Metabolic and functional consequences of cytosolic 5′-nucleotidase-IA overexpression in neonatal rat cardiomyocytes

Adenosine exerts a spectrum of energy-preserving actions on the heart negative chronotropic effects. The pathways leading to adenosine formation have remained controversial. In particular, although cytosolic 5′-nucleotidases can catalyze adenosine formation in cardiomyocytes, their contribution to the actions of adenosine has not been documented previously. We recently cloned two closely related AMP-preferring cytosolic 5′-nucleotidases (cN-IA and -IB); the A form predominates in the heart. In this study, we overexpressed pigeon cN-IA in neonatal rat cardiomyocytes using an adenovirus. cN-IA overexpression increased adenosine formation and release into the medium caused by simulated hypoxia and by isoproterenol in the absence and presence of inhibitors of adenosine metabolism. Adenosine release was not affected by an ecto-5′-nucleotidase inhibitor, α,β-methylene-ADP, but was affected by a nucleoside transporter, dipyridamole. The positive chronotropic effect of isoproterenol (130 ±3 vs. 100 ±4 beats/min) was inhibited (107 ±3 vs. 94 ±3 beats/min) in cells overexpressing cN-IA, and this was reversed by the addition of the adenosine receptor antagonist 8-(p-sulfophenyl)theophilline (120 ± 3 vs. 90 ± 4 beats/min). Our results demonstrate that overexpressed cN-IA can be sufficiently active in cardiomyocytes to generate physiologically effective concentrations of adenosine at its receptors.Fil: Sala-Newby, Graciela B.. University of Bristol; Reino UnidoFil: Freeman, Nicola V. E.. University of Bristol; Reino UnidoFil: Curto, Maria de Los Angeles. University of Bristol; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Newby, Andrew C.. University of Bristol; Reino Unid

Nonlinear interfaces: intrinsically nonparaxial regimes and effects

The behaviour of optical solitons at planar nonlinear boundaries is a problem rich in intrinsically nonparaxial regimes that cannot be fully addressed by theories based on the nonlinear Schrödinger equation. For instance, large propagation angles are typically involved in external refraction at interfaces. Using a recently proposed generalized Snell's law for Helmholtz solitons, we analyse two such effects: nonlinear external refraction and total internal reflection at interfaces where internal and external refraction, respectively, would be found in the absence of nonlinearity. The solutions obtained from the full numerical integration of the nonlinear Helmholtz equation show excellent agreement with the theoretical predictions

Nanoantenna-enhanced ultrafast nonlinear spectroscopy of a single gold nanoparticle

Optical nanoantennas are a novel tool to investigate previously unattainable dimensions in the nanocosmos. Just like their radio-frequency equivalents, nanoantennas enhance the light-matter interaction in their feed gap. Antenna enhancement of small signals promises to open a new regime in linear and nonlinear spectroscopy on the nanoscale. Without antennas especially the nonlinear spectroscopy of single nanoobjects is very demanding. Here, we present for the first time antenna-enhanced ultrafast nonlinear optical spectroscopy. In particular, we utilize the antenna to determine the nonlinear transient absorption signal of a single gold nanoparticle caused by mechanical breathing oscillations. We increase the signal amplitude by an order of magnitude which is in good agreement with our analytical and numerical models. Our method will find applications in linear and nonlinear spectroscopy of nanoobjects, ranging from single protein binding events via nonlinear tensor elements to the limits of continuum mechanics

The HARPS search for southern extra-solar planets XXXV. The interesting case of HD41248: stellar activity, no planets?

The search for planets orbiting metal-poor stars is of uttermost importance for our understanding of the planet formation models. However, no dedicated searches have been conducted so far for very low mass planets orbiting such objects. Only a few cases of low mass planets orbiting metal-poor stars are thus known. Amongst these, HD41248 is a metal-poor, solar-type star on which a resonant pair of super-Earth like planets has In the present paper we present a new planet search program that is using the HARPS spectrograph to search for Neptunes and Super-Earths orbiting a sample of metal-poor FGK dwarfs. We then present a detailed analysis of an additional 162 radial velocity measurements of HD41248, obtained within this program, with the goal of confirming the existence of the proposed planetary system. We analyzed the precise radial velocities, obtained with the HARPS spectrograph, together with several stellar activity diagnostics and line profile indicators. A careful analysis shows no evidence for the planetary system previously announced. One of the signals, with a period of about 25 days, is shown to be related to the rotational period of the star, and is clearly seen in some of the activity proxies. The remaining signal (P~18 days) could not be convincingly retrieved in the new data set. We discuss possible causes for the complex (evolving) signals observed in the data of HD41248, proposing that they may be explained by the appearance and disappearance of active regions on the surface of a star with strong differential rotation, or by a combination of the sparse data sampling and active region evolution.Comment: Accepted for publication in A&

