The negative impact of the automotive industry on climate change can be tackled by changing from fossil driven vehicles towards battery electric vehicles with no tailpipe emissions. However their adoption mainly depends on the willingness to pay for the extra cost of the traction battery. The goal of this paper is to predict the cost of a battery pack in 2030 when considering two aspects: firstly a decade of research will ensure an improvement in material sciences altering a battery’s chemical composition. Secondly by considering the price erosion due to the production cost optimization, by maturing of the market and by evolving towards to a mass-manufacturing situation. The cost of a lithium Nickel Manganese Cobalt Oxide (NMC) battery (Cathode: NMC 6:2:2 ; Anode: graphite) as well as silicon based lithium-ion battery (Cathode: NMC 6:2:2 ; Anode: silicon alloy), expected to be on the market in 10 years, will be predicted to tackle the first aspect. The second aspect will be considered by combining process-based cost calculations with learning curves, which takes the increasing battery market into account. The 100 dollar/kWh sales barrier will be reached respectively between 2020-2025 for silicon based lithium-ion batteries and 2025–2030 for NMC batteries, which will give a boost to global electric vehicle adoption.

RAS/MAPK activation is associated with reduced tumor-infiltrating lymphocytes in triple-negative breast cancer: therapeutic cooperation between MEK and PD-1/PD-L1 immune checkpoint inhibitors

Abstract: Purpose: Tumor-infiltrating lymphocytes (TILs) in the residual disease (RD) of triple-negative breast cancers (TNBCs) after neoadjuvant chemotherapy (NAC) are associated with improved survival, but insight into tumor cell-autonomous molecular pathways affecting these features are lacking. Experimental Design: We analyzed TILs in the RD of clinically and molecularly characterized TNBCs after NAC and explored therapeutic strategies targeting combinations of MEK inhibitors with PD-1/PD-L1-targeted immunotherapy in mouse models of breast cancer. Results: Presence of TILs in the RD was significantly associated with improved prognosis. Genetic or transcriptomic alterations in Ras/MAPK signaling were significantly correlated with lower TILs. MEK inhibition up-regulated cell-surface major histocompatibility complex (MHC) expression and PD-L1 in TNBC cells both in vivo and in vitro. Moreover, combined MEK and PDL-1/PD-1 inhibition enhanced anti-tumor immune responses in mouse models of breast cancer. Conclusions: These data suggest the possibility that Ras/MAPK pathway activation promotes immune-evasion in TNBC, and support clinical trials combining MEK- and PD-L1-targeted therapies. Furthermore, Ras/MAPK activation and MHC expression may be predictive biomarkers of response to immune checkpoint inhibitors.

The human pancreatic islet transcriptome: expression of candidate genes for type 1 diabetes and the impact of pro-inflammatory cytokines.

Abstract: Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic beta cells are killed by infiltrating immune cells and by cytokines released by these cells. Signaling events occurring in the pancreatic beta cells are decisive for their survival or death in diabetes. We have used RNA sequencing (RNA-seq) to identify transcripts, including splice variants, expressed in human islets of Langerhans under control conditions or following exposure to the pro-inflammatory cytokines interleukin-1β (IL-1β) and interferon-γ (IFN-γ). Based on this unique dataset, we examined whether putative candidate genes for T1D, previously identified by GWAS, are expressed in human islets. A total of 29,776 transcripts were identified as expressed in human islets. Expression of around 20% of these transcripts was modified by pro-inflammatory cytokines, including apoptosis- and inflammation-related genes. Chemokines were among the transcripts most modified by cytokines, a finding confirmed at the protein level by ELISA. Interestingly, 35% of the genes expressed in human islets undergo alternative splicing as annotated in RefSeq, and cytokines caused substantial changes in spliced transcripts. Nova1, previously considered a brain-specific regulator of mRNA splicing, is expressed in islets and its knockdown modified splicing. 25/41 of the candidate genes for T1D are expressed in islets, and cytokines modified expression of several of these transcripts. The present study doubles the number of known genes expressed in human islets and shows that cytokines modify alternative splicing in human islet cells. Importantly, it indicates that more than half of the known T1D candidate genes are expressed in human islets. This, and the production of a large number of chemokines and cytokines by cytokine-exposed islets, reinforces the concept of a dialog between pancreatic islets and the immune system in T1D. This dialog is modulated by candidate genes for the disease at both the immune system and beta cell level.

Determination of soluble and membrane protein structure by Fourier transform infrared spectroscopy. I. Assignments and model compounds.

Abstract: The basic knowledge accumulated over the last twenty years on the different vibrations of polypeptides were reviewed in Chapter 8. Because of the complexity of naturally occurring proteins, most of these data have been obtained from the study of model compounds, from simple amino acid derivatives to large synthetic polypeptides, which can be crystallized in a single secondary structure. This chapter covers biologically synthesized proteins. Data on this subject are much more recent because the advent of the new generation of Fourier transform spectrophotometers only now provides high quality spectra. Simultaneously, manipulations of the spectra have been made possible by the concomitant digitalization of the spectra and the availability of low cost computers in laboratories. It was only in 1986 that the race for determination of secondary structure from manipulated IR spectra started with a paper by Byler and Susi (1986), although it is only fair to say that the results of several attempts to obtain secondary structures had been published before. The number of papers using infrared spectros-copy (IR) to obtain secondary structures has been growing exponentially ever since. One purpose of the present review is to point out, through the description and the comparison of the different methods, that interpretation of the results still needs caution. Indeed, while some spectral features of the main secondary structures are well established, others are not. Moreover, no agreement exists on a “correct” mathematical treatment of the spectra. Both the intrinsic uncertainties in the assignments and the methodological diversity open the door to flawed conclusions if the user is not properly aware of these problems. Such warnings have been issued previously (Haris and Chapman, 1992; Surewicz et al., 1993; Haris and Chapman, 1992).