Coupling of Smoothened to inhibitory G proteins reduces voltage-gated K

SMO (Smoothened), the central transducer of Hedgehog signaling, is coupled to heterotrimeric Gi proteins in many cell types, including cardiomyocytes. In this study, we report that activation of SMO with SHH (Sonic Hedgehog) or a small agonist, purmorphamine, rapidly causes a prolongation of the action potential duration that is sensitive to a SMO inhibitor. In contrast, neither of the SMO agonists prolonged the action potential in cardiomyocytes from transgenic GiCT/TTA mice, in which Gi signaling is impaired, suggesting that the effect of SMO is mediated by Gi proteins. Investigation of the mechanism underlying the change in action potential kinetics revealed that activation of SMO selectively reduces outward voltage-gated K+ repolarizing (Kv) currents in isolated cardiomyocytes and that it induces a down-regulation of membrane levels of Kv4.3 in cardiomyocytes and intact hearts from WT but not from GiCT/TTA mice. Moreover, perfusion of intact hearts with Shh or purmorphamine increased the ventricular repolarization time (QT interval) and induced ventricular arrhythmias. Our data constitute the first report that acute, noncanonical Hh signaling mediated by Gi proteins regulates K+ currents density in cardiomyocytes and sensitizes the heart to the development of ventricular arrhythmias. © 2018 Cheng et al

Spectroscopy of High-Redshift Supernovae from the ESSENCE Project: The First Two Years

We present the results of spectroscopic observations of targets discovered during the first two years of the ESSENCE project. The goal of ESSENCE is to use a sample of ~200 Type Ia supernovae (SNe Ia) at moderate redshifts (0.2 < z < 0.8) to place constraints on the equation of state of the Universe. Spectroscopy not only provides the redshifts of the objects, but also confirms that some of the discoveries are indeed SNe Ia. This confirmation is critical to the project, as techniques developed to determine luminosity distances to SNe Ia depend upon the knowledge that the objects at high redshift are the same as the ones at low redshift. We describe the methods of target selection and prioritization, the telescopes and detectors, and the software used to identify objects. The redshifts deduced from spectral matching of high-redshift SNe Ia with low-redshift SNe Ia are consistent with those determined from host-galaxy spectra. We show that the high-redshift SNe Ia match well with low-redshift templates. We include all spectra obtained by the ESSENCE project, including 52 SNe Ia, 5 core-collapse SNe, 12 active galactic nuclei, 19 galaxies, 4 possibly variable stars, and 16 objects with uncertain identifications.Comment: 38 pages, 9 figures (many with multiple parts), submitted to A

Another challenge for scientists

By nature, scientists contribute to our understanding of nature and ourselves. As communities undergo significant changes, new challenges are presented. Here, we offer alternative views on recent changes in society

The problem of choice

Convictions are a driving force for actions. Considering that every individual has a different set of convictions and larger groups act once a consensus decision is reached, one can see that debate is an inherent exercise in decision-making. This requires a sustainably generated surplus to allow time for intellectual exchange, gathering of information and dissemination of findings. It is essential that the full spectrum of options remain treated equally. At the end of this process, a choice has to be made. Looking back at a later time point, a retrospective analysis sometimes reveals that the choice was neither completely free nor a truly conscious one. Leaving the issue of consequences of a once made decision aside, we wish to contribute to the debate of the problem of choice

To know or not to know: archiving and the under-appreciated historical value of data

Surplus goods, produced by a community, allow individuals to dedicate their efforts to abstract problems, while enjoying the benefits of support from the community. In return, the community benefits from the intellectual work, say, efficiently producing goods or profound medical aid. In further elevating quality of life, we need to understand nature and biology on the most detailed level. Inevitably, research costs are increasing along with the need for more scientists to specialize their efforts. As a result, a vast amount of data and information is generated that needs to be archived and made openly accessible with the permission to re-use and re-distribute. With economies undergoing crises and prosperity in an almost cyclic manner, it seems that funding for science and technology follows a similar pattern. Another aspect to the problem of the loss of data is the human propensity, at the level of each individual researcher, to passively discard data in the course of daily life and through a career. In a typical laboratory, significant amounts of information is still stored on disks in file cabinets or on isolated computers, and is lost when a research group disbands. Being conscientious to one's data, to see that it reaches a place in which it can persist beyond the lifespan of any one individual requires responsibility on the part of its creator

Stable isotopes in hair reveal dietary protein sources with links to socioeconomic status and health

