Cerebrovascular and blood-brain barrier impairments in Huntington's disease: Potential implications for its pathophysiology: Vascular impairments in HD

ObjectiveAlthough the underlying cause of Huntington's disease (HD) is well established, the actual pathophysiological processes involved remain to be fully elucidated. In other proteinopathies such as Alzheimer's and Parkinson's diseases, there is evidence for impairments of the cerebral vasculature as well as the blood–brain barrier (BBB), which have been suggested to contribute to their pathophysiology. We investigated whether similar changes are also present in HD.MethodsWe used 3‐ and 7‐Tesla magnetic resonance imaging as well as postmortem tissue analyses to assess blood vessel impairments in HD patients. Our findings were further investigated in the R6/2 mouse model using in situ cerebral perfusion, histological analysis, Western blotting, as well as transmission and scanning electron microscopy.ResultsWe found mutant huntingtin protein (mHtt) aggregates to be present in all major components of the neurovascular unit of both R6/2 mice and HD patients. This was accompanied by an increase in blood vessel density, a reduction in blood vessel diameter, as well as BBB leakage in the striatum of R6/2 mice, which correlated with a reduced expression of tight junction‐associated proteins and increased numbers of transcytotic vesicles, which occasionally contained mHtt aggregates. We confirmed the existence of similar vascular and BBB changes in HD patients.InterpretationTaken together, our results provide evidence for alterations in the cerebral vasculature in HD leading to BBB leakage, both in the R6/2 mouse model and in HD patients, a phenomenon that may, in turn, have important pathophysiological implications. Ann Neurol 2015;78:160–17

Benchmarking carbon fluxes of the ISIMIP2a biome models

The purpose of this study is to evaluate the eight ISIMIP2a biome models against independent estimates of long-term net carbon fluxes (i.e. Net Biome Productivity, NBP) over terrestrial ecosystems for the recent four decades (1971–2010). We evaluate modeled global NBP against 1) the updated global residual land sink (RLS) plus land use emissions (E LUC) from the Global Carbon Project (GCP), presented as R + L in this study by Le Quéré et al (2015), and 2) the land CO2 fluxes from two atmospheric inversion systems: Jena CarboScope s81_v3.8 and CAMS v15r2, referred to as F Jena and F CAMS respectively. The model ensemble-mean NBP (that includes seven models with land-use change) is higher than but within the uncertainty of R + L, while the simulated positive NBP trend over the last 30 yr is lower than that from R + L and from the two inversion systems. ISIMIP2a biome models well capture the interannual variation of global net terrestrial ecosystem carbon fluxes. Tropical NBP represents 31 ± 17% of global total NBP during the past decades, and the year-to-year variation of tropical NBP contributes most of the interannual variation of global NBP. According to the models, increasing Net Primary Productivity (NPP) was the main cause for the generally increasing NBP. Significant global NBP anomalies from the long-term mean between the two phases of El Niño Southern Oscillation (ENSO) events are simulated by all models (p < 0.05), which is consistent with the R + L estimate (p = 0.06), also mainly attributed to NPP anomalies, rather than to changes in heterotrophic respiration (Rh). The global NPP and NBP anomalies during ENSO events are dominated by their anomalies in tropical regions impacted by tropical climate variability. Multiple regressions between R + L, F Jena and F CAMS interannual variations and tropical climate variations reveal a significant negative response of global net terrestrial ecosystem carbon fluxes to tropical mean annual temperature variation, and a non-significant response to tropical annual precipitation variation. According to the models, tropical precipitation is a more important driver, suggesting that some models do not capture the roles of precipitation and temperature changes adequately

Coupling of the deoxygenation of benzoic acid with the oxidation of propylene as a new tool to elucidate the architecture of Mo-based oxide catalysts

This work aimed to develop in a two-step strategy the deoxygenation of benzoic acid as a new probe reaction of the oxidation catalysts "at work". This choice was based on the experimental fact that the distribution of the potential main products, namely benzaldehyde, toluene and benzene depends on the presence and the mutual disposition of oxygen vacancies at the surface of the oxide catalysts. Indeed, it is claimed in the literature that single oxygen vacancies selectively produces benzaldehyde, twin oxygen vacancies (i.e. two oxygen vacancies separated by about 2Å) induce the formation of toluene while the benzene production does not need the presence of any oxygen vacancies. Two molybdenum based catalytic systems were chosen to test the new probe reaction : the molybdenum (sub)oxides and the metal molybdates. By the way of a new and original coupling between the probe reaction and the oxidation of propylene, we planned to correlate in real time the formation of the superficial oxygen vacancies monitored by the deoxygenation of benzoic acid and the activity in an oxidation reaction. Such an experimental coupling is a promising and a powerful tool which allows the fine characterization of the active catalytic site at work in an oxidation reaction.(AGRO 3)--UCL, 200

The deoxygenation of benzoic acid as a probe reaction to determine the impact of superficial oxygen vacancies (isolated or twin) on the oxidation performances of Mo-based oxide catalysts

