Reinfection with Schistosoma haematobium following school-based chemotherapy with praziquantel in four highly endemic villages in Côte d'Ivoire

We present the comparative evaluation of school-based chemotherapy with praziquantel on Schistosoma haematobium reinfection patterns, 6, 12, 18 and 24 months after systematic treatment of schoolchildren in four villages of south-central Côte d'Ivoire. At baseline, very high S. haematobium infection prevalences of 88–94% were found in Taabo Village, located adjacent to a large man-made lake, and in Batera and Bodo, where small dams were constructed. In Assinzé, a village with no man-made environmental alterations, the baseline infection prevalence was significantly lower (67%). The parasitological cure rate, assessed 4 weeks after praziquantel administration in the village with the highest prevalence and intensity of infection, was high (82%), and showed a clear association with infection intensity prior to treatment. Six months after chemotherapy, significant reductions in the prevalence and intensity of infection were observed in all villages. However, infection prevalence was again high in Taabo Village (63%) and in Batera (49%). Different patterns of reinfection occurred in the four villages: rapid reinfection in Taabo Village to reach almost baseline infection prevalence 12 months post-treatment; slow but gradual increase in the prevalence and intensity of infection in Bodo; marked increase in prevalence and intensity of infection during the second year of the follow-up in Assinzé; and prevalence and intensity of infection that remained almost constant between 6 and 24 months post-treatment in Batera. Our study confirms that S. haematobium reinfection patterns largely depend on the local epidemiological setting, which is of central importance to tailoring treatment strategies that are well adapted to these different settings.

A sponge allelochemical induces ascidian settlement but inhibits metamorphosis

Secondary metabolites synthesised by sessile invertebrates appear to play a role in creating and maintaining space on hard substrata by repelling competitors. In this study, we investigated the responses of the larvae of the ascidian Herdmania curvata to haliclonacyclamine A (HA), the major component of a suite of cytotoxic alkaloids extracted from the sponge Haliclona sp. 628. Both Haliclona sp. 628 and Herdmania curvata inhabit the crest and slope of Heron Island Reef. High rates of settlement were induced in competent H. curvata larvae by a range of concentrations of HA, all lower than that naturally occurring in the sponge. HA did not induce precompetent larvae to settle. Although early metamorphosis of HA-induced larvae was normal, larvae exposed to all but the lowest concentration of HA were developmentally arrested after completion of tail resorption, at about 4 h after the initiation of metamorphosis. These postlarvae underwent extensive cellular necrosis within 24 h. We also demonstrate that the addition of a transcriptional inhibitor, actinomycin D, to larvae also causes inhibition of metamorphosis after tail resorption is completed. Analyses of incorporation of radiolabelled nucleotides to measure levels of transcription during normal development and after the addition of the transcriptional inhibitor indicate that there is a significant burst of transcriptional activity just after tail resorption is completed. Despite inhibiting metamorphosis at the same stage as actinomycin D, HA increases initial rates of RNA synthesis after induction of metamorphosis in a manner similar to that observed in normal postlarvae until the onset of cellular necrosis. We conclude that HA initially induces H. curvata larvae to settle and progress through early metamorphosis possibly by engaging the same pathway as other artificial and environmental cues but subsequently inhibits completion of metamorphosis, resulting in death of the postlarvae. Since HA does not affect overall transcription rates, it appears to disrupt another important developmental process during early metamorphosis.

Cleavage of hemoglobin by hookworm cathespin D aspartic proteases and its potential contribution to host specificity

Hookworms routinely reach the gut of nonpermissive hosts but fail to successfully feed, develop, and reproduce. To investigate the effects of host-parasite coevolution on the ability of hookworms to feed in nonpermissive hosts, we cloned and expressed aspartic proteases from canine and human hookworms. We show here that a cathepsin D-like protease from the canine hookworm Ancylosotoma caninum (Ac-APR-1) and the orthologous protease from the human hookworm Necator americanus (Na-APR-1) are expressed in the gut and probably exert their proteolytic activity extracellularly. Both proteases were detected immunologically and enzymatically in somatic extracts of adult worms. The two proteases were expressed in baculovirus, and both cleaved human and dog hemoglobin (Hb) in vitro. Each protease digested Hb from its permissive host between twofold (whole molecule) and sixfold (synthetic peptides) more efficiently than Hb from the nonpermissive host, despite the two proteases' having identical residues lining their active site clefts. Furthermore, both proteases cleaved Hb at numerous distinct sites and showed different substrate preferences. The findings suggest that the paradigm of matching the molecular structure of the food source within a host to the molecular structure of the catabolic proteases of the parasite is an important contributing factor for host-parasite compatibility and host species range.

Total synthesis and absolute stereochemistry of plakortone D

The first total synthesis of plakortone D is described and thereby establishes the structure and absolute stereochemistry of the most biologically active member of the marine-derived plakortone family. The sterically congested bicyclic lactone core results from a Pd(II)-induced hydroxycyclization−carbonylation−lactonization sequence on an enediol whose chirality was installed by AD-technology. Attachment of the side chain, also constructed using AD-methodology, was achieved by using a modified Julia coupling. The described approach enables acquisition of other plakortones and analogues, in the correct (natural) stereochemical series.

