Spatial prediction of malaria prevalence in an endemic area of Bangladesh

Background

Malaria is a major public health burden in Southeastern Bangladesh, particularly in the Chittagong Hill Tracts region. Malaria is endemic in 13 districts of Bangladesh and the highest prevalence occurs in Khagrachari (15.47%).

Methods

A risk map was developed and geographic risk factors identified using a Bayesian approach. The Bayesian geostatistical model was developed from previously identified individual and environmental covariates (p < 0.2; age, different forest types, elevation and economic status) for malaria prevalence using WinBUGS 1.4. Spatial correlation was estimated within a Bayesian framework based on a geostatistical model. The infection status (positives and negatives) was modeled using a Bernoulli distribution. Maps of the posterior distributions of predicted prevalence were developed in geographic information system (GIS).

Results

Predicted high prevalence areas were located along the north-eastern areas, and central part of the study area. Low to moderate prevalence areas were predicted in the southwestern, southeastern and central regions. Individual age and nearness to fragmented forest were associated with malaria prevalence after adjusting the spatial auto-correlation.

Conclusion

A Bayesian analytical approach using multiple enabling technologies (geographic information systems, global positioning systems, and remote sensing) provide a strategy to characterize spatial heterogeneity in malaria risk at a fine scale. Even in the most hyper endemic region of Bangladesh there is substantial spatial heterogeneity in risk. Areas that are predicted to be at high risk, based on the environment but that have not been reached by surveys are identified.

     

Association between microscopic brain damage as indicated by magnetization transfer imaging and anticardiolipin antibodies in neuropsychiatric lupus

The pathogenetic role of anticardiolipin antibodies (aCLs) in patients with neuropsychiatric systemic lupus erythematosus (NPSLE) without cerebral infarcts remains elusive. Magnetization transfer imaging (MTI) has proved to be a sensitive tool for detecting diffuse microscopic brain damage in NPSLE patients. In this study we examined the correlation between grey and white matter magnetization transfer ratio (MTR) parameters and the presence of IgM and IgG aCLs and lupus anticoagulant in 18 patients with systemic lupus erythematosus and a history of NPSLE but without cerebral infarcts on conventional magnetic resonance imaging. Lower grey matter mean MTR (P < 0.05), white matter mean MTR (P < 0.05), white matter peak location (P < 0.05) and grey matter peak location (trend toward statistical significance) were observed in IgM aCL-positive patients than in IgM aCL-negative patients. No significant differences were found in MTR histogram parameters with respect to IgG aCL and lupus anticoagulant status, nor with respect to anti-dsDNA or anti-ENA (extractable nuclear antigen) status. This is the first report of an association between the presence of aCLs and cerebral damage in grey and white matter in NPSLE. Our findings suggest that aCLs are associated with diffuse brain involvement in NPSLE patients.     

Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells

Endothelial nitric oxide synthase (eNOS) is essential for neovascularization. Here we show that the impaired neovascularization in mice lacking eNOS is related to a defect in progenitor cell mobilization. Mice deficient in eNOS (Nos3(-/-)) show reduced vascular endothelial growth factor (VEGF)-induced mobilization of endothelial progenitor cells (EPCs) and increased mortality after myelosuppression. Intravenous infusion of wild-type progenitor cells, but not bone marrow transplantation, rescued the defective neovascularization of Nos3(-/-) mice in a model of hind-limb ischemia, suggesting that progenitor mobilization from the bone marrow is impaired in Nos3(-/-) mice. Mechanistically, matrix metalloproteinase-9 (MMP-9), which is required for stem cell mobilization, was reduced in the bone marrow of Nos3(-/-) mice. These findings indicate that eNOS expressed by bone marrow stromal cells influences recruitment of stem and progenitor cells. This may contribute to impaired regeneration processes in ischemic heart disease patients, who are characterized by a reduced systemic NO bioactivity.     

Redox regulatory and anti-apoptotic functions of thioredoxin depend on S-nitrosylation at cysteine 69

Thioredoxin 1 (Trx) is a known redox regulator that is implicated in the redox control of cell growth and apoptosis inhibition. Here we show that Trx is essential for maintaining the content of S-nitrosylated molecules in endothelial cells. Trx itself is S-nitrosylated at cysteine 69 under basal conditions, and this S-nitrosylation is required for scavenging reactive oxygen species and for preserving the redox regulatory activity of Trx. S-nitrosylation of Trx also contributes to the anti-apoptotic function of Trx. Thus, Trx can exert its complete redox regulatory and anti-apoptotic functions in endothelial cells only when cysteine 69 is S-nitrosylated.     

不同季节和冬眠时相中达乌尔黄鼠视前区温敏神经元特性和下丘脑内NA代谢的变化

比较了不同季节和冬眠时相中达乌尔黄鼠 (Citelleusdauricus)下丘脑内去甲肾上腺素 (noradrenaline ,NA)代谢和视前区 (POA)脑片中各类温敏神经元的比例、温度敏感性、放电活动的临界温度及下限温度 .结果表明 :与夏季动物相比 ,( 1)冬眠各时相中POA温敏神经元的比例和温敏性产生了与冬眠体温调节特性相关的适应性改变 ;( 2 )冬季和冬眠中POA神经元放电的下限温度和温敏神经元活动的临界温度均显著下移 ;( 3 )冬眠中POA神经元对NA反应的敏感性增高 ,冷敏神经元对NA的反应从夏季的抑制型转变为冬眠时的兴奋型 ;( 4)入眠和深冬眠时下丘脑内NA的含量和代谢水平下降 ,出眠时代谢水平升高 .这些变化可能解释动物入眠时主动降低体温和出眠时从深低体温中快速地升温的温度调节机理 .     

