Increased Na+/H+ antiport activity in the renal brush border membrane of SHR

Increased Na+/H+ antiport activity in the renal brush border membrane of SHR. Defect in renal salt excretion may play an important role in the pathogenesis of hypertension. We examined sodium (Na+) uptake by brush border membrane (BBM) vesicles of young (6 week old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) of the same age. SHR had lower urinary Na+ excretion (223.1 ± 9.3 vs. 266.3 ± 3.7 µEq/day/lOO g, N = 8, P < 0.01) and higher systolic blood pressure (98.9 ± 1.2 vs. 82.9 ± 1.8mm Hg, N = 8, P < 0.01) than WKY. BBM vesicle Na+ uptake, measured by rapid filtration technique, was higher in SHR when compared to WKY (1.44 ± 0.03 vs. 1.01 ± 0.06 nmol/mg/5 sec, N = 4, N < 0.01). This increase in Na+ influx was apparent only in the present of an outward-directed proton (H+) gradient and was abolished by 1mM amiloride. BBM permeability to H+ as assessed by acridine orange quenching was not different between SHR and WKY. Kinetic analyses of the amiloride-sensitive BBM Na+ uptake revealed a higher Vmax (2.13 ± 0.27 vs. 0.70 ± 0.30 nmol/mg/5 sec, N = 4, P < 0.01) and a higher km for Na+ (3.55 ± 0.32 vs. 1.23 ± 0.14mM, N = 4, P < 0.05) in SHR. These findings thus demonstrate an intrinsic derangement in BBM Na+ transport in young SHR which is characterized by increased Na+/H+ antiport activity. This alteration in antiport activity is not attributable to changes in membrane permeability to H+, and is characterized by higher Vmax and km. Similar reports of increased Na+/H+ antiport activity in other tissues of SHR suggest that a generalized membrane transport disorder may exist in this model of genetic hypertension

The equivalence of numbers: The social value of avoiding health decline: An experimental web-based study

BACKGROUND: Health economic analysis aimed at informing policy makers and supporting resource allocation decisions has to evaluate not only improvements in health but also avoided decline. Little is known however, whether the "direction" in which changes in health are experienced is important for the public in prioritizing among patients. This experimental study investigates the social value people place on avoiding (further) health decline when directly compared to curative treatments in resource allocation decisions. METHODS: 127 individuals completed an interactive survey that was published in the World Wide Web. They were confronted with a standard gamble (SG) and three person trade-off tasks, either comparing improvements in health (PTO-Up), avoided decline (PTO-Down), or both, contrasting health changes of equal magnitude differing in the direction in which they are experienced (PTO-WAD). Finally, a direct priority ranking of various interventions was obtained. RESULTS: Participants strongly prioritized improving patients' health rather than avoiding decline. The mean substitution rate between health improvements and avoided decline (WAD) ranged between 0.47 and 0.64 dependent on the intervention. Weighting PTO values according to the direction in which changes in health are experienced improved their accuracy in predicting a direct prioritization ranking. Health state utilities obtained by the standard gamble method seem not to reflect social values in resource allocation contexts. CONCLUSION: Results suggest that the utility of being cured of a given health state might not be a good approximation for the societal value of avoiding this health state, especially in cases of competition between preventive and curative interventions

