Kidney regeneration: common themes from the embryo to the adult

The vertebrate kidney has an inherent ability to regenerate following acute damage. Successful regeneration of the injured kidney requires the rapid replacement of damaged tubular epithelial cells and reconstitution of normal tubular function. Identifying the cells that participate in the regeneration process as well as the molecular mechanisms involved may reveal therapeutic targets for the treatment of kidney disease. Renal regeneration is associated with the expression of genetic pathways that are necessary for kidney organogenesis, suggesting that the regenerating tubular epithelium may be “reprogrammed” to a less-differentiated, progenitor state. This review will highlight data from various vertebrate models supporting the hypothesis that nephrogenic genes are reactivated as part of the process of kidney regeneration following acute kidney injury (AKI). Emphasis will be placed on the reactivation of developmental pathways and how our understanding of the resulting regeneration process may be enhanced by lessons learned in the embryonic kidney.Fil: Cirio, Maria Cecilia. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Groh, Eric D.. University of Pittsburgh; Estados UnidosFil: de Caestecker, Mark P.. Vanderbilt University; Estados UnidosFil: Davidson, Alan J.. The University of Auckland; Nueva ZelandaFil: Hukriede, Neil A.. University of Pittsburgh; Estados Unido

Reproducibility of left atrial ablation with high-intensity focused ultrasound energy in a calf model

ObjectiveAchieving transmural tissue ablation might be necessary for successful treatment of atrial fibrillation. The purpose of this study was to evaluate the reproducibility of transmural left atrial ablation using a high-intensity focused ultrasound energy system in a calf model.MethodsNine heparinized bovines underwent a beating-heart left atrial ablation with a single application of the high-intensity focused ultrasound device. All animals were acutely killed, and the left atrium was fixed in formalin. Protocolized histological sections (5 μm) were obtained throughout each lesion and prepared with Masson trichrome and hematoxylin and eosin staining. Measurements were performed on a total of 359 slides from the 9 lesions. In addition, fresh left atrial tissues from 18 unused human donor hearts that did not meet the criteria for cardiac transplantation were measured at the site where the high-intensity focused ultrasound device is normally applied.ResultsCalf left atrial thickness ranged between 2.5 and 20.1 mm, with a mean of 9.10 mm. High-intensity focused ultrasound ablation consistently produced a 100% transmural lesion in left atrial thickness up to 6 mm. In addition, a transmural lesion was observed in 91% of tissues that were up to 10 mm thick and in 85% that were up to 15 mm thick. Human left atrial thickness ranged between 1.2 to 6 mm, with a mean of 3.7 mm.ConclusionsCalf left atrial thickness in this study was greater than human left atrial thickness. Human left atrial thickness is generally less than 6 mm, and in this range high-intensity focused ultrasound ablation achieved 100% transmurality. These histological results might correlate with a high success rate of atrial fibrillation ablation by using the high-intensity focused ultrasound system

Phase Coexistence of a Stockmayer Fluid in an Applied Field

We examine two aspects of Stockmayer fluids which consists of point dipoles that additionally interact via an attractive Lennard-Jones potential. We perform Monte Carlo simulations to examine the effect of an applied field on the liquid-gas phase coexistence and show that a magnetic fluid phase does exist in the absence of an applied field. As part of the search for the magnetic fluid phase, we perform Gibbs ensemble simulations to determine phase coexistence curves at large dipole moments, $\mu$. The critical temperature is found to depend linearly on $\mu^2$ for intermediate values of $\mu$ beyond the initial nonlinear behavior near $\mu=0$ and less than the $\mu$ where no liquid-gas phase coexistence has been found. For phase coexistence in an applied field, the critical temperatures as a function of the applied field for two different $\mu$ are mapped onto a single curve. The critical densities hardly change as a function of applied field. We also verify that in an applied field the liquid droplets within the two phase coexistence region become elongated in the direction of the field.Comment: 23 pages, ReVTeX, 7 figure

