The need for muscle co-contraction prior to a landing

In landings from a flight phase the mass centre of an athlete experiences rapid decelerations. This study investigated the extent to which co-contraction is beneficial or necessary in drop landings, using both experimental data and computer simulations. High speed video and force recordings were made of an elite martial artist performing drop landings onto a force plate from heights of 1.2, 1.5 and 1.8 m. Matching simulations of these landings were produced using a planar 8-segment torque-driven subject-specific computer simulation model. It was found that there was substantial co-activation of joint flexor and extensor torques at touchdown in all three landings. Optimisations were carried out to determine whether landings could be effected without any co-contraction at touchdown. The model was not capable of landing from higher than 1.05 m with no initial flexor or extensor activations. Due to the force–velocity properties of muscle, co-contraction with net zero joint torque at touchdown leads to increased extensor torque and decreased flexor torque as joint flexion velocity increases. The same considerations apply in any activity where rapid changes in net joint torque are required, as for example in jumps from a running approach.     

Modeling a viscoelastic gymnastics landing mat during impact

Landing mats that can undergo a large amount of area deformation are now essential for the safe completion of landings in gymnastics. The objective of this study was to develop an analytical model of a landing mat that reproduces the key characteristics of the mat-ground force during impact with minimal simulation run time. A force plate and two high-speed video cameras were used to record the mat deformation during vertical drop testing of a 24-kg impactor. Four increasingly complex point mass spring-damper models, from a single mass spring-damper system, Model 1, to a 3-layer mass spring-damper system, Model 4, were constructed using Matlab to model the mat's behavior during impact. A fifth model composed of a 3-layer mass spring-damper system was developed using visual Nastran 4D. The results showed that Models 4 and 5 were able to match the loading phase of the impact with simulation times of less than 1 second for Model 4 and 28 seconds for Model 5. Both Models 4 and 5 successfully reproduced the key force-time characteristics of the mat-ground interface, such as peak forces, time of peak forces, interpeak minima and initial rates of loading, and could be incorporated into a gymnast-mat model.     

Complete genome sequence of Mycobacterium phlei type strain RIVM601174

Mycobacterium phlei is a rapidly growing nontuberculous Mycobacterium species that is typically nonpathogenic, with few reported cases of human disease. Here we report the whole genome sequence of M. phlei type strain RIVM601174.     

Amyloid-like fibril formation by polyQ proteins: a critical balance between the polyQ length and the constraints imposed by the host protein

Nine neurodegenerative disorders, called polyglutamine (polyQ) diseases, are characterized by the formation of intranuclear amyloid-like aggregates by nine proteins containing a polyQ tract above a threshold length. These insoluble aggregates and/or some of their soluble precursors are thought to play a role in the pathogenesis. The mechanism by which polyQ expansions trigger the aggregation of the relevant proteins remains, however, unclear. In this work, polyQ tracts of different lengths were inserted into a solvent-exposed loop of the β-lactamase BlaP and the effects of these insertions on the properties of BlaP were investigated by a range of biophysical techniques. The insertion of up to 79 glutamines does not modify the structure of BlaP; it does, however, significantly destabilize the enzyme. The extent of destabilization is largely independent of the polyQ length, allowing us to study independently the effects intrinsic to the polyQ length and those related to the structural integrity of BlaP on the aggregating properties of the chimeras. Only chimeras with 55Q and 79Q readily form amyloid-like fibrils; therefore, similarly to the proteins associated with diseases, there is a threshold number of glutamines above which the chimeras aggregate into amyloid-like fibrils. Most importantly, the chimera containing 79Q forms amyloid-like fibrils at the same rate whether BlaP is folded or not, whereas the 55Q chimera aggregates into amyloid-like fibrils only if BlaP is unfolded. The threshold value for amyloid-like fibril formation depends, therefore, on the structural integrity of the β-lactamase moiety and thus on the steric and/or conformational constraints applied to the polyQ tract. These constraints have, however, no significant effect on the propensity of the 79Q tract to trigger fibril formation. These results suggest that the influence of the protein context on the aggregating properties of polyQ disease-associated proteins could be negligible when the latter contain particularly long polyQ tracts.     

TEM-1 beta-lactamase folds in a nonhierarchical manner with transient non-native interactions involving the C-terminal region

The conformational stability and kinetics of refolding and unfolding of the W290F mutant of TEM-1 beta-lactamase have been determined as a function of guanidinium chloride concentration. The activity and spectroscopic properties of the mutant enzyme did not differ significantly from those of the wild type, indicating that the mutation has only a very limited effect on the structure of the protein. The stability of the folded protein is reduced, however, by 5-10 kJ mol-1 relative to that of the molten globule intermediate (H), but the values of the folding rate constants are unchanged, suggesting that Trp-290 becomes organized in its nativelike environment only after the rate-limiting step; i.e., the C-terminal region of the enzyme folds very late. In contrast to the significant increase in fluorescence intensity seen in the dead time (3-4 ms) of refolding of the wild-type protein, no corresponding burst phase was observed with the mutant enzyme, enabling the burst phase to be attributed specifically to the C-terminal Trp-290. This residue is suggested to be buried in a nonpolar environment from which it has to escape during subsequent folding steps. With both proteins, fast early collapse leads to a folding intermediate in which the C-terminal region of the polypeptide chain is trapped in a non-native structure, consistent with a nonhierarchical folding process.     

Effect of starvation and diabetes on the activity of the eukaryotic initiation factor eIF-2 in rat skeletal muscle

The ability of the initiation factor eIF-2 in skeletal muscle extracts to form ternary initiation complexes ([Met-tRNA(f).eIF-2.GDP]) is decreased by either starvation or diabetes. These conditions also impair the ability of muscle extracts to dissociate [eIF-2.GDP], suggesting inhibition of the guanine nucleotide exchange reaction essential for eIF-2 recycling. We could not, however, detect any change in the phosphorylation state of the alpha subunit of eIF-2. This suggests that eIF-2 activity may be regulated in this system by a mechanism not involving its phosphorylation.     

Reversible inhibition of penicillinase by quinacillin: evaluation of mechanisms involving two conformational states of the enzyme.

Staphylococcal penicillinase (EC 3.5.2.6) is shown to undergo partial, fully reversible inactivation of benzylpenicillinase activity on incubation with the substrate quinacillin, the hydrolysis of which follows a corresponding biphasic time-course. The kinetics fit a scheme involving slow isomerization of the enzyme between conformational states that differ in K_m and V_max for quinacillin. The possibility that inactivation is related to formation of a previously observed covalent enzyme-quinacillin conjugate is ruled out because the kinetics of its formation differ from those of inactivation. This implies that the conjugate arises from a state of the enzyme substrate complex present during the normal catalytic cycle. The multiplicity of binding sites found suggests that a reactive catalytic intermediate substitutes several amino-acid side chains during denaturation of the enzyme-quinacillin mixture, thus providing an explanation of earlier results.