Development of a satellite SAR image spectra and altimeter wave height data assimilation system for ERS-1

The applicability of ERS-1 wind and wave data for wave models was studied using the WAM third generation wave model and SEASAT altimeter, scatterometer and SAR data. A series of global wave hindcasts is made for the surface stress and surface wind fields by assimilation of scatterometer data for the full 96-day SEASAT and also for two wind field analyses for shorter periods by assimilation with the higher resolution ECMWF T63 model and by subjective analysis methods. It is found that wave models respond very sensitively to inconsistencies in wind field analyses and therefore provide a valuable data validation tool. Comparisons between SEASAT SAR image spectra and theoretical SAR spectra derived from the hindcast wave spectra by Monte Carlo simulations yield good overall agreement for 32 cases representing a wide variety of wave conditions. It is concluded that SAR wave imaging is sufficiently well understood to apply SAR image spectra with confidence for wave studies if supported by realistic wave models and theoretical computations of the strongly nonlinear mapping of the wave spectrum into the SAR image spectrum. A closed nonlinear integral expression for this spectral mapping relation is derived which avoids the inherent statistical errors of Monte Carlo computations and may prove to be more efficient numerically

Greenhouse Gas Emissions from European Croplands - Specific Study CarboEurope GHG - Synthesis of the European Greenhouse Gas Budget

Agriculture is a significant source of the three main biogenic greenhouse gases. Since agricultural management is resonsible for much of this flux, there is potential within the EU-15 to reduce this flux or to sequester soil carbon. By comparing country submissions to the UNFCCC with estimates from IPCC defaults and other sources, discrepancies at the national level within the EU can be seen, though total EU-15 figures are similar across methods. Previous studies have focused on the potential for carbon sequestration and have shown quite significant potential. This study, which examinex the sequestration likely to occur by 2010, suggests that without incentives for carbon sequestration in the future, cropland carbon sequestration under Article 3.4 of the Kyoto Protocol will not be an option in EU-15. For reducing emissions of N2O and CH4, there are a number of options that offer significant GHG mitigation, most of which rely upon better fertiliser (mineral and orgnic) use and water management. The livestock and manure management sectors offer greater mitigation potential for methane. There may be trade-offs betweeen different greenhouse gases, especially between carbon dioxide and nitrous oxide, so it is important to assess potential mitigation options for their impact upon all greenhouse gases.JRC.H.2-Climate chang

Greenhouse Gas Emissions from European Grasslands - Specific Study CarboEurope GHG - Synthesis of the European Grennhouse Gas Budget

In the EU 15, there were about 55 million ha of grasslands in the year 2000. Since 1990 some 3 Mha were converted to arable land. Within the EU, grasslands are likely to be a net sink of carbon emission processes, there is potential within the EU to reduce the net GHG flux, expressed in CO2 equivalents. There are clear trade-offs and synergies between different greenhouse gases, which are only now beginning to be quantified. Increased soil carbon storage associated with increased fertiliser use can be offset by increased N2O emissions, while changes to reduce CH4 emissions may cause similar interactions. It is therefore important to assess potential mitigation options for their impact upon all greenhouse gases.JRC.H.2-Climate chang

Inhibition of P2Y6 Signaling in AgRP Neurons Reduces Food Intake and Improves Systemic Insulin Sensitivity in Obesity

Uridine-diphosphate (UDP) and its receptor P2Y6 have recently been identified as regulators of AgRP neurons. UDP promotes feeding via activation of P2Y6 receptors on AgRP neurons, and hypothalamic UDP concentrations are increased in obesity. However, it remained unresolved whether inhibition of P2Y6 signaling pharmacologically, globally, or restricted to AgRP neurons can improve obesity-associated metabolic dysfunctions. Here, we demonstrate that central injection of UDP acutely promotes feeding in diet-induced obese mice and that acute pharmacological blocking of CNS P2Y6 receptors reduces food intake. Importantly, mice with AgRP-neuron-restricted inactivation of P2Y6 exhibit reduced food intake and fat mass as well as improved systemic insulin sensitivity with improved insulin action in liver. Our results reveal that P2Y6 signaling in AgRP neurons is involved in the onset of obesity-associated hyperphagia and systemic insulin resistance. Collectively, these experiments define P2Y6 as a potential target to pharmacologically restrict both feeding and systemic insulin resistance in obesity

