In conditions of limited chromophore supply rods entrap 11-cis-retinal leading to loss of cone function and cell death

RPE65 is a retinoid isomerase required for the production of 11-cis-retinal, the chromophore of both cone and rod visual pigments. We recently established an R91W knock-in mouse strain as homologous animal model for patients afflicted by this mutation in RPE65. These mice have impaired vision and can only synthesize minute amounts of 11-cis-retinal. Here, we investigated the consequences of this chromophore insufficiency on cone function and pathophysiology. We found that the R91W mutation caused cone opsin mislocalization and progressive geographic cone atrophy. Remnant visual function was mostly mediated by rods. Ablation of rod opsin corrected the localization of cone opsin and improved cone retinal function. Thus, our analyses indicate that under conditions of limited chromophore supply rods and cones compete for 11-cis-retinal that derives from regeneration pathway(s) which are reliant on RPE65. Due to their higher number and the instability of cone opsin, rods are privileged under this condition while cones suffer chromophore deficiency and degenerate. These findings reinforce the notion that in patients any effective gene therapy with RPE65 needs to target the cone-rich macula directly to locally restore the cones' chromophore supply outside the reach of rod

Fenologia do cafeeiro: condições agrometeorológicas e balanço hídrico do ano agrícola 2004-2005.

Durante todas as fases fenológicas do cafeeiro, o clima exerce grande infl uência sobre a incidência de pragas e doenças e, consequentemente, atua sobre a produtividade do cafeeiro e a qualidade da bebida. Adversidades climáticas, como acentuada defi ciência hídrica e extremos de temperatura do ar, podem resultar em redução drástica de produtividade do cafeeiro, embora os efeitos dependam da duração e da intensidade dessas adversidades, e também do estádio fenológico da planta. O monitoramento agrometeorológico da cultura do café é um recurso precioso para avaliar como esses elementos climáticos interferem diretamente na fenologia e na incidência de pragas e doenças no cafeeiro. Nesse monitoramento, devem ser caracterizados os períodos com excedente e com defi ciência hídrica, ao longo do ano, por meio do balanço hídrico sequencial, que é feito utilizandose uma das seguintes bases: diária, decendial (com frequência de 10 dias), semanal e mensal. Também devem ser analisadas as condições termopluviométricas do período em questão, segundo as fases fenológicas da planta, assim como deve ser considerado o levantamento de pragas e doenças no decorrer do ciclo do cafeeiro. Para dar continuidade ao trabalho iniciado no ano agrícola 2002?2003, este documento interpreta os balanços hídricos e as condições termopluviométricas referentes ao ano agrícola 2004?2005, de algumas regiões cafeeiras dos estados de Minas Gerais, São Paulo e Paraná. A importância desse monitoramento está no suporte técnico que ele oferece a tomadores de decisão, graças à disponibilização de informações agrometeorológicas históricas, relacionadas ao cafeeiro arábica produzido nessas regiões.bitstream/item/29356/1/Fenologia-do-cafeeiro.pd

Potentiale zur Integration von Elektrofahrzeugen in innerstädtischen Verkehrsstrukturen : Schlußbericht zum Forschungs- und Entwicklungsvorhaben FE-Nr. 70386/92 des Bundesministers für Verkehr, Bonn

Die vorliegende Studie untersucht, aufgrund umfangreicher Erfahrungen aus Praxistests, welche Energie in kWh/km bisher gebaute Elektrofahrzeuge mit unterschiedlichen Batterien bei unterschiedlichen Tagesfahrleistungen verbrauchen. Die für die Ladung der Traktionsbatterien notwendigen "Stromtankstellen", unterteilt in Haupt- und Nachladestellen, können auf der Basis der vorhandenen Technik installiert werden, wobei Normungen durchgeführt und Genehmigungsverfahren vereinfacht werden sollten. Hauptladestellen werden hauptsächlich Steckdosen in Garagen und privaten Parkanlagen sein, die mit geringen Kosten installierbar sind. Durch den Ersatz von Fahrzeugen mit konventionellem Otto- und Dieselantrieb durch Elektrofahrzeuge läßt sich der verkehrsbedingte CO2-Ausstoß mindern, wenn die CO2-Emissionen bei der Bereitstellung des elektrischen Stroms geringer sind als die mit der Nutzung fossiler Treibstoffe verbundenen Emissionen. Eine Minderung der CO2-Emissionen bei der Stromemerzeugung kann insbesondere durch die Nutzung von CO2-freien Energieträgern erreicht werden. Das Forschungsvorhaben zeigt, daß Elektrofahrzeuge kaufbar sind, die Infrastruktur für ihre Energieversorgung mit der heutigen Technik geschaffen und die Energie für 2 Mio. Elektrofahrzeuge von dem heutigen Kraftwerkspark - vor allem während der Nacht - zur Verfügung gestellt werden kann

