Structures Illuminate Cardiac Ion Channel Functions in Health and in Long QT Syndrome

The cardiac action potential is critical to the production of a synchronized heartbeat. This electrical impulse is governed by the intricate activity of cardiac ion channels, among them the cardiac voltage-gated potassium (Kv) channels KCNQ1 and hERG as well as the voltage-gated sodium (Nav) channel encoded by SCN5A. Each channel performs a highly distinct function, despite sharing a common topology and structural components. These three channels are also the primary proteins mutated in congenital long QT syndrome (LQTS), a genetic condition that predisposes to cardiac arrhythmia and sudden cardiac death due to impaired repolarization of the action potential and has a particular proclivity for reentrant ventricular arrhythmias. Recent cryo-electron microscopy structures of human KCNQ1 and hERG, along with the rat homolog of SCN5A and other mammalian sodium channels, provide atomic-level insight into the structure and function of these proteins that advance our understanding of their distinct functions in the cardiac action potential, as well as the molecular basis of LQTS. In this review, the gating, regulation, LQTS mechanisms, and pharmacological properties of KCNQ1, hERG, and SCN5A are discussed in light of these recent structural findings

Biola Hour Highlights, 1975 - 11

Free for the Taking by Joseph R. Cooke What is Demon Possession? by Henry W. Holloman Psalm 139 by Al Sanders II Corinthians by Richard Chase Revelation No.151 by Lloyd Anderson October Panel by Richard Chase, Charles Feinberg, and Samuel Sutherlandhttps://digitalcommons.biola.edu/bhhs/1021/thumbnail.jp

1943: Abilene Christian College Bible Lectures - Full Text

Delivered in the Auditorium of Abilene Christian College February, 1943 Price: $1.00 FIRM FOUNDATION PUBLISHING HOUSE Austin, Texas Copyright, 1943 By Firm Foundation Publishing House Austin, Texa

COMMENTARY: ETHICAL ISSUES OF CURRENT HEALTH-PROTECTION POLICIES ON LOW-DOSE IONIZING RADIATION

The linear no-threshold (LNT) model of ionizing-radiation-induced cancer is based on the assumption that every radiation dose increment constitutes increased cancer risk for humans. The risk is hypothesized to increase linearly as the total dose increases. While this model is the basis for radiation safety regulations, its scientific validity has been questioned and debated for many decades. The recent memorandum of the International Commission on Radiological Protection admits that the LNT-model predictions at low doses are “speculative, unproven, undetectable and ‘phantom’.” Moreover, numerous experimental, ecological, and epidemiological studies show that low doses of sparsely-ionizing or sparsely-ionizing plus highly-ionizing radiation may be beneficial to human health (hormesis/adaptive response). The present LNT-model-based regulations impose excessive costs on the society. For example, the median-cost medical program is 5000 times more cost-efficient in saving lives than controlling radiation emissions. There are also lives lost: e.g., following Fukushima accident, more than 1000 disaster-related yet non-radiogenic premature deaths were officially registered among the population evacuated due to radiation concerns. Additional negative impacts of LNT-model-inspired radiophobia include: refusal of some patients to undergo potentially life-saving medical imaging; discouragement of the study of low-dose radiation therapies; motivation for radiological terrorism and promotion of nuclear proliferation

Evidence for the Role of Endosymbionts in Regional-Scale Habitat Partitioning by Hydrothermal Vent Symbioses

Deep-sea hydrothermal vents are populated by dense communities of animals that form symbiotic associations with chemolithoautotrophic bacteria. To date, our understanding of which factors govern the distribution of host/symbiont associations (or holobionts) in nature is limited, although host physiology often is invoked. In general, the role that symbionts play in habitat utilization by vent holobionts has not been thoroughly addressed. Here we present evidence for symbiont-influenced, regional-scale niche partitioning among symbiotic gastropods (genus Alviniconcha) in the Lau Basin. We extensively surveyed Alviniconcha holobionts from four vent fields using quantitative molecular approaches, coupled to characterization of high-temperature and diffuse vent-fluid composition using gastight samplers and in situ electrochemical analyses, respectively. Phylogenetic analyses exposed cryptic host and symbiont diversity, revealing three distinct host types and three different symbiont phylotypes (one ε-proteobacteria and two γ-proteobacteria) that formed specific associations with one another. Strikingly, we observed that holobionts with ε-proteobacterial symbionts were dominant at the northern fields, whereas holobionts with γ-proteobacterial symbionts were dominant in the southern fields. This pattern of distribution corresponds to differences in the vent geochemistry that result from deep subsurface geological and geothermal processes. We posit that the symbionts, likely through differences in chemolithoautotrophic metabolism, influence niche utilization among these holobionts. The data presented here represent evidence linking symbiont type to habitat partitioning among the chemosynthetic symbioses at hydrothermal vents and illustrate the coupling between subsurface geothermal processes and niche availability.Organismic and Evolutionary Biolog

The Farthest Known Supernova: Support for an Accelerating Universe and a Glimpse of the Epoch of Deceleration

We present photometric observations of an apparent Type Ia supernova (SN Ia) at a redshift of ~1.7, the farthest SN observed to date. SN 1997ff, was discovered in a repeat observation by the HST of the HDF-), and serendipitously monitored with NICMOS on HST throughout the GTO campaign. The SN type can be determined from the host galaxy type:an evolved, red elliptical lacking enough recent star formation to provide a significant population of core-collapse SNe. The class- ification is further supported by diagnostics available from the observed colors and temporal behavior of the SN, both of which match a typical SN Ia. The photo- metric record of the SN includes a dozen flux measurements in the I, J, and H bands spanning 35 days in the observed frame. The redshift derived from the SN photometry, z=1.7+/-0.1, is in excellent agreement with the redshift estimate of z=1.65+/-0.15 derived from the U_300,B_450,V_606,I_814,J_110,J_125,H_160, H_165,K_s photometry of the galaxy. Optical and near-infrared spectra of the host provide a very tentative spectroscopic redshift of 1.755. Fits to observations of the SN provide constraints for the redshift-distance relation of SNe~Ia and a powerful test of the current accelerating Universe hypothesis. The apparent SN brightness is consistent with that expected in the decelerating phase of the preferred cosmological model, Omega_M~1/3, Omega_Lambda~2/3. It is inconsistent with grey dust or simple luminosity evolution, candidate astro- physical effects which could mimic past evidence for an accelerating Universe from SNe Ia at z~0.5.We consider several sources of possible systematic error including lensing, SN misclassification, selection bias, and calibration errors. Currently, none of these effects appears likely to challenge our conclusions.Comment: Accepted to the Astrophysical Journal 38 pages, 15 figures, Pretty version available at http://icarus.stsci.edu/~stefano/ariess.tar.g