Walking with Music Is a Safe and Viable Tool for Gait Training in Parkinson's Disease: The Effect of a 13-Week Feasibility Study on Single and Dual Task Walking

This study explored the viability and efficacy of integrating cadence-matched, salient music into a walking intervention for patients with Parkinson's disease (PD). Twenty-two people with PD were randomised to a control (CTRL, n = 11) or experimental (MUSIC, n = 11) group. MUSIC subjects walked with an individualised music playlist three times a week for the intervention period. Playlists were designed to meet subject's musical preferences. In addition, the tempo of the music closely matched (±10–15 bpm) the subject's preferred cadence. CTRL subjects continued with their regular activities during the intervention. The effects of training accompanied by “walking songs” were evaluated using objective measures of gait score. The MUSIC group improved gait velocity, stride time, cadence, and motor symptom severity following the intervention. This is the first study to demonstrate that music listening can be safely implemented amongst PD patients during home exercise

Cell-Type Specific Roles for PTEN in Establishing a Functional Retinal Architecture

BACKGROUND: The retina has a unique three-dimensional architecture, the precise organization of which allows for complete sampling of the visual field. Along the radial or apicobasal axis, retinal neurons and their dendritic and axonal arbors are segregated into layers, while perpendicular to this axis, in the tangential plane, four of the six neuronal types form patterned cellular arrays, or mosaics. Currently, the molecular cues that control retinal cell positioning are not well-understood, especially those that operate in the tangential plane. Here we investigated the role of the PTEN phosphatase in establishing a functional retinal architecture. METHODOLOGY/PRINCIPAL FINDINGS: In the developing retina, PTEN was localized preferentially to ganglion, amacrine and horizontal cells, whose somata are distributed in mosaic patterns in the tangential plane. Generation of a retina-specific Pten knock-out resulted in retinal ganglion, amacrine and horizontal cell hypertrophy, and expansion of the inner plexiform layer. The spacing of Pten mutant mosaic populations was also aberrant, as were the arborization and fasciculation patterns of their processes, displaying cell type-specific defects in the radial and tangential dimensions. Irregular oscillatory potentials were also observed in Pten mutant electroretinograms, indicative of asynchronous amacrine cell firing. Furthermore, while Pten mutant RGC axons targeted appropriate brain regions, optokinetic spatial acuity was reduced in Pten mutant animals. Finally, while some features of the Pten mutant retina appeared similar to those reported in Dscam-mutant mice, PTEN expression and activity were normal in the absence of Dscam. CONCLUSIONS/SIGNIFICANCE: We conclude that Pten regulates somal positioning and neurite arborization patterns of a subset of retinal cells that form mosaics, likely functioning independently of Dscam, at least during the embryonic period. Our findings thus reveal an unexpected level of cellular specificity for the multi-purpose phosphatase, and identify Pten as an integral component of a novel cell positioning pathway in the retina

Modified Cav1.4 Expression in the Cacna1fnob2 Mouse Due to Alternative Splicing of an ETn Inserted in Exon 2

The Cacna1fnob2 mouse is reported to be a naturally occurring null mutation for the Cav1.4 calcium channel gene and the phenotype of this mouse is not identical to that of the targeted gene knockout model. We found two mRNA species in the Cacna1fnob2 mouse: approximately 90% of the mRNA represents a transcript with an in-frame stop codon within exon 2 of CACNA1F, while approximately 10% of the mRNA represents a transcript in which alternative splicing within the ETn element has removed the stop codon. This latter mRNA codes for full length Cav1.4 protein, detectable by Western blot analysis that is predicted to differ from wild type Cav1.4 protein in a region of approximately 22 amino acids in the N-terminal portion of the protein. Electrophysiological analysis with either mouse Cav1.4wt or Cav1.4nob2 cDNA revealed that the alternatively spliced protein does not differ from wild type with respect to activation and inactivation characteristics; however, while the wild type N-terminus interacted with filamin proteins in a biochemical pull-down experiment, the alternatively spliced N-terminus did not. The Cacna1fnob2 mouse electroretinogram displayed reduced b-wave and oscillatory potential amplitudes, and the retina was morphologically disorganized, with substantial reduction in thickness of the outer plexiform layer and sprouting of bipolar cell dendrites ectopically into the outer nuclear layer. Nevertheless, the spatial contrast sensitivity (optokinetic response) of Cacna1fnob2 mice was generally similar to that of wild type mice. These results suggest the Cacna1fnob2 mouse is not a CACNA1F knockout model. Rather, alternative splicing within the ETn element can lead to full-length Cav1.4 protein, albeit at reduced levels, and the functional Cav1.4 mutant may be incapable of interacting with cytoskeletal filamin proteins. These changes, do not alter the ability of the Cacna1fnob2 mouse to detect and follow moving sine-wave gratings compared to their wild type counterparts

