Astrochemical relevance of VUV ionization of large PAH cations.

CONTEXT: As a part of interstellar dust, polycyclic aromatic hydrocarbons (PAHs) are processed by the interaction with vacuum ultra-violet (VUV) photons that are emitted by hot young stars. This interaction leads to the emission of the well-known aromatic infrared bands but also of electrons, which can significantly contribute to the heating of the interstellar gas. AIMS: Our aim is to investigate the impact of molecular size on the photoionization properties of cationic PAHs. METHODS: Trapped PAH cations of sizes between 30 and 48 carbon atoms were submitted to VUV photons in the range of 9 to 20 eV from the DESIRS beamline at the synchrotron SOLEIL. All resulting photoproducts including dications and fragment cations were mass-analyzed and recorded as a function of photon energy. RESULTS: Photoionization is found to be predominant over dissociation at all energies, which differs from an earlier study on smaller PAHs. The photoionization branching ratio reaches 0.98 at 20 eV for the largest studied PAH. The photoionization threshold is observed to be between 9.1 and 10.2 eV, in agreement with the evolution of the ionization potential with size. Ionization cross sections were indirectly obtained and photoionization yields extracted from their ratio with theoretical photoabsorption cross sections, which were calculated using time-dependent density functional theory. An analytical function was derived to calculate this yield for a given molecular size. CONCLUSIONS: Large PAH cations could be efficiently ionized in H i regions and provide a contribution to the heating of the gas by photoelectric effect. Also, at the border of or in H ii regions, PAHs could be exposed to photons of energy higher than 13.6 eV. Our work provides recipes to be used in astronomical models to quantify these points.

Detection of Buckminsterfullerene emission in the diffuse interstellar medium.

Emission of fullerenes in their infrared vibrational bands has been detected in space near hot stars. The proposed attribution of the diffuse interstellar bands at 9577 and 9632 Å to electronic transitions of the buckminsterfullerene cation (i.e. [Formula: see text]) was recently supported by new laboratory data, confirming the presence of this species in the diffuse interstellar medium (ISM). In this letter, we present the detection, also in the diffuse ISM, of the 17.4 and 18.9 µm emission bands commonly attributed to vibrational bands of neutral C60. According to classical models that compute the charge state of large molecules in space, C60 is expected to be mostly neutral in the diffuse ISM. This is in agreement with the abundances of diffuse C60 we derive here from observations. We also find that C60 is less abundant in the diffuse ISM than in star-forming regions, supporting the theory that C60 can be formed in these regions.

Morphofunctional alterations in ventral tegmental area dopamine neurons in acute and prolonged opiates withdrawal. A computational perspective.

Dopamine (DA) neurons of the ventral tegmental area (VTA) play a key role in the neurobiological basis of goal-directed behaviors and addiction. Morphine (MOR) withdrawal induces acute and long-term changes in the morphology and physiology of VTA DA cells, but the mechanisms underlying these modifications are poorly understood. Because of their predictive value, computational models are a powerful tool in neurobiological research, and are often used to gain further insights and deeper understanding on the molecular and physiological mechanisms underlying the development of various psychiatric disorders. Here we present a biophysical model of a DA VTA neuron based on 3D morphological reconstruction and electrophysiological data, showing how opiates withdrawal-driven morphological and electrophysiological changes could affect the firing rate and discharge pattern. The model findings suggest how and to what extent a change in the balance of GABA/GLU inputs can take into account the experimentally observed hypofunction of VTA DA neurons during acute and prolonged withdrawal, whereas morphological changes may play a role in the increased excitability of VTA DA cell to opiate administration observed during opiate withdrawal.

A new potassium-based intermediate and its role in the desorption properties of the K-Mg-N-H system.

New insights into the reaction pathways of different potassium/magnesium amide-hydride based systems are discussed. In situ SR-PXD experiments were for the first time performed in order to reveal the evolution of the phases connected with the hydrogen releasing processes. Evidence of a new K-N-H intermediate is shown and discussed with particular focus on structural modification. Based on these results, a new reaction mechanism of amide-hydride anionic exchange is proposed.

Neuroprotective and anti-inflammatory properties of a novel non-thiazolidinedione PPARγ agonist in vitro and in MPTP-treated mice.

