Interaction of leptospira elongation factor tu with plasminogen and complement factor h: a metabolic leptospiral protein with moonlighting activities

The elongation factor Tu (EF-Tu), an abundant bacterial protein involved in protein synthesis, has been shown to display moonlighting activities. Known to perform more than one function at different times or in different places, it is found in several subcellular locations in a single organism, and may serve as a virulence factor in a range of important human pathogens. Here we demonstrate that Leptospira EF-Tu is surface-exposed and performs additional roles as a cell-surface receptor for host plasma proteins. It binds plasminogen in a dose-dependent manner, and lysine residues are critical for this interaction. Bound plasminogen is converted to active plasmin, which, in turn, is able to cleave the natural substrates C3b and fibrinogen. Leptospira EF-Tu also acquires the complement regulator Factor H (FH). FH bound to immobilized EF-Tu displays cofactor activity, mediating C3b degradation by Factor I (FI). In this manner, EF-Tu may contribute to leptospiral tissue invasion and complement inactivation. To our knowledge, this is the first description of a leptospiral protein exhibiting moonlighting activities

Stochastic gravito-inertial modes discovered by CoRoT in the hot Be star HD51452

Context. Be stars are rapidly rotating stars with a circumstellar decretion disk. They usually undergo pressure and/or gravity pulsation modes excited by the κ-mechanism, i.e. an effect of the opacity of iron-peak elements in the envelope of the star. In the Milky Way, p-modes are observed in stars that are hotter than or equal to the B3 spectral type, while g-modes are observed at the B2 spectral type and cooler. Aims. We observed a B0IVe star, HD51452, with the high-precision, high-cadence photometric CoRoT satellite and high-resolution, ground-based HARPS and SOPHIE spectrographs to study its pulsations in great detail. We also used the lower resolution spectra available in the BeSS database. Methods. We analyzed the CoRoT and spectroscopic data with several methods: Clean-NG, FreqFind, and a sliding window method. We also analyzed spectral quantities, such as the violet over red (V/R) emission variations, to obtain information about the variation in the circumstellar environment. We calculated a stellar structure model with the ESTER code to test the various interpretation of the results. Results. We detect 189 frequencies of variations in the CoRoT light curve in the range between 0 and 4.5 c d−1. The main frequencies are also recovered in the spectroscopic data. In particular we find that HD51452 undergoes gravito-inertial modes that are not in the domain of those excited by the κ-mechanism. We propose that these are stochastic modes excited in the convective zones and that at least some of them are a multiplet of r-modes (i.e. subinertial modes mainly driven by the Coriolis acceleration). Stochastically excited gravito-inertial modes had never been observed in any star, and theory predicted that their very low amplitudes would be undetectable even with CoRoT. We suggest that the amplitudes are enhanced in HD51452 because of the very rapid stellar rotation. In addition, we find that the amplitude variations of these modes are related to the occurrence of minor outbursts. Conclusions. Thanks to CoRoT data, we have detected a new kind of pulsations in HD51452, which are stochastically excited gravito-inertial modes, probably due to its very rapid rotation. These modes are probably also present in other rapidly rotating hot Be stars.

A galaxy model from Two Micron All Sky Survey star counts in the whole sky, including the plane

We use the star count model of Ortiz & L´epine to perform an unprecedented exploration of the most important Galactic parameters comparing the predicted counts with the Two Micron All Sky Survey observed star counts in the J, H, and KS bands for a grid of positions covering the whole sky. The comparison is made using a grid of lines of sight given by the HEALPix pixelization scheme. The resulting best-fit values for the parameters are: 2120 ± 200 pc for the radial scale length and 205 ± 40 pc for the scale height of the thin disk, with a central hole of 2070+2000 −800 pc for the same disk, 3050 ± 500 pc for the radial scale length and 640 ± 70 pc for the scale height of the thick disk, 400 ± 100 pc for the central dimension of the spheroid, 0.0082 ± 0.0030 for the spheroid to disk density ratio, and 0.57 ± 0.05 for the oblate spheroid parameter.

