A study of physical activity comparing people with Charcot Marie Tooth disease to normal control subjects

PURPOSE: Charcot Marie Tooth disease (CMT) describes a group of hereditary neuropathies that present with distal weakness, wasting and sensory loss. Small studies indicate that people with CMT have reduced daily activity levels. This raises concerns as physical inactivity increases the risk of a range of co- morbidities, an important consideration in the long-term management of this disease. This study aimed to compare physical activity, patterns of sedentary behavior and overall energy expenditure of people with CMT and healthy matched controls. METHODS: We compared 20 people with CMT and 20 matched controls in a comparison of physical activity measurement over seven days, using an activity monitor. Patterns of sedentary behavior were explored through a power law analysis. RESULTS: Results showed a decrease in daily steps taken in the CMT group, but somewhat paradoxically, they demonstrate shorter bouts of sedentary activity and more frequent transitions from sedentary to active behaviors. No differences were seen in energy expenditure or time spent in sedentary, moderate or vigorous activity. CONCLUSION: The discrepancy between energy expenditure and number of steps could be due to higher energy requirements for walking, but also may be due to an over-estimation of energy expenditure by the activity monitor in the presence of muscle wasting. Alternatively, this finding may indicate that people with CMT engage more in activities or movement not related to walking. Implications for Rehabilitation Charcot-Marie-Tooth disease: • People with Charcot-Marie-Tooth disease did not show a difference in energy expenditure over seven days compared to healthy controls, but this may be due to higher energy costs of walking, and/or an over estimation of energy expenditure by the activity monitor in a population where there is muscle wasting. This needs to be considered when interpreting activity monitor data in people with neuromuscular diseases. • Compared to healthy controls, people with Charcot-Marie-Tooth disease had a lower step count over seven days, but exhibited more frequent transitions from sedentary to active behaviors • High Body Mass Index and increased time spent sedentary were related factors that have implications for general health status. • Understanding the profile of physical activity and behavior can allow targeting of rehabilitation interventions to address mobility and fitness

Genomic Determinants of Protein Evolution and Polymorphism in Arabidopsis

Recent results from Drosophila suggest that positive selection has a substantial impact on genomic patterns of polymorphism and divergence. However, species with smaller population sizes and/or stronger population structure may not be expected to exhibit Drosophila-like patterns of sequence variation. We test this prediction and identify determinants of levels of polymorphism and rates of protein evolution using genomic data from Arabidopsis thaliana and the recently sequenced Arabidopsis lyrata genome. We find that, in contrast to Drosophila, there is no negative relationship between nonsynonymous divergence and silent polymorphism at any spatial scale examined. Instead, synonymous divergence is a major predictor of silent polymorphism, which suggests variation in mutation rate as the main determinant of silent variation. Variation in rates of protein divergence is mainly correlated with gene expression level and breadth, consistent with results for a broad range of taxa, and map-based estimates of recombination rate are only weakly correlated with nonsynonymous divergence. Variation in mutation rates and the strength of purifying selection seem to be major drivers of patterns of polymorphism and divergence in Arabidopsis. Nevertheless, a model allowing for varying negative and positive selection by functional gene category explains the data better than a homogeneous model, implying the action of positive selection on a subset of genes. Genes involved in disease resistance and abiotic stress display high proportions of adaptive substitution. Our results are important for a general understanding of the determinants of rates of protein evolution and the impact of selection on patterns of polymorphism and divergence

Natural variation in Populus tremula flowering time gene PtCO2B

Trees dominate terrestrial ecosystems and produce most of the terrestrial biomass, additionally the increasing worldwide demand for timber, pulp and paper and biofuels means trees are of high economical important, consequently the study of trees is important for both ecological and industrial purposes. Dormancy, bud flush and bud set are important traits both ecologically and for breeding purposes, and forest trees display extensive natural variation in these traits for adaptation to the wide range of climates which they inhabit. The candidate genes PtCO2B and PtCO2A are used in an association mapping approach to investigate the natural variation of these traits. The CONSTANS gene is widely known to be involved in photoperiod responsive pathway of flowering in Arabidopsis, and has recently been shown to be involved in flowering and dormancy in Populus. Here the two Populus homologues of CONSTANS are sequenced within a natural population of Populus tremula collected along a latitudinal gradient. The results show that these genes have less nucleotide diversity than other genes studied in the same population, most of the diversity is found in the single intron and that they have an excess of low frequency mutants. These results suggest that the coding region of these genes is conserved and does not tolerate many mutants. Regression analysis showed that none of the polymorphisms found in PtCO2B were associated with any of the phenotypic traits scores within this population. Future phenotyping within this population may find association with other interesting traits involved in the photoperiod pathway

