TIGAR, a p53-inducible regulator of glycolysis and apoptosis

The p53 tumor-suppressor protein prevents cancer development through various mechanisms, including the induction of cell-cycle arrest, apoptosis, and the maintenance of genome stability. We have identified a p53-inducible gene named TIGAR (TP53-induced glycolysis and apoptosis regulator). TIGAR expression lowered fructose-2,6-bisphosphate levels in cells, resulting in an inhibition of glycolysis and an overall decrease in intracellular reactive oxygen species (ROS) levels. These functions of TIGAR correlated with an ability to protect cells from ROS-associated apoptosis, and consequently, knockdown of endogenous TIGAR expression sensitized cells to p53-induced death. Expression of TIGAR may therefore modulate the apoptotic response to p53, allowing survival in the face of mild or transient stress signals that may be reversed or repaired. The decrease of intracellular ROS levels in response to TIGAR may also play a role in the ability of p53 to protect from the accumulation of genomic damage.     

Anaerobic fermentation of glycerol: a path to economic viability for the biofuels industry

Although biofuels such as biodiesel and bioethanol represent a secure, renewable and environmentally safe alternative to fossil fuels, their economic viability is a major concern. The implementation of biorefineries that co-produce higher value products along with biofuels has been proposed as a solution to this problem. The biorefinery model would be especially advantageous if the conversion of byproducts or waste streams generated during biofuel production were considered. Glycerol-rich streams generated in large amounts by the biofuels industry, especially during the production of biodiesel, present an excellent opportunity to establish biorefineries. Once considered a valuable 'co-product', crude glycerol is rapidly becoming a 'waste product' with a disposal cost attributed to it. Given the highly reduced nature of carbon in glycerol and the cost advantage of anaerobic processes, fermentative metabolism of glycerol is of special interest. This review covers the anaerobic fermentation of glycerol in microbes and the harnessing of this metabolic process to convert abundant and low-priced glycerol streams into higher value products, thus creating a path to viability for the biofuels industry. Special attention is given to products whose synthesis from glycerol would be advantageous when compared with their production from common sugars.     

Structure-Based Mutational Analysis of the C-Terminal DNA-Binding Domain of Human Immunodeficiency Virus Type 1 Integrase: Critical Residues for Protein Oligomerization and DNA Binding

The C-terminal domain of human immunodeficiency virus type 1 (HIV-1) integrase (IN) is a dimer that binds to DNA in a nonspecific manner. The structure of the minimal region required for DNA binding (IN_220–270) has been solved by nuclear magnetic resonance spectroscopy. The overall fold of the C-terminal domain of HIV-1 IN is similar to those of Src homology region 3 domains. Based on the structure of IN_220–270, we studied the role of 15 amino acid residues potentially involved in DNA binding and oligomerization by mutational analysis. We found that two amino acid residues, arginine 262 and leucine 234, contribute to DNA binding in the context of IN_220–270, as indicated by protein-DNA UV cross-link analysis. We also analyzed mutant proteins representing portions of the full-length IN protein. Amino acid substitution of residues located in the hydrophobic dimer interface, such as L241A and L242A, results in the loss of oligomerization of IN; consequently, the levels of 3′ processing, DNA strand transfer, and intramolecular disintegration are strongly reduced. These results suggest that dimerization of the C-terminal domain of IN is important for correct multimerization of IN.     

The functional status of the Helicobacter pylori sabB adhesin gene as a putative marker for disease outcome

Background. Helicobacter pylori factors that contribute to disease outcome are largely unknown, but intimate contact with host cells mediated by outer membrane proteins is thought to play an important role. Expression of the outer membrane proteins OipA, HopZ, SabA, and SabB is regulated by phase‐variable dinucleotide repeats in the coding regions of the respective genes. We have evaluated the correlation between the expression status of these four genes and disease outcome of H. pylori infection in a Dutch patient population. Materials and Methods. H. pylori strains, isolated from 96 Dutch patients with gastritis (n = 29), duodenal ulcer (n = 28), gastric ulcer (n = 21), gastric carcinoma (n = 9), and lymphoma (n = 9), were analyzed for the ‘on/off’ expression status of the H. pylori genes oipA, hopZ, sabA, and sabB by direct DNA sequence analysis of amplified fragments. Results. The off‐status of sabB was significantly associated with duodenal ulcer (p = .036), but not with gastric ulcer. In contrast, the expression status of oipA, hopZ, and sabA did not correlate with disease outcome. Furthermore, lymphoma strains appeared to express a significantly smaller amount of putative adhesins when compared to gastritis, gastric ulcer, duodenal ulcer and gastric carcinoma strains (p < .02 for all groups tested). Conclusion. The off‐status of sabB was found to be associated with duodenal ulcer disease, and thus represents a putative marker for disease outcome. Assuming that SabB is involved in bacterial adhesion, this association suggests that adherent H. pylori are more prone to elimination by the host immune system.     