Peroxisome proliferator-activated receptor (PPAR)γ is a potential pharmacological target for disease-modification in Parkinson's disease (PD), mainly acting by modulating the neuroinflammatory response. However, currently available agonists thiazolidinediones (TZDs) present limitations due to safety concerns. We evaluated a novel thiobarbituric-like compound MDG548, which acts as a functional PPARγ agonist displaying higher and selective binding affinity as compared to TZDs. Neuroprotection by MDG548 was tested in vitro and in a mouse MPTP model of PD, and neuroinflammation was investigated as a putative underlying mechanism. Viability assay on rat cortical neurons showed lack of cytotoxic effect in the dose-range of 100 nM-10 µM, which was therefore used for testing in vitro protection against H2O2 and MPP+ neurotoxicity. MDG548 dose-dependently increased cell viability of rat cortical neurons co-treated with H2O2 or pre-exposed to MDG548 prior to H2O2. Moreover, MDG548 induced neuroprotection in MPP+-treated PC12 cells. NF-kB activation was investigated to assess anti-inflammatory activity. MDG548 dose-dependently decreased NF-kB activation induced by LPS (100 ng/100ml) in HEK-Blue-hTLR4 cells. Given the supposed cancer risk of other PPARγ agonists, Ames test for genotoxicity was performed in Salmonella typhimurium TA100 and TA98 strains, showing that MDG548 was not genotoxic. In vivo, BL/6J mice were treated with MPTP (20mg/kg i.p. once/day for 4 days) in association with saline or MDG548 (2, 5, 10 mg/kg i.p.). Stereological counting showed that MDG548 prevented the MPTP-induced reduction in TH-positive cells in the substantia nigra compacta (SNc) at all doses tested. Moreover, MDG548 reduced reactive microglia and iNOS induction in the SNc. MDG548, being a non-TZD compound with high PPARγ affinity, void of genotoxicity, and with in vitro as well as in vivo neuroprotective properties, provides a promising alternative in the search for safer PPARγ agonists to be tested as potential disease-modifying drugs in PD.

Understanding oscillatory phenomena in molecular hydrogen generation via sodium borohydride hydrolysis.

The hydrolysis of borohydride salts represents one of the most promising processes for the generation of high purity molecular hydrogen under mild conditions. In this work we show that the sodium borohydride hydrolysis exhibits a fingerprinting periodic oscillatory transient in the hydrogen flow over a wide range of experimental conditions. We disproved the possibility that flow oscillations are driven by supersaturation phenomena of gaseous bubbles in the reactive mixture or by a nonlinear thermal feedback according to a thermokinetic model. Our experimental results indicate that the NaBH4 hydrolysis is a spontaneous inorganic oscillator, in which the hydrogen flow oscillations are coupled to an "oscillophor" in the reactive solution. The discovery of this original oscillator paves the way for a new class of chemical oscillators, with fundamental implications not only for testing the general theory on oscillations, but also with a view to chemical control of borohydride systems used as a source of hydrogen based green fuel.

A new magnetic resonance imaging approach for discriminating Sardinian sheep milk cheese made from heat-treated or raw milk.

The evaluation of milk heat treatment on dairy products via reliable analytical methods is a challenging issue that involves both industrial and fundamental research. We describe a new magnetic resonance imaging (MRI) protocol for discriminating Sardinian sheep milk cheese originating from heat-treated or raw milk. Thirty-six samples (18 pecorino cheeses manufactured from heat-treated milk and 18 Fiore Sardo cheeses made from raw milk) were investigated by means of MRI and bi-exponential signal decay analysis. The protocol is capable of discerning cheeses by virtue of the different distribution of the transversal (T2) relaxation time constant. Cheeses from heat-treated milk showed a significantly higher area fraction (≈70-80%), corresponding to the fast relaxing water protons (T2 ≈ 9 ms), compared with raw milk cheeses, whereas the opposite was observed for the long T2 (T2 ≈ 35 ms) proton population. The MRI protocol described is rapid and nondestructive, and it provides statistically significant discrimination between ewe milk cheeses made from heat-treated and raw milk.

High-resolution infrared absorption spectroscopy of thermally excited naphthalene. Measurements and calculations of anharmonic parameters and vibrational interactions.

We report in this paper the recording and analysis of the vibrational spectrum of naphthalene in the 1.6-200 microm (50-6000 cm(-1)) spectral range with a resolution of 0.005 cm(-1). The spectrum, recorded at room temperature, shows several complex structures in the Q branches of the c-type bands, which can be assigned to hot-band sequences as well as combination bands and overtones. To analyse the experimental data, we developed a model based on anharmonic calculations which predicts the transitions (positions and intensities) involving the vibrational levels populated at room temperature. This work permits us to estimate the validity and limitations of our calculations, which can be used to predict the band profiles of naphthalene (and larger PAHs) at various temperatures, with potential astrophysical applications.

