Inhibition of membrane erythrocyte (Ca2+ + Mg2+)-ATPase by hemin

Red blood cell lysis is a common symptom following severe or prolonged oxidative stress. Oxidative processes occur commonly in sickle cells, probably mediated through denatured hemoglobin and the accumulation of ferric hemes in the membranes. Calmodulin-stimulated (Ca2+ + Mg2+)-ATPase from sickle red cell membranes is partially inactivated (Leclerc et al. (1987) Biochim. Biophys. Acta 897, 33-40). In this study (Ca2+ + Mg2+)-ATPase activity from normal adult erythrocyte membranes was measured in the presence of hemin. We report a time- and concentration-dependent inhibition of the activity of the enzyme by hemin due to a decrease in the maximum velocity. Only a mild inhibitory effect was observed in the presence of iron-free protoporphyrin IX, indicating the catalytic influence of the iron. Experiments carried out with hemin (ferric iron) liganded with imidazole or with reduced protoheme (ferrous iron) liganded with carbon monoxide, demonstrated that the inhibition requires that hemin be capable of binding additional ligands. The inhibition was not influenced by the absence of oxygen but was prevented by addition of bovine serum albumin. Addition of butylated hydroxytoluene, a protective agent of lipid peroxidation, failed to prevent the inhibition of calmodulin-stimulated (Ca2+ + Mg2+)-ATPase. As dithiothreitol partially restores the enzyme activity, we postulated that hemin interacts with the thiol groups of the enzyme.     

Effect of ischemia/reperfusion sequence on cytosolic iron status and its release in the coronary effluent in isolated rat hearts

The hypothesis that oxygen-derived free radicals play an important role in myocardial ischemic and reperfusion injury has received a lot of support. In the presence of catalytic amounts of transition metals such as iron, superoxide anions, and hydrogen peroxide can be transformed into a highly reactive hydroxyl radical °OH (Haber-Weiss reaction). In view of this, we have undertaken this study to investigate whether iron is involved in the reperfusion syndrome and therefore could aggravate free radicals injury. Coronary effluent iron concentrations and cardiac cytosolic iron levels were evaluated in rat hearts subjected to an ischemia/reperfusion sequences. In the case of total ischemia, iron concentration in coronary effluents peaked immediately in the first sample collected upon reperfusion. However, in the case of partial ischemia, iron concentration in coronary effluents peaked rather exclusively during ischemia period. Cardiac cytosolic iron level augmented significantly after 30 min of total ischemia and non significantly in the other ischemia protocols compared to perfused control hearts. It also appears that the iron released is not protein-bound, and could therefore have a marked catalytic activity. The results of the present study suggest that in the oxygen paradox, iron plays an important role in inducing alterations during reoxygenation.     

Effects of 5'deoxy-5'-methylthioadenosine on the metabolism of S-adenosyl methionine

The treatment of transformed rat cells with micromolar amounts of 5'deoxy 5'methyl thioadenosine induces rapid effects on the rate of methylation of DNA concomitantly with alterations of intracellular pools of S-adenosyl methionine and S-adenosyl homocysteine. Pulse chase labelling experiments indicate that 5'deoxy 5'methylthioadenosine does not inhibit the degradation of S-adenosyl homocysteine but inhibits the consumption of S-adenosyl methionine. In vitro transmethylation assays performed with heterologous DNA show that low doses of the thioethernucleoside do not significantly affect the DNA methyltransferase activity of cellular extracts. The biological role of 5'deoxy 5'methylthioadenosine, a natural molecule formed during the synthesis of polyamines is discussed.     

Effect of flower traits and hosts on the abundance of parasitoids in perennial multiple species wildflower strips sown within oilseed rape (<Emphasis Type="Italic">Brassica napus</Emphasis>) crops

