Quantitative Determination of Cellular Farnesyltransferase Activity: Towards Defining the Minimum Substrate Reactivity for Biologically Relevant Protein Farnesylation

Prenylation is a post‐translational modification wherein an isoprenoid group is attached to a protein substrate by a protein prenyltransferase. Hundreds of peptide sequences are in vitro substrates for protein farnesyltransferase (FTase), but it remains unknown which of these sequences can successfully compete for in vivo prenylation. Translating in vitro studies to predict in vivo protein farnesylation requires determining the minimum reactivity needed for modification by FTase within the cell. Towards this goal, we developed a reporter protein series spanning several orders of magnitude in FTase reactivity as a calibrated sensor for endogenous FTase activity. Our approach provides a minimally invasive method to monitor changes in cellular FTase activity in response to environmental or genetic factors. Determining the reactivity “threshold” for in vivo prenylation will help define the prenylated proteome and identify prenylation‐dependent pathways for therapeutic targeting.     

Mapping of background air pollution at a fine spatial scale across the European Union

Background

There is a need to understand much more about the geographic variation of air pollutants. This requires the ability to extrapolate from monitoring stations to unsampled locations. The aim was to assess methods to develop accurate and high resolution maps of background air pollution across the EU.

Methods

We compared the validity of ordinary kriging, universal kriging and regression mapping in developing EU-wide maps of air pollution on a 1 × 1 km resolution. Predictions were made for the year 2001 for nitrogen dioxide (NO₂), fine particles < 10 µm (PM₁₀), ozone (O₃), sulphur dioxide (SO₂) and carbon monoxide (CO) using routine monitoring data in Airbase. Predictor variables from EU-wide databases were land use, road traffic, population density, meteorology, altitude, topography and distance to sea. Models were developed for the global, rural and urban scale separately. The best method to model concentrations was selected on the basis of predefined performance measures (R², Root Mean Square Error (RMSE)).

Results

For NO₂, PM₁₀ and O₃ universal kriging performed better than regression mapping and ordinary kriging. Validation of the final universal kriging estimates with results from all validation sites gave R²-values and RMSE-values of 0.61 and 6.73 µg/m³ for NO₂; 0.45 and 5.19 µg/m³ for PM₁₀; and 0.70 and 7.69 µg/m³ for O₃. For SO₂ and CO none of the three methods was able to provide a satisfactory prediction.

Conclusion

Reasonable prediction models were developed for NO₂, PM₁₀ and O₃ on an EU-wide scale. Our study illustrates that it is possible to develop detailed maps of background air pollution using EU-wide databases.     

Land cover mapping with patch-derived landscape indices

Automated-classification procedures of satellite imagery are mainly based on surface reflectance and generally ignore shape and size of landforms. On the other hand, quantitative landscape ecology has been focused on the patch concept as a landscape unit due to its relevance in the theory and practice of the conservation of species in human-modelled landscapes. The present paper explores how landscape metrics can introduce the component of spatial pattern of landscape elements to enhance land cover classification reliability. In particular, a method is proposed to extract patch-derived indices and to introduce them in a supervised classification of Landsat Thematic Mapper (TM) images as neo-channels. To extract patch-derived indices, an image segmentation method based on edge detection was used to define patches without an a priori knowledge of land cover classes. We calculated four patch indices: area, perimeter, shape index and fractal dimension. These indices were introduced in the classification to test the improvement of classification reliability. Well-known additional information (texture and topographic features) was also tested for comparison purposes. The method was tested for mapping land cover types in a mountainous region in the French Pyrenees, the Massif of Arize. The results of classification reliability allowed us to conclude that patch indices and topographic features significantly improved the discrimination of land cover classes. The combination of these additional information types by means of data fusion is useful for land cover classification purposes.     

Bacterial formation of tooeleite and mixed arsenic(III) or arsenic(V)-iron(III) gels in the Carnoulès acid mine drainage,France. A XANES,XRD, and SEM study

The oxidation of Fe(II) in acid mine drainage (AMD) leads to the precipitation of Fe(III) compounds which may incorporate toxic elements, such as arsenic (As), within their structure or adsorb them at their surface, thus limiting their mobility. The present work provides evidence for spatial and seasonal variations of microbial activity that influence arsenite oxidation and As immobilization in the heavily contaminated AMD from the Carnoulès mine, Gard, France ([As III] = 80 to 280 mg x L(-1) in the acidic spring draining the waste-pile). In the first tens of meters of the AMD, the rapid oxidation of Fe(II) leads to the coprecipitation of large amounts of As with Fe(III) in bacterial mats. XRD, XANES, and SEM analyses of sediments and stromatolite samples revealed the unusual formation of As(III)-rich compounds, especially nanocrystalline tooeleite, Fe6(AsO3)4(SO4)(OH)4 x 4H2O, a rare ferric arsenite sulfate oxy-hydroxide mineral, together with XRD-amorphous mixed As(III)/As(V)-Fe(III) oxy-hydroxide compounds. In the wet season, the suspended sediments of the upstream zone essentially consist of tooeleite associated with am-As(III)-Fe(III) oxy-hydroxides, while am-As(V)-Fe(III) oxy-hydroxides, having As:Fe molar ratios as high as 0.6-0.8, dominate in the dry season. Comparing natural and bioassay samples revealed that the formation of As(III)-rich compounds in the wet season may be related to the metabolic activity of bacterial strains able to oxidize Fe(II) but not As(III). One of these strains, having an Acidithiobacillus ferrooxidans genotype, has been isolated from the Carnoulès AMD. In contrast, the formation of As(V)-rich compounds in the dry season can be related to both biotic and abiotic oxidation of As(III) to As(V). Some Thiomonas strains isolated from the Carnoulès AMD were shown to be able to catalyze the oxidation of As(III) to As(V) in solution. Therefore, they can promote the formation of mixed As(V)-Fe(III) oxy-hydroxides, provided enough Fe(II) oxidizes. These results yield a better understanding of natural processes at this site and may help in designing efficient As-removal processes.     

