The relationship between whole-body external loading and body-worn accelerometry during team sports movements

Purpose: The aim of this study was to investigate the relationship between whole-body accelerations and body-worn accelerometry during team sports movements. Methods: Twenty male team sport players performed forward running, and anticipated 45° and 90° side-cuts at approach speeds of 2, 3, 4 and 5 m·s-1. Whole-body Centre of Mass (CoM) accelerations were determined from ground reaction forces collected from one foot-ground-contact and segmental accelerations were measured from a commercial GPS/accelerometer unit on the upper trunk. Three higher specification accelerometers were also positioned on the GPS unit, the dorsal aspect of the pelvis, and the shaft of the tibia. Associations between mechanical load variables (peak acceleration, loading rate and impulse) calculated from both CoM accelerations and segmental accelerations were explored using regression analysis. In addition one-dimensional Statistical Parametric Mapping (SPM) was used to explore the relationships between peak segmental accelerations and CoM acceleration profiles during the whole foot-ground-contact. Results: A weak relationship was observed for the investigated mechanical load variables regardless of accelerometer location and task (R2 values across accelerometer locations and tasks: peak acceleration 0.08-0.55, loading rate 0.27-0.59 and impulse 0.02-0.59). Segmental accelerations generally overestimated whole-body mechanical load. SPM analysis showed that peak segmental accelerations were mostly related to CoM accelerations during the first 40-50% of contact phase. Conclusions: Whilst body-worn accelerometry correlates to whole-body loading in team sports movements and can reveal useful estimates concerning loading, these correlations are not strong. Body-worn acclerometry should therefore be used with caution to monitor whole-body mechanical loading in the field

The dynamics of single spike-evoked adenosine release in the cerebellum

The purine adenosine is a potent neuromodulator in the brain, with roles in a number of diverse physiological and pathological processes. Modulators such as adenosine are difficult to study as once released they have a diffuse action (which can affect many neurones) and, unlike classical neurotransmitters, have no inotropic receptors. Thus rapid postsynaptic currents (PSCs) mediated by adenosine (equivalent to mPSCs) are not available for study. As a result the mechanisms and properties of adenosine release still remain relatively unclear. We have studied adenosine release evoked by stimulating the parallel fibres in the cerebellum. Using adenosine biosensors combined with deconvolution analysis and mathematical modelling, we have characterised the release dynamics and diffusion of adenosine in unprecedented detail. By partially blocking K+ channels, we were able to release adenosine in response to a single stimulus rather than a train of stimuli. This allowed reliable sub-second release of reproducible quantities of adenosine with stereotypic concentration waveforms that agreed well with predictions of a mathematical model of purine diffusion. We found no evidence for ATP release and thus suggest that adenosine is directly released in response to parallel fibre firing and does not arise from extracellular ATP metabolism. Adenosine release events showed novel short-term dynamics, including facilitated release with paired stimuli at millisecond stimulation intervals but depletion-recovery dynamics with paired stimuli delivered over minute time scales. These results demonstrate rich dynamics for adenosine release that are placed, for the first time, on a quantitative footing and show strong similarity with vesicular exocytosis

Plant polyphenols inhibit functional amyloid and biofilm formation in <i>Pseudomonas</i> strains by directing monomers to off-pathway oligomers

Self-assembly of proteins to &beta;-sheet rich amyloid fibrils is commonly observed in various neurodegenerative diseases. However, amyloid also occurs in the extracellular matrix of bacterial biofilm, which protects bacteria from environmental stress and antibiotics. Many Pseudomonas strains produce functional amyloid where the main component is the highly fibrillation-prone protein FapC. FapC fibrillation may be inhibited by small molecules such as plant polyphenols, which are already known to inhibit formation of pathogenic amyloid, but the mechanism and biological impact of inhibition is unclear. Here, we elucidate how polyphenols modify the self-assembly of functional amyloid, with particular focus on epigallocatechin gallate (EGCG), penta-O-galloyl-&beta;-d-glucose (PGG), baicalein, oleuropein, and procyanidin B2. We find EGCG and PGG to be the best inhibitors. These compounds inhibit amyloid formation by redirecting the aggregation of FapC monomers into oligomeric species, which according to small-angle X-ray scattering (SAXS) measurements organize into core-shell complexes of short axis diameters 25&ndash;26 nm consisting of ~7 monomers. Using peptide arrays, we identify EGCG-binding sites in FapC&rsquo;s linker regions, C and N-terminal parts, and high amyloidogenic sequences located in the R2 and R3 repeats. We correlate our biophysical observations to biological impact by demonstrating that the extent of amyloid inhibition by the different inhibitors correlated with their ability to reduce biofilm, highlighting the potential of anti-amyloid polyphenols as therapeutic agents against biofilm infections

Disentangling astroglial physiology with a realistic cell model in silico

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+ channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+ hotspots. We show how intracellular Ca2+ buffers affect Ca2+ waves and why the classical Ca2+ sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+ imaging

Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow

We review modeling of astrocyte ion dynamics with a specific focus on the implications of so-called spatial potassium buffering, where excess potassium in the extracellular space (ECS) is transported away to prevent pathological neural spiking. The recently introduced Kirchoff-Nernst-Planck (KNP) scheme for modeling ion dynamics in astrocytes (and brain tissue in general) is outlined and used to study such spatial buffering. We next describe how the ion dynamics of astrocytes may regulate microscopic liquid flow by osmotic effects and how such microscopic flow can be linked to whole-brain macroscopic flow. We thus include the key elements in a putative multiscale theory with astrocytes linking neural activity on a microscopic scale to macroscopic fluid flow.Comment: 27 pages, 7 figure