Receptor for Fc on the surfaces of schistosomes

Schistosoma mansoni masks its surface with adsorbed host proteins including erythrocyte antigens, immunoglobulins, major histocompatibility complex class I, and beta (2)-microglobulin (beta (2)m), presumably as a means of avoiding host immune responses, How this is accomplished has not been explained. To identify surface receptors for host proteins, we biotinylated the tegument of live S, mansoni adults and mechanically transformed schistosomula and then removed the parasite surface with detergent, Incubation of biotinylated schistosome surface extracts witt l human immunoglobulin G (IgG) Fc-Sepharose resulted in purification of a 97-kDa protein that was subsequently identified as paramyosin (Pmy), using antiserum specific for recombinant Pmy, Fc also bound recombinant S. mansoni Pmy and native S. japonicum Pmy, Antiserum to Pmy decreased the binding of Pmy to Fc-Sepharose, and no proteins bound after removal of Pmy from extracts. Fluoresceinated human Fe bound to the surface, vestigial penetration glands, and nascent oral cavity of mechanically transformed schistosomula, and rabbit anti-Pmy Fab fragments ablated the binding of Fc to the schistosome surface, Pmy coprecipitated with host IgG from parasite surface extracts, indicating that complexes formed on the parasite surface as well as in vitro. Binding of Pmy to Fe was not inhibited by soluble protein A, suggesting that Pmy does not bind to the region between the CH2 and CH3 domains used by many other Fc-binding proteins. beta (2)m did not bind to the schistosome Fc receptor (Pmy), a finding that contradicts reports from earlier workers but did bind to a heteromultimer of labeled schistosomula surface proteins, This is the first report of the molecular identity of a schistosome Fc receptor; moreover it demonstrates an additional aspect of the unusual and multifunctional properties of Pmy from schistosomes and other parasitic flatworms.

Efficacy of praziquantel against Schistosoma japonicum: field evaluation in an area with repeated chemotherapy compared with a newly identified endemic focus in Hunan, China

This study conducted in 1999/2000 was designed to evaluate the efficacy of praziquantel against Schistosoma japonicum in an area with repeated chemotherapy (Area A) compared with a newly identified endemic focus (Area B) in Hunan Province, China. The population size was 2015 and 2180 in Areas A and B, respectively, of which 1129 and 1298 subjects received stool examination. A total of 230 subjects were identified by the Kato-Katz technique (4 smears per person) as being infected with S. japonicum, 124 in Area A (prevalence 11 %) and 106 in Area B (prevalence 8.2%). They were treated with a single oral dose of praziquantel (40 mg/kg) in the non-transmission season. A follow-up stool examination was made 50 days after treatment. Among the 220 cases followed, 22 were found stool-egg-positive, with an overall cure rate of 90 %, and 99 % reduction of infection intensity (eggs per gram stool). No significant difference was found in cure rates between the 2 areas (89.7% vs 90.3%). The efficacy of the drug in the area with repeated chemotherapy was not significantly different from that in the newly identified endemic focus. This study, therefore, suggests that the efficacy of praziquantel against S. japonicum has not changed in the Dongting Lake region after more than 14 years of mass chemotherapy, and there is no evidence of tolerance or resistance of S. japonicum against praziquantel.

Gulliver, a long terminal repeat retrotransposon from the genome of the oriental blood fluke Schistosoma japonicum

We characterized the consensus sequence and structure of a long terminal repeat (LTR) retrotransposon from the genome of the human blood fluke, Schistosoma japonicum, and have earned this element, Gulliver. The full length, consensus Gulliver LTR retrotransposon was 4788 bp, and it was flanked at its 5'- and 3'-ends by LTRs of 259 bp. Each LTR included RNA polymerase II promoter sequences, a CAAT signal and a TATA box, Gulliver exhibited features characteristic of a functional LTR retrotransposon including two read through (termination) ORFs encoding retroviral gag and pol proteins of 312 and 1071 amino acid residues, respectively. The gag ORF encoded motifs conserved in nucleic acid binding proteins, while the pol ORF encoded conserved domains of aspartic protease, reverse transcriptase (RT), RNaseH and integrase, in that order, a pol pattern conserved in the gypsy lineage of LTR retrotransposons. Whereas the sequence and structure of Gulliver was similar to that of gypsy, phylogenetic analysis revealed that Gulliver did not group particularly closely with the gypsy family. Rather, its closest relatives were a LTR retrotransposon from Caenorhabditis elegans, mag from Bombyx mori and, to a lesser extent, easel from the salmon Oncorhynchus keta. Dot blot hybridizations indicated that Gulliver was present at between 100 and several thousand copies in the S. japonicum genome, and Southern hybridization analysis suggested its probable presence in the genome of Schistosoma mansoni. Transcripts encoding the RT domain of Gulliver were detected by RT-PCR in larval and adult stages of S. japonicum, indicating that (at least) the RT domain of Gulliver is transcribed. This is the first report of the sequence and structure of an LTR retrotransposon from any schistosome or indeed from any species belonging to the phylum Platyhelminthes. (C) 2001 Elsevier Science B.V. All rights reserved.