Ethylene- and shade-induced hypocotyl elongation share transcriptome patterns and functional regulators

Plants have evolved shoot elongation mechanisms to escape from diverse environmental stresses such as flooding and vegetative shade. The apparent similarity in growth responses suggests a possible convergence of the signaling pathways. Shoot elongation is mediated by passive ethylene accumulating to high concentrations in flooded plant organs and by changes in light quality and quantity under vegetation shade. Here, we study hypocotyl elongation as a proxy for shoot elongation and delineate Arabidopsis (Arabidopsis thaliana) hypocotyl length kinetics in response to ethylene and shade. Based on these kinetics, we further investigated ethylene- and shade-induced genome-wide gene expression changes in hypocotyls and cotyledons separately. Both treatments induced a more extensive transcriptome reconfiguration in the hypocotyls compared with the cotyledons. Bioinformatics analyses suggested contrasting regulation of growth promotion- and photosynthesis-related genes. These analyses also suggested an induction of auxin, brassinosteroid, and gibberellin signatures and the involvement of several candidate regulators in the elongating hypocotyls. Pharmacological and mutant analyses confirmed the functional involvement of several of these candidate genes and physiological control points in regulating stress-escape responses to different environmental stimuli. We discuss how these signaling networks might be integrated and conclude that plants, when facing different stresses, utilize a conserved set of transcriptionally regulated genes to modulate and fine-tune growth

Ethylene- and shade-induced hypocotyl elongation share transcriptome patterns and functional regulators

Plants have evolved shoot elongation mechanisms to escape from diverse environmental stresses such as flooding and vegetative shade. The apparent similarity in growth responses suggests a possible convergence of the signaling pathways. Shoot elongation is mediated by passive ethylene accumulating to high concentrations in flooded plant organs and by changes in light quality and quantity under vegetation shade. Here, we study hypocotyl elongation as a proxy for shoot elongation and delineate Arabidopsis (Arabidopsis thaliana) hypocotyl length kinetics in response to ethylene and shade. Based on these kinetics, we further investigated ethylene- and shade-induced genome-wide gene expression changes in hypocotyls and cotyledons separately. Both treatments induced a more extensive transcriptome reconfiguration in the hypocotyls compared with the cotyledons. Bioinformatics analyses suggested contrasting regulation of growth promotion- and photosynthesis-related genes. These analyses also suggested an induction of auxin, brassinosteroid, and gibberellin signatures and the involvement of several candidate regulators in the elongating hypocotyls. Pharmacological and mutant analyses confirmed the functional involvement of several of these candidate genes and physiological control points in regulating stress-escape responses to different environmental stimuli. We discuss how these signaling networks might be integrated and conclude that plants, when facing different stresses, utilize a conserved set of transcriptionally regulated genes to modulate and fine-tune growth

Splicing Variation at a FLOWERING LOCUS C Homeolog Is Associated With Flowering Time Variation in the Tetraploid Capsella bursa-pastoris

The long-term fates of duplicate genes are well studied both empirically and theoretically, but how the short-term evolution of duplicate genes contributes to phenotypic variation is less well known. Here, we have studied the genetic basis of flowering time variation in the disomic tetraploid Capsella bursa-pastoris. We sequenced four duplicate candidate genes for flowering time and 10 background loci in samples from western Eurasia and China. Using a mixed-model approach that accounts for population structure, we found that polymorphisms at one homeolog of two candidate genes, FLOWERING LOCUS C (FLC) and CRYPTOCHROME1 (CRY1), were associated with natural flowering time variation. No potentially causative polymorphisms were found in the coding region of CRY1; however, at FLC two splice site polymorphisms were associated with early flowering. Accessions harboring nonconsensus splice sites expressed an alternatively spliced transcript or did not express this FLC homeolog. Our results are consistent with the function of FLC as a major repressor of flowering in Arabidopsis thaliana and imply that nonfunctionalization of duplicate genes could provide an important source of phenotypic variation