Macrophages overexpressing tartrate-resistant acid phosphatase show altered profile of free radical production and enhanced capacity of bacterial killing

Activated macrophages and osteoclasts express high amounts of tartrate-resistant acid phosphatase (TRACP, acp5). TRACP has a binuclear iron center with a redox-active iron that has been shown to catalyze the formation of reactive oxygen species (ROS) by Fenton's reaction. Previous studies suggest that ROS generated by TRACP may participate in degradation of endocytosed bone matrix products in resorbing osteoclasts and degradation of foreign compounds during antigen presentation in activated macrophages. Here we have compared free radical production in macrophages of TRACP overexpressing (TRACP+) and wild-type (WT) mice. TRACP overexpression increased both ROS levels and superoxide production. Nitric oxide production was increased in activated macrophages of WT mice, but not in TRACP+ mice. Macrophages from TRACP+ mice showed increased capacity of bacterial killing. Recombinant TRACP enzyme was capable of bacterial killing in the presence of hydrogen peroxide. These results suggest that TRACP has an important biological function in immune defense system

COBRAS/SAMBA: The European space mission to map the CBR anisotropy

COBRAS/SAMBA is an ESA mission designed for extensive, accurate mapping of the anisotropies of the Cosmic Background Radiation, with angular sensitivity from sub-degree scales up to and overlapping with the COBE-DMR resolution. This will allow a fun identification of the primordial density perturbations which grew to form the large-scale structures observed in the present universe. Here we present the scientific goals and the key characteristics of the model payload and observation strategy

COBRAS/SAMBA - THE ESA MEDIUM-SIZE MISSION FOR MEASUREMENTS OF CBR ANISOTROPY

The COBRAS/SAMBA mission is designed for extensive, accurate mapping of the anisotropy of the cosmic Background Radiation, with angular sensitivity from scales of a few arcminutes up to and over-lapping with the > 7 degrees COBE-DMR resolution. This will allow a full identification of the primordial density perturbations which grew to form the large-scale structures observed in the present universe. The COBRAS/SAMBA maps will provide a major source of information relevant to several cosmological and astrophysical issues, such as testing theories of the early universe and the origin of cosmic structure. One of the main diffuse foreground emissions will be from interstellar dust, and the mission will provide relevant information on its components and emission properties. A combination of bolometric and radiometric detection techniques will ensure the sensitivity and wide spectral coverage required for accurate foreground discrimination. A far-Earth orbit has been selected to minimize the unwanted emission from the Earth as a source of contamination. The project is currently undergoing a feasibility study within the European Space Agency M3 programme

The COBRAS/SAMBA space mission

COBRAS/SAMBA is an ESA mission designed fur extensive, accurate mapping of the anisotropies of the Cosmic Background Radiation, with angular sensitivity from sub-degree scales up to and overlapping with the COBE-DMR resolution. This will allow a full identification of the primordial density perturbations which grew to form the large-scale structures observed in the present universe. The COBRAS/SAMBA maps will provide powerful tests for the inflationary model and decisive answers on the origin of cosmic structure. A combination of bolometric and radiometric instrumentation will ensure the sensitivity and nide spectral coverage required for accurate foreground discrimination, A far-Earth orbit has been selected to minimize the unwanted emission fi om the Ear th. The project is currently in the Phase A study within the European Space Agency M3 programme

Time dependent neuroprotection of mycophenolate mofetil: effects on temporal dynamics in glial proliferation, apoptosis, and scar formation

BACKGROUND: Immunosuppressants such as mycophenolate mofetil (MMF) have the capacity to inhibit microglial and astrocytic activation and to reduce the extent of cell death after neuronal injury. This study was designed to determine the effective neuroprotective time frame in which MMF elicits its beneficial effects, by analyzing glial cell proliferation, migration, and apoptosis. METHODS: Using organotypic hippocampal slice cultures (OHSCs), temporal dynamics of proliferation and apoptosis after N-methyl-D-aspartate (NMDA)-mediated excitotoxicity were analyzed by quantitative morphometry of Ki-67 or cleaved caspase-3 immunoreactive glial cells. Treatment on NMDA-lesioned OHSCs with mycophenolate mofetil (MMF)100 μg/mL was started at different time points after injury or performed within specific time frames, and the numbers of propidium iodide (PI)(+) degenerating neurons and isolectin (I)B(4)(+) microglial cells were determined. Pre-treatment with guanosine 100 μmol/l was performed to counteract MMF-induced effects. The effects of MMF on reactive astrocytic scar formation were investigated in the scratch-wound model of astrocyte monolayers. RESULTS: Excitotoxic lesion induction led to significant increases in glial proliferation rates between 12 and 36 hours after injury and to increased levels of apoptotic cells between 24 and 72 hours after injury. MMF treatment significantly reduced glial proliferation rates without affecting apoptosis. Continuous MMF treatment potently reduced the extent of neuronal cell demise when started within the first 12 hours after injury. A crucial time-frame of significant neuroprotection was identified between 12 and 36 hours after injury. Pre-treatment with the neuroprotective nucleoside guanosine reversed MMF-induced antiproliferative effects on glial cells. In the scratch-wound model, gap closure was reached within 48 hours in controls, and was potently inhibited by MMF. CONCLUSIONS: Our data indicate that immunosuppression by MMF significantly attenuates the extent of neuronal cell death when administered within a crucial time frame after injury. Moreover, long-lasting immunosuppression, as required after solid-organ transplantation, does not seem to be necessary. Targeting inosine 5-monophosphate dehydrogenase, the rate-limiting enzyme of purine synthesis, is an effective strategy to modulate the temporal dynamics of proliferation and migration of microglia and astrocytes, and thus to reduce the extent of secondary neuronal damage and scar formation

A method for incorporating climate variability in climate change impact assessments: sensitivity of river flows in the Eden catchment to precipitation scenarios

Interest in the impacts of climate change is ever increasing. This is particularly true of the water sector where understanding potential changes in the occurrence of both floods and droughts is important for strategic planning. Climate variability has been shown to have a significant impact on UK climate and accounting for this in future climate cahgne projections is essential to fully anticipate potential future impacts. In this paper a new resampling methodology is developed which includes the variability of both baseline and future precipitation. The resampling methodology is applied to 13 CMIP3 climate models for the 2080s, resulting in an ensemble of monthly precipitation change factors. The change factors are applied to the Eden catchment in eastern Scotland with analysis undertaken for the sensitivity of future river flows to the changes in precipitation. Climate variability is shown to influence the magnitude and direction of change of both precipitation and in turn river flow, which are not apparent without the use of the resampling methodology. The transformation of precipitation changes to river flow changes display a degree of non-linearity due to the catchment's role in buffering the response. The resampling methodology developed in this paper provides a new technique for creating climate change scenarios which incorporate the important issue of climate variability