Gene delivery properties of end-modified poly(beta-amino ester)s

Here, we present the synthesis of a library of end-modified poly(beta-amino ester)s and assess their utility as gene delivery vehicles. Polymers were synthesized using a rapid, two-step approach that involves initial preparation of an acrylate-terminated polymer followed by a postpolymerization amine-capping step to generate end-functionalized polymers. Using a highly efficient poly(beta-amino ester), C32, we show that the terminal amine can greatly affect and improve polymer properties relevant to gene delivery. Specifically, the in vitro transfection levels can be increased by 30% and the optimal polymer:DNA ratio lowered 5-fold by conjugation of the appropriate end group. The most effective modifications were made by grafting primary diamine molecules to the chain termini. The added charge and hydrophobicity of some derivatives enhanced DNA binding and resulted in the formation of polymer-DNA complexes less than 100 nm in diameter. In addition, cellular uptake was improved 5-fold over unmodified C32. The end-modified poly(beta-amino ester)s presented here are some of the most effective gene-delivery polycations, superior to polyethylenimine and previously reported poly(beta-amino ester)s. These results show that the end-modification of poly(beta-amino ester)s is a general strategy to alter functionality and improve the delivery performance of these materials.     

The nucleolar channel system of human endometrium is related to endoplasmic reticulum and R-rings

The nucleolar channel system (NCS) is a well-established ultrastructural hallmark of the postovulation endometrium. Its transient presence has been associated with human fertility. Nevertheless, the biogenesis, composition, and function of these intranuclear membrane cisternae are unknown. Membrane systems with a striking ultrastructural resemblance to the NCS, termed R-rings, are induced in nuclei of tissue culture cells by overexpression of the central repeat domain of the nucleolar protein Nopp140. Here we provide a first molecular characterization of the NCS and compare the biogenesis of these two enigmatic organelles. Like the R-rings, the NCS consists of endoplasmic reticulum harboring the marker glucose-6-phosphatase. R-ring formation initiates at the nuclear envelope, apparently by a calcium-mediated Nopp140-membrane interaction, as supported by the calcium-binding ability of Nopp140, the inhibition of R-ring formation by calcium chelators, and the concentration of Nopp140 and complexed calcium in R-rings. Although biogenesis of the NCS may initiate similarly, the reduced presence of complexed calcium and Nopp140 suggests the involvement of additional factors.     

Relative vs. absolute physiological measures as predictors of mountain bike cross-country race performance

The aims of this study were to document the effect terrain has on the physiological responses and work demands (power output) of riding a typical mountain bike cross-country course under race conditions. We were particularly interested in determining whether physiological measures relative to mass were better predictors of race performance than absolute measures. Eleven A-grade male cross-country mountain bike riders (VO2max 67.1 +/- 3.6 ml x kg(-1) x min(-1)) performed 2 tests: a laboratory-based maximum progressive exercise test, and a 15.5-km (six 2.58-km laps) mountain bike cross-country time trial. There were significant differences among the speed, cadence, and power output measured in each of 8 different terrain types found in the cross-country time trial course. The highest average speed was measured during the 10-15% downhill section (22.7 +/- 2.6 km x h(-1)), whereas the cadence was highest in the posttechnical flat sections (74.3 +/- 5.6 rpm) and lowest on the 15-20% downhill sections (6.4 +/- 12.1 rpm). The highest mean heart rate (HR) was obtained during the steepest (15-20% incline) section of the course (179 +/- 8 b x min(-1)), when the power output was greatest (419.8 +/- 39.7 W). However, HR remained elevated relative to power output in the downhill sections of the course. Physiological measures relative to total rider mass correlated more strongly to average course speed than did absolute measures (peak power relative to mass r = 0.93, p < 0.01, vs. peak power r = 0.64, p < 0.05; relative VO2max r = 0.80, p < 0.05, vs. VO2max r = 0.66, p < 0.05; power at anaerobic threshold relative to mass r = 0.78, p < 0.05, vs. power at anaerobic threshold r = 0.5, p < 0.05). This suggests that mountain bike cross-country training programs should focus upon improving relative physiological values rather than focusing upon maximizing absolute values to improve performance.     