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Phenotyping the retina using the behavioural optokinetic response

Bibliography: p. 111-121Some pages are in colour

Depressive-like behaviour of mice lacking cellular prion protein

Cellular Prion Protein (PrP(C)) is known to mediate a protective role in several neurological conditions such as ischemia and epilepsy. However, so far, little information is available concerning the role of PrP(C) in psychiatric disorders such as depression. Here, we have used PrP(C) null mice to examine a putative role of PrP(C) in depressive-like states. Prion protein null mice exhibited depressive-like behaviour when compared to wild-type mice in both the Forced Swimming Test (FST) and Tail Suspension Test (TST). The clinical antidepressant drug imipramine and the NMDA receptor antagonist MK-801 reversed the depressive-like behaviour observed for knockout mice in the TST. The present data thus indicate that PrP(C) exerts a critical role in modulating the depressive-like state in mice, reinforcing the notion that PrP(C) might be associated with alterations in mood disorder states, and suggests a possible role of PrP(C) as a potential drug target for treating depressive disorders

Walking with Music Is a Safe and Viable Tool for Gait Training inParkinson's Disease: The Effect of a 13-Week Feasibility Study onSingle and Dual Task Walking

This study explored the viability and efficacy of integrating cadence-matched, salient music into a walking intervention for patients with Parkinson's disease (PD). Twenty-two people with PD were randomised to a control (CTRL, n=11) or experimental (MUSIC, n=11) group. MUSIC subjects walked with an individualised music playlist three times a week for the intervention period. Playlists were designed to meet subject's musical preferences. In addition, the tempo of the music closely matched (±10–15 bpm) the subject's preferred cadence. CTRL subjects continued with their regular activities during the intervention. The effects of training accompanied by “walking songs” were evaluated using objective measures of gait score. The MUSIC group improved gait velocity, stride time, cadence, and motor symptom severity following the intervention. This is the first study to demonstrate that music listening can be safely implemented amongst PD patients during home exercise.Peer Reviewe

No association found between body checking experience and injury or concussion rates in adolescent ice hockey players

Objectives To compare rates of injury and concussion among U-15 (ages 13–14 years) ice hockey players playing in leagues allowing body checking, but who have a varying number of years of body checking experience. Methods This 5-year longitudinal cohort included U-15 ice hockey players playing in leagues where policy allowed body checking. Years of body checking experience were classified based on national/local body checking policy. All ice hockey game-related injuries were identified using a validated injury surveillance methodology. Players with a suspected concussion were referred to a study sport medicine physician. Multiple multilevel Poisson regression analysis was performed, adjusting for important covariates and a random effect at a team level (offset by game exposure hours), to estimate injury and concussion incidence rate ratios (IRRs). Results In total, 1647 players participated, contributing 1842 player-seasons (195 players participating in two seasons). Relative to no body checking experience, no significant differences were found in the adjusted IRRs for game-related injury for players with 1 year (IRR=1.06; 95% CI: 0.77 to 1.45) or 2+ years (IRR=1.16; 95% CI: 0.74 to 1.84) body checking experience. Similarly, no differences were found in the rates of concussion for players with 1 year (IRR=0.92; 95% CI: 0.59 to 1.42) or 2+ years (IRR=0.69; 95% CI: 0.38 to 1.25) body checking experience. Conclusions Among ice hockey players aged 13–14 years participating in leagues permitting body checking, the adjusted rates of all injury and concussion were not significantly different between those that had body checking experience and those that did not. Based on these findings, no association was found between body checking experience and rates of injury or concussion specifically in adolescent ice hockey