Current and Future Treatment of Mucopolysaccharidosis (MPS) Type II: Is Brain-Targeted Stem Cell Gene Therapy the Solution for This Devastating Disorder?

Mucopolysaccharidosis type II (Hunter Syndrome) is a rare, x-linked recessive, progressive, multi-system, lysosomal storage disease caused by the deficiency of iduronate-2-sulfatase (IDS), which leads to the pathological storage of glycosaminoglycans in nearly all cell types, tissues and organs. The condition is clinically heterogeneous, and most patients present with a progressive, multi-system disease in their early years. This article outlines the pathology of the disorder and current treatment strategies, including a detailed review of haematopoietic stem cell transplant outcomes for MPSII. We then discuss haematopoietic stem cell gene therapy and how this can be employed for treatment of the disorder. We consider how preclinical innovations, including novel brain-targeted techniques, can be incorporated into stem cell gene therapy approaches to mitigate the neuropathological consequences of the condition

What helps Christians grow? An exploratory study distinguishing among four distinctive pathways

This study draws on a detailed survey completed by 1,123 churchgoers attending churches within the West Midlands region of England in order to identify indicators of Christian growth and distinctive pathways to growth. Factor and reliability analyses distinguished between two indicators of Christian growth (depth of discipleship and strength of vocation) and four distinctive pathways to growth (growth through group activity, growth through Christian experience, growth through church worship, and growth through public engagement). Regression analyses, taking into account individual differences in sex, age, education, church support and challenges to faith, identified growth through Christian experience as the most important factor in helping Christians to grow, while public engagement added weight to depth of discipleship and group activities added weight to strength of vocation. The implications of these findings are discussed for future research and for Discipleship Learning programmes within the Church

Interacting anyons in topological quantum liquids: The golden chain

We discuss generalizations of quantum spin Hamiltonians using anyonic degrees of freedom. The simplest model for interacting anyons energetically favors neighboring anyons to fuse into the trivial (`identity') channel, similar to the quantum Heisenberg model favoring neighboring spins to form spin singlets. Numerical simulations of a chain of Fibonacci anyons show that the model is critical with a dynamical critical exponent z=1, and described by a two-dimensional conformal field theory with central charge c=7/10. An exact mapping of the anyonic chain onto the two-dimensional tricritical Ising model is given using the restricted-solid-on-solid (RSOS) representation of the Temperley-Lieb algebra. The gaplessness of the chain is shown to have topological origin.Comment: 5 pages, 4 figure

Characterisation of the sarcomeric myosin heavy chain multigene family in the laboratory guinea pig

BACKGROUND:Several chronic conditions leading to skeletal muscle dysfunction are known to be associated with changes in the expression of myosin heavy chain (MHC) isoforms at both the mRNA and protein level. Many of these conditions are modelled, pre-clinically, in the guinea pig due to similar disease onset and progression to the human condition, and their generally well-characterised anatomy. MHC composition is amenable to determination by protein and mRNA based methodologies, the latter quantifying the expression of MHC isoform-specific gene transcripts allowing the detection of earlier, and more subtle changes. As such, the MHC mRNAs, and specific oligonucleotide primers of all common laboratory species have been available for some time. However, due to incomplete genomic annotation, assessment of guinea pig MHC mRNA expression has not been previously possible, precluding the full characterisation of early changes in skeletal muscle in response to disease and disease modulation.The purpose of this study was to characterise the multigenic structure of the sarcomeric MHC family in the guinea pig, and to design and validate specific oligonucleotide primers to enable the assessment of the predominant adult-muscle associated MHC mRNAs in relevant disease models.RESULTS:Using a combination of ligase-mediated rapid amplification of 5' and 3' cDNA ends (RACE) and bioinformatics, mRNAs to the four main skeletal-muscle isoforms of MHC were determined. Specific oligonucleotide primers were designed, and following verification of their specificity, found to successfully determine the expression of each MHC mRNA independently.CONCLUSIONS:Because of their utilisation in the in vivo modelling of disease, there is a requirement to develop molecular methods that accurately differentiate the different MHC mRNAs in the guinea pig to enable rapid profiling of muscle composition in appropriate disease models. The methods developed here are suitable for the characterisation of muscle MHC expression at the molecular level from animal tissue samples and biopsy material. The publication of these specific oligonucleotide primers for the guinea pig MHC variants will enable researchers to rapidly and accurately quantify acute changes in MHC mRNA expression in either developmental or in guinea pig disease models where a marker of altered skeletal muscle function is required

