No Dose-Response Effect of Carbohydrate Mouth Rinse Concentration on 5-km Running Performance in Recreational Athletes.

Clarke, ND, Thomas, JR, Kagka, M, Ramsbottom, R, and Delextrat, A. No dose-response effect of carbohydrate mouth rinse concentration on 5-km running performance in recreational athletes. J Strength Cond Res 31(3): 715-720, 2017-Oral carbohydrate rinsing has been demonstrated to provide beneficial effects on exercise performance of durations of up to 1 hour, albeit predominately in a laboratory setting. The aim of the present study was to investigate the effects of different concentrations of carbohydrate solution mouth rinse on 5-km running performance. Fifteen healthy men (n = 9; mean ± SD age; 42 ± 10 years; height, 177.6 ± 6.1 cm; body mass, 73.9 ± 8.9 kg) and women (n = 6; mean ± SD age, 43 ± 9 years; height, 166.5 ± 4.1 cm; body mass, 65.7 ± 6.8 kg) performed a 5-km running time trial on a track on 4 separate occasions. Immediately before starting the time trial and then after each 1 km, subjects rinsed 25 ml of 0, 3, 6, or 12% maltodextrin for 10 seconds. Mouth rinsing with 0, 3, 6, or 12% maltodextrin did not have a significant effect on the time to complete the time trial (0%, 26:34 ± 4:07 minutes:seconds; 3%, 27:17 ± 4:33 minutes:seconds; 6%, 27:05 ± 3:52 minutes:seconds; 12%, 26:47 ± 4.31 minutes:seconds; p = 0.071; (Equation is included in full-text article.)= 0.15), heart rate (p = 0.095; (Equation is included in full-text article.)= 0.16), rating of perceived exertion (p = 0.195; (Equation is included in full-text article.)= 0.11), blood glucose (p = 0.920; (Equation is included in full-text article.)= 0.01), and blood lactate concentration (p = 0.831; (Equation is included in full-text article.)= 0.02), with only nonsignificant trivial to small differences between concentrations. Results of this study suggest that carbohydrate mouth rinsing provides no ergogenic advantage over an acaloric placebo (0%) and that there is no dose-response relationship between carbohydrate solution concentration and 5-km track running performance.

Accelerated molecular dynamics and protein conformational change: a theoretical and practical guide using a membrane embedded model neurotransmitter transporter.

Molecular dynamics simulation provides a powerful and accurate method to model protein conformational change, yet timescale limitations often prevent direct assessment of the kinetic properties of interest. A large number of molecular dynamic steps are necessary for rare events to occur, which allow a system to overcome energy barriers and conformationally transition from one potential energy minimum to another. For many proteins, the energy landscape is further complicated by a multitude of potential energy wells, each separated by high free-energy barriers and each potentially representative of a functionally important protein conformation. To overcome these obstacles, accelerated molecular dynamics utilizes a robust bias potential function to simulate the transition between different potential energy minima. This straightforward approach more efficiently samples conformational space in comparison to classical molecular dynamics simulation, does not require advanced knowledge of the potential energy landscape and converges to the proper canonical distribution. Here, we review the theory behind accelerated molecular dynamics and discuss the approach in the context of modeling protein conformational change. As a practical example, we provide a detailed, step-by-step explanation of how to perform an accelerated molecular dynamics simulation using a model neurotransmitter transporter embedded in a lipid cell membrane. Changes in protein conformation of relevance to the substrate transport cycle are then examined using principle component analysis.

Structural dynamics of the monoamine transporter homolog LeuT from accelerated conformational sampling and channel analysis.

The bacterial leucine transporter LeuT retains significant secondary structure similarities to the human monoamine transporters (MAT) such as the dopamine and serotonin reuptake proteins. The primary method of computational study of the MATs has been through the use of the crystallized LeuT structure. Different conformations of LeuT can give insight into mechanistic details of the MAT family. A conformational sampling performed through accelerated molecular dynamics simulations testing different combinations of the leucine substrate and bound sodium ions revealed seven distinct conformational clusters. Further analysis has been performed to target salt-bridge residues R30-D404, Y108-F253, and R5-D369 and transmembrane domains on both the seven isolated structures and the total trajectories. In addition, solvent accessibility of LeuT and its substrate binding pockets has been analyzed using a program for calculating channel radii. Occupation of the Na2 site stabilizes the outward conformation and should bind to the open outward conformation before the leucine and Na1 sodium while two possible pathways were found to be available for intracellular transport.

LeuT conformational sampling utilizing accelerated molecular dynamics and principal component analysis.

Monoamine transporters (MATs) function by coupling ion gradients to the transport of dopamine, norepinephrine, or serotonin. Despite their importance in regulating neurotransmission, the exact conformational mechanism by which MATs function remains elusive. To this end, we have performed seven 250 ns accelerated molecular dynamics simulations of the leucine transporter, a model for neurotransmitter MATs. By varying the presence of binding-pocket leucine substrate and sodium ions, we have sampled plausible conformational states representative of the substrate transport cycle. The resulting trajectories were analyzed using principal component analysis of transmembrane helices 1b and 6a. This analysis revealed seven unique structures: two of the obtained conformations are similar to the currently published crystallographic structures, one conformation is similar to a proposed open inward structure, and four conformations represent novel structures of potential importance to the transport cycle. Further analysis reveals that the presence of binding-pocket sodium ions is necessary to stabilize the locked-occluded and open-inward conformations.

Recurring breakpoints of 1p13 approximately p22 in osteochondroma.

Cytogenetic studies of osteochondromas are scarce but have previously shown recurring clonal aberrations involving chromosome 8. We have studied a series of eight tumors and have found recurring aberrations not only involving chromosome 8, but also chromosome 1 in five of the seven abnormal tumors. Surprisingly, three of the chromosome 1 aberrations involved pericentric inversions. Four tumors showed aberrations involving the region 1p13 approximately p22 by mechanisms including inversion, insertion, and translocation. These findings indicate that aberrations of chromosome 1p, in a region spanning 1p13 approximately p22, may be nonrandomly involved in the cytogenetic progression of osteochondroma.