Assessment of the Red Cell Proteome of Young Patients with Unexplained Hemolytic Anemia by Two-Dimensional Differential In-Gel Electrophoresis (DIGE)

Erythrocyte cytosolic protein expression profiles of children with unexplained hemolytic anemia were compared with profiles of close relatives and controls by two-dimensional differential in-gel electrophoresis (2D-DIGE). The severity of anemia in the patients varied from compensated (i.e., no medical intervention required) to chronic transfusion dependence. Common characteristics of all patients included chronic elevation of reticulocyte count and a negative workup for anemia focusing on hemoglobinopathies, morphologic abnormalities that would suggest a membrane defect, immune-mediated red cell destruction, and evaluation of the most common red cell enzyme defects, glucose-6-phosphate dehydrogenase and pyruvate kinase deficiency. Based upon this initial workup and presentation during infancy or early childhood, four patients classified as hereditary nonspherocytic hemolytic anemia (HNSHA) of unknown etiology were selected for proteomic analysis. DIGE analysis of red cell cytosolic proteins clearly discriminated each anemic patient from both familial and unrelated controls, revealing both patient-specific and shared patterns of differential protein expression. Changes in expression pattern shared among the four patients were identified in several protein classes including chaperons, cytoskeletal and proteasome proteins. Elevated expression in patient samples of some proteins correlated with high reticulocyte count, likely identifying a subset of proteins that are normally lost during erythroid maturation, including proteins involved in mitochondrial metabolism and protein synthesis. Proteins identified with patient-specific decreased expression included components of the glutathione synthetic pathway, antioxidant pathways, and proteins involved in signal transduction and nucleotide metabolism. Among the more than 200 proteins identified in this study are 21 proteins not previously described as part of the erythrocyte proteome. These results demonstrate the feasibility of applying a global proteomic approach to aid characterization of red cells from patients with hereditary anemia of unknown cause, including the identification of differentially expressed proteins as potential candidates with a role in disease pathogenesis

Spatio- temporal variability of vegetation cover over Morocco (1982-2008) : linkages with large scale climate and predictability

The dominant patterns of vegetation cover interannual variability over Morocco are isolated using rotated extended empirical orthogonal functions applied to AVHRR NDVI data (1982-2008). The three leading modes capture the NDVI signal at the vegetation peak for three distinct locations: mode 1 (18.7% of total variance) is located along the Atlantic coastline, mode 2 (13.1%) is southwest of the Riff Mountain whilst mode 3 (11.2%) is along the Mediterranean coastline. Correlations between the NDVI time coefficients for the modes Atlantic' and Mediterranean' dominated by annuals and precipitation amount during the early stage of the vegetation cycle (NDJ) are found. Significant fluctuations of NDVI time coefficients are isolated: a quasi-biennial signal is present in the three modes and an additional quasi-quadriennial (approximate to 4.4 years) signal is identified for the Atlantic' mode only. Connection between vegetation activity and atmospheric and oceanic climate signals are sought using time-lag correlation analyses. The NAO during fall-beginning of winter (NDJ) is found to impact vegetation peak for the Atlantic' mode while the Scandinavian Pattern is related to NDVI peak over the Atlantic' and Riff' latter in the season (DJF). A significant connection is also found between vegetation over the Atlantic' mode and the Riff' and the Atlantic Nino' mode leading the SST variability in the equatorial Atlantic with a 6-months lag. Finally, linkages between NDVI and climate information are used to build a seasonal prediction model for NDVI using multiple linear regression. The NDVI anomalies during March-April may be predicted with a reasonable accuracy from January with 79% of explained variance, 60% and 72% for the Atlantic', the Riff' and the Mediterranean' regions, respectively. Results have (1) direct impacts for a better understanding of the role of large-scale climate signals on vegetation cover over Morocco and (2) contribute to the implementation of an agricultural early warning system

Impact of hospital proportion and volume on primary percutaneous coronary intervention performance in England and Wales.

To quantify the determinants of primary percutaneous coronary intervention (PCI) performance in England and Wales between 2004 and 2007

The nucleolar protein Nop19p interacts preferentially with Utp25p and Dhr2p and is essential for the production of the 40S ribosomal subunit in Saccharomyces cerevisiae

In eukaryotes, ribosome biogenesis is a process of major interest that requires more than 200 factors acting coordinately in time and space. Using genetic and proteomic studies, most of the components have now been identified. Based on its nucleolar localization, we characterized the protein encoded by the open reading frame YGR251W, we renamed Nop19p as playing an essential role in ribosome biogenesis. Depletion of the Nop19p in yeast impairs pre-rRNA processing at sites A0, A1 and A2, leading to a strong decrease in 18S rRNA and 40S subunit levels. Nop19p is a component of 90S preribosomes which assembly is believed to result from stepwise incorporation of UTP modules. We show that Nop19p depletion does not impair the incorporation of UTP subcomplexes on preribosomes and conversely that depletion of UTP subcomplexes does not affect Nop19p recruitment on 90S preribosomes. TAP experiments under stringent conditions revealed that Nop19p interacts preferentially with the DEAH-box RNA helicase Dhr2p and Utp25p, both required for A0, A1 and A2 cleavages. Nop19p appeared essential for the incorporation of Utp25p in preribosomes. In addition, our results suggest that in absence of Nop19p, Dhr2p remains trapped within aberrant preribosomes