Recent additions have expanded the interleukin (IL)-1 gene family to 10 members. We have determined the order, orientation, and intergenic distance of the nine IL-1 family genes that lie on human ...chromosome 2. We report cDNA sequences for the mouse orthologs of three of these genes. The order and orientation of the mouse genes have been mapped, and the mouse locus compared with the human locus. There is a break in the mouse locus of > 100 kb, compared with the human locus, located between Il1b and the most centromere-proximal of the novel mouse genes. The mouse seems to be missing an ortholog of human IL1F7.
Folates have a key role in metabolism, and the folate-dependent generation of DNA precursors in the form of deoxythymidine 5′-phosphate is particularly important for the replication of malaria ...parasites. Although Plasmodium falciparum can synthesize folate derivatives de novo , a long-standing mystery has been the apparent absence of a key enzyme, dihydroneopterin aldolase, in the classical folate biosynthetic pathway of this organism. The discovery that a different enzyme, pyruvoyltetrahydropterin synthase, can produce the necessary substrate for the subsequent step in folate synthesis raises the question of whether this solution is unique to P. falciparum . Bioinformatic analyses suggest otherwise and indicate that an alternative route to folate could be widespread among diverse microorganisms and could be a target for novel drugs.
The glycine-cleavage complex (GCV) and serine hydroxymethyltransferase represent the two systems of one-carbon transfer that are employed in the biosynthesis of active folate cofactors in eukaryotes. ...Although the understanding of this area of metabolism in
Plasmodium falciparum is still at an early stage, we discuss evidence that genes and transcription products of the GCV are present and expressed in this parasite. The potential role of the GCV and its relevance to the life cycle and pathogenesis of the malaria erythrocytic stages are also considered. According to its expression profile, the GCV seems to be particularly active in gametocytes. The GCV enzyme dihydrolipoamide dehydrogenase has two isoforms encoded by two different genes. It has been demonstrated recently that both genes are functional, with one of them identified as being part of a pyruvate dehydrogenase complex that is present exclusively in the apicoplast of
Plasmodium species. The other isoform probably forms part of the
Plasmodium GCV. The GCV is the first enzyme complex involved in folate metabolism in this parasite that can be assumed, with a good degree of certainty, to be located in the mitochondria.
The folate pathway represents a powerful target for combating rapidly dividing systems such as cancer cells, bacteria and malaria parasites. Whereas folate metabolism in mammalian cells and bacteria ...has been studied extensively, it is understood less well in malaria parasites. In two articles, we attempt to reconstitute the malaria folate pathway based on available information from mammalian and microbial systems, in addition to
Plasmodium-genome-sequencing projects. In part I, we focused on folate enzymes that are already used clinically as anticancer drug targets or that are under development in drug-discovery programs. In this article, we discuss mammalian folate enzymes that have not yet been exploited as potential drug targets, and enzymes that function in the
de novo folate-synthesis pathway of the parasite – a particularly attractive area of attack because of its absence from the mammalian host.
Sediment samples were collected from a dry wash in Nelson, Nevada where the Techatticup Mine and Mill operated between 1850 and 1960. Samples were used to evaluate movement and behavior of certain ...metals and metalloids including aluminum, arsenic, barium, cadmium, copper, iron, manganese, lead, and vanadium. The data show that some metals and metalloids are more concentrated on larger particles whereas others show the opposite tendency. For example, As was greatest on silt fractions and least on coarse fractions, while Se was detected only on silts. Chromium, Cu, Fe, Mn, Pb, and Zn concentrations all increased with decreasing particle size (silt > sand > coarse), whereas Al, Ba, and V showed the opposite trend (silt < sands < coarse).
Three-dimensional (3D) topological insulator (TI) has emerged as a unique state of quantum matter and generated enormous interests in condensed matter physics. The surfaces of a 3D TI consist of a ...massless Dirac cone, which is characterized by the Z
2
topological invariant. Introduction of magnetism on the surface of a TI is essential to realize the quantum anomalous Hall effect and other novel magneto-electric phenomena. Here, by using a combination of first-principles calculations, magneto-transport and angle-resolved photoemission spectroscopy (ARPES), we study the electronic properties of gadolinium (Gd)-doped Sb
2
Te
3
. Our study shows that Gd doped Sb
2
Te
3
is a spin-orbit-induced bulk band-gap material, whose surface is characterized by a single topological surface state. Our results provide a new platform to investigate the interactions between dilute magnetism and topology in magnetic doped topological materials.
We sought to determine the SAG2 genotypes of Toxoplasma gondii associated with cases of acute human toxoplasmosis in England and Wales. The samples examined were collected from a wide range of cases ...including congenital infections, AIDS and immunosuppressed patients and were derived from a number of different tissues. Parasite DNA was detected by PCR amplification without the need for prior template purification, and SAG2 genotype was determined by both restriction enzyme analysis and direct DNA sequencing of the PCR amplification products. Parasites of both SAG2 type I and type II genotypes were seen with approximately equal frequency amongst the samples examined. Neither of these genotypes was found to be more frequently associated with a particular clinical presentation or sample tissue. Unexpectedly, we found clear evidence of mixed (SAG2 type I+type II) infections in approximately the same number of samples as were seen to be associated with either type I or II alone. Our use of direct DNA sequencing rather than simple restriction analysis was essential for the detection of mixed infections since incomplete restriction digestion of samples containing a single parasite type was occasionally observed. It is possible that the presence of more than one type of parasite in single samples might be related to our recent demonstration that mixtures of SAG2 type I and type II parasites are present in a significant proportion of commercial meat preparations. Moreover, the presence of mixed infections in single patients might offer a direct molecular method of assessing risk factors for infection.
The high hemeozoin (beta-hemeatin) content of Plasmodium falciparum lysates imposes severe limitations on the analysis of the malarial proteome, in particular compromising the loading capacities of ...two-dimensional gels. Here we report on the adaptation of a recently developed solution-phase isoelectric focusing-based fractionation technique as a prefractionation strategy for efficient containment of hemeoglobin-derived products and complexity reduction, to facilitate the high-resolution gel-based quantitative analysis of plasmodial lysates. Keywords: malaria • proteomics • serine hydroxymethyltransferase • two-dimensional gel electrophoresis • quantitation
The reclamation and redevelopment of abandoned mine sites into parks, golf courses, and residential communities in arid and hyperarid regions has been caused, in part, to rising land costs. A ...laboratory experiment using three columns was monitored for 273 days to evaluate trace metal and metalloid availability. The sediment from the Three Kids Mine that was used in this study is documented to contain high levels of trace metals and metalloids. The experiment simulated agricultural activities over time to assess whether fertilizers would mobilize trapped contaminants. Results indicate that irrigation and fertilizers can provide conditions for Pb, Mn, Zn, Al, Ba, Cu, and As to become mobile, though on a limited basis. There was an increase in Pb, Mn, Zn, Al, Ba, Cu, and As within the first 30 days followed by a decrease at 90 days. Concentrations of Pb, Mn, and Zn increased at 273 days due to application of fertilizer-fortified waters. This study shows the potential for mobilized trace metals and metalloids to enter the wider environment after developmental activities are finished.
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