The Youngest Galactic Supernova Remnant: G1.9+0.3

Our 50 ks Chandra observation of the small radio supernova remnant (SNR) G1.9+0.3 shows a complete shell structure with strong bilateral symmetry, about $100''$ in diameter. The radio morphology is also shell-like, but only about $84''$ in diameter, based on observations made in 1985. We attribute the size difference to expansion between 1985 and our Chandra observations of 2007. Expansion is confirmed in comparing radio images from 1985 and 2008. We deduce that G1.9+0.3 is of order 100 years old -- the youngest supernova remnant in the Galaxy. Based on a very high absorbing column density of $5.5 \times 10^{22}$ cm$^{-2}$, we place G1.9+0.3 near the Galactic Center, at a distance of about 8.5 kpc, where the mean remnant radius would be about 2 pc, and the required expansion speed about $14,000$ km s$^{-1}$. The X-ray spectrum is featureless and well-described by the exponentially cut off synchrotron model {\tt srcut}. With the radio flux at 1 GHz fixed at 0.9 Jy, we find a spectral index of 0.65 and a rolloff frequency of $1.4 \times 10^{18}$ Hz. The implied characteristic rolloff electron energy of about $94 (B/10 \mu{\rm G})^{-1/2}$ TeV is the highest ever reported for a shell supernova remnant. It can easily be reached by standard diffusive shock acceleration, given the very high shock velocities; it can be well described by either age-limited or synchrotron-loss-limited acceleration. Not only is G1.9+0.3 the youngest known Galactic remnant, it is also only the fourth Galactic X-ray synchrotron-dominated shell supernova remnant.Comment: 4 pages, 5 figures; revised to include new radio data and accepted for ApJ

Self-similar scaling and evolution in the galaxy cluster X-ray Luminosity-Temperature relation

We investigate the form and evolution of the X-ray luminosity-temperature (LT) relation of a sample of 114 galaxy clusters observed with Chandra at 0.1<z<1.3. The clusters were divided into subsamples based on their X-ray morphology or whether they host strong cool cores. We find that when the core regions are excluded, the most relaxed clusters (or those with the strongest cool cores) follow an LT relation with a slope that agrees well with simple self-similar expectations. This is supported by an analysis of the gas density profiles of the systems, which shows self-similar behaviour of the gas profiles of the relaxed clusters outside the core regions. By comparing our data with clusters in the REXCESS sample, which extends to lower masses, we find evidence that the self-similar behaviour of even the most relaxed clusters breaks at around 3.5keV. By contrast, the LT slopes of the subsamples of unrelaxed systems (or those without strong cool cores) are significantly steeper than the self-similar model, with lower mass systems appearing less luminous and higher mass systems appearing more luminous than the self-similar relation. We argue that these results are consistent with a model of non-gravitational energy input in clusters that combines central heating with entropy enhancements from merger shocks. Such enhancements could extend the impact of central energy input to larger radii in unrelaxed clusters, as suggested by our data. We also examine the evolution of the LT relation, and find that while the data appear inconsistent with simple self-similar evolution, the differences can be plausibly explained by selection bias, and thus we find no reason to rule out self-similar evolution. We show that the fraction of cool core clusters in our (non-representative) sample decreases at z>0.5 and discuss the effect of this on measurements of the evolution in the LT relation.Comment: 21 pages, 15 figures. Submitted to MNRAS. Comments welcom

Protein Microarray On-Demand: A Novel Protein Microarray System

We describe a novel, simple and low-cost protein microarray strategy wherein the microarrays are generated by printing expression ready plasmid DNAs onto slides that can be converted into protein arrays on-demand. The printed expression plasmids serve dual purposes as they not only direct the synthesis of the protein of interest; they also serve to capture the newly synthesized proteins through a high affinity DNA-protein interaction. To accomplish this we have exploited the high-affinity binding (∼3–7×10 −13 M) of E. coli Tus protein to Ter, a 20 bp DNA sequence involved in the regulation of E. coli DNA replication. In our system, each protein of interest is synthesized as a Tus fusion protein and each expression construct directing the protein synthesis contains embedded Ter DNA sequence. The embedded Ter sequence functions as a capture reagent for the newly synthesized Tus fusion protein. This “all DNA” microarray can be converted to a protein microarray on-demand without need for any additional capture reagent.

