Differentiation of human fetal mesenchymal stem cells into cells with an oligodendrocyte phenotype

This article is available open access through the publisher’s website at the link below. Copyright @ 2009 Landes Bioscience.The potential of mesenchymal stem cells (MSC) to differentiate into neural lineages has raised the possibility of autologous cell transplantation as a therapy for neurodegenerative diseases. We have identified a population of circulating human fetal mesenchymal stem cells (hfMSC) that are highly proliferative and can readily differentiate into mesodermal lineages such as bone, cartilage, fat and muscle. Here, we demonstrate for the first time that primary hfMSC can differentiate into cells with an oligodendrocyte phenotype both in vitro and in vivo. By exposing hfMSC to neuronal conditioned medium or by introducing the pro-oligodendrocyte gene, Olig-2, hfMSC adopted an oligodendrocyte-like morphology, expressed oligodendrocyte markers and appeared to mature appropriately in culture. Importantly we also demonstrate the differentiation of a clonal population of hfMSC into both mesodermal (bone) and ectodermal (oligodendrocyte) lineages. In the developing murine brain transplanted hfMSC integrated into the parenchyma but oligodendrocyte differentiation of these naïve hfMSC was very low. However, the proportion of cells expressing oligodendrocyte markers increased significantly (from 0.2% to 4%) by pre-exposing the cells to differentiation medium in vitro prior to transplantation. Importantly, the process of in vivo differentiation occurred without cell fusion. These findings suggest that hfMSC may provide a potential source of oligodendrocytes for study and potential therapy

Replica symmetry breaking in an adiabatic spin-glass model of adaptive evolution

We study evolutionary canalization using a spin-glass model with replica theory, where spins and their interactions are dynamic variables whose configurations correspond to phenotypes and genotypes, respectively. The spins are updated under temperature T_S, and the genotypes evolve under temperature T_J, according to the evolutionary fitness. It is found that adaptation occurs at T_S < T_S^{RS}, and a replica symmetric phase emerges at T_S^{RSB} < T_S < T_S^{RS}. The replica symmetric phase implies canalization, and replica symmetry breaking at lower temperatures indicates loss of robustness.Comment: 5pages, 2 figure

Funnel landscape and mutational robustness as a result of evolution under thermal noise

In biological systems, expression dynamics to shape a fitted phenotype for function has evolved through mutations to genes, as observed in the evolution of funnel landscape in protein. We study this evolutionary process with a statistical-mechanical model of interacting spins, where the fitted phenotype is represented by a configuration of a given set of "target spins" and interaction matrix J among spins is genotype evolving over generations. The expression dynamics is given by stochastic process with temperature T_S to decrease energy for a given set of J. The evolution of J is also stochastic with temperature T_J, following mutation in J and selection based on a fitness given by configurations of the target spins. Below a certain temperature T_S^{c2}, the highly adapted J evolves, whereasanother phase transition characterised by frustration occurs at T_S^{c1}<T_S^{c2}. At temperature lower than T_S^{c1}, the Hamiltonian exhibits a spin-glass like phase, where the dynamics requires long time steps to produce the fitted phenotype, and the fitness often decreases drastically by single mutation. In contrast, in the intermediate temperature phase between T_S^{c1} and T_S^{c2}, the evolved genotypes, that have no frustration around the target spins (we call "local Mattis state"), give a funnel-like rapid expression dynamics and are robust to mutation. These results imply that evolution under thermal noise beyond a certain level leads to funnel dynamics and mutational robustness. We will explain its mechanism with the statistical-mechanical method.Comment: 4pages, 4figure

Shaping Robust System through Evolution

Biological functions are generated as a result of developmental dynamics that form phenotypes governed by genotypes. The dynamical system for development is shaped through genetic evolution following natural selection based on the fitness of the phenotype. Here we study how this dynamical system is robust to noise during development and to genetic change by mutation. We adopt a simplified transcription regulation network model to govern gene expression, which gives a fitness function. Through simulations of the network that undergoes mutation and selection, we show that a certain level of noise in gene expression is required for the network to acquire both types of robustness. The results reveal how the noise that cells encounter during development shapes any network's robustness, not only to noise but also to mutations. We also establish a relationship between developmental and mutational robustness through phenotypic variances caused by genetic variation and epigenetic noise. A universal relationship between the two variances is derived, akin to the fluctuation-dissipation relationship known in physics

