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171.
Leonie K. Ashman Hans-Jrg Bühring Gabriella W. Aylett Virginia C. Broudy Claudia Müller 《Journal of cellular physiology》1994,158(3):545-554
Three monoclonal antibodies (MAbs) to the human c-kit receptor tyrosine kinase (P145c-kit), derived in independent laboratories, have been extensively used in studies of c-kit expression and the role of its ligand, steel factor (SLF), in hemopoiesis and mast cell differentiation and function. In this study, the relationship between the epitopes they identify, and their effects on SLF binding, receptor internalization, and signal transduction are compared. Epitope mapping studies carried out on the high P145c-kit-expressing cell line HEL-DR showed that SR-1 identifies an epitope independent of those bound by YB5.B8 and 17F11, while the latter two antibodies bound to distinct but interacting epitopes. SR-1 potently blocked the binding of SLF to P145c-kit on these cells and also on cells of the factor-dependent line MO7e. In contrast, YB5.B8 and 17F11 had minimal effects on ligand binding. Conversely, SLF partially blocked the binding of SR-1 and YB5.B8 to cells, while binding of 17F11 was actually enhanced by SLF on some target cells. Preincubation of HEL-DR and MO7e cells with MAbs prior to exposure to SLF revealed that 17F11 itself brought about partial down-regulation of P145c-kit and did not inhibit SLF-mediated down-regulation. SR-1 caused minimal down-regulation and inhibited SLF-mediated receptor internalization. YB5.B8 had minimal effects on either cell line in this assay. To determine whether the antibodies had any agonist activity, they were compared with SLF for their ability to bring about receptor phosphorylation in intact MO7e cells. All three antibodies induced detectable tyrosine phosphorylation with 17F11 being the most effective, while YB5.B8 was the least effective. Finally, the ability of the antibodies to influence the proliferation of the MO7e cells was examined. As expected, SR-1 potently inhibited the proliferative response to SLF, while 17F11 weakly inhibited and YB5.B8 had negligible effect. In the absence of SLF both 17F11 and YB5.B8 displayed very weak but reproducible agonist activity. © 1994 Wiley-Liss, Inc. 相似文献
172.
Phospholipid synthesis by activated human B lymphocytes 总被引:1,自引:0,他引:1
Pokeweed mitogen- (PWM) stimulated DNA and Ig synthesis in human B cells is dependent on the presence of T cells and adherent cells, but the influence of these regulatory cells on earlier activation events is unknown. We have studied the T cell and monocyte influence on the incorporation of [methyl-14C]choline chloride into B cell phospholipids (PL) after varying periods of in vitro culture with or without pokeweed mitogen (PWM). By separating B and T cells after choline pulsing, a peak in PWM-induced PL synthesis of B cells at days 1 to 2 was revealed, whereas the T cell response was later (days 2 to 3). In the first 4 hr of culture, the purified B cell plus monocyte fraction incorporated choline four to six times faster than the T cell fraction, but PWM did not increase choline incorporation, whether these fractions were cultured separately or together. When cultures were pulsed with choline between 16 and 20 hr with or without PWM, monocytes incorporated choline six to nine times faster than T cells, and B cells were intermediate. Also at 16 to 20 hr of culture, a significant PWM-induced increase in choline incorporation by B cells was evident and was dependent on the presence of T cells and monocytes. The monocytes showed no increased choline incorporation due to PWM. Thus, the influence of regulatory cells on the PWM response in B cells is evident within the first 24 hr. 相似文献
173.
Nenninger AA Robinson LS Hammer ND Epstein EA Badtke MP Hultgren SJ Chapman MR 《Molecular microbiology》2011,81(2):486-499
Curli are extracellular amyloid fibres produced by Escherichia coli that are critical for biofilm formation and adhesion to biotic and abiotic surfaces. CsgA and CsgB are the major and minor curli subunits, respectively, while CsgE, CsgF and CsgG direct the extracellular localization and assembly of curli subunits into fibres. The secretion and stability of CsgA and CsgB are dependent on the outer membrane lipoprotein CsgG. Here, we identified functional interactions between CsgG and CsgE during curli secretion. We discovered that CsgG overexpression restored curli production to a csgE strain under curli-inducing conditions. In antibiotic sensitivity and protein secretion assays, CsgG expression alone allowed translocation of erythromycin and small periplasmic proteins across the outer membrane. Coexpression of CsgE with CsgG blocked non-specific protein and antibiotic passage across the outer membrane. However, CsgE did not block secretion of proteins containing a 22-amino-acid putative outer membrane secretion signal of CsgA (A22). Finally, using purified proteins, we found that CsgE prohibited the self-assembly of CsgA into amyloid fibres. Collectively, these data indicate that CsgE provides substrate specificity to the curli secretion pore CsgG, and acts directly on the secretion substrate CsgA to prevent premature subunit assembly. 相似文献
174.