Growth of Ag nanometre-sized particles in solution: molecular dynamics simulations.

This work focuses on the growth of nanometre-sized Ag clusters in solution. Molecular dynamics simulations have been employed to gain the necessary detail on the dynamics of solute species and to study the mechanistic features of the processes governing the association of solute atoms in aggregates. Supersaturated liquid solutions of Ag in tetrachloromethane have been considered. A systematic variation of the concentration of Ag atoms in solution permitted us to show the different mechanistic scenarios responsible for the growth processes of solid Ag clusters. It is shown that such processes are limited by the thermal diffusion of solute in the solution bulk at relatively low supersaturation degrees, whereas the growth is limited by interfacial effects at relatively high supersaturation degrees.

Apolipoprotein B, apolipoprotein E, and angiotensin-converting enzyme polymorphisms in 2 Italian populations at different risk for coronary artery disease and comparison of allele frequencies among European populations.

Polymorphisms at the apolipoprotein B (APOB XbaI, EcoRI, insertion-deletion), apolipoprotein E (APOE), and angiotensin-converting enzyme (ACE) loci are thought to be involved in susceptibility to coronary artery disease (CAD) and myocardial infarction. The aim of this study was to determine whether the allele distribution of the APOB, APOE, and ACE polymorphisms is different in 2 Italian regions with higher (northern Italy) and lower (Sardinia) CAD occurrence. The frequencies of the APOB and APOE alleles that are considered CAD risk factors were higher in northern Italy (APOB X- = 0.655; APOB R- = 0.198; APOB insertion = 0.757; APOE*4 = 0.110) than in Sardinia (APOB X- = 0.568; APOB R- = 0.159; APOB insertion = 0.680; APOE*4 = 0.052), although only APOE allele frequencies differed significantly (p = 0.001). ACE deletion allele frequencies in the 2 geographic areas showed an opposite pattern (northern Italy = 0.658; Sardinia = 0.721). Furthermore, we investigated the impact of APOB and APOE polymorphisms on interindividual variation in total cholesterol level in the 2 Italian samples, which differ in dietary habits. Only APOE phenotypes showed different mean levels of total cholesterol; the association was significant only in northern Italy (p = 0.04), where continental dietary habits and higher mean cholesterol levels prevail. These results support the suggestion that the cholesterol increasing effect of APOE*4 is environmentally mediated. Analysis of allele distributions among European populations, with remarkable differences in CAD prevalence, revealed a constant positive relationship between APOE*4 allele frequency and CAD incidence. The highest frequencies of APOB X- and R- were observed in Finland, where the incidence of CAD is high, and there is a partial agreement between APOB R- frequency and CAD occurrence across Europe, while APOB insertion and ACE deletion alleles are evenly distributed among European populations.

Hb Puttelange [beta 140(H19)Ala-->Val] in an Italian man with polycythemia.

Hb Puttelange [beta 140(H18)Ala-->Val] was found in a 51-year-old Italian man who had mild polycythemia. The variant eluted from ion exchange high performance liquid chromatography at a position between Hb A and Hb A2. It comprised approximately 34% of the total hemoglobin, was weakly unstable and exhibited an increased oxygen affinity. Amplification of the beta-globin exons and nucleotide sequencing revealed a heterozygosity for a GCC-->GTC mutation in codon 140 corresponding to an Ala-->Val replacement. This substitution accounts for the altered functional properties, probably by producing indirect perturbation of the 2 3-diphosphoglycerate pocket through the nearby lysine residue at beta 82(EF6).

Apolipoprotein E polymorphism in Italy investigated in native plasma by a simple polyacrylamide gel isoelectric focusing technique. Comparison with frequency data of other European populations.