Annual and Seasonal Variations of Hydrological Processes Under Climate Change Scenarios in Two Sub-Catchments of a Complex Watershed

The Elbow River watershed, located in the rain shadow of the Rocky Mountains in western Canada, is characterized by a complex hydrological regime due to significant differences in climate and geomorphological settings between the west and east sub-catchments. This watershed has experienced several extreme droughts and floods in the recent decades, which might be accentuated with climate change. This study was undertaken to investigate the average annual and seasonal variations of surface and sub-surface hydrological processes in the west and east sub-catchments along with and the entire watershed under five plausible GCM-scenarios up to 2070 using the physically-based, distributed MIKE SHE/MIKE 11 model. Most of the scenarios indicate a reduction in the average annual overland flow, groundwater recharge and baseflow in the east sub-catchment. The pattern of seasonal change generally exhibits a rise in overland flow, baseflow, evapotranspiration, groundwater recharge, and streamflow in winter-spring and a decline in summer-fall. The induced changes in hydrological processes are proportionally more perceptible in the east sub-catchment compared to the west sub-catchment. However, the west sub-catchment governs the watershed behaviour and determines the future changes, over-riding the stronger climate change signal in the east. This investigation indicates that a greater understanding of climate change impacts on the water balance of a watershed with significant differences in sub-regional settings is achieved when capturing the surface and subsurface hydrological process responses of each sub-catchment individually along with the entire watershed. Such information can guide water resources management by providing a more rigorous assessment of the processes involved in the watershed.     

Le stress per?u et son influence sur le comportement alimentaire des étudiants de l'Université de Moncton, Campus de Moncton

Objectif. Mesurer et analyser le lien entre le stress per?u et le comportement alimentaire d'étudiants de première (Et1) et de quatrième année (Et4) à l'Université de Moncton au début (T1) et à la fin (T2) du trimestre universitaire. Méthodes. Quatre-vingt-quatorze sujets de divers programmes universitaires ont participé à l'étude. Le stress per?u a été mesuré à l'aide de la Perceived Stress Scale, la consommation alimentaire par un journal alimentaire de trois jours et la fréquence de consommation alimentaire par un questionnaire de fréquence. Résultats. Au début du trimestre, les Et1 et Et4 présentent un niveau de stress faible. Au T2, le stress per?u des Et4 augmente significativement (22,3+/-1,4; p=0,005). Le profil alimentaire mesuré selon le niveau de conformité au "Guide alimentaire canadien pour manger sainement" montre, avec l'accroissement du stress, une augmentation de la consommation de lait et produits laitiers (p=0,05) chez les Et1,T1 et de produits céréaliers (p=0,02) chez les Et4,T2. Une corrélation négative significative est observée chez les Et4 entre le stress per?u et l'ingestion de thiamine (r=-0,48, p=0,006) et de zinc (r=-0,42, p=0,02). Aucune corrélation n'est observée entre le stress, l'apport en calories et la consommation des autres nutriments étudiés. Conclusion. Ces résultats révèlent l'importance d'intervenir auprès des étudiants universitaires et d'implanter des sessions d'information favorisant la gestion du stress et l'adoption de comportements alimentaires sains.     

Synthesis and structure-activity study of quaternary ammonium functionalized beta-cyclodextrin-carboxymethylcellulose polymers

Carboxymethylcellulose (CMC) and beta-cyclodextrin (beta-CD)-based polymers functionalized with two types of quaternary ammonium compounds (QACs), the alkaquat DMB-451 (N-alkyl (50% C14, 40% C12, 10% C10) dimethylbenzylammonium chloride) (DMD-451) named polymer DMB-451, and FMB 1210-8 (a blend of 32 w% N-alkyl (50% C14, 40% C12, 10% C10) dimethylbenzylammonium chloride and 48 w% of didecyldimethylammonium chloride) named polymer FMB 1210-8, were synthethized and characterized by Fourier transform infrared spectroscopy. The antimicrobial activities of these polymers against Eschericia coli were also evaluated at 25 degrees C in wastewater. The results have indicated that the polymer FMB 1210-8 possesses a high-affinity binding with bacterial cells that induces a rapid disinfection process. Moreover, in the same experimental conditions of disinfection (mixture of 1.0 g of polymer and 100 mL of wastewater), the polymer FMB 1210-8 has a higher antimicrobial efficiency (99.90%) than polymer DMB-451 (92.8%). This phenomenon might be associated to a stronger interaction with bacterial cells due to stronger binding affinity for E. coli cells and greater killing efficiency of the C10 alkyl chains QAC of polymer FMB 1210-8 to disrupt the bacterial cell membrane as compared to N-alkyl (50% C14, 40% C12, 10% C10) dimethylbenzylammonium chloride. Together, these results suggest that the polymer FMB 1210-8 could constitute a good disinfectant against Escherichia coli, which could be advantageously used in wastewater treatments due to the low toxicity of beta-CD and CMC, and moderated toxicity of FMB 1210-8 to human and environment.     

