Skeletal myofiber VEGF deficiency leads to mitochondrial, structural and contractile alterations in mouse diaphragm

Diaphragm dysfunction accompanies cardiopulmonary disease and impaired oxygen delivery. Vascular endothelial growth factor (VEGF) regulates oxygen delivery through angiogenesis, capillary maintenance, and contraction-induced perfusion. We hypothesized that myofiber-specific VEGF deficiency contributes to diaphragm weakness and fatigability. Diaphragm protein expression, capillarity and fiber morphology, mitochondrial respiration and hydrogen peroxide (H2O2) generation, and contractile function were compared between adult mice with conditional gene ablation of skeletal myofiber VEGF (SkmVEGF-/-; n=12) and littermate controls (n=13). Diaphragm VEGF protein was ~50 % lower in SkmVEGF-/- than littermate controls (1.45±0.65 vs. 3.04±1.41 pg/total protein; P=0.001). This was accompanied by an ~15% impairment in maximal isometric specific force (F[1,23] = 15.01, P=0.001) and a trend for improved fatigue resistance (P=0.053). Mean fiber cross-sectional area and type I fiber cross-sectional area were lower in SkmVEGF-/- by ~40 % and ~25% (P0.05). However mitochondrial-derived reactive oxygen species (ROS) flux was lower in SkmVEGF-/- (P=0.0003). In conclusion, myofiber-specific VEGF gene deletion resulted in a lower capillary-to-fiber ratio, type I fiber atrophy, actin loss, and contractile dysfunction in the diaphragm. In contrast, mitochondrial respiratory function was preserved alongside lower ROS generation, which may play a compensatory role to preserve fatigue resistance in the diaphragm

Bigger or better: the relative benefits of protected area network expansion and enforcement for the conservationof an exploited species

The global portfolio of protected areas is growing rapidly, despite widely recognizedshortfalls in management effectiveness. Pressure to meet area-coverage and manage-ment effectiveness objectives makes it essential to determine how limited conserva-tion funds should be allocated between expanding protected area networks and betterenforcing existing reserves. We formally explore this question for the particular caseof an exploited species in a partially protected system, using a general model linkingprotection, enforcement and legal/illegal resource extraction. We show that, on aver-age, funds should be disproportionately invested in enforcement rather than expan-sion. Further, expansion alone, without additional enforcement, can actually reduceconservation outcomes. To help guide future decisions, we calculate the optimal allo-cation of resources between these two actions given any current level of enforcementand protected area coverage. In most cases, simultaneously investing in expansion andenforcement is the optimal decision. However, in places with low enforcement andhigh protection, protected area contraction, or strategically concentrating enforcementeffort, produces the greatest benefits

Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke

<p>Abstract</p> <p>Background</p> <p>Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more than one year to evaluate the effect of edaravone which might reduce ischemic damage.</p> <p>Methods</p> <p>We sequentially enrolled acute ischemic stroke patients, who admitted between April 2003 and March 2004, into the edaravone(-) group (n = 83) and, who admitted between April 2004 and March 2005, into the edaravone(+) group (n = 93). Because, edaravone has been used as the standard treatment after April 2004 in our hospital. To assess the temporal profile of the stroke lesion size, the ratio of the area [T2-weighted magnetic resonance images (T2WI)/iffusion-weighted magnetic resonance images (DWI)] were calculated. Observations on T2WI were continued beyond one year, and observational times were classified into subacute (1-2 months after the onset), early chronic (3-6 month), late chronic (7-12 months) and old (≥13 months) stages. Neurological deficits were assessed by the National Institutes of Health Stroke Scale upon admission and at discharge and by the modified Rankin Scale at 1 year following stroke onset.</p> <p>Results</p> <p>Stroke lesion size was significantly attenuated in the edaravone(+) group compared with the edaravone(-) group in the period of early and late chronic observational stages. However, this reduction in lesion size was significant within a year and only for the small-vessel occlusion stroke patients treated with edaravone. Moreover, patients with small-vessel occlusion strokes that were treated with edaravone showed significant neurological improvement during their hospital stay, although there were no significant differences in outcome one year after the stroke.</p> <p>Conclusion</p> <p>Edaravone treatment reduced the volume of the infarct and improved neurological deficits during the subacute period, especially in the small-vessel occlusion strokes.</p

Social deprivation and exposure to health promotion. A study of the distribution of health promotion resources to schools in England

This article has been made available through the Brunel Open Access Publishing Fund and is available from the specified link - Copyright @ 2010 Chivu and ReidpathBACKGROUND: Area deprivation is a known determinant of health. It is also known that area deprivation is associated with lower impact health promotion. It is less well known, however, whether deprived areas are less responsive to health promotion, or whether they are less exposed. Using data from a national, school-based campaign to promote vaccination against the human papilloma virus (HPV), the relationship between area deprivation and exposure was examined. METHODS: Taking advantage of a health promotion campaign to provide information to schools about HPV vaccination, a cross sectional study was conducted to examine the relationship between area level, social deprivation, and take-up of (i.e., exposure to) available health promotion material. The sample was 4,750 schools across England, including government maintained and independent schools. The relationship between area deprivation and exposure was examined using bi- and multivariate logistic regression. RESULTS: It was found that schools in the least deprived quintile had 1.32 times the odds of requesting health promotion materials than schools in the most deprived areas (p = .01). This effect was independent of the school size, the type of school, and the geographic region. Conclusion The relationship between area deprivation and the impact of health promotion may be due, at least in part, to differential levels of exposure. The study was limited in scope, pointing to the need for more research, but also points to potentially important policy implications

