Time and length scales of autocrine signals in three dimensions

A model of autocrine signaling in cultures of suspended cells is developed on the basis of the effective medium approximation. The fraction of autocrine ligands, the mean and distribution of distances traveled by paracrine ligands before binding, as well as the mean and distribution of the ligand lifetime are derived. Interferon signaling by dendritic immune cells is considered as an illustration.Comment: 15 page

Hybrid neuromuscular training promotes musculoskeletal adaptations in inactive overweight and obese women: A training-detraining randomized controlled trial

This is the author accepted manuscript. The final version is available from Taylor and Francis via the DOI in this recordThis study investigated the effects of a 10-month high-intensity interval-type neuromuscular training program on musculoskeletal fitness in overweight and obese women. Forty-nine inactive females (36.4±4.4 yrs) were randomly assigned to either a control (N=21), a training (N=14, 10 months) or a training-detraining group (N=14, 5 months training followed by 5 months detraining). Training used progressive loaded fundamental movement patterns with prescribed work-to-rest intervals (1:2, 1:1, 2:1) in a circuit fashion (2-3 rounds). Muscular strength and endurance, flexibility, passive range of motion (PRoM), static balance, functional movement screen (FMS) and bone mass density (BMD) and content (BMC) were measured at pre-, mid-, and post-intervention. Ten months of training induced greater changes than the controls in (i) BMD (+1.9%, p<0.001) and BMC (+1.5%, p=0.023) ii) muscular strength (25%-53%, p=0.001-0.005); iii) muscular endurance (103%-195%, p<0.001); and iv) mobility (flexibility: 40%, p<0.001; PRoM [24%-53%, p=0.001-0.05;]; balance: 175%, p=0.058; FMS: +58%, p<0.001). The response rate to training was exceptionally high (86-100%). Five months of detraining reduced but not abolished training-induced adaptations. These results suggest that a hybrid-type exercise approach integrating endurance-based bodyweight drills with resistance-based alternative modes into a real-world gym setting may promote musculoskeletal fitness in overweight or obese women

Manipulation of Signaling Thresholds in “Engineered Stem Cell Niches” Identifies Design Criteria for Pluripotent Stem Cell Screens

In vivo, stem cell fate is regulated by local microenvironmental parameters. Governing parameters in this stem cell niche include soluble factors, extra-cellular matrix, and cell-cell interactions. The complexity of this in vivo niche limits analyses into how individual niche parameters regulate stem cell fate. Herein we use mouse embryonic stem cells (mESC) and micro-contact printing (µCP) to investigate how niche size controls endogenous signaling thresholds. µCP is used to restrict colony diameter, separation, and degree of clustering. We show, for the first time, spatial control over the activation of the Janus kinase/signal transducer and activator of transcription pathway (Jak-Stat). The functional consequences of this niche-size-dependent signaling control are confirmed by demonstrating that direct and indirect transcriptional targets of Stat3, including members of the Jak-Stat pathway and pluripotency-associated genes, are regulated by colony size. Modeling results and empirical observations demonstrate that colonies less than 100 µm in diameter are too small to maximize endogenous Stat3 activation and that colonies separated by more than 400 µm can be considered independent from each other. These results define parameter boundaries for the use of ESCs in screening studies, demonstrate the importance of context in stem cell responsiveness to exogenous cues, and suggest that niche size is an important parameter in stem cell fate control

Hydrodynamics of the Vadose Zone of a Layered Soil Column

Getting into the heart of the water movement into the vadose zone is essential due to the direct impact on the aquifer recharge, the flood hazards, the irrigation planning and the water resources management in general. Since soil profiles in nature appear in layers, the present study accomplishes a deep investigation of the water&rsquo;s motion through soil layers with different hydraulic properties. A series of experiments were conducted in the laboratory where infiltration, tension, soil moisture and hydraulic conductivity data were collected and analyzed. In particular, a transparent column was filled with two soils (loamy sand over sand), and TDR probes, along with ceramic capsules connected to pressure transducers, were set to the column. Using the experimental data and the unsaturated zone modeling, hydraulic parameters were obtained, along with water motion simulation and prediction. An investigation into the drainage, imbibition, infiltration, soil water characteristic curves and, in general, the hydrodynamics of the vadose zone of the soil layers has been achieved. The results of the current study suggest a method to estimate the crucial hydraulic parameters that are involved in the soil-water interaction and have an impact on infiltration, runoff, aquifer horizon recharge, water management and water saving

