Disease-specific, neurosphere-derived cells as models for brain disorders

There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson's disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery

A search for edge-on galaxy lenses in the CFHT Legacy Survey

[ABRIDGED] The new generation of wide field optical imaging like the Canada France Hawaii Telescope Legacy Survey (CFHTLS) enables discoveries of all types of gravitational lenses present in the sky. The Strong Lensing Legacy Survey (SL2S) project has started an inventory, respectively for clusters or groups of galaxies lenses, and for Einstein rings around distant massive ellipticals. Here we attempt to extend this inventory by finding lensing events produced by massive edge-on disk galaxies which remains a poorly documented class of lenses. We implement and test an automated search procedure of edge-on galaxy lenses in the CFHTLS Wide fields with magnitude 18Comment: several major edits, 8 pages, A&A accepte

\u27Vitamin D and cognition in older adults\u27: updated international recommendations.

BACKGROUND: Hypovitaminosis D, a condition that is highly prevalent in older adults aged 65 years and above, is associated with brain changes and dementia. Given the rapidly accumulating and complex contribution of the literature in the field of vitamin D and cognition, clear guidance is needed for researchers and clinicians. METHODS: International experts met at an invitational summit on \u27Vitamin D and Cognition in Older Adults\u27. Based on previous reports and expert opinion, the task force focused on key questions relating to the role of vitamin D in Alzheimer\u27s disease and related disorders. Each question was discussed and voted using a Delphi-like approach. RESULTS: The experts reached an agreement that hypovitaminosis D increases the risk of cognitive decline and dementia in older adults and may alter the clinical presentation as a consequence of related comorbidities; however, at present, vitamin D level should not be used as a diagnostic or prognostic biomarker of Alzheimer\u27s disease due to lack of specificity and insufficient evidence. This population should be screened for hypovitaminosis D because of its high prevalence and should receive supplementation, if necessary; but this advice was not specific to cognition. During the debate, the possibility of \u27critical periods\u27 during which vitamin D may have its greatest impact on the brain was addressed; whether hypovitaminosis D influences cognition actively through deleterious effects and/or passively by loss of neuroprotection was also considered. CONCLUSIONS: The international task force agreed on five overarching principles related to vitamin D and cognition in older adults. Several areas of uncertainty remain, and it will be necessary to revise the proposed recommendations as new findings become available

The Sloan Digital Sky Survey Quasar Lens Search. IV. Statistical Lens Sample from the Fifth Data Release

We present the second report of our systematic search for strongly lensed quasars from the data of the Sloan Digital Sky Survey (SDSS). From extensive follow-up observations of 136 candidate objects, we find 36 lenses in the full sample of 77,429 spectroscopically confirmed quasars in the SDSS Data Release 5. We then define a complete sample of 19 lenses, including 11 from our previous search in the SDSS Data Release 3, from the sample of 36,287 quasars with i<19.1 in the redshift range 0.6<z<2.2, where we require the lenses to have image separations of 1"<\theta<20" and i-band magnitude differences between the two images smaller than 1.25 mag. Among the 19 lensed quasars, 3 have quadruple-image configurations, while the remaining 16 show double images. This lens sample constrains the cosmological constant to be \Omega_\Lambda=0.84^{+0.06}_{-0.08}(stat.)^{+0.09}_{-0.07}(syst.) assuming a flat universe, which is in good agreement with other cosmological observations. We also report the discoveries of 7 binary quasars with separations ranging from 1.1" to 16.6", which are identified in the course of our lens survey. This study concludes the construction of our statistical lens sample in the full SDSS-I data set.Comment: 37 pages, 2 figures and 5 tables, accepted to A

A fusion of minicircle DNA and nanoparticle delivery technologies facilitates therapeutic genetic engineering of autologous canine olfactory mucosal cells

