Sphingosine 1-phosphate receptors: do they have a therapeutic potential in cardiac fibrosis?

Sphingosine 1-phosphate (S1P) is a bioactive lipid that is characterized by a peculiar mechanism of action. In fact, S1P, which is produced inside the cell, can act as an intracellular mediator, whereas after its export outside the cell, it can act as ligand of specific G-protein coupled receptors, which were initially named endothelial differentiation gene (Edg) and eventually renamed sphingosine 1-phosphate receptors (S1PRs). Among the five S1PR subtypes, S1PR1, S1PR2 and S1PR3 isoforms show broad tissue gene expression, while S1PR4 is primarily expressed in immune system cells, and S1PR5 is expressed in the central nervous system. There is accumulating evidence for the important role of S1P as a mediator of many processes, such as angiogenesis, carcinogenesis and immunity, and, ultimately, fibrosis. After a tissue injury, the imbalance between the production of extracellular matrix (ECM) and its degradation, which occurs due to chronic inflammatory conditions, leads to an accumulation of ECM and, consequential, organ dysfunction. In these pathological conditions, many factors have been described to act as pro- and anti-fibrotic agents, including S1P. This bioactive lipid exhibits both pro- and anti-fibrotic effects, depending on its site of action. In this review, after a brief description of sphingolipid metabolism and signaling, we emphasize the involvement of the S1P/S1PR axis and the downstream signaling pathways in the development of fibrosis. The current knowledge of the therapeutic potential of S1PR subtype modulators in the treatment of the cardiac functions and fibrinogenesis are also examined

The Hierarchical Origins of Observed Galaxy Morphology

Galaxies grow primarily via accretion-driven star formation in discs and merger-driven growth of bulges. These processes are implicit in semi-analytical models of galaxy formation, with bulge growth in particular relating directly to the hierarchical build-up of halos and their galaxies. In this paper, we consider several implementations of two semi-analytical models. Focusing on implementations in which bulges are formed during mergers only, we examine the fractions of elliptical galaxies and both passive and star-forming disk galaxies as functions of stellar and halo mass, for central and satellite systems. This is compared to an observational cross-matched SDSS+RC3 z ~ 0 sample of galaxies with accurate visual morphological classifications and M_{stellar} > 10^10.5 M_{sol}. The models qualitatively reproduce the observed increase of elliptical fraction with stellar mass, and with halo mass for central galaxies, supporting the idea that observed ellipticals form during major mergers. However, the overall elliptical fraction produced by the models is much too high compared with the z ~ 0 data. Since the "passive" -- i.e. non-star-forming -- fractions are approximately reproduced, and since the fraction which are star-forming disc galaxies is also reproduced, the problem is that the models overproduce ellipticals at the expense of passive S0 and spiral galaxies. Bulge-growth implementations (tuned to reproduce simulations) which allow the survival of residual discs in major mergers still destroy too much of the disc. Increasing the lifetime of satellites, or allowing significant disc regrowth around merger remnants, merely increases the fraction of star-forming disc galaxies. Instead, it seems necessary to reduce the mass ratios of merging galaxies, so that most mergers produce modest bulge growth in disc-galaxy remnants instead of ellipticals. [Abridged]Comment: latex, 20 pages, 13 figures. Accepted by Monthly Notices. Source package includes full version of Table 1 from paper (file sdssrc3_table_for_paper.tab

A warm mode of gas accretion on forming galaxies

We present results from high--resolution cosmological hydrodynamical simulations of a Milky--Way-sized halo, aimed at studying the effect of feedback on the nature of gas accretion. Simulations include a model of inter-stellar medium and star formation, in which SN explosions provide effective thermal feedback. We distinguish between gas accretion onto the halo, which occurs when gas particles cross the halo virial radius, and gas accretion onto the central galaxy, which takes place when gas particles cross the inner one-tenth of the virial radius. Gas particles can be accreted through three different channels, depending on the maximum temperature value, $T_{\rm max}$, reached during the particles' past evolution: a cold channel for $T_{\rm max}10^6$K, and a warm one for intermediate values of $T_{\rm max}$. We find that the warm channel is at least as important as the cold one for gas accretion onto the central galaxy. This result is at variance with previous findings that the cold mode dominates gas accretion at high redshift. We ascribe this difference to the different supernova feedback scheme implemented in our simulations. While results presented so far in the literature are based on uneffective SN thermal feedback schemes and/or the presence of a kinetic feedback, our simulations include only effective thermal feedback. We argue that observational detections of a warm accretion mode in the high--redshift circum-galactic medium would provide useful constraints on the nature of the feedback that regulates star formation in galaxies.Comment: 6 pages, 3 figures, accepted for publication in ApJ

A semi-analytic model comparison - gas cooling and galaxy mergers

We use stripped-down versions of three semi-analytic galaxy formation models to study the influence of different assumptions about gas cooling and galaxy mergers. By running the three models on identical sets of merger trees extracted from high-resolution cosmological N-body simulations, we are able to perform both statistical analyses and halo-by-halo comparisons. Our study demonstrates that there is a good statistical agreement between the three models used here, when operating on the same merger trees, reflecting a general agreement in the underlying framework for semi-analytic models. We also show, however, that various assumptions that are commonly adopted to treat gas cooling and galaxy mergers can lead to significantly different results, at least in some regimes. In particular, we find that the different models adopted for gas cooling lead to similar results for mass scales comparable to that of our own Galaxy. Significant differences, however, arise at larger mass scales. These are largely (but not entirely) due to different treatments of the `rapid cooling' regime, and different assumptions about the hot gas distribution. At this mass regime, the predicted cooling rates can differ up to about one order of magnitude, with important implications on the relative weight that these models give to AGN feedback in order to counter-act excessive gas condensation in relatively massive haloes at low redshift. Different assumptions in the modelling of galaxy mergers can also result in significant differences in the timings of mergers, with important consequences for the formation and evolution of massive galaxies.Comment: 21 pages, 14 figures. Accepted for publication in MNRAS