Hydrodynamics of the Vadose Zone of a Layered Soil Column

Getting into the heart of the water movement into the vadose zone is essential due to the direct impact on the aquifer recharge, the flood hazards, the irrigation planning and the water resources management in general. Since soil profiles in nature appear in layers, the present study accomplishes a deep investigation of the water’s motion through soil layers with different hydraulic properties. A series of experiments were conducted in the laboratory where infiltration, tension, soil moisture and hydraulic conductivity data were collected and analyzed. In particular, a transparent column was filled with two soils (loamy sand over sand), and TDR probes, along with ceramic capsules connected to pressure transducers, were set to the column. Using the experimental data and the unsaturated zone modeling, hydraulic parameters were obtained, along with water motion simulation and prediction. An investigation into the drainage, imbibition, infiltration, soil water characteristic curves and, in general, the hydrodynamics of the vadose zone of the soil layers has been achieved. The results of the current study suggest a method to estimate the crucial hydraulic parameters that are involved in the soil-water interaction and have an impact on infiltration, runoff, aquifer horizon recharge, water management and water saving

Stochastic Model of Autocrine and Paracrine Signals in Cell Culture Assays

Autocrine signaling systems are commonly studied under cell culture conditions. In a typical cell culture assay, a layer of liquid medium covers a random two-dimensional dispersion of cells, which secrete ligands. In a growing number of experiments, it is important to characterize the spatial range of autocrine and paracrine cell communication. Currently, the spatial distribution of diffusing signals can be analyzed only indirectly, from their effects on the intracellular signaling or physiological responses of autocrine cells. To directly characterize the spatial range of secreted ligands, we propose a stochastic model for autocrine cell cultures and analyze it using a combination of analytical and computational tools. The two main results derived within the framework of this model are 1), an expression for the fraction of autocrine trajectories, i.e., the probability for a ligand to be trapped by the same cell from which it has been secreted; and 2), an expression for the spatial distribution of trapping points of paracrine trajectories. We test these analytical results by stochastic simulations with efficient Brownian dynamics code and apply our model to analyze the spatial operation of autocrine epidermal growth factor receptor systems

Ligand Accumulation in Autocrine Cell Cultures

Cell-culture assays are routinely used to analyze autocrine signaling systems, but quantitative experiments are rarely possible. To enable the quantitative design and analysis of experiments with autocrine cells, we develop a biophysical theory of ligand accumulation in cell-culture assays. Our theory predicts the ligand concentration as a function of time and measurable parameters of autocrine cells and cell-culture experiments. The key step of our analysis is the derivation of the survival probability of a single ligand released from the surface of an autocrine cell. An expression for this probability is derived using the boundary homogenization approach and tested by stochastic simulations. We use this expression in the integral balance equations, from which we find the Laplace transform of the ligand concentration. We demonstrate how the theory works by analyzing the autocrine epidermal growth factor receptor system and discuss the extension of our methods to other experiments with cultured autocrine cells