Inflationary signatures of single-field models beyond slow-roll

If the expansion of the early Universe was not close to de Sitter, the statistical imprints of the primordial density perturbation on the cosmic microwave background can be quite different from those derived in slow-roll inflation. In this paper we study the inflationary signatures of all single-field models which are free of ghost-like instabilities. We allow for a rapid change of the Hubble parameter and the speed of sound of scalar fluctuations, in a way that is compatible with a nearly scale-invariant spectrum of perturbations, as supported by current cosmological observations. Our results rely on the scale-invariant approximation, which is different from the standard slow-roll approximation. We obtain the propagator of scalar fluctuations and compute the bispectrum, keeping next-order corrections proportional to the deviation of the spectral index from unity. These theories offer an explicit example where the shape and scale-dependences of the bispectrum are highly non-trivial whenever slow-roll is not a good approximation.Comment: v1: 36 pages, including tables, appendices and references. v2: abstract improved, references added, minor clarifications throughout the text; matches version published in JCA

DISFUNZIONE MULTIORGANO (MOF) IN CORSO DI ENCEFALOPATIA NEONATALE. INDAGINE EPIDEMIOLOGICA SU UN CAMPIONE DI NEONATI OSSERVATI NEL PERIODO GENNAIO 2009 - MAGGIO 2016

encefalopatia, disfunzione multirogan

Metabolic Treatment of Wolfram Syndrome

Wolfram Syndrome (WS) is a very rare genetic disorder characterized by several symptoms that occur from childhood to adulthood. Usually, the first clinical sign is non-autoimmune diabetes even if other clinical features (optic subatrophy, neurosensorial deafness, diabetes insipidus) may be present in an early state and may be diagnosed after diabetes' onset. Prognosis is poor, and the death occurs at the median age of 39 years as a consequence of progressive respiratory impairment, secondary to brain atrophy and neurological failure. The aim of this paper is the description of the metabolic treatment of the WS. We reported the experience of long treatment in patients with this syndrome diagnosed in pediatric age and followed also in adult age. It is known that there is a correlation between metabolic control of diabetes, the onset of other associated symptoms, and the progression of the neurodegenerative alterations. Therefore, a multidisciplinary approach is necessary in order to prevent, treat and carefully monitor all the comorbidities that may occur. An extensive understanding of WS from pathophysiology to novel possible therapy is fundamental and further studies are needed to better manage this devastating disease and to guarantee to patients a better quality of life and a longer life expectancy

Chemical abundances of 1111 FGK stars from the HARPS GTO planet search program.Galactic stellar populations and planets

We performed a uniform and detailed abundance analysis of 12 refractory elements (Na, Mg, Al, Si, Ca, Ti, Cr, Ni, Co, Sc, Mn and V) for a sample of 1111 FGK dwarf stars from the HARPS GTO planet search program. 109 of these stars are known to harbour giant planetary companions and 26 stars are hosting exclusively Neptunians and super-Earths. The main goals of this paper are i) to investigate whether there are any differences between the elemental abundance trends for stars of different stellar populations; ii) to characterise the planet host and non-host samples in term of their [X/H]. The extensive study of this sample, focused on the abundance differences between stars with and without planets will be presented in a parallel paper. The equivalent widths of spectral lines are automatically measured from HARPS spectra with the ARES code. The abundances of the chemical elements are determined using a LTE abundance analysis relative to the Sun, with the 2010 revised version of the spectral synthesis code MOOG and a grid of Kurucz ATLAS9 atmospheres. To separate the Galactic stellar populations we applied both a purely kinematical approach and a chemical method. We found that the chemically separated (based on the Mg, Si, and Ti abundances) thin and thick discs are also chemically disjunct for Al, Sc, Co and Ca. Some bifurcation might also exist for Na, V, Ni, and Mn, but there is no clear boundary of their [X/Fe] ratios. We confirm that an overabundance in giant-planet host stars is clear for all the studied elements.We also confirm that stars hosting only Neptunian-like planets may be easier to detect around stars with similar metallicities as non-planet hosts, although for some elements (particulary alpha-elements) the lower limit of [X/H] are very abrupt.Comment: 14 pages, 12 figures, 6 tables. accepted for publication in Astronomy & Astrophysic

Decomposition of the tensor product of two Hilbert modules

Given a pair of positive real numbers $\alpha, \beta$ and a sesqui-analytic function $K$ on a bounded domain $\Omega \subset \mathbb C^m$, in this paper, we investigate the properties of the sesqui-analytic function $\mathbb K^{(\alpha, \beta)}:= K^{\alpha+\beta}\big(\partial_i\bar{\partial}_j\log K\big )_{i,j=1}^ m,$ taking values in $m\times m$ matrices. One of the key findings is that $\mathbb K^{(\alpha, \beta)}$ is non-negative definite whenever $K^\alpha$ and $K^\beta$ are non-negative definite. In this case, a realization of the Hilbert module determined by the kernel $\mathbb K^{(\alpha,\beta)}$ is obtained. Let $\mathcal M_i$, $i=1,2,$ be two Hilbert modules over the polynomial ring $\mathbb C[z_1, \ldots, z_m]$. Then $\mathbb C[z_1, \ldots, z_{2m}]$ acts naturally on the tensor product $\mathcal M_1\otimes \mathcal M_2$. The restriction of this action to the polynomial ring $\mathbb C[z_1, \ldots, z_m]$ obtained using the restriction map $p \mapsto p_{|\Delta}$ leads to a natural decomposition of the tensor product $\mathcal M_1\otimes \mathcal M_2$, which is investigated. Two of the initial pieces in this decomposition are identified