DNA Methylation Analysis Validates Organoids as a Viable Model for Studying Human Intestinal Aging.

Background & aimsThe epithelia of the intestine and colon turn over rapidly and are maintained by adult stem cells at the base of crypts. Although the small intestine and colon have distinct, well-characterized physiological functions, it remains unclear if there are fundamental regional differences in stem cell behavior or region-dependent degenerative changes during aging. Mesenchyme-free organoids provide useful tools for investigating intestinal stem cell biology in vitro and have started to be used for investigating age-related changes in stem cell function. However, it is unknown whether organoids maintain hallmarks of age in the absence of an aging niche. We tested whether stem cell-enriched organoids preserved the DNA methylation-based aging profiles associated with the tissues and crypts from which they were derived.MethodsTo address this, we used standard human methylation arrays and the human epigenetic clock as a biomarker of age to analyze in vitro-derived, 3-dimensional, stem cell-enriched intestinal organoids.ResultsWe found that human stem cell-enriched organoids maintained segmental differences in methylation patterns and that age, as measured by the epigenetic clock, also was maintained in vitro. Surprisingly, we found that stem cell-enriched organoids derived from the small intestine showed striking epigenetic age reduction relative to organoids derived from colon.ConclusionsOur data validate the use of organoids as a model for studying human intestinal aging and introduce methods that can be used when modeling aging or age-onset diseases in vitro

Enclosure utilisation and activity budgets of disabled Malayan sun bears ( Helarctos malayanus )

Captive bears are housed in environments that differ greatly from their natural habitat, restricting their ability to perform normal species-specific behaviours. This may be detrimental to welfare, with disabled individuals at particular risk. The effect of physical disability on behaviour and enclosure utilisation was assessed in 12 adult Malayan sun bears (Helarctos malayanus) using 10 min interval scan sampling. Amputees spent less time performing locomotor behaviours than able-bodied bears, used their enclosures less evenly, but did not exhibit obvious stereotypies. This was possibly due to the increased energy demands of locomotion, or residual pain in amputated limbs. Amputees spent less time grooming, but did not differ in time spent climbing compared with non-amputees. Partially sighted bears did not differ from able-bodied controls in enclosure use or behaviour. Age was positively correlated with stereotypical behaviour, and negatively correlated with maintenance and resting. Medication use was associated with more resting and grooming, and reduced stereotypy. The findings suggest that enclosures for amputees can be smaller than those for able-bodied bears, but should still contain a variety of climbing structures. Partially sighted bears fare well in enclosures designed for able-bodied bears, not requiring any special provision

National data on coercion in psychiatry from Wales

A lack of adequate and accurate data in relation to coercion means that there is little information to guide benchmarking and service planning. The aim of this study was to collate and analyse data for restrictive physical interventions (RPIs) across Wales. All health boards in Wales were asked to provide information on restrictive physical interventions across all specialties. Information requested allowed calculations per 100 admissions and per 100 occupied bed days per month, which reduce bias attributed to levels of admissions and occupancy. Full data sets were obtained for 2013 from all health boards. There was a wide level of variation between health boards. Uniform data gathering is required. Benchmarking may be a useful tool to develop strategies to reduce regional variations. </jats:p

An assessment of myotube morphology, matrix deformation, and myogenic mRNA expression in custom-built and commercially available engineered muscle chamber configurations

There are several three-dimensional (3D) skeletal muscle (SkM) tissue engineered models reported in the literature. 3D SkM tissue engineering (TE) aims to recapitulate the structure and function of native (in vivo) tissue, within an in vitro environment. This requires the differentiation of myoblasts into aligned multinucleated myotubes surrounded by a biologically representative extracellular matrix (ECM). In the present work, a new commercially available 3D SkM TE culture chamber manufactured from polyether ether ketone (PEEK) that facilitates suitable development of these myotubes is presented. To assess the outcomes of the myotubes within these constructs, morphological, gene expression, and ECM remodeling parameters were compared against a previously published custom-built model. No significant differences were observed in the morphological and gene expression measures between the newly introduced and the established construct configuration, suggesting biological reproducibility irrespective of manufacturing process. However, TE SkM fabricated using the commercially available PEEK chambers displayed reduced variability in both construct attachment and matrix deformation, likely due to increased reproducibility within the manufacturing process. The mechanical differences between systems may also have contributed to such differences, however, investigation of these variables was beyond the scope of the investigation. Though more expensive than the custom-built models, these PEEK chambers are also suitable for multiple use after autoclaving. As such this would support its use over the previously published handmade culture chamber system, particularly when seeking to develop higher-throughput systems or when experimental cost is not a factor

