Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress:from mouse to man

Individual susceptibility to anxiety disorders after maladaptive responses to stress is not well understood. We now report that while exploring stress responses in mice after traumatic brain injury (TBI), a condition associated to stress susceptibility, we observed that the anxiogenic effects of either TBI or exposure to life-threatening experiences (predator) were blocked when both stressors were combined. Because TBI increases the entrance into the brain of serum insulin-like growth factor I (IGF-I), a known modulator of anxiety with a wide range of concentrations in the human population, we then determined whether circulating IGF-I is related to anxiety measures. In mice, anxiety-like responses to predator were inversely related to circulating IGF-I levels. Other indicators of mood regulation such as sensitivity to dexamethasone suppression and expression levels of blood and brain FK506 binding protein 5 (FKBP5), a co-chaperone of the glucocorticoid receptor that regulates its activity, were also associated to circulating IGF-I. Indeed, brain FKBP5 expression in mice was stimulated by IGF-I. In addition, we observed in a large human cohort (n = 2686) a significant relationship between plasma IGF-I and exposure to recent stressful life events, while FKBP5 expression in blood cells was significantly associated to plasma IGF-I levels. Collectively, these data indicate that circulating IGF-I appears to be involved in mood homeostasis across different species. Furthermore, the data in mice allow us to indicate that IGF-I may be acting at least in part by modulating FKBP5 expression

Deficiency of the TLR4 analogue RP105 aggravates vein graft disease by inducing a pro-inflammatory response.

Venous grafts are often used to bypass occlusive atherosclerotic lesions; however, poor patency leads to vein graft disease. Deficiency of TLR4, an inflammatory regulator, reduces vein graft disease. Here, we investigate the effects of the accessory molecule and TLR4 analogue RadioProtective 105 (RP105) on vein graft disease. RP105 deficiency resulted in a 90% increase in vein graft lesion area compared to controls. In a hypercholesterolemic setting (LDLr(-/-)/RP105(-/-) versus LDLr(-/-) mice), which is of importance as vein graft disease is usually characterized by excessive atherosclerosis, total lesion area was not affected. However we did observe an increased number of unstable lesions and intraplaque hemorrhage upon RP105 deficiency. In both setups, lesional macrophage content, and lesional CCL2 was increased. In vitro, RP105(-/-) smooth muscle cells and mast cells secreted higher levels of CCL2. In conclusion, aggravated vein graft disease caused by RP105 deficiency results from an increased local inflammatory response

APAC treatment limits collar-induced carotid atherosclerotic plaque development in apoE-/- mice

Biopharmaceutic

Biopolymer-based structuring of liquid oil into soft solids and oleogels using water-continuous emulsions as templates

Physical trapping of a hydrophobic liquid oil in a matrix of water-soluble biopolymers was achieved using a facile two-step process by first formulating a surfactant-free oil-in-water emulsion stabilized by biopolymers (a protein and a polysaccharide) followed by complete removal of the water phase (by either high- or low-temperature drying of the emulsion) resulting in structured solid systems containing a high concentration of liquid oil (above 97 wt %). The microstructure of these systems was revealed by confocal and cryo-scanning electron microscopy, and the effect of biopolymer concentrations on the consistency of emulsions as well as the dried product was evaluated using a combination of small-amplitude oscillatory shear rheometry and large deformation fracture studies. The oleogel prepared by shearing the dried product showed a high gel strength as well as a certain degree of thixotropic recovery even at high temperatures. Moreover, the reversibility of the process was demonstrated by shearing the dried product in the presence of water to obtain reconstituted emulsions with rheological properties comparable to those of the fresh emulsion

Dust Masses, PAH Abundances, and Starlight Intensities in the SINGS Galaxy Sample