Synthesis and structural properties of patellamide a derivatives and their copper(II) compounds

The synthesis, characterization and copper(II) coordination chemistry of three new cyclic peptide ligands, PatJ(1) (cyclo-(Ile -Thr- (Gly)Thz-lle-Thr(Gly)Thz)), PatJ(2) (cyclo-(Ile-Thr(Gly)Thz-(D)-Ile-Thr-(Gly)Thz)), and PatL (cyclo-(Ile-Ser-(Gly)Thz-Ile-Ser(Gly)Thz)) are reported. All of these cyclic peptides and PatN (cyclo-(Ile-Ser(Gly)Thz-Ile-Thr-(Gly)Thz)) are derivatives of patellamide A and have a [24]azacrown-8 macrocyclic structure. All four synthetic cyclic peptides have two thiazole rings but, in contrast to patellamide A, no oxazoline rings. The molecular structure of PatJ1, determined by X-ray crystallography, has a saddle conformation with two close-to-co-parallel thiazole rings, very similar to the geometry of patellamide D. The two coordination sites of PatJ1 with thiazole-N and amide-N donors are each well preorganized for transition metal ion binding. The coordination of copper(II) was monitored by UV/Vis spectroscopy, and this reveals various (meta)stable mono- and dinuclear copper(II) complexes whose stoichiometry was confirmed by mass spectra. Two types of dinuclear copper(II) complexes, [Cu-2(H4L)(OH2)(n)](2+) (n = 6, 8) and [Cu-2(H4L)(OH2)(n)] (n=4, 6; L=PatN, PatL, PatJ1, PatJ2) have been identified and analyzed structurally by EPR spectroscopy and a combination of spectra simulations and molecular mechanics calculations (MM-EPR). The four structures are similar to each other and have a saddle conformation, that is, derived from the crystal structure of PatJ(1) by a twist of the two thiozole rings. The small but significant structural differences are characterized by the EPR simulations.

The nexus of value chain integration and e-business applications on public sector agriculture R&D management

We examine the potential impact of interconnectivity of value chain partnerships through electronic means (e-business practices) on the management of Public Sector Agriculture R&D in Australia. We review the changing forms of managing research and development, the forces driving these changes, and R&D processes that are theoretically consistent with the move towards value chain involvement and the increase in active constituents in Public Sector Agriculture R&D. We then explore the potential of emerging e-business models to change the patterns of inter-connectivity, speed and omnipresence of partners in the value chain. Three e-business R&D management practices are identified that provide the prerequisite flexibility necessary to take advantage of opportunistic markets. These R&D business practices are: compressing R&D to reduce time to market, fostering co-development to enter a market at the last moment and building flexible products that allow adjustment at the last possible moment. Some fundamental reallocation of existing resources will be required to meet these markets. Implications of these e-business practices for R&D management are discussed.

Urine D-arabinitol/L-arabinitol ratio in diagnosing Candida infection in patients with haematological malignancy and HIV infection

Adult patients with hematologic malignancies along with HIV infected patients were prospectively studied to determine the performance of urine D-arabinitol/L-arabinitol (DA/LA) ratio in diagnosing invasive candidiasis. Ten evaluable febrile neutropenic patients had proven invasive candidiasis and elevated DA/LA ratios were found in 5. Invasive candidiasis with normal DA/LA ratios was most frequently due to Candida krusei infection. This Candida species is a non-producer of arabinitol. Only 4 of 81 febrile neutropenic patients given either antifungal prophylaxis or empiric antifungal treatment had elevated DA/LA ratios. Only 1 of 15 HIV positive patients with either oropharyngeal or esophageal candidiasis had elevated DA/LA ratios. Widespread use of fluconazole prophylaxis in bone marrow transplantation patients at the study hospital has led to an increased prevalence of C. krusei infection. This is the likely reason for the low sensitivity of the test in proven and suspected invasive Candida infections reported here. (C) 2002 Elsevier Science Inc. All rights reserved.

High resolution 3-D imaging via multi-pass SAR

Spaceborne/airborne synthetic aperture radar (SAR) systems provide high resolution two-dimensional terrain imagery. The paper proposes a technique for combining multiple SAR images, acquired on flight paths slightly separated in the elevation direction, to generate high resolution three-dimensional imagery. The technique could be viewed as an extension to interferometric SAR (InSAR) in that it generates topographic imagery with an additional dimension of resolution. The 3-D multi-pass SAR imaging system is typically characterised by a relatively short ambiguity length in the elevation direction. To minimise the associated ambiguities we exploit the relative phase information within the set of images to track the terrain landscape. The SAR images are then coherently combined, via a nonuniform DFT, over a narrow (in elevation) volume centred on the 'dominant' terrain ground plane. The paper includes a detailed description of the technique, background theory, including achievable resolution, and the results of an experimental study.

