Human pharmacogenomic variation of antihypertensive drugs: from population genetics to personalized medicine.

AIM: To investigate the human pharmacogenetic variation related to antihypertensive drugs, providing a survey of functional interpopulation differences in hypertension pharmacogenes. MATERIALS & METHODS: The study was divided into two stages. In the first stage, we analyzed 1249 variants located in 57 hypertension pharmacogenes. This first-stage analysis confirmed that geographic origin strongly affects hypertension pharmacogenomic variation and that 31 pharmacogenes are geographically differentiated. In the second stage, we focused our attention on the ethnic-differentiated pharmacogenes, investigating 55,521 genetic variants. In silico analyses were performed to predict the effect of genetic variation. RESULTS: Our analyses indicated functional interpopulation differences, suggesting insight into the mechanisms of antihypertensive drug response. Moreover, our data suggested that rare variants mainly determine the functionality of genes related to antihypertensive drugs. CONCLUSION: Our study provided important knowledge about the genetics of the antihypertensive drug response, suggesting that next-generation sequencing technologies may develop reliable pharmacogenetic tests for antihypertensive drugs

Detection and characterization of a 500 μm dust emissivity excess in the Galactic plane using Herschel/Hi-GAL observations

Context. Past and recent observations have revealed unexpected variations in the far-infrared – millimeter (FIR-mm) dust emissivity in the interstellar medium. In the Herschel spectral range, those are often referred to as a 500 μm emission excess. Several dust emission models have been developed to interpret astrophysical data in the FIR-mm domain. However, these are commonly unable to fully reconcile theoretical predictions with observations. In contrast, the recently revised two level system (TLS) model, based on the disordered internal structure of amorphous dust grains, seems to provide a promising way of interpreting existing data. Aims. The newly available Herschel infrared GALactic (Hi-GAL) data, which covers most of the inner Milky Way, offers a unique opportunity to investigate possible variations in the dust emission properties both with wavelength and environment. The goal of our analysis is to constrain the internal structure of the largest dust grains on Galactic scales, in the framework of the TLS model. Methods. By combining the IRIS (Improved Reprocessing of the IRAS Survey) 100 μm with the Hi-GAL 160, 250, 350, and 500 μm data, we model the dust emission spectra in each pixel of the Hi-GAL maps, using both the TLS model and, for comparison, a single modified black-body fit. The effect of temperature mixing along the line of sight is investigated to test the robustness of our results. Results. We find a slight decrease in the dust temperature with distance from the Galactic center, confirming previous results. We also report the detection of a significant 500 μm emissivity excess in the peripheral regions of the plane (35° < |l| < 70°) of about 13–15% of the emissivity, which can reach up to 20% in some HII regions. We present the spatial distributions of the best-fit values for the two main parameters of the TLS model, i.e. the charge correlation length, lc, used to characterize the disordered charge distribution (DCD) part of the model, and the amplitude A of the TLS processes with respect to the DCD effect. These distributions illustrate the variations in the dust properties with environment, in particular the plausible existence of an overall gradient with distance to the Galactic center. A comparison with previous findings in the solar neighborhood shows that the local value of the excess is less than expected from the Galactic gradient observed here

Detailed study of the microwave emission of the supernova remnant 3C 396

We have observed the supernova remnant 3C~396 in the microwave region using the Parkes 64-m telescope. Observations have been made at 8.4 GHz, 13.5 GHz, and 18.6 GHz and in polarisation at 21.5 GHz. We have used data from several other observatories, including previously unpublished observations performed by the Green Bank Telescope at 31.2 GHz, to investigate the nature of the microwave emission of 3C 396. Results show a spectral energy distribution dominated by a single component power law emission with $\alpha=(-0.364 \pm 0.017)$. Data do not favour the presence of anomalous microwave emission coming from the source. Polarised emission at 21.5 GHz is consistent with synchrotron-dominated emission. We present microwave maps and correlate them with infrared (IR) maps in order to characterise the interplay between thermal dust and microwave emission. IR vs. microwave TT plots reveal poor correlation between mid-infrared and microwave emission from the core of the source. On the other hand, a correlation is detected in the tail emission of the outer shell of 3C 396, which could be ascribed to Galactic contamination.Comment: published in MNRA

