277 research outputs found
Mitochondrial contact site and cristae organizing system (MICOS) machinery supports heme biosynthesis by enabling optimal performance of ferrochelatase
Heme is an essential cofactor required for a plethora of cellular processes in eukaryotes. In metazoans the heme biosynthetic pathway is typically partitioned between the cytosol and mitochondria, with the first and final steps taking place in the mitochondrion. The pathway has been extensively studied and its biosynthetic enzymes structurally characterized to varying extents. Nevertheless, understanding of the regulation of heme synthesis and factors that influence this process in metazoans remains incomplete. Therefore, we investigated the molecular organization as well as the physical and genetic interactions of the terminal pathway enzyme, ferrochelatase (Hem15), in the yeast Saccharomyces cerevisiae. Biochemical and genetic analyses revealed dynamic association of Hem15 with Mic60, a core component of the mitochondrial contact site and cristae organizing system (MICOS). Loss of MICOS negatively impacts Hem15 activity, affects the size of the Hem15 high-mass complex, and results in accumulation of reactive and potentially toxic tetrapyrrole precursors that may cause oxidative damage. Restoring intermembrane connectivity in MICOS-deficient cells mitigates these cytotoxic effects. These data provide new insights into how heme biosynthetic machinery is organized and regulated, linking mitochondrial architecture-organizing factors to heme homeostasis
1960: Abilene Christian College Lectures - Full Text
Table of Contents:
Theme Speeches: Christian Faith in the Modern World
Basis of Faith - Leonard Mullens - 9
Authority in Christianity - John T. Smithson, Jr. - 27
Origin and Preservation of the Bible - Neil R. Lightfoot - 44
Alleged Discrepancies of the Bible - David H. Bobo - 62
The Unity of the Bible - Jack Meyer - 91
Faith and Reason - Joe Sanders - 115
The Reasonableness of Supernaturalism - Virgil Trout - 126
The Present Statue of the Doctrine of Organic Evolution - J.D. Thomas - 146
The Nature of Man - Roy F. Osborne, Jr. - 181
Modern Challenges to Christian Morals - Carl Spain - 199
The Christ, Whose Son is He? - Gordon Teel - 232
Special Speeches
Teaching the Word of God in Korea - L. Haskell Chessfire - 255
The Influence of Christian Education - Judge Jack Pope - 276
Mission Opportunities in the Far East - Harry Robert Fox - 288
Mission Work in Austria - Robert Skelton - 303
Report from Switzerland - Heinrich Blum - 313
The Work in Nigeria - Rees Byrant - 320
The Training of Evangelists in Foreign Fields - Reiner Kallus - 331
Christian Scholarships - Everett Ferguson - 340
Evangelizing the World - A.R. Holton - 349
Panel Discussions
The Significance of the Dead Sea Scrolls
The Scrolls and the Text of the Bible - Paul Rotenberry - 357
The Relation between the Religion of the Essenes and that of Early Christians - Jay Smith - 366
Biblical Interpretation
Expediency and Pattern Authority - J.W. Roberts - 381
Examples in Pattern Authority - Thomas B. Warren - 392
Mental Health and Sin
The Present State of Mental Health Knowledge - Donald R. Sime - 409
The Relationship of Mental Health Problems to Sin - Paul Easley - 421
The Teenager
The Problems of Youth - Mack Wayne Craig - 432
Influences for Good - Wyatt Sawyer - 443
The Benefits of Abilene Christian College
To the Church - Hulen Jackson - 451
To The Home - Robert S. Bell - 459
\u27To the Community - Louie Welch - 465
Expenses At Abilene Christian College - James C. Kerr - 469
The Graduate School at Abilene Christian College
What I Am Getting Now in the ACC Graduate Program - Harold Vanderpool - 475
How the ACC Graduate Program Has Stood Up - Everett Ferguson - 481
What the ACC Graduate Program Ought To Be - Frank Pack - 486
The Importance to the Church of the ACC Graduate Program A.R. Holton - 490
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Assesing use and suitability of scanning electron microscopy in the analysis of micro remains in dental calculus