Moore KJ Turconi S Ashman S Ruediger M Haupts U Emerick V Pope AJ 《Journal of biomolecular screening》1999,4(6):335-354
Fluorescence assay technologies used for miniaturized high throughput screening are broadly divided into two classes. Macroscopic fluorescence techniques (encompassing conventional fluorescence intensity, anisotropy [also often referred to as fluorescence polarization] and energy transfer) monitor the assay volume- and time-averaged fluorescence output from the ensemble of emitting fluorophores. In contrast, single-molecule detection (SMD) techniques and related approaches, such as fluorescence correlation spectroscopy (FCS), stochastically sample the fluorescence properties of individual constituent molecules and only then average many such detection events to define the properties of the assay system as a whole. Analysis of single molecular events is accomplished using confocal optics with an illumination/detection volume of approximately 1 fl (10(-15) L) such that the signal is insensitive to miniaturization of HTS assays to 1 μl or below. In this report we demonstrate the general applicability of one SMD technique (FCS) to assay configuration for target classes typically encountered in HTS and confirm the equivalence of the rate/equilibrium constants determined by FCS and by macroscopic techniques. Advantages and limitations of the current FCS technology, as applied here, and potential solutions, particularly involving alternative SMD detection techniques, are also discussed. 相似文献
175.
Produced by many Enterobacteriaceae spp., curli are biologically important amyloid fibres that have been associated with biofilm formation, host cell adhesion and invasion, and immune system activation. CsgA is the major fibre subunit and CsgE, CsgF and CsgG are non-structural proteins involved in curli biogenesis. We have characterized the role of CsgG in curli subunit secretion across the outer membrane. Directed mutagenesis of CsgG confirmed that its activity is dependent on localization to the outer membrane. Rotary Shadow electron microscopy of purified CsgG suggested that this protein assembles into an oligomeric complex with an apparent central pore. Oligomeric CsgG complexes were confirmed using co-purification experiments. Antibiotic sensitivity assays demonstrated that overexpression of CsgG rendered Escherichia coli susceptible to the antibiotic erythromycin. A 22-amino-acid sequence at the N-terminus of CsgA was sufficient to direct heterologous proteins to the CsgG secretion apparatus. Finally, we determined that CsgG participates in an outer membrane complex with two other curli assembly proteins, CsgE and CsgF. 相似文献
176.
The development of the lymphoid tissues in a macropod marsupial is described. The liver is the only functional haemopoietic tissue at birth. Large lymphocytes first appear in the cervical thymus at 2 days, and in the thoracic thymus at 4 days after birth. Small lymphocytes appear 1-2 days later. The histological development of the two glands is similar, but the thoracic thymus develops much more slowly than the cervical. The appearance of Hassall's corpuscles in both thymus glands correlates with the onset of humoral immune responses in this animal. Lymph nodes first appear as aggregates of lymphocytes around the lymphatic vessels at 5 days, differentiate into cortex and medulla at about 14 days, but do not develop germinal centres until about 90 days. Small lymphocytes are not observed in the spleen until the 2nd week, and reactive centres do not appear until after 90 days of pouch life. Peyer's patches are not found until 60 days of age. Large lymphocytes are seen in the bone marrow at 14 days, but small lymphocytes are not found until the 1st month. Although the sequence of lymphoid development is similar to that seen in other animals, the rapidly with which it becomes functional suggests that it is an adaptive response to early contact with environment pathogens. 相似文献
177.
