Gamma-ray and X-ray emission from the Galactic centre: Hints on the nuclear star cluster formation history

The Milky Way centre exhibits an intense flux in the gamma and X-ray bands, whose origin is partly ascribed to the possible presence of a large population of millisecond pulsars (MSPs) and cataclysmic variables (CVs), respectively. However, the number of sources required to generate such an excess is much larger than what is expected from in situ star formation and evolution, opening a series of questions about the formation history of the Galactic nucleus. In this paper, we make use of direct N-body simulations to investigate whether these sources could have been brought to the Galactic centre by a population of star clusters that underwent orbital decay and formed the Galactic nuclear star cluster (NSC). Our results suggest that the gamma-ray emission is compatible with a population of MSPs that were mass segregated in their parent clusters, while the X-ray emission is consistent with a population of CVs born via dynamical interactions in dense star clusters. Combining observations with our modelling, we explore how the observed γ -ray flux can be related to different NSC formation scenarios. Finally, we show that the high-energy emission coming from the galactic central regions can be used to detect black holes heavier than 105M⊙ in nearby dwarf galaxies. © 2018 The Author(s). Published by Oxford University Press on behalf of The Royal Astronomical Society

Prevalence and pharmacologic management of familial hypercholesterolemia in an unselected contemporary cohort of patients with stable coronary artery disease

INTRODUCTION: Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) associated with premature cardiovascular disease. METHODS: Using the data from the START (STable Coronary Artery Diseases RegisTry) study, a nationwide, prospective survey on patients with stable coronary artery disease (CAD), we described prevalence and lipid lowering strategies commonly employed in these patients. The study population was divided into "definite/probable FH," defined as a Dutch Lipid Clinic Network (DLCN) score ≥6, "possible FH" with DLCN 3-5, and "unlikely FH" in presence of a DLCN <3. RESULTS: Among the 4030 patients with the DLCN score available, 132 (3.3%) were classified as FH (2.3% with definite/probable and 1.0% with possible FH) and 3898 (96.7%) had unlikely FH. Patients with both definite/probable and possible FH were younger compared to patients not presenting FH. Mean on-treatment LDL-C levels were 107.8 ± 41.5, 84.4 ± 40.9, and 85.8 ± 32.3 (P < 0.0001) and a target of ≤70 mg/dL was reached in 10.9%, 30.0%, and 22.0% (P < 0.0001) of patents with definite/probable, possible FH, and unlikely FH, respectively. Statin therapy was prescribed in 85 (92.4%) patients with definite/probable FH, in 38 (95.0%) with possible FH, and in 3621 (92.9%) with unlikely FH (P = 0.86). The association of statin and ezetimibe, in absence of other lipid-lowering therapy, was more frequently used in patients with definite/probable FH compared to patients without FH (31.5% vs 17.5% vs 9.5%; P < 0.0001). CONCLUSIONS: In this large cohort of consecutive patients with stable CAD, FH was highly prevalent and generally undertreated with lipid lowering therapies

Evaluation of polygenic determinants of non-alcoholic fatty liver disease (NAFLD) by a candidate genes resequencing strategy

NAFLD is a polygenic condition but the individual and cumulative contribution of identified genes remains to be established. To get additional insight into the genetic architecture of NAFLD, GWAS-identified GCKR, PPP1R3B, NCAN, LYPLAL1 and TM6SF2 genes were resequenced by next generation sequencing in a cohort of 218 NAFLD subjects and 227 controls, where PNPLA3 rs738409 and MBOAT7 rs641738 genotypes were also obtained. A total of 168 sequence variants were detected and 47 were annotated as functional. When all functional variants within each gene were considered, only those in TM6SF2 accumulate in NAFLD subjects compared to controls (P = 0.04). Among individual variants, rs1260326 in GCKR and rs641738 in MBOAT7 (recessive), rs58542926 in TM6SF2 and rs738409 in PNPLA3 (dominant) emerged as associated to NAFLD, with PNPLA3 rs738409 being the strongest predictor (OR 3.12, 95% CI, 1.8-5.5, P 0.28 was associated with a 3-fold increased risk of NAFLD. Interestingly, rs61756425 in PPP1R3B and rs641738 in MBOAT7 genes were predictors of NAFLD severity. Overall, TM6SF2, GCKR, PNPLA3 and MBOAT7 were confirmed to be associated with NAFLD and a score based on these genes was highly predictive of this condition. In addition, PPP1R3B and MBOAT7 might influence NAFLD severity

2,7-Bis(pyridin-3-ylethynyl)fluoren-9-one

2,7-bis(pyridin-3-ylethynyl)fluoren-9-one [(3-PyE)2FO] was synthesized in one step by the Sonogashira coupling reaction between 3-ethynylpyridine and 2,7-dibromofluoren-9-one. The title compound was fully characterized, and its crystal structure was determined through single-crystal XRD analysis

Dose-dependent effects of L-Arginine on PROP bitterness intensity and latency and characteristics of the chemical interaction between PROP and L-Arginine

