Deficits in the way to achieve balance related to mechanisms of dynamic stability control in the elderly

The purpose of this study was to examine the postural corrections related to components of dynamic stability aimed to increase our understanding of successful postural control among the elderly population. This was done by comparing balance behaviour of older adults who were able to recover stability (stable) and others who failed to regain stability (unstable) with a single step after a forward fall. Thirty-eight old male adults (64+/-3yr, 176+/-6cm, 78.5+/-7.8kg) had to recover balance after a sudden induced forward fall. All participants performed maximal isometric ankle plantarflexion and knee extension contractions on a dynamometer. The elongation of the gastrocnemius medialis and the vastus lateralis tendon and aponeuroses during isometric contraction was examined by ultrasonography. There were no differences in leg-extensor muscle strength or tendon stiffness between the two groups showing that the muscle tendon capacities may not be the reason for the observed differences in dynamic stability control. The unstable participants created a higher horizontal ground reaction push-off force of the support limb in the second part ( approximately 260ms after release) of the phase until touchdown leading to an unstable body position at touchdown. The results indicate deficits in the way to achieve balance related to mechanisms responsible for dynamic stability control within the elderly population.     

Superoxide radical formation in diverse organs of rats with experimentally induced obstructive jaundice

Oxidative stress seems to be a cardinal feature of cholestasis, implicated in the pathophysiology of organ injury not only in the liver, but also in several extrahepatic tissues. The present study was designed to assess directly oxidative stress in vital organs of experimentally jaundiced rats by measuring the key oxidative stress marker superoxide radical (O2(*-)). Twelve male Wistar rats underwent laparotomy and were divided into two groups - group I (n = 6) sham operated, and group II (n = 6) bile-duct ligated. Ten days later, the O2(*-) formation rate was quantified in liver, intestine, kidney and heart of all animals. These measurements were done by application of a new ultrasensitive fluorescent assay for the in vivo quantification of O2(*-), which is based on the 1:1 molar stoichiometric reaction of O2(*-) with dihydroethidine (DHE, an O2(*-) trap) that results in the formation of the specific product 2-OH-ethidium. 2-OH-Ethidium was measured by fluorescence in rats' organs and its formation rate was converted to O2(*-) production rate. As compared to sham-operated rats, in jaundiced rats there was a significant increase of O2(*-) in the intestine (136%, P < 0.01), liver (104%, P < 0.01), and kidney (95%, P < 0.01), whereas there was no significant difference in heart O2(*-) levels. Superoxide radical may play an important role in the pathophysiology of cholestatic liver injury, intestinal barrier failure and renal failure, associated with postoperative morbidity and mortality in obstructive jaundice. On the contrary, O2(*-) and oxidative stress are possibly not implicated in the pathophysiology of hepatic cardiomyopathy.     

Hexokinases link DJ-1 to the PINK1/parkin pathway

Background

Hyperexcitability of neuronal networks can lead to excessive release of the excitatory neurotransmitter glutamate, which in turn can cause neuronal damage by overactivating NMDA-type glutamate receptors and related signaling pathways. This process (excitotoxicity) has been implicated in the pathogenesis of many neurological conditions, ranging from childhood epilepsies to stroke and neurodegenerative disorders such as Alzheimer’s disease (AD). Reducing neuronal levels of the microtubule-associated protein tau counteracts network hyperexcitability of diverse causes, but whether this strategy can also diminish downstream excitotoxicity is less clear.

Methods

We established a cell-based assay to quantify excitotoxicity in primary cultures of mouse hippocampal neurons and investigated the role of tau in exicitotoxicity by modulating neuronal tau expression through genetic ablation or transduction with lentiviral vectors expressing anti-tau shRNA or constructs encoding wildtype versus mutant mouse tau.

Results

We demonstrate that shRNA-mediated knockdown of tau reduces glutamate-induced, NMDA receptor-dependent Ca²⁺ influx and neurotoxicity in neurons from wildtype mice. Conversely, expression of wildtype mouse tau enhances Ca²⁺ influx and excitotoxicity in tau-deficient (Mapt ^−/−) neurons. Reconstituting tau expression in Mapt ^−/− neurons with mutant forms of tau reveals that the tau-related enhancement of Ca²⁺ influx and excitotoxicity depend on the phosphorylation of tau at tyrosine 18 (pY18), which is mediated by the tyrosine kinase Fyn. These effects are most evident at pathologically elevated concentrations of glutamate, do not involve GluN2B–containing NMDA receptors, and do not require binding of Fyn to tau’s major interacting PxxP motif or of tau to microtubules.