Presenilin-1 but not amyloid precursor protein mutations present in Mouse models of alzheimer's disease attenuate the response of cultured Cells to gamma-secretase modulators regardless of their potency and Structure

P>gamma-Secretase modulators (GSMs) inhibit the generation of amyloidogenic A beta 42 peptides and are promising agents for treatment or prevention of Alzheimer's disease (AD). Recently, a second generation of GSMs with favorable pharmacological properties has emerged, but preclinical studies to assess their efficacy in vivo are lacking. Such studies rely on transgenic mouse models that express amyloid precursor protein (APP) and presenilin (PSEN) mutations associated with early-onset familial AD. Previously, we have shown that certain PSEN1 mutations attenuated the response of cultured cells to GSMs and potentially confound in vivo studies in AD mouse models. However, different combinations of familial AD mutations might have synergistic or opposing effects, and we have now systematically determined the response of APP and PSEN1 mutations present in current AD models. Using a potent acidic GSM, we found that APP mutations, either single mutations or in combination, did not affect the potency of GSMs. In contrast, all PSEN1 mutations that have been used to accelerate pathological changes in AD models strongly attenuated the A beta 42-lowering activity of GSMs with two exceptions (M146L, A246E). Similar results were obtained with potent non-acidic GSMs indicating that the attenuating effect of PSEN1 mutations cannot simply be overcome by increased potency or structural changes. Notably, two non-acidic compounds fully compensated the attenuating effect of the PSEN1-G384A mutation. Taken together, our findings indicate that most AD models with rapid pathology and advanced phenotypes are unsuitable for preclinical GSM studies. However, we also provide evidence that additional compound screens could discover GSMs that are able to break the attenuating effects of PSEN mutations

Food Perception Primes Hepatic ER Homeostasis via Melanocortin-Dependent Control of mTOR Activation

Adaptation of liver to the postprandial state requires coordinated regulation of protein synthesis and folding aligned with changes in lipid metabolism. Here we demonstrate that sensory food perception is sufficient to elicit early activation of hepatic mTOR signaling, Xbp1 splicing, increased expression of ER-stress genes, and phosphatidylcholine synthesis, which translate into a rapid morphological ER remodeling. These responses overlap with those activated during refeeding, where they are maintained and constantly increased upon nutrient supply. Sensory food perception activates POMC neurons in the hypothalamus, optogenetic activation of POMC neurons activates hepatic mTOR signaling and Xbp1 splicing, whereas lack of MC4R expression attenuates these responses to sensory food perception. Chemogenetic-POMC-neuron activation promotes sympathetic nerve activity (SNA) subserving the liver, and norepinephrine evokes the same responses in hepatocytes in vitro and in liver in vivo as observed upon sensory food perception. Collectively, our experiments unravel that sensory food perception coordinately primes postprandial liver ER adaption through a melanocortin-SNA-mTOR-Xbp1s axis

Mild Impairment of Mitochondrial OXPHOS Promotes Fatty Acid Utilization in POMC Neurons and Improves Glucose Homeostasis in Obesity

Mitochondrial oxidative phosphorylation (OXPHOS) and substrate utilization critically regulate the function of hypothalamic proopiomelanocortin (POMC)expressing neurons. Here, we demonstrate that inactivation of apoptosis-inducing factor (AIF) in POMC neurons mildly impairs mitochondria! respiration and decreases firing of POMC neurons in lean mice. In contrast, under diet-induced obese conditions, POMC-Cre-specific inactivation of AIF prevents obesity-induced silencing of POMC neurons, translating into improved glucose metabolism, improved leptin, and insulin sensitivity, as well as increased energy expenditure in AIF(Delta POMC) mice. On a cellular level, AIF deficiency improves mitochondrial morphology, facilitates the utilization of fatty acids for mitochondrial respiration, and increases reactive oxygen species (ROS) formation in POMC neurons from obese mice, ultimately leading to restored POMC firing upon HFD feeding. Collectively, partial impairment of mitochondrial function shifts substrate utilization of POMC neurons from glucose to fatty acid metabolism and restores their firing properties, resulting in improved systemic glucose and energy metabolism in obesity