The effects of Cstb duplication on APP/amyloid-β pathology and cathepsin B activity in a mouse model

People with Down syndrome (DS), caused by trisomy of chromosome 21 have a greatly increased risk of developing Alzheimer's disease (AD). This is in part because of triplication of a chromosome 21 gene, APP. This gene encodes amyloid precursor protein, which is cleaved to form amyloid-β that accumulates in the brains of people who have AD. Recent experimental results demonstrate that a gene or genes on chromosome 21, other than APP, when triplicated significantly accelerate amyloid-β pathology in a transgenic mouse model of amyloid-β deposition. Multiple lines of evidence indicate that cysteine cathepsin activity influences APP cleavage and amyloid-β accumulation. Located on human chromosome 21 (Hsa21) is an endogenous inhibitor of cathepsin proteases, CYSTATIN B (CSTB) which is proposed to regulate cysteine cathepsin activity in vivo. Here we determined if three copies of the mouse gene Cstb is sufficient to modulate amyloid-β accumulation and cathepsin activity in a transgenic APP mouse model. Duplication of Cstb resulted in an increase in transcriptional and translational levels of Cstb in the mouse cortex but had no effect on the deposition of insoluble amyloid-β plaques or the levels of soluble or insoluble amyloid-β42, amyloid-β40, or amyloid-β38 in 6-month old mice. In addition, the increased CSTB did not alter the activity of cathepsin B enzyme in the cortex of 3-month or 6-month old mice. These results indicate that the single-gene duplication of Cstb is insufficient to elicit a disease-modifying phenotype in the dupCstb x tgAPP mice, underscoring the complexity of the genetic basis of AD-DS and the importance of multiple gene interactions in disease

Regional scale rain-forest height mapping using regression-kriging of spaceborne and airborne lidar data : application on French Guiana

LiDAR data has been successfully used to estimate forest parameters such as canopy heights and biomass. Major limitation of LiDAR systems (airborne and spaceborne) arises from their limited spatial coverage. In this study, we present a technique for canopy height mapping using airborne and spaceborne LiDAR data (from the Geoscience Laser Altimeter System (GLAS)). First, canopy heights extracted from both airborne and spaceborne LiDAR were extrapolated from available environmental data. The estimated canopy height maps using Random Forest (RF) regression from airborne or GLAS calibration datasets showed similar precisions (~6 m). To improve the precision of canopy height estimates, regression-kriging was used. Results indicated an improvement in terms of root mean square error (RMSE, from 6.5 to 4.2 m) using the GLAS dataset, and from 5.8 to 1.8 m using the airborne LiDAR dataset. Finally, in order to investigate the impact of the spatial sampling of future LiDAR missions on canopy height estimates precision, six subsets were derived from the initial airborne LiDAR dataset. Results indicated that using the regression-kriging approach a precision of 1.8 m on the canopy height map was achievable with a flight line spacing of 5 km. This precision decreased to 4.8 m for flight line spacing of 50 km

LAV@HAZARD: A Web-Gis interface for volcanic hazard assessment

Satellite data, radiative power of hot spots as measured with remote sensing, historical records, on site geological surveys, digital elevation model data, and simulation results together provide a massive data source to investigate the behavior of active volcanoes like Mount Etna (Sicily,Italy) over recent times. The integration of these eterogeneous data into a coherent visualization framework is important for their practical exploitation. It is crucial to fill in the gap between experimental and numerical data, and the direct human perception of their meaning. Indeed, the people in charge of safety planning of an area need to be able to quickly assess hazards and other relevant issues even during critical situations. With this in mind, we developed LAV@HAZARD, a web-based geographic information system that provides an interface for the collection of all of the products coming from the LAVA project research activities. LAV@HAZARD is based on Google Maps application programming interface, a choice motivated by its ease of use and the user-friendly interactive environment it provides. In particular, the web structure consists of four modules for satellite applications (time-space evolution of hot spots, radiant flux and effusion rate), hazard map visualization, a database of ca. 30,000 lava-flow simulations, and real-time scenario forecasting by MAGFLOW on Compute Unified Device Architecture