Conclusions

Although tau has been implicated in diverse neurological diseases, its most pathogenic forms remain to be defined. Our study suggests that reducing the formation or level of pY18-tau can counteract excitotoxicity by diminishing NMDA receptor-dependent Ca²⁺ influx.

     

Acetylation increases access of remodelling complexes to their nucleosome targets to enhance initiation of V(D)J recombination

Targeted chromatin remodelling is essential for many nuclear processes, including the regulation of V(D)J recombination. ATP-dependent nucleosome remodelling complexes are important players in this process whose activity must be tightly regulated. We show here that histone acetylation regulates nucleosome remodelling complex activity to boost RAG cutting during the initiation of V(D)J recombination. RAG cutting requires nucleosome mobilization from recombination signal sequences. Histone acetylation does not stimulate nucleosome mobilization per se by CHRAC, ACF or their catalytic subunit, ISWI. Instead, we find the more open structure of acetylated chromatin regulates the ability of nucleosome remodelling complexes to access their nucleosome templates. We also find that bromodomain/acetylated histone tail interactions can contribute to this targeting at limited concentrations of remodelling complex. We therefore propose that the changes in higher order chromatin structure associated with histone acetylation contribute to the correct targeting of nucleosome remodelling complexes and this is a novel way in which histone acetylation can modulate remodelling complex activity.     

A mathematical high bar–human body model for analysing and interpreting mechanical-energetic processes on the high bar

The aims of this study were:

1. To study the transfer of energy between the high bar and the gymnast.

2. To develop criteria from the utilisation of high bar elasticity and the utilisation of muscle capacity to assess the effectiveness of a movement solution.

3. To study the influence of varying segment movement upon release parameters.

For these purposes a model of the human body attached to the high bar (high bar–human body model) was developed. The human body was modelled using a 15-segment body system. The joint-beam element method (superelement) was employed for modelling the high bar. A superelement consists of four rigid segments connected by joints (two Cardan joints and one rotational–translational joint) and springs (seven rotation springs and one tension–compression spring). The high bar was modelled using three superelements. The input data required for the high bar–human body model were collected with video-kinematographic (50 Hz) and dynamometric (500 Hz) techniques. Masses and moments of inertia of the 15 segments were calculated using the data from the Zatsiorsky et al. (1984) model. There are two major phases characteristic of the giant swing prior to dismounts from the high bar. In the first phase the gymnast attempts to supply energy to the high bar–human body system through muscle activity and to store this energy in the high bar. The difference between the energy transferred to the high bar and the reduction in the total energy of the body could be adopted as a criterion for the utilisation of high bar elasticity. The energy previously transferred into the high bar is returned to the body during the second phase. An advantageous increase in total body energy at the end of the exercise could only be obtained through muscle energy supply. An index characterising the utilisation of muscle capacity was developed out of the difference between the increase in total body energy and the energy returned from the high bar. A delayed and initially slow but even reduction of hip and shoulder angles provided more advantageous release conditions. The total body energy could be improved by up to 15%, the vertical CM release velocity by up to 10% and the angular momentum by up to 35%.     

Differences between measured and resultant joint moments during isometric contractions at the ankle joint

The purpose of this study was to examine two hypotheses: (a) during voluntary and electrically induced isometric contractions the moments measured at the dynamometer are different from the resultant moments in the same plane around the ankle joint and (b) at a given resultant moment during electrically induced isometric contractions the ankle angle while loading is different from the ankle angle while unloading. Twenty-seven long distance runners participated in the study. All subjects performed isometric maximal voluntary contractions (MVC) and contractions induced by electrostimulation at four different ankle-knee angle combinations on a Biodex-dynamometer. The kinematics of the leg were recorded using the vicon 624 system with eight cameras operating at 120 Hz. The main findings were: (a) the resultant moment at the ankle joint and the moment measured by the Biodex-dynamometer during isometric contractions are different, (b) during a plantar flexion effort the ankle angle changes significantly, whereas the knee angle shows only small and in most cases not significant changes, and (c) at identical resultant ankle joint moments the ankle angles are different between the loading and the unloading phases. The observed differences may lead to erroneous conclusions concerning the following: (a) diagnostic of muscle architecture, (b) estimation of the moment-ankle angle relationship and (c) estimation of the strain and hysteresis of tendons and aponeuroses.     