Interannual variability (2000–2013) of mesopelagic and bathypelagic particle fluxes in relation to variable sea ice cover in the eastern Fram Strait

The Fram Strait connects the Atlantic and Arctic Oceans and is a key conduit for sea ice advected southward by the Transpolar Drift and northward inflow of warm Atlantic Waters. Continued sea ice decline and “Atlantification” are expected to influence pelagic–benthic coupling in the Fram Strait and Arctic as a whole. However, interannual variability and the impact of changing ice conditions on deepwater particle fluxes in the Arctic remain poorly characterized. Here, we present long-term sediment trap records (2000–2013) from mesopelagic (200 m) and bathypelagic (2,300 m) depths at two locations (HGIV and HGN) in the Fram Strait subjected to variable ice conditions. Sediment trap catchment areas were estimated and combined with remote sensing data and a high-resolution model to determine the ice cover, chlorophyll concentration, and prevailing stratification regimes. Surface chlorophyll increased between 2000 and 2013, but there was no corresponding increase in POC flux, suggesting a shift in the efficiency of the biological carbon pump. A decrease in particulate biogenic Si flux, %opal, Si:POC, and Si:PIC at mesopelagic depths indicates a shift away from diatom-dominated export as a feasible explanation. Biogenic components accounted for 72% ± 16% of mass flux at 200 m, but were reduced to 34% ± 11% at 2,300 m, substituted by a residual (lithogenic) material. Total mass fluxes of biogenic components, including POC, were higher in the bathypelagic. Biomarkers and ∂13C values suggest both lateral advection and ice-rafted material contribute to benthic carbon input, although constraining their precise contribution remains challenging. The decadal time series was used to describe two end-members of catchment area conditions representing the maximum temperatures of Atlantic inflow water in 2005 at HGIV and high ice coverage and a meltwater stratification regime at HGN in 2007. Despite similar chlorophyll concentrations, bathypelagic POC flux, Si flux, Si:POC, and Si:PIC were higher and POC:PIC was lower in the high-ice/meltwater regime. Our findings suggest that ice concentration and associated meltwater regimes cause higher diatom flux. It is possible this will increase in the future Arctic as meltwater regimes increase, but it is likely to be a transient feature that will disappear when no ice remains

Noninvasive, In Vivo Assessment of Mouse Retinal Structure Using Optical Coherence Tomography

BACKGROUND: Optical coherence tomography (OCT) is a novel method of retinal in vivo imaging. In this study, we assessed the potential of OCT to yield histology-analogue sections in mouse models of retinal degeneration. METHODOLOGY/PRINCIPAL FINDINGS: We achieved to adapt a commercial 3(rd) generation OCT system to obtain and quantify high-resolution morphological sections of the mouse retina which so far required in vitro histology. OCT and histology were compared in models with developmental defects, light damage, and inherited retinal degenerations. In conditional knockout mice deficient in retinal retinoblastoma protein Rb, the gradient of Cre expression from center to periphery, leading to a gradual reduction of retinal thickness, was clearly visible and well topographically quantifiable. In Nrl knockout mice, the layer involvement in the formation of rosette-like structures was similarly clear as in histology. OCT examination of focal light damage, well demarcated by the autofluorescence pattern, revealed a practically complete loss of photoreceptors with preservation of inner retinal layers, but also more subtle changes like edema formation. In Crb1 knockout mice (a model for Leber's congenital amaurosis), retinal vessels slipping through the outer nuclear layer towards the retinal pigment epithelium (RPE) due to the lack of adhesion in the subapical region of the photoreceptor inner segments could be well identified. CONCLUSIONS/SIGNIFICANCE: We found that with the OCT we were able to detect and analyze a wide range of mouse retinal pathology, and the results compared well to histological sections. In addition, the technique allows to follow individual animals over time, thereby reducing the numbers of study animals needed, and to assess dynamic processes like edema formation. The results clearly indicate that OCT has the potential to revolutionize the future design of respective short- and long-term studies, as well as the preclinical assessment of therapeutic strategies

Diagnosis of rabies and eastern and western equine viral encephalitides in equids by multiplex Hemi-Nested RT-PCR technique

Financial support: CNPq and Pasteur Institute of São PauloTrabalho apresentado à 23ª Reunião Internacional da Raiva nas Américas, 2012, São Paulo