On the space of subgroups of Baumslag-Solitar groups I: perfect kernel and phenotype

Given a Baumslag-Solitar group, we study its space of subgroups from a topological and dynamical perspective. We first determine its perfect kernel (the largest closed subset without isolated points). We then bring to light a natural partition of the space of subgroups into one closed subset and countably many open subsets that are invariant under the action by conjugation. One of our main results is that the restriction of the action to each piece is topologically transitive. This partition is described by an arithmetically defined function, that we call the phenotype, with values in the positive integers or infinity. We eventually study the closure of each open piece and also the closure of their union. We moreover identify in each phenotype a (the) maximal compact invariant subspace.Comment: 60 pages, companion webpage available at https://doi.org/10.5281/zenodo.7225585 . Comments welcome

Trade-Off between Bile Resistance and Nutritional Competence Drives Escherichia coli Diversification in the Mouse Gut

Bacterial diversification is often observed, but underlying mechanisms are difficult to disentangle and remain generally unknown. Moreover, controlled diversification experiments in ecologically relevant environments are lacking. We studied bacterial diversification in the mammalian gut, one of the most complex bacterial environments, where usually hundreds of species and thousands of bacterial strains stably coexist. Herein we show rapid genetic diversification of an Escherichia coli strain upon colonisation of previously germ-free mice. In addition to the previously described mutations in the EnvZ/OmpR operon, we describe the rapid and systematic selection of mutations in the flagellar flhDC operon and in malT, the transcriptional activator of the maltose regulon. Moreover, within each mouse, the three mutant types coexisted at different levels after one month of colonisation. By combining in vivo studies and determination of the fitness advantages of the selected mutations in controlled in vitro experiments, we provide evidence that the selective forces that drive E. coli diversification in the mouse gut are the presence of bile salts and competition for nutrients. Altogether our results indicate that a trade-off between stress resistance and nutritional competence generates sympatric diversification of the gut microbiota. These results illustrate how experimental evolution in natural environments enables identification of both the selective pressures that organisms face in their natural environment and the diversification mechanisms

No-splitting property and boundaries of random groups

We prove that random groups in the Gromov density model, at any density, satisfy property (FA), i.e. they do not act non-trivially on trees. This implies that their Gromov boundaries, defined at density less than 1/2, are Menger curves.Comment: 20 page

Quilamine HQ1-44, an iron chelator vectorized toward tumor cells by the polyamine transport system, inhibits HCT116 tumor growth without adverse effect

International audienceTumor cell growth requires large iron quantities and the deprivation of this metal induced by synthetic metal chelators is therefore an attractive method for limiting the cancer cell proliferation. The antiproliferative effect of the Quilamine HQ1-44, a new iron chelator vectorized toward tumor cells by a polyamine chain, is related to its high selectivity for the Polyamine Transport System (PTS), allowing its preferential uptake by tumoral cells. The difference in PTS activation between healthy cells and tumor cells enables tumor cells to be targeted, whereas the strong dependence of these cells on iron ensures a secondary targeting. Here, we demonstrated in vitro that HQ1-44 inhibits DNA synthesis and cell proliferation of HCT116 cells by modulating the intracellular metabolism of both iron and polyamines. Moreover, in vivo, in xenografted athymic nude mice, we found that HQ1-44 was as effective as cis-platin in reducing HCT116 tumor growth, without its side effects. Furthermore, as suggested by in vitro data, the depletion in exogenous or endogenous polyamines, known to activate the PTS, dramatically enhanced the antitumor efficiency of HQ1-44. These data support the need for further studies to assess the value of HQ1-44 as an adjuvant treatment in cance

Recent advances in cancer treatment by Iron Chelators

International audienceThe development of new therapeutic alternatives for cancers is a major public health priority. Among the more promising approaches, the iron depletion strategy based on metal chelation in the tumoral environment has been particularly studied in recent decades. After a short description of the importance of iron for cancer cell proliferation, we will review the different iron chelators developed as potential chemotherapeutics. Finally, the recent efforts to vectorize the chelating agents specifically in the microtumoral environment will be discussed in detai

Dissecting the Genetic Components of Adaptation of Escherichia coli to the Mouse Gut

While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in EnvZ/OmpR two-component signal transduction system, which controls more than 100 genes. The selective advantage conferred by the mutations that modulate EnvZ/OmpR activities was the result of their independent and additive effects on flagellin expression and permeability. These results obtained in vivo thus suggest that global regulators may have evolved to coordinate activities that need to be fine-tuned simultaneously during adaptation to complex environments and that mutations in such regulators permit adjustment of the boundaries of physiological adaptation when switching between two very distinct environments

Développement de nouveaux ligands polyaminés du fer pour la vectorisation anticancéreuse (synthèse, caractérisation et évaluation biologique)

The aim of this work is the development of new and selective iron (III) chelators bearing polyamine moieties to target the PTS and to induce specifically an iron depletion into tumor cells. These hybrid molecules, named Quilamines, are based on the association of 8-hydroxyquinoline with different polyamine chains. Synthesis and biological studies of different polyamine moieties, analogues of spermidine and spermine, showed that the homospermidine chain was the best choice for an efficient vectorization. Biological analysis highlighted a great PTS selectivity and a promising antiproliferative activity for some Quilamines. Structural modifications of the ligands allowed to modulate the iron complexation properties and to increase the selectivity and efficiency. Finally, for one compound, potentiometric titrations showed a high iron affinity constant and a good selectivity toward other biological metals such as cooper and zinc.L'objectif de ce travail de thèse est de développer de nouveaux ligands, spécifiques du fer (III), comportant une partie polyaminée pour la vectorisation par le STP afin d'induire spécifiquement une déplétion en fer dans les cellules tumorales et inhiber leur prolifération. Ces molécules chimères, appelées Quilamines, sont basées sur l'association de la 8-hydroxyquinoléine avec différentes chaînes polyaminées. La synthèse et l'étude biologique de différents motifs polyaminés dérivant de la sperdimine et de la spermidine ont montré que la chaîne homospermidine apparaît comme un vecteur de choix. De plus, des tests cellulaires de cytotoxicité ont mis en avant une forte sélectivité pour le STP ainsi qu'une activité antiproliférative prometteuse de certaines Quilamines. Des modifications structurales des ligands ont permis de changer le mode de coordination du fer et moduler leur efficacité ainsi que leur sélectivité pour le STP. Enfin, pour un des composés, l'analyse potentiométrique a mis en évidence une forte constante d'affinité pour le fer ainsi qu'une sélectivité vis-à-vis des autres métaux d'intérêt biologique comme le cuivre et le zinc.NANTES-BU Sciences (441092104) / SudocSudocFranceF

On dense totipotent free subgroups in full groups

International audienceWe study probability measure preserving (p.m.p.) non-free actions of free groups and the associated IRS's. The perfect kernel of a countable group Γ is the largest closed subspace of the space of subgroups of Γ without isolated points. We introduce the class of totipotent ergodic p.m.p. actions of Γ: those for which almost every point-stabilizer has dense conjugacy class in the perfect kernel. Equivalently, the support of the associated IRS is as large as possible, namely it is equal to the whole perfect kernel. We prove that every ergodic p.m.p. equivalence relation R of cost < r can be realized by the orbits of an action of the free group F r on r generators that is totipotent and such that the image in the full group [R] is dense. We explain why these actions have no minimal models. This also provides a continuum of pairwise orbit inequivalent invariant random subgroups of F r , all of whose supports are equal to the whole space of infinite index subgroups. We are led to introduce a property of topologically generating pairs for full groups (we call evanescence) and establish a genericity result about their existence. We show that their existence characterizes cost 1