Effects of submaximal and maximal long-lasting contractions on the compliance of vastus lateralis tendon and aponeurosis in vivo

The present study investigated the effects of submaximal sustained and maximal repetitive contractions on the compliance of human vastus lateralis (VL) tendon and aponeurosis in vivo using two different fatiguing protocols. Twelve male subjects performed three maximum voluntary isometric contractions (MVC) of the knee extensors before and after two fatiguing protocols on a dynamometer. The first fatiguing protocol consisted of a long-lasting sustained isometric knee extension contraction at 25% MVC until failure (inability to hold the defined load). The second fatiguing protocol included long-lasting isokinetic (90°/s) knee extension contractions, where maximum moment was exerted and failure was proclaimed when this value fell below 70% of unfatigued maximum isokinetic moment. Ultrasonography was used to determine the elongation and strain of the VL tendon and aponeurosis. Muscle fatigue was indicated by a significant decrease in maximum resultant knee extension moment (p < 0.05) observed during the MVCs after both long-lasting contractions. No significant (p > 0.05) differences in elongation and strain of the VL tendon and aponeurosis were found, when compared every 300 N (tendon force) before and after the fatiguing protocols. The present data indicate, that the VL tendon and aponeurosis in vivo do not suffer from changes in the compliance neither after long-lasting static mechanical loading (strain ～3.2%) nor after long-lasting cyclic mechanical loading (strain 6.2–5.5%).     

Mechanical and morphological properties of human quadriceps femoris and triceps surae muscle-tendon unit in relation to aging and running

The purpose of this study was to examine the effects of aging and endurance running on the mechanical and morphological properties of different muscle-tendon units (MTUs) in vivo. The investigation was conducted on 30 elderly and 19 young adult males. For the analysis of possible MTU adaptation in response to endurance running the subjects were divided into two subgroups: non-active vs. endurance-runners. All subjects performed isometric maximal voluntary plantarflexion and knee extension contractions on a dynamometer. The distal aponeurosis of the gastrocnemius medialis (GM) and vastus lateralis (VL) during plantarflexion and knee extensions and the muscle architecture of the GM and VL were visualized by ultrasonography. The maximal knee and ankle joint moment were higher for the young compared to the elderly population (p<0.05). No identifiable differences in muscle architecture between young and elderly subjects were detected in VL and GM. Aging results in a reduced (p<0.05) normalized stiffness of the quadriceps femoris tendon and aponeurosis, which were not identifiable for the triceps surae. In contrast, the properties of both MTUs showed no major differences between endurance-runners and the non-active group (p>0.05). Only pennation angle at the GM were higher for the runners compared to the non-active group (p<0.05). The present results indicate that tendon changes related to aging do not occur proportionally in different MTUs. Furthermore, it seems that the extra stress and load imposed on high-load-bearing MTUs during endurance running may not be sufficient to produce significant adaptative processes in the mechanical parameters analyzed.     

Reproducibility of energy parameters in the pole vault

The purpose of this study was to analyze the reproducibility of kinematic, dynamometric and derived mechanical energy parameters in the pole vault as a main precondition for the practical applicability of the concept of energy exchange in the pole vault. A total of 46 vaults of six experienced vaulters were analyzed. On the basis of 3D kinematic data of the athlete and the pole and ground reaction forces measured at the end of the pole in the planting box the reproducibility of parameters that describe the energy transfer into the pole and the energy exchange between the athlete and the pole during the vault was proofed. Intraclass correlation, mean root mean square and the coefficient of variance were determined, additionally the Wilcoxon Test was applied. Parameters of the athlete's 3D total mechanical energy, e.g. initial energy and final energy, and the pole energy (maximum pole energy, energy of the pole due to compressive force and bending moment) were highly reproducible. The distribution of the energy transferred into the pole due to compressive force and bending moment, the same as the energy gain of the vaulter-pole system during the vault, which indicates the strategy of interacting with the pole, were also reproducible. With this the concept of energy exchange in the pole vault can be used to analyze the impact of training interventions, changes in movement pattern respectively, on the vaulters performance during different phases of the vault. The analysis of one trial of an athlete should be sufficient to identify changes in the athlete's interaction with the elastic pole.