Mutations in the Catalytic Loop HRD Motif Alter the Activity and Function of Drosophila Src64

The catalytic loop HRD motif is found in most protein kinases and these amino acids are predicted to perform functions in catalysis, transition to, and stabilization of the active conformation of the kinase domain. We have identified mutations in a Drosophila src gene, src64, that alter the three HRD amino acids. We have analyzed the mutants for both biochemical activity and biological function during development. Mutation of the aspartate to asparagine eliminates biological function in cytoskeletal processes and severely reduces fertility, supporting the amino acid's critical role in enzymatic activity. The arginine to cysteine mutation has little to no effect on kinase activity or cytoskeletal reorganization, suggesting that the HRD arginine may not be critical for coordinating phosphotyrosine in the active conformation. The histidine to leucine mutant retains some kinase activity and biological function, suggesting that this amino acid may have a biochemical function in the active kinase that is independent of its side chain hydrogen bonding interactions in the active site. We also describe the phenotypic effects of other mutations in the SH2 and tyrosine kinase domains of src64, and we compare them to the phenotypic effects of the src64 null allele

Conserved Genes Act as Modifiers of Invertebrate SMN Loss of Function Defects

Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species

Mobility, turnover and storage of pollutants in soils, sediments and waters : achievements and results of the EU project AquaTerra : a review.

AquaTerra is one of the first environmental projects within the 6th Framework program by the European Commission. It began in June 2004 with a multidisciplinary team of 45 partner organizations from 13 EU countries, Switzerland, Serbia, Romania and Montenegro. Results from sampling and modeling in 4 large river basins (Ebro, Danube, Elbe and Meuse) and one catchment of the Brévilles Spring in France led to new evaluations of diffuse and hotspot input of persistent organic and metal pollutants including dynamics of pesticides and polycyclic aromatic hydrocarbons, as well as metal turnover and accumulation. While degradation of selected organic compounds could be demonstrated under controlled conditions in the laboratory, turnover of most persistent pollutants in the field seems to range from decades to centuries. First investigations of long-term cumulative and degradation effects, particularly in the context of climate change, have shown that it is also necessary to consider the predictions of more than one climate model when trying to assess future impacts. This is largely controlled by uncertainties in climate model responses. It is becoming evident, however, that changes to the climate will have important impacts on the diffusion and degradation of pollutants in space and time that are just at the start of their exploration

SiPM-based neutron Anger camera with auto-calibration capabilities

International audienceWe present characterization results of a neutron Anger camera based on a lithium-6 loaded cerium activated silicate glass scintillator (33.3 × 33.3 × 1 mm3) and an array of 64 silicon photomultipliers. Reconstruction of the scintillation events is performed with a statistical method, implemented on a graphics processing unit (GPU). We demonstrate that the light response model of the detector can be obtained from flood irradiation calibration data using an unsupervised iterative procedure. The useful field of view is 28 × 28 mm2. The spatial resolution measured at 2.5 Å neutron beam is better than 0.6 mm FWHM and the energy resolution at the neutron peak is 11%