A role for GPx3 in activity of normal and leukemia stem cells

The determinants of normal and leukemic stem cell self-renewal remain poorly characterized. We report that expression of the reactive oxygen species (ROS) scavenger glutathione peroxidase 3 (GPx3) positively correlates with the frequency of leukemia stem cells (LSCs) in Hoxa9+Meis1-induced leukemias. Compared with a leukemia with a low frequency of LSCs, a leukemia with a high frequency of LSCs showed hypomethylation of the Gpx3 promoter region, and expressed high levels of Gpx3 and low levels of ROS. LSCs and normal hematopoietic stem cells (HSCs) engineered to express Gpx3 short hairpin RNA (shRNA) were much less competitive in vivo than control cells. However, progenitor cell proliferation and differentiation was not affected by Gpx3 shRNA. Consistent with this, HSCs overexpressing Gpx3 were significantly more competitive than control cells in long-term repopulation experiments, and overexpression of the self-renewal genes Prdm16 or Hoxb4 boosted Gpx3 expression. In human primary acute myeloid leukemia samples, GPX3 expression level directly correlated with adverse prognostic outcome, revealing a potential novel target for the eradication of LSCs

UFGM - 2006 Annual Report

INGV, SEZIONE DI CATANIAPublished2.6. TTC - Laboratorio di gravimetria, magnetismo ed elettromagnetismo in aree attiveope

Image labeling and grouping by minimizing linear functionals over cones

We consider energy minimization problems related to image labeling, partitioning, and grouping, which typically show up at mid-level stages of computer vision systems. A common feature of these problems is their intrinsic combinatorial complexity from an optimization pointof-view. Rather than trying to compute the global minimum - a goal we consider as elusive in these cases - we wish to design optimization approaches which exhibit two relevant properties: First, in each application a solution with guaranteed degree of suboptimality can be computed. Secondly, the computations are based on clearly defined algorithms which do not comprise any (hidden) tuning parameters. In this paper, we focus on the second property and introduce a novel and general optimization technique to the field of computer vision which amounts to compute a sub optimal solution by just solving a convex optimization problem. As representative examples, we consider two binary quadratic energy functionals related to image labeling and perceptual grouping. Both problems can be considered as instances of a general quadratic functional in binary variables, which is embedded into a higher-dimensional space such that sub optimal solutions can be computed as minima of linear functionals over cones in that space (semidefinite programs). Extensive numerical results reveal that, on the average, sub optimal solutions can be computed which yield a gap below 5% with respect to the global optimum in case where this is known

Effects of proton versus photon irradiation on (lymph) angiogenic, inflammatory, proliferative and anti-tumor immune responses in head and neck squamous cell carcinoma

International audienceThe proximity of organs at risk makes the treatment of head and neck squamous cell carcinoma (HNSCC) challenging by standard radiotherapy. The higher precision in tumor targeting of proton (P) therapy could promote it as the treatment of choice for HNSCC. Besides the physical advantage in dose deposition, few is known about the biological impact of P versus photons (X) in this setting. To investigate the comparative biological effects of P versus X radiation in HNSCC cells, we assessed the relative biological effectiveness (RBE), viability, proliferation and mRNA levels for genes involved in (lymph)angiogenesis, inflammation, proliferation and anti-tumor immunity. These parameters, particularly VEGF-C protein levels and regulations, were documented in freshly irradiated and/or long-term surviving cells receiving low/high-dose, single (SI)/multiple (MI) irradiations with P/X. The RBE was found to be 1.1 Key (lymph)angiogenesis and inflammation genes were downregulated (except for vegf-c) after P and upregulated after X irradiation in MI surviving cells, demonstrating a more favorable profile after P irradiation. Both irradiation types stimulated vegf-c promoter activity in a NF-κB-dependent transcriptional regulation manner, but at a lesser extent after P, as compared to X irradiation, which correlated with mRNA and protein levels. The cells surviving to MI by P or X generated tumors with higher volume, anarchic architecture and increased density of blood vessels. Increased lymphangiogenesis and a transcriptomic analysis in favor of a more aggressive phenotype were observed in tumors generated with X-irradiated cells. Increased detection of lymphatic vessels in relapsed tumors from patients receiving X radiotherapy was consistent with these findings. This study provides new data about the biological advantage of P, as compared to X irradiation. In addition to its physical advantage in dose deposition, P irradiation may help to improve treatment approaches for HNSCC