Modelling and inference reveal nonlinear length-dependent suppression of somatic instability for small disease associated alleles in myotonic dystrophy type 1 and Huntington disease

More than 20 human genetic diseases are associated with inheriting an unstable expanded DNA simple sequence tandem repeat, for example, CTG (cytosine–thymine–guanine) repeats in myotonic dystrophy type 1 (DM1) and CAG (cytosine–adenine–guanine) repeats in Huntington disease (HD). These sequences mutate by changing the number of repeats not just between generations, but also during the lifetime of affected individuals. Levels of somatic instability contribute to disease onset and progression but as changes are tissue-specific, age- and repeat length-dependent, interpretation of the level of somatic instability in an individual is confounded by these considerations. Mathematical models, fitted to CTG repeat length distributions derived from blood DNA, from a large cohort of DM1-affected or at risk individuals, have recently been used to quantify inherited repeat lengths and mutation rates. Taking into account age, the estimated mutation rates are lower than predicted among individuals with small alleles (inherited repeat lengths less than 100 CTGs), suggesting that these rates may be suppressed at the lower end of the disease-causing range. In this study, we propose that a length-specific effect operates within this range and tested this hypothesis using a model comparison approach. To calibrate the extended model, we used data derived from blood DNA from DM1 individuals and, for the first time, buccal DNA from HD individuals. In a novel application of this extended model, we identified individuals whose effective repeat length, with regards to somatic instability, is less than their actual repeat length. A plausible explanation for this distinction is that the expanded repeat tract is compromised by interruptions or other unusual features. We quantified effective length for a large cohort of DM1 individuals and showed that effective length better predicts age of onset than inherited repeat length, thus improving the genotype–phenotype correlation. Under the extended model, we removed some of the bias in mutation rates making them less length-dependent. Consequently, rates adjusted in this way will be better suited as quantitative traits to investigate cis- or trans-acting modifiers of somatic mosaicism, disease onset and progression.     

Designing to Facilitate Browsing: A Look Back at the Hyperties Workstation Browser

Since browsing hypertext can present a formidable cognitive challenge, user interface design plays a major role in determining acceptability. In the Unix workstation version of Hyperties, a research-oriented prototype, we focussed on design features that facilitate browsing. We first give a general overview of Hyperties and its markup language. Customizable documents can be generated by the conditional text feature that enables dynamic and selective display of text and graphics. In addition we present: — an innovative solution to link identification: pop-out graphical buttons of arbitrary shape.

— application of pie menus to permit low cognitive load actions that reduce the distraction of common actions, such as page turning or window selection.

— multiple window selection strategies that reduce clutter and housekeeping effort. We preferred piles-of-tiles, in which standard-sized windows were arranged in a consistent pattern on the display and actions could be done rapidly, allowing users to concentrate on the contents.

     

Evaluation of ascorbic acid and sugar degradation products during fruit dessert processing under conventional or ohmic heating treatment

The effects of conventional heating (C) or ohmic heating (O) treatment on the degradation of sugar and ascorbic acid (AA) were evaluated in chunky fruit desserts prepared with apple puree (Golden Delicious var.) and chunky peach (Panavi var.) pieces. Concentrations of 5-HMF, furfural (F), 3-hydroxy-2-pyrone (3H2P) and 2-furoic acid (FA) were determined to assess the importance of oxidative and/or thermal reactions during processing. Depending on the thermal processing, 5-HMF and F levels in samples ranged from not detected to 3260 and from not detected to 570 μg/100 g FW respectively. Production of 3H2P and FA ranged from 480 to 2670 and from 84 to 420 μg/100 g FW respectively. Results showed that the impact of final heating treatment on the formation of AA degradation products (3H2P and FA) was minor, if any. Thus, AA degradation during apple products processing mainly depended on oxidative reactions pathway. Likewise, ohmic heating processing had very little effect on the formation of 5-HMF and F, in opposite to conventional heating.     

Intergranular Oxidation of Nickel-Base Alloys: Potentialities of Focused Ion Beam Tomography

Oxidation of Metals - The present work focuses on the intergranular oxidation of Alloy 600 and its weld material Alloy 82 after exposure in simulated primary water at 340–360 °C...     

