Biomechanical properties of bone in a mouse model of Rett syndrome

Rett syndrome (RTT) is an X-linked genetic disorder and a major cause of intellectual disability in girls. Mutations in the methyl-CpG binding protein 2 (<i>MECP2</i>) gene are the primary cause of the disorder. Despite the dominant neurological phenotypes, <i>MECP2</i> is expressed ubiquitously throughout the body and a number of peripheral phenotypes such as scoliosis, reduced bone mineral density and skeletal fractures are also common and important clinical features of the disorder. In order to explore whether MeCP2 protein deficiency results in altered structural and functional properties of bone and to test the potential reversibility of any defects, we have conducted a series of histological, imaging and biomechanical tests of bone in a functional knockout mouse model of RTT. Both hemizygous <i>Mecp2</i><sup>stop/y</sup> male mice in which <i>Mecp2</i> is silenced in all cells and female <i>Mecp2</i><sup>stop/+</sup> mice in which <i>Mecp2</i> is silenced in ~ 50% of cells as a consequence of random X-chromosome inactivation, revealed significant reductions in cortical bone stiffness, microhardness and tensile modulus. Microstructural analysis also revealed alterations in both cortical and cancellous femoral bone between wild-type and MeCP2-deficient mice. Furthermore, unsilencing of <i>Mecp2</i> in adult mice cre-mediated stop cassette deletion resulted in a restoration of biomechanical properties (stiffness, microhardness) towards wild-type levels. These results show that MeCP2-deficiency results in overt, but potentially reversible, alterations in the biomechanical integrity of bone and highlights the importance of targeting skeletal phenotypes in considering the development of pharmacological and gene-based therapies

Structured Speaker Variability in Spontaneous Japanese Stop Contrast Production

Studies of speaker variability in the realisation of stop voicing contrasts have demonstrated that differences across speakers are highly structured both within and across phonetic categories. These studies have focused on languages with similar voicing systems in scripted speech; it remains unclear how stop realisation varies in spontaneous speech more generally. This study examines speaker variability in two acoustic cues to stop voicing–Voice Onset Time and Voicing During Closure–in a corpus of spontaneous Japanese, a language undergoing change in its voicing contrast. Whilst speakers vary in both measures, this variability is highly structured: speakers with less aspirated stops are more likely to initiate voicing during the closure. However, no corresponding relationship is observed between how the two cues are used to mark the contrast. These findings extend previous work to demonstrate the structure of speaker variability in spontaneous speech

Toward “English” phonetics: variability in the pre-consonantal voicing effect across English dialects and speakers

Recent advances in access to spoken-language corpora and development of speech processing tools have made possible the performance of “large-scale” phonetic and sociolinguistic research. This study illustrates the usefulness of such a large-scale approach—using data from multiple corpora across a range of English dialects, collected, and analyzed with the SPADE project—to examine how the pre-consonantal Voicing Effect (longer vowels before voiced thanvoiceless obstruents, in e.g., bead vs. beat) is realized in spontaneous speech, and varies across dialects and individual speakers. Compared with previous reports of controlled laboratory speech, the Voicing Effect was found to be substantially smaller in spontaneous speech, but still influenced by the expected range of phonetic factors. Dialects of English differed substantially from each other in the size of the Voicing Effect, whilst individual speakers varied little relative to their particular dialect. This study demonstrates the value of large-scale phonetic research as a means of developing our understanding of the structure of speech variability, and illustrates how large-scale studies, such as those carried out within SPADE, can be applied to other questions in phonetic and sociolinguistic research

Toward “English” phonetics: variability in the pre-consonantal voicing effect across English dialects and speakers

Recent advances in access to spoken-language corpora and development of speech processing tools have made possible the performance of “large-scale” phonetic and sociolinguistic research. This study illustrates the usefulness of such a large-scale approach—using data from multiple corpora across a range of English dialects, collected, and analyzed with the SPADE project—to examine how the pre-consonantal Voicing Effect (longer vowels before voiced thanvoiceless obstruents, in e.g., bead vs. beat) is realized in spontaneous speech, and varies across dialects and individual speakers. Compared with previous reports of controlled laboratory speech, the Voicing Effect was found to be substantially smaller in spontaneous speech, but still influenced by the expected range of phonetic factors. Dialects of English differed substantially from each other in the size of the Voicing Effect, whilst individual speakers varied little relative to their particular dialect. This study demonstrates the value of large-scale phonetic research as a means of developing our understanding of the structure of speech variability, and illustrates how large-scale studies, such as those carried out within SPADE, can be applied to other questions in phonetic and sociolinguistic research

