Bone marrow suppression and severe anaemia associated with persistent Plasmodium falciparum infection in African children with microscopically undetectable parasitaemia

In sub-Saharan Africa the highest overlap between malaria and HIV infections occurs in female adolescents. Yet control activities for these infections are directed to different target groups, using disparate channels. This reflects the lack of priority given to adolescents and the absence of an accepted framework for delivering health and health-related interventions to this high-risk group. In this paper it is argued that female adolescents require a continuum of care for malaria and HIV – prior to conception, during and after pregnancy and that this should be provided through adolescent services. The evidence for this conclusion is presented. A number of African countries are commencing to formulate and implement adolescent-friendly policies and services and disease control programs for malaria and HIV will need to locate their interventions within such programs to ensure widespread coverage of this important target group. Failure to prioritize adolescent health in this way will seriously limit the success of disease control programs for malaria and HIV prevention.     

Confidence interval construction for relative toxicity endpoints such as LD50 or LD90 ratios

A common measure of the relative toxicity is the ratio of median lethal doses for responses estimated in two bioassays. Robertson and Preisler previously proposed a method for constructing a confidence interval for the ratio. The applicability of this technique in common experimental situations, especially those involving small samples, may be questionable because the sampling distribution of this ratio estimator may be highly skewed. To examine this possibility, we did a computer simulation experiment to evaluate the coverage properties of the Robertson and Preisler method. The simulation showed that the method provided confidence intervals that performed at the nominal confidence level for the range of responses often observed in pesticide bioassays. Results of this study provide empirical support for the continued use this technique.     

不同地理飞蝗种群的遗传多样性

用GenBank中飞蝗Locusta migratoriaL.的序列来设计微卫星引物,并对这些引物的有效性进行验证。结果表明,在所设计的3对引物中,只有1对为有效引物,可扩增出微卫星位点。序列分析表明本位点是一个不连续的重复微卫星位点。该多态微卫星位点含有14个等位基因,不同飞蝗地理种群的等位基因数目、大小和频率都存在较大的差异。对该位点各等位基因型进行χ2检验,基因型频率的观察和期望杂合度分别为0.4578和0.8836,该位点不属于Hardy-Weinberg平衡位点(χ2=733.12,P=0.0000)。该微卫星位点表现出高度的多态性说明是分析飞蝗种群遗传多样性的优良分子遗传标记。     

Artificial cranial deformation in Pleistocene Australians: the Coobool Creek sample

Several authors have suggested that some Pleistocene Australian crania have been altered by artificial cranial deformation. The large sample from Coobool Creek has featured prominently in this debate. The present study reevaluates the evidence for artificial cranial deformation in this population using both a larger cranial sample and a more comprehensive set of measurements than those used in earlier work on this subject. Additionally, random expectation statistics are used to calculate statistical significance for these examinations. The results of this study agree with prior work indicating that a portion of this sample shows evidence for artificial deformation of the cranial vault. Many Coobool Creek crania display strong shape similarities with a population of known deformed individuals from New Britain. Coobool Creek crania 1, 41, 65, and 66 show the strongest evidence for deformation, but several other individuals from this sample also show clear evidence for culturally manipulated changes in cranial shape. This project provides added support for the argument that at least some Pleistocene Australian groups were practicing artificial cranial deformation.     

On the influence of polyvalent ligands on membrane curvature

The suggestion is made that a polyvalent ligand attached to a membrane will induce a curvature in that membrane which is concave toward the side to which that ligand is bound. This article presents a semiquantitative thermodynamic analysis predicting this effect for a simple system. The criterion for equilibrium of the ligand membrane complex is stated and for the simple system this is calculated for an arbitrary set of parameters. The influence of changes in these parameters is discussed. The energies calculated for this effect are of the order of 0·1 kcal/mol suggesting that for observable effects on curvature an array of such ligands will be needed. Some real systems in which this effect may be playing a role are discussed.     

Kinetic analysis of the histamine N-methyltransferase reaction as used in the histamine radioenzymatic assay: Optimization of assay specificity

The specificity of the histamine N-methyltransferase (HNMT) based radioenzymatic assay for histamine has been questioned since N-α-methylhistamine is also a substrate for this enzyme. Purification of HNMT for use in the radioenzymatic assay improves sensitivity and specificity of this procedure. In this investigation, further improvements in specificity, with respect to other HNMT substrates, were attained by optimization of reaction conditions based on the evaluation of HNMT kinetic parameters. These studies demonstrate that appropriate control of reaction temperature and concentration of both the enzyme and the radiolabeled methyl donor improve the specificity of this assay for histamine.     

Microsatellite loci for the small hive beetle, Aethina tumida, a nest parasite of honey bees

Aethina tumida, a beetle parasite of honey bee colonies, has recently and dramatically expanded its range and now parasitizes honey bees on three continents. Polymorphic microsatellite loci for this beetle species will help map this continuing range expansion, and will also prove useful for exploring the mating system and local gene flow patterns for this important parasite. We describe 15 loci that are polymorphic in both the native and introduced ranges of this species, showing from two to 22 alleles.     