Improving the LSST dithering pattern and cadence for dark energy studies

The Large Synoptic Survey Telescope (LSST) will explore the entire southern sky over 10 years starting in 2022 with unprecedented depth and time sampling in six filters, $ugrizy$. Artificial power on the scale of the 3.5 deg LSST field-of-view will contaminate measurements of baryonic acoustic oscillations (BAO), which fall at the same angular scale at redshift $z \sim 1$. Using the HEALPix framework, we demonstrate the impact of an "un-dithered" survey, in which $17\%$ of each LSST field-of-view is overlapped by neighboring observations, generating a honeycomb pattern of strongly varying survey depth and significant artificial power on BAO angular scales. We find that adopting large dithers (i.e., telescope pointing offsets) of amplitude close to the LSST field-of-view radius reduces artificial structure in the galaxy distribution by a factor of $\sim$10. We propose an observing strategy utilizing large dithers within the main survey and minimal dithers for the LSST Deep Drilling Fields. We show that applying various magnitude cutoffs can further increase survey uniformity. We find that a magnitude cut of $r < 27.3$ removes significant spurious power from the angular power spectrum with a minimal reduction in the total number of observed galaxies over the ten-year LSST run. We also determine the effectiveness of the observing strategy for Type Ia SNe and predict that the main survey will contribute $\sim$100,000 Type Ia SNe. We propose a concentrated survey where LSST observes one-third of its main survey area each year, increasing the number of main survey Type Ia SNe by a factor of $\sim$1.5, while still enabling the successful pursuit of other science drivers.Comment: 9 pages, 6 figures, published in SPIE proceedings; corrected typo in equation

Novel methods for spatial prediction of soil functions within landscapes (SP0531)

Previous studies showed that soil patterns could be predicted in agriculturally managed landscapes by modelling and extrapolating from extensive existing but related integrated datasets. Based on these results we proposed to develop and apply predictive models of the relationships between environmental data and known soil patterns to predict capacity for key soil functions within diverse landscapes for which there is little detailed underpinning soil information available. Objectives were: To develop a high-level framework in which the non-specialist user-community could explore questions. To generate digital soil maps for three selected catchments at a target resolution of 1:50000 to provide the base information for soil function prediction. To use a modelling approach to predict the performance of key soil functions in catchments undergoing change but where only sparse or low resolution soil survey data are available. To use a modelling approach to assess the impact of different management scenarios and/or environmental conditions on the delivery of multiple soil functions within a catchment. To create a detailed outline of the requirements for ground-truthing to test the predicted model outputs at a catchment scale. To contribute to the development of a high-level framework for decision makers

An optical fiber hydrogen sensor using a palladium-coated ball lens

A self-referenced optical fiber refractometer using a ball lens as a sensor head has been developed and characterized. A 350-μm ball lens created at the tip of a single mode fiber has been coated with a 40-nm optically thin layer of palladium that reacts with hydrogen to form a hydride, which has a lower reflectivity than pure palladium. Optical reflectance measurements from the tip of the ball lens were performed to determine the hydrogen response. The change in reflectivity is proportional to the hydrogen concentration in the range 0% to 1% hydrogen in air with a detection limit down to 10 ppm (1σ) in air. This technique offers a simple sensor head arrangement, with a larger sampling area (~40 times) than a typical single-mode fiber core. A statistical image analysis of a palladium film, with cracks created by accelerated failure, confirms that the anticipated sensor area for a ball lens sensor head has a more predictable reflectivity than that of a bare fiber core

The role of microRNAs in glucocorticoid action - literature review

Glucocorticoids (GCs) are steroids with profound anti-inflammatory and immunomodulatory activities. Synthetic GCs are widely used for managing chronic inflammatory and autoimmune conditions, as immunosuppressants in transplantation, and as antitumor agents in certain hematological cancers. However, prolonged GC exposure can cause adverse effects. A detailed understanding of GCs' mechanisms of action may enable harnessing of their desirable actions while minimizing harmful effects. Here, we review the impact on GC biology of microRNAs, small noncoding RNAs that posttranscriptionally regulate gene expression. Emerging evidence indicates that microRNAs modulate GC production by the adrenal glands and cells' responses to GCs. Furthermore, GCs influence cell proliferation, survival, and function at least in part by regulating microRNA expression. We propose that the beneficial effects of GCs may be enhanced through combination with reagents targeting specific microRNAs