Evolutionary state of magnetic chemically peculiar stars

We present a comprehensive statistical investigation of the evolution of magnetic CP stars, aimed at providing constraints to the theories that deal with the origin of the magnetic field in these stars. We have collected from the literature data for 150 magnetic CP stars with accurate Hipparcos parallaxes. We have retrieved from the ESO archive 142 FORS1 observations of circularly polarized spectra for 100 stars. From these spectra we have measured the mean longitudinal magnetic field, and discovered 48 new magnetic CP stars (five of which belonging to the rare class of rapidly oscillating Ap stars). We have determined effective temperature and luminosity, then mass and position in the H-R diagram for a final sample of 194 magnetic CP stars. We found that magnetic stars with M>3Msun are homogeneously distributed along the main sequence. Instead, there are statistical indications that lower mass stars (especially those with M<=2Msun) tend to concentrate in the centre of the main sequence band. We show that this inhomogeneous age distribution cannot be attributed to the effects of random errors and small number statistics. Our data suggest also that the surface magnetic flux of CP stars increases with stellar age and mass, and correlates with the rotation period. For stars with M>3Msun, rotation periods decrease with age in a way consistent with the conservation of the angular momentum, while for less massive magnetic CP stars an angular momentum loss cannot be ruled out. The mechanism that originates and sustains the magnetic field in the upper main sequence stars may be different in CP stars of different mass.Comment: Accepted by A&A; 13 pages, 10 figure

Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain

The glial environment influences neurological disease progression, yet much of our knowledge still relies on preclinical animal studies, especially regarding astrocyte heterogeneity. In murine models of traumatic brain injury, beneficial functions of proliferating reactive astrocytes on disease outcome have been unraveled, but little is known regarding if and when they are present in human brain pathology. Here we examined a broad spectrum of pathologies with and without intracerebral hemorrhage and found a striking correlation between lesions involving blood-brain barrier rupture and astrocyte proliferation that was further corroborated in an assay probing for neural stem cell potential. Most importantly, proteomic analysis unraveled a crucial signaling pathway regulating this astrocyte plasticity with GALECTIN3 as a novel marker for proliferating astrocytes and the GALECTIN3-binding protein LGALS3BP as a functional hub mediating astrocyte proliferation and neurosphere formation. Taken together, this work identifies a therapeutically relevant astrocyte response and their molecular regulators in different pathologies affecting the human cerebral cortex. Intracerebral hemorrhage triggers astrocyte proliferation and mediates neural stem cell potential via Galectin3 signaling

Patterns of genetic diversity in clonally evolving bacteria

All bacteria reproduce asexually, and most rely on the transfer of genetic material by parasexual means to adapt through the acquisition of novel genotypes and to remove deleterious mutations. A handful of bacterial species do not undergo any such horizontal gene transfer (HGT), and evolve in a fully clonal manner. They gain novel genotypes solely through the accumulation of de novo mutations, and can only remove deleterious mutations by genome-wide selective sweeps. These clonally evolving bacteria include some of the most pathogenic species known to humans. As a consequence of their restricted means of increasing diversity and frequent purges of variation due to genome-wide sweeps, these species have very limited genetic diversity. The low resolution of the earliest molecular typing methods led to the members of these clonal species being considered identical clones, whose genetic diversity was negligible. The advent of whole genome sequencing (WGS) has revealed this assumption to be incorrect, by providing high-resolution characterisation of their genomes and revealing their existing diversity. The detailed data provided by WGS has so far been used primarily for tracking transmission and detecting drug resistance mutations, but it has potential as the basis for an exploration of population-level patterns in diversity and evolutionary selection. In this thesis, I develop a method of rapid and scalable analysis of these patterns that is suitable to large datasets, with thousands of genomes and thousands of genes. This allows for the full diversity of the population to be considered at once. I apply this method extensively to Mycobacterium tuberculosis, the best-studied clonal bacterial species and a widespread human pathogen. Lastly I compare the patterns in M. tuberculosis to three bacterial species which do undertake HGT, Campylobacter jejuni, Staphylococcus aureus and Neisseria meningitidis, to elucidate the patterns specific to clonally evolving bacteria

