Clonal analysis of stem cells in differentiation and disease.

Tracking the fate of individual cells and their progeny by clonal analysis has redefined the concept of stem cells and their role in health and disease. The maintenance of cell turnover in adult tissues is achieved by the collective action of populations of stem cells with an equal likelihood of self-renewal or differentiation. Following injury stem cells exhibit striking plasticity, switching from homeostatic behavior in order to repair damaged tissues. The effects of disease states on stem cells are also being uncovered, with new insights into how somatic mutations trigger clonal expansion in early neoplasia.BC and PHJ are supported by a core grant from the Wellcome Trust to the Wellcome Trust Sanger Institute. PHJ acknowledges support from a Cancer Research UK Programme Grant (C609/A17257).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.ceb.2016.07.00

Internet-based psychoeducation for bipolar disorder: a qualitative analysis of feasibility, acceptability and impact

<p>Background: In a recent exploratory randomised trial we found that a novel, internet-based psychoeducation programme for bipolar disorder (Beating Bipolar) was relatively easy to deliver and had a modest effect on psychological quality of life. We sought to explore the experiences of participants with respect to feasibility, acceptability and impact of Beating Bipolar.</p> <p>Methods: Participants were invited to take part in a semi-structured interview. Thematic analysis techniques were employed; to explore and describe participants’ experiences, the data were analysed for emerging themes which were identified and coded.</p> <p>Results: The programme was feasible to deliver and acceptable to participants where they felt comfortable using a computer. It was found to impact upon insight into illness, health behaviour, personal routines and positive attitudes towards medication. Many participants regarded the programme as likely to be most beneficial for those recently diagnosed.</p> <p>Conclusions: An online psychoeducation package for bipolar disorder, such as Beating Bipolar, is feasible and acceptable to patients, has a positive impact on self-management behaviours and may be particularly suited to early intervention. Alternative (non-internet) formats should also be made available to patients.</p&gt

Septo-hippocampal networks in chronic epilepsy

The medial septum inhibits the appearance of interictal spikes and seizures through theta rhythm generation. We have determined that medial septal neurons increase their firing rates during chronic epilepsy and that the GABAergic neurons from both medial and lateral septal regions are highly and selectively vulnerable to the epilepsy process. Since the lateral septal region receives a strong projection from the hippocampus and its neurons are vulnerable to epilepsy, their functional properties are probably altered by this disorder. Using the pilocarpine model of temporal lobe epilepsy we examined the pilocarpine-induced functional alterations of lateral septal neurons and provided additional observations on the pilocarpine-induced functional alterations of medial septal neurons. Simultaneous extracellular recordings of septal neurons and hippocampal field potentials were obtained from chronic epileptic rats under urethane anesthesia. Our results show that: (1) the firing rates of lateral septal neurons were chronically decreased by epilepsy, (2) a subset of lateral septal neurons increased their firing rates before and during hippocampal interictal spikes, (3) the discharges of those lateral septal neurons were well correlated to the hippocampal interictal spikes, (4) in contrast, the discharges of medial septal neurons were not correlated with the hippocampal interictal spikes. We conclude that epilepsy creates dysfunctional and uncoupled septohippocampal networks. The elucidation of the roles of altered septo-hippocampal neuronal populations and networks during temporal lobe epilepsy will help design new and effective interventions dedicated to reduce or suppress epileptic activity

Complex organic molecules in comets C/2012 F6 (Lemmon) and C/2013 R1 (Lovejoy): detection of ethylene glycol and formamide

A spectral survey in the 1 mm wavelength range was undertaken in the long-period comets C/2012 F6 (Lemmon) and C/2013 R1 (Lovejoy) using the 30 m telescope of the Institut de radioastronomie millim\'etrique (IRAM) in April and November-December 2013. We report the detection of ethylene glycol (CH$_2$OH)$_2$ (aGg' conformer) and formamide (NH$_2$CHO) in the two comets. The abundances relative to water of ethylene glycol and formamide are 0.2-0.3% and 0.02% in the two comets, similar to the values measured in comet C/1995 O1 (Hale-Bopp). We also report the detection of HCOOH and CH$_3$CHO in comet C/2013 R1 (Lovejoy), and a search for other complex species (methyl formate, glycolaldehyde).Comment: Accepted for publication as a Letter in Astronomy and Astrophysic

In vivo absorption behaviour of theophylline from starch-methyl methacrylate matrix tablets in beagle dogs

This study evaluates in vivo the drug absorption profiles from potato starch-methyl methacrylate matrices∗ using theophylline as a model drug. Healthy beagle dogs under fasting conditions were used for in vivo studies and plasma samples were analyzed by a fluorescence polarization immunoassay analysis (FPIA method). Non-compartmental and compartmental (population approach) analysis was performed to determine the pharmacokinetic parameters. The principle of superposition was applied to predict multiple dose plasma concentrations from experimental single dose data. An in vitro-in vivo correlation (IVIVC) was also assessed. The sustained absorption kinetics of theophylline from these formulations was demonstrated by comparison with two commercially available oral sustained-release theophylline products (Theo-Dur® and Theolair®). A one-compartment model with first order kinetics without lag-time best describes the absorption/disposition of theophylline from the formulations. Results revealed a theophylline absorption rate in the order FD-HSMMA Theo-Dur®OD-CSMMA > Theolair®FD-CSMMA. On the basis of simulated plasma theophylline levels, a twice daily dosage (every 12 h) with the FD-CSMMA tablets should be recommended. A Level C IVIVC was found between the in vitro t50% and the in vivo AUC/D, although further optimization of the in vitro dissolution test would be needed to adequately correlate with in vivo data.Ministerio de Educación y Ciencia MAT2004-0159