Effect of starting stance on initial sprint performance

The effect of different starting stances from a standing position on short sprint times and the subsequent variability in times was investigated in this study. A dual-beam timing light system was used to measure 5- and 10-m times for 3 different standing starts commonly found in the sporting environment: parallel (feet parallel to the start line), split (lead left foot on start line, right leg back), and false (initial parallel start, right leg drops back to split start when movement initiated). The parallel start was found to be significantly (alpha < 0.05) slower than the other 2 stances for both the 5- ( approximately 8.3%) and the 10-m (approximately 5.9%) distances. Within the trial, variation of the different starting stances was equally consistent; however, there was less variability for the 10-m distance (CV = 1.16-1.67%) than the 5-m distance (CV = 1.43-2.15%) for each start for both men and women. The split and false start seem to offer the best option as a movement strategy for minimizing short-distance sprint times. However, the benefits of these 2 starts are less clear if total movement time is the variable of interest.     

Predictors of sprint start speed: the effects of resistive ground-based vs. inclined treadmill training

There is currently no consensus with regard to the most effective method to train for improved acceleration, or with regard to which kinematic variable provides the greatest opportunity for improvement in this important performance characteristic. The purpose of this study was to determine the effects of resistive ground-based speed training and incline treadmill speed training on speed-related kinematic measures and sprint start speed. The hypothesis tested was that incline treadmill training would improve sprint start time, while the ground-based resistive training would not. Corollary hypotheses were that treadmill training would increase stride frequency and ground-based training would not affect kinematics during the sprint start. Thirty-one high school female soccer players (15.7 +/- 0.5 years) were assigned to either treadmill (n = 17) or ground-based (n = 14) training groups and trained 2 times a week for 6 weeks. The treadmill group utilized incline speed training on a treadmill, while the ground-based group utilized partner band resistance ground-based techniques. Three-dimensional motion analysis was used (4.5 m mark) before and after training to quantify kinematics during the fastest of 3 recorded sprint starts (9.1 m). Both groups decreased average sprint start time from 1.75 +/- 0.12 to 1.68 +/- 0.08 seconds (p < 0.001). Training increased stride frequency (p = 0.030) but not stride length. After training, total vertical pelvic displacement and stride length predicted 62% of the variance in sprint start time for the resistive ground-based group, while stride length and stride frequency accounted for 67% prediction of the variance in sprint start time for the treadmill group. The results of this study indicate that both incline treadmill and resistive ground-based training are effective at improving sprint start speed, although they potentially do so through differing mechanisms.     

Age and sex differentially affect regional changes in one repetition maximum strength

To assess the influences of age and sex on regional changes in 1 repetition maximum (1RM) strength, 10 young men (20-30 years), 8 young women (20-30 years), 11 older men (65- 75 years), and 10 older women (65-75 years) were studied before and after a 24-week whole-body strength training program. Changes in 1RM strength were analyzed for each individual exercise, as well as by calculating a total body score (TBS), an upper body score (UBS), and a lower body score (LBS). The effect of age and sex on changes in 1RM strength was analyzed using a repeated measures analysis of variance. When changes in strength for individual exercises were analyzed, the chest press, lat pulldown, shoulder press, and triceps pushdown were affected by both age (p < 0.05) and sex (p < 0.05), while the biceps curls were only influenced by age (p < 0.05). For the lower body, the leg press changes in 1RM strength were influenced by age (p < 0.0001), while leg extension was influenced by sex (p < 0.05). Total body score, UBS, and LBS showed significant increases with 24 weeks of ST (p < 0.001, all). Changes in TBS and UBS were affected by age (p < 0.001, both) and sex (p < 0.05 and p < 0.001, respectively). Younger subjects showed a greater increase in strength than older subjects, and men showed a greater increase in strength compared with women. Changes in LBS were affected by age (p < 0.001), with younger subjects showing a greater increase in strength compared with the older subjects, but not by sex (p = 0.464). These data indicate that regional increases in strength are differentially affected by age and sex.     

Biopolymer-based materials: the nanoscale components and their hierarchical assembly

Protein and nucleic acid biopolymers are well appreciated for their high-performance capabilities for molecular recognition, catalysis and information storage. Increasingly, these biopolymers are being examined for materials applications. Less tractable are polysaccharides and polymers of phenols, which, despite being nature's most abundant macromolecules, remain largely ignored for advanced materials applications. In our opinion, it seems certain that biology will contribute two major capabilities for materials biofabrication - the means to generate biopolymeric components with nanoscale precision, and the mechanisms for the hierarchical assembly of nanocomponents. These capabilities will enable unprecedented control of materials structure and provide exciting opportunities at the convergence of molecular biology and macromolecular science.