Clustering of activated microglia occurs before the formation of dystrophic neurites in the evolution of Aβ plaques in Alzheimer’s disease.

Alzheimer’s disease (AD) is a late-onset disease that has proved difficult to model. Microglia are implicated in AD, but reports vary on precisely when and how in the sequence of pathological changes they become involved. Here, post-mortem human tissue from two differentially affected regions of the AD brain and from non-demented individuals with a high load of AD-type pathology (high pathology controls) was used to model the disease time course in order to determine how microglial activation relates temporally to the deposition of hallmark amyloid-β (Aβ) and hyperphosphorylated microtubule associated protein tau pathology. Immunofluorescence against the pan-microglial marker, ionised calcium-binding adapter molecule 1 (IBA1), Aβ and tau, was performed in the primary motor cortex (PMC), a region relatively spared of AD pathological changes, and compared to the severely affected inferior temporal cortex (ITC) in the same cases. Unlike the ITC, the PMC in the AD cases was spared of any degenerative changes in cortical thickness and the density of Betz cells and total neurons. The clustering of activated microglia was greatest in the PMC of AD cases and high pathology controls compared to the ITC. This suggests microglial activation is most prominent in the early phases of AD pathophysiology. Nascent tau inclusions were found in neuritic plaques in the PMC but were more numerous in the ITC of the same case. This shows that tau positive neuritic plaques begin early in AD which is likely of pathogenic importance, however major tau deposition follows the accumulation of Aβ and clustering of activated microglia. Importantly, findings presented here demonstrate that different states of microglial activation, corresponding to regional accumulations of Aβ and tau, are present simultaneously in the same individual; an important factor for consideration if targeting these cells for therapeutic intervention

Flexible and stretchable power sources for wearable electronics.

Flexible and stretchable power sources represent a key technology for the realization of wearable electronics. Developing flexible and stretchable batteries with mechanical endurance that is on par with commercial standards and offer compliance while retaining safety remains a significant challenge. We present a unique approach that demonstrates mechanically robust, intrinsically safe silver-zinc batteries. This approach uses current collectors with enhanced mechanical design, such as helical springs and serpentines, as a structural support and backbone for all battery components. We show wire-shaped batteries based on helical band springs that are resilient to fatigue and retain electrochemical performance over 17,000 flexure cycles at a 0.5-cm bending radius. Serpentine-shaped batteries can be stretched with tunable degree and directionality while maintaining their specific capacity. Finally, the batteries are integrated, as a wearable device, with a photovoltaic module that enables recharging of the batteries

Techno-economic assessment of poly-3-hydroxybutyrate (PHB) production from methane - the case for thermophilic bioprocessing

A major obstacle preventing the large scale production of polyhydroxyalkanoates (PHAs) has been the lack of a reliable, low cost, large volume feedstock. The abundance and relatively low price of methane therefore marks it as a substrate of interest. This paper presents a techno-economic assessment of the production of poly-3-hydroxybutyrate (PHB) from methane. ASPEN Plus was used for process design and simulation. The design and economic evaluation is presented for production of 100,000 t/a PHB through methanotrophic fermentation and acetone-water solvent extraction. Production costs were estimated at $4.1-$6.8/kg PHA, which compares against a median price of $7.5/kg from other studies. Raw material costs are reduced from 30 to 50$3.2-5.4/kg PHA; it is noted that PHB producing thermophilic methanotrophs are yet to be isolated. Energy consumption for air compression and biomass drying were also identified as significant capital and operating costs and therefore optimisation of bioreactor height and pressure and biomass moisture content should be considered in future research

The association of a single-nucleotide polymorphism in the nuclear factor (erythroid derived 2)-like 2 gene with adverse drug reactions, multimorbidity and frailty in older people

Susceptibility to adverse drug reactions (ADRs), multimorbidity, and frailty are associated with human ageing, yet there is wide variation in the severity and age at which individuals are afflicted. Identifying genetic markers of increased risk of this phenotype would help stratify individuals to specialist interventions. Nuclear factor erythroid derived-2 like 2 (Nrf2) regulates a cell’s response to stressors, including the expression of enzymes involved in drug-metabolism. Its expression has been shown to decline in animal ageing models. In this study we tested the hypothesis that Nrf2 gene transcription/translation decline in human ageing, and that single nucleotide polymorphisms (SNPs) in the Nrf2 gene are associated with increased ADR risk, multi-morbidity, and frailty in older people. Gene expression and protein levels were measured in peripheral blood mononuclear cells (PBMCs) donated from healthy patients aged 18-80 years old. Nrf2 genotypes were determined at three loci in a sub-population of patients recruited to the PRIME study (a multicentre prospective cohort study that followed older adults for 8-weeks post-discharge to determine ADR). Both Nrf2 gene and protein expression declined significantly with age in human PBMCs. In the PRIME sub-study population, the rs35652124 Nrf2 SNP was associated with increased ADR risk, and decreased frailty and multi-morbidity scores

SNPedia: a wiki supporting personal genome annotation, interpretation and analysis

SNPedia (http://www.SNPedia.com) is a wiki resource of the functional consequences of human genetic variation as published in peer-reviewed studies. Online since 2006 and freely available for personal use, SNPedia has focused on the medical, phenotypic and genealogical associations of single nucleotide polymorphisms. Entries are formatted to allow associations to be assigned to single genotypes as well as sets of genotypes (genosets). In this article, we discuss the growth of this resource and its use by affiliated software to create personal genome reports

Thermodynamics of natural images

The scale invariance of natural images suggests an analogy to the statistical mechanics of physical systems at a critical point. Here we examine the distribution of pixels in small image patches and show how to construct the corresponding thermodynamics. We find evidence for criticality in a diverging specific heat, which corresponds to large fluctuations in how "surprising" we find individual images, and in the quantitative form of the entropy vs. energy. The energy landscape derived from our thermodynamic framework identifies special image configurations that have intrinsic error correcting properties, and neurons which could detect these features have a strong resemblance to the cells found in primary visual cortex

Comparison of Parent Questionnaires, Examiner-Led Assessment and Parents' Concerns at 14 Months of Age as Indicators of Later Diagnosis of Autism.

Parents participating in a prospective longitudinal study of infants with older siblings with autism completed an autism screening questionnaire and were asked about any concerns relating to their child's development, and children were administered an interactive assessment conducted by a researcher at 14 months. Scores on the parent questionnaire were highest for children later diagnosed with autism. Parental concerns and scores from the examiner-led assessment distinguished children with later developmental difficulties (both autism and other developmental atypicalities) from those who were developing typically. Children about whom parents expressed concern scored higher on both the questionnaire and the interactive assessment than those without concerns. There were no significant associations between total or individual item scores from the questionnaire and interactive assessment

Analysing point patterns on networks — A review

We review recent research on statistical methods for analysing spatial patterns of points on a network of lines, such as road accident locations along a road network. Due to geometrical complexities, the analysis of such data is extremely challenging, and we describe several common methodological errors. The intrinsic lack of homogeneity in a network militates against the traditional methods of spatial statistics based on stationary processes. Topics include kernel density estimation, relative risk estimation, parametric and non-parametric modelling of intensity, second-order analysis using the K-function and pair correlation function, and point process model construction. An important message is that the choice of distance metric on the network is pivotal in the theoretical development and in the analysis of real data. Challenges for statistical computation are discussed and open-source software is provided