A novel serine phosphorylation site detected in the N-terminal domain of estrogen receptor isolated from human breast cancer cells.

Activated estrogen receptor (ERalpha) plays a critical role in breast cancer development and is a major target for drug treatment. Serine phosphorylation within the N-terminal domain (NTD) contributes to ERalpha activation and may also cause drug resistance. Previous biochemical identification of phosphorylated ERalpha residues was limited to protein artificially overexpressed in transfected cell lines.

Three-dimensional remote sensing by optical scanning holography.

A technique is presented by which holograms can be recorded when an object or scene is scanned with an optically heterodyned Fresnel zone pattern. The experimental setup, based on optical scanning holography, is described and experimental results are presented. We apply the scanning holography technique to three-dimensional reflective objects for the first time to our knowledge and address the unique requirements for such a system.

Comparison of technicians' ability to detect clinical signs in rats housed in wire-bottom versus solid-bottom cages with bedding.

Rodent toxicology studies have historically been performed in wire-bottom cages, but the 1996 Guide for the Care and Use of Laboratory Animals recommends solid-bottom caging with bedding. Some investigators have expressed concern that changing to solid-bottom cages would interfere with technicians' ability to detect clinical signs. To test this hypothesis, rats were housed in both types of caging and given compounds to induce a variety of subtle clinical signs common to toxicology studies including chromodacryorrhea, soft stool, stereotypic behaviors, mild hypoactivity, abnormal postures, and discolored urine.

Monoblock laser for a low-cost, eyesafe, microlaser range finder.

A small, lightweight, low-cost prototype laser has been developed for use in a microlaser range finder (muLRF). The laser design is based on a flash-lamp-pumped, Nd:YAG laser with a Cr(4+) passive Q switch. The design incorporates a monolithic potassium titanyl arsenide (KTA) optical parametric oscillator (OPO) in an intracavity configuration, producing output at 1.

Partial acetylation of lysine residues improves intraprotein cross-linking.

Intramolecular cross-linking coupled with mass spectrometric identification of cross-linked amino acids is a rapid method for elucidating low-resolution protein tertiary structures or fold families. However, previous cross-linking studies on model proteins, such as cytochrome c and ribonuclease A, identified a limited number of peptide cross-links that are biased toward only a few of the potentially reactive lysine residues. Here, we report an approach to improve the diversity of intramolecular protein cross-linking starting with a systematic quantitation of the reactivity of lysine residues of a model protein, bovine cytochrome c.

Three-dimensional holographic fluorescence microscopy.

Most commonly used methods for three-dimensional (3D) fluorescence microscopy make use of sectioning techniques that require that the object be physically scanned in a series of two-dimensional (2D) sections along the z axis. The main drawback in these approaches is the need for these sequential 2D scans. An alternative approach to fluorescence imaging in three dimensions has been developed that is based on optical scanning holography.

Force-velocity, impulse-momentum relationships: implications for efficacy of purposefully slow resistance training.

The purpose of this brief review is to explain the mechanical relationship between impulse and momentum when resistance exercise is performed in a purposefully slow manner (PS). PS is recognized by ~10s concentric and ~4-10s eccentric actions. While several papers have reviewed the effects of PS, none has yet explained such resistance training in the context of the impulse-momentum relationship.

In-tube extraction for enrichment of volatile organic hydrocarbons from aqueous samples.

In-tube extraction (ITEX) is a novel solventless extraction technique in which a headspace syringe with a needle body filled with a sorbent (here: Tenax TA) is used. The analytes are extracted from sample headspace by dynamic extraction. The needle body is surrounded by a separate heater, which is used for thermal desorption of analytes into the injection port of a GC system.

Three-dimensional location of fluorescent inhomogeneities in turbid media by scanning heterodyne holography.

We describe and illustrate experimentally a method aimed at the three-dimensional (3-D) imaging of fluorescent inhomogeneities embedded in a turbid medium. The method utilizes incoherent scanning holography to capture 3-D information in a single two-dimensional scan and phase-sensitive heterodyne detection to reject multiply scattered light and to produce a single-sideband holographic record. The 3-D imaging capability of the method is illustrated by an example.