Vowel duration and the voicing effect across dialects of English

The ‘voicing effect’ – the durational difference in vowels preceding voiced and voiceless consonants – is a well-documented phenomenon in English, where it plays a key role in the production and perception of the English final voicing contrast. Despite this supposed importance, little is known as to how robust this effect is in spontaneous connected speech, which is itself subject to a range of linguistic factors. Similarly, little attention has focused on variability in the voicing effect across dialects of English, bar analysis of specific varieties. Our findings show that the voicing of the following consonant exhibits a weaker-than-expected effect in spontaneous speech, interacting with manner, vowel height, speech rate, and word frequency. English dialects appear to demonstrate a continuum of potential voicing effect sizes, where varieties with dialect-specific phonological rules exhibit the most extreme values. The results suggest that the voicing effect in English is both substantially weaker than previously assumed in spontaneous connected speech, and subject to a wide range of dialectal variability

Recent advances in understanding resistance exercise training-induced skeletal muscle hypertrophy in humans

Skeletal muscle plays a pivotal role in the maintenance of physical and metabolic health and, critically, mobility. Accordingly, strategies focused on increasing the quality and quantity of skeletal muscle are relevant, and resistance exercise is foundational to the process of functional hypertrophy. Much of our current understanding of skeletal muscle hypertrophy can be attributed to the development and utilization of stable isotopically labeled tracers. We know that resistance exercise and sufficient protein intake act synergistically and provide the most effective stimuli to enhance skeletal muscle mass; however, the molecular intricacies that underpin the tremendous response variability to resistance exercise-induced hypertrophy are complex. The purpose of this review is to discuss recent studies with the aim of shedding light on key regulatory mechanisms that dictate hypertrophic gains in skeletal muscle mass. We also aim to provide a brief up-to-date summary of the recent advances in our understanding of skeletal muscle hypertrophy in response to resistance training in humans

Understanding the effects of nutrition and post-exercise nutrition on skeletal muscle protein turnover: insights from stable isotope studies

Skeletal muscle is the largest organ of the human body and plays a pivotal role in whole-body homeostasis through the maintenance of physical and metabolic health. Establishing strategies aimed at increasing the amount, and minimising loss, of muscle mass are of upmost importance. Muscle mass is primarily dictated by the meal-to-meal fluctuations in muscle protein synthesis (MPS) and muscle protein breakdown (MPB), each of which can be quantified through the use of stable isotopically labelled tracers. Importantly, both MPS and MPB can be influenced by external factors such as nutritional manipulation, specifically protein ingestion, and changes in loading via exercise. To date, research involving stable isotopic tracers has focused on determining the optimal dose, timing surrounding bouts of exercise, distribution and composition of protein to maximally stimulate MPS and inhibit MPB, both at rest and following exercise. In this review we focus on the use of these stable isotopically-labeled tracers to unravel the intricacies of skeletal muscle protein turnover in response to specific nutritional interventions

Bayesian power-spectrum inference for Large Scale Structure data

We describe an exact, flexible, and computationally efficient algorithm for a joint estimation of the large-scale structure and its power-spectrum, building on a Gibbs sampling framework and present its implementation ARES (Algorithm for REconstruction and Sampling). ARES is designed to reconstruct the 3D power-spectrum together with the underlying dark matter density field in a Bayesian framework, under the reasonable assumption that the long wavelength Fourier components are Gaussian distributed. As a result ARES does not only provide a single estimate but samples from the joint posterior of the power-spectrum and density field conditional on a set of observations. This enables us to calculate any desired statistical summary, in particular we are able to provide joint uncertainty estimates. We apply our method to mock catalogs, with highly structured observational masks and selection functions, in order to demonstrate its ability to reconstruct the power-spectrum from real data sets, while fully accounting for any mask induced mode coupling.Comment: 25 pages, 15 figure