Toll-like receptor-mediated signaling cascade as a regulator of the inflammation network during alcoholic liver disease

Chronic abuse of alcohol leads to various histological abnormalities in the liver. These are conditions collectively known as alcoholic liver disease (ALD). Currently, ALD is considered to be one of the major causes of death worldwide. An impaired intestinal barrier with related endotoxemia is among the various pathogenetic factors. This is mainly characterized by circulating levels of lipopolysaccharide (LPS), considered critical for the onset of intra-hepatic inflammation. This in turn promotes hepatocellular damage and fibrosis in ALD. Elevated levels of LPS exert their effects by binding to Toll-like receptors (TLRs) which are expressed by all liver-resident cells. The activation of TLR signaling triggers an overproduction and release of some cytokines, which promote an autocatalytic cascade of other proinflammatory signals. In this review, we provide an overview of the mechanisms that sustain LPS-mediated activation of TLR signaling, reporting current experimental and clinical evidence of its role during inflammation in ALD

Scaling behaviour of trapped bosonic particles in two dimensions at finite temperature

In the framework of the trap-size scaling theory, we study the scaling properties of the Bose-Hubbard model in two dimensions in the presence of a trapping potential at finite temperature. In particular, we provide results for the particle density and the density-density correlator at the Mott transitions and within the superfluid phase. For the former quantity, numerical outcomes are also extensively compared to Local Density Approximation predictions.Comment: 8 pages, 9 figure

New quantum chemical computations of formamide deuteration support a gas-phase formation of this prebiotic molecule

Based on recent work, formamide might be a potentially very important molecule in the emergence of terrestrial life. Although detected in the interstellar medium for decades, its formation route is still debated, whether in the gas phase or on the dust grain surfaces. Molecular deuteration has proven to be, in other cases, an efficient way to identify how a molecule is synthesised. For formamide, new published observations towards the IRAS16293-2422 B hot corino show that its three deuterated forms have all the same deuteration ratio, 2--5%, and that this is a factor 3--8 smaller than that measured for H2CO towards the IRAS16293-2422 protostar. Following a previous work on the gas-phase formamide formation via the reaction NH2 + H2CO -> HCONH2 + H, we present here new calculations of the rate coefficients for the production of monodeuterated formamide through the same reaction, starting from monodeuterated NH2 or H2CO. Some misconceptions regarding our previous treatment of the reaction are also cleared up. The results of the new computations show that, at the 100 K temperature of the hot corino, the rate of deuteration of the three forms is the same, within 20%. On the contrary, the reaction between non-deuterated species proceeds three times faster than that with deuterated ones. These results confirm that a gas-phase route for the formation of formamide is perfectly in agreement with the available observations.Comment: MNRAS in pres

Sulphur-bearing species in the star forming region L1689N

We report observations of the expected main S-bearing species (SO, SO2 and H2S) in the low-mass star forming region L1689N. We obtained large scale (~300''x200'') maps of several transitions from these molecules with the goal to study the sulphur chemistry, i.e. how the relative abundances change in the different physical conditions found in L1689N. We identified eight interesting regions, where we carried out a quantitative comparative study: the molecular cloud (as reference position), five shocked regions caused by the interaction of the molecular outflows with the cloud, and the two protostars IRAS16293-2422 and 16293E. In the cloud we carefully computed the gas temperature and density by means of a non-LTE LVG code, while in other regions we used previous results. We hence derived the column density of SO, SO2 and H2S, together with SiO and H2CO - which were observed previously - and their relevant abundance ratios. We find that SiO is the molecule that shows the largest abundance variations in the shocked regions, whereas S-bearing molecules show more moderate variations. Remarkably, the region of the brightest SiO emission in L1689N is undetected in SO2, H2S and H2CO and only marginally detected in SO. In the other weaker SiO shocks, SO2 is enhanced with respect to SO. We propose a schema in which the different molecular ratios correspond to different ages of the shocks. Finally, we find that SO, SO2 and H2S have significant abundance jumps in the inner hot core of IRAS16293-2422 and discuss the implications of the measured abundances.Comment: Accepted 08/10/0

Gas phase formation of the prebiotic molecule formamide: insights from new quantum computations