Very Massive Stars in the local Universe

Recent studies have claimed the existence of very massive stars (VMS) up to 300 M ⊙ in the local Universe. As this finding may represent a paradigm shift for the canonical stellar upper-mass limit of 150 M ⊙, it is timely to discuss the status of the data, as well as the far-reaching implications of such objects. We held a Joint Discussion at the General Assembly in Beijing to discuss (i) the determination of the current masses of the most massive stars, (ii) the formation of VMS, (iii) their mass loss, and (iv) their evolution and final fate. The prime aim was to reach broad consensus between observers and theorists on how to identify and quantify the dominant physical processe

MutLα heterodimers modify the molecular phenotype of Friedreich ataxia

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. Methodology/Principal Findings: To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. Conclusions/Significance: Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription. © 2014 Ezzatizadeh et al.This article has been made available through the Brunel Open Access Publishing Fund

Characterizing 51 Eri b from 1-5 μ\mum: a partly-cloudy exoplanet

We present spectro-photometry spanning 1-5 $\mu$m of 51 Eridani b, a 2-10 M$_\text{Jup}$ planet discovered by the Gemini Planet Imager Exoplanet Survey. In this study, we present new $K1$ (1.90-2.19 $\mu$m) and $K2$ (2.10-2.40 $\mu$m) spectra taken with the Gemini Planet Imager as well as an updated $L_P$ (3.76 $\mu$m) and new $M_S$ (4.67 $\mu$m) photometry from the NIRC2 Narrow camera. The new data were combined with $J$ (1.13-1.35 $\mu$m) and $H$ (1.50-1.80 $\mu$m) spectra from the discovery epoch with the goal of better characterizing the planet properties. 51 Eri b photometry is redder than field brown dwarfs as well as known young T-dwarfs with similar spectral type (between T4-T8) and we propose that 51 Eri b might be in the process of undergoing the transition from L-type to T-type. We used two complementary atmosphere model grids including either deep iron/silicate clouds or sulfide/salt clouds in the photosphere, spanning a range of cloud properties, including fully cloudy, cloud free and patchy/intermediate opacity clouds. Model fits suggest that 51 Eri b has an effective temperature ranging between 605-737 K, a solar metallicity, a surface gravity of $\log$(g) = 3.5-4.0 dex, and the atmosphere requires a patchy cloud atmosphere to model the SED. From the model atmospheres, we infer a luminosity for the planet of -5.83 to -5.93 ($\log L/L_{\odot}$), leaving 51 Eri b in the unique position as being one of the only directly imaged planet consistent with having formed via cold-start scenario. Comparisons of the planet SED against warm-start models indicates that the planet luminosity is best reproduced by a planet formed via core accretion with a core mass between 15 and 127 M$_{\oplus}$.Comment: 27 pages, 19 figures, Accepted for publication in The Astronomical Journa

Commissioning of the vacuum system of the KATRIN Main Spectrometer

The KATRIN experiment will probe the neutrino mass by measuring the beta-electron energy spectrum near the endpoint of tritium beta-decay. An integral energy analysis will be performed by an electro-static spectrometer (Main Spectrometer), an ultra-high vacuum vessel with a length of 23.2 m, a volume of 1240 m^3, and a complex inner electrode system with about 120000 individual parts. The strong magnetic field that guides the beta-electrons is provided by super-conducting solenoids at both ends of the spectrometer. Its influence on turbo-molecular pumps and vacuum gauges had to be considered. A system consisting of 6 turbo-molecular pumps and 3 km of non-evaporable getter strips has been deployed and was tested during the commissioning of the spectrometer. In this paper the configuration, the commissioning with bake-out at 300{\deg}C, and the performance of this system are presented in detail. The vacuum system has to maintain a pressure in the 10^{-11} mbar range. It is demonstrated that the performance of the system is already close to these stringent functional requirements for the KATRIN experiment, which will start at the end of 2016.Comment: submitted for publication in JINST, 39 pages, 15 figure