Molecular gas in the galaxy M83 : Its distribution, kinematics, and relation to star formation

The barred spiral galaxy M83 (NGC5236) has been observed in the 12CO J=1–0 and J=2–1 millimetre lines with the Swedish-ESO Submillimetre Telescope (SEST). The sizes of the CO maps are 100×100, and they cover the entire optical disk. The CO emission is strongly peaked toward the nucleus. The molecular spiral arms are clearly resolved and can be traced for about 360º. The total molecular gas mass is comparable to the total Hi mass, but H2 dominates in the optical disk. Iso-velocity maps show the signature of an inclined, rotating disk, but also the effects of streaming motions along the spiral arms. The dynamical mass is determined and compared to the gas mass. The pattern speed is determined from the residual velocity pattern, and the locations of various resonances are discussed. The molecular gas velocity dispersion is determined, and a trend of decreasing dispersion with increasing galactocentric radius is found. A total gas (H2+Hi+He) mass surface density map is presented, and compared to the critical density for star formation of an isothermal gaseous disk. The star formation rate (SFR) in the disk is estimated using data from various star formation tracers. The different SFR estimates agree well when corrections for extinctions, based on the total gas mass map, are made. The radial SFR distribution shows features that can be associated with kinematic resonances. We also find an increased star formation efficiency in the spiral arms. Different Schmidt laws are fitted to the data. The star formation properties of the nuclear region, based on high angular resolution HST data, are also discussed.

The complement system of the goat: haemolytic assays and isolation of major proteins

[EN] Background: The aim of the present study was to develop a haemolytic assay for the study of the complement system in dairy goats (Capra aegagrus hircus) and to characterize the major goat complement system proteins. Results: The commonly used sheep erythrocyte sensitized with rabbit antibodies were not sensitive to lysis by goat serum, but the combination of human red blood cells (RBC) plus rabbit antibodies was the best option found for goat complement assay. A buffer based on HEPES instead of the classical veronal (barbitone) was developed. Three proteins were isolated: factor H, C1q and C3 and these were compared with the corresponding human proteins. A novel affinity chromatography technique was developed for isolation of factor H. Conclusions: Human RBC plus rabbit antibodies were a suitable option for haemolytic assays. The isolated proteins are similar to the human counterparts.

The Universe 10 Billion years ago: Morphologies, Star-formation rates and Galactic-scale winds in z ∼ 2 Galaxies

This thesis is devoted to the study of the properties of high-redsfhit galaxies in the epoch 1 < z < 3, when a substantial fraction of galaxy mass was assembled, and when the evolution of the star-formation rate density peaked. Following a multi-perspective approach and using the most recent and high-quality data available (spectra, photometry and imaging), the morphologies and the star-formation properties of high-redsfhit galaxies were investigated. Through an accurate morphological analyses, the built up of the Hubble sequence was placed around z ~ 2.5. High-redshift galaxies appear, in general, much more irregular and asymmetric than local ones. Moreover, the occurrence of morphological k-­correction is less pronounced than in the local Universe. Different star-formation rate indicators were also studied. The comparison of ultra-violet and optical based estimates, with the values derived from infra-red luminosity showed that the traditional way of addressing the dust obscuration is problematic, at high-redshifts, and new models of dust geometry and composition are required. Finally, by means of stacking techniques applied to rest-frame ultra-violet spectra of star-forming galaxies at z~2, the warm phase of galactic-scale outflows was studied. Evidence was found of escaping gas at velocities of ~ 100 km/s. Studying the correlation of inter-­stellar absorption lines equivalent widths with galaxy physical properties, the intensity of the outflow-related spectral features was proven to depend strongly on a combination of the velocity dispersion of the gas and its geometry.

The evolution of massive clumps in star forming regions

In this thesis two related arguments are investigated: - The first stages of the process of massive star formation, investigating the physical conditions and -properties of massive clumps in different evolutionary stages, and their CO depletion; - The influence that high-mass stars have on the nearby material and on the activity of star formation. I characterise the gas and dust temperature, mass and density of a sample of massive clumps, and analyse the variation of these properties from quiescent clumps, without any sign of active star formation, to clumps likely hosting a zero-age main sequence star. I briefly discuss CO depletion and recent observations of several molecular species, tracers of Hot Cores and/or shocked gas, of a subsample of these clumps. The issue of CO depletion is addressed in more detail in a larger sample consisting of the brightest sources in the ATLASGAL survey: using a radiative tranfer code I investigate how the depletion changes from dark clouds to more evolved objects, and compare its evolution to what happens in the low-mass regime. Finally, I derive the physical properties of the molecular gas in the photon-dominated region adjacent to the HII region G353.2+0.9 in the vicinity of Pismis 24, a young, massive cluster, containing some of the most massive and hottest stars known in our Galaxy. I derive the IMF of the cluster and study the star formation activity in its surroundings. Much of the data analysis is done with a Bayesian approach. Therefore, a separate chapter is dedicated to the concepts of Bayesian statistics.

The core mass function in star-forming region NGC6357

The aim of this work was to study the dense cloud structures and to obtain the mass distribution of the dense cores (CMF) within the NGC6357 complex, from observations of the dust continuum at 450 and 850~$\mu$m of a 30 $\times$ 30 arcmin$^2$ region containing the H\textsc{ii} regions, G353.2+0.9 and G353.1+0.6.

