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51.
Ignatius R Gahutu JB Klotz C Steininger C Shyirambere C Lyng M Musemakweri A Aebischer T Martus P Harms G Mockenhaupt FP 《PLoS neglected tropical diseases》2012,6(6):e1677
Background
Giardia duodenalis is highly endemic in East Africa but its effects on child health, particularly of submicroscopic infections, i.e., those below the threshold of microscopy, and of genetic subgroups (assemblages), are not well understood. We aimed at addressing these questions and at examining epidemiological characteristics of G. duodenalis in southern highland Rwanda.Methodology/Principal Findings
In 583 children <5 years of age from communities and health facilities, intestinal parasites were assessed by triplicate light microscopy and by PCR assays, and G. duodenalis assemblages were genotyped. Cluster effects of villages were taken into account in statistical analysis. The prevalence of G. duodenalis as detected by microscopy was 19.8% but 60.1% including PCR results. Prevalence differed with residence, increased with age, and was reduced by breastfeeding. In 492 community children without, with submicroscopic and with microscopic infection, underweight (weight-for-age z-score <−2 standard deviations) was observed in 19.7%, 22.1%, and 33.1%, respectively, and clinically assessed severe malnutrition in 4.5%, 9.5%, and 16.7%. Multivariate analysis identified microscopically detectable G. duodenalis infection as an independent predictor of underweight and clinically assessed severe malnutrition. Submicroscopic infection showed respective trends. Overall, G. duodenalis was not associated with gastrointestinal symptoms but assemblages A parasites (proportion, 13%) were increased among children with vomiting and abdominal pain.Conclusions/Significance
The prevalence of G. duodenalis in high-endemicity areas may be greatly underestimated by light microscopy, particularly when only single stool samples are analysed. Children with submicroscopic infections show limited overt manifestation, but constitute unrecognized reservoirs of transmission. The predominance of assemblage B in Rwanda may be involved in the seemingly unimposing manifestation of G. duodenalis infection. However, the association with impaired child growth points to its actual relevance. Longitudinal studies considering abundant submicroscopic infections are needed to clarify the actual contribution of G. duodenalis to morbidity in areas of high endemicity. 相似文献52.
Neural crest-derived pigment cell development has been used extensively to study cell fate specification, migration, proliferation, survival and differentiation. Many of the genes and regulatory mechanisms required for pigment cell development are conserved across vertebrates. The zebrafish mutant colgate (col)/histone deacetylase1 (hdac1) has reduced numbers, delayed differentiation and decreased migration of neural crest-derived melanophores and their precursors. In hdac1col mutants normal numbers of premigratory neural crest cells are induced. Later, while there is only a slight reduction in the number of neural crest cells in hdac1col mutants, there is a severe reduction in the number of mitfa-positive melanoblasts suggesting that hdac1 is required for melanoblast specification. Concomitantly, there is a significant increase in and prolonged expression of foxd3 in neural crest cells in hdac1col mutants. We found that partially reducing Foxd3 expression in hdac1col mutants rescues mitfa expression and the melanophore defects in hdac1col mutants. Furthermore, we demonstrate the ability of Foxd3 to physically interact at the mitfa promoter. Because mitfa is required for melanoblast specification and development, our results suggest that hdac1 is normally required to suppress neural crest foxd3 expression thus de-repressing mitfa resulting in melanogenesis by a subset of neural crest-derived cells. 相似文献
53.
Szeto IM Aziz A Das PJ Taha AY Okubo N Reza-Lopez S Giacca A Anderson GH 《American journal of physiology. Regulatory, integrative and comparative physiology》2008,295(2):R575-R582
The effect of high multivitamin intake during pregnancy on the metabolic phenotype of rat offspring was investigated. Pregnant Wistar rats (n=10 per group) were fed the AIN-93G diet with the recommended vitamin (RV) content or a 10-fold increase [high vitamin (HV) content]. In experiment 1, male and female offspring were followed for 12 wk after weaning; in experiment 2, only males were followed for 28 wk. Body weight (BW) was measured weekly. Every 4 wk, after an overnight fast, food intake over 1 h was measured 30 min after a gavage of glucose or water. An oral glucose tolerance test was performed every 3-5 wk. Postweaning fasting glucose, insulin, ghrelin, glucagon-like peptide-1, and systolic blood pressure were measured. No difference in BW at birth or litter size was observed. Food intake was greater in males born to HV dams (P<0.05), and at 28 wk after weaning, BW was 8% higher (P<0.05) and fat pad mass was 27% higher (P<0.05). Food intake reduction after the glucose preload was nearly twofold less in males born to HV dams at 12 wk after weaning (P<0.05). Fasting glucose, insulin, and ghrelin were 11%, 62%, and 41% higher in males from HV dams at 14 wk after weaning (P<0.05). Blood glucose response was 46% higher at 23 wk after weaning (P<0.01), and systolic blood pressure was 16% higher at 28 wk after weaning (P<0.05). In conclusion, high multivitamin intake during pregnancy programmed the male offspring for the development of the components of metabolic syndrome in adulthood, possibly by its effects on central mechanisms of food intake control. 相似文献
54.
Protein post-translational modifications are crucial to the function of many proteins. In this study, we have investigated the structural environment of 8378 incidences of 44 types of post-translational modifications with 19 different approaches. We show that modified amino acids likely to be involved in protein-protein interactions, such as ester-linked phosphorylation, methylarginine, acetyllysine, sulfotyrosine, hydroxyproline, and hydroxylysine, are clearly surface associated. Other modifications, including O-GlcNAc, phosphohistidine, 4-aspartylphosphate, methyllysine, and ADP-ribosylarginine, are either not surface associated or are in a protein's core. Artifactual modifications were found to be randomly distributed throughout the protein. We discuss how the surface accessibility of post-translational modifications can be important for protein-protein interactivity. 相似文献
55.