Urinary desmosine as a biomarker in acute lung injury.

Acute lung injury (ALI) is a complex disorder associated with an acute inflammatory response thought to contribute to tissue injury. Desmosine, a cross-linking amino acid present in elastin, is released during matrix degradation and cleared by the kidney. Results from animal models and human disease studies have suggested that ALI is associated with the release of desmosine, resulting in increased urinary desmosine. A radioimmunoassay was used to monitor urinary desmosine levels over 10 days in ten patients with ALI. The concentration of desmosine was measured with and without acid hydrolysis. Baseline urinary desmosine was increased in two of ten patients. The concentration of desmosine at baseline did not appear to be related to age, gender, neutrophil elastase (NE)/alpha(1)-antiprotease complex concentration or P(a)O(2)/F(i)O(2) ratio. No meaningful changes in desmosine levels were noted after removal from mechanical ventilation. Baseline desmosine concentrations did not appear to correlate with the risk of death. The limited sensitivity, predictive correlations and dynamic modulation would suggest that urine desmosine has a limited role as a biomarker for ALI. Hydrolysis of urine samples appears necessary for optimal measurement of urine desmosine.     

Substitution bias, rapid saturation, and the use of mtDNA for nematode systematics

Only relatively recently have researchers turned to molecular methods for nematode phylogeny reconstruction. Thus, we lack the extensive literature on evolutionary patterns and phylogenetic usefulness of different DNA regions for nematodes that exists for other taxa. Here, we examine the usefulness of mtDNA for nematode phylogeny reconstruction and provide data that can be used for a priori character weighting or for parameter specification in models of sequence evolution. We estimated the substitution pattern for the mitochondrial ND4 gene from intraspecific comparisons in four species of parasitic nematodes from the family Trichostrongylidae (38-50 sequences per species). The resulting pattern suggests a strong mutational bias toward A and T, and a lower transition/transversion ratio than is typically observed in other taxa. We also present information on the relative rates of substitution at first, second, and third codon positions and on relative rates of saturation of different types of substitutions in comparisons ranging from intraspecific to interordinal. Silent sites saturate extremely quickly, presumably owing to the substitution bias and, perhaps, to an accelerated mutation rate. Results emphasize the importance of using only the most closely related sequences in order to infer patterns of substitution accurately for nematodes or for other taxa having strongly composition-biased DNA. ND4 also shows high amino acid polymorphism at both the intra- and interspecific levels, and in higher level comparisons, there is evidence of saturation at variable amino acid sites. In general, we recommend using mtDNA coding genes only for phylogenetics of relatively closely related nematode species and, even then, using only nonsynonymous substitutions and the more conserved mitochondrial genes (e.g., cytochrome oxidases). On the other hand, the high substitution rate in genes such as ND4 should make them excellent for population genetics studies, identifying cryptic species, and resolving relationships among closely related congeners when other markers show insufficient variation.      

Identification of an alpha3-fucosyltransferase and a novel alpha2- fucosyltransferase activity in cercariae of the schistosome Trichobilharzia ocellata: biosynthesis of the Fucalpha1-->2Fucalpha1-- >3[Gal(NAc)beta1-->4]GlcNAc sequence

Fucose is a major constituent of the protein- and lipid-linked glycans of the various life-cycle stages of schistosomes. These fucosylated glycans are highly antigenic and seem to play a role in the pathology of schistosomiasis. In this article we describe the identification and characterization of two fucosyltransferases (FucTs) in cercariae of the avian schistosome Trichobilharzia ocellata, a GDP-Fuc:[Galbeta1-- >4]GlcNAcbeta-R alpha1-->3-FucT and a novel GDP-Fuc:Fucalpha-R alpha1-- >2-FucT. Triton X-100 extracts of cercariae were assayed for FucT activity using a variety of acceptor substrates. Type 1 chain (Galbeta1- ->3GlcNAc) based compounds were poor acceptors, whereas those based on a type 2 chain (Galbeta1-->4GlcNAc), whether alpha2'-fucosylated, alpha3'-sialylated, or unsubstituted, and whether present as oligosaccharide or contained in a glycopeptide or glycoprotein, all served as acceptor substrates. In this respect the schistosomal alpha3- FucT resembles human FucT V and VI rather than other known FucTs. N- ethylmaleimide, an inhibitor of several human FucTs, had no effect on the activity of the schistosomal alpha3-FucT, whereas GDP-beta-S was strongly inhibitory. Large scale incubations were carried out with Galbeta1-->4GlcNAc, GalNAcbeta1-->4GlcNAcbeta-O -(CH2)8COOCH3 and Fucalpha1-->3GlcNAcbeta1-->2Man as acceptor substrates and the products of the incubations were isolated using a sequence of chromatographic techniques. By methylation analysis and 2D-TOCSY and ROESY1H-NMR spectroscopy the products formed were shown to be Galbeta1-- >4[Fucalpha1-->2Fucalpha1-->3]GlcNAc, GalNAcbeta1-->4[Fucalpha1-- >2Fucalpha1-->3]GlcNAcbe ta-O-(CH2)8COOCH3, and Fucalpha1-->2Fucalpha1-- >3GlcNAcbeta1-->2Man, respectively. It is concluded that the alpha2- FucT and alpha3-FucT are involved in the biosynthesis of the (oligomeric) Lewisx sequences and the Fucalpha1-->2Fucalpha1-->3GlcNAc structural element that have been described on schistosomal glycoconjugates.