New insights into the formation of interstellar formamide, a species of great relevance in prebiotic chemistry, are provided by electronic structure and kinetic calculations for the reaction NH2 + H2CO -> NH2CHO + H. Contrarily to what previously suggested, this reaction is essentially barrierless and can, therefore, occur under the low temperature conditions of interstellar objects thus providing a facile formation route of formamide. The rate coefficient parameters for the reaction channel leading to NH2CHO + H have been calculated to be A = 2.6x10^{-12} cm^3 s^{-1}, beta = -2.1 and gamma = 26.9 K in the range of temperatures 10-300 K. Including these new kinetic data in a refined astrochemical model, we show that the proposed mechanism can well reproduce the abundances of formamide observed in two very different interstellar objects: the cold envelope of the Sun-like protostar IRAS16293-2422 and the molecular shock L1157-B2. Therefore, the major conclusion of this Letter is that there is no need to invoke grain-surface chemistry to explain the presence of formamide provided that its precursors, NH2 and H2CO, are available in the gas-phase.Comment: MNRAS Letters, in pres

Hot and dense water in the inner 25 AU of SVS13-A

In the context of the ASAI (Astrochemical Surveys At IRAM) project, we carried out an unbiased spectral survey in the millimeter window towards the well known low-mass Class I source SVS13-A. The high sensitivity reached (3-12 mK) allowed us to detect at least 6 HDO broad (FWHM ~ 4-5 km/s) emission lines with upper level energies up to Eu = 837 K. A non-LTE LVG analysis implies the presence of very hot (150-260 K) and dense (> 3 10^7 cm-3) gas inside a small radius ($\sim$ 25 AU) around the star, supporting, for the first time, the occurrence of a hot corino around a Class I protostar. The temperature is higher than expected for water molecules are sublimated from the icy dust mantles (~ 100 K). Although we cannot exclude we are observig the effects of shocks and/or winds at such small scales, this could imply that the observed HDO emission is tracing the water abundance jump expected at temperatures ~ 220-250 K, when the activation barrier of the gas phase reactions leading to the formation of water can be overcome. We derive X(HDO) ~ 3 10-6, and a H2O deuteration > 1.5 10-2, suggesting that water deuteration does not decrease as the protostar evolves from the Class 0 to the Class I stage.Comment: MNRAS Letter

The influence of permeability through bacterial porins in whole-cell compound accumulation

The lack of new drugs for Gram-negative pathogens is a global threat to modern medicine. The complexity of their cell envelope, with an additional outer membrane, hinders internal accumulation and thus, the access of molecules to their targets. Our limited understanding of the molecular basis for compound influx and efflux from these pathogens is a major bottleneck for the discovery of effective antibacterial compounds. Here we analyse the correlation between the whole-cell compound accumulation of ~200 molecules and their predicted porin permeability coefficient (influx), using a recently developed scoring function. We found a strong linear relationship (74%) between the two, confirming porins key in compound uptake in Gram-negative bacteria. The analysis of this unique dataset aids to better understand the molecular descriptors behind whole-cell accumulation and molecular uptake in Gram-negative bacteria

Mediastinitis and sternal prosthesis infection successfully treated by minimally invasive omental flap transposition

Purulent mediastinitis is a possible serious complication after mediastinal surgery. We report the case of a localized sternal plasmocytoma treated by sternectomy and prosthetic repair, who needed a second surgery for a fistulizing mediastinitis. Five months earlier, in another Hospital, the patient underwent sternal resection and reconstruction with a “sandwich” prosthesis (Methyl-methacrylate and Marlex mesh). Suppurative mediastinitis occurred and septic shock resolution was observed after the spontaneous opening of a mediastinal cutaneous fistula. After referring to our Unit the patient underwent extensive local and systemic preparation and nutritional support; the infected prosthesis was then removed and the gap filled by a laparoscopically-prepared omental flap. Adequate preoperative management, removal of any infected material and minimally invasive omental flap transposition allowed the successful treatment of this life-threatening condition

7Be and 22Na radionuclides for a new therapy for cancer

10B isotopes have been almost exclusively used in the neutron-capture radiation therapy (NCT) of cancer for decades. We have identified two other nuclides suitable for radiotherapy, which have ca. ten times larger cross section of absorption for neutrons and emit heavy charged particles. This would provide several key advantages for potential NCT, such as the possibility to use a lower nuclide concentration in the target tissues or a lower neutron irradiation flux. By detecting the characteristic γ radiation from the spontaneous decay of the radionuclides, one can image their biodistribution. These advantages could open up new possibilities for NCT applications as a safer and more efficient cancer therapy