Lanczos subspace time-independent wave packet calculations of S(D-1)+H-2 reactive scattering

In this paper. we present the results of quantum dynamical simulations of the S (D-1) + H-2 insertion reaction on a newly developed potential energy surface (J. Chem. Phys. 2001, 114, 320). State-to-state reaction probabilities. product state distributions, and initial-state resolved cumulative reaction probabilities from a given incoming reactant channel are obtained from a time-independent wave packet analysis, performed within a single Lanczos subspace. Integral reaction cross sections are then estimated by J-shifting method and compared with the results from molecular beam experiment and QCT calculations.

Caractéristiques diphasiques des écoulements sur les coursiers en marches d'escalier

Stepped cascades and spillways have been used for more than 3,500 years. The recent regain of interest for the stepped chute design is associated with the introduction of new construction techniques, the development of new design techniques and newer applications. Stepped chute flows are characterised by significant free-surface aeration that cannot be neglected. Two-phase flow measurements were conducted in a large-size model (h =0.10 m, α = 22o). Experimental observations demonstrate the existence of a transition flow regime for a relatively wide range of flow rates. Detailed air-water flow measurements were conducted for both skimming flows and transition flows. Skimming flows exhibit gradual variations of the air-water flow properties, whereas transition flows are characterised by rapid flow redistributions between adjacent steps.

Control of dimethylsulfoxide reductase expression in Rhodobacter capsulatus: the role of carbon metabolites and the response regulators DorR and RegA

Regulation of the expression of dimethylsulfoxide (DMSO) reductase was investigated in the purple phototrophic bacterium Rhodobacter capsulatus. Under phototrophic, anaerobic conditions with malate as carbon source, DMSO caused an approximately 150-fold induction of DMSO reductase activity. The response regulator DorR was required for DMSO-dependent induction and also appeared to slightly repress DMSO reductase expression in the absence of substrate. Likewise, when pyruvate replaced malate as carbon source there was an induction of DMSO reductase activity in cells grown at low light intensity (16 W m(-2)) and again this induction was dependent on DorR. The level of DMSO reductase activity in aerobically grown cells was elevated when pyruvate replaced malate as carbon source. One possible explanation for this is that acetyl phosphate, produced from pyruvate, may activate expression of DMSO reductase by direct phosphorylation of DorR, leading to low levels of induction of dor gene expression in the absence of DMSO. A mutant lacking the global response regulator of photosynthesis gene expression, RegA, exhibited high levels of DMSO reductase in the absence of DMSO, when grown phototrophically with malate as carbon source. This suggests that phosphorylated RegA acts as a repressor of dor operon expression under these conditions. It has been proposed elsewhere that RegA-dependent expression is negatively regulated by the cytochrome cbb(3) oxidase. A cco mutant lacking cytochrome cbb(3) exhibited significantly higher levels of Phi[dorA::lacZ] activity in the presence of DMSO compared to wild-type cells and this is consistent with the above model. Pyruvate restored DMSO reductase expression in the regA mutant to the same pattern as found in wild-type cells. These data suggest that R. capsulatus contains a regulator of DMSO respiration that is distinct from DorR and RegA, is activated in the presence of pyruvate, and acts as a negative regulator of DMSO reductase expression.

Upstream porthole injection in a 2-D scramjet model

Injection from portholes upstream of the combustion chamber was investigated as a method of delivering fuel into a scramjet. This method reduces the viscous drag on a model by allowing a reduction in the length of the combustion chamber. At experimental enthalpies of 3.0 MJ/kg in the T4 shock tunnel, there was no evidence of combustion in the intake, either by shadowgraph or pressure measurements. Combustion was observed in the combustion chamber. A theoretical extension of these results is made to a hot wall scenario.

Hepatic covalent adduct formation with zomepirac in the CD26-deficient mouse

Background and Aims: Zomepirac (ZP), a non-steroidal anti-inflammatory drug (NSAID), has been reported to cause immune-mediated liver injury. In vivo, ZP is metabolized to a chemically reactive acyl glucuronide conjugate (ZAG) which can undergo covalent adduct formation with proteins. Such acyl glucuronide-derived drug-protein adducts may be important in the development of immune and toxic responses caused by NSAID. We have shown using immunoabsorptions that the 110 kDa CD26 (dipeptidyl peptidase IV) is one of the hepatic target proteins for covalent modification by ZAG. In the present study, a CD26-deficient mouse strain was used to examine protein targets for covalent modification by ZP/metabolites in the liver. Methods and Results: The CD26-deficient phenotype was confirmed by immunohistochemistry, flow cytometry analysis, RT-PCR, enzyme assay and immunoblotting. Moreover, by using monoclonal antibody immunoblots, CD26 was not detected in the livers of ZP-treated CD26-deficient mice. Immunoblots using a polyclonal antiserum to ZP on liver from ZP-treated mice showed three major sizes of protein bands, in the 70, 110 and 140 kDa regions. Most, but not all, of the anti-ZP immunoreactivity in the 110 kDa region was absent from ZP-treated CD26-deficient mice. Conclusion: These data definitively showed that CD26 was a component of ZP-modified proteins in vivo. In addition, the data suggested that at least one other protein of approximately 110 kDa was modified by covalent adduct formation with ZAG. (C) 2002 Blackwell Science Asia Pty Ltd.