Carbon and nitrogen isotope ratios in hair sampled from 65 communities across the central and intermountain regions of the United States and more intensively throughout 29 ZIP codes in the Salt Lake Valley, Utah, revealed a dietary divergence related to socioeconomic status as measured by cost of living, household income, and adjusted gross income. Corn-fed, animal-derived proteins were more common in the diets of lower socioeconomic status populations than were plant-derived proteins, with individual estimates of animal-derived protein diets as high as 75%; United States towns and cities averaged 57%. Similar patterns were seen across the socioeconomic status spectrum in the Salt Lake Valley. It is likely that corn-fed animal proteins were associated with concentrated animal-feeding operations, a common practice for industrial animal production in the United States today. Given recent studies highlighting the negative impacts of animal-derived proteins in our diets, hair carbon isotope ratios could provide an approach for scaling assessments of animal-sourced foods and health risks in communities across the United States.Fil: Ehleringer, James R.. University Of Utah. Department Of Biology; Estados UnidosFil: Covarrubias Avalos, Stephannie. University Of Utah. Department Of Biology; Estados UnidosFil: Tipple, Brett J.. University Of Utah. Department Of Biology; Estados UnidosFil: Valenzuela, Luciano Oscar. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales. Departamento de Arqueología. Laboratorio de Ecología Evolutiva Humana (Sede Quequén); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; ArgentinaFil: Cerling, Thure E.. University Of Utah. Department Of Biology; Estados Unido

Implementation of AMI Systems in CFE-Distribution, Mexico

The Smart Grid concept has been conceived as the integration of the electrical grid (generation, transmission and distribution) and the communications network of an electric utility. Although, traditional communications interfaces, protocols and standards has been used in the electrical grid in an isolated manner, modern communications networks are considered as the fundamental enabling technologies within a Smart Grid environment. Emerging communications technologies, protocol architectures and standards can help to build a common communications network infrastructure for data transport between customer premises, power substations, power distribution systems, utility control centers and utility data centers. The Smart Grid will support traditional applications such as supervisory control and data acquisition (SCADA), distribution automation (DA), energy management systems (EMS), demand site management (DSM) and automated meter reading (AMR), etc., as well as new applications like advanced metering infrastructure (AMI), substation automation (SA), microgrids, distributed generation (DG), grid monitoring and control, data storage and analysis, among others. To make this possible, the Smart Grid requires a two-way wide area communications network between different dispersed areas, from generation to consumer premises. An AMI system uses communication technologies for smart meter reading several times a day to get data consumption of electricity, as well as sending outage alarm information and meter tampering almost in real time, from the meter to the control center. Currently, there are various communication technologies to implement AMI systems. This paper presents an overview of the most relevant communications technologies that can be used to implement AMI communications infrastructure such as neighborhood area networks (NAN), field area networks (FAN) and wide area networks (WAN) using different transmission media such as fiber optics, spread spectrum radio frequency, microwave, WiMax, Wi-Fi, ZigBee, cellular, and power line carrier. In addition, a review of the current state of various AMI projects around the world, including the progress in the implementation of AMI systems in Mexico, besides the evaluation performance of CFE´s AMI networks

Optical Light Curve of the Type Ia Supernova 1998bu in M96 and the Supernova Calibration of the Hubble Constant

We present the UBVRI light curves of the Type Ia supernova SN 1998bu which appeared in the nearby galaxy M96 (NGC 3368). M96 is a spiral galaxy in the Leo I group which has a Cepheid-based distance. Our photometry allows us to calculate the absolute magnitude and reddening of this supernova. These data, when combined with measurements of the four other well-observed supernovae with Cepheid based distances, allow us to calculate the Hubble constant with respect to the Hubble flow defined by the distant Calan/Tololo Type Ia sample. We find a Hubble constant of 64.0 +/- 2.2(internal) +/- 3.5(external) km/s/Mpc, consistent with most previous estimates based on Type Ia supernovae. We note that the two well-observed Type Ia supernovae in Fornax, if placed at the Cepheid distance to the possible Fornax spiral NGC 1365, are apparently too faint with respect to the Calan/Tololo sample calibrated with the five Type Ia supernovae with Cepheid distances to the host galaxies.Comment: AAS LaTeX, 20 pages, 4 figures, 6 tables, accepted for publication in the Astronomical Journal. Figure 1 (finding chart) not include

The SuperMACHO Microlensing Survey

We present the first results from our next-generation microlensing survey, the SuperMACHO project. We are using the CTIO 4m Blanco telescope and the MOSAIC imager to carry out a search for microlensing toward the Large Magellanic Cloud (LMC). We plan to ascertain the nature of the population responsible for the excess microlensing rate seen by the MACHO project. Our observing strategy is optimized to measure the differential microlensing rate across the face of the LMC. We find this derivative to be relatively insensitive to the details of the LMC's internal structure but a strong discriminant between Galactic halo and LMC self lensing. In December 2003 we completed our third year of survey operations. 2003 also marked the first year of real-time microlensing alerts and photometric and spectroscopic followup. We have extracted several dozen microlensing candidates, and we present some preliminary light curves and related information. Similar to the MACHO project, we find SNe behind the LMC to be a significant contaminant - this background has not been completely removed from our current single-color candidate sample. Our follow-up strategy is optimized to discriminate between SNe and true microlensing.Comment: To appear in Proceedings of IAU Symposium 225: Impact of Gravitational Lensing on Cosmology, 6 page