Relativistic Dynamics and Extreme Mass Ratio Inspirals

It is now well-established that a dark, compact object (DCO), very likely a massive black hole (MBH) of around four million solar masses is lurking at the centre of the Milky Way. While a consensus is emerging about the origin and growth of supermassive black holes (with masses larger than a billion solar masses), MBHs with smaller masses, such as the one in our galactic centre, remain understudied and enigmatic. The key to understanding these holes - how some of them grow by orders of magnitude in mass - lies in understanding the dynamics of the stars in the galactic neighbourhood. Stars interact with the central MBH primarily through their gradual inspiral due to the emission of gravitational radiation. Also stars produce gases which will subsequently be accreted by the MBH through collisions and disruptions brought about by the strong central tidal field. Such processes can contribute significantly to the mass of the MBH and progress in understanding them requires theoretical work in preparation for future gravitational radiation millihertz missions and X-ray observatories. In particular, a unique probe of these regions is the gravitational radiation that is emitted by some compact stars very close to the black holes and which could be surveyed by a millihertz gravitational wave interferometer scrutinizing the range of masses fundamental to understanding the origin and growth of supermassive black holes. By extracting the information carried by the gravitational radiation, we can determine the mass and spin of the central MBH with unprecedented precision and we can determine how the holes "eat" stars that happen to be near them.Comment: Update from the first version, 151 pages, accepted for publication @ Living Reviews in Relativit

Type 1 Fimbriae, a Colonization Factor of Uropathogenic Escherichia coli, Are Controlled by the Metabolic Sensor CRP-cAMP

Type 1 fimbriae are a crucial factor for the virulence of uropathogenic Escherichia coli during the first steps of infection by mediating adhesion to epithelial cells. They are also required for the consequent colonization of the tissues and for invasion of the uroepithelium. Here, we studied the role of the specialized signal transduction system CRP-cAMP in the regulation of type 1 fimbriation. Although initially discovered by regulating carbohydrate metabolism, the CRP-cAMP complex controls a major regulatory network in Gram-negative bacteria, including a broad subset of genes spread into different functional categories of the cell. Our results indicate that CRP-cAMP plays a dual role in type 1 fimbriation, affecting both the phase variation process and fimA promoter activity, with an overall repressive outcome on fimbriation. The dissection of the regulatory pathway let us conclude that CRP-cAMP negatively affects FimB-mediated recombination by an indirect mechanism that requires DNA gyrase activity. Moreover, the underlying studies revealed that CRP-cAMP controls the expression of another global regulator in Gram-negative bacteria, the leucine-responsive protein Lrp. CRP-cAMP-mediated repression is limiting the switch from the non-fimbriated to the fimbriated state. Consistently, a drop in the intracellular concentration of cAMP due to altered physiological conditions (e.g. growth in presence of glucose) increases the percentage of fimbriated cells in the bacterial population. We also provide evidence that the repression of type 1 fimbriae by CRP-cAMP occurs during fast growth conditions (logarithmic phase) and is alleviated during slow growth (stationary phase), which is consistent with an involvement of type 1 fimbriae in the adaptation to stress conditions by promoting biofilm growth or entry into host cells. Our work suggests that the metabolic sensor CRP-cAMP plays a role in coupling the expression of type 1 fimbriae to environmental conditions, thereby also affecting subsequent attachment and colonization of host tissues

Fragile x syndrome and autism: from disease model to therapeutic targets

Autism is an umbrella diagnosis with several different etiologies. Fragile X syndrome (FXS), one of the first identified and leading causes of autism, has been modeled in mice using molecular genetic manipulation. These Fmr1 knockout mice have recently been used to identify a new putative therapeutic target, the metabotropic glutamate receptor 5 (mGluR5), for the treatment of FXS. Moreover, mGluR5 signaling cascades interact with a number of synaptic proteins, many of which have been implicated in autism, raising the possibility that therapeutic targets identified for FXS may have efficacy in treating multiple other causes of autism