The use of isotopic carbon in a study of the metabolism of anthanilic acid in Neurospora

The finding by Tatum, Banner, and Beadle (l), that the tryptophanless Neurospora mutant strain 10575 accumulates anthranilic acid, which in turn can be utilized for growth of strain 40008, has provided evidence that anthranilic acid is a biochemical precursor of tryptophan in this organism. It has been further established that indole is an intermediate in this conversion (2-5). More recent work with a number of mutants of Neurospora (6-8) has established that tryptophan is a biochemical precursor to niacin with kynurenine and hydroxyanthranilic acid as intermediates. The accumulated evidence has indicated the existence in the mold of the following series of reactions: → Anthranilic acid → indole → tryptophan → kynurenine → 3-hydroxyanthranilic acid → nicotinic acid In the light of this evidence the present work was undertaken to trace the carbon in the carboxyl group of anthranilic acid in order to estimate its contribution as a structural unit in the formation of niacin and tryptophan. The organism chosen for this investigation was a biochemical mutant strain of Neurospora designated as strain 40008. This mutant utilizes anthranilic acid, indole, or tryptophan for growth. The mutant was grown in the presence of anthranilic acid containing Cl4 in the carboxyl group. Niacin and tryptophan were isolated from the mold mycelium and tested for radioactivity

Surface photochemistry of the herbicide napropamide. The role of the media and environmental factors in directing the fates of intermediates

The photochemical behaviour of the herbicide napropamide is studied on cellulose and silica surfaces, using steady-state and laser-flash diffuse ectance techniques. The results are used to probe how the reaction sites of the host matrices influence the photo-reactive pathways. Napropamide undergoes reaction when irradiated with UV (lamps) or visible (sunlight) radiation on both solid supports. The nature of the intermediates and final products depend strongly on the presence or absence of molecular oxygen. The triplet state of napropamide adsorbed on cellulose is detected by both time-resolved luminescence and transient absorption spectroscopies. The triplet sate was not observed on silica, but transients which include the participation of molecular oxygen are detected during. ash photolysis studies. The keto intermediates of the photo-Claisen rearrangement products are observed on both solids. Substituted 1-naphthols from photo-Claisen reactions and 1-naphthol are among the main reaction products. 1,4-Naphthoquinone is a major photoproduct in the presence of molecular oxygen and is expected to be prevalent when napropamide undergoes photodegradation in the environment (i. e., after being applied to plants and fields)

iTRAQ Analysis of Complex Proteome Alterations in 3xTgAD Alzheimer's Mice: Understanding the Interface between Physiology and Disease

Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with accumulation of amyloid β-peptide, synaptic degeneration and the death of neurons in the hippocampus, and temporal, parietal and frontal lobes of the cerebral cortex. Analysis of postmortem brain tissue from AD patients can provide information on molecular alterations present at the end of the disease process, but cannot discriminate between changes that are specifically involved in AD versus those that are simply a consequence of neuronal degeneration. Animal models of AD provide the opportunity to elucidate the molecular changes that occur in brain cells as the disease process is initiated and progresses. To this end, we used the 3xTgAD mouse model of AD to gain insight into the complex alterations in proteins that occur in the hippocampus and cortex in AD. The 3xTgAD mice express mutant presenilin-1, amyloid precursor protein and tau, and exhibit AD-like amyloid and tau pathology in the hippocampus and cortex, and associated cognitive impairment. Using the iTRAQ stable-isotope-based quantitative proteomic technique, we performed an in-depth proteomic analysis of hippocampal and cortical tissue from 16 month old 3xTgAD and non-transgenic control mice. We found that the most important groups of significantly altered proteins included those involved in synaptic plasticity, neurite outgrowth and microtubule dynamics. Our findings have elucidated some of the complex proteome changes that occur in a mouse model of AD, which could potentially illuminate novel therapeutic avenues for the treatment of AD and other neurodegenerative disorders

The use of isotopic nitrogen in a study of the conversion of 3-hydroxyanthranilic acid to nicotinic acid in Neurospora