High-Yield Hydrogen Production from Starch and Water by a Synthetic Enzymatic Pathway

BACKGROUND: The future hydrogen economy offers a compelling energy vision, but there are four main obstacles: hydrogen production, storage, and distribution, as well as fuel cells. Hydrogen production from inexpensive abundant renewable biomass can produce cheaper hydrogen, decrease reliance on fossil fuels, and achieve zero net greenhouse gas emissions, but current chemical and biological means suffer from low hydrogen yields and/or severe reaction conditions. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate a synthetic enzymatic pathway consisting of 13 enzymes for producing hydrogen from starch and water. The stoichiometric reaction is C(6)H(10)O(5) (l)+7 H(2)O (l)→12 H(2) (g)+6 CO(2) (g). The overall process is spontaneous and unidirectional because of a negative Gibbs free energy and separation of the gaseous products with the aqueous reactants. CONCLUSIONS: Enzymatic hydrogen production from starch and water mediated by 13 enzymes occurred at 30°C as expected, and the hydrogen yields were much higher than the theoretical limit (4 H(2)/glucose) of anaerobic fermentations. SIGNIFICANCE: The unique features, such as mild reaction conditions (30°C and atmospheric pressure), high hydrogen yields, likely low production costs ($∼2/kg H(2)), and a high energy-density carrier starch (14.8 H(2)-based mass%), provide great potential for mobile applications. With technology improvements and integration with fuel cells, this technology also solves the challenges associated with hydrogen storage, distribution, and infrastructure in the hydrogen economy

Long-lived stops in MSSM scenarios with a neutralino LSP

This work investigates the possibility of a long-lived stop squark in supersymmetric models with the neutralino as the lightest supersymmetric particle (LSP). We study the implications of meta-stable stops on the sparticle mass spectra and the dark matter density. We find that in order to obtain a sufficiently long stop lifetime so as to be observable as a stable R-hadron at an LHC experiment, we need to fine tune the mass degeneracy between the stop and the LSP considerably. This increases the stop-neutralino coanihilation cross section, leaving the neutralino relic density lower than what is expected from the WMAP results for stop masses ~1.5 TeV/c^2. However, if such scenarios are realised in nature we demonstrate that the long-lived stops will be produced at the LHC and that stop-based R-hadrons with masses up to 1 TeV/c^2 can be detected after one year of running at design luminosity

Gravity waves and the LHC: Towards high-scale inflation with low-energy SUSY

It has been argued that rather generic features of string-inspired inflationary theories with low-energy supersymmetry (SUSY) make it difficult to achieve inflation with a Hubble scale H > m_{3/2}, where m_{3/2} is the gravitino mass in the SUSY-breaking vacuum state. We present a class of string-inspired supergravity realizations of chaotic inflation where a simple, dynamical mechanism yields hierarchically small scales of post-inflationary supersymmetry breaking. Within these toy models we can easily achieve small ratios between m_{3/2} and the Hubble scale of inflation. This is possible because the expectation value of the superpotential relaxes from large to small values during the course of inflation. However, our toy models do not provide a reasonable fit to cosmological data if one sets the SUSY-breaking scale to m_{3/2} < TeV. Our work is a small step towards relieving the apparent tension between high-scale inflation and low-scale supersymmetry breaking in string compactifications.Comment: 21+1 pages, 5 figures, LaTeX, v2: added references, v3: very minor changes, version to appear in JHE

Selected acute phase CSF factors in ischemic stroke: findings and prognostic value

<p>Abstract</p> <p>Background</p> <p>Study aimed at investigation of pathogenic role and prognostic value of several selected cerebrospinal fluid acute phase factors that can reflect the severity of ischemic brain damage.</p> <p>Methods</p> <p>Ninety five acute ischemic stroke patients were investigated. Ischemic region visualized at the twenty fourth hour by conventional Magnetic Resonance Imaging. Stroke severity evaluated by National Institute Health Stroke Scale. One month outcome of disease was assessed by Barthel Index. Cerebrospinal fluid was taken at the sixth hour of stroke onset. CSF pro- and anti-inflammatory cytokines were studied by Enzyme Linked Immunosorbent Assay. Nitric Oxide and Lipoperoxide radical were measured by Electron Paramagnetic Resonance. CSF Nitrate levels were detected using the Griess reagent. Statistics performed by SPSS-11.0.</p> <p><b>Results</b></p> <p>At the sixth hour of stroke onset, cerebrospinal fluid cytokine levels were elevated in patients against controls. Severe stroke patients had increased interleukin-6 content compared to less severe strokes (P < 0.05). Cerebrospinal fluid Electron Paramagnetic Resonance signal of nitric oxide was increased in patients against controls. Severe stroke group had an elevated Electron Paramagnetic Resonance signal of lipoperoxiradical compared to less severe stroke. Cerebrospinal fluid nitrate levels in less severe stroke patients were higher than those for severe stroke and control. Positive correlation was established between the initial interleukin-6 content and ischemic lesion size as well as with National Institute Health Stroke Scale score on the seventh day. Initial interleukin-6 and nitrate levels in cerebrospinal fluid found to be significant for functional outcome of stroke at one month.</p> <p><b>Conclusion</b></p> <p>According to present study the cerebrospinal fluid contents of interleukin-6 and nitrates seem to be the most reliable prognostic factors in acute phase of ischemic stroke.</p