The effect of alkaline pH on the succinate oxidase system of sub-mitochondrial particles from beef heart muscle

The spectrophotometric method for the determination of the acid nonextractable flavin in the proteolytic digest of the trichloroacetic acid precipitate from the heart muscle preparation has been examined for the interference of the degraded hemeproteins. The proteolytic digest was chromatographically separated into the heme and flavin fractions. Spectrophotometric determinations made on the separated fractions have indicated that the heme interference is negligible for the heart muscle preparation. The validity of this method has thus been demonstrated. In the course of the proteolysis, cytochrome c₁ and c are evidently degraded to hemepeptides. The spectral behavior of the hemepeptides has been presented. Based on the fluorescent characteristics of the acid non-extractable flavin, a fluorometric method has been devised. This method is approximately 100 times more sensitive than the spectrophotometric assay. Results from these two methods are in good agreement. It is suggested that the fluorometric method may be more suitable for samples containing high concentrations of pigments adsorbing in the 450-530 mu region of the spectrum. Alkaline inactivation of the succinate oxidase activity of the heart muscle preparation in the absence of substrate and presence of oxygen has been used by Keilin and King to prepare a particle which supplies all of the respiratory components except succinate dehydrogenase for reconstitution of succinate oxidase. The succinate dehydrogenase protein, as measured by its flavin coenzyme, was found to be dissociated from the particulate heart muscle preparation by alkaline treatment. The dissociation occurred at the same rate as the inactivation of the succinate oxidase. It was therefore concluded that the original site of binding of the dehydrogenase to the particle is available to bind active succinate dehydrogenase during reconstitution of the system. The inactivation of succinate oxidase under the experimental conditions used was found to follow zero order kinetics. The apparent zero order rate constant varied as the first power of the initial enzyme concentration and the second power of the hydroxyl ion concentration. The temperature dependence of the apparent zero order rate constant was complex. A mechanism is presented which is consistant with the observed kinetics. The equilibrium dissociation of the succinate oxidase system by alkaline treatment in the presence of succinate and absence of oxygen was studied using the acid nonextractable flavin content as a measure of the succinate dehydrogenase concentration. The percent of the dehydrogenase which was soluble was a linear function of the hydroxyl ion concentration and the concentration of the soluble dehydrogenase was proportional to the total concentration bound and soluble, confirming the report of King. The equilibrium constant for the dissociation decreased with increasing temperature and buffer concentration

Weaving the Strands of Life (Iiná Bitł’ool): History of Genetic Research Involving Navajo People

To date, some genetic studies offer medical benefits, but lack a clear pathway to benefit for people from underrepresented backgrounds. Historically Indigenous people, including the Diné (Navajo people), have raised concerns about the lack of benefits, misuse of DNA samples, lack of consultation, and ignoring cultural and traditional ways of knowing. Shortly after the Navajo Nation Human Research Review Board was established in 1996, the Navajo Nation recognized growing concerns about genetic research and established a moratorium on human genetic research studies in 2002. The moratorium effectively has protected their citizens from potential genetic research harms. Despite the placement of the moratorium, some genetic research studies have continued using blood and DNA samples from Navajo people. In order to understand the history of genetic research involving Navajo people, we conducted a literature review of 79 genetic or genetic-related research publications that involved Navajo people from the years 1925 to 2018. In this review, we divided the genetic research studies into the following general classifications: a) bacteria or virus genetics studies, b) blood and human leukocyte antigen, c) complex diseases, d) forensics, e) hereditary diseases, and f) population genetics and migration. We evaluated the methods for each study, described the number of Navajo individuals included in each study, recorded the academic or tribal approval statements, and noted whether the study considered Diné cultural values. Several studies focused on Severe Combined Immunodeficiency Disease, population history, neuropathy, albinism, eye and skin disorders that affect Navajo people. We found genetic research publications involving Navajo people spanning over the course of 93 years. To our knowledge, no known literature reviews have examined the history of genetic research in the Navajo community. In our Discussion, we contextualize Diné ways of knowing related to genetics and health with Western scientific concepts to acknowledge the complex philosophy and belief system that guides Diné people and recognizes Indigenous science. We encourage researchers consider cultural perspectives and traditional knowledge that has the potential to create stronger conclusions and better informed, ethical, and respectful science

Delineating the topography of amyloid-associated cortical atrophy in Down syndrome

Older adults with Down syndrome (DS) often have Alzheimer's disease (AD) neuropathologies. Although positron emission tomography imaging studies of amyloid deposition (beta amyloid, Aβ) have been associated with worse clinical prognosis and cognitive impairment, their relationships with cortical thickness remain unclear in people with DS. In a sample of 44 DS adults who underwent cognitive assessments, [C]-PiB positron emission tomography, and T1-weighted magnetization-prepared rapid gradient echo, we used mixed effect models to evaluate the spatial relationships between Aβ binding with patterns of cortical thickness. Partial Spearman correlations were used to delineate the topography of local Aβ-associated cortical thinning. [C]-PiB nondisplaceable binding potential was negatively associated with decreased cortical thickness. Locally, regional [C]-PiB retention was negatively correlated with cortical thickness in widespread cortices, predominantly in temporoparietal regions. Contrary to the prevailing evidence in established AD, we propose that our findings implicate Aβ in spatial patterns of atrophy that recapitulated the “cortical signature” of neurodegeneration in AD, conferring support to recent recommendations for earlier disease-interventions

Longitudinal trajectories of amyloid deposition, cortical thickness, and tau in Down syndrome: A deep-phenotyping case report.

