Machine grinding as an alternative method for creating functional surfaces for controlling cell behaviour

There is extensive evidence to show that certain cellular behaviours including cell proliferation, migration and adhesion can be controlled by culturing cells on surfaces containing different micro-metre- and nanometre-scale features. This paper will introduce the use of machine grinding to generate surfaces with micro-sized features and their ability to affect cell behaviour. Results are presented which show that polyurethane castings of the ground surfaces can promote cell adhesion and migration. This study demonstrates the usefulness of surface grinding as a cost-effective method for generating functional surfaces for modifying cell behaviour

Implementation of routine outcome measurement in child and adolescent mental health services in the United Kingdom: a critical perspective

The aim of this commentary is to provide an overview of clinical outcome measures that are currently recommended for use in UK Child and Adolescent Mental Health Services (CAMHS), focusing on measures that are applicable across a wide range of conditions with established validity and reliability, or innovative in their design. We also provide an overview of the barriers and drivers to the use of Routine Outcome Measurement (ROM) in clinical practice

The critical role of logarithmic transformation in Nernstian equilibrium potential calculations

The membrane potential, arising from uneven distribution of ions across cell membranes containing selectively permeable ion channels, is of fundamental importance to cell signaling. The necessity of maintaining the membrane potential may be appreciated by expressing Ohm’s law as current = voltage/resistance and recognizing that no current flows when voltage = 0, i.e., transmembrane voltage gradients, created by uneven transmembrane ion concentrations, are an absolute requirement for the generation of currents that precipitate the action and synaptic potentials that consume >80% of the brain’s energy budget and underlie the electrical activity that defines brain function. The concept of the equilibrium potential is vital to understanding the origins of the membrane potential. The equilibrium potential defines a potential at which there is no net transmembrane ion flux, where the work created by the concentration gradient is balanced by the transmembrane voltage difference, and derives from a relationship describing the work done by the diffusion of ions down a concentration gradient. The Nernst equation predicts the equilibrium potential and, as such, is fundamental to understanding the interplay between transmembrane ion concentrations and equilibrium potentials. Logarithmic transformation of the ratio of internal and external ion concentrations lies at the heart of the Nernst equation, but most undergraduate neuroscience students have little understanding of the logarithmic function. To compound this, no current undergraduate neuroscience textbooks describe the effect of logarithmic transformation in appreciable detail, leaving the majority of students with little insight into how ion concentrations determine, or how ion perturbations alter, the membrane potential

Geographic Coincidence of Increased Malaria Transmission Hazard and Vulnerability Occurring at the Periphery of two Tanzanian Villages.

The goal of malaria elimination necessitates an improved understanding of any fine-scale geographic variations in transmission risk so that complementary vector control tools can be integrated into current vector control programmes as supplementary measures that are spatially targeted to maximize impact upon residual transmission. This study examines the distribution of host-seeking malaria vectors at households within two villages in rural Tanzania. Host-seeking mosquitoes were sampled from 72 randomly selected households in two villages on a monthly basis throughout 2008 using CDC light-traps placed beside occupied nets. Spatial autocorrelation in the dataset was examined using the Moran's I statistic and the location of any clusters was identified using the Getis-Ord Gi* statistic. Statistical associations between the household characteristics and clusters of mosquitoes were assessed using a generalized linear model for each species. For both Anopheles gambiae sensu lato and Anopheles funestus, the density of host-seeking females was spatially autocorrelated, or clustered. For both species, houses with low densities were clustered in the semi-urban village centre while houses with high densities were clustered in the periphery of the villages. Clusters of houses with low or high densities of An. gambiae s.l. were influenced by the number of residents in nearby houses. The occurrence of high-density clusters of An. gambiae s.l. was associated with lower elevations while An. funestus was also associated with higher elevations. Distance from the village centre was also positively correlated with the number of household occupants and having houses constructed with open eaves. The results of the current study highlight that complementary vector control tools could be most effectively targeted to the periphery of villages where the households potentially have a higher hazard (mosquito densities) and vulnerability (open eaves and larger households) to malaria infection

Thinking about Later Life: Insights from the Capability Approach

A major criticism of mainstream gerontological frameworks is the inability of such frameworks to appreciate and incorporate issues of diversity and difference in engaging with experiences of aging. Given the prevailing socially structured nature of inequalities, such differences matter greatly in shaping experiences, as well as social constructions, of aging. I argue that Amartya Sen’s capability approach (2009) potentially offers gerontological scholars a broad conceptual framework that places at its core consideration of human beings (their values) and centrality of human diversity. As well as identifying these key features of the capability approach, I discuss and demonstrate their relevance to thinking about old age and aging. I maintain that in the context of complex and emerging identities in later life that shape and are shaped by shifting people-place and people-people relationships, Sen’s capability approach offers significant possibilities for gerontological research

Reinspection of a Clinical Proteomics Tumor Analysis Consortium (CPTAC) Dataset with Cloud Computing Reveals Abundant Post-Translational Modifications and Protein Sequence Variants.