pido, a non-long terminal repeat retrotransposon of the chicken repeat 1 family from the genome of the Oriental blood fluke, Schistosoma japonicum

A newly described non-long terminal repeat (non-LTR) retrotransposon element was isolated from the genome of the Oriental schistosome, Schistosoma japonicum. At least 1000 partial copies of the element, which was named pido, were dispersed throughout the genome of S. japonicum. As is usual with non-LTR retrotransposons, it is expected that many pido elements will be 5'-truncated. A consensus sequence of 3564 bp of the truncated pido element was assembled from several genomic fragments that contained pido-hybridizing sequences. The sequence encoded part of the first open reading frame (ORF), the entire second ORF and, at its 3'-terminus, a tandemly repetitive, A-rich (TA(6)TA(5)TA(8)) tail, The ORF1 of pido encoded a nucleic acid binding protein and ORF2 encoded a retroviral-like polyprotein that included apurinic/apyrimidinic endonuclease (EN) and reverse transcriptase (RT) domains, in that order. Based on its sequence and structure, and phylogenetic analyses of both the RT and EN domains, pido belongs to the chicken repeat 1 (CR1)-like lineage of elements known from the chicken, turtle, puffer fish, mosquitoes and other taxa. pido shared equal similarity with CRI from chicken, an uncharacterized retrotransposon from Caenorhabditis elegans and SR1 (a non-LTR retrotransposon) from the related blood fluke Schistosoma mansoni; the level of similarity between pido and SR1 indicated that these two schistosome retrotransposons were related but not orthologous. The findings indicate that schistosomes have been colonized by at least two discrete CRI-like elements. Whereas pido did not appear to have a tight target site specificity, at least one copy of pido has inserted into the 3'-untranslated region of a protein-encoding gene (GeriBank AW736757) of as yet unknown identity. mRNA encoding the RT of pido was detected by reverse transcription-polymerase chain reaction in the egg, miracidium. and adult developmental stages of S. japonicum, indicating that the RT domain was transcribed and suggesting that pido was replicating actively and mobile within the S. japonicum genome. (C) 2002 Elsevier Science B.V. All rights reserved.

Immune correlate study on human Schistosoma japonicum in a well-defined population in Leyte, Philippines: I. Assessment of 'resistance' versus 'susceptibility' to S-japonicum infection

This study describes the categorical classification of 155 individuals living in an endemic village in Macanip, Leyte, Philippines as 'resistant' or 'susceptible' to Schistosoma japonicum infection using available exposure, infection and reinfection data collected from a 3-year water contact (WC) study. Epidemiological parameters including age, sex, and infection intensities in relation to observed reinfection patterns are also described. This classification was used in subsequent immunological studies described in two accompanying papers to identify protective immune mechanisms among resistant individuals induced by defined candidate vaccine molecules for S. japonicum. The study suggests that individuals who were most vulnerable to rapid reinfection were children belonging to the 5-14 age group. A drop in incidence at age group 15-19 and decreased intensity of infection starting at this age group and older (15+) suggests development of immunity. Controlling for the effect of the other variables, a multivariate analysis showed significant association for sex, in that females were more likely to be resistant. This implies that other than acquired immunity to infection, some age-dependent host factors may also play an important role in the overall changes of reinfection patterns seen in schistosomiasis japonica in this population. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved.

A baseline study of importance of bovines for human Schistosoma Japonicum infections around Poyang Lake, China: Villages studied and snail sampling strategy

An epidemiologic survey among four administrative villages around Poyang Lake, in Jiangxi Province, China (two experimental and two controls) is being conducted to determine if bovine infections are responsible for the persistence of human schistosomiasis transmission on Yangtze River marshlands. A previously published paper presented the experimental design and baseline data for humans and bovines. This paper presents basic data for the four villages using remote sensing, and baseline data for snails that includes geographic information systems and remote sensing technology to classify the areas of bovine grazing ranges and habitats suitable for snails. A new method for sampling Oncomelania snails in China is used to determine the distribution, density, and infection rates of snails throughout the grazing ranges from season to season over a four-year period. Hypothetically, treating bovines should reduce infection rates in snails to below the critical number necessary to maintain infections in man and bovines.

Ultrasound organometry: the importance of body height adjusted normal ranges in assessing liver and spleen parameters among Chinese subjects with Schistosoma japonicum infection

Hepatosplenic measurements among 550 Chinese subjects, aged 3-59 years from Yueyang city-a nonendemic area for schistosomiasis in Hunan province, China-were performed to define normal ranges of ultrasound organometry for assessing hepatosplenic, morbidity in Schistosoma japonicum infection. Measurements included the size of the liver (left lobe and right lobe), the main portal vein stem, the peripheral periportal vein branches, and spleen length and thickness. The results document the significant relationship between body height and organometric parameters. The reference values stratified by body height improve the accuracy of assessment. Thus, height-based normal ranges established in this study can be applied in hospital routine and in field studies of patients infected with S. japonicum in Hunan province and in other endemic areas of China. (C) 2004 Elsevier B.V. All rights reserved.