Skeletal muscle phenotype and game performance in elite women football players

We combined game activity analyses with skeletal muscle phenotypes and comprehensive physiological testing to elucidate factors of importance for physical performance in elite women's football. GPS-data from an experimental game, sprint and endurance testing, and muscle tissue analysis of metabolic enzyme activity, protein expression and fiber type composition were completed for international top-level women players (n = 20; age; 23 ± 4 yrs, height; 166 ± 10 cm, weight; 60 ± 8 kg; VO2max; 51 ± 6 ml/min/kg). Muscle monocarboxylate transporter 4 (MCT4) protein expression explained 46% of the variance in total game distance, while the ability to maintain high-intensity running (HIR) during the final 15 min of the game correlated to myosin heavy chain 1 (MHCI) and Na+-K+ ATPase β1, FXYD1 (phospholemman) and superoxide dismutase 2 (SOD2) protein expression (range: r = 0.51–0.71; all p &lt; 0.05). Total HIR distance correlated with (MHCIIa) protein expression (r = 0.51; p &lt; 0.05), while muscle Na+/H+ exchanger 1 (NHE1) protein explained 36% of the variance in game sprint distance (p &lt; 0.05). Total game accelerations (actions &gt;4 m/s2) correlated with platelet endothelial cell adhesion molecule (PECAM-1) protein expression (r = 0.51; p &lt; 0.05), while concentric knee flexor strength explained 42–62% of the variance in intense decelerations (&gt;4 m/s2). In conclusion, for elite women players’ game endurance performance and resistance to end-game fatigue were affected by monocarboxylate transporter expression and myosin heavy chain profile. HIR was also correlated to ion transporter expression and muscle antioxidative capacity. Finally, the importance of functional strength and measures of muscle vascularization in relation to total game decelerations and accelerations, respectively, illustrates the complex physiological demands in elite women's football. © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Effect of whey vs. soy protein supplementation on recovery kinetics following speed endurance training in competitive male soccer players: a randomized controlled trial

Background: Soccer-specific speed-endurance training induces short-term neuromuscular fatigue and performance deterioration over a 72-h recovery period, associated with elevated markers of exercise-induced muscle damage. We compared the effects of whey vs. soy protein supplementation on field activity, performance, muscle damage and redox responses following speed-endurance training in soccer players. Methods: Ten well-trained, male soccer players completed three speed-endurance training trials, receiving whey protein (WP), soy protein (SP) or an isoenergetic placebo (PL; maltodextrin) according to a randomized, double-blind, crossover, repeated-measures design. A pre-loading period was applied in each trial during which protein supplementation was individually adjusted to reach a total protein intake of 1.5 g/kg/day, whereas in PL protein intake was adjusted at 0.8–1 g/kg/day. Following pre-loading, two speed-endurance training sessions (1 and 2) were performed 1 day apart, over a 3-day experimental period. During each session, field activity and heart rate were continuously monitored using global positioning system and heart rate monitors, respectively. Performance (isokinetic strength of knee extensors and flexors, maximal voluntary isometric contraction, speed, repeated sprint ability, countermovement jump), muscle damage (delayed-onset of muscle soreness, creatine kinase activity) and redox status (glutathione, total antioxidant capacity, protein carbonyls) were evaluated at baseline (pre), following pre-loading (post-load), and during recovery from speed-endurance training. Results: High-intensity and high-speed running decreased (P ≤ 0.05) during speed-endurance training in all trials, but WP and SP mitigated this response. Isokinetic strength, maximal voluntary isometric contraction, 30-m speed, repeated sprint ability and countermovement jump performance were similarly deteriorated during recovery following speed-endurance training in all trials (P ≤ 0.05). 10 m speed was impaired at 24 h only in PL. Delayed-onset of muscle soreness, creatine kinase, total antioxidant capacity and protein carbonyls increased and glutathione decreased equally among trials following speed-endurance training (P ≤ 0.05), with SP inducing a faster recovery of protein carbonyls only at 48 h (P ≤ 0.05) compared to WP and PL. Conclusions: In conclusion, increasing daily protein intake to 1.5 g/kg through ingestion of either whey or soy protein supplements mitigates field performance deterioration during successive speed-endurance training sessions without affecting exercise-induced muscle damage and redox status markers. Trial registration: Name of the registry: clinicaltrials.gov. Trial registration: NCT03753321. Date of registration: 12/10/2018. © 2021, The Author(s)