Doris Bachtrog Judith E. Mank Catherine L. Peichel Mark Kirkpatrick Sarah P. Otto Tia-Lynn Ashman Matthew W. Hahn Jun Kitano Itay Mayrose Ray Ming Nicolas Perrin Laura Ross Nicole Valenzuela Jana C. Vamosi The Tree of Sex Consortium 《PLoS biology》2014,12(7)
Sexual reproduction is an ancient feature of life on earth, and the familiar X and Y chromosomes in humans and other model species have led to the impression that sex determination mechanisms are old and conserved. In fact, males and females are determined by diverse mechanisms that evolve rapidly in many taxa. Yet this diversity in primary sex-determining signals is coupled with conserved molecular pathways that trigger male or female development. Conflicting selection on different parts of the genome and on the two sexes may drive many of these transitions, but few systems with rapid turnover of sex determination mechanisms have been rigorously studied. Here we survey our current understanding of how and why sex determination evolves in animals and plants and identify important gaps in our knowledge that present exciting research opportunities to characterize the evolutionary forces and molecular pathways underlying the evolution of sex determination. 相似文献
178.
Reproductive traits are tightly linked to plant fitness and may therefore be mechanisms driving biological invasions, including
the greater success of more phylogenetically novel introduced species in some systems. We present a phylogenetic comparative
analysis of “Baker’s law’’, that introduced plants with the ability to reproduce autogamous or asexually may be better able
to establish on introduction. We gathered data from both published and unpublished sources on pollen limitation of 141 species,
including 26 introduced species and 115 native species. Our analysis compared differences in the proportion of autonomous
autogamy, asexual reproduction, and pollen limitation among native, introduced noninvasive, and introduced invasive plant
species, and included the phylogenetic novelty of the introduced species to the native species in that community. Introduced
species were more likely to be autogamous than native species, consistent with Baker’s law. On the other hand, introduced
species were less likely to have the ability to reproduce asexually. Further, among species with no autonomous autogamy, pollen
limitation was greater for introduced compared to native species. Such a result is consistent with the idea that plants entering
a new continent receive lower quality or quantity of services from resident pollinators than species native to that continent.
Finally, more phylogenetically novel invasive species had lower pollen limitation than less novel invasive species, potentially
because they experience less competition for pollinators. This is the first evidence that enhanced pollination may be one
mechanism driving the greater invasiveness of phylogenetically novel introduced species observed in some systems. 相似文献
179.
Background and Aims
Although pollen limitation of reproduction (PL) has been widely studied, our understanding of its occurrence in tropical communities, especially for bird-pollinated plants, is underdeveloped. In addition, inclusion of both quantity and quality aspects in studies of PL are generally lacking. Within hummingbird-pollinated plants, a prediction was made for higher PL for the quality than quantity aspects and a minor effect of temporal variation because hummingbirds are constant and efficient pollen vectors but they may transfer low quality pollen.Methods
Field hand and open pollination experiments were conducted on 21 species in a tropical montane rain forest over 2 years. The quantity (fruit set and seeds per fruit) and quality (seed weight and germination) aspects of reproduction were assessed as the response to open pollination relative to outcross hand pollination. The relationships between the effect size of quantity and quality aspects of reproduction and predictive plant features (self-incompatibility, autogamy, density and pollinator specialization level) were assessed with phylogenetic generalized linear models.Key Results
Just over half of all the species expressed PL for one or more response variables. On average, the severity of PL was strong for one quality variable (seed germination; 0·83), but insignificant for another (seed weight; –0·03), and low to moderate for quantity variables (0·31 for seeds per fruit and 0·39 for fruit set). There was only a minor contribution of temporal variation to PL within the studied species. Common predictors of PL, i.e. phylogenetic relatedness, self-incompatibility, autogamy, plant density and pollinator specialization level, did not adequately explain variation in PL within this community.Conclusions
Despite the measurable degree of PL within these hummingbird-pollinated plants, the causes of pollen quality and quantity insufficiency are not clear. Variables other than those tested may contribute to PL or causes of PL may vary among species and cannot adequately be accounted for when assessed from the within-community perspective. 相似文献180.
Conchita Alonso Carmen M. Navarro-Fernández Gerardo Arceo-Gómez George A. Meindl Víctor Parra-Tabla Tia-Lynn Ashman 《Annals of botany》2013,112(7):1461-1469