Cytoadherence and sequestration in Plasmodium falciparum: defining the ties that bind

Infected erythrocytes containing the more mature stages of the human malaria Plasmodium falciparum may adhere to endothelial cells and uninfected red cells. These phenomena, called sequestration and rosetting, respectively, are involved in both host pathogenesis and parasite survival. This review provides a critical summary of recent advances in the characterization of the molecules of the infected red blood cell involved in adhesion, i.e. parasite-encoded molecules (PfEMP1, MESA, rifins, stevor, clag 9, histidine-rich protein), a modified host membrane protein (band 3) and exofacial exposure of phosphatidylserine, as well as receptors on the endothelium, i.e. thrombospondin, CD36, ICAM-1 (intercellular adhesion molecule), and chondroitin sulfate.     

Effects of intraperitoneally administered lipoic acid,vitamin E,and linalool on the level of total lipid and fatty acids in guinea pig brain with oxidative stress induced by H2O2

The aim of our study was to investigate the protective effects of intraperitoneally-administrated vitamin E, dlalpha lipoic acid, and linalool on the level of total lipid and fatty acid in guinea pig brains with oxidative stress that was induced by H2O2. The total brain lipid content in the H2O2 group decreased when compared to the H2O2 + vitamin E (p<0.05), H2O2+ linalool (p<0.05), ALA (p<0.05), control (p<0.01), linalool (p<0.01), and vitamin E (p<0.01) groups. While the proportion of total saturated fatty acid ( infinity SFA) in the H2O2 group significantly increased (p<0.005) when compared to the vitamin E group, it only slightly increased (p<0.01) when compared to the control and H2O2 + vitamin E groups. The ratio of the total unsaturated fatty acid (infinity USFA) in the H2O2 groups was lower (p<0.05) than the control, vitamin E, and H2O2+ vitamin E groups. The level of the total polyunsaturated fatty acid (infinity USFA) in the H2O2 group decreased in when compared to the control, vitamin E, and H2O2+vitamin E groups. While the proportion of the total w3 (omega 3), w6 (omega 6), and PUFA were found to be lowest in the H2O2 group, they were slightly increased (p<0.05) in the lipoic acid group when compared to the control and H2O2 + lipoic acid groups. However, the level of infinity SFA in the H2O2 group was highest; the level of infinity USFA in same group was lowest. As the proportion of infinity USFA and infinity PUFA were found to be highest in the linalool group, they were decreased in the H2O2 group when compared to the control group. Our results show that linalool has antioxidant properties, much the same as vitamin E and lipoic acid, to prevent lipid peroxidation. Additionally, vitamin E, lipoic acid, and linalool could lead to therapeutic approaches for limiting damage from oxidation reaction in unsaturated fatty acids, as well as for complementing existing therapy for the treatment of complications of oxidative damage.     

Symbiotic Bradyrhizobium japonicum Reduces N2O Surrounding the Soybean Root System via Nitrous Oxide Reductase

N₂O reductase activity in soybean nodules formed with Bradyrhizobium japonicum was evaluated from N₂O uptake and conversion of ¹⁵N-N₂O into ¹⁵N-N₂. Free-living cells of USDA110 showed N₂O reductase activity, whereas a nosZ mutant did not. Complementation of the nosZ mutant with two cosmids containing the nosRZDFYLX genes of B. japonicum USDA110 restored the N₂O reductase activity. When detached soybean nodules formed with USDA110 were fed with ¹⁵N-N₂O, they rapidly emitted ¹⁵N-N₂ outside the nodules at a ratio of 98.5% of ¹⁵N-N₂O uptake, but nodules inoculated with the nosZ mutant did not. Surprisingly, N₂O uptake by soybean roots nodulated with USDA110 was observed even in ambient air containing a low concentration of N₂O (0.34 ppm). These results indicate that the conversion of N₂O to N₂ depends exclusively on the respiratory N₂O reductase and that soybean roots nodulated with B. japonicum carrying the nos genes are able to remove very low concentrations of N₂O.     

Effects of gene dosage and sequence modification on the frequency and timing of transposition of the maize element Activator (Ac) in tobacco

The effect of Ac copy number on the frequency and timing of germinal transposition in tobacco was investigated using the streptomycin phosphotransferase gene (SPT) as an excision marker. The activity of one and two copies of the element was compared by selecting heterozygous and homozygous progeny of transformants carrying single SPT::Ac inserts. It was observed that increasing gene copy not only increases the transposition frequency, but also occasionally alters the timing of transposition such that earlier events are obtained. The result is that some homozygous plants generate multiple streptomycin resistant progeny carrying the same transposed Ac (trAc) element. We have also investigated the effect of modification of the sequence in the region around 82 bp downstream of the polyadenylation site and 177 bp from the 3 end of the element on germinal excision frequencies. Alteration of three bases to create a BglII site at this location caused a minor decrease in germinal excision events, but insertion of four bases to create a Cla I site caused a 10-fold decrease in the transposition activity of the Ac element.     