Cosmic Ray Abundances of Sn, Te, Xe, and Ba Nuclei Measured on HEAO 3

Elements with even atomic number ( Z) in the interval 50 ~ Z ~ 56 have been resolved in the cosmic radiation using the Heavy Nuclei Experiment on the HEAO 3 satellite. The observation that 50Sn and 56Ba are more abundant than 52Te Elements with even atomic number ( Z) in the interval 50 ~ Z ~ 56 have been resolved in the cosmic radiation using the Heavy Nuclei Experiment on the HEAO 3 satellite. The observation that 50Sn and 56Ba are more abundant than 52Te and 54Xe is inconsistent with a purer-process cosmic-ray source. Adjustment of source abundances for an enhancement of those elements with a low first ionization potential does not change this conclusion and 54Xe is inconsistent with a purer-process cosmic-ray source. Adjustment of source abundances for an enhancement of those elements with a low first ionization potential does not change this conclusion

Grief and loss in people living with dementia: a review and metasynthesis of qualitative studies

OBJECTIVES: This review seeks to synthesise qualitative studies that focus on the experience of grief and loss in people living with dementia. METHODS: Included studies were quality appraised, synthesised and analysed using inductive thematic analysis. RESULTS: 19 studies were selected for inclusion in the final review and metasynthesis, including 486 participants (115 participants living with dementia, 152 family carers, 219 professionals). Five key dimensions of grief in people living with dementia were identified during the analysis process: grieving for the person I used to be, grieving for how others see me, grieving for the person I will become, grieving for those who have died and what helps me with my grief. CONCLUSION: It is evident that people living with dementia can experience grief related to a range of previous, current and anticipated losses. Many of the studies included in this review did not directly include people living with dementia in their research and did not ask participants directly about their experience of grief and loss. As grief is a highly personal and individual experience, further research addressing the experience of grief that directly includes participants living with dementia is required, in order to improve awareness of grief-related needs and to develop and deliver support to meet these needs

Implications of Ultraheavy Cosmic-Ray Source Composition Derived from Observations by the HEAO-3 Heavy Nuclei Experiment

We have derived the contribution of r-process and s-process nucleosynthesis to the Cameron (1980) solar system (SS) abundances for Z~33. In the interval 34 ~Zs; 40 our HEA0-3 data extrapolated to the cosmic-ray source (CRS) fit the solar system mix better than r-process. In the interval 26 < Z < 40 the HEA0-3 results for CRS/SS follow the same general correlation with first ionization potential as for the lighter eiements although there are deviations in detail

Abundances of Cosmic Ray Nuclei for 26 ≤ Z ≤ 40 From HEAO-3 Heavy Nuclei Experiment

Individual elements in the cosmic radiation of even atomic number (Z)in the interval 26≤ Z ≤ 40 have been resolved and their relative abundances measured. The results are inconsistent with a cosmic-ray source whose composition in this charge interval is dominated by r-process nucleosynthesis

Cosmic-ray abundances of elements with atomic number 26 ≤ Z ≤ 40 measured on HEAO 3

Individual elements in the cosmic radiation of even atomic number (Z) in the interval 26 ≤ Z ≤ 40 have been resolved and their relative abundances measured. The results are inconsistent with a cosmic-ray source whose composition in this charge interval is dominated by r-process nucleosynthests. The ratios of cosmic-ray source abundances to solar system abundances in this interval follow the same general correlation with first ionization potential as for the lighter elements although there are deviations in detail

Optical Morphologies of Millijansky Radio Galaxies Observed by HST and in the VLA FIRST Survey

We report on a statistical study of the 51 radio galaxies at the millijansky flux level from the Faint Images of the Radio Sky at Twenty centimeters, including their optical morphologies and structure obtained with the Hubble Space Telescope. Our optical imaging is significantly deeper (~2 mag) than previous studies with the superior angular resolution of space-based imaging. We that find 8/51 (16%) of the radio sources have no optically identifiable counterpart to AB~24 mag. For the remaining 43 sources, only 25 are sufficiently resolved in the HST images to reliably assign a visual classification: 15 (60%) are elliptical galaxies, 2 (8%) are late-type spiral galaxies, 1 (4%) is an S0, 3 (12%) are point-like objects (quasars), and 4 (16%) are merger systems. We find a similar distribution of optical types with measurements of the Sersic index. The optical magnitude distribution of these galaxies peaks at I~20.7+-0.5 AB mag, which is ~3 mag brighter than the depth of our typical HST field and is thus not due to the WFPC2 detection limit. This supports the luminosity-dependent density evolutionary model, where the majority of faint radio galaxies typically have L*-optical luminosities and a median redshift of z~0.8 with a relatively abrupt redshift cut-off at z>~2. We discuss our results in the context of the evolution of elliptical galaxies and active galactic nuclei.Comment: 20 pages, 8 figures, 51 galaxy images, and 5 tables. Uses emulateapj.cls and natbib.sty. Accepted to ApJS. High resolution images are available upon reques