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Biomedical subjects

Robert Stanton

Publications and source records attributed to Robert Stanton.

9 recordsLinked to original sources
PubMed2004

Performance of 3D-database molecular docking studies into homology models.

The performance of docking studies into protein active sites constructed by homology model building was investigated using CDK2 and factor VIIa screening data sets. When the sequence identity between model and template near the binding site area is greater than approximately 50%, roughly 5 times more active compounds are identified than would be found randomly. This performance is comparable to docking to crystal structures.

Binding Sites↗
PubMed2004

Activation of the hexosamine pathway causes oxidative stress and abnormal embryo gene expression: involvement in diabetic teratogenesis.

BACKGROUND: Oxidative stress is critical to the teratogenic effects of diabetic pregnancy, yet the specific biochemical pathways responsible for oxidative stress have not been fully elucidated. The hexosamine pathway is activated in many tissues during diabetes and could contribute to oxidative stress by inhibiting the pentose shunt pathway, thereby diminishing production of the cellular antioxidant, reduced glutathione (GSH). METHODS: To test the hypothesis that activation of the hexosamine pathway might contribute to the teratogenic effects of diabetic pregnancy, pregnant mice were injected with glucose, to induce hyperglycemia, or glucosamine, to directly activate the hexosamine pathway. Embryo tissue fragments were also cultured in physiological glucose, high glucose, or physiological glucose plus glucosamine, to test effects on oxidative stress and embryo gene expression. RESULTS: Glucosamine increased hexosamine synthesis and inhibited pentose shunt activity. There was a trend for transient hyperglycemia to have the same effects, but they did not reach statistical significance. However, both glucose and glucosamine significantly decreased GSH, and increased oxidative stress, as indicated by 2',7'-dichloro-dihydrofluorescein fluorescence. Glucose and glucosamine inhibited expression of Pax-3, a gene required for neural tube closure both in vivo and in vitro, and increased neural tube defects (NTDs) in vivo; these effects were prevented by GSH ethyl ester. High glucose and glucosamine inhibited Pax-3 expression by embryo culture, but culture in glutamine-free media to block the hexosamine pathway prevented the inhibition of Pax-3 expression by high glucose. CONCLUSIONS: Activation of the hexosamine pathway causes oxidative stress through depletion of GSH and consequent disruption of embryo gene expression. Activation of this pathway may contribute to diabetic teratogenesis.

Animals↗
PubMed2004

The effect of short-term Swiss ball training on core stability and running economy.

The purpose of this study was to investigate the effect of a short-term Swiss ball training on core stability and running economy. Eighteen young male athletes (15.5 +/- 1.4 years; 62.5 +/- 4.7 kg; sigma9 skinfolds 78.9 +/- 28.2 mm; VO2max 55.3 +/- 5.7 ml.kg(-1).min(-1)) were divided into a control (n = 10) and experimental (n = 8) groups. Athletes were assessed before and after the training program for stature, body mass, core stability, electromyographic activity of the abdominal and back muscles, treadmill VO2max, running economy, and running posture. The experimental group performed 2 Swiss ball training sessions per week for 6 weeks. Data analysis revealed a significant effect of Swiss ball training on core stability in the experimental group (p < 0.05). No significant differences were observed for myoelectric activity of the abdominal and back muscles, treadmill VO2max, running economy, or running posture in either group. It appears Swiss ball training may positively affect core stability without concomitant improvements in physical performance in young athletes. Specificity of exercise selection should be considered.

Abdominal Muscles↗
PubMed2003

Conformational analysis by intersection: CONAN.

As high throughput techniques in chemical synthesis and screening improve, more demands are placed on computer assisted design and virtual screening. Many of these computational methods require one or more three-dimensional conformations for molecules, creating a demand for a conformational analysis tool that can rapidly and robustly cover the low-energy conformational spaces of small molecules. A new algorithm of intersection is presented here, which quickly generates (on average <0.5 seconds/stereoisomer) a complete description of the low energy conformational space of a small molecule. The molecule is first decomposed into nonoverlapping nodes N (usually rings) and overlapping paths P with conformations (N and P) generated in an offline process. In a second step the node and path data are combined to form distinct conformers of the molecule. Finally, heuristics are applied after intersection to generate a small representative collection of conformations that span the conformational space. In a study of approximately 97,000 randomly selected molecules from the MDDR, results are presented that explore these conformations and their ability to cover low-energy conformational space.

Journal Article↗
PubMed2002

Self-reported training habits of Australian outrigger canoe paddlers.

The purpose of this descriptive study was to investigate training habits of Australian outrigger canoe paddlers. A 1-page questionnaire was hand-delivered to 101 paddlers. The survey addressed training factors, use of supplementary training, ergogenic aids, sports performance professionals, and injury history. Paddlers train for an average of 3.2 on-water sessions per week, with each session lasting an average of 1.7 hours. The 6-person canoe is favored by 55% of paddlers surveyed. Seventy-one percent of paddlers use strength training to accompany paddling with a mean frequency of 2.5 sessions per week. Seventy-four percent of paddlers report additional cross-training, with a mean of 3.1 sessions per week. Ergogenic aids are used by 55% of paddlers, and 52% utilize the services of sports science or sports medicine personnel. Forty-nine percent of paddlers (n = 49) report injuries related to paddling, with the most common sites being the shoulder and lower back.

Adult↗
PubMedDate not supplied

A novel subshape molecular descriptor.

Molecules with similar shapes and features often have similar biological activity. Several computational approaches search chemical databases for new leads or templates based on overall molecular shape similarity. However, active molecules often present critical subshapes that are required for binding, which may be missed by comparing overall shape similarity. We present a new approach to compare molecular shapes of different sizes and to calculate subshape similarity. We developed a skeletal representation of the shape which is topologically unrelated to covalent chemical connectivity. This simplifies rotational and translational sampling. We test initial possible alignments by matching similar triangles. This triangle-matching filter rapidly eliminates most geometrically impossible matches. Surviving matches are filtered further in successive stages. These stages involve direction, feature, and shape matching procedures. Our approach is applied to several situations demonstrating lead discovery and evolution.

Journal Article↗