Direct participation of potassium ion in the catalysis of coenzyme B(12)-dependent diol dehydratase.

The direct ion-dipolar interactions between potassium ion (K(+)) and the two hydroxyl groups of the substrate are the most striking feature of the crystal structure of coenzyme B(12)-dependent diol dehydratase. We carried out density-functional-theory computations to determine whether K(+) can assist the 1,2-shift of the hydroxyl group in the substrate-derived radical. Between a stepwise abstraction/recombination reaction proceeding via a direct hydroxide abstraction by K(+) and a concerted hydroxyl group migration assisted by K(+), only a transition state for the latter concerted mechanism was found from our computations. The barrier height for the transition state from the complexed radical decreases by only 2.3 kcal/mol upon coordination of the migrating hydroxyl group to K(+), which corresponds to a 42-fold rate acceleration at 37 degrees C. The net binding energy upon replacement of the K(+)-bound water for substrate was calculated to be 10.7 kcal/mol. It can be considered that such a large binding energy is at least partly used for the substrate-induced conformational changes in the enzyme that trigger the homolytic cleavage of the Co-C bond of the coenzyme and the subsequent catalysis by a radical mechanism. We propose here a new mechanism for diol dehydratase in which K(+) plays a direct role in the catalysis.     

Distribution of albatross remains in the Far East regions during the Holocene, based on zooarchaeological remains

Many albatross remains have been found in the Japanese Islands and the surrounding areas, such as Sakhalin and South Korea. These remains are interesting for two reasons: numerous sites from which albatross remains have been found are located in coastal regions of the Far East where no albatrosses have been distributed recently, and there are some sites in which albatross remains represent a large portion of avian remains, although albatrosses are not easily preyed upon by human beings. We collected data on albatross remains from archaeological sites in the Far East regions during the Holocene and arranged the remains geographically, temporally and in terms of quantity. Based on these results, we showed that coastal areas along the Seas of Okhotsk and Japan have rarely been used by albatrosses in Modern times, though formerly there were many albatrosses. We proposed two explanations for the shrinkage of their distributional range: excessive hunting in the breeding areas, and distributional changes of prey for albatrosses.     

Folding of the Tetrahymena ribozyme by polyamines: importance of counterion valence and size

Polyamines are abundant metabolites that directly influence gene expression. Although the role of polyamines in DNA condensation is well known, their role in RNA folding is less understood. Non-denaturing gel electrophoresis was used to monitor the equilibrium folding transitions of the Tetrahymena ribozyme in the presence of polyamines. All of the polyamines tested induce near-native structures that readily convert to the native conformation in Mg(2+). The stability of the folded structure increases with the charge of the polyamine and decreases with the size of the polyamine. When the counterion excluded volume becomes large, the transition to the native state does not go to completion even under favorable folding conditions. Brownian dynamics simulations of a model polyelectrolyte suggest that the kinetics of counterion-mediated collapse and the dimensions of the collapsed RNA chains depend on the structure of the counterion. The results are consistent with delocalized condensation of polyamines around the RNA. However, the effective charge of the counterions is lowered by their excluded volume. The stability of the folded RNA is enhanced when the spacing between amino groups matches the distance between adjacent phosphate groups. These results show how changes in intracellular polyamine concentrations could alter RNA folding pathways.     

Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26

The inhibition of the caspase-3 enzyme is reported to increase neuronal cell survival following cerebral ischemia. The peptide Z-DEVD-FMK is a specific caspase inhibitor, which significantly reduces vulnerability to the neuronal cell death. However, this molecule is unable to cross the blood-brain barrier (BBB) and to diffuse into the brain tissue. Thus, the development of an effective delivery system is needed to provide sufficient drug concentration into the brain to prevent cell death. Using the avidin (SA)-biotin (BIO) technology, we describe here the design of chitosan (CS) nanospheres conjugated with poly(ethylene glycol) (PEG) bearing the OX26 monoclonal antibody whose affinity for the transferrin receptor (TfR) may trigger receptor-mediated transport across the BBB. These functionalized CS-PEG-BIO-SA/OX26 nanoparticles (NPs) were characterized for their particle size, zeta potential, drug loading capacity, and release properties. Fluorescently labeled CS-PEG-BIO-SA/OX26 nanoparticles were administered systemically to mice in order to evaluate their efficacy for brain translocation. The results showed that an important amount of nanoparticles were located in the brain, outside of the intravascular compartment. These findings, which were also confirmed by electron microscopic examination of the brain tissue indicate that this novel targeted nanoparticulate drug delivery system was able to translocate into the brain tissue after iv administration. Consequently, these novel nanoparticles are promising carriers for the transport of the anticaspase peptide Z-DEVD-FMK into the brain.