Microvesicles as vehicles for tissue regeneration: Changing of the guards

Purpose of Review: Microvesicles (MVs) have been recognised as mediators of stem cell function, enabling and guiding their regenerative effects. Recent Findings: MVs constitute one unique size class of extracellular vesicles (EVs) directly shed from the cell plasma membrane. They facilitate cell-to-cell communication via intercellular transfer of proteins, mRNA and microRNA (miRNA). MVs derived from stem cells, or stem cell regulatory cell types, have proven roles in tissue regeneration and repair processes. Their role in the maintenance of healthy tissue function throughout the life course and thus in age related health span remains to be elucidated. Summary: Understanding the biogenesis and mechanisms of action of MVs may enable the development of cell-free therapeutics capable of assisting in tissue maintenance and repair for a variety of age-related degenerative diseases. This review critically evaluates recent work published in this area and highlights important new findings demonstrating the use of MVs in tissue regeneration

Colouring random graphs and maximising local diversity

We study a variation of the graph colouring problem on random graphs of finite average connectivity. Given the number of colours, we aim to maximise the number of different colours at neighbouring vertices (i.e. one edge distance) of any vertex. Two efficient algorithms, belief propagation and Walksat are adapted to carry out this task. We present experimental results based on two types of random graphs for different system sizes and identify the critical value of the connectivity for the algorithms to find a perfect solution. The problem and the suggested algorithms have practical relevance since various applications, such as distributed storage, can be mapped onto this problem.Comment: 10 pages, 10 figure

Focused Local Search for Random 3-Satisfiability

A local search algorithm solving an NP-complete optimisation problem can be viewed as a stochastic process moving in an 'energy landscape' towards eventually finding an optimal solution. For the random 3-satisfiability problem, the heuristic of focusing the local moves on the presently unsatisfiedclauses is known to be very effective: the time to solution has been observed to grow only linearly in the number of variables, for a given clauses-to-variables ratio $\alpha$ sufficiently far below the critical satisfiability threshold $\alpha_c \approx 4.27$. We present numerical results on the behaviour of three focused local search algorithms for this problem, considering in particular the characteristics of a focused variant of the simple Metropolis dynamics. We estimate the optimal value for the ``temperature'' parameter $\eta$ for this algorithm, such that its linear-time regime extends as close to $\alpha_c$ as possible. Similar parameter optimisation is performed also for the well-known WalkSAT algorithm and for the less studied, but very well performing Focused Record-to-Record Travel method. We observe that with an appropriate choice of parameters, the linear time regime for each of these algorithms seems to extend well into ratios $\alpha > 4.2$ -- much further than has so far been generally assumed. We discuss the statistics of solution times for the algorithms, relate their performance to the process of ``whitening'', and present some conjectures on the shape of their computational phase diagrams.Comment: 20 pages, lots of figure

Lifelongα-tocopherol supplementation increases the median life span of C57BL/6 mice in the cold but has only minor effects on oxidative damage

The effects of dietary antioxidant supplementation on oxidative stress and life span are confused. We maintained C57BL/6 mice at 7 ± 2°C and supplemented their diet with α-tocopherol from 4 months of age. Supplementation significantly increased (p = 0.042) median life span by 15% (785 days, n = 44) relative to unsupplemented controls (682 days, n = 43) and also increased maximum life span (oldest 10%, p = 0.028). No sex or sex by treatment interaction effects were observed on life span, with treatment having no effect on resting or daily metabolic rate. Lymphocyte and hepatocyte oxidative DNA damage and hepatic lipid peroxidation were unaffected by supplementation, but hepatic oxidative DNA damage increased with age. Using a cDNA macroarray, genes associated with xenobiotic metabolism were significantly upregulated in the livers of female mice at 6 months of age (2 months supplementation). At 22 months of age (18 months supplementation) this response had largely abated, but various genes linked to the p21 signaling pathway were upregulated at this time. We suggest that α-tocopherol may initially be metabolized as a xenobiotic, potentially explaining why previous studies observe a life span extension generally when lifelong supplementation is initiated early in life. The absence of any significant effect on oxidative damage suggests that the life span extension observed was not mediated via any antioxidant properties of α-tocopherol. We propose that the life span extension observed following α-tocopherol supplementation may be mediated via upregulation of cytochrome p450 genes after 2 months of supplementation and/or upregulation of p21 signaling genes after 18 months of supplementation. However, these signaling pathways now require further investigation to establish their exact role in life span extension following α-tocopherol supplementation

The ionising cluster of 30 Doradus.IV. Stellar kinematics

On the basis of multislit spectroscopy of 180 stars in the ionising cluster of 30 Doradus we present reliable radial velocities for 55 stars. We calculate a radial velocity dispersion of ~35 km/s for the cluster and we analyse the possible influence of spectroscopic binaries in this rather large velocity dispersion. We use numerical simulations to show that the observations are consistent with the hypothesis that all the stars in the cluster are binaries, and the total mass of the cluster is ~5E+5 solar masses. A simple test shows only marginal evidence for dynamical mass segregation which if present is most likely not due to dynamical relaxation.Comment: accepted for publication in Astronomy and Astrophysic

Global Commercial Surrogacy and International Adoption: Parallels and Differences

Over the decades, there have been numerous trends in the formation of family for those experiencing infertility. Adoption – initially domestic but now mostly international – has long been a prevailing method, with a dual outcome of also finding homes for parentless children. Those would-be parents with a stronger desire for genetic relatedness have turned to assisted reproductive technologies for the creation of their families. In the 21st century, capitalising on globalisation and advances in medical sciences and communication, global commercial surrogacy (GCS) is emerging as a dominant method of family formation. In seeking to publish this article in Adoption & Fostering, our primary objective was to provide its readership with an introductory look at GCS, thereby expanding an awareness of surrogacy to an audience whose work has traditionally been concerned with the care and protection of children through foster care and adoption. A secondary aim was to see where the long-standing field of adoption could potentially inform the burgeoning field of global commercial surrogacy. To achieve these objectives, we use international adoption and the adoption triangle as a framework, as we look at the similarities and differences between: (1) the adoptive and commissioning parents; (2) the birth mother and the surrogate; and (3) the adopted children and the children born of global surrogacy