A new polyacrylamide gel isoelectric focusing (PAGIEF) technique has been developed that allows rapid and reliable identification of Apolipoprotein E (APOE) phenotypes directly from plasma or serum without any prior treatment. This method was used to determine the APOE phenotypes in samples from Central and Southern Italy, Sicily, and Sardinia. The frequencies observed for the APOE*2, APOE*3, and APOE*4 alleles in Central and Southern Italy (Sicily included) were similar (0.066, 0.851, 0.083 and 0.056, 0.858, 0.085 respectively) though lower APOE*4 frequencies were found in the more southern regions. The Sardinian population showed APOE gene frequencies (APOE*2 = 0.050, APOE*3 = 0.898, APOE*4 = 0.052) to be significantly different from those of the rest of Italy owing to the low APOE*4 frequency, the lowest among Caucasian populations. The frequencies were compared with those found in other European populations. A clear cut North-South decreasing cline was found for APOE*4 allele frequencies and an opposite trend was found for APOE*3 frequencies. The overall dispersion of European populations as determined by the three APOE allele frequencies was graphically represented using coordinate analysis. The tendency of the APOE*4 frequency to decline with latitude both at the Italian and at the European level was discussed with reference to similar trends observed for dietary habits (saturated fat intake).

Distribution of ORM1, C6, C7 and APO C-II allele frequencies in populations from mainland Italy and Sardinia.

The genetic variation of the human plasma proteins ORM1, C6, C7 and APO C-II was investigated by isoelectric focusing followed by immunoblotting in populations from mainland Italy and Sardinia. The frequencies of ORM1*1 were 0.621 and 0.564, while those of C6*A were 0.657 and 0.706 on mainland Italy and in Sardinia, respectively. In the Roman sample, 8 heterozygotes with C6 variant alleles were encountered, while none were observed in Sardinians. For C7 and APO C-II a number of heterozygotes with the rare alleles C7*2 and APO C-II*2 were found, but their frequency did not reach polymorphic levels in either population. The two populations showed a significant difference in the gene frequencies distribution for ORM1.

Genetic polymorphisms of the A and B subunits of human coagulation factor XIII in mainland Italy and Sardinia: description of a new FXIIIA variant allele.

The distribution of the two alleles of FXIIIA and the three alleles of FXIIIB were studied in populations from mainland Italy and from Sardinia. The frequencies of the FXIIIA*2 allele were 0.266 and 0.265. The frequencies of FXIIIB*1 were 0.787 and 0.765; of B*2, 0.070 and 0.094; of B*3, 0.143 and 0.141. A new cathodal FXIIIA allele (A*7) was described in the Rome sample. No significant difference in the distribution of allele frequencies for either system was found between the two populations studied. For typing both markers, good results were also obtained by using whole blood instead of plasma.

Fibrinopeptide A and B beta 15-42 in liver cirrhosis.

In order to detect even minimal fibrinolysis activation in liver cirrhosis, we measured fibrinopeptide B beta 15-42 (B beta 15-42), an indicator of plasmin activity in vivo and alpha 2-antiplasmin (alpha 2-AP) in a group of cirrhotic patients. The second goal of this study was to investigate whether an increased fibrinolytic activity is related to a chronic disseminated intravascular coagulation. For this purpose we concomitantly measured fibrinopeptide A (FPA), marker of thrombin activity in vivo. Results show significantly higher levels of B beta 15-42 in cirrhotic patients than in control (p less than 0.01). In patients with high FPA levels we found significantly higher values than in patients with normal FPA (p less than 0.01). alpha 2-AP was lower in patients with high FPA levels than in patients with normal FPA (p less than 0.05). A significant negative correlation was found between FPA and alpha 2-AP only in patients with high FPA (p less than 0.05). There was no relationship between B beta 15-42 and FPA nor between B beta 15-42 and alpha 2-AP when all patients were considered. These findings confirm that in liver cirrhosis fibrinolysis activation may occur. The primary pathogenetic role of DIC may be important in this respect. However the lack of correlation between FPA and B beta 15-42 suggests that other pathogenetic factors may be involved in determining fibrinolysis activation.

Relationship between elevated fibrinopeptide A levels and alpha-2-antiplasmin.

In order to investigate whether alpha 2-antiplasmin (alpha 2-AP) levels may be related to thrombin activity, we measured alpha 2-AP and fibrinopeptide A (FPA) in 51 patients with clinical conditions frequently associated with increased thrombin activity. The diagnoses were: atherosclerotic disease, chronic inflammatory disease and hematological neoplastic disease. A significant negative correlation was found between alpha 2-AP and FPA (p less than 0.01). When patients were divided into three subgroups on the basis of their FPA levels, a significant reduction in alpha 2-AP was found in patients with the highest FPA concentration (greater than 9 ng/ml). Accordingly, a significant negative relationship between alpha 2-AP and FPA was found only in this subgroup (p less than 0.01). Our data suggest that the partial consumption of alpha 2-AP in patients with elevated FPA levels may reflect a subclinical fibrinolysis activation secondary to increased thrombin activity.