Genetic variation in the ability to taste the bitterness of 6-n-propylthiouracil (PROP) is a complex trait that has been used to predict food preferences and eating habits. PROP tasting is primarily controlled by polymorphisms in the TAS2R38 gene. However, a variety of factors are known to modify the phenotype. Principle among them is the salivary protein Ps-1 belonging to the basic proline-rich protein family (bPRP). Recently, we showed that oral supplementation with Ps-1 as well as its related free amino acids (L-Arg and L-Lys) enhances PROP bitterness perception, especially for PROP non-tasters who have low salivary levels of Ps-1. Here, we show that salivary L-Arg levels are higher in PROP super-tasters compared to medium tasters and non-tasters, and that oral supplementation with free L-Arg enhances PROP bitterness intensity as well as reduces bitterness latency in a dose-dependent manner, particularly in individuals with low salivary levels of both free L-Arg and Ps-1 protein. Supplementation with L-Arg also enhanced the bitterness of caffeine. We also used 1H-NMR spectroscopy and quantum-mechanical calculations carried out by Density Functional Theory (DFT) to characterize the chemical interaction between free L-Arg and the PROP molecule. Results showed that the -NH2 terminal group of the L-ArgH+ side chain interacts with the carbonyl or thiocarbonyl groups of PROP by forming two hydrogen bonds with the resulting charged adduct. The formation of this PROP•ArgH+ hydrogen-bonded adduct could enhance bitterness intensity by increasing the solubility of PROP in saliva and its availability to receptor sites. Our data suggest that L-Arg could act as a 'carrier' of various bitter molecules in saliva

Coordination Chemistry and Sensing Properties Towards Anions and Metal Ions of a Simple Fluorescent Urea

The coordination and sensing properties towards anions and transition metal ions of the simple novel fluorescent urea 1-(2-aminophenyl)-3-(naphthalen-1)-yl)urea (L) were investigated in solution, and in the solid state. An electron donating amine group in the molecular skeleton of L decreased the acidity of the urea NHs that are usually deprotonated by basic anions and allowed for a good degree of affinity towards fluoride in DMSO-d6-0.5 %H2O. Moreover, the amine moiety acted as a further binding group for metal ions. Indeed, L was able to bind Zn2+ both in solution and in the solid state, and to respond to the presence of this metal ion in MeCN with an enhancement of the fluorescence emission. Although solution studies evidenced the formation of a 1 : 1 complex of L with Zn2+, complexes with a 2 : 1 ligand-to-metal stoichiometry were isolated in the solid state. DFT calculations helped to clarify the stability reasons behind these results

Valence band modification of Cr2O3 by Ni-doping: creating a high figure of merit p-type TCO

p-Type transparent conductors and semiconductors still suffer from remarkably low performance compared to their more widespread n-type counterparts, despite extensive investigation into their development. In this contribution, we present a comparative study on the defect chemistry of potential p-type transparent conducting oxides Mg-doped and Ni-doped Cr 2 O 3 . Conductivities as high as 28 S cm -1 were achieved by Ni-doping. By benchmarking crystallography and spectroscopy characterization against density functional theory calculations, we show that the incorporation of Ni into Cr 2 O 3 contributes to the composition of the valence band, making the formed holes more delocalized, while Mg states do not interact with the valence band in Mg-doped Cr 2 O 3 . Furthermore, it is experimentally proven that Ni has a higher solubility in Cr 2 O 3 than Mg, at least in the highly non-thermodynamic deposition conditions used for these experiments, which directly translates into a higher acceptor concentration. The combination of these two effects means that Ni is a more effective acceptor in Cr 2 O 3 than Mg and explains the improved conductivity observed for the former

Achievement of therapeutic target in subjects on statin treatment in clinical practice. Results of the STAR (Statins Target Assessment in Real practice) study

The primary aim of the STAR Study (Statins Target Assessment in Real practice) was to determine the LDLcholesterol reduction and to analyse patient’s and therapeutic factors associated to LDL-cholesterol target attainment in newly treated subjects with statins in an unselected population in clinical practice setting. Administrative databases (including pharmaceutical prescriptions and hospital admissions) and laboratory test databases (including LDL-cholesterol values) of five Local Health Units, distributed in Emilia Romagna, Toscana and Umbria, were linked. A retrospective cohort study was conducted and all subjects aged ≥18 years with a first prescription for statins (newly treated subjects) between January 1st, 2007 and June 30th, 2008 were included. All statin prescriptions over a 12 months follow-up period were considered and used to calculate adherence to treatment. Baseline and follow-up LDL-cholesterol, respectively, were defined according to the nearest determination to the first prescription for statins and to the end of the follow-up period. A total of 3.232 subjects was included, 1.516 males (47%) and 1.716 females (53%), with an average age equal to 65,9 ± 11,3 years. Among included subjects, 22,6% had a gap to LDL-cholesterol target <10%, 30,0% between 10 and 29%, 20,7% between 30 and 49%, and 26,7% ≥50%. Among those with a gap to target ≥50%, 30-49%, and 10-29%, respectively, LDLcholesterol target was attained by 7,1%, 41,8%, and 62,3% of subjects. LDL-cholesterol target attainment was associated to gap to target, adherence with treatment, and type of statin