Dileucine motif is sufficient for internalization and synaptic vesicle targeting of vesicular acetylcholine transporter

Efficient cholinergic transmission requires accurate targeting of vesicular acetylcholine transporter (VAChT) to synaptic vesicles (SVs). However, the signals that regulate this vesicular targeting are not well characterized. Although previous studies suggest that the C-terminus of the transporter is required for its SV targeting, it is not clear whether this region is sufficient for this process. Furthermore, a synaptic vesicle-targeting motif (SVTM) within this sequence remains to be identified. Here we use a chimeric protein, TacA, between an unrelated plasma membrane protein, Tac, and the C-terminus of VAChT to demonstrate the sufficiency of the C-terminus for targeting to synaptic vesicle-like vesicles (SVLVs) in PC12 cells. TacA shows colocalization and cosedimentation with the SV marker synaptophysin. Deletion mutation analysis of TacA demonstrates that a short, dileucine motif-containing sequence is required and sufficient to direct this targeting. Dialanine mutation analysis within this sequence suggests indistinguishable signals for both internalization and SV sorting. Using additional chimeras as controls, we confirm the specificity of this region for SVLVs targeting. Therefore, we suggest that the dileucine-containing motif is sufficient as a dual signal for both internalization and SV targeting during VAChT trafficking.     

Short rotation coppice culture of willows and poplars as energy crops on metal contaminated agricultural soils

Phytoremediation, more precisely phytoextraction, has been placed forward as an environmental friendly remediation technique, that can gradually reduce increased soil metal concentrations, in particular the bioavailable fractions. The aim of this study was to investigate the possibilities of growing willows and poplars under short rotation coppice (SRC) on an acid, poor, sandy metal contaminated soil, to combine in this way soil remediation by phytoextraction on one hand, and production of biomass for energy purposes on the other. Above ground biomass productivities were low for poplars to moderate for willows, which was not surprising, taking into account the soil conditions that are not very favorable for growth of these trees. Calculated phytoextraction efficiency was much longer for poplars than these for willows. We calculated that for phytoextraction in this particular case it would take at least 36 years to reach the legal threshold values for cadmium, but in combination with production of feedstock for bioenergy processes, this type of land use can offer an alternative income for local farmers. Based on the data of the first growing cycle, for this particular case, SRC of willows should be recommended.     

Biochemical systems theory: increasing predictive power by using second-order derivatives measurements

Models based on the power-law formalism provide a useful tool for analyzing metabolic systems. Within this methodology, the S-system variant furnishes the best strategy. In this paper we explore an extension of this formalism by considering second-order derivative terms of the Taylor series which the power-law is based upon. Results show that the S-system equations which include second-order Taylor coefficients give better accuracy in predicting the response of the system to a perturbation. Hence, models based on this new approach could provide a useful tool for quantitative purposes if one is able to measure the required derivatives experimentally. In particular we show the utility of this approach when it comes to discriminating between two mechanisms that are equivalent in the S-system a representation based on first-order coefficients. However, the loss of analytical tractability is a serious disadvantage for using this approach as a general tool for studying metabolic systems.     

Comment

Conclusion  In such a situation the only approach possible, even for a prospective LCA study, is to aggregate data from the possible sources of delivery and to use this as an input to the study. Weidema states in his article that actual average data is more difficult to collect than data for a marginal situation. But this is no argument against using average data when this is what most correctly portrays the actual situation. We would argue that this is also the only correct approach for a global commodity, since this will be the real situation for any new product. The material going into it will potentially be an average of the existing material on the market.     

Short interfering RNA-mediated gene targeting in the zebrafish

Short interfering RNAs (siRNAs) have proved to be a useful tool in studying gene function in plants, invertebrates and mammalian systems. Here we report the use of siRNAs for targeting the zebrafish dystrophin gene. This study demonstrates the efficacy of siRNA-based gene silencing in this vertebrate model species, and illustrates the potential of this approach for determining the roles of multiple protein products expressed by a single gene during the early stages of development. In addition this study illustrates the usefulness of zebrafish as a model for muscle disease, and highlights the potential of siRNA-based gene targeting for disease analysis in this model organism.     

A high-throughput fluorescence resonance energy transfer (FRET)-based endothelial cell apoptosis assay and its application for screening vascular disrupting agents

In this study, we developed a high-throughput endothelial cell apoptosis assay using a fluorescence resonance energy transfer (FRET)-based biosensor. After exposure to apoptotic inducer UV-irradiation or anticancer drugs such as paclitaxel, the fluorescence of the cells changed from green to blue. We developed this method into a high-throughput assay in 96-well plates by measuring the emission ratio of yellow fluorescent protein (YFP) to cyan fluorescent protein (CFP) to monitor the activation of a key protease, caspase-3, during apoptosis. The Z' factor for this assay was above 0.5 which indicates that this assay is suitable for a high-throughput analysis. Finally, we applied this functional high-throughput assay for screening vascular disrupting agents (VDA) which could induce endothelial cell apoptosis from our in-house compounds library and dioscin was identified as a hit. As this assay allows real time and sensitive detection of cell apoptosis, it will be a useful tool for monitoring endothelial cell apoptosis in living cell situation and for identifying new VDA candidates via a high-throughput screening.     

