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Using a battery of seven lectin-ferritin conjugates as probes for cell surface glycoconjugates, we have studied the pattern of plasmalemmal differentiation of cells in the embryonic rat pancreas from day 15 in utero to the early postpartum stage. Our results indicate that differentiation of plasmalemmal glycoconjugates on acinar, endocrine, and centroacinar cells is temporally correlated with development and is unique for each cell type, as indicated by lectin-ferritin binding. Specifically, (a) expression of adult cell surface saccharide phenotype can be detected on presumptive acinar cells as early as 15 d in utero, as indicated by soybean agglutinin binding, and precedes development of intracellular organelles characteristic of mature acinar cells; (b) maturation of the plasmalemma of acinar cells is reached after intracellular cytodifferentiation is completed, as indicated by appearance of Con A and fucoselectin binding sites only at day 19 of development; conversely, maturation of the endocrine cell plasmalemma is accompanied by "loss" (masking) of ricinus communis II agglutinin receptors; and (c) binding sites for fucose lectins and for soybean agglutinin are absent on endocrine and centroacinar cells at all stages examined. We conclude that acinar, centroacinar, and endocrine cells develop from a common progenitor cell(s) whose plasmalemmal carbohydrate composition resembles most closely that of the adult centroacinar cell. Finally, appearance of acinar lumina beginning at approximately 17 d in utero is accompanied by differenetiation of apical and basolateral plasmalemmal domains of epithelial cells, as indicated by enhanced binding of several lectin-ferritin conjugates to the apical plasmalemmal, a pattern that persists from this stage through adult life. 相似文献
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Alain Gagnon Matthew S. Miller Stacey A. Hallman Robert Bourbeau D. Ann Herring David JD. Earn Joaquín Madrenas 《PloS one》2013,8(8)
The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889–90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics.
“The war is over – and I must go” Egon Schiele, 1890–1918.相似文献
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Felkner M Suarez L Liszka B Brender JD Canfield M 《Birth defects research. Part A, Clinical and molecular teratology》2007,79(8):617-621
BACKGROUND: Previous findings for the Texas Neural Tube Defects Project suggested that while maternal access to nutrients is adequate, bioavailability of nutrients to the fetus is compromised in NTD-affected pregnancies. Helicobacter pylori could cause nutrient loss to the fetus. Folate, B12, and ferritin are depleted in H. pylori infection; these same deficiencies are related to NTD risk. METHODS: Using H. pylori IgG ELISA Test System, we tested for H. pylori serum antibodies in participants in the population-based case-control study component of the Texas Neural Tube Defect Project conducted along the Texas-Mexico border. Case-women had pregnancies affected by NTD (anencephalus, spina bifida, encephalocele) and resided and delivered in one of the 14 Texas-Mexico border counties from 1995 through 2000. Control-women were study area residents delivering normal live births during the same period. RESULTS: Of 225 case- and 378 control-women, 103 cases and 156 controls provided questionnaire and H. pylori antibody data. H. pylori seropositivity was modestly associated with NTD-affected pregnancies (OR 1.4; 95% CI: 0.8-2.4). ORs of 2.0 or greater were seen in women younger than age 25 and with less than 7 years education. CONCLUSIONS: Our findings intimate that H. pylori could play a role in NTD causation in certain populations. While results did not provide compelling support for this proposal, subgroup findings prompt us to advocate an evaluation of this hypothesis in developing nations among populations with higher prevalence of H. pylori, marginal nutrient intake, and young childbearing age. 相似文献
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PJ?MumbyEmail author JD?Hedley JRM?Chisholm CD?Clark H?Ripley J?Jaubert 《Coral reefs (Online)》2004,23(2):171-183
Trends in coral cover are widely used to indicate the health of coral reefs but are costly to obtain from field survey over large areas. In situ studies of reflected spectra at the coral surface show that living and recently dead colonies can be distinguished. Here, we investigate whether such spectral differences can be detected using an airborne remote sensing instrument. The Compact Airborne Spectrographic Imager (Itres Research Ltd, Canada) was flown in two configurations: 10 spectral bands with 1-m2 pixels and 6 spectral bands with 0.25-m2 pixels. First, we show that an instrument with 10 spectral bands possesses adequate spectral resolution to distinguish living Porites, living Pocillopora spp., partially dead Porites, recently dead
Porites (total colony mortality within 6 months), old dead (>6 months) Porites,
Halimeda spp., and coralline red algae when there is no water column to confuse spectra. All substrata were distinguished using fourth-order spectral derivatives around 538 nm and 562 nm. Then, at a shallow site (Tivaru) at Rangiroa Atoll, Tuamotu Archipelago (French Polynesia), we show that live and dead coral can be distinguished from the air to a depth of at least 4 m using first- and fourth-order spectral derivatives between 562–580 nm. However, partially dead and recently dead Porites
colonies could not be distinguished from an airborne platform. Spectral differences among substrata are then exploited to predict the cover of reef substrata in ten 25-m2 plots at nearby Motu Nuhi (max depth 8 m). The actual cover in these plots was determined in situ using quadrats with a 0.01-m2 grid. Considerable disparity occurred between field and image-based measures of substrate cover within individual 25-m2 quadrats. At this small scale, disparity, measured as the absolute difference in cover between field and remote-sensing methods, reached 25% in some substrata but was always less than 10% for living coral (99% of which consisted of
