A case study in model-driven synthetic biology

We report on a case study in synthetic biology, demonstrating the modeldriven design of a self-powering electrochemical biosensor. An essential result of the design process is a general template of a biosensor, which can be instantiated to be adapted to specific pollutants. This template represents a gene expression network extended by metabolic activity. We illustrate the model-based analysis of this template using qualitative, stochastic and continuous Petri nets and related analysis techniques, contributing to a reliable and robust design

A comparison of once versus twice per week training on leg press strength in women

The purpose of this study was to compare strength differences between 2 groups of untrained women, who performed a single set of the leg press exercise once or twice per week. Methods. Twenty-one women were divided randomly into 2 groups: Group 1 (n=10) performed a single set of the leg press exercise once per week, while Group 2 (n=11) performed a single set of the leg press exercise twice per week for a period of 8 weeks. Throughout the duration of the study, an amount of resistance was utilized that allowed for a single set of 6 to 10 repetitions to muscular failure. At the conclusion of the study, subjects were tested for their 6-RM strength. A 2x2 ANOVA was used to compare strength differences. The a level was set at 0.05 in order for differences to be considered significant. Results. The 2X2 ANOVA demonstrated that strength increases were significant between tests {P=0.0001), but not significant between groups (P=0.757). Conclusion. These results indicate that performing a single set of the leg press once or twice per week results in statistically similar strength gains in untrained women

Impact of Water and Soils Having High Source-Sink Potentials on Water and Salinity Management Under Irrigation in the Upper Colorado River Basin

Water management in irrigation projects is one potential method for reducing downstream salinity in the Colorado River. An important contribution can be made to developing more effective irrigation water management practices for water conservation and salinity control through identification and better understanding of the soil and water interactions that result in soils behaving as salt sources or as salt sinks. The interactions identified in this study were examined to determine the effects of various management alternatives on the quality and quantity of salt in subsurface return flow from irrigation projects. A soil solution chemistry model was developed to describe the soil-irrigation water interactions. The model includes the effect of cation exchange capacity. The model was calibrated and checked with data obtained from lysimeters. A water management model that contained a soil solution chemistry component was calibrated for the Ashley Valley of Utah and was used to determine the sensitivity of stream flows and salinity to irrigation water management alternatives. The source-sink behavior of soils was found to depent on water quality, residual soil salinity, and water management practices. The key relationships are described. In applying these relationships, site specific conditions must be examined to determine the effectiveness of proposed irrigation management changes that are expected to affect downstream salinity

MCT1 genetic polymorphism influence in high intensity circuit training: A pilot study

Monocarboxylate Transporter 1 (MCT1) mediates the transport of the main fraction of lactate across the sarcolemma. A common polymorphic MCT1 variant has been identified, but its role in high intensity exercise performance has not been defined. We investigated the influence of MCT1 A1470T polymorphism (rs1049434) on lactate accumulation after high intensity circuit training. Ten men aged 20–26 performed three controlled circuit training (CWT) sessions at 60%, 70%, and 80% of the 15 repetition maximum (15 RM), in non-consecutive days. CWT included three sets of a circuit of eight exercises, obtaining lactate measurements immediately after each set had been completed. Two independent variables were analysed: MTC1 genotypes according to the presence or absence of the A1470T polymorphism, and the intensity of circuit training. Genotype distributions were in Hardy–Weinberg equilibrium, being 30% wild-type, 50% heterozygotes, and 20% mutated homozygotes. Mean lactate concentration at 80% of 15 RM were significantly higher than the mean lactate values at the other intensities (p < 0.01). Significant differences between genetic groups were found in the lactate accumulation slope at 80% of 15 RM (p = 0.02) and in the maximal lactate concentration reached by all subjects in the study (Lmax) (p = 0.03). The carriers of the A1470T polymorphism in the MTC1 gene seem to exhibit a worse lactate transport capability into the less active muscle cells for oxidation

EXERCISE AND BLOOD FLOW RESTRICTION

Pope, ZK, Willardson, JM, and Schoenfeld, BJ. Exercise and blood flow restriction. J Strength Cond Res 27(10): 2914– 2926, 2013—A growing body of research has demonstrated the effectiveness of exercise (low-intensity resistance training, walking, cycling) combined with blood flow restriction (BFR) for increased muscular strength and hypertrophy. The BFR is achieved via the application of external pressure over the proximal portion of the upper or lower extremities. The external pressure applied is sufficient to maintain arterial inflow while occluding venous outflow of blood distal to the occlusion site. With specific reference to low-intensity resistance training, the ability to significantly increase muscle strength and hypertrophy when combined with BFR is different from the traditional paradigm, which suggests that lifting only higher intensity loads increases such characteristics. The purpose of this review was to discuss the relevant literature with regard to the type and magnitude of acute responses and chronic adaptations associated with BFR exercise protocols vs. traditional non-BFR exercise protocols. Furthermore, the mechanisms that stimulate such responses and adaptations will be discussed in the context of neural, endocrine, and metabolic pathways. Finally, recommendations will be discussed for the practitioner in the prescription of exercise with BFR