A Mendelian randomization study of the causal association between anxiety phenotypes and schizophrenia

Schizophrenia shows a genetic correlation with both anxiety disorder and neuroticism, a trait strongly associated with anxiety. However, genetic correlations do not discern causality from genetic confounding. We therefore aimed to investigate whether anxiety-related phenotypes lie on the causal pathway to schizophrenia using Mendelian randomization (MR). Four MR methods, each with different assumptions regarding instrument validity, were used to investigate casual associations of anxiety and neuroticism related phenotypes on schizophrenia, and vice versa: inverse variance weighted (IVW), weighted median, weighted mode, and, when appropriate, MR Egger regression. MR provided evidence of a causal effect of neuroticism on schizophrenia (IVW odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.12-1.59), but only weak evidence of a causal effect of anxiety on schizophrenia (IVW OR: 1.10, 95% CI: 1.01-1.19). There was also evidence of a causal association from schizophrenia liability to anxiety disorder (IVW OR: 1.28, 95% CI: 1.18-1.39) and worry (IVW beta: 0.05, 95% CI: 0.03-0.07), but effect estimates from schizophrenia to neuroticism were inconsistent in the main analysis. The evidence of neuroticism increasing schizophrenia risk provided by our results supports future efforts to evaluate neuroticism- or anxiety-based therapies to prevent onset of psychotic disorders

Dust and the spectral energy distribution of the OH/IR star OH 127.8+0.0: Evidence for circumstellar metallic iron

We present a fit to the spectral energy distribution of OH 127.8+0.0, a typical asymptotic giant branch star with an optically thick circumstellar dust shell. The fit to the dust spectrum is achieved using non-spherical grains consisting of metallic iron, amorphous and crystalline silicates and water ice. Previous similar attempts have not resulted in a satisfactory fit to the observed spectral energy distributions, mainly because of an apparent lack of opacity in the 3--8 micron region of the spectrum. Non-spherical metallic iron grains provide an identification for the missing source of opacity in the near-infrared. Using the derived dust composition, we have calculated spectra for a range of mass-loss rates in order to perform a consistency check by comparison with other evolved stars. The L-[12 micron] colours of these models correctly predict the mass-loss rate of a sample of AGB stars, strengthening our conclusion that the metallic iron grains dominate the near-infrared flux. We discuss a formation mechanism for non-spherical metallic iron grains.Comment: 10 pages, 6 figures, accepted for publication by A&

Blind component separation for polarized observations of the CMB

We present in this paper the PolEMICA (Polarized Expectation-Maximization Independent Component Analysis) algorithm which is an extension to polarization of the SMICA (Spectral Matching Independent Component Analysis) temperature multi-detectors multi-components (MD-MC) component separation method (Delabrouille et al. 2003). This algorithm allows us to estimate blindly in harmonic space multiple physical components from multi-detectors polarized sky maps. Assuming a linear noisy mixture of components we are able to reconstruct jointly the anisotropies electromagnetic spectra of the components for each mode T, E and B, as well as the temperature and polarization spatial power spectra, TT, EE, BB, TE, TB and EB for each of the physical components and for the noise on each of the detectors. PolEMICA is specially developed to estimate the CMB temperature and polarization power spectra from sky observations including both CMB and foreground emissions. This has been tested intensively using as a first approach full sky simulations of the Planck satellite polarized channels for a 14-months nominal mission assuming a simplified linear sky model including CMB, and optionally Galactic synchrotron emission and a Gaussian dust emission. Finally, we have applied our algorithm to more realistic Planck full sky simulations, including synchrotron, realistic dust and free-free emissions.Comment: 20 pages, 21 figures, 1 table, TeX file, accepted for publication in MNRA