Physical dust models are presented for 65 galaxies in SINGS that are strongly detected in the four IRAC bands and three MIPS bands. For each galaxy we estimate (1) the total dust mass, (2) the fraction of the dust mass contributed by PAHs, and (3) the intensity of the starlight heating the dust grains. We find that spiral galaxies have dust properties resembling the dust in the local region of the Milky Way, with similar dust-to-gas ratio and similar PAH abundance. The observed SEDs, including galaxies with SCUBA photometry, can be reproduced by dust models that do not require "cold" (T ≾ 10 K) dust. The dust-to-gas ratio is observed to be dependent on metallicity. In the interstellar media of galaxies with A_O ≡ 12 + log_(10)(O/H) > 8.1, grains contain a substantial fraction of interstellar Mg, Si, and Fe. Galaxies with A_O 8.1 have a median q_(PAH) = 3.55%. The derived dust masses favor a value X_(CO) ≈ 4 × 10^(20) cm^(-2) (K km s^(-1))^(-1) for the CO-to-H_2 conversion factor. Except for some starbursting systems (Mrk 33, Tol 89, NGC 3049), dust in the diffuse ISM dominates the IR power

Three-micron spectra of AGB stars and supergiants in nearby galaxies

The dependence of stellar molecular bands on the metallicity is studied using infrared L-band spectra of AGB stars (both carbon-rich and oxygen-rich) and M-type supergiants in the Large and Small Magellanic Clouds (LMC and SMC) and in the Sagittarius Dwarf Spheroidal Galaxy. The spectra cover SiO bands for oxygen-rich stars, and acetylene (C2H2), CH and HCN bands for carbon-rich AGB stars. The equivalent width of acetylene is found to be high even at low metallicity. The high C2H2 abundance can be explained with a high carbon-to-oxygen (C/O) ratio for lower metallicity carbon stars. In contrast, the HCN equivalent width is low: fewer than half of the extra-galactic carbon stars show the 3.5micron HCN band, and only a few LMC stars show high HCN equivalent width. HCN abundances are limited by both nitrogen and carbon elemental abundances. The amount of synthesized nitrogen depends on the initial mass, and stars with high luminosity (i.e. high initial mass) could have a high HCN abundance. CH bands are found in both the extra-galactic and Galactic carbon stars. None of the oxygen-rich LMC stars show SiO bands, except one possible detection in a low quality spectrum. The limits on the equivalent widths of the SiO bands are below the expectation of up to 30angstrom for LMC metallicity. Several possible explanations are discussed. The observations imply that LMC and SMC carbon stars could reach mass-loss rates as high as their Galactic counterparts, because there are more carbon atoms available and more carbonaceous dust can be formed. On the other hand, the lack of SiO suggests less dust and lower mass-loss rates in low-metallicity oxygen-rich stars. The effect on the ISM dust enrichment is discussed.Comment: accepted for A&

Warm molecular hydrogen in the Spitzer SINGS galaxy sample

(simplified) Results on the properties of warm H2 in 57 normal galaxies are derived from H2 rotational transitions, obtained as part of SINGS. This study extends previous extragalactic surveys of H2, the most abundant constituent of the molecular ISM, to more common systems (L_FIR = e7 to 6e10 L_sun) of all morphological and nuclear types. The S(1) transition is securely detected in the nuclear regions of 86% of SINGS galaxies with stellar masses above 10^9.5 M_sun. The derived column densities of warm H2 (T > ~100 K), even though averaged over kiloparsec-scale areas, are commensurate with those of resolved PDRs; the median of the sample is 3e20 cm-2. They amount to between 1% and >30% of the total H2. The power emitted in the sum of the S(0) to S(2) transitions is on average 30% of the [SiII] line power, and ~4e-4 of the total infrared power (TIR) within the same area for star-forming galaxies, which is consistent with excitation in PDRs. The fact that H2 emission scales tightly with PAH emission, even though the average radiation field intensity varies by a factor ten, can also be understood if both tracers originate predominantly in PDRs, either dense or diffuse. A large fraction of the 25 LINER/Sy targets, however, strongly depart from the rest of the sample, in having warmer H2 in the excited states, and an excess of H2 emission with respect to PAHs, TIR and [SiII]. We propose a threshold in H2 to PAH power ratios, allowing the identification of low-luminosity AGNs by an excess H2 excitation. A dominant contribution from shock heating is favored in these objects. Finally, we detect, in nearly half the star-forming targets, non-equilibrium ortho to para ratios, consistent with FUV pumping combined with incomplete ortho-para thermalization by collisions, or possibly non-equilibrium PDR fronts advancing into cold gas.Comment: ApJS, in pres