Patterns of genetic diversity in clonally evolving bacteria

All bacteria reproduce asexually, and most rely on the transfer of genetic material by parasexual means to adapt through the acquisition of novel genotypes and to remove deleterious mutations. A handful of bacterial species do not undergo any such horizontal gene transfer (HGT), and evolve in a fully clonal manner. They gain novel genotypes solely through the accumulation of de novo mutations, and can only remove deleterious mutations by genome-wide selective sweeps. These clonally evolving bacteria include some of the most pathogenic species known to humans. As a consequence of their restricted means of increasing diversity and frequent purges of variation due to genome-wide sweeps, these species have very limited genetic diversity. The low resolution of the earliest molecular typing methods led to the members of these clonal species being considered identical clones, whose genetic diversity was negligible. The advent of whole genome sequencing (WGS) has revealed this assumption to be incorrect, by providing high-resolution characterisation of their genomes and revealing their existing diversity. The detailed data provided by WGS has so far been used primarily for tracking transmission and detecting drug resistance mutations, but it has potential as the basis for an exploration of population-level patterns in diversity and evolutionary selection. In this thesis, I develop a method of rapid and scalable analysis of these patterns that is suitable to large datasets, with thousands of genomes and thousands of genes. This allows for the full diversity of the population to be considered at once. I apply this method extensively to Mycobacterium tuberculosis, the best-studied clonal bacterial species and a widespread human pathogen. Lastly I compare the patterns in M. tuberculosis to three bacterial species which do undertake HGT, Campylobacter jejuni, Staphylococcus aureus and Neisseria meningitidis, to elucidate the patterns specific to clonally evolving bacteria.</p

Patterns of genetic diversity in clonally evolving bacteria

All bacteria reproduce asexually, and most rely on the transfer of genetic material by parasexual means to adapt through the acquisition of novel genotypes and to remove deleterious mutations. A handful of bacterial species do not undergo any such horizontal gene transfer (HGT), and evolve in a fully clonal manner. They gain novel genotypes solely through the accumulation of de novo mutations, and can only remove deleterious mutations by genome-wide selective sweeps. These clonally evolving bacteria include some of the most pathogenic species known to humans. As a consequence of their restricted means of increasing diversity and frequent purges of variation due to genome-wide sweeps, these species have very limited genetic diversity. The low resolution of the earliest molecular typing methods led to the members of these clonal species being considered identical clones, whose genetic diversity was negligible. The advent of whole genome sequencing (WGS) has revealed this assumption to be incorrect, by providing high-resolution characterisation of their genomes and revealing their existing diversity. The detailed data provided by WGS has so far been used primarily for tracking transmission and detecting drug resistance mutations, but it has potential as the basis for an exploration of population-level patterns in diversity and evolutionary selection. In this thesis, I develop a method of rapid and scalable analysis of these patterns that is suitable to large datasets, with thousands of genomes and thousands of genes. This allows for the full diversity of the population to be considered at once. I apply this method extensively to Mycobacterium tuberculosis, the best-studied clonal bacterial species and a widespread human pathogen. Lastly I compare the patterns in M. tuberculosis to three bacterial species which do undertake HGT, Campylobacter jejuni, Staphylococcus aureus and Neisseria meningitidis, to elucidate the patterns specific to clonally evolving bacteria.</p

Excessive local host-graft connectivity in aging and amyloid-loaded brain

Transplantation is a clinically relevant approach for brain repair, but much remains to be understood about influences of the disease environment on transplant connectivity. To explore the effect of amyloid pathology in Alzheimer’s disease (AD) and aging, we examined graft connectivity using monosynaptic rabies virus tracing in APP/PS1 mice and in 16- to 18-month-old wild-type (WT) mice. Transplanted neurons differentiated within 4 weeks and integrated well into the host visual cortex, receiving input from the appropriate brain regions for this area. Unexpectedly, we found a prominent several-fold increase in local inputs, in both amyloid-loaded and aged environments. State-of-the-art deep proteome analysis using mass spectrometry highlights complement system activation as a common denominator of environments promoting excessive local input connectivity. These data therefore reveal the key role of the host pathology in shaping the input connectome, calling for caution in extrapolating results from one pathological condition to another

A comprehensive resource for Bordetella genomic epidemiology and biodiversity studies

International audienceThe genus Bordetella includes bacteria that are found in the environment and/or associated with humans and other animals. A few closely related species, including Bordetella pertussis , are human pathogens that cause diseases such as whooping cough. Here, we present a large database of Bordetella isolates and genomes and develop genotyping systems for the genus and for the B. pertussis clade. To generate the database, we merge previously existing databases from Oxford University and Institut Pasteur, import genomes from public repositories, and add 83 newly sequenced B. bronchiseptica genomes. The public database currently includes 2582 Bordetella isolates and their provenance data, and 2085 genomes ( https://bigsdb.pasteur.fr/bordetella/ ). We use core-genome multilocus sequence typing (cgMLST) to develop genotyping systems for the whole genus and for B. pertussis , as well as specific schemes to define antigenic, virulence and macrolide resistance profiles. Phylogenetic analyses allow us to redefine evolutionary relationships among known Bordetella species, and to propose potential new species. Our database provides an expandable resource for genotyping of environmental and clinical Bordetella isolates, thus facilitating evolutionary and epidemiological research on whooping cough and other Bordetella infections