Striking Denervation of Neuromuscular Junctions without Lumbar Motoneuron Loss in Geriatric Mouse Muscle

Reasons for the progressive age-related loss of skeletal muscle mass and function, namely sarcopenia, are complex. Few studies describe sarcopenia in mice, although this species is the mammalian model of choice for genetic intervention and development of pharmaceutical interventions for muscle degeneration. One factor, important to sarcopenia-associated neuromuscular change, is myofibre denervation. Here we describe the morphology of the neuromuscular compartment in young (3 month) compared to geriatric (29 month) old female C57Bl/6J mice. There was no significant difference in the size or number of motoneuron cell bodies at the lumbar level (L1–L5) of the spinal cord at 3 and 29 months. However, in geriatric mice, there was a striking increase (by ∼2.5 fold) in the percentage of fully denervated neuromuscular junctions (NMJs) and associated deterioration of Schwann cells in fast extensor digitorum longus (EDL), but not in slow soleus muscles. There were also distinct changes in myofibre composition of lower limb muscles (tibialis anterior (TA) and soleus) with a shift at 29 months to a faster phenotype in fast TA muscle and to a slower phenotype in slow soleus muscle. Overall, we demonstrate complex changes at the NMJ and muscle levels in geriatric mice that occur despite the maintenance of motoneuron cell bodies in the spinal cord. The challenge is to identify which components of the neuromuscular system are primarily responsible for the marked changes within the NMJ and muscle, in order to selectively target future interventions to reduce sarcopenia

Gravitational Wave Detection by Interferometry (Ground and Space)

Significant progress has been made in recent years on the development of gravitational wave detectors. Sources such as coalescing compact binary systems, neutron stars in low-mass X-ray binaries, stellar collapses and pulsars are all possible candidates for detection. The most promising design of gravitational wave detector uses test masses a long distance apart and freely suspended as pendulums on Earth or in drag-free craft in space. The main theme of this review is a discussion of the mechanical and optical principles used in the various long baseline systems in operation around the world - LIGO (USA), Virgo (Italy/France), TAMA300 and LCGT (Japan), and GEO600 (Germany/U.K.) - and in LISA, a proposed space-borne interferometer. A review of recent science runs from the current generation of ground-based detectors will be discussed, in addition to highlighting the astrophysical results gained thus far. Looking to the future, the major upgrades to LIGO (Advanced LIGO), Virgo (Advanced Virgo), LCGT and GEO600 (GEO-HF) will be completed over the coming years, which will create a network of detectors with significantly improved sensitivity required to detect gravitational waves. Beyond this, the concept and design of possible future "third generation" gravitational wave detectors, such as the Einstein Telescope (ET), will be discussed.Comment: Published in Living Reviews in Relativit

A longitudinal study of racing Thoroughbreds: performance during the first years of racing

To develop a profile of the racing careers of Thoroughbred horses in south-eastern Queensland, and to examine factors that affect racing during the first years of racing.A longitudinal study using the racing records of a defined cohort of Thoroughbred horses that were born on or within 12 months following 1 August 1991. Data collection commenced in 1996 and will continue until all horses cease racing. In this paper two measures of performance were examined: race earnings during the first year of racing and cumulative proportion of horses still racing up to 2 years after their first start. Univariable and multivariable methods were used to describe and identify factors associated with the performance of these horses.By 31 July 1997, 1804 horses were enrolled in the study including 916, 701, 152 and 35 horses that first raced at 2, 3, 4 and 5 years of age, respectively. During their first year of racing, half the horses earned no more than A$450 from race earnings, and 710 (39.4%) horses earned no money at all. In comparison to poorly performing horses, well-performing horses were more likely to be male, to have started as 2-year-olds and to have had more starts during this year. Of the horses that first started as 2 and 3-year-olds, only 71 and 46% continued racing for at least 1 and 2 years after their first start, respectively. Length of racing life was associated with performance during the first year of racing (number of starts and average earnings per race), and with sex, date of birth and age at first start.The study confirmed a high wastage among racing Thoroughbreds. As expected, premature retirement from racing was linked to poor performance. During the first year of racing, the race earnings of an estimated 1567 (86.9%) horses were insufficient to cover training costs. The 2-year-old racing cohort outperformed the older racing cohorts in each of the performance measures under investigation. Interpretation of this result, and the long-term effects of 2-year-old racing, was limited by the problem of confounding