Protocol for a prospective, longitudinal cohort of people with COVID-19 and their household members to study factors associated with disease severity: the Predi-COVID study.

Introduction: A few major clinical factors such as sex, obesity or comorbidities have already been associated with COVID-19 severity, but there is a need to identify new epidemiological, clinical, digital and biological characteristics associated with severity and perform deep phenotyping of patients according to severity. The objectives of the Predi-COVID study are (1) to identify new determinants of COVID-19 severity and (2) to conduct deep phenotyping of patients by stratifying them according to risk of complications, as well as risk factors for infection among household members of Predi-COVID participants (the Predi-COVID-H ancillary study).

Methods And Analysis: Predi-COVID is a prospective, hybrid cohort study composed of laboratory-confirmed COVID-19 cases in Luxembourg who will be followed up remotely for 1 year to monitor their health status and symptoms.

Data on quantification of signaling pathways activated by KIT and PDGFRA mutants.

The present data are related to the article entitled "Insights into ligand stimulation effects on gastro-intestinal stromal tumors signaling" (C. Bahlawane, M. Schmitz, E.

Insights into ligand stimulation effects on gastro-intestinal stromal tumors signalling.

Mutations in KIT or PDGFRA are responsible for >85% of gastrointestinal stromal tumors. The introduction of imatinib in the GIST therapy scheme revolutionized the patient outcome. Unfortunately, the therapy allows the disease stabilization instead of curation.

Hypoxia-responsive miR-210 promotes self-renewal capacity of colon tumor-initiating cells by repressing ISCU and by inducing lactate production.

Low oxygen concentrations (hypoxia) are known to affect the cellular metabolism and have been suggested to regulate a subpopulation of cancer cells with tumorigenic properties, the so-called tumor-initiating cells (TICs). To better understand the mechanism of hypoxia-induced TIC activation, we set out to study the role of hypoxia-responsive miRNAs in recently established colon cancer patient-derived TICs. We were able to show that low oxygen concentrations consistently lead to the upregulation of miR-210 in different primary TIC-enriched cultures.

Genome-wide analysis of chromosomal import patterns after natural transformation of Helicobacter pylori.

Recombination plays a dominant role in the evolution of the bacterial pathogen Helicobacter pylori, but its dynamics remain incompletely understood. Here we use an in vitro transformation system combined with genome sequencing to study chromosomal integration patterns after natural transformation. A single transformation cycle results in up to 21 imports, and repeated transformations generate a maximum of 92 imports (8% sequence replacement).

A Probabilistic Boolean Network Approach for the Analysis of Cancer-Specific Signalling: A Case Study of Deregulated PDGF Signalling in GIST.

Background: Signal transduction networks are increasingly studied with mathematical modelling approaches while each of them is suited for a particular problem. For the contextualisation and analysis of signalling networks with steady-state protein data, we identified probabilistic Boolean network (PBN) as a promising framework which could capture quantitative changes of molecular changes at steady-state with a minimal parameterisation.

Results And Conclusion: In our case study, we successfully applied the PBN approach to model and analyse the deregulated Platelet-Derived Growth Factor (PDGF) signalling pathway in Gastrointestinal Stromal Tumour (GIST).

The oncogenic FIP1L1-PDGFRα fusion protein displays skewed signaling properties compared to its wild-type PDGFRα counterpart.

Aberrant activation of oncogenic kinases is frequently observed in human cancers, but the underlying mechanism and resulting effects on global signaling are incompletely understood. Here, we demonstrate that the oncogenic FIP1L1-PDGFRα kinase exhibits a significantly different signaling pattern compared to its PDGFRα wild type counterpart. Interestingly, the activation of primarily membrane-based signal transduction processes (such as PI3-kinase- and MAP-kinase- pathways) is remarkably shifted toward a prominent activation of STAT factors.

Constitutive activation of oncogenic PDGFRα-mutant proteins occurring in GIST patients induces receptor mislocalisation and alters PDGFRα signalling characteristics.

Background: Gastrointestinal stromal tumours (GIST) are mainly characterised by the presence of activating mutations in either of the two receptor tyrosine kinases c-KIT or platelet-derived growth factor receptor-α (PDGFRα). Most mechanistic studies dealing with GIST mutations have focused on c-KIT and far less is known about the signalling characteristics of the mutated PDGFRα proteins. Here, we study the signalling capacities and corresponding transcriptional responses of the different PDGFRα proteins under comparable genomic conditions.

The nucleotide excision repair (NER) system of Helicobacter pylori: role in mutation prevention and chromosomal import patterns after natural transformation.

Background: Extensive genetic diversity and rapid allelic diversification are characteristics of the human gastric pathogen Helicobacter pylori, and are believed to contribute to its ability to cause chronic infections. Both a high mutation rate and frequent imports of short fragments of exogenous DNA during mixed infections play important roles in generating this allelic diversity. In this study, we used a genetic approach to investigate the roles of nucleotide excision repair (NER) pathway components in H.

Hierarchical regulation of the NikR-mediated nickel response in Helicobacter pylori.

Nickel is an essential metal for Helicobacter pylori, as it is the co-factor of two enzymes crucial for colonization, urease and hydrogenase. Nickel is taken up by specific transporters and its intracellular homeostasis depends on nickel-binding proteins to avoid toxicity. Nickel trafficking is controlled by the Ni(II)-dependent transcriptional regulator NikR.

The structure of the Helicobacter pylori ferric uptake regulator Fur reveals three functional metal binding sites.

Fur, the ferric uptake regulator, is a transcription factor that controls iron metabolism in bacteria. Binding of ferrous iron to Fur triggers a conformational change that activates the protein for binding to specific DNA sequences named Fur boxes. In Helicobacter pylori, HpFur is involved in acid response and is important for gastric colonization in model animals.

Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families.

Our understanding of basic evolutionary processes in bacteria is still very limited. For example, multiple recent dating estimates are based on a universal inter-species molecular clock rate, but that rate was calibrated using estimates of geological dates that are no longer accepted. We therefore estimated the short-term rates of mutation and recombination in Helicobacter pylori by sequencing an average of 39,300 bp in 78 gene fragments from 97 isolates.

Sinorhizobium meliloti regulator MucR couples exopolysaccharide synthesis and motility.

In order to enter symbiosis with its legume partner, Sinorhizobium meliloti requires regulatory systems for the appropriate responses to its environment. For example, motility is required for the chemotactic movement of bacteria toward the compounds released by its host, and exopolysaccharides (EPS) are required for bacterial attachment to the root or for invasion of the infection thread. Previous research has shown that ExoR/ExoS/ChvI as well as the ExpR/Sin quorum-sensing system inversely regulate both motility and EPS production, although the regulation mechanisms were unknown.

Fine-tuning of galactoglucan biosynthesis in Sinorhizobium meliloti by differential WggR (ExpG)-, PhoB-, and MucR-dependent regulation of two promoters.

Depending on the phosphate concentration encountered in the environment Sinorhizobium meliloti 2011 synthesizes two different exopolysaccharides (EPS). Galactoglucan (EPS II) is produced under phosphate starvation but also in the presence of extra copies of the transcriptional regulator WggR (ExpG) or as a consequence of a mutation in mucR. The galactoglucan biosynthesis gene cluster contains the operons wga (expA), wge (expE), wgd (expD), and wggR (expG).