Dark Matter Subhalos in the Ursa Minor Dwarf Galaxy

Through numerical simulations, we study the dissolution timescale of the Ursa Minor cold stellar clump, due to the combination of phase-mixing and gravitational encounters with compact dark substructures in the halo of Ursa Minor. We compare two scenarios; one where the dark halo is made up by a smooth mass distribution of light particles and one where the halo contains 10% of its mass in the form of substructures (subhalos). In a smooth halo, the stellar clump survives for a Hubble time provided that the dark matter halo has a big core. In contrast, when the point-mass dark substructures are added, the clump survives barely for \sim 1.5 Gyr. These results suggest a strong test to the \Lambda-cold dark matter scenario at dwarf galaxy scale.Comment: accepted for publication in Ap

Cores in warm dark matter haloes: a Catch 22 problem

The free streaming of warm dark matter particles dampens the fluctuation spectrum, flattens the mass function of haloes and imprints a fine grained phase density limit for dark matter structures. The phase space density limit is expected to imprint a constant density core at the halo center on the contrary to what happens for cold dark matter. We explore these effects using high resolution simulations of structure formation in different warm dark matter scenarios. We find that the size of the core we obtain in simulated haloes is in good agreement with theoretical expectations based on Liouville's theorem. However, our simulations show that in order to create a significant core, (r_c~1 kpc), in a dwarf galaxy (M~1e10 Msun), a thermal candidate with a mass as low as 0.1 keV is required. This would fully prevent the formation of the dwarf galaxy in the first place. For candidates satisfying large scale structure constrains (m_wdm larger than 1-2 keV) the expected size of the core is of the order of 10 (20) pc for a dark matter halo with a mass of 1e10 (1e8) Msun. We conclude that "standard" warm dark matter is not viable solution for explaining the presence of cored density profiles in low mass galaxies.Comment: 9 pages, 8 figures, new theory section, fig 8 updated, conclusions unchanged, accepted for publication on MNRA

Heme oxygenase-1 induction restores high-blood-flow-dependent remodeling and endothelial function in mesenteric arteries of old rats

BACKGROUND: Aging is associated with reduced structural and functional adaptation to chronic changes in blood flow (shear stress) in small arteries. As heme oxygenase-1 (HO-1) is induced by hemodynamic forces in vascular smooth muscle and endothelial cells, we hypothesized that it might improve flow-dependent remodeling in aging. METHOD: First-order mesenteric arteries from 3 and 16-month-old rats were exposed to high, low, or normal flow by alternate ligation in vivo. Rats were treated with the HO-1 inducer, cobalt protoporphyrin (CoPP, 5 mg/kg) or vehicle. 14 days later, local blood flow was measured in vivo, and arteries were studied in vitro. RESULTS: Despite an equivalent change in blood flow, diameter enlargement in the high-flow arteries was blunted in old compared to young rats and was associated with decreased endothelium-dependent relaxation to acetylcholine. In old rats, HO-1 induction with CoPP restored outward remodeling, via a paradoxical reactive oxygen species-dependent mechanism, and was associated with a Mn-superoxide dismutase (SOD) overexpression, as well as a significant reduction of mitochondrial aconitase activity, used as a biomarker for oxidative stress. The heme oxygenase activity inhibitor, Sn-protoporphyrin, and the SOD-mimetic, TEMPOL, prevented the effect of CoPP on remodeling and oxidative status in old rats. Furthermore, HO-1 induction improved endothelial function, in association with increased endothelial nitric oxide synthase protein expression and phosphorylation (Ser-1177). In low-flow arteries, inward remodeling was unaffected by aging or by CoPP. Thus, in old rats, CoPP-induced up-regulation of HO-1 restored high-flow-dependent remodeling (diameter enlargement) and improved endothelial function in mesenteric arteries. CONCLUSION: This opens new perspectives in the treatment of ischemic diseases in aging

Syzygium jambolanum treatment improves survival in lethal sepsis induced in mice

<p>Abstract</p> <p>Background</p> <p>The leaves and the fruits from <it>Syzygium jambolanum </it>DC.(Myrtaceae), a plant known in Brazil as sweet olive or 'jambolão', have been used by native people to treat infectious diseases, diabetes, and stomachache. Since the bactericidal activity of <it>S. jambolanum </it>has been confirmed <it>in vitro</it>, the aim of this work was to evaluate the effect of the prophylactic treatment with <it>S. jambolanum </it>on the <it>in vivo </it>polymicrobial infection induced by cecal ligation and puncture (CLP) in mice.</p> <p>Methods</p> <p>C57Bl/6 mice were treated by the subcutaneous route with a hydroalcoholic extract from fresh leaves of <it>S. jambolanum </it>(HCE). After 6 h, a bacterial infection was induced in the peritoneum using the lethal CLP model. The mice were killed 12 h after the CLP induction to evaluate the cellular influx and local and systemic inflammatory mediators' production. Some animals were maintained alive to evaluate the survival rate.</p> <p>Results</p> <p>The prophylactic HCE treatment increased the mice survival, the neutrophil migration to infectious site, the spreading ability and the hydrogen peroxide release, but decreased the serum TNF and nitrite. Despite the increased migration and activation of peritoneal cells the HCE treatment did not decrease the number of CFU. The HCE treatment induced a significant decrease on the bone marrow cells number but did not alter the cell number of the spleen and lymph node.</p> <p>Conclusion</p> <p>We conclude that the treatment with <it>S. jambolanum </it>has a potent prophylactic anti-septic effect that is not associated to a direct microbicidal effect but it is associated to a recruitment of activated neutrophils to the infectious site and to a diminished systemic inflammatory response.</p

J Med Genet

BACKGROUND: Mitochondrial DNA (mtDNA) diseases are rare disorders whose prevalence is estimated around 1 in 5000. Patients are usually tested only for deletions and for common mutations of mtDNA which account for 5-40% of cases, depending on the study. However, the prevalence of rare mtDNA mutations is not known. METHODS: We analysed the whole mtDNA in a cohort of 743 patients suspected of manifesting a mitochondrial disease, after excluding deletions and common mutations. Both heteroplasmic and homoplasmic variants were identified using two complementary strategies (Surveyor and MitoChip). Multiple correspondence analyses followed by hierarchical ascendant cluster process were used to explore relationships between clinical spectrum, age at onset and localisation of mutations. RESULTS: 7.4% of deleterious mutations and 22.4% of novel putative mutations were identified. Pathogenic heteroplasmic mutations were more frequent than homoplasmic mutations (4.6% vs 2.8%). Patients carrying deleterious mutations showed symptoms before 16 years of age in 67% of cases. Early onset disease (16 years) were associated with mutations in tRNA genes. MTND5 and MTND6 genes were identified as 'hotspots' of mutations, with Leigh syndrome accounting for the large majority of associated phenotypes. CONCLUSIONS: Rare mitochondrial DNA mutations probably account for more than 7.4% of patients with respiratory chain deficiency. This study shows that a comprehensive analysis of mtDNA is essential, and should include young children, for an accurate diagnosis that is now accessible with the development of next generation sequencing technolog