Spatial genetic structure and recruitment dynamics of burbot (Lota lota) in Eastern Lake Michigan and Michigan tributaries

Burbot (Lota lota) are the only freshwater member of the Cod like (Lotidae) family that have a circumpolar distribution and occupy the widest geographic distribution of all Laurentian Great Lakes fish species. Information regarding burbot spatial genetic structure and recruitment dynamics is critical for the development of effective management strategies. Although burbot are a species of conservation concern throughout their range, little demographic or behavioral information exists. We estimated levels of genetic diversity within, and the degree of spatial population structure between samples collected from Lake Michigan and tributaries of the Manistee River, MI. Measures of genetic diversity across 10 microsatellite loci were moderately high. Disparities between adult groups sampled in Lake Michigan and the Manistee River were notable for observed heterozygosity (0.662 vs 0.488) and allelic richness (11.7 vs 6.6). Significant levels of inter-population variance in microsatellite allele frequencies (F_ST 0.154 to 0.208) were detected between Lake Michigan and the Manistee River samples. Results indicate reproductive isolation between what plausibly may be riverine and lacustrine spawning life history types. Pedigree analyses for three cohorts sampled in the Manistee River revealed that a sizeable number of adults contributed reproductively to multiple cohorts, indicating spawning philopatry. While data were collected from restricted areas in lacustrine and river habitats, analyses revealing microgeographic genetic structuring, potentially attributed to life history polymorphisms, have significant implications for burbot management in the Great Lakes.     

Expressive control during a disappointment: Variations related to preschoolers' behavior problems.

Individual differences in expressive control during a disappointment were examined in relation to preschool boys' and girls' concurrent behavior and to their risk for developing disruptive behavior disorders. A disappointment paradigm was used to examine expressive control in 79 4- and 5-yr-old children with low, moderate, or high risk. Boys at risk showed more negative emotion in the experimenter's (E's) presence than low-risk boys. In E's absence, low-risk boys' negative emotion was equivalent to at-risk boys'. Boys' negative emotion, particularly anger, predicted their disruptiveness during the disappointment and general symptoms of oppositionality. At-risk girls differed from low-risk girls after E left, displaying less negative emotion than low-risk girls. Girls' minimization of negative emotion predicted attention deficit and conduct disorder symptoms. Gender-specific expressive control is discussed in terms of gender differences in emotion regulation and psychopathology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Determinants of late allograft nephrectomy

When loss of graft function occurs more than six months after transplantation, allograft nephrectomy is not routinely performed at the time of graft failure. It is usually performed only on those patients who subsequently develop specific complications. However, little is known about the characteristics that make patients more likely to require allograft nephrectomy. The purpose of our study was to identify risk factors for the subsequent need for allograft nephrectomy in patients with graft failure occurring more than 6 months after transplantation. Forty-one patients were studied. Inclusion criteria were: loss of graft function > or = 6 months after transplantation, resumption of dialysis and initiation of weaning from immunosuppression. Thirty patients were treated with cyclosporine + prednisone +/- azathioprine and 11 with azathioprine + prednisone. Mean follow-up time was 17.8 months, ranging from 6 months to 6.1 years. Recipient age, sex and race, original renal disease, donor, donor source (cadaveric vs living related), HLA compatibility, levels of panel reactive antibodies, occurrence of initial delayed graft function, causes of graft failure and tapering of immunosuppression were similar in patients with and without allograft nephrectomy. Using univariate analysis, allograft nephrectomy was found to be significantly more frequent in patients with a history of 2 or more episodes of acute rejection than in patients with no rejection episode: 83% vs 30% (p = 0.03). In addition, allograft nephrectomy was found to be significantly more frequent if the immunosuppressive regimen included cyclosporine (62% vs 27.3%; p = 0.04). Using multivariate analysis however, the number of previous episodes of rejection was found to be the only significant predictor for allograft nephrectomy. None of the other variables considered in the multivariate analysis, including the type of immunosuppressive therapy, was identified as a significant predictor for the need to perform allograft nephrectomy. In summary, the need for late allograft nephrectomy was correlated with the number of previous episodes of acute rejection. Patients with a history of numerous rejection episodes should thus be considered more likely to require allograft nephrectomy once immunosuppression is withdrawn. Possible interventions to reduce or prevent the need for nephrectomy include more gradual tapering of immunosuppression at the time of graft failure or indefinite low-dose immunosuppressive therapy.