The specificity of neuroprotection by antioxidants

<p>Abstract</p> <p>Background</p> <p>Reactive oxygen species (ROS) play an important role in aging and age-related diseases such as Parkinson's disease and Alzheimer's disease. Much of the ROS production under conditions of toxic stress is from mitochondria, and multiple antioxidants prevent ROS accumulation. The aim of this study is to examine the specificity of the interaction between the antioxidants and ROS production in stressed cells.</p> <p>Methods</p> <p>Using fluorescent dyes for ROS detection and mitochondrial inhibitors of known specificities, we studied ROS production under three conditions where ROS are produced by mitochondria: oxidative glutamate toxicity, state IV respiration induced by oligomycin, and tumor necrosis factor-induced cell death.</p> <p>Results</p> <p>We demonstrated that there are at least four mitochondrial ROS-generating sites in cells, including the flavin mononucleotide (FMN) group of complex I and the three ubiquinone-binding sites in complexes I, II and III. ROS production from these sites is modulated in an insult-specific manner and the sites are differentially accessible to common antioxidants.</p> <p>Conclusion</p> <p>The inhibition of ROS accumulation by different antioxidants is specific to the site of ROS generation as well as the antioxidant. This information should be useful for devising new interventions to delay aging or treat ROS-related diseases.</p

A Proposed Methodology to Characterize the Accuracy of Life Cycle Cost Estimates for DoD Programs

For decades, the DoD has employed numerous reporting and monitoring tools for characterizing the acquisition cost of its major programs. These tools have resulted in dozens of studies thoroughly documenting the magnitude and extent of DoD acquisition cost growth. Curiously, though, there have been extremely few studies regarding the behavior of the other cost component of a system\u27s life cycle: Operating and Support (O&S) costs. This is particularly strange considering that O&S costs tend to dominate the total life cycle cost (LCC) of a program, and that LCCs are widely regarded as the preferred metric for assessing actual program value. The upshot for not examining such costs is that the DoD has little knowledge of how LCC estimates behave over time, and virtually no insights regarding their accuracy. In recent years, however, enough quality LCC data has amassed to conduct a study to address these deficiencies. This paper describes a method for conducting such a study, and represents (to the authors’ knowledge) the first broad-based attempt to do so. The results not only promise insights into the nature of current LCC estimates, but also suggest the possibility of improving the accuracy of DoD LCC estimates via a stochastically-based model

Cruise summaries of Oceanus cruises 205, leg 8, and 216

A study of the upper ocean thermal and density structure in the northwestern Atlantic in 1989 compared temperature and density measurements made with Expendable Bathythermograph (XBT) and Conductivity-Temperature-Depth instruments with current data from an acoustic Doppler current profiler and satellite infrared imagery and altimetry. Two cruises were made in the spring and winter of 1989 with the goal of directly measuring the upper ocean currents and variabilty of the Gulf Stream. The XBT observations were used to extend the measured velocities geostrophically from the near-surface region to depths of 750 meters, thereby allowing transport estimates to be made for the upper ocean. In April the measurments were compared and used with the GEOSAT altimeter which, unfortunately, was not operating during the December cruise.Funding was provided by the National Science Foundation through Grant No. OCE-SS-1769S

Placental Pathology in Spontaneous and Iatrogenic Preterm Birth: Different Entities With Unique Pathologic Features

INTRODUCTION: Placental pathology is an important contributor to the understanding of preterm birth and reveals major differences between spontaneous preterm birth (SPTB) and iatrogenic preterm birth (IPTB). The aim of this study was to investigate these relationships. METHODS: Research midwives collected placentas from 1101 women with singleton pregnancies who were enrolled in the Safe Passage Study. Trained pathology technologists prepared and processed placenta specimens for macroscopic and microscopic examination by designated pathologists. Statistical analyses were done with STATISTICA version 13. RESULTS: In SPTB we found more cases of accelerated villous maturation; however, the other features of maternal vascular malperfusion (MVM) were not present. The prevalence rate of funisitis was also increased. In IPTB, multiple features of MVM - accelerated villous maturation, distal villous hypoplasia, decidual arteriopathy, increased syncytial knots, increased perivillous fibrin, and prominent extravillous trophoblast were increased, as were features of fetal vascular malperfusion (FVM) - umbilical cord vessel thrombosis, avascular villi, and fetal vascular thrombosis. Increased syncytial knots were found in 26% of preterm stillbirths and in 29% of preterm infant demises as compared to 81% of IPTB infants alive at one year. DISCUSSION: SPTB and IPTB differ. The detected abnormal accelerated villous maturation pattern in SPTB and preterm demises, suggests an inability of the placenta to adapt and may be a trigger for SPTB. Funisitis was the only inflammatory response significant for SPTB. MVM and FVM are implicated in IPTB, but not an inflammatory process

NBS monograph

From Abstract: "This document is the final report of research carried on in the Electron Physics Section of the National Bureau of Standards during the period from February 1, 1955 to March 1962 in developing an electron optical method for the visualization of low-pressure gas flow.

