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

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Pax6 is required intrinsically by thalamic progenitors for the normal molecular patterning of thalamic neurons but not the growth and guidance of their axons

BACKGROUND: In mouse embryos, the Pax6 transcription factor is expressed in the progenitors of thalamic neurons but not in thalamic neurons themselves. Its null-mutation causes early mis-patterning of thalamic progenitors. It is known that thalamic neurons generated by Pax6(−/−) progenitors do not develop their normal connections with the cortex, but it is not clear why. We investigated the extent to which defects intrinsic to the thalamus are responsible. RESULTS: We first confirmed that, in constitutive Pax6(−/−) mutants, the axons of thalamic neurons fail to enter the telencephalon and, instead, many of them take an abnormal path to the hypothalamus, whose expression of Slits would normally repel them. We found that thalamic neurons show reduced expression of the Slit receptor Robo2 in Pax6(−/−) mutants, which might enhance the ability of their axons to enter the hypothalamus. Remarkably, however, in chimeras comprising a mixture of Pax6(−/−) and Pax6(+/+) cells, Pax6(−/−) thalamic neurons are able to generate axons that exit the diencephalon, take normal trajectories through the telencephalon and avoid the hypothalamus. This occurs despite abnormalities in their molecular patterning (they express Nkx2.2, unlike normal thalamic neurons) and their reduced expression of Robo2. In conditional mutants, acute deletion of Pax6 from the forebrain at the time when thalamic axons are starting to grow does not prevent the development of the thalamocortical tract, suggesting that earlier extra-thalamic patterning and /or morphological defects are the main cause of thalamocortical tract failure in Pax6(−/−) constitutive mutants. CONCLUSIONS: Our results indicate that Pax6 is required by thalamic progenitors for the normal molecular patterning of the thalamic neurons that they generate but thalamic neurons do not need normal Pax6-dependent patterning to become competent to grow axons that can be guided appropriately

Changing trends in mastitis

<p>Abstract</p> <p>The global dairy industry, the predominant pathogens causing mastitis, our understanding of mastitis pathogens and the host response to intramammary infection are changing rapidly. This paper aims to discuss changes in each of these aspects. Globalisation, energy demands, human population growth and climate change all affect the dairy industry. In many western countries, control programs for contagious mastitis have been in place for decades, resulting in a decrease in occurrence of <it>Streptococcus agalactiae </it>and <it>Staphylococcus aureus </it>mastitis and an increase in the relative impact of <it>Streptococcus uberis </it>and <it>Escherichia coli </it>mastitis. In some countries, <it>Klebsiella </it>spp. or <it>Streptococcus dysgalactiae </it>are appearing as important causes of mastitis. Differences between countries in legislation, veterinary and laboratory services and farmers' management practices affect the distribution and impact of mastitis pathogens. For pathogens that have traditionally been categorised as contagious, strain adaptation to human and bovine hosts has been recognised. For pathogens that are often categorised as environmental, strains causing transient and chronic infections are distinguished. The genetic basis underlying host adaptation and mechanisms of infection is being unravelled. Genomic information on pathogens and their hosts and improved knowledge of the host's innate and acquired immune responses to intramammary infections provide opportunities to expand our understanding of bovine mastitis. These developments will undoubtedly contribute to novel approaches to mastitis diagnostics and control.</p