Introduction:Comorbid Alzheimer disease pathologies are frequently found in people with Down syndrome (DS). We report a deep phenotyping study undertaken over 7 years in a participant with DS who was nondemented at baseline but developed dementia after 5 years. Methods:Throughout the course of the study, the participant was seen 4 times (2010, 2013, 2015, and 2017). Multimodal neuroimaging, including three serial scans of [11C]-PiB-PET, four structural magnetic resonance imagings, as well as a [18F]-AV1451 scan, was interpreted alongside detailed neuropsychological assessments over the study period. Results:Amyloid beta accumulation preceded the onset of dementia and cognitive decline, which in turn corresponded to the predominant deposition of tau in temporoparietal cortices. Discussion:Until now, data on the longitudinal trajectories of amyloid accumulation, tau pathology, and brain atrophy over multiple time points remain scarce in DS. This case report highlights the potential for deep phenotyping imaging to elucidate the substrates of cognitive decline in DS, although further longitudinal studies are necessary to clarify the relative contributions of both amyloid and tau

Staggered-grid finite-difference acoustic modeling with the Time-Domain Atmospheric Acoustic Propagation Suite (TDAAPS).

This document is intended to serve as a users guide for the time-domain atmospheric acoustic propagation suite (TDAAPS) program developed as part of the Department of Defense High-Performance Modernization Office (HPCMP) Common High-Performance Computing Scalable Software Initiative (CHSSI). TDAAPS performs staggered-grid finite-difference modeling of the acoustic velocity-pressure system with the incorporation of spatially inhomogeneous winds. Wherever practical the control structure of the codes are written in C++ using an object oriented design. Sections of code where a large number of calculations are required are written in C or F77 in order to enable better compiler optimization of these sections. The TDAAPS program conforms to a UNIX style calling interface. Most of the actions of the codes are controlled by adding flags to the invoking command line. This document presents a large number of examples and provides new users with the necessary background to perform acoustic modeling with TDAAPS

Fruit crops: a summary of research, 1998

Pesticide deposition in orchards: effects of pesticide type, tree canopy, timing, cultivar, and leaf type / Franklin R. Hall, Jane A. Cooper, and David C. Ferree -- The influence of a synthetic foraging attractant, Bee-Scent™, on the number of honey bees visiting apple blossoms and on subsequent fruit production / James E. Tew and David C. Ferree -- The reliability of three traps vs. a single trap for determining population levels of codling moth in commercial northern Ohio apple orchards / Ted W. Gastier -- Evaluation of an empirical model for predicting sooty blotch and flyspeck of apples in Ohio / Michael A. Ellis, Laurence V. Madden, and L. Lee Wilson -- Influence of pesticides and water stress on photosynthesis and transpiration of apple / David C. Ferree, Franklin R. Hall, Charles R. Krause, Bruce R. Roberts, and Ross D. Brazee -- Influence of temporary bending and heading on branch development and flowering of vigorous young apple trees / David C. Ferree and John C. Schmid -- The effect of apple fruit bruising on total returns / Richard C. Funt, Ewen A. Cameron, and Nigel H. Banks -- Yield, berry quality, and economics of mechanical berry harvest in Ohio / Richard C. Funt, Thomas E. Wall, and Joseph C. Scheerens -- Monitoring flower thrips activities in strawberry fields at two Ohio locations / Roger N. Williams, M. Sean Ellis, Dan S. Fickle, and Carl M. Pelland -- Cluster thinning effects on fruit weight, juice quality, and fruit skin characteristics in 'Reliance' grapes / Yu Gao and Garth A. Cahoon -- Effects of various fungicide programs on powdery mildew control, percent berry sugar, yield, and vine vigor of 'Concord' grapes in Ohio / Michael A. Ellis, Laurence V. Madden, L. Lee Wilson, and Gregory R. Johns -- Influence of growth regulators, cropping, and number on replacement trunks of winter-injured 'Vidal Blanc' grapes / David C. Ferree, David M. Scurlock, and Rick Evans -- Effect of new herbicides on tissue-cultured black raspberry plants / Richard C. Funt, Thomas E. Wall, and B. Dale Stokes -- Investigating the relationship between vine vigor and berry set of field-grown 'Seyval Blanc' grapevines / Steven J. McArtney and David C. Ferree -- Summary of Ohio Fruit Growers Society apple cider competition, 1993-1997 / Winston Bash and Diane Mille

The pattern of amyloid accumulation in the brains of adults with Down syndrome.

INTRODUCTION: Adults with Down syndrome (DS) invariably develop Alzheimer's disease (AD) neuropathology. Understanding amyloid deposition in DS can yield crucial information about disease pathogenesis. METHODS: Forty-nine adults with DS aged 25-65 underwent positron emission tomography with Pittsburgh compound-B (PIB). Regional PIB binding was assessed with respect to age, clinical, and cognitive status. RESULTS: Abnormal PIB binding became evident from 39 years, first in striatum followed by rostral prefrontal-cingulo-parietal regions, then caudal frontal, rostral temporal, primary sensorimotor and occipital, and finally parahippocampal cortex, thalamus, and amygdala. PIB binding was related to age, diagnostic status, and cognitive function. DISCUSSION: PIB binding in DS, first appearing in striatum, began around age 40 and was strongly associated with dementia and cognitive decline. The absence of a substantial time lag between amyloid accumulation and cognitive decline contrasts to sporadic/familial AD and suggests this population's suitability for an amyloid primary prevention trial.This research was generously supported by a grant from the Medical Research Council (grant ID number: 98480). Additional support came from the NIHR Cambridge Biomedical Research Centre, the NIHR Collaborations in Leadership for Applied Health Research and Care (CLAHRC) for the East of England, the NIHR Cambridge Dementia Biomedical Research Unit, The Down Syndrome Association, and The Health Foundation.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jalz.2015.07.49

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

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined