Repository of the University of Namur
Not a member yet
94692 research outputs found
Sort by
Yet another fast variant of Newton’s method for nonconvex optimization
No full textA class of second-order algorithms is proposed for minimizing smooth nonconvex functions that alternates between regularized Newton and negative curvature steps in an iteration-dependent subspace. In most cases, the Hessian matrix is regularized with the square root of the current gradient and an additional term taking moderate negative curvature into account, a negative curvature step being taken only exceptionally. Practical variants are detailed where the subspaces are chosen to be the full space, or Krylov subspaces. In the first case, the proposed method only requires the solution of a single linear system at nearly all iterations. We establish that at most (Formula presented) evaluations of the problem’s objective function and derivatives are needed for algorithms in the new class to obtain an ∊-approximate first-order minimizer, and at most (Formula presented) to obtain a second-order one. Encouraging initial numerical experiments with two full-space and two Krylov-subspaces variants are finally presented.</p
Towards a unified framework for the function of endoplasmic reticulum exit sites
No full textEndoplasmic reticulum exit sites (ERES) are specialized, ribosome-free ER subdomains that serve as dynamic portals for COPII-mediated export of proteins from the ER. Beyond their role in the secretory pathway, ERES are implicated in diverse processes, including autophagy and the maturation of lipid droplets, highlighting their functional plasticity. ERES integrate cargo load, membrane tension and spatial cues to remodel their architecture and function in real time. This Roadmap synthesizes our current knowledge on the biogenesis, structural diversity and regulatory logic of ERES. We highlight key unanswered questions in the field, particularly concerning how ERES integrate signals to coordinate protein trafficking under varying cellular states. Finally, we propose a multidisciplinary framework — leveraging advances in high-resolution imaging, synthetic reconstitution and computational modelling — to delineate the principles governing the function and plasticity of ERES. Understanding these mechanisms holds significant potential for developing targeted therapeutic strategies in diseases linked to trafficking dysfunction.</p
Structural and Enzymological Characterization of Phosphoserine Phosphatase From Brucella melitensis
No full textAmino acid L-serine (L-Ser) is a precursor of various biomolecules, including other amino acids, glutathione, and nucleotides. The metabolism of this amino acid is crucial in diseases such as brucellosis. Previous studies have revealed that the enzymes involved in L-Ser biosynthesis are essential for Brucella replication, making them potential targets for the development of new drugs. Here, we focus on Brucella melitensis phosphoserine phosphatase (BmPSP), which catalyzes the dephosphorylation of phosphoserine in L-Ser. The enzyme is characterized through enzymatic and structural studies, leading to the discovery of its first crystallographic structures. The interactions of BmPSP with different ligands are also investigated. We demonstrate that the substitution of its Mg2+ cofactor with Ca2+ inhibits the enzyme and results in a slight movement of catalytic residues in the active site. Crystallographic structures of BmPSP in complex with substrate, reaction products, and substrate analogs are also detailed, revealing the interaction between these molecules and the active site residues. This structural study provides a better understanding of phosphoserine phosphatases, highlighting the involvement of two highly conserved residues in the mechanism of substrate entry into the active site.</p
Corrigendum to “Partition sums for molecules and their isotopologues for HITRAN2024” [Journal of Quantitative Spectroscopy & Radiative Transfer 345 (2025) 109568] (Journal of Quantitative Spectroscopy and Radiative Transfer (2025) 345, (S0022407325002304), (10.1016/j.jqsrt.2025.109568))
No full textThe authors regret that in the determination of the partition sums for 16O14N18O, a python code building a dictionary of the term values from Marinina et al. [JQSRT 2022; 290: 108312] neglected the symmetry designations in the quantum numbers (+ or −) leading to half the term values not being used. We thank Dr. Valery Perevalov for pointing this out to us. The partitions sums were corrected and new versions of the codes, TIPS2024_v1p1.FOR and TIPS2024_v1p1.py, are available at ZENODO (10.5281/zenodo.16411169). The authors would like to apologise for any inconvenience caused.</p
Conserved and distinct expression of circular RNAs in commercially used Marek’s disease vaccine viruses