Physics-based gene identification: proof of concept for Plasmodium falciparum

The ab initio prediction of new genes in eukaryotic genomes represents a difficult task, notably for the identification of complex split genes. A Physics-Based Gene Identification (PBGI) method was formulated recently (Yeramian, Gene, 255, 139-150, 151-168, 2000a,b) to address this problem, taking as a model the Plasmodium falciparum genome. Here, the predictive power of this method is put under experimental test for this genome. The presented results demonstrate the usefulness of the PBGI as a gene-identification tool for P. falciparum, notably for the discovery of new genes with no homology to known genes. Perspectives opened by this new method for other eukaryotic genomes are also mentioned.     

Gene Duplication as a Mechanism of Genetic Adaptation in SACCHAROMYCES CEREVISIAE

It has been shown that specific mutations of the gene that codes for the general acid monophophatase (Aphtase) of S. cerevisiae can increase the affinity of this enzyme for beta-glycerophosphate (BGP) and thereby provide this organism with the capacity to exploit extremely low concentrations of this organic phosphate (Francis and Hansche 1973). In this report two additional avenues are demonstrated to be available to this organism for increasing its capacity to exploit low concentrations of organic phosphates. One avenue is through mutations that increase the amount of Aphtase that associates with the cell wall, where it catalizes the hydrolysis of exogenous organic phosphates. The other avenue is through duplication of the gene that codes for Aphtase, doubling the amount of Aphtase synthesized.--The spontaneous duplication of the structural gene of Aphtase and the incorporation of the duplicate into this experimental population as a means of exploiting low concentrations of exogenous organic phosphates provides direct support for the first step of the mechanism through which new metabolic functions are postulated to evolve.     

Treatment of Onchocerciasis with ivermectin in Central America

The success o f ivermectin in controlling transmission of Onchocerca volvulus in Guatemala suggests a broader role for this drug than morbidity control alone. In this article Ed Cupp reviews recent findings from a three-year pilot study in that country which evaluated the effects of recurrent semiannual treatment on several important factors associated with the biology o f river blindness. These results illustrate the range o f beneficial effects that occur not only for this disease but for other parasitisms when this drug is administered at the community level.     

Effective testing of gene-disease associations.

We propose a method for testing any hypothesized association between a candidate allele, for which there is a specific laboratory test, and a common chronic disease. Families in which this allele is segregating are identified through index individuals who are homozygous or heterozygous for the allele. The sample consists of the subset of identified families who also have at least one member with the common disease of interest. For each independent family in this subset, select one person with the disease and determine if he or she is heterozygous for the allele. The observed proportion of heterozygotes in this sample is compared to the proportion expected on the basis of each diseased relative's null probability of being heterozygous for the allele; this null probability depends only on the relative's relationship to the index individual and the population allele frequency. We provide these null probabilities, develop appropriate inference procedures, discuss sample size requirements, and compare this method to a standard case-control design. Results using this method are unlikely to be influenced by confounders, systematic bias, or genetic heterogeneity.     

Age and growth in Peale's dolphin (Lagenorhynchus australis) in subantarctic waters off southern South America

The Peale's dolphin, Lagenorhynchus australis, is a mainly coastal and one of the most often seen species off southernmost South America from 33°S off Chile and 38°S off Argentina to south of Cape Horn. Although a common species, its IUCN status is “Data Defficient”, so any information on this species is relevant. Age, growth and physical maturity were examined in skeletons of 57 specimens of this species, mostly from the coasts of Tierra del Fuego, Argentina; this represents most of the known specimens of this species available in museum and private collections. Most specimens were by-catch in shore-set gillnets or had been harpooned for crab bait. Age was determined for 23 specimens, all from Tierra del Fuego. The maximum age was 13 years for a 199 cm female. The largest female in this survey was 210 cm, the largest male 205 cm in total length (12 years), but this probably does not represent the maximum length for this species. Only two animals, of 12 and 13 years, were physically mature. Animals reach asymptotic length (188 cm) with less than the 30% of the vertebral epiphyses fused. The animals in this study were mainly subadults, as has been found for other southern by-caught dolphins. Growth was studied for total length using 18 osteological characters with the Gompertz model. We propose that zygomatic width can be used to estimate total length for incomplete beach-cast specimens.     

Seasonality of birth: two findings from the decennial census

The enigmatic seasonality of births in the US has been analyzed extensively, but gaps in the knowledge of this phenomenon exist along dimensions not accessed by the national vital registration system. Live births in the US have for some time followed a pattern of spring trough and summer peak--at least since the initiation of the national birth registration system in 1933. The pattern is known to be more pronounced for the South than for other regions and for blacks than for whites. In this study it has been shown that this pattern existed as far back as the 1890's, and currently is more pronounced for lower than for higher socioeconomic groups. These findings come from an analysis of census population data, rather than vital registration data. In this way census data have been used in an innovative way to address 2 aspects of the phenomenon which had heretofore not been adequately treated.