Extracellular vesicles, ageing, and therapeutic interventions

A more comprehensive understanding of the human ageing process is required to help mitigate the increasing burden of age-related morbidities in a rapidly growing global demographic of elderly individuals. One exciting novel strategy that has emerged to intervene involves the use of extracellular vesicles to engender tissue regeneration. Specifically, this employs their molecular payloads to confer changes in the epigenetic landscape of ageing cells and ameliorate the loss of functional capacity. Understanding the biology of extracellular vesicles and the specific roles they play during normative ageing will allow for the development of novel cell-free therapeutic interventions. Hence, the purpose of this review is to summarise the current understanding of the mechanisms that drive ageing, critically explore how extracellular vesicles affect ageing processes and discuss their therapeutic potential to mitigate the effects of age-associated morbidities and improve the human health span

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

On the push&pull protocol for rumour spreading

The asynchronous push&pull protocol, a randomized distributed algorithm for spreading a rumour in a graph $G$, works as follows. Independent Poisson clocks of rate 1 are associated with the vertices of $G$. Initially, one vertex of $G$ knows the rumour. Whenever the clock of a vertex $x$ rings, it calls a random neighbour $y$: if $x$ knows the rumour and $y$ does not, then $x$ tells $y$ the rumour (a push operation), and if $x$ does not know the rumour and $y$ knows it, $y$ tells $x$ the rumour (a pull operation). The average spread time of $G$ is the expected time it takes for all vertices to know the rumour, and the guaranteed spread time of $G$ is the smallest time $t$ such that with probability at least $1-1/n$, after time $t$ all vertices know the rumour. The synchronous variant of this protocol, in which each clock rings precisely at times $1,2,\dots$, has been studied extensively. We prove the following results for any $n$-vertex graph: In either version, the average spread time is at most linear even if only the pull operation is used, and the guaranteed spread time is within a logarithmic factor of the average spread time, so it is $O(n\log n)$. In the asynchronous version, both the average and guaranteed spread times are $\Omega(\log n)$. We give examples of graphs illustrating that these bounds are best possible up to constant factors. We also prove theoretical relationships between the guaranteed spread times in the two versions. Firstly, in all graphs the guaranteed spread time in the asynchronous version is within an $O(\log n)$ factor of that in the synchronous version, and this is tight. Next, we find examples of graphs whose asynchronous spread times are logarithmic, but the synchronous versions are polynomially large. Finally, we show for any graph that the ratio of the synchronous spread time to the asynchronous spread time is $O(n^{2/3})$.Comment: 25 page

The strange-quark chemical potential as an experimentally accessible "order parameter" of the deconfinement phase transition for finite baryon-density

We consider the change of the strange-quark chemical potential in the phase diagram of nuclear matter, employing the Wilson loop and scalar quark condensate order parameters, mass-scaled partition functions and enforcing flavor conservation. Assuming the region beyond the hadronic phase to be described by massive, correlated and interacting quarks, in the spirit of lattice and effective QCD calculations, we find the strange-quark chemical potential to change sign: from positive in the hadronic phase - to zero upon deconfinement - to negative in the partonic domain. We propose this change in the sign of the strange-quark chemical potential to be an experimentally accessible order parameter and a unique, concise and well-defined indication of the quark-deconfinement phase transition in nuclear matter.Comment: 22 pages, 14 figures within text, 2 figures(6,B3) as separate files. To be published in J.Phys.G: Nucl.&Part.Phys. G28 (2002

Model of Centauro and strangelet production in heavy ion collisions

We discuss the phenomenological model of Centauro event production in relativistic nucleus-nucleus collisions. This model makes quantitative predictions for kinematic observables, baryon number and mass of the Centauro fireball and its decay products. Centauros decay mainly to nucleons, strange hyperons and possibly strangelets. Simulations of Centauro events for the CASTOR detector in Pb-Pb collisions at LHC energies are performed. The signatures of these events are discussed in detail.Comment: 19 pages, LaTeX+revtex4, 14 eps-figures and 3 table