The deoxygenation of benzoic acid (DBA) is a probe reaction of the organisation of oxygen vacancies at the surface of molybdenum based oxide catalysts. In the present work, the DBA was used in coupling with the selective oxidation of propylene so that it could offer an insight into the nature of oxygen vacancies involved in the later reaction. By correlating the superficial oxidation state of the catalytic elements measured by X-ray photoelectron spectroscopy with the information provided by the DBA probe reaction, it was possible to progress in the description of the atomic scale architecture of the oxidation sites at work. Sites bringing boosted performances in the oxidation of propylene are those which are slightly reduced thanks to the presence of single (isolated) oxygen vacancies. Conversely, twin oxygen vacancies do not participate in the oxidation reaction. (C) 2006 Elsevier B.V. All rights reserved

Interaction of N2O(as gas dope) with nickel molybdate catalysts during the oxidative dehydrogenation of propane to propylene

We report effects brought about by the introduction of N2O as gas dope in the reaction feed during the oxidative dehydrogenation of propane to propylene on nickel molybdate catalysts. The addition of N2O modifies the catalytic performances. At low concentration (300 ppm) of N2O, the conversion of propane decreases, the yield in propylene increases and the selectivity to propylene is improved. Decreases in the oxygen consumption, in the yield and in the selectivity in CO2 were also observed. N2O induces the reduction of Mo at the surface of the catalyst. This is supposed to occur through an inhibition of the adsorption Of O-2 because of the presence of N2O at the surface of the catalyst, which thus slows down the reoxidation rate of the catalyst. In presence of N2O, catalytic sites thus work in a more reduced state. At higher concentrations of N2O (1-10% in volume), the selectivity in propylene decreases, the oxygen consumption and the selectivity to CO2 decrease further. The catalyst is more deeply reduced and carbonaceous products is formed. These observations are interpreted as being due to the inhibition effect evoked at low concentration but additionally to a direct reduction of the catalytic surface brought about by N2O. Propylene is produced from propane in presence of pure N2O. But this probably occurs only under transitory conditions as N2O probably needs the presence of molecular oxygen to produce propylene durably. This work shows that adjusting the concentration of promoters, like N2O and CO2, could be a useful tool to modulate the oxidation state of oxide catalysts at work during the catalytic reaction, and thus their catalytic performances. (C) 2003 Elsevier Science B.V. All rights reserved

Coupling the deoxygenation of benzoic acid with the oxidation of propylene on a Co molybdate catalyst

An innovating coupling between the deoxygenation of benzoic acid and the oxidation of propylene was set up and gave new information about the mechanism involved in the oxidation of propylene on a Co-Mo based oxide catalyst. The production of CO, during the catalytic reaction is bound to the formation of benzene and benzaldehyde. The first case corresponds to the removal of the carboxyl function of the benzoic acid. The second case is the evidence that benzaldehyde and products coining from the oxidation of propylene are formed on the same catalytic sites during the Mars, and van Krevelen cycle. In this cycle, the oxygen atoms used for the oxidation come from the benzoic acid by the intermediate of the oxide lattice. In particular, it has been demonstrated that the oxidation of propylene involves lattice oxygen atoms far from each other in such a way that the reaction leaves single oxygen vacancies at the surface of the catalyst. Such coupling between a deoxygenation reaction and an oxidation one is reported for the first time. (c) 2005 Elsevier B.V. All rights reserved

Probing the reduction state of Mo oxide catalysts by the deoxygenation of carboxylic acid

This work investigates the potentiality of the deoxygenation of benzoic acid in the presence of hydrogen as a probe of the reduction state of molybdenum oxide in catalytic processes. On one hand, a complicated hysteresis phenomenon is observed when measuring the conversion of benzoic acid and selectivities to benzene, toluene and benzaldehyde Of Mo8O23 along a cycle of temperatures between 628 and 723 K. On the other hand, Mo8O23 undergoes a reduction to Mo4O11 and MoO2 throughout the catalytic reaction. These results, together with the performances Of Mo4O11 and MoO2 under the same conditions, allow to understand the reduction pathway Of Mo8O23. The proposed pathway fits with that suggested in the literature, thus confirming the deoxygenation of benzoic acid as a promising probe reaction of the behavior of molybdenum based oxides at work. (C) 2004 Elsevier B.V. All rights reserved

Tuning the selectivity of MoOx supported catalysts for cyclohexane photo oxidehydrogenation

The photocatalytic properties of sulphated MoOx/gamma-Al2O3 catalysts in cyclohexane oxidative dehydrogenation have been determined in a two-dimensional fluidized bed photoreactor and compared to those of sulphated MoOx/TiO2 catalysts. Photocatalytic tests on MoOx/gamma-Al2O3 at 8 wt% MoO3 and various sulphate contents showed the selective (100%) formation of cyclohexene, without production of benzene, as instead found with MoOx/TiO2. These results show that the selectivity of photocatalytic cyclohexane oxydehydrogenation is dramatically influenced by the catalyst support. Maximum cyclohexane conversion and cyclohexene yield of 11% were obtained for SO4 content of 2.6 wt% at 120 degrees C. Physico-chemical characterisation of catalysts indicates the presence of both octahedral polymolybdate and sulphate species on alumina surface, as previously found for titania. Increasing sulphate load, thermogravimetry evidenced the presence of up to three sulphate species at different thermal stability. The lower activity observed at high sulphate content is likely due to polymolybdate decoration by sulphates. (c) 2007 Elsevier B.V. All rights reserved