Relationship of jumping and agility performance in female volleyball athletes.

Court sports often require more frequent changes of direction (COD) than field sports. Most court sports require 180 degrees turns over a small distance, so COD in such sports might be best evaluated with an agility test involving short sprints and sharp turns. The purposes of this study were to (a) quantify vertical and horizontal force during a COD task, (b) identify possible predictors of court-sport-specific agility performance, and (c) examine performance difference between National Collegiate Athletic Association Division I, II, and III athletes.

Efficacy of prior eccentric exercise in attenuating impaired exercise performance after muscle injury in resistance trained men.

Previous research has demonstrated that prior exercise may reduce the magnitude of muscle soreness and impaired function (i.e., repeated bout effect [RBE]) observed during subsequent eccentric exercise.

Twin-image elimination experiments for three-dimensional images in optical scanning holography.

Twin-image elimination in the context of optical scanning holography has recently been proposed. The proposed technique involves simultaneously acquiring sine and cosine Fresnel holograms. A complex hologram is then formed by complex addition of the holograms, and twin-image rejection is predicted by computer simulations.

Prior exercise and antioxidant supplementation: effect on oxidative stress and muscle injury.

Background: Both acute bouts of prior exercise (preconditioning) and antioxidant nutrients have been used in an attempt to attenuate muscle injury or oxidative stress in response to resistance exercise. However, most studies have focused on untrained participants rather than on athletes. The purpose of this work was to determine the independent and combined effects of antioxidant supplementation (vitamin C + mixed tocopherols/tocotrienols) and prior eccentric exercise in attenuating markers of skeletal muscle injury and oxidative stress in resistance trained men.

Parkinson's disease and resistive exercise: rationale, review, and recommendations.

Individuals with Parkinson's disease (PD) are not only burdened with disease-specific symptoms (i.e., bradykinesia, rigidity, and tremor), but are also confronted with age-associated progressive loss of physical function, perhaps to a greater extent than neurologically normal adults.

Identification of LpxL, a late acyltransferase of Francisella tularensis.

Lipopolysaccharide (LPS) is a major component of the outer membrane of gram-negative bacteria, and the lipid A region of LPS mediates stimulation of the immune system in a structure-dependent manner. Unlike the LPS of many other gram-negative bacteria, the LPS of Francisella tularensis isolated from in vitro cultures is not proinflammatory. This observed lack of proinflammatory prowess may reflect structural features of the lipid A, such as the number and length of the acyl chains and the single-phosphate group.

The influence of muscle fiber type composition on the patterns of responses for electromyographic and mechanomyographic amplitude and mean power frequency during a fatiguing submaximal isometric muscle action.

The purpose of this investigation was to examine the influence of muscle fiber type composition on the patterns of responses for electromyographic (EMG) and mechanomyographic (MMG) amplitude and mean power frequency (MPF) during a fatiguing submaximal isometric muscle action. Five resistance-trained (mean +/- SD age = 23.2 +/- 3.

Nonclinical safety evaluation of muraglitazar, a novel PPARalpha/gamma agonist.

The toxicity of muraglitazar, an oxybenzylglycine, nonthiazolidinedione peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist, was evaluated in a comprehensive nonclinical toxicology program that included single-dose oral toxicity studies in mice, rats, and monkeys; repeat-dose toxicity studies in rats, dogs, and monkeys; a battery of in vitro and in vivo genetic toxicity studies; carcinogenicity studies in mice and rats; reproductive and developmental toxicity studies in rats and rabbits; and studies to investigate species-specific findings. Pharmacologically mediated changes, similar to those observed with other PPARgamma agonists, were observed following chronic administration and included subcutaneous edema, hematologic/hematopoietic and serum chemistry alterations, and morphologic findings in the heart and adipose tissue in rats and monkeys. In dogs, a species highly sensitive to PPARgamma agonists, muraglitazar caused pronounced species-specific clinical toxicity and degenerative changes in the brain, spinal cord, and testes at high doses and exposures.