56.
Lin R Lu Y Wetter SK Connolly PJ Turchi IJ Murray WV Emanuel SL Gruninger RH Fuentes-Pesquera AR Adams M Pandey N Moreno-Mazza S Middleton SA Jolliffe LK 《Bioorganic & medicinal chemistry letters》2005,15(9):2221-2224
A novel series of 2,6-diamino-3-acylpyridines were designed and synthesized as cyclin-dependent kinase (CDK) inhibitors. The representative compounds 2r and 11 showed potent CDK1 and CDK2 inhibitory activities and inhibited cellular proliferation in HeLa, HCT116, and A375 tumor cells. 相似文献
57.
E Laiho J Ignatius H Mikkola V C Yee D C Teller K M Niemi U Saarialho-Kere J Kere A Palotie 《American journal of human genetics》1997,61(3):529-538
Autosomal recessive congenital ichthyosis (ARCI) is a rare, heterogenous keratinization disorder of the skin, classically divided into two clinical subtypes, lamellar ichthyosis (LI) and nonbullous congenital ichthyosiformis erythroderma (CIE). Recently, strong evidence for the involvement of the transglutaminase 1 gene (TGM1) in LI has evolved. We have studied ARCI in the isolated Finnish population, in which recessive disorders are often caused by single mutations enriched by a founder effect. Surprisingly, five different mutations of TGM1 (Arg141His, Arg142Cys, Gly217Ser, Val378Leu, and Arg395Leu) were found in Finnish ARCI patients. In addition to affected LI patients, we also identified TGM1 mutations in CIE patients. Moreover, haplotype analysis of the chromosomes carrying the most common mutation, a C-->T transition changing Arg142 to Cys, revealed that the same mutation has been introduced twice in the Finnish population. In addition to this Arg142Cys mutation, three other mutations, in Arg141 and Arg142, have been described elsewhere, in other populations. These findings suggest that this region of TGM1 is more susceptible to mutation. The corresponding amino acid sequence is conserved in other transglutaminases, but, for example, coagulation factor XIII (FXIII) mutations do not cluster in this region. Protein modeling of the Arg142Cys mutation suggested disruption or destabilization of the protein. In transfection studies, the closely related transglutaminase FXIII protein with the corresponding mutation was shown to be susceptible to degradation in COS cells, further supporting evidence of the destabilizing effect of the Arg142Cys mutation in TGM1. 相似文献
58.
Raf and Fibroblast Growth Factor Phosphorylate Elk1 and Activate the Serum Response Element of the Immediate Early Gene pip92 by Mitogen-Activated Protein Kinase-Independent as Well as -Dependent Signaling Pathways 总被引:2,自引:0,他引:2 下载免费PDF全文
59.
Signal transduction pathways involved in mechanical regulation of HB-GAM expression in osteoblastic cells 总被引:1,自引:0,他引:1
Liedert A Kaspar D Claes L Ignatius A 《Biochemical and biophysical research communications》2006,342(4):1070-1076
Protein kinase C (PKC), protein kinase A (PKA), prostaglandin synthesis, and various mitogen-activated protein kinases (MAPKs) have been reported to be activated in bone cells by mechanical loading. We studied the involvement of these signal transduction pathways in the downregulation of HB-GAM expression in osteoblastic cells after cyclic stretching. Specific antagonists and agonists of these signal transduction pathways were added to cells before loading and to non-loaded control cells. Quantitative RT-PCR was used to evaluate gene expression. The data demonstrated that the extracellular signal-regulated kinase (ERK) 1/2 pathway, PKC, PKA, p38, and c-Jun N-terminal kinase MAPK participated in the mechanical downregulation of HB-GAM expression, whereas prostaglandin synthesis did not seem to be involved. 相似文献
60.
E. Petter Axelsson Kevin C. Grady Maria L. T. Lardizabal Ignatius B. S. Nair Daideth Rinus Ulrik Ilstedt 《Restoration Ecology》2020,28(1):156-165
Effective reforestation of degraded tropical forests depends on selecting planting material suited to the stressful environments typical at restoration sites that can be exacerbated by increased duration and intensity of dry spells expected with climate change. While reforestation efforts in nontropical systems are incorporating drought‐adapted genotypes into restoration programs to cope with drier conditions, such approaches have not been tested or implemented in tropical forests. As the first effort to examine genetic variation in plant response to drought in a tropical wet forest, we established a watering experiment using five replicated maternal lines (i.e. seedlings from different maternal trees) of five dipterocarp species native to Borneo. Apart from the expected species level variation in growth and herbivory (3‐fold variation in both cases), we also found intraspecific variation so that growth in some cases varied 2‐fold, and herbivory 3‐fold, among genetically different maternal lines. In two species we found that among‐maternal line variation in growth rate was negatively correlated with tolerance to water limitation, that is, the maternal lines that performed the best in the high water treatment lost proportionally more of their growth during water limitation. We argue that selection for tolerance to future drier conditions is not only likely to impact population genetics of entire forests, but likely extends from forest trees to the communities of canopy arthropods associated with these trees. In tropical reforestation efforts where increased drought is predicted from climate change, including plant material resilient to drier conditions may improve restoration effectiveness. 相似文献