531 research outputs found

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

    Get PDF
    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

    "New" Veneziano amplitudes from "old" Fermat (hyper) surfaces

    Get PDF
    The history of discovery of bosonic string theory is well documented. This theory evolved as an attempt to find a multidimensional analogue of Euler's beta function. Such an analogue had in fact been known in mathematics literature at least in 1922 and was studied subsequently by mathematicians such as Selberg, Weil and Deligne among others. The mathematical interpretation of this multidimensional beta function is markedly different from that described in physics literature. This paper aims to bridge the gap between the existing treatments. Preserving all results of conformal field theories intact, developed formalism employing topological, algebro-geometric, number-theoretic and combinatorial metods is aimed to provide better understanding of the Veneziano amplitudes and, thus, of string theories.Comment: 92 pages LaTex, some typos removed, discussion section is added along with several additional latest reference

    Introducing the “analogs for Venus’ geologically recent surfaces” initiative: an opportunity for identifying and analyzing recently active volcano-tectonic areas of Venus trough a comparative study with terrestrial analogs

    Get PDF
    Several missions to Venus have been recently selected for launch [1–6], opening a new era for the exploration of the planet. One of the key questions that the future missions need to address is whether Venus is presently volcanically active [7–15]. Studying areas of active volcanism and tectonism on Venus is crucial to reveal clues about the geologic past of the planet, as well as provide information about the volatile content of its interior and the formation of its dense atmosphere. The “Analogsfor VENus’ GEologically Recent Surfaces” (AVENGERS) initiative aims to build a comprehensive database of terrestrial analog sites for the comparative study of recent and possibly on- going volcanic activity on Venus. Besides its scientific relevance, the AVENG- ERS initiative also acts as a bridge for international scientific collaboration, including the leadership and/or team members from the currently selected missions to Venus

    Can serum hyaluronic acid replace simple non-invasive indexes to predict liver fibrosis in HIV/Hepatitis C coinfected patients?

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Hyaluronic acid (HA) serum levels correlate with the histological stages of liver fibrosis in hepatitis C virus (HCV) monoinfected patients, and HA alone has shown very good diagnostic accuracy as a non-invasive assessment of fibrosis and cirrhosis. The aim of this study was to evaluate serum HA levels as a simple non-invasive diagnostic test to predict hepatic fibrosis in HIV/HCV-coinfected patients and to compare its diagnostic performance with other previously published simple non-invasive indexes consisting of routine parameters (HGM-1, HGM-2, Forns, APRI, and FIB-4).</p> <p>Methods</p> <p>We carried out a cross-sectional study on 201 patients who all underwent liver biopsies and had not previously received interferon therapy. Liver fibrosis was determined via METAVIR score. The diagnostic accuracy of HA was assessed by area under the receiver operating characteristic curves (AUROCs).</p> <p>Results</p> <p>The distribution of liver fibrosis in our cohort was 58.2% with significant fibrosis (F≥2), 31.8% with advanced fibrosis (F≥3), and 11.4% with cirrhosis (F4). Values for the AUROC of HA levels corresponding to significant fibrosis (F≥2), advanced fibrosis (F≥3) and cirrhosis (F4) were 0.676, 0.772, and 0.863, respectively. The AUROC values for HA were similar to those for HGM-1, HGM-2, FIB-4, APRI, and Forns indexes. The best diagnostic accuracy of HA was found for the diagnosis of cirrhosis (F4): the value of HA at the low cut-off (1182 ng/mL) excluded cirrhosis (F4) with a negative predictive value of 99% and at the high cut-off (2400 ng/mL) confirmed cirrhosis (F4) with a positive predictive value of 55%. By utilizing these low and high cut-off points for cirrhosis, biopsies could have theoretically been avoided in 52.2% (111/201) of the patients.</p> <p>Conclusions</p> <p>The diagnostic accuracy of serum HA levels increases gradually with the hepatic fibrosis stage. However, HA is better than other simple non-invasive indexes using parameters easily available in routine clinical practice only for the diagnosing of cirrhosis.</p
    corecore