The intriguing Cyclophilin A-HIV-1 Vpr interaction: prolyl cis/trans isomerisation catalysis and specific binding

<p>Abstract</p> <p>Background</p> <p>Cyclophilin A (CypA) represents a potential target for antiretroviral therapy since inhibition of CypA suppresses human immunodeficiency virus type 1 (HIV-1) replication, although the mechanism through which CypA modulates HIV-1 infectivity still remains unclear. The interaction of HIV-1 viral protein R (Vpr) with the human peptidyl prolyl isomerase CypA is known to occur <it>in vitro </it>and <it>in vivo</it>. However, the nature of the interaction of CypA with Pro-35 of N-terminal Vpr has remained undefined.</p> <p>Results</p> <p>Characterization of the interactions of human CypA with N-terminal peptides of HIV-1 Vpr has been achieved using a combination of nuclear magnetic resonace (NMR) exchange spectroscopy and surface plasmon resonance spectroscopy (SPR). NMR data at atomic resolution indicate prolyl <it>cis</it>/<it>trans </it>isomerisation of the highly conserved proline residues Pro-5, -10, -14 and -35 of Vpr are catalyzed by human CypA and require only very low concentrations of the isomerase relative to that of the peptide substrates. Of the N-terminal peptides of Vpr only those containing Pro-35 bind to CypA in a biosensor assay. SPR studies of specific N-terminal peptides with decreasing numbers of residues revealed that a seven-residue motif centred at Pro-35 consisting of RHFPRIW, which under membrane-like solution conditions comprises the loop region connecting helix 1 and 2 of Vpr and the two terminal residues of helix 1, is sufficient to maintain strong specific binding.</p> <p>Conclusions</p> <p>Only N-terminal peptides of Vpr containing Pro-35, which appears to be vital for manifold functions of Vpr, bind to CypA in a biosensor assay. This indicates that Pro-35 is essential for a specific CypA-Vpr binding interaction, in contrast to the general prolyl <it>cis</it>/<it>trans </it>isomerisation observed for all proline residues of Vpr, which only involve transient enzyme-substrate interactions. Previously suggested models depicting CypA as a chaperone that plays a role in HIV-1 virulence are now supported by our data. In detail the SPR data of this interaction were compatible with a two-state binding interaction model that involves a conformational change during binding. This is in accord with the structural changes observed by NMR suggesting CypA catalyzes the prolyl <it>cis/trans </it>interconversion during binding to the RHFP³⁵RIW motif of N-terminal Vpr.</p

Appetite and gut hormone responses to moderate-intensity continuous exercise versus high-intensity interval exercise, in normoxic and hypoxic conditions.

This study investigated the effects of continuous moderate-intensity exercise (MIE) and high-intensity interval exercise (HIIE) in combination with short exposure to hypoxia on appetite and plasma concentrations of acylated ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Twelve healthy males completed four, 2.6 h trials in a random order: 1) MIE-normoxia, 2) MIE-hypoxia, 3) HIIE-normoxia, and 4) HIIE-hypoxia. Exercise took place in an environmental chamber. During MIE, participants ran for 50 min at 70% of altitude-specific maximal oxygen uptake ( 2max) and during HIIE performed 6 x 3 min running at 90% 2max interspersed with 6 x 3 min active recovery at 50% 2max with a 7 min warm-up and cool-down at 70% 2max (50 min total). In hypoxic trials, exercise was performed at a simulated altitude of 2,980 m (14.5% O2). Exercise was completed after a standardised breakfast. A second meal standardised to 30% of participants’ daily energy requirements was provided 45 min after exercise. Appetite was suppressed more in hypoxia than normoxia during exercise, post-exercise, and for the full 2.6 h trial period (linear mixed modelling, p 0.05). These findings demonstrate that short exposure to hypoxia causes suppressions in appetite and plasma acylated ghrelin concentrations. Furthermore, appetite responses to exercise do not appear to be influenced by exercise modality

Individual variation in hunger, energy intake and ghrelin responses to acute exercise

Purpose This study aimed to characterize the immediate and extended effect of acute exercise on hunger, energy intake, and circulating acylated ghrelin concentrations using a large data set of homogenous experimental trials and to describe the variation in responses between individuals. Methods Data from 17 of our group's experimental crossover trials were aggregated yielding a total sample of 192 young, healthy males. In these studies, single bouts of moderate to high-intensity aerobic exercise (69% ± 5% V˙O2 peak; mean ± SD) were completed with detailed participant assessments occurring during and for several hours postexercise. Mean hunger ratings were determined during (n = 178) and after (n = 118) exercise from visual analog scales completed at 30-min intervals, whereas ad libitum energy intake was measured within the first hour after exercise (n = 60) and at multiple meals (n = 128) during the remainder of trials. Venous concentrations of acylated ghrelin were determined at strategic time points during (n = 118) and after (n = 89) exercise. Results At group level, exercise transiently suppressed hunger (P < 0.010, Cohen's d = 0.77) but did not affect energy intake. Acylated ghrelin was suppressed during exercise (P < 0.001, Cohen's d = 0.10) and remained significantly lower than control (no exercise) afterward (P < 0.024, Cohen's d = 0.61). Between participants, there were notable differences in responses; however, a large proportion of this spread lay within the boundaries of normal variation associated with biological and technical assessment error. Conclusion In young men, acute exercise suppresses hunger and circulating acylated ghrelin concentrations with notable diversity between individuals. Care must be taken to distinguish true interindividual variation from random differences within normal limits

A Modified View on Octocorals: Heteroxenia fuscescens Nematocysts Are Diverse, Featuring Both an Ancestral and a Novel Type

Cnidarians are characterized by the presence of stinging cells containing nematocysts, a sophisticated injection system targeted mainly at prey-capture and defense. In the anthozoan subclass Octocorallia nematocytes have been considered to exist only in low numbers, to be small, and all of the ancestral atrichous-isorhiza type. This study, in contrast, revealed numerous nematocytes in the octocoral Heteroxenia fuscescens. The study demonstrates the applicability of cresyl-violet dye for differential staining and stimulating discharge of the nematocysts. In addition to the atrichous isorhiza-type of nematocysts, a novel type of macrobasic-mastigophore nematocysts was found, featuring a shaft, uniquely comprised of three loops and densely packed arrow-like spines. In contrast to the view that octocorals possess a single type of nematocyst, Heteroxenia fuscescens features two distinct types, indicating for the first time the diversification and complexity of nematocysts for Octocorallia