Flunisolide Decreases Exhaled Nitric Oxide and Nitrotyrosine Levels in Asthmatic Children

Background. Exhaled nitric oxide (FeNO) has been reported to be elevated in the oxidative stress involved in asthmatic patients, and the reaction of nitric oxide (NO) with superoxide anions results in the formation of nitrotyrosine. The purpose of this study was to investigate the effect of inhaled steroid treatment on nitrotyrosine levels collected by exhaled breath condensate (EBC) and on FeNO. Methods. This was a single-blind placebo-controlled study. The lung function, FeNO, and nitrotyrosine levels were evaluated in 10 asthmatic children. Results. The nitrotyrosine levels were stable during the placebo period (T0 = 1.16 ng/ml versus T1 = 1.05 ng/ml; NS.), whereas they decreased after the treatment with flunisolide (T2 = 1.14 ng/ml versus T3 = 0.88 ng/ml; P < .001). No significant reduction in FeNO levels was observed after placebo treatment (T0 = 38.4 ppb versus T1 = 34.7 ppb, NS.). In contrast, FeNO values decreased significantly being at T3 = 14.9 ppb (T1 versus T3; P = .024). Conclusions. This study shows that corticosteroid treatment reduces nitrotyrosine levels in EBC of asthmatic subjects

Quantum characterization of superconducting photon counters

We address the quantum characterization of photon counters based on transition-edge sensors (TESs) and present the first experimental tomography of the positive operator-valued measure (POVM) of a TES. We provide the reliable tomographic reconstruction of the POVM elements up to 11 detected photons and M=100 incoming photons, demonstrating that it is a linear detector.Comment: 3 figures, NJP (to appear

Quantal Two-Centre Coulomb Problem treated by means of the Phase-Integral Method II. Quantization Conditions in the Symmetric Case Expressed in Terms of Complete Elliptic Integrals. Numerical Illustration

The contour integrals, occurring in the arbitrary-order phase-integral quantization conditions given in a previous paper, are in the first- and third-order approximations expressed in terms of complete elliptic integrals in the case that the charges of the Coulomb centres are equal. The evaluation of the integrals is facilitated by the knowledge of quasiclassical dynamics. The resulting quantization conditions involving complete elliptic integrals are solved numerically to obtain the energy eigenvalues and the separation constants of the $1s\sigma$ and $2p\sigma$ states of the hydrogen molecule ion for various values of the internuclear distance. The accuracy of the formulas obtained is illustrated by comparison with available numerically exact results.Comment: 19 pages, RevTeX 4, 4 EPS figures, submitted to J. Math. Phy

Variations of the spectral index of dust emissivity from Hi-GAL observations of the Galactic plane

Original article can be found at: http://www.aanda.org/ Copyright The European Southern ObservatoryContext. Variations in the dust emissivity are critical for gas mass determinations derived from far-infrared observations, but also for separating dust foreground emission from the Cosmic Microwave Background (CMB). Hi-GAL observations allow us for the first time to study the dust emissivity variations in the inner regions of the Galactic plane at resolution below 1°. Aims. We present maps of the emissivity spectral index derived from the combined Herschel PACS 160 μm, SPIRE 250 μm, 350 μm, and 500 μm data, and the IRIS 100 μm data, and we analyze the spatial variations of the spectral index as a function of dust temperature and wavelength in the two science demonstration phase Hi-GAL fields, centered at l = 30° and l = 59°. Methods. Applying two different methods, we determine both dust temperature and emissivity spectral index between 100 and 500 μm, at an angular resolution (θ) of 4'. Results. Combining both fields, the results show variations of the emissivity spectral index in the range 1.8–2.6 for temperatures between 14 and 23 K. The median values of the spectral index are similar in both fields, i.e. 2.3 in the range 100–500 μm, while the median dust temperatures are equal to 19.1 K and 16.0 K in the l = 30° and l = 59° field, respectively. Statistically, we do not see any significant deviations in the spectra from a power law emissivity between 100 and 500 μm. We confirm the existence of an inverse correlation between the emissivity spectral index and dust temperature, found in previous analyses.Peer reviewe