Porites spp.). At the scale of the reef (all ten 25-m2 quadrats), however, disparities in percent cover between imagery and field data were less than 10% for all substrata and extremely low for some classes (e.g. <3% for living
Porites, recently dead Porites
and Halimeda). The least accurately estimated substrata were sand and coralline red algae, which were overestimated by absolute values 7.9% and 6.6%, respectively. The precision of sampling was similar for field and remote-sensing methods: field methods required 19 plots to detect a 10% difference in coral cover among three reefs with a statistical power of 95%. Remote-sensing methods required 21 plots. However, it took 1 h to acquire imagery over 92,500 m2 of reef, which represents 3,700 plots of 25 m2 each, compared with 3 days to survey 10 such plots underwater. There were no significant differences in accuracy between 1-m2 and 0.25-m2 image resolutions, suggesting that the advantage of using smaller pixels is offset by reduced spectral information and an increase in noise (noise was observed to be 1.6–1.8 times greater in 0.25-m2 pixels). We show that airborne remote sensing can be used to monitor coral and algal cover over large areas, providing that water is shallow and clear, and that brown fleshy macroalgae are scarce, that depth is known independently (e.g. from sonar survey). 相似文献
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Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F 总被引:2,自引:0,他引:2
Kuestner RE Taft DW Haran A Brandt CS Brender T Lum K Harder B Okada S Ostrander CD Kreindler JL Aujla SJ Reardon B Moore M Shea P Schreckhise R Bukowski TR Presnell S Guerra-Lewis P Parrish-Novak J Ellsworth JL Jaspers S Lewis KE Appleby M Kolls JK Rixon M West JW Gao Z Levin SD 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(8):5462-5473
The proinflammatory cytokines IL-17A and IL-17F have a high degree of sequence similarity and share many biological properties. Both have been implicated as factors contributing to the progression of inflammatory and autoimmune diseases. Moreover, reagents that neutralize IL-17A significantly ameliorate disease severity in several mouse models of human disease. IL-17A mediates its effects through interaction with its cognate receptor, the IL-17 receptor (IL-17RA). We report here that the IL-17RA-related molecule, IL-17RC is the receptor for IL-17F. Notably, both IL-17A and IL-17F bind to IL-17RC with high affinity, leading us to suggest that a soluble form of this molecule may serve as an effective therapeutic antagonist of IL-17A and IL-17F. We generated a soluble form of IL-17RC and demonstrate that it effectively blocks binding of both IL-17A and IL-17F, and that it inhibits signaling in response to these cytokines. Collectively, our work indicates that IL-17RC functions as a receptor for both IL-17A and IL-17F and that a soluble version of this protein should be an effective antagonist of IL-17A and IL-17F mediated inflammatory diseases. 相似文献
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Sébastien JD Giroux Celmar Alves-Leiva Yann Lécluse Patrick Martin Olivier Albagli Isabelle Godin 《BMC developmental biology》2007,7(1):79
Background
Hematopoietic development in vertebrate embryos results from the sequential contribution of two pools of precursors independently generated. While intra-embryonic precursors harbour the features of hematopoietic stem cells (HSC), precursors formed earlier in the yolk sac (YS) display limited differentiation and self-renewal potentials. The mechanisms leading to the generation of the precursors in both sites are still largely unknown, as are the molecular basis underlying their different potential. A possible approach to assess the role of candidate genes is to transfer or modulate their expression/activity in both sites. We thus designed and compared transduction protocols to target either native extra-embryonic precursors, or hematopoietic precursors. 相似文献8.
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Peter JD Andrews Helen Louise Sinclair Claire G Battison Kees H Polderman Giuseppe Citerio Luciana Mascia Bridget A Harris Gordon D Murray Nino Stocchetti David K Menon Haleema Shakur Daniel De Backer 《Trials》2011,12(1):1-13
Background
Severe malaria remains a major cause of global morbidity and mortality. Despite the use of potent anti-parasitic agents, the mortality rate in severe malaria remains high. Adjunctive therapies that target the underlying pathophysiology of severe malaria may further reduce morbidity and mortality. Endothelial activation plays a central role in the pathogenesis of severe malaria, of which angiopoietin-2 (Ang-2) has recently been shown to function as a key regulator. Nitric oxide (NO) is a major inhibitor of Ang-2 release from endothelium and has been shown to decrease endothelial inflammation and reduce the adhesion of parasitized erythrocytes. Low-flow inhaled nitric oxide (iNO) gas is a US FDA-approved treatment for hypoxic respiratory failure in neonates.Methods/Design
This prospective, parallel arm, randomized, placebo-controlled, blinded clinical trial compares adjunctive continuous inhaled nitric oxide at 80 ppm to placebo (both arms receiving standard anti-malarial therapy), among Ugandan children aged 1-10 years of age with severe malaria. The primary endpoint is the longitudinal change in Ang-2, an objective and quantitative biomarker of malaria severity, which will be analysed using a mixed-effects linear model. Secondary endpoints include mortality, recovery time, parasite clearance and neurocognitive sequelae.Discussion
Noteworthy aspects of this trial design include its efficient sample size supported by a computer simulation study to evaluate statistical power, meticulous attention to complex ethical issues in a cross-cultural setting, and innovative strategies for safety monitoring and blinding to treatment allocation in a resource-constrained setting in sub-Saharan Africa.Trial Registration
ClinicalTrials.gov Identifier: NCT01255215 相似文献10.
Margaret I Butler Jeremy Gray Timothy JD Goodwin Russell TM Poulter 《BMC evolutionary biology》2006,6(1):42-26