Dental calculus is increasingly recognized as a major reservoir of dietary information. Palaeodietary studies using plant and animal micro remains (e.g. phytoliths, pollen, sponge spicules, and starch grains) trapped in calculus have the potential to revise our knowledge of the dietary role of plants in past populations. The conventional methods used to isolate and identify these micro remains rely on removing them from their microenvironment in the calculus, thus the microenvironment that traps and preserves micro remains is not understood. By using scanning electron microscopy and energy dispersive X-ray spectroscopy (SEMeEDX) on modern chimpanzee calculus from the Taï Forest, Côte d¿Ivoire, and human calculus from the Chalcolithic site of Camino del Molino, Spain, we present the first reported observations on characteristics of the matrix setting that are conducive to the survival of starch in dental calculus. We also assess the potential for SEMeEDX to detect starch and differentiate it from structurally and molecularly similar substrates. We demonstrate that SEMeEDX may offer a nondestructive technique for studying micro remains in certain contexts. Finally, we compare traditional optical analytical techniques (OM) with less invasive electron microscopy. The results indicate that SEM-EDX and OM are both effective for observing micro remains in calculus, but differ in their analytical resolution to identify different micro remains, and we therefore recommend a sequential use of both techniques
The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe
The preponderance of matter over antimatter in the early Universe, the
dynamics of the supernova bursts that produced the heavy elements necessary for
life and whether protons eventually decay --- these mysteries at the forefront
of particle physics and astrophysics are key to understanding the early
evolution of our Universe, its current state and its eventual fate. The
Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed
plan for a world-class experiment dedicated to addressing these questions. LBNE
is conceived around three central components: (1) a new, high-intensity
neutrino source generated from a megawatt-class proton accelerator at Fermi
National Accelerator Laboratory, (2) a near neutrino detector just downstream
of the source, and (3) a massive liquid argon time-projection chamber deployed
as a far detector deep underground at the Sanford Underground Research
Facility. This facility, located at the site of the former Homestake Mine in
Lead, South Dakota, is approximately 1,300 km from the neutrino source at
Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino
charge-parity symmetry violation and mass ordering effects. This ambitious yet
cost-effective design incorporates scalability and flexibility and can
accommodate a variety of upgrades and contributions. With its exceptional
combination of experimental configuration, technical capabilities, and
potential for transformative discoveries, LBNE promises to be a vital facility
for the field of particle physics worldwide, providing physicists from around
the globe with opportunities to collaborate in a twenty to thirty year program
of exciting science. In this document we provide a comprehensive overview of
LBNE's scientific objectives, its place in the landscape of neutrino physics
worldwide, the technologies it will incorporate and the capabilities it will
possess.Comment: Major update of previous version. This is the reference document for
LBNE science program and current status. Chapters 1, 3, and 9 provide a
comprehensive overview of LBNE's scientific objectives, its place in the
landscape of neutrino physics worldwide, the technologies it will incorporate
and the capabilities it will possess. 288 pages, 116 figure
β-Blockers and Mortality After Acute Myocardial Infarction in Patients Without Heart Failure or Ventricular Dysfunction
Background: For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if β-blockers are associated with reduced mortality. Objectives: The goal of this study was to determine the association between β-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD). Methods: This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of β-blockers and 1-year mortality. Results: Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non–ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received β-blockers, respectively. For the entire cohort, with >163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received β-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without β-blocker use (average treatment effect [ATE] coefficient: 0.07; 95% confidence interval [CI]: −0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: −0.98 to 1.58; p = 0.637) and non–ST-segment elevation myocardial infarction (ATE coefficient: −0.07; 95% CI: −0.68 to 0.54; p = 0.819). Conclusions: Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of β-blockers was not associated with a lower risk of death at any time point up to 1 year. (β-Blocker Use and Mortality in Hospital Survivors of Acute Myocardial Infarction Without Heart Failure; NCT02786654)
LSST Science Book, Version 2.0
A survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes
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