Does Impairment of Adult Neurogenesis Contribute to Pathophysiology of Alzheimer's Disease? A Still Open Question

Adult hippocampal neurogenesis is a physiological mechanism contributing to hippocampal memory formation. Several studies associated altered hippocampal neurogenesis with aging and Alzheimer's disease (AD). However, whether amyloid-\u3b2 protein (A\u3b2)/tau accumulation impairs adult hippocampal neurogenesis and, consequently, the hippocampal circuitry, involved in memory formation, or altered neurogenesis is an epiphenomenon of AD neuropathology contributing negligibly to the AD phenotype, is, especially in humans, still debated. The detrimental effects of A\u3b2/tau on synaptic function and neuronal viability have been clearly addressed both in in vitro and in vivo experimental models. Until some years ago, studies carried out on in vitro models investigating the action of A\u3b2/tau on proliferation and differentiation of hippocampal neural stem cells led to contrasting results, mainly due to discrepancies arising from different experimental conditions (e.g., different cellular/animal models, different A\u3b2 and/or tau isoforms, concentrations, and/or aggregation profiles). To date, studies investigating in situ adult hippocampal neurogenesis indicate severe impairment in most of transgenic AD mice; this impairment precedes by several months cognitive dysfunction. Using experimental tools, which only became available in the last few years, research in humans indicated that hippocampal neurogenesis is altered in cognitive declined individuals affected by either mild cognitive impairment or AD as well as in normal cognitive elderly with a significant inverse relationship between the number of newly formed neurons and cognitive impairment. However, despite that such information is available, the question whether impaired neurogenesis contributes to AD pathogenesis or is a mere consequence of A\u3b2/pTau accumulation is not definitively answered. Herein, we attempted to shed light on this complex and very intriguing topic by reviewing relevant literature on impairment of adult neurogenesis in mouse models of AD and in AD patients analyzing the temporal relationship between the occurrence of altered neurogenesis and the appearance of AD hallmarks and cognitive dysfunctions

Interstellar dust in the BOOMERanG maps

Interstellar dust (ISD) emission is present in the mm-wave maps obtained by the BOOMERanG experiment at intermediate and high Galactic latitudes. We find that, while being sub-dominant at the lower frequencies (90,150, 240 GHz), thermal emission from ISD is dominant at 410 GHz, and is well correlated with the IRAS map at 100 µm. We find also that the angular power spectrum of ISD fluctuations at 410 GHz is a power law, and its level is negligible with respect to the angular power spectrum of the Cosmic Microwave Background (CMB) at 90 and 150 GHz

Spitzer and Herschel Multiwavelength Characterization of the Dust Content of Evolved H II Regions

We have analyzed a uniform sample of 16 evolved H II regions located in a 2° × 2° Galactic field centered at (l,b) = (30°, 0°) and observed as part of the Herschel Hi-GAL survey. The evolutionary stage of these H II regions was established using ancillary radio-continuum data. By combining Hi-GAL PACS (70 μm, 160 μm) and SPIRE (250 μm, 350 μm, and 500 μm) measurements with MIPSGAL 24 μm data, we built spectral energy distributions of the sources and showed that a two-component gray-body model is a good representation of the data. In particular, wavelengths >70 μm appear to trace a cold dust component, for which we estimated an equilibrium temperature of the big grains (BGs) in the range 20-30 K, while for λ < 70 μm, the data indicate the presence of a warm dust component at temperatures of the order of 50-90 K. This analysis also revealed that dust is present in the interior of H II regions, although likely not in a large amount. In addition, the data seem to corroborate the hypothesis that the main mechanism responsible for the (partial) depletion of dust in H II regions is radiation-pressure-driven drift. In this framework, we speculated that the 24 μm emission that spatially correlates with ionized gas might be associated with either very small grain or BG replenishment, as recently proposed for the case of wind-blown bubbles. Finally, we found that evolved H II regions are characterized by distinctive far-IR and submillimeter colors, which can be used as diagnostics for their identification in unresolved Galactic and extragalactic regions