Modelling the influence of RKIP on the ERK signalling pathway using the stochastic process algebra PEPA

This paper examines the influence of the Raf Kinase Inhibitor Protein (RKIP) on the Extracellular signal Regulated Kinase (ERK) signalling pathway [5] through modelling in a Markovian process algebra, PEPA [11]. Two models of the system are presented, a reagent-centric view and a pathway-centric view. The models capture functionality at the level of subpathway, rather than at a molecular level. Each model affords a different perspective of the pathway and analysis. We demonstrate the two models to be formally equivalent using the timing-aware bisimulation defined over PEPA models and discuss the biological significance

Detection of Formaldehyde Towards the Extreme Carbon Star IRC+10216

We report the detection of H2CO (formaldehyde) around the carbon-rich AGB star, IRC+10216. We find a fractional abundance with respect to molecular hydrogen of x(H2CO)= (1.3 {+1.5}{-0.8}) x 10^{-8}. This corresponds to a formaldehyde abundance with respect to water vapor of x(H2CO)/x(H2O)=(1.1 +/- 0.2) x 10^{-2}, in line with the formaldehyde abundances found in Solar System comets, and indicates that the putative extrasolar cometary system around IRC+10216 may have a similar chemical composition to Solar System comets. However, we also failed to detect CH3OH (methanol) around IRC+10216 and our upper limit of x(CH3OH)/x(H2O) < 7.7 x 10^{-4}, (3 sigma), indicates that methanol is substantially underabundant in IRC+10216, compared to Solar System comets. We also conclude, based on offset observations, that formaldehyde has an extended source in the envelope of IRC+10216 and may be produced by the photodissociation of a parent molecule, similar to the production mechanism for formaldehyde in Solar System comet comae. Preliminary mapping observations also indicate a possible asymmetry in the spatial distribution of formaldehyde around IRC+10216, but higher signal-to-noise observations are required to confirm this finding. This study is based on observations carried out with the IRAM 30m telescope. IRAM is supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain). (abridged)Comment: accepted to ApJ, 45 pages, 11 figure

Optimal interactions of light with magnetic and electric resonant particles

This work studies the limits of far and near-field electromagnetic response of sub-wavelength scatterers, like the unitary limit and of lossless scatterers, and the ideal absorption limit of lossy particles. These limit behaviors are described in terms of analytic formulas that approximate finite size effects while rigorously including radiative corrections. This analysis predicts the electric and/or magnetic limit responses of both metallic and dielectric nanoparticles while quantitatively describing near-field enhancements.Comment: 9 pages, 8 figures, 2 table

Distributed neural system for general intelligence revealed by lesion mapping

General intelligence (g) captures the performance variance shared across cognitive tasks and correlates with real-world success. Yet it remains debated whether g reflects the combined performance of brain systems involved in these tasks or draws on specialized systems mediating their interactions. Here we investigated the neural substrates of g in 241 patients with focal brain damage using voxel-based lesion–symptom mapping. A hierarchical factor analysis across multiple cognitive tasks was used to derive a robust measure of g. Statistically significant associations were found between g and damage to a remarkably circumscribed albeit distributed network in frontal and parietal cortex, critically including white matter association tracts and frontopolar cortex. We suggest that general intelligence draws on connections between regions that integrate verbal, visuospatial, working memory, and executive processes

Gray matter correlates of cognitive ability tests used for vocational guidance

<p>Abstract</p> <p>Background</p> <p>Individual differences in cognitive abilities provide information that is valuable for vocational guidance, but there is an ongoing debate about the role of ability factors, including general intelligence (<it>g</it>), compared to individual tests. Neuroimaging can help identify brain parameters that may account for individual differences in both factors and tests. Here we investigate how eight tests used in vocational guidance correlate to regional gray matter. We compare brain networks identified by using scores for ability factors (general and specific) to those identified by using individual tests to determine whether these relatively broad and narrow approaches yield similar results.</p> <p>Findings</p> <p>Using MRI and voxel-based morphometry (VBM), we correlated gray matter with independent ability factors (general intelligence, speed of reasoning, numerical, spatial, memory) and individual test scores from a battery of cognitive tests completed by 40 individuals seeking vocational guidance. Patterns of gray matter correlations differed between group ability factors and individual tests. Moreover, tests within the same factor showed qualitatively different brain correlates to some degree.</p> <p>Conclusions</p> <p>The psychometric factor structure of cognitive tests can help identify brain networks related to cognitive abilities beyond a general intelligence factor (<it>g</it>). Correlates of individual ability tests with gray matter, however, appear to have some differences from the correlates for group factors.</p