Get PDFCircular RNAs (circRNAs) are covalently closed RNA molecules, supporting a wide diversity of functions. While aberrant circRNA expression stands as a recognized hallmark of cancer development, our attention has turned to investigating their role in viral infections, specifically Mardivirus Gallidalpha 2 (GaHV-2, Marek’s disease virus) infection. In a previous study focused on the virulent GaHV-2 strain, RB-1B, we extensively catalogued circRNAs produced from virulence genes, notably from the MEQ-vIL-8 locus and the latency-associated transcripts (LATs) gene. Building upon this groundwork, our current investigation uncovers novel loci expressing viral circRNAs in distinct stages of GaHV-2 infection. Furthermore, we extend our focus to viral circRNA signatures in three commonly used Marek’s disease vaccines, the avirulent GaHV-2 (CVI988/Rispens strain), non-oncogenic Mardivirus Gallidalpha 3 (GaHV-3) and non-oncogenic Mardivirus Meleagridalpha 1 (MeHV-1) commercially called herpesvirus of turkey. In these vaccine viruses, we identified viral circRNA expression from a locus antisense to the ICP4 immediate early gene, a conserved feature across the three species. This region has been characterized herein for the first time in terms of candidate LATs’ exons and introns for GaHV-3 and MeHV-1. LATs’ circRNAs were then deeply analysed, and we observed both similarities and distinctions when compared with those of the virulent GaHV-2. Another conserved gene, encoding the DNA packaging protein, was identified as a source of circRNAs in all three species. Eventually, different levels of circRNAs were found to be expressed from the meq locus between virulent and avirulent GaHV-2 strains. Our findings highlight a conserved pattern of virus-derived circRNAs in these related avian alphaherpesviruses. This conservation underscores the potential significance of these transcripts in completing the viral cycle and facilitating viral spread.</p
Author Correction:Parathyroid hormone receptor agonists in the management of osteoporosis (Nature Reviews Rheumatology, (2025), 21, 10, (599-611), 10.1038/s41584-025-01287-w)
No full textCorrection to: Nature Reviews Rheumatologyhttps://doi.org/10.1038/s41584-025-01287-w, published online 11 August 2025. In the version of the article initially published, in Fig. 1, the box reading “↑ OPG” should have read “↓ OPG”. In the Fig. 1 caption, the text “..results in increased expression of receptor activator of NF-ᴋB ligand (RANKL) and osteoprotegerin (OPG) in osteoclasts, and sustained RANKL–OPG signalling supports osteoclast activation, resulting in bone resorption” should have read “..results in increased expression of receptor activator of NF-ᴋB ligand (RANKL) and downregulation of osteoprotegerin (OPG) in osteoclasts, leading to osteoclast activation, and resultant bone resorption”. These corrections have now been made to the HTML and PDF versions of the article.</p
Analytical subcellular fractionation of microglial BV-2 cells with peroxisomal beta-oxidation defect
No full textPeroxisomes have gained increasing attention and are now considered vital players in normal physiological functions. To gain further insight into how peroxisomal defects influence cellular functions, we developed BV-2 microglial models featuring CRISPR/Cas9 gene-edited mutations in peroxisomal Acox1 or Abcd1 and Abcd2 genes. The Acox1−/− BV-2 cell line we generated lacks acyl-CoA oxidase 1, the key enzyme that initiates peroxisomal β-oxidation. In contrast, the double mutant Abcd1/d2−/− BV-2 cell line carries mutations in the genes encoding the membranous ABC transporters ABCD1 and ABCD2, which are responsible for transporting fatty acyl-thioesters inside peroxisome. Here, for the first time, we used analytical fractionation to compare these three genotypes. Through flow cytometry, we observed an increase in cell granularity in these mutant cells, which could be associated with alterations in peroxisome distribution and mitochondrial dynamics. Additionally, the analysis of organelle markers in microglial cells, employing differential centrifugation, exhibited an enrichment of peroxisomes particularly in both L and P fractions of these BV-2 cell line models. The use of an isopycnic Nycodenz density gradient showed that peroxisomes sedimented with a median density of 1.18 g/ml. Notably, our results revealed no significant differences in the distribution profiles of organelles when comparing microglial BV-2 Wt cells with deficient Acox1‒/‒ or Abcd1/d2−/‒ BV-2 cells, which lack peroxisomal fatty acid beta-oxidation. Our study is the first to report on the fractionation of brain-derived microglial cells, laying valuable groundwork for future proteomic and/or metabolomic analyses of peroxisome fractions.</p