Structural determinants of odorant recognition by the human olfactory receptors OR1A1 and OR1A2.

An interaction of odorants with olfactory receptors is thought to be the initial step in odorant detection. However, ligands have been reported for only 6 out of 380 human olfactory receptors, with their structural determinants of odorant recognition just beginning to emerge. Guided by the notion that amino acid positions that interact with specific odorants would be conserved in orthologs, but variable in paralogs, and based on the prediction of a set of 22 of such amino acid positions, we have combined site-directed mutagenesis, rhodopsin-based homology modelling, and functional expression in HeLa/Olf cells of receptors OR1A1 and OR1A2.

Mitochondrial oxidative stress causes hyperphosphorylation of tau.

Age-related neurodegenerative disease has been mechanistically linked with mitochondrial dysfunction via damage from reactive oxygen species produced within the cell. We determined whether increased mitochondrial oxidative stress could modulate or regulate two of the key neurochemical hallmarks of Alzheimer's disease (AD): tau phosphorylation, and beta-amyloid deposition. Mice lacking superoxide dismutase 2 (SOD2) die within the first week of life, and develop a complex heterogeneous phenotype arising from mitochondrial dysfunction and oxidative stress.

Small-scale immunopurification of cytochrome c oxidase for a high-throughput multiplexing analysis of enzyme activity and amount.

COX (cytochrome c oxidase) deficiency is one of the main causes of genetic mitochondrial disease and presents with multiple phenotypes, depending on whether the causative mutation exists in a mitochondrial or nuclear gene and on whether it involves an altered catalytic or structural component or an assembly factor for this membrane-embedded 13-subunit enzyme complex. COX deficiency is routinely observed in AD (Alzheimer's disease), although there is continuing debate about whether this is a causative or a secondary consequence of the condition. Altered levels of COX and reduced oxidative phosphorylation capacity have been reported in other common diseases, including cancer, and are seen as unwanted side effects in a number of drug treatments, particularly with antiretroviral and antibiotic treatments.

Rodent carcinogenicity profile of the antidiabetic dual PPAR alpha and gamma agonist muraglitazar.

The carcinogenic potential of muraglitazar, a dual human peroxisome proliferator-activated receptor alpha/gamma agonist, was evaluated in 2-year studies in mice (1, 5, 20, and 40 mg/kg) and rats (1, 5, 30, and 50 mg/kg). Benign gallbladder adenomas occurred at low incidences in male mice at 20 and 40 mg/kg (area under the curve [AUC] exposures > or = 62 times human exposure at 5 mg/day) and were considered drug related due to an increased incidence of gallbladder mucosal hyperplasia at these doses. There was a dose-related increased incidence of transitional cell papilloma and carcinoma of the urinary bladder in male rats at 5, 30, and 50 mg/kg (AUC exposures > or = 8 times human exposure at 5 mg/day).

Characterization of lipid A acylation patterns in Francisella tularensis, Francisella novicida, and Francisella philomiragia using multiple-stage mass spectrometry and matrix-assisted laser desorption/ionization on an intermediate vacuum source linear ion trap.

Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria. The lipid A region of LPS stimulates the immune system in a structure-dependent manner. We have previously identified the two major lipid A species from Francisella tularensis as asymmetric tetraacylated structures containing four long acyl chains (16 and 18 carbons) and a single phosphate group that is partially modified by galactosamine (Phillips, N.

Anthropometric and performance variables discriminating elite American junior men weightlifters.

The purpose of this study is to identify physical and performance variables that discriminate elite American junior-aged men weightlifters from nonelite performers. Using a cross-sectional design, multiple discriminant analysis was used to determine field tests identifying elite male junior weightlifters. Young men who were participants (n = 115) at the Junior National and Junior Olympics Weightlifting Championships volunteered as subjects (mean +/- SD age = 14.