A semi-analytic model comparison: testing cooling models against hydrodynamical simulations

We compare predictions of cooled masses and cooling rates from three stripped-down Semi-Analytic Models (SAMs) of galaxy formation with the results of N-body+SPH simulations with gas particle mass of 3.9x10^6 Msun, where radiative cooling of a gas of primordial composition is implemented. We also run a simulation where cooling is switched on at redshift ~2, in order to test cooling models in a regime in which their approximations are expected to be valid. We confirm that cooling models implemented in SAMs are able to predict the amount of cooled mass at z=0 to within ~20 per cent. However, some relevant discrepancies are found. (i) When the contribution from poorly resolved halos is subtracted out, SAMs tend to under-predict by ~30 per cent the mass that cools in the infall-dominated regime. (ii) At large halo masses SAMs tend to over-predict cooling rates, though the numerical result may be affected by the use of SPH. (iii) As found in our previous work, cooling rates are found to be significantly affected by model details: simulations disfavour models with large cores and with quenching of cooling at major mergers. (iv) When cooling is switched on at z~2, cold gas accumulates very quickly in the simulated halos. This accumulation is reproduced by SAMs with varying degrees of accuracy.Comment: 20 pages, 12 figures, accepted by MNRA

What determines the fraction of elliptical galaxies in clusters?

We study the correlation between the morphological mix of cluster galaxies and the assembly history of the parent cluster by taking advantage of two independently developed semi-analytic models for galaxy formation and evolution. In our models, both the number of cluster members and that of elliptical members increase as a function of cluster mass, in such a way that the resulting elliptical fractions are approximately independent of cluster mass. The population of cluster ellipticals exhibit a marked bimodal distribution as a function of galaxy stellar mass, with a dip at masses $\sim 10^{10}\,{\rm M}_{\odot}$. In the framework of our models, this bimodality originates from the combination of a strongly decreasing number of galaxies with increasing stellar mass, and a correspondingly increasing probability of experiencing major mergers. We show that the correlation between the measured elliptical fraction and the assembly history of the parent cluster is weak, and that it becomes stronger in models that adopt longer galaxy merger times. We argue that this results from the combined effect of a decreasing bulge production due to a reduced number of mergers, and an increasing survival probability of pre-existing ellipticals, with the latter process being more important than the former.Comment: 8 pages, 3 figures, accepted for publication in MNRA

Signal transduction in the Sertoli cell: serum modulation of the response to FSH

Immature Sertoli cells of the testicular seminiferous tubule maintain the expression of their differentiated phenotype when cultured in unsupplemented medium. In preliminary experiments we observed that foetal bovine serum (FBS) stimulates polyphosphoinositides (PI) hydrolysis in Sertoli cells. We then evaluated the effect of serum on the function of the immature Sertoli cell in culture, in terms of cAMP and estrogen production. Treatment of Sertoli cells for 30 min with 1–10% FBS had no effect on basal cAMP accumulation but abolished the response to FSH. The serum concentration producing half-maximal inhibition of the FSH-dependent cAMP accumulation was 0.5–1%. Comparison of the FSH-dose-response in the absence or presence of serum showed a decreased maximal response when serum was present. Sertoli cells exposed to serum were also less responsive to the β-adrenergic agonist isoproterenol, to cholera toxin, and to forskolin. The serum inhibition was rapidly reversed upon removal of serum or incubating the cells with the phosphodiesterase inhibitor MIX (methyl-isobutyl-xanthine). Similarly to what observed with cAMP, serum affected androgen aromatization stimulated by FSH, isoproterenol, cholera toxin, forskolin and dibutyryl cAMP. These data indicate that factors present in serum can act as modulators of the Sertoli cell function in vitro by rapidly and reversibly inhibiting the cAMP and steroidogenic response of the Sertoli cell to FSH

The effect of thermally pulsating asymptotic giant branch stars on the evolution of the rest-frame near-infrared galaxy luminosity function

We address the fundamental question of matching the rest-frame K-band luminosity function (LF) of galaxies over the Hubble time using semi-analytic models, after modification of the stellar population modelling. We include the Maraston evolutionary synthesis models, that feature a higher contribution by the Thermally Pulsating - Asymptotic Giant Branch (TP-AGB) stellar phase, into three different semi-analytic models, namely the De Lucia and Blaizot version of the Munich model, MORGANA and the Menci model. We leave all other input physics and parameters unchanged. We find that the modification of the stellar population emission can solve the mismatch between models and the observed rest-frame K-band luminosity from the brightest galaxies derived from UKIDSS data at high redshift. For all explored semi-analytic models this holds at the redshifts - between 2 and 3 - where the discrepancy was recently pointed out. The reason for the success is that at these cosmic epochs the model galaxies have the right age (~1 Gyr) to contain a well-developed TP-AGB phase which makes them redder without the need of changing their mass or age. At the same time, the known overestimation of the faint end is enhanced in the K-band when including the TP-AGB contribution. At lower redshifts (z<2) some of the explored models deviate from the data. This is due to too short merging timescales and inefficient 'radio-mode' AGN feedback. Our results show that a strong evolution in mass predicted by hierarchical models is compatible with no evolution on the bright-end of the K-band LF from z=3 to the local universe. This means that, at high redshifts and contrary to what is commonly accepted, K-band emission is not necessarily a good tracer of galaxy mass.Comment: 10 pages, 5 figures, accepted by MNRA