Caffeine Does Not Augment Markers of Muscle Damage or Leukocytosis Following Resistance Exercise

The purpose of this study was to evaluate the effects of caffeine ingestion before a resistance exercise session on markers of muscle damage (CK, LDH, ALT, AST) and leukocyte levels. Methods: Fifteen soccer athletes completed two resistance exercise sessions that differed only in the ingestion of caffeine or a placebo preworkout. Results: CK concentration increased significantly following the caffeine session (415.8 ± 62.8 to 542.0 ± 73.5) and the placebo session (411.5 ± 43.3 to 545.8 ± 59.9), with no significant differences between sessions. Similarly, LDH concentration increased significantly following the caffeine session (377.5 ± 18.0 to 580.5 ± 36.1) and the placebo session (384.8 ± 13.9 to 570.4 ± 36.1), with no significant differences between sessions. Both sessions resulted in significant increases in the total leukocyte count (caffeine = 6.24 ± 2.08 to 8.84 ± 3.41; placebo = 6.36 ± 2.34 to 8.77 ± 3.20), neutrophils (caffeine = 3.37 ± 0.13 to 5.15 ± 0.28; placebo = 3.46 ± 0.17 to 5.12 ± 0.24), lymphocytes (caffeine = 2.19 ± 0.091 to 2.78 ± 0.10; placebo = 2.17 ± 0.100 to 2.75 ± 0.11), and monocytes (caffeine = 0.53 ± 0.02 to 0.72 ± 0.06; placebo = 0.56 ± 0.03 to 0.69 ± 0.04), with no significant differences between sessions. Conclusion: Ingestion of caffeine at 4.5 mg⋅kg−1 did not augment markers of muscle damage or leukocyte levels above that which occurs through resistance exercise alone

Creatine Supplementation Improves Muscular Performance without Additional Impact on the Cardiovascular System in Trained Women

Creatine monohydrate supplementation in females is largely under-represented in the literature, and their potentially differential hemodynamic responses are unknown. Methods: Twenty-eight resistance-trained women (25.5 ± 6.1 years, 59.7 ± 6.3 kg, 163 ± 5 cm) were randomly assigned to the supplement creatine monohydrate (CRE; 5 g creatine monohydrate + 5 g dextrose) or placebo (PLA; 10 g dextrose) four times per day for 7 days in a double-blind fashion. Each subject subsequently completed resistance training sessions (3 × week) for four weeks with four sets to muscular failure of both half-squat and leg press exercises. The change in body mass (BM), exercise repetition number (REP), rated perceived exertion (RPE), and cardiovascular variables were assessed (sessions 1, 6, and 12). Statistical analyses were performed at a significance level of p ≤ 0.05. Results: Analyses revealed a significant CRE-specific BM increase (p = 0.013), as well as significantly greater half-squat (p = 0.006) and leg press (p = 0.017) REP per set versus PLA. Additionally, CRE demonstrated significantly lower relative RPE values at session 12 compared with previous sessions. Any significant main or interaction effects were observed for the studied cardiovascular variable. Conclusions: The present data substantiate the creatine’s efficacy to improve muscular performance in females while demonstrating the safety of combined creatine monohydrate supplementation and resistance training on cardiovascular parameters

Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition

Hedgehog signaling drives oncogenesis in several cancers and strategies targeting this pathway have been developed, most notably through inhibition of Smoothened. However, resistance to Smoothened inhibitors occurs via genetic changes of Smoothened or other downstream Hedgehog components. Here, we overcome these resistance mechanisms by modulating GLI transcription via inhibition of BET bromodomain proteins. We show the BET bromodomain protein, BRD4, regulates GLI transcription downstream of SMO and SUFU and chromatin immunoprecipitation studies reveal BRD4 directly occupies GLI1 and GLI2 promoters, with a substantial decrease in engagement of these sites upon treatment with JQ1, a small molecule inhibitor targeting BRD4. Globally, genes associated with medulloblastoma-specific GLI1 binding sites are downregulated in response to JQ1 treatment, supporting direct regulation of GLI activity by BRD4. Notably, patient- and GEMM-derived Hedgehog-driven tumors (basal cell carcinoma, medulloblastoma and atypical teratoid/rhabdoid tumor) respond to JQ1 even when harboring genetic lesions rendering them resistant to Smoothened antagonists