Search

Personality traits and cardiorespiratory fitness in older adults are reliable predictors of health and longevity. We examined the association between personality traits and energy expenditure at rest (basal metabolic rate) and during normal and maximal sustained walking. Personality traits and oxygen (VO(2)) consumption were assessed in 642 participants from the Baltimore Longitudinal Study of Aging. Results indicate that personality traits were mostly unrelated to resting metabolic rate and energy expenditure at normal walking pace. However, those who scored lower on neuroticism (r = -0.12) and higher on extraversion (r = 0.11), openness (r = 0.13), and conscientiousness (r = 0.09) had significantly higher energy expenditure at peak walking pace. In addition to greater aerobic capacity, individuals with a more resilient personality profile walked faster and were more efficient in that they required less energy per meter walked. The associations between personality and energy expenditure were not moderated by age or sex, but were in part explained by the proportion of fat mass. In conclusion, differences in personality may matter the most during more challenging activities that require cardiorespiratory fitness. These findings suggest potential pathways that link personality to health outcomes, such as obesity and longevity.

In the BACHD mouse model of Huntington's disease (HD), deletion of the N17 domain of the Huntingtin gene (BACHDΔN17, Q97) has been reported to lead to nuclear accumulation of mHTT and exacerbation of motor deficits, neuroinflammation and striatal atrophy (Gu et al., 2015). Here we characterized the effect of N17 deletion on dorsolateral striatal medium spiny neurons (MSNs) in BACHDΔN17 (Q97) and BACWTΔN17 (Q31) mice by comparing them to MSNs in wildtype (WT) mice. Mice were characterized on a series of motor tasks and subsequently whole cell patch clamp recordings with simultaneous biocytin filling of MSNs in in vitro striatal slices from these mice were used to comprehensively assess their physiological and morphological features. Key findings include that: Q97 mice exhibit impaired gait and righting reflexes but normal tail suspension reflexes and normal coats while Q31 mice do not differ from WT; intrinsic membrane and action potential properties are altered -but differentially so- in MSNs from Q97 and from Q31 mice; excitatory and inhibitory synaptic currents exhibit higher amplitudes in Q31 but not Q97 MSNs, while excitatory synaptic currents occur at lower frequency in Q97 than in WT and Q31 MSNs; there is a reduced total dendritic length in Q31 -but not Q97- MSNs compared to WT, while spine density and number did not differ in MSNs in the three groups. The findings that Q31 MSNs differed from Q97 and WT neurons with regard to some physiological features and structurally suggest a novel role of the N17 domain in the function of WT Htt. The motor phenotype seen in Q97 mice was less robust than that reported in an earlier study (Gu et al., 2015), and the alterations to MSN physiological properties were largely consistent with changes reported previously in a number of other mouse models of HD. Together this study indicates that N17 plays a role in the modulation of the properties of MSNs in both mHtt and WT-Htt mice, but does not markedly exacerbate HD-like pathogenesis in the BACHD model.

Huntington's Disease (HD) is an autosomal dominant, progressive neurodegenerative disorder caused by deleterious expansion of CAG repeats in the Huntingtin gene and production of neurotoxic mutant Huntingtin protein (mHTT). The key pathological feature of HD is a profound degeneration of the striatum and a loss of cortical volume. The initial loss of indirect pathway (D2) medium spiny neuron (MSN) projections in early stages of HD, followed by a loss of direct pathway (D1) projections in advanced stages has important implications for the trajectory of motor and cognitive dysfunction in HD, but is not yet understood. Mouse models of HD have yielded important information on the effects and mechanisms of mHTT toxicity; however, whether these models recapitulate differential vulnerability of D1 vs. D2 MSNs is unknown. Here, we employed 12-month-old Q175+/- x D2-eGFP mice to examine the detailed structural and functional properties of D1 vs. D2 MSNs. While both D1 and D2 MSNs exhibited increased input resistance, depolarized resting membrane potentials and action potential threshold, only D1 MSNs showed reduced rheobase, action potential amplitude and frequency of spontaneous excitatory postsynaptic currents. Furthermore, D1 but not D2 MSNs showed marked proliferative changes to their dendritic arbors and reductions in spine density. Immunohistochemical assessment showed no loss of glutamatergic afferent inputs from cortical and subcortical sources onto identified D1 and D2 MSNs. Computational models constrained by empirical data predict that the increased dendritic complexity in Q175+/- D1 MSNs likely leads to greater dendritic filtering and attenuation of signals propagating to the soma from the dendrites. Together these findings reveal that, by twelve months, D1 and D2 MSNs exhibit distinctive responses to the presence of mHTT in this important mouse model of HD. This further highlights the need to incorporate findings from D1 and D2 MSNs independently in the context of HD models.

Accurate modeling of enzyme activity and stability is an important goal of the protein engineering community. However, studies seeking to evaluate current progress are limited by small data sets of quantitative kinetic constants and thermal stability measurements. Here, we report quantitative measurements of soluble protein expression in E. coli, thermal stability, and Michaelis-Menten constants (kcat, KM, and kcat/KM) for 129 designed mutants of a glycoside hydrolase. Statistical analyses reveal that functional Tm is independent of kcat, KM, and kcat/KM in this system, illustrating that an individual mutation can modulate these functional parameters independently. In addition, this data set is used to evaluate computational predictions of protein stability using the established Rosetta and FoldX algorithms. Predictions for both are found to correlate only weakly with experimental measurements, suggesting improvements are needed in the underlying algorithms.