Reducing the use of insecticides is an important issue for agriculture today. Sowing wildflower strips along field margins or within crops represents a promising tool to support natural enemy populations in agricultural landscapes and, thus, enhance conservation biological control. However, it is important to sow appropriate flower species that attract natural enemies efficiently. The presence of prey and hosts may also guide natural enemies to wildflower strips, potentially preventing them from migrating into adjacent crops. Here, we assessed how seven flower traits, along with the abundance of pollen beetles (Meligethes spp., Coleoptera: Nitidulidae) and true weevils (Ceutorhynchus spp., Coleoptera: Curculionidae), affect the density of parasitoids of these two coleopterans in wildflower strips sown in an oilseed rape field in Gembloux (Belgium). Only flower traits, not host (i.e. pollen beetles and true weevils) abundance, significantly affected the density of parasitoids. Flower colour, ultraviolet reflectance and nectar availability were the main drivers affecting parasitoids. These results demonstrate how parasitoids of oilseed rape pests react to flower cues under field conditions. Similar analyses on the pests and natural enemies of other crops are expected to help to develop perennial flower mixtures able to enhance biological control throughout a rotation system.     

Rab35 GTPase and cancer: Linking membrane trafficking to tumorigenesis

Rab35 is a small GTPase that is involved in many cellular processes, including membrane trafficking, cell polarity, lipid homeostasis, immunity, phagocytosis and cytokinesis. Recent studies showed that activating mutations confer Rab35 with oncogenic properties. Conversely, downregulation of Rab35 inverts apico‐basal cell polarity and promotes cell migration. Here we review Rab35’s known functions in membrane trafficking and signaling, cell division and cell migration in cancer cells and discuss the importance of Rab35‐dependent membrane trafficking in cancer progression.      

Death and brain death: a new formulation for Canadian medicine. Canadian Congress Committee on Brain Death.

Between June 1984 and December 1986, 35 patients with acute myocardial infarction received streptokinase intravenously within 3 hours after the beginning of chest pain and underwent percutaneous transluminal coronary angioplasty (PTCA) either immediately (in 2 cases) or 1 to 19 (mean 4.4) days later (in 33). The rate of successful PTCA was 89%. Reocclusion occurred in one patient. The mean percentage of stenosis decreased from 86% to 11%. The mean trans-stenotic gradient was reduced from 41 to 11 mm Hg. The results suggest that in patients whose condition is stable, PTCA performed a few days after thrombolysis is a valuable alternative to more aggressive treatment with immediate PTCA.     

RNA and β-Hemolysin of Group B Streptococcus Induce Interleukin-1β (IL-1β) by Activating NLRP3 Inflammasomes in Mouse Macrophages

The inflammatory cytokine IL-1β is critical for host responses against many human pathogens. Here, we define Group B Streptococcus (GBS)-mediated activation of the Nod-like receptor-P3 (NLRP3) inflammasome in macrophages. NLRP3 activation requires GBS expression of the cytolytic toxin, β-hemolysin, lysosomal acidification, and leakage. These processes allow the interaction of GBS RNA with cytosolic NLRP3. The present study supports a model in which GBS RNA, along with lysosomal components including cathepsins, leaks out of lysosomes and interacts with NLRP3 to induce IL-1β production.     

Topography and Land Cover of Watersheds Predicts the Distribution of the Environmental Pathogen Mycobacterium ulcerans in Aquatic Insects

Background

An understanding of the factors driving the distribution of pathogens is useful in preventing disease. Often we achieve this understanding at a local microhabitat scale; however the larger scale processes are often neglected. This can result in misleading inferences about the distribution of the pathogen, inhibiting our ability to manage the disease. One such disease is Buruli ulcer, an emerging neglected tropical disease afflicting many thousands in Africa, caused by the environmental pathogen Mycobacterium ulcerans. Herein, we aim to describe the larger scale landscape process describing the distribution of M. ulcerans.

Methodology

Following extensive sampling of the community of aquatic macroinvertebrates in Cameroon, we select the 5 dominant insect Orders, and conduct an ecological niche model to describe how the distribution of M. ulcerans positive insects changes according to land cover and topography. We then explore the generalizability of the results by testing them against an independent dataset collected in a second endemic region, French Guiana.

Principal Findings

We find that the distribution of the bacterium in Cameroon is accurately described by the land cover and topography of the watershed, that there are notable seasonal differences in distribution, and that the Cameroon model does not predict the distribution of M. ulcerans in French Guiana.

Conclusions/Significance

Future studies of M. ulcerans would benefit from consideration of local structure of the local stream network in future sampling, and further work is needed on the reasons for notable differences in the distribution of this species from one region to another. This work represents a first step in the identification of large-scale environmental drivers of this species, for the purposes of disease risk mapping.