Sequestration of the Aβ Peptide Prevents Toxicity and Promotes Degradation In Vivo

An engineered protein prevents aggregation of the Aβ peptide and facilitates clearance of Aβ from the brain in a fruit fly model of Alzheimer's disease

The Caravan Rolls On

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68409/2/10.1177_107554707900100103.pd

Searching for dark matter annihilation in recently discovered Milky Way satellites with Fermi-LAT

We search for excess γ-ray emission coincident with the positions of confirmed and candidate Milky Way satellite galaxies using six years of data from the Fermi Large Area Telescope (LAT). Our sample of 45 stellar systems includes 28 kinematically confirmed dark-matter-dominated dwarf spheroidal galaxies (dSphs) and 17 recently discovered systems that have photometric characteristics consistent with the population of known dSphs. For each of these targets, the relative predicted γ-ray flux due to dark matter annihilation is taken from kinematic analysis if available, and estimated from a distance-based scaling relation otherwise, assuming that the stellar systems are DM-dominated dSphs. LAT data coincident with four of the newly discovered targets show a slight preference (each ~2σ local) for γ-ray emission in excess of the background. However, the ensemble of derived γ-ray flux upper limits for individual targets is consistent with the expectation from analyzing random blank-sky regions, and a combined analysis of the population of stellar systems yields no globally significant excess (global significance 1 TeV and mDM,t+t-> 70 GeV) and weakening by a factor of ~1.5 at lower masses relative to previously observed limits

Phase behaviour of Ag2CrO4 under compression: Structural, vibrational, and optical properties

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Physical Chemistry C, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jp401524sWe have performed an experimental study of the crystal structure, lattice dynamics, and optical properties of silver chromate (Ag2CrO4) at ambient temperature and high pressures. In particular, the crystal structure, Raman-active phonons, and electronic band gap have been accurately determined. When the initial orthorhombic Pnma Ag2CrO4 structure (phase I) is compressed up to 4.5 GPa, a previously undetected phase (phase II) has been observed with a 0.95% volume collapse. The structure of phase II can be indexed to a similar orthorhombic cell as phase I, and the transition can be considered to be an isostructural transition. This collapse is mainly due to the drastic contraction of the a axis (1.3%). A second phase transition to phase III occurs at 13 GPa to a structure not yet determined. First-principles calculations have been unable to reproduce the isostructural phase transition, but they propose the stabilization of a spinel-type structure at 11 GPa. This phase is not detected in experiments probably because of the presence of kinetic barriers. Experiments and calculations therefore seem to indicate that a new structural and electronic description is required to model the properties of silver chromate.This study was supported by the Spanish government MEC under grants MAT2010-21270-C04-01/03/04 and CTQ2009-14596-C02-01, by the Comunidad de Madrid and European Social Fund (S2009/PPQ1551 4161893), by the MALTA Consolider Ingenio 2010 project (CSD2007-00045), and by the Vicerrectorado de Investigacion y Desarrollo of the Universidad Politecnica de Valencia (UPV2011-0914 PAID-05-11 and UPV2011-0966 PAID-06-11). A.M. and P.R.-H. acknowledge computing time provided by Red Espanola de Supercomputacion (RES) and MALTA-Cluster. J.A.S. acknowledges Juan de la Cierva Fellowship Program for its financial support. Diamond and ALBA Synchrotron Light Sources are acknowledged for provisions of beam time. We also thank Drs. Peral, Popescu, and Fauth for technical support.Santamaría Pérez, D.; Bandiello, E.; Errandonea, D.; Ruiz-Fuertes, J.; Gomis Hilario, O.; Sans, JÁ.; Manjón Herrera, FJ.... (2013). Phase behaviour of Ag2CrO4 under compression: Structural, vibrational, and optical properties. Journal of Physical Chemistry C. 117(23):12239-12248. https://doi.org/10.1021/jp401524sS12239122481172

Learning to live together: mutualism between self-splicing introns and their hosts

Group I and II introns can be considered as molecular parasites that interrupt protein-coding and structural RNA genes in all domains of life. They function as self-splicing ribozymes and thereby limit the phenotypic costs associated with disruption of a host gene while they act as mobile DNA elements to promote their spread within and between genomes. Once considered purely selfish DNA elements, they now seem, in the light of recent work on the molecular mechanisms regulating bacterial and phage group I and II intron dynamics, to show evidence of co-evolution with their hosts. These previously underappreciated relationships serve the co-evolving entities particularly well in times of environmental stress