Active site structure and stability of the thiol protease papain studied by electron paramagnetic resonance employing a methanethiosulfonate spin label

The benzodiazepine receptor antagonist flumazenil (2.5-20 mg/kg i.p.) increased acetylcholine (ACh) release by up to 85% in the hippocampus of freely moving rats. In contrast, the benzodiazepine receptor full agonist diazepam (2.5-10 mg/kg i.p.) decreased ACh release up to a maximum of 45% in the same brain area. Injection of flumazenil (10 pmol) or diazepam (10 pmol) into the medial septum increased (95%) or reduced (50%), respectively, ACh release in the hippocampus. The maximum effect produced by those drugs was of the same magnitude as that observed after systemic injection. The changes in hippocampal cholinergic function elicited by activation and blockade of benzodiazepine receptors in the medial septum may thus play a crucial role in the alterations of the cognitive processes elicited by benzodiazepine receptor ligands.     

Relative reduction rates of fatty acid isomers by hydrazine

Mixtures of fatty acids and of hydrocarbons have been reduced by hydrazine in ethyl alcohol solution at 50 C. Samples were removed during reduction for analysis and the relative reduction rates calculated by digital computer.cis-15-Octadecenoic acid is reduced 1.3 times as fast as itscis-9-isomer. No differences were found amongcis-6,9- and -12-octadecenoic acids.cis-3-Octadecene was also reduced 1.3 times as fast as thecis-9-isomer andcis-1-octadecene 8.6 times as fast. Elaidic acid was reduced 1.27 times as fast as oleic. Presented at the AOCS Meeting, Chicago, October 1967. No. Utiliz. Res. Dev. Div., ARS, USDA.     

Preparation of 9,15-octadecadienoate isomers1

Linolenic acid was reduced with hydrazine to produce a mixture containing a max of dienoic acids. After methylation this mixture was separated into trienoic, dienoic, monoenoic, and saturated esters by countercurrent distribution (CCD) with acetonitrile and hexane. The dienoic ester was further fractionated by CCD with methanolic silver nitrate and hexane to separate purecis,cis-9,15-octadecadienoate and the equimixture ofcis,cis-9,12- and 12,15-octadecadienoates. Following isomerization of thecis,cis-9,15-octadecadienoate with selenium, the geometric isomers were fractionated by CCD with methanolic silver nitrate and hexane. Puretrans,trans and purecis,cis isomers were isolated, as well as an unresolved mixture ofcis,trans andtrans,cis isomers. The characteristics of these isomers and related compounds are compared as determined by CCD, IR absorption, and capillary gas-liquid chromatography (GLC). Presented at the AOCS meeting in Minneapolis, 1963. A laboratory of the No. Utiliz. Res. and Dev. Div., ARS, USDA.     

Redox proteomics identification of 4‐hydroxynonenal‐modified brain proteins in Alzheimer's disease: Role of lipid peroxidation in Alzheimer's disease pathogenesis

Numerous studies have shown that neuronal lipids are highly susceptible to oxidative stress including in those brain areas directly involved in the neurodegenerative process of Alzheimer's disease (AD). Lipid peroxidation directly damages membranes and also generates a number of secondary biologically active products (toxic aldehydes)that are capable of easily attacking lipids, proteins, and DNA. Accumulating evidence has demonstrated regionally increased brain lipid peroxidation in patients with AD; however, extensive studies on specific targets of lipid peroxidation‐induced damage are still missing. The present study represents a further step in understanding the relationship between oxidative modification of protein and neuronal death associated with AD. We used a proteomics approach to determine specific targets of lipid peroxidation in AD brain, both in hippocampus and inferior parietal lobule, by coupling immunochemical detection of 4‐hydroxynonenal‐bound proteins with 2‐D polyacrylamide gel electrophoresis and MS analysis. We identified 4‐hydroxynonenal‐bound proteins in the hippocampus and inferior parietal lobule brain regions of subjects with AD. The identified proteins play different biological functions including energy metabolism, antioxidant system, and structural proteins, thus impairing multiple molecular pathways. Our results provide further evidence for the role of lipid peroxidation in the pathogenesis of AD.     

Mechanising a formal model of flash memory

We present second steps in the construction of formal models of NAND flash memory, based on a recently emerged open standard for such devices. The model is intended as a key part of a pilot project to develop a verified file store system based on flash memory. The project was proposed by Joshi and Holzmann as a contribution to the Grand Challenge in Verified Software, and involves constructing a highly assured flash file store for use in space-flight missions. The model is at a level of abstraction that captures the internal architecture of NAND flash devices. In this paper, we focus on mechanising the state model and its initialisation operation, where most of the conceptual complexity resides.     

Effects of exercise on carpal tunnel syndrome symptoms

This is a study of whether participation in an exercise programme for increasing upper extremity flexibility, strength, and circulation has any effects on symptoms of carpal tunnel syndrome (CTS). Two groups (exercise and control) of seven participants each who did repetitive hand motion tasks were studied. The exercise group participated in daily arm, hand, and other upper-extremity exercises for 8 weeks. The control group did not participate in the exercise programme. Dependent (response) variables monitored were motor nerve conduction latency through the carpal tunnel, grip strength, and subjective comfort in the dominant hands of participants. Test results indicated no statistically significant differences in nerve conduction latency or subjective comfort between the two groups. Significant differences did develop in grip strengths over time, suggesting that the exercise group may have benefited physiologically from the exercise programme.     

Chlorination of model drinking water biofilm: implications for growth and organic carbon removal

The influence of chlorine on biofilm in low organic carbon environments typical of drinking water or industrial process water was examined by comparing biomass and kinetic parameters for biofilm growth in a chlorinated reactor to those in a non-chlorinated control. Mixed-population heterotrophic biofilms were developed in rotating annular reactors under low concentration, carbon-limited conditions (< 2 mg/L as carbon) using three substrate groups (amino acids, carbohydrates and humic substances). Reactors were operated in parallel under identical conditions with the exception that chlorine was added to one reactor at a dose sufficient to maintain a free chlorine residual of 0.09-0.15 mg/L in the effluent. The presence of free chlorine resulted in development of less biofilm biomass compared to the control for all substrates investigated. However, specific growth and organic carbon removal rates were on the average five times greater for chlorinated biofilm compared to the control. Observed yield values were less for chlorinated biofilm. Although chlorinated biofilm's specific organic carbon removal rate was high, the low observed yield indicated organic carbon was being utilized for purposes other than creating new cell biomass. The impacts of free chlorine on mixed-population biofilms in low-nutrient environments were different depending upon the available substrate. Biofilms grown using amino acids exhibited the least difference between control and chlorinated kinetic parameters; biofilm grown using carbohydrates had the greatest differences. These findings are particularly relevant to the fundamental kinetic parameters used in models of biofilm growth in piping systems that distribute chlorinated, low-carbon-concentration water.     

Kinetic rate constants determined by a digital computer

The difficulty of determining rate constants for complex reactions has been overcome with the development of a general digital computer program that can determine up to 10 rate constants in any reaction scheme which can contain as many as 10 components. A given reaction to which the experimental data are to be fit is described to the computer in a short one-step integration subprogram, which solves the differential equations representing the scheme. Only this subprogram needs to be rewritten to change the reaction scheme. Special features of the program and length of calculations are discussed. A copper-chromite hydrogenation of a mixture of linolenate and conjugated linoleate demonstrates what the program does and what is a typical output.