Landscape Effects on the Presence,Abundance and Diversity of Mosquitoes in Mediterranean Wetlands

Environment determines the distribution of mosquito-borne diseases in that it influences the vector-host-pathogen transmission cycle, including vector distribution, abundance and diversity. In this study, we analyse the relationship between environmental variables estimated by remote sensing and the spatial distribution (presence, abundance and diversity) of seven mosquito species vectors of West Nile and other pathogens (Usutu, avian malaria and dirofilariasis) in the Doñana Natural Park, Spain. Traps were distributed over an area of 54,984 ha divided into six ecological units: marshland, sand dunes, scrubland, ricefields, crops and fishponds. We collected mosquitoes once a month from up to 112 locations using BG-Sentinel traps baited with BG-lure and CO₂ during March-November 2010. Hydroperiod, NDVI and Inundation surface were estimated at several resolution scales (100, 250, 500, 1000 and 2000 metres) from corrected and normalized Landsat Images. We sampled 972,346 female mosquitoes, the most abundant species being Culex theileri, Ochlerotatus caspius, Culex modestus, Culex perexiguus, Culex pipiens, Anopheles atroparvus and Ochlerotatus detritus. Our results suggest that: (1) hydroperiod, inundation surface and NDVI are strongly related to the spatial distribution of mosquitoes; (2) the spatial scales used to measure these variables affected quantification of these relationships, the larger scale being more informative; (3) these relationships are species-specific; (4) hydroperiod is negatively related to mosquito presence and richness; (5) Culex abundance is positively related to hydroperiod; (6) NDVI is positively related to mosquito diversity, presence and abundance, except in the case of the two salt marsh species (Oc. caspius and Oc. detritus); and (7) inundation surfaces positively condition the abundance and richness of most species except the salt marsh mosquitoes. Remote sensing data provided reliable information for monitoring mosquito populations. Landscape significantly affected mosquito distribution and abundance, and as a result may alter disease risk. These results suggest that while environmental conditions affect the distribution and abundance of mosquitoes, other factors such as human modification of landscapes may give rise to significant changes in mosquito populations and consequently disease risk.     

Global abundance of planktonic heterotrophic protists in the deep ocean

The dark ocean is one of the largest biomes on Earth, with critical roles in organic matter remineralization and global carbon sequestration. Despite its recognized importance, little is known about some key microbial players, such as the community of heterotrophic protists (HP), which are likely the main consumers of prokaryotic biomass. To investigate this microbial component at a global scale, we determined their abundance and biomass in deepwater column samples from the Malaspina 2010 circumnavigation using a combination of epifluorescence microscopy and flow cytometry. HP were ubiquitously found at all depths investigated down to 4000 m. HP abundances decreased with depth, from an average of 72±19 cells ml⁻¹ in mesopelagic waters down to 11±1 cells ml⁻¹ in bathypelagic waters, whereas their total biomass decreased from 280±46 to 50±14 pg C ml⁻¹. The parameters that better explained the variance of HP abundance were depth and prokaryote abundance, and to lesser extent oxygen concentration. The generally good correlation with prokaryotic abundance suggested active grazing of HP on prokaryotes. On a finer scale, the prokaryote:HP abundance ratio varied at a regional scale, and sites with the highest ratios exhibited a larger contribution of fungi molecular signal. Our study is a step forward towards determining the relationship between HP and their environment, unveiling their importance as players in the dark ocean''s microbial food web.     

Seed germination responses to soil hydraulic conductivity and polyethylene glycol (PEG) osmotic solutions

Plant and Soil - Seed germination is one of the most important processes in plant biology and ecology because it determines the timing and magnitude of seedling emergence events every growing...