Phosphoenolpyruvate carboxylase dentified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism

Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in thePlasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10Δpepc), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10Δpepc had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using 13C-U-D-glucose and 13C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10Δpepc and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of 13C,15N-U-glutamine was similar in both parasite lines, although the flux was lower in D10Δpepc; it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery

Simvastatin Sodium Salt and Fluvastatin Interact with Human Gap Junction Gamma-3 Protein

Finding pleiomorphic targets for drugs allows new indications or warnings for treatment to be identified. As test of concept, we applied a new chemical genomics approach to uncover additional targets for the widely prescribed lipid-lowering pro-drug simvastatin. We used mRNA extracted from internal mammary artery from patients undergoing coronary artery surgery to prepare a viral cardiovascular protein library, using T7 bacteriophage. We then studied interactions of clones of the bacteriophage, each expressing a different cardiovascular polypeptide, with surface-bound simvastatin in 96-well plates. To maximise likelihood of identifying meaningful interactions between simvastatin and vascular peptides, we used a validated photo-immobilisation method to apply a series of different chemical linkers to bind simvastatin so as to present multiple orientations of its constituent components to potential targets. Three rounds of biopanning identified consistent interaction with the clone expressing part of the gene GJC3, which maps to Homo sapiens chromosome 7, and codes for gap junction gamma-3 protein, also known as connexin 30.2/31.3 (mouse connexin Cx29). Further analysis indicated the binding site to be for the N-terminal domain putatively ‘regulating’ connexin hemichannel and gap junction pores. Using immunohistochemistry we found connexin 30.2/31.3 to be present in samples of artery similar to those used to prepare the bacteriophage library. Surface plasmon resonance revealed that a 25 amino acid synthetic peptide representing the discovered N-terminus did not interact with simvastatin lactone, but did bind to the hydrolysed HMG CoA inhibitor, simvastatin acid. This interaction was also seen for fluvastatin. The gap junction blockers carbenoxolone and flufenamic acid also interacted with the same peptide providing insight into potential site of binding. These findings raise key questions about the functional significance of GJC3 transcripts in the vasculature and other tissues, and this connexin’s role in therapeutic and adverse effects of statins in a range of disease states

Two-Hop-Based Geographic Opportunistic Routing in WSNs

Existing work Geographic opportunistic routing (GOR) selects a forwarding sensor node to progress data packets on the basis of geographic distance. Similarly, the multipath routing uses multiple paths to achieve both reliability and delay. However, geographic opportunistic routing results in lower packet delivery rate and high latency. The multipath routing introduces channel contention, interference, and quick depletion of energy of the sensor node in an asymmetric link wireless environment. The existing work Efficient QoS-aware Geographic Opportunistic Routing (EQGOR) elects and prioritize the forwarding nodes to achieve different QoS parameters. However, inEQGOR, the count of forwarding nodes increases with the increase in the required reliability. To improve energy efficiency, delay, and successful ratio of packet delivery in WSNs, we propose a Two-Hop Geographic Opportunistic Routing (THGOR) protocol that selects a subset of 2-hop neighbors of node which has high packet reception ratio and residual energy at the next forwarder node, and the selected 1-hop neighbors of node has supreme coverage of 2-hop neighbors as relay nodes. THGOR is comprehensively evaluated through ns-2 simulator and compared with existing protocols EQGOR and GOR. Simulation results show that THGOR significant improvement in packet advancement, delay, reliable transmission, and energy efficient

A study on the status of fluoride ion in groundwater of coastal hard rock aquifers of south India

India has an increasing incidence of fluorosis, dental and skeletal, with nearly about 62 million people at risk. High fluoride groundwaters are present especially in the hard rock areas of the country. This paper analyzes the most extensive database on fluoride and other chemical constituent distribution in the coastal hard rock aquifers of Thoothukudi district. A total of 135 samples were collected and analyzed for major cations and anions to assess the geochemical process. The fluoride concentration in drinking waters varied from BDL to 3.2 mg l-1 in the study area. Majority of the samples do not comply with WHO standards for most of the water quality parameters. The saturation index of fluorite saturation index was used to correlate with F- to identify their relationship to increase of fluoride levels. The correlation between the F- concentration and the water type was also attempted. Spatial distribution of fluoride in groundwater was studied to understand the influencing factors. The relationship of F- with HCO- 3, Na+ and pH concentrations were studied and found that HCO- 3, has good correlation with F- than the other parameters

Delineation of Natural and Anthropogenic Process Controlling Hydrogeochemistry of Layered Aquifer Sequence

Groundwater is the source for many activities in urban regions and the quality plays a significant role in determination of its usage. In coastal regions the situation becomes more complex due to the interplay of complex chemical processes like natural weathering, anthropogenic activities and sea water intrusion. Hence an attempt has been made in this study to delineate these processes and to identify the regions dominated by them. In this regard, 92 groundwater samples were collected and analysed for major cations and anions. Among the analysed parameters the ratios of the cations like Ca/Mg, (Ca + Mg)*/HCO3:(Na + K)*/HCO3 were used to identify the process of weathering. Moreover, the ternary plots of cations and selected anions were also used to identify the weathering and the anthropogenic processes. HCO3 − and SiO2 in groundwater were used to unravel the nature of weathering, supported by pH and pCO2 observations. HCO3 −-derived by the carbonate dissolution and silicate weathering were calculated from the total HCO3 − and it was found that HCO3 − derived from the carbonate rock dissolution is dominant in alluvium, tertiary and cretaceous formations due to the presence of kankar, calcareous sandstone and limestone. The (HCO3 + SiO2)/(Cl + NO3) ratios were used to demarcate the regions of weathering and anthropogenic activities and it was found that the central and north eastern part of the study area is dominated by the anthropogenic activities