Reinforcement versus Fluidization in Cytoskeletal Mechanoresponsiveness

Every adherent eukaryotic cell exerts appreciable traction forces upon its substrate. Moreover, every resident cell within the heart, great vessels, bladder, gut or lung routinely experiences large periodic stretches. As an acute response to such stretches the cytoskeleton can stiffen, increase traction forces and reinforce, as reported by some, or can soften and fluidize, as reported more recently by our laboratory, but in any given circumstance it remains unknown which response might prevail or why. Using a novel nanotechnology, we show here that in loading conditions expected in most physiological circumstances the localized reinforcement response fails to scale up to the level of homogeneous cell stretch; fluidization trumps reinforcement. Whereas the reinforcement response is known to be mediated by upstream mechanosensing and downstream signaling, results presented here show the fluidization response to be altogether novel: it is a direct physical effect of mechanical force acting upon a structural lattice that is soft and fragile. Cytoskeletal softness and fragility, we argue, is consistent with early evolutionary adaptations of the eukaryotic cell to material properties of a soft inert microenvironment

Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage

An investigation of the effect of post-injection schemes on soot reduction potential using optical diagnostics in a single-cylinder optical diesel engine

This work employs a combination of pressure trace analysis, high-speed optical measurements and laser-based techniques for the assessment of the effects of various post-injection schemes on the soot reduction potential in an optical single-cylinder light-duty diesel engine. The engine was operated under a multiple injection scheme of two pilot and one main injection, typical of a partially premixed combustion mode, at the lower end of the load and engine speed range (ca 2.0 bar IMEP at 1200 r/min). Experiments considering the influence of the post-injection fuel amount (up to 15% of the total fuel quantity per cycle) and the post-injection timing within the expansion stroke (5, 10 and 15 CAD aTDC), under a constant total fuel mass per cycle, have been conducted. Findings were analysed via means of pressure trace and apparent rate of heat transfer analyses, as well as a series of optical diagnostic techniques, namely, high-speed flame natural luminosity imaging, CH*, C∗2 and OH* line-of-sight chemiluminescence, as well as planar laser-induced incandescence measurements at 31 and 50 CAD aTDC. The combination of post-injection fuel amount and timing has substantial effects on charge reactivity and soot oxidation potential. The analysis reveals that an amount of fuel (7% of the total fuel mass per cycle) injected more than 10 CAD after the main combustion event leads to higher levels of soot emissions, while a larger amount of fuel (15% of the total fuel mass) injected 5 CAD after the main combustion event appears to have a beneficial effect on the soot oxidation processes. Overall, results indicate that a post-injection scheme close to the main combustion phasing could reduce soot levels and improve engine performance, that is, higher IMEP levels at the same fuel consumption rates, although it could increase engine noise