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has provided some of the most in-depth analyses of the phenotypes of human tumors ever constructed. Today, the majority of proteomic data analysis is still performed using software housed on desktop computers which limits the number of sequence variants and post-translational modifications that can be considered. The original CPTAC studies limited the search for PTMs to only samples that were chemically enriched for those modified peptides. Similarly, the only sequence variants considered were those with strong evidence at the exon or transcript level. In this multi-institutional collaborative reanalysis, we utilized unbiased protein databases containing millions of human sequence variants in conjunction with hundreds of common post-translational modifications. Using these tools, we identified tens of thousands of high-confidence PTMs and sequence variants. We identified 4132 phosphorylated peptides in nonenriched samples, 93% of which were confirmed in the samples which were chemically enriched for phosphopeptides. In addition, our results also cover 90% of the high-confidence variants reported by the original proteogenomics study, without the need for sample specific next-generation sequencing. Finally, we report fivefold more somatic and germline variants that have an independent evidence at the peptide level, including mutations in ERRB2 and BCAS1. In this reanalysis of CPTAC proteomic data with cloud computing, we present an openly available and searchable web resource of the highest-coverage proteomic profiling of human tumors described to date

Direct and Inverse Computation of Jacobi Matrices of Infinite Homogeneous Affine I.F.S

We introduce a new set of algorithms to compute Jacobi matrices associated with measures generated by infinite systems of iterated functions. We demonstrate their relevance in the study of theoretical problems, such as the continuity of these measures and the logarithmic capacity of their support. Since our approach is based on a reversible transformation between pairs of Jacobi matrices, we also discuss its application to an inverse / approximation problem. Numerical experiments show that the proposed algorithms are stable and can reliably compute Jacobi matrices of large order.Comment: 20 pages 6 figure

Extracellular ascorbate modulates glutamate dynamics: role of behavioral activation

<p>Abstract</p> <p>Background</p> <p>A physiological increase in extracellular ascorbate (AA), an antioxidant vitamin found throughout the striatum, elevates extracellular glutamate (GLU). To determine the role of behavioral arousal in this interaction, microdialysis was used to measure striatal GLU efflux in rats tested in either a lights-off or lights-on condition while reverse dialysis either maintained the concentration of AA at 250 μM or increased it to 1000 μM to approximate endogenous changes.</p> <p>Results</p> <p>When lights were off, both locomotion and GLU increased regardless of AA dose. In contrast, animals in the lights-on condition were behaviorally inactive, and infusion of 1000, but not 250, μM AA significantly increased extracellular GLU. Interestingly, when ambient light returned to the lights-off group, 1000 μM prolonged the GLU increase relative to the 250 μM group.</p> <p>Conclusion</p> <p>Our results not only support evidence that elevated striatal AA increases extracellular GLU but also indicate that this effect depends on behavioral state and the corresponding level of endogenous GLU release.</p

Aphids acquired symbiotic genes via lateral gene transfer

<p>Abstract</p> <p>Background</p> <p>Aphids possess bacteriocytes, which are cells specifically differentiated to harbour the obligate mutualist <it>Buchnera aphidicola </it>(γ-Proteobacteria). <it>Buchnera </it>has lost many of the genes that appear to be essential for bacterial life. From the bacteriocyte of the pea aphid <it>Acyrthosiphon pisum</it>, we previously identified two clusters of expressed sequence tags that display similarity only to bacterial genes. Southern blot analysis demonstrated that they are encoded in the aphid genome. In this study, in order to assess the possibility of lateral gene transfer, we determined the full-length sequences of these transcripts, and performed detailed structural and phylogenetic analyses. We further examined their expression levels in the bacteriocyte using real-time quantitative RT-PCR.</p> <p>Results</p> <p>Sequence similarity searches demonstrated that these fully sequenced transcripts are significantly similar to the bacterial genes <it>ldcA </it>(product, LD-carboxypeptidase) and <it>rlpA </it>(product, rare lipoprotein A), respectively. <it>Buchnera </it>lacks these genes, whereas many other bacteria, including <it>Escherichia coli</it>, a close relative of <it>Buchnera</it>, possess both <it>ldcA </it>and <it>rlpA</it>. Molecular phylogenetic analysis clearly demonstrated that the aphid <it>ldcA </it>was derived from a rickettsial bacterium closely related to the extant <it>Wolbachia </it>spp. (α-Proteobacteria, Rickettsiales), which are intracellular symbionts of various lineages of arthropods. The evolutionary origin of <it>rlpA </it>was not fully resolved, but it was clearly demonstrated that its double-ψ β-barrel domain is of bacterial origin. Real-time quantitative RT-PCR demonstrated that <it>ldcA </it>and <it>rlpA </it>are expressed 11.6 and 154-fold higher in the bacteriocyte than in the whole body, respectively. LdcA is an enzyme required for recycling murein (peptidoglycan), which is a component of the bacterial cell wall. As <it>Buchnera </it>possesses a cell wall composed of murein but lacks <it>ldcA</it>, a high level of expression of the aphid <it>ldcA </it>in the bacteriocyte may be essential to maintain <it>Buchnera</it>. Although the function of RlpA is not well known, conspicuous up-regulation of the aphid <it>rlpA </it>in the bacteriocyte implies that this gene is also essential for <it>Buchnera</it>.</p> <p>Conclusion</p> <p>In this study, we obtained several lines of evidence indicating that aphids acquired genes from bacteria via lateral gene transfer and that these genes are used to maintain the obligately mutualistic bacterium, <it>Buchnera</it>.</p