Reconstruction and in silico analysis of the MAPK signaling pathways in the human blood fluke, Schistosoma japonicum

At present, little is known about signal transduction mechanisms in schistosomes, which cause the disease of schistosomiasis. The mitogen-activated protein kinase (MAPK) signaling pathways, which are evolutionarily conserved from yeast to Homo sapiens, play key roles in multiple cellular processes. Here, we reconstructed the hypothetical MAPK signaling pathways in Schistosoma japonicum and compared the schistosome pathways with those of model eukaryote species. We identified 60 homologous components in the S. japoncium MAPK signaling pathways. Among these, 27 were predicted to be full-length sequences. Phylogenetic analysis of these proteins confirmed the evolutionary conservation of the MAPK signaling pathways. Remarkably, we identified S. japonicum homologues of GTP-binding protein beta and alpha-I subunits in the yeast mating pathway, which might be involved in the regulation of different life stages and female sexual maturation processes as well in schistosomes. In addition, several pathway member genes, including ERK, JNK, Sja-DSP, MRAS and RAS, were determined through quantitative PCR analysis to be expressed in a stage-specific manner, with ERK, JNK and their inhibitor Sja-DSP markedly upregulated in adult female schistosomes. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

The structure of quantum Lie algebras for the classical series, B-l, C-l and D-l

The structure constants of quantum Lie algebras depend on a quantum deformation parameter q and they reduce to the classical structure constants of a Lie algebra at q = 1. We explain the relationship between the structure constants of quantum Lie algebras and quantum Clebsch-Gordan coefficients for adjoint x adjoint --> adjoint We present a practical method for the determination of these quantum Clebsch-Gordan coefficients and are thus able to give explicit expressions for the structure constants of the quantum Lie algebras associated to the classical Lie algebras B-l, C-l and D-l. In the quantum case the structure constants of the Cartan subalgebra are non-zero and we observe that they are determined in terms of the simple quantum roots. We introduce an invariant Killing form on the quantum Lie algebras and find that it takes values which are simple q-deformations of the classical ones.

Type specific and genotype cross reactive B epitopes of the L1 protein of HPV16 defined by a panel of monoclonal antibodies

Mouse monoclonal antibodies (mAbs) were raised against the major capsid protein, L1, of human papillomavirus type 16 (HPV16), produced in Escherichia coil with the expression plasmid pTrcL1. Epitope specificity could be assigned to 11 of these 12 antibodies using a series of linear peptides and fusion proteins from HPV16. One mAb (MC53) recognized a novel linear epitope that appears to be unique to the HPV16 genotype. A further 11 mAbs were characterized as recognizing novel and previously defined linear and conformational epitopes shared among more than one HPV genotype. The apparently genotype specific mAb could be useful for the development of diagnostic tests for vegetative virus infection in clinical specimens. (C) 1998 Academic Press.

Callyspongynes A and B: New polyacetylenic lipids from a southern Australian marine sponge, Callyspongia sp.

A Callyspongia sp. collected by SCUBA off Barwon Heads, Australia, has afforded two new polyacetylenic lipids, callyspongynes A and B, the structures of which were assigned by spectroscopic analysis and chemical derivatization.

A new synthesis of chiral aminoalkyloxazolecarboxylate esters from isoxazol-5(2H)-ones: the synthesis of almazoles A and B

2-(1-Aminoalkyl)oxazole-4 and 5-carboxylates are available, without detectable racemisation, by a sequence involving N-acylation of isoxazol-5(2H)one carboxylates with phthalimidoamino acids, photolysis of the acylated product, and hydrazinolysis. An application of the procedure to the synthesis of almazole A and B is described (C) 1998 Elsevier Science Ltd. All rights reserved.

mRNA differential display of 2-amino-1-methyl-6-phenylinlidazo[4,5-b]pyridine-induced rat mammary gland tumors

The mRNA differential display technique was used to compare mRNAs between normal mammary gland and turner-derived epithelial cells from female Sprague-Dawley rat mammary gland tumors induced by the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by a high-fat diet (23.5% corn oil). Two genes, beta-casein and transferrin, were identified as differentially expressed. The expression of these genes was examined across a bank of rat mammary gland tumors derived from animals on a low-fat diet (5% corn oil) or the high-fat diet. Carcinomas had over a 10- and 50-fold lower expression of beta-casein and transferrin, respectively than normal mammary gland. In addition, carcinomas from animals on the high-fat diet showed on average a 5-fold higher expression of beta-casein, and transferrin than carcinomas from animals on the low-fat diet. The results indicate the process of mammary gland tumorigenesis alters the expression of certain genes in the mammary gland, and that the level of dietary fat further modulates the expression of these genes.

The synthesis of almazoles A and B

Almazoles A (1) and B (2) are formed in seven steps from phenylalanine without any racemization. The key step is the N-acylation of the isoxazol-5(2H)-one (5) with the phthalimide-protected amino acid, and photolysis of the product at 300 nm in acetone.