Olfactory ensheathing cells (OECs) promote axonal regeneration and improve locomotor function when transplanted into the injured spinal cord. A recent clinical trial demonstrated improved motor function in domestic dogs with spinal injury following autologous OEC transplantation. Their utility in canines offers promise for human translation, as dogs are comparable to humans in terms of clinical management and genetic/environmental variation. Moreover, the autologous, minimally invasive derivation of OECs makes them viable for human spinal injury investigation. Genetic engineering of transplant populations may augment their therapeutic potential, but relies heavily on viral methods which have several drawbacks for clinical translation. We present here the first proof that magnetic particles deployed with applied magnetic fields and advanced DNA minicircle vectors can safely bioengineer OECs to secrete a key neurotrophic factor, with an efficiency approaching that of viral vectors. We suggest that our alternative approach offers high translational potential for the delivery of augmented clinical cell therapies

OC6 Phase I: Investigating the underprediction of low-frequency hydrodynamic loads and responses of a floating wind turbine

Phase I of the OC6 project is focused on examining why offshore wind design tools underpredict the response (loads/motion) of the OC5-DeepCwind semisubmersible at its surge and pitch natural frequencies. Previous investigations showed that the underprediction was primarily related to nonlinear hydrodynamic loading, so two new validation campaigns were performed to separately examine the different hydrodynamic load components. In this paper, we validate a variety of tools against this new test data, focusing on the ability to accurately model the low-frequency loads on a semisubmersible floater when held fixed under wave excitation and when forced to oscillate in the surge direction. However, it is observed that models providing better load predictions in these two scenarios do not necessarily produce a more accurate motion response in a moored configuration.The authors would like to acknowledge the support of the MARINET2 project (European Union’s Horizon 2020 grant agreement 731084), which supplied the tank test time and travel support to accomplish the testing campaign. The support of MARIN in the preparation, execution of the modeltests, and the evaluation of the uncertainties was essential for this study. MARIN’s contribution was partly funded by the Dutch Ministry of Economic Affairs through TKI-ARD funding programs. This work was authored in part by the National Renewable Energy Laboratory, operated by Alliance for Sustainable Energy, LLC, for the U.S. Department of Energy (DOE) under Contract No. DE-AC36- 08GO28308. Funding provided by the U.S. Department of Energy Office of Energy Efficiency and Renewable Energy Wind Energy Technologies Office. The views expressed in the article do not necessarily represent the views of the DOE or the U.S. Government. The U.S. Government retains and the publisher, by accepting the article for publication, acknowledges that the U.S. Government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this work, or allow others to do so, for U.S. Government purposes

Overview of the Chemistry-Aerosol Mediterranean Experiment/Aerosol Direct Radiative Forcing on the Mediterranean Climate (ChArMEx/ADRIMED) summer 2013 campaign

