Quantitative Gait Analysis Using a Motorized Treadmill System Sensitively Detects Motor Abnormalities in Mice Expressing ATPase Defective Spastin

The hereditary spastic paraplegias (HSPs) are genetic conditions in which there is progressive axonal degeneration in the corticospinal tract. Autosomal dominant mutations, including nonsense, frameshift and missense changes, in the gene encoding the microtubule severing ATPase spastin are the most common cause of HSP in North America and northern Europe. In this study we report quantitative gait analysis using a motorized treadmill system, carried out on mice knocked-in for a disease-associated mutation affecting a critical residue in the Walker A motif of the spastin ATPase domain. At 4 months and at one year of age homozygous mutant mice had a number of abnormal gait parameters, including in stride length and stride duration, compared to heterozygous and wild-type littermates. Gait parameters in heterozygous animals did not differ from wild-type littermates. We conclude that quantitative gait analysis using the DigiGait system sensitively detects motor abnormalities in a hereditary spastic paraplegia model, and would be a useful method for analyzing the effects of pharmacological treatments for HSP.     

Circadian Rhythms in 6-Sulphatoxymelatonin and Nocturnal Sleep in Blind Children

This article describes the relationship between melatonin secretion and sleep quality and subjective complaints about sleep in totally blind children. Eleven boarding-school children (mean age 15.2 years) participated. The major urinary melatonin metabolite 6-sulphatoxymelatonin (aMT6s) was measured five times a day for 48 h. Sleep-wake cycles were recorded by continuous actigraphic recordings during the same time period. Results showed that delayed secretory peaks in aMT6s were significantly associated with disturbed nocturnal sleep and with complaints about morning fatigue.     

The law of the sea and the prospects for deep seabed mining: The position of the European community

This article explores the options that the Norwegian government has when it comes to the management of harvesting a new resource (redfeed) in the politically tense area surrounding Svalbard. The article argues that, by preparing a blueprint regime solely for redfeed rather than allowing the resource to be a catalyst for conflict, the impacts of introducing the fishery will be less dramatic.     

BRAF Drives Synovial Fibroblast Transformation in Rheumatoid Arthritis

Synovial fibroblasts destroy articular cartilage and bone in rheumatoid arthritis, but the mechanism of fibroblast transformation remains elusive. Because gain-of-function mutations of BRAF can transform fibroblasts, we examined BRAF in rheumatoid synovial fibroblasts. The strong gain-of-function mutation, V600R, of BRAF found in melanomas and other cancers was identified in first passage synovial fibroblasts from two of nine rheumatoid arthritis patients and confirmed by restriction site mapping. BRAF-specific siRNA inhibited proliferation of synovial fibroblasts with V600R mutations. A BRAF aberrant splice variant with an intact kinase domain and partial loss of the N-terminal autoinhibitory domain was identified in fibroblasts from an additional patient, and fibroblast proliferation was inhibited by BRAF-specific siRNA. Our finding is the first to establish mechanisms for fibroblast transformation responsible for destruction of articular cartilage and bone in rheumatoid arthritis and establishes a new target for therapeutic intervention.     

Using Co-Occurrence to Evaluate Belief Coherence in a Large Non Clinical Sample

Much of the recent neuropsychological literature on false beliefs (delusions) has tended to focus on individual or single beliefs, with few studies actually investigating the relationship or co-occurrence between different types of co-existing beliefs. Quine and Ullian proposed the hypothesis that our beliefs form an interconnected web in which the beliefs that make up that system must somehow “cohere” with one another and avoid cognitive dissonance. As such beliefs are unlikely to be encapsulated (i.e., exist in isolation from other beliefs). The aim of this preliminary study was to empirically evaluate the probability of belief co-occurrence as one indicator of coherence in a large sample of subjects involving three different thematic sets of beliefs (delusion-like, paranormal & religious, and societal/cultural). Results showed that the degree of belief co-endorsement between beliefs within thematic groupings was greater than random occurrence, lending support to Quine and Ullian’s coherentist account. Some associations, however, were relatively weak, providing for well-established examples of cognitive dissonance.     

The 50s Cliff: Perceptuo-Motor Learning Rates across the Lifespan

We recently found that older adults show reduced learning rates when learning a new pattern of coordinated rhythmic movement. The purpose of this study was to extend that finding by examining the performance of all ages across the lifespan from the 20 s through to the 80 s to determine how learning rates change with age. We tested whether adults could learn to produce a novel coordinated rhythmic movement (90° relative phase) in a visually guided unimanual task. We determined learning rates to quantify changes in learning with age and to determine at what ages the changes occur. We found, as before, that learning rates of participants in their 70 s and 80 s were half those of participants in their 20 s. We also found a gradual slow decline in learning rate with age until approximately age 50, when there was a sudden drop to a reduced learning rate for the 60 though 80 year olds. We discuss possible causes for the “50 s cliff” in perceptuo-motor learning rates and suggest that age related deficits in perception of complex motions may be the key to understanding this result.