Circulating Mesenchymal Stem Cells Microparticles in Patients with Cerebrovascular Disease

Preclinical and clinical studies have shown that the application of CD105+ mesenchymal stem cells (MSCs) is feasible and may lead to recovery after stroke. In addition, circulating microparticles are reportedly functional in various disease conditions. We tested the levels of circulating CD105+ microparticles in patients with acute ischemic stroke. The expression of CD105 (a surface marker of MSCs) and CXCR4 (a CXC chemokine receptor for MSC homing) on circulating microparticles was evaluated by flow cytometry of samples from 111 patients and 50 healthy subjects. The percentage of apoptotic CD105 microparticles was determined based on annexin V (AV) expression. The relationship between serum levels of CD105+/AV− microparticles, stromal cells derived factor-1α (SDF-1α), and the extensiveness of cerebral infarcts was also evaluated. CD105+/AV− microparticles were higher in stroke patients than control subjects. Correlation analysis showed that the levels of CD105+/AV− microparticles increased as the baseline stroke severity increased. Multivariate testing showed that the initial severity of stroke was independently associated with circulating CD105+/AV− microparticles (OR, 1.103 for 1 point increase in the NIHSS score on admission; 95% CI, 1.032–1.178) after adjusting for other variables. The levels of CD105+/CXCR4+/AV− microparticles were also increased in patients with severe disability (r = 0.192, p = 0.046 for NIHSS score on admission), but were decreased with time after stroke onset (r = −0.204, p = 0.036). Risk factor profiles were not associated with the levels of circulating microparticles or SDF-1α. In conclusion, our data showed that stroke triggers the mobilization of MSC-derived microparticles, especially in patients with extensive ischemic stroke

Targeting Huntington’s disease through histone deacetylases

Huntington’s disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condition remain limited. Aberrant post-translational modification (PTM) of proteins is emerging as an important element in the pathogenesis of HD. These PTMs include acetylation, phosphorylation, methylation, sumoylation and ubiquitination. Several families of proteins are involved with the regulation of these PTMs. In this review, I discuss the current evidence linking aberrant PTMs and/or aberrant regulation of the cellular machinery regulating these PTMs to HD pathogenesis. Finally, I discuss the evidence suggesting that pharmacologically targeting one of these protein families the histone deacetylases may be of potential therapeutic benefit in the treatment of HD

Sensitivity of the Cherenkov Telescope Array for probing cosmology and fundamental physics with gamma-ray propagation

The Cherenkov Telescope Array (CTA), the new-generation ground-based observatory for γ astronomy, provides unique capabilities to address significant open questions in astrophysics, cosmology, and fundamental physics. We study some of the salient areas of γ cosmology that can be explored as part of the Key Science Projects of CTA, through simulated observations of active galactic nuclei (AGN) and of their relativistic jets. Observations of AGN with CTA will enable a measurement of γ absorption on the extragalactic background light with a statistical uncertainty below 15% up to a redshift z=2 and to constrain or detect γ halos up to intergalactic-magnetic-field strengths of at least 0.3 pG . Extragalactic observations with CTA also show promising potential to probe physics beyond the Standard Model. The best limits on Lorentz invariance violation from γ astronomy will be improved by a factor of at least two to three. CTA will also probe the parameter space in which axion-like particles could constitute a significant fraction, if not all, of dark matter. We conclude on the synergies between CTA and other upcoming facilities that will foster the growth of γ cosmology.</p

Sensitivity of the Cherenkov Telescope Array to a dark matter signal from the Galactic centre

We provide an updated assessment of the power of the Cherenkov Telescope Array (CTA) to search for thermally produced dark matter at the TeV scale, via the associated gamma-ray signal from pair-annihilating dark matter particles in the region around the Galactic centre. We find that CTA will open a new window of discovery potential, significantly extending the range of robustly testable models given a standard cuspy profile of the dark matter density distribution. Importantly, even for a cored profile, the projected sensitivity of CTA will be sufficient to probe various well-motivated models of thermally produced dark matter at the TeV scale. This is due to CTA's unprecedented sensitivity, angular and energy resolutions, and the planned observational strategy. The survey of the inner Galaxy will cover a much larger region than corresponding previous observational campaigns with imaging atmospheric Cherenkov telescopes. CTA will map with unprecedented precision the large-scale diffuse emission in high-energy gamma rays, constituting a background for dark matter searches for which we adopt state-of-the-art models based on current data. Throughout our analysis, we use up-to-date event reconstruction Monte Carlo tools developed by the CTA consortium, and pay special attention to quantifying the level of instrumental systematic uncertainties, as well as background template systematic errors, required to probe thermally produced dark matter at these energies