The Chemistry-Aerosol Mediterranean Experiment (ChArMEx; http://charmex.lsce.ipsl.fr) is a collaborative research program federating international activities to investigate Mediterranean regional chemistry-climate interactions. A special observing period (SOP-1a) including intensive airborne measurements was performed in the framework of the Aerosol Direct Radiative Impact on the regional climate in the MEDiterranean region (ADRIMED) project during the Mediterranean dry season over the western and central Mediterranean basins, with a focus on aerosol-radiation measurements and their modeling. The SOP-1a took place from 11 June to 5 July 2013. Airborne measurements were made by both the ATR-42 and F-20 French research aircraft operated from Sardinia (Italy) and instrumented for in situ and remote-sensing measurements, respectively, and by sounding and drifting balloons, launched in Minorca. The experimental setup also involved several ground-based measurement sites on islands including two ground-based reference stations in Corsica and Lampedusa and secondary monitoring sites in Minorca and Sicily. Additional measurements including lidar profiling were also performed on alert during aircraft operations at EARLINET/ACTRIS stations at Granada and Barcelona in Spain, and in southern Italy. Remote-sensing aerosol products from satellites (MSG/SEVIRI, MODIS) and from the AERONET/PHOTONS network were also used. Dedicated meso-scale and regional modeling experiments were performed in relation to this observational effort. We provide here an overview of the different surface and aircraft observations deployed during the ChArMEx/ADRIMED period and of associated modeling studies together with an analysis of the synoptic conditions that determined the aerosol emission and transport. Meteorological conditions observed during this campaign (moderate temperatures and southern flows) were not favorable to producing high levels of atmospheric pollutants or intense biomass burning events in the region. However, numerous mineral dust plumes were observed during the campaign, with the main sources located in Morocco, Algeria and Tunisia, leading to aerosol optical depth (AOD) values ranging between 0.2 and 0.6 (at 440 nm) over the western and central Mediterranean basins. One important point of this experiment concerns the direct observations of aerosol extinction onboard the ATR-42, using the CAPS system, showing local maxima reaching up to 150Mm(-1) within the dust plume. Non-negligible aerosol extinction (about 50Mm(-1)) has also been observed within the marine boundary layer (MBL). By combining the ATR- 42 extinction coefficient observations with absorption and scattering measurements, we performed a complete optical closure revealing excellent agreement with estimated optical properties. This additional information on extinction properties has allowed calculation of the dust single scattering albedo (SSA) with a high level of confidence over the western Mediterranean. Our results show a moderate variability from 0.90 to 1.00 (at 530 nm) for all flights studied compared to that reported in the literature on this optical parameter. Our results underline also a relatively low difference in SSA with values derived near dust sources. In parallel, active remote-sensing observations from the surface and onboard the F-20 aircraft suggest a complex vertical structure of particles and distinct aerosol layers with sea spray and pollution located within the MBL, and mineral dust and/or aged North American smoke particles located above (up to 6–7 km in altitude). Aircraft and balloon-borne observations allow one to investigate the vertical structure of the aerosol size distribution showing particles characterized by a large size (> 10 μm in diameter) within dust plumes. In most of cases, a coarse mode characterized by an effective diameter ranging between 5 and 10 μm, has been detected above the MBL. In terms of shortwave (SW) direct forcing, in situ surface and aircraft observations have been merged and used as inputs in 1-D radiative transfer codes for calculating the aerosol direct radiative forcing (DRF). Results show significant surface SW instantaneous forcing (up to (-90)Wm(-2) at noon). Aircraft observations provide also original estimates of the vertical structure of SW and LW radiative heating revealing significant instantaneous values of about 5 K per day in the solar spectrum (for a solar angle of 30 ) within the dust layer. Associated 3-D modeling studies from regional climate (RCM) and chemistry transport (CTM) models indicate a relatively good agreement for simulated AOD compared with observations from the AERONET/PHOTONS network and satellite data, especially for long-range dust transport. Calculations of the 3-D SW (clear-sky) surface DRF indicate an average of about -10 to -20Wm(-2) (for the whole period) over the Mediterranean Sea together with maxima (-50Wm(-2)) over northern Africa. The top of the atmosphere (TOA) DRF is shown to be highly variable within the domain, due to moderate absorbing properties of dust and changes in the surface albedo. Indeed, 3-D simulations indicate negative forcing over the Mediterranean Sea and Europe and positive forcing over northern Africa. Finally, a multiyear simulation, performed for the 2003 to 2009 period and including an ocean–atmosphere (O–A) coupling, underlines the impact of the aerosol direct radiative forcing on the sea surface temperature, O–A fluxes and the hydrological cycle over the Mediterranean.French National Research Agency (ANR) ANR-11-BS56-0006ADEMEFrench Atomic Energy CommissionCNRS-INSU and Meteo-France through the multidisciplinary programme MISTRALS (Mediterranean Integrated Studies aT Regional And Local Scales)CORSiCA project - Collectivite Territoriale de Corse through Fonds Europeen de Developpement Regional of the European Operational ProgramContrat de Plan Etat-RegionEuropean Union's Horizon 2020 research and innovation program 654169Spanish Ministry of Economy and Competitivity TEC2012-34575Science and Innovation UNPC10-4E-442European Union (EU)Department of Economy and Knowledge of the Catalan Autonomous Government SGR 583Andalusian Regional Government P12-RNM-2409Spanish Government CGL2013-45410-R 26225