Electrosynthesis of hierarchical Cu2O–Cu(OH)2 nanodendrites supported on carbon nanofibers/poly(para-phenylenediamine) nanocomposite as high-efficiency catalysts for methanol electrooxidation

The development of highly efficient catalysts using inexpensive and earth-abundant metals is a crucial factor in a large-scale commercialization of direct methanol fuel cells (DMFCs). In this study, we explored a new catalyst based on copper nanodendrites (CuNDs) supported on carbon nanofibers/poly (para-phenylenediamine) (CNF/PpPD) nanocomposite for methanol oxidation reaction (MOR). The catalyst support was prepared on a carbon paste electrode by electropolymerization of para-phenylenediamine monomer on a drop-cast carbon nanofibers network. Afterwards, CuNDs were electrodeposited on the nanocomposite through a potentiostatic method. The morphology and the structure of the prepared nanomaterials were characterized by transmission electron microscope, scanning electron microscope, energy dispersive X-ray, X-ray diffraction, and X-ray photoelectron spectroscope. The results suggested that a three-dimensional nanodendritic structure consisting of Cu₂O and Cu(OH)₂ formed on the hybrid CNF/PpPD nanocomposite. The catalytic performance of CuNDs supported on CNF, PpPD and CNF/PpPD was evaluated for MOR under alkaline conditions. The CNF/PpPD/CuNDs exhibits a highest activity (50 mA cm^?2) and stability toward MOR over 6 h, with respect to CNF/CuNDs (40 mA cm^?2) and PpPD/CuNDs (36 mA cm^?2). This inexpensive catalyst with high catalytic activity and stability is a promising anode catalyst for alkaline DMFC applications.     

Sources and Bioactive Properties of Conjugated Dietary Fatty Acids

The group of conjugated fatty acids known as conjugated linoleic acid (CLA) isomers have been extensively studied with regard to their bioactive potential in treating some of the most prominent human health malignancies. However, CLA isomers are not the only group of potentially bioactive conjugated fatty acids currently undergoing study. In this regard, isomers of conjugated α‐linolenic acid, conjugated nonadecadienoic acid and conjugated eicosapentaenoic acid, to name but a few, have undergone experimental assessment. These studies have indicated many of these conjugated fatty acid isomers commonly possess anti‐carcinogenic, anti‐adipogenic, anti‐inflammatory and immune modulating properties, a number of which will be discussed in this review. The mechanisms through which these bioactivities are mediated have not yet been fully elucidated. However, existing evidence indicates that these fatty acids may play a role in modulating the expression of several oncogenes, cell cycle regulators, and genes associated with energy metabolism. Despite such bioactive potential, interest in these conjugated fatty acids has remained low relative to the CLA isomers. This may be partly attributed to the relatively recent emergence of these fatty acids as bioactives, but also due to a lack of awareness regarding sources from which they can be produced. In this review, we will also highlight the common sources of these conjugated fatty acids, including plants, algae, microbes and chemosynthesis.     

Inactivation efficacy of plasma-activated water: influence of plasma treatment time,exposure time and bacterial species

This study aimed to evaluate the influence of plasma treatment time, bacterial exposure time to PAW and bacterial species on the inactivation efficacy of plasma-activated water (PAW), with additional investigation of the inactivation mechanisms of PAW. Six bacterial species, including Listeria innocua, Staphyloccus aureus, Escherichia coli, Pseudomonas fluorescens, Shewanella putrefaciens and Aeromonas hydrophila were selected as the representative bacteria. The initial bacterial concentration was around 7 log CFU ml⁻¹ after mixing with PAW, and the inactivation efficacy was measured after different exposure times during the 4 °C storage. Scanning electron microscopy (SEM) images of the bacteria after PAW treatment were carried out to inspect the cell structure damage, and physicochemical properties of PAW, including pH, conductivity and long-living reactive species of H₂O₂, , and , were examined. The results showed that the inactivation efficacy of PAW was positively correlated with plasma treatment time and bacterial exposure time, and for the species examined in this study, the Gram-negative species were more sensitive to PAW than the Gram-positive species. Cell structure damage, including shrinkage, distortion, or holes, was observed after PAW treatment. The pH of PAW was acidified to 2.5–2.9, and conductivity was significantly increased to 518.0 μs cm⁻¹. and H₂O₂ were reduced during the 48 h storage, while an increased concentration was observed for . This study demonstrated that the processing parameters of plasma treatment time, exposure time and characteristics of bacteria can significantly affect the inactivation efficacy of PAW.