Tracing AGN accretion and star formation in Herschel galaxies

In this Thesis, we study the physical properties and the cosmic evolution of AGN and their host galaxies since z∼3. Our analysis exploits samples of star forming galaxies detected with Herschel at far-IR wavelengths (from 70 up to 500 micron) in different extragalactic surveys, such as COSMOS and the deep GOODS (South and North) fields. The broad-band ancillary data available in COSMOS and the GOODS fields, allows us to implement Herschel and Spitzer photometry with multi-wavelength ancillary data. We perform a multicomponent SED-fitting decomposition to decouple the emission due to star formation from that due to AGN accretion, and to estimate both host-galaxy parameters (such as stellar mass, M* and star formation rate, SFR), and nuclear intrinsic bolometric luminosities. We use the individual estimates of AGN bolometric luminosity obtained through SED-fitting decomposition to reconstruct the redshit evolution of the AGN bolometric luminosity function since z∼3. The resulting trends are used to estimate the overall AGN accretion rate density at different cosmic epochs and to trace the first ever estimate of the AGN accretion history from an IR survey. Later on, we focus our study on the connection between AGN accretion and integrated galaxy properties. We analyse the relationships of AGN accretion with galaxy properties in the SFR-M* plane and at different cosmic epochs. Finally, we infer what is the parameter that best correlates with AGN accretion, comparing our results with previous studies and discussing their physical implications in the context of current scenarios of AGN/galaxy evolution.

Monospecific high-affinity and complement activating anti-GM1 antibodies are determinants in experimental axonal neuropathy

It has been difficult to replicate consistently the experimental model of axonal Guillain-Barré syndrome (GBS). We immunized rabbits with two lipo-oligosaccharides (LOS1 and LOS2) derived from the same C. jejuni strain and purified in a slightly different way. LOS1 did not contain proteins whereas several proteins were present in LOS2. In spite of a robust anti-GM1 antibody response in all animals the neuropathy developed only in rabbits immunized with LOS1. To explain this discrepancy we investigated fine specificity, affinity and ability to activate the complement of anti-GM1 antibodies. Only rabbits immunized with LOS1 showed monospecific high-affinity antibodies which activated more effectively the complement. Although it is not well understood how monospecific high-affinity antibodies are induced these are crucial for the induction of experimental axonal neuropathy. Only a strict adherence to the protocols demonstrated to be successful may guarantee the reproducibility and increase the confidence in the animal model as a reliable tool for the study of the human axonal GBS.

IVIG blocks complement deposition mediated by anti-GM1 antibodies in multifocal motor neuropathy

The pathogenesis of multifocal motor neuropathy (MMN) has yet to be established. MMN patients often carry anti-GM1 IgM antibodies, suggesting an autoimmune process involving complement. Intravenous immunoglobulin (IVIG) is the first line treatment, but its action mechanism is unknown.

A hypoxia complement differentiates the muscle response to endurance exercise

Metabolic stress is believed to constitute an important signal for training-induced adjustments of gene expression and oxidative capacity in skeletal muscle. We hypothesized that the effects of endurance training on expression of muscle-relevant transcripts and ultrastructure would be specifically modified by a hypoxia complement during exercise due to enhanced glycolytic strain. Endurance training of untrained male subjects in conditions of hypoxia increased subsarcolemmal mitochondrial density in the recruited vastus lateralis muscle and power output in hypoxia more than training in normoxia, i.e. 169 versus 91% and 10 versus 6%, respectively, and tended to differentially elevate sarcoplasmic volume density (42 versus 20%, P = 0.07). The hypoxia-specific ultrastructural adjustments with training corresponded to differential regulation of the muscle transcriptome by single and repeated exercise between both oxygenation conditions. Fine-tuning by exercise in hypoxia comprised gene ontologies connected to energy provision by glycolysis and fat metabolism in mitochondria, remodelling of capillaries and the extracellular matrix, and cell cycle regulation, but not fibre structure. In the untrained state, the transcriptome response during the first 24 h of recovery from a single exercise bout correlated positively with changes in arterial oxygen saturation during exercise and negatively with blood lactate. This correspondence was inverted in the trained state. The observations highlight that the expression response of myocellular energy pathways to endurance work is graded with regard to metabolic stress and the training state. The exposed mechanistic relationship implies that the altitude specificity of improvements in aerobic performance with a 'living low-training high' regime has a myocellular basis.

T2 star relaxation times for assessment of articular cartilage at 3 T: a feasibility study

T2 mapping techniques use the relaxation constant as an indirect marker of cartilage structure, and the relaxation constant has also been shown to be a sensitive parameter for cartilage evaluation. As a possible additional robust biomarker, T2* relaxation time is a potential, clinically feasible parameter for the biochemical evaluation of articular cartilage.