Recent studies with mutant strains of Neurospora indicated that 3-hydroxyanthranilic acid (3-hydroxy-2-aminobenzoic acid) is an intermediate in the metabolic conversion of tryptophan to nicotinic acid. Evidence for this conversion in mammals is found in the report that 3-hydroxyanthranilic acid can maintain the growth of rats on a nicotinic acid-deficient diet and in the work of Albert, Scheer, and Deuel, who found an increased excretion of N-methylnicotinamide by rats fed this substance. The isotopic experiments of Heidelberger, Abraham, and Lepkovsky demonstrated that the carboxyl carbon of 3-hydroxyanthranilic acid is the precursor of the carboxyl carbon atom of nicotinic acid. To study the mechanism of the conversion of the benzene ring into a pyridine derivative, a mutant strain of Neurospora crassa C-86, requiring 3-hydroxyanthranilic acid or a precursor for growth, was grown in a medium which contained non-labeled synthetic 3-hydroxyanthranilic acid and Nls ammonium chloride as the only sources of nitrogen. Thus the absence of N16 in excess in nicotinic acid isolated from the mold would indicate that the amino group of 3-hydroxyanthranilic acid is the precursor of the pyridine nitrogen in nicotinic acid

RENAL FUNCTION, ELECTROLYTE EXCRETION AND BODY FLUIDS IN PATIENTS WITH CHRONIC RENAL INSUFFICIENCY BEFORE AND AFTER SODIUM DEPRIVATION

L'azotemie par manque de sel is a descriptive phrase coined by Blum, Graber, and van Caulaert (1, 2) to describe the azotemia and hypochloremia which developed in certain diabetic patients main-tained on low salt diets immediately after recovery from coma. When sodium chloride was adminis-tered to these patients the plasma chloride con-centration increased and nitrogen retention dimin-ished or cleared. Pre-existing renal disease, anuria, or acidosis per se were not contributory factors. Blum and his associates (2) concluded that the development of azotemia was a compensa-tory response to decreased molecular concentra-tion and osmotic activity of the blood. This view has not been widely accepted because it is known (3) that all membranes in the body are freely per-meable to urea. Subsequent work with man (4) and other animals (5) has revealed that severe salt depletion is usually associated with loss and redistribution of body water that may lead to cir-culatory collapse and renal dysfunction. Marked sodium depletion is necessary to induce renal vasoconstriction and diminished glomerular filtration sufficient to cause nitrogen retention in normal human subjects and it is usually associated with obvious dehydration, weight loss, muscular weakness, apathy, and anorexia (4). In patients with renal insufficiency secondary to renal disease much less severe sodium depletion suffices to pre-' These studies have been made possible through the aid of a grant from the New York Heart Association. 2Preliminary report of some of these data has bee

Strategic and cultural contexts of real options reasoning in innovation portfolios

Decision makers find creating an innovation portfolio challenging, because more innovative projects are associated with a higher degree of uncertainty. In this study, we investigate the potential benefits of applying real options reasoning (ROR) in innovation portfolio management from an attention‐based view. Using a sample of 137 innovation portfolios with multiple informants, we investigate ROR's influence on portfolio innovativeness and, ultimately, on portfolio success in a mediated model. Further, we analyze the moderating influence of an innovation portfolio's organizational context—entrepreneurial orientation and innovation climate—on ROR's application. The results support ROR's positive relationship to portfolio innovativeness and portfolio success. The analysis also supports the positive interaction between entrepreneurial orientation and ROR with respect to portfolio innovativeness. This study contributes to the literature by demonstrating the relationship between ROR and portfolio success, mediated by portfolio innovativeness. In addition, the study's analysis offers an explanation of previously mixed findings regarding ROR's benefits by considering the firm's strategic and cultural innovation contexts. The findings underline the relevance of strategic support for ROR's effectiveness in innovation portfolio management. Furthermore, the findings encourage managers to implement ROR, but also stress the essential contribution an entrepreneurial orientation makes when the managers do so

The identification and relative distribution of the metabolites of radioactive nicotinic acid and nicotinamide /

This report is based on LADC-901.Work performed at the Los Alamos Scientific Laboratory.April 9, 1951. (TIS issuance date).Includes bibliographical references (page 5)Mode of access: Internet

The gross metabolism of radioactive pentobarbital in mice /

Work performed at the Los Alamos Scientific Laboratory."AECU-84; (LADC-574)."Includes bibliographical references.Mode of access: Internet