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Antigen presenting cells (APCs) in skin can promote either antigen-specific effector functions or antigen tolerance, and thus determine clearance or persistence of cutaneous viral infections. Human papillomavirus (HPV) infections can persist in squamous epithelium in immunocompetent individuals, and some persisting HPV infections, particularly with HPV16, promote malignant epithelial transformation. Here, we investigate whether local expression of the HPV16 protein most associated with malignant transformation, HPV16-E7, affects the phenotype and function of APC subsets in the skin. We demonstrate an expanded population of Langerhans cells in HPV16-E7 transgenic skin with distinct cell surface markers which express immune-modulatory enzymes and cytokines not expressed by cells from non transgenic skin. Furthermore, HPV16-E7 transgene expression in keratinocytes attracts new APC subsets to the epidermis. In vivo migration and transport of antigen to the draining lymph node by these APCs is markedly enhanced in HPV16-E7 expressing skin, whereas antigen-processing, as measured by proteolytic cleavage of DQ-OVA and activation of T cells in vivo by APCs, is significantly impaired. These data suggest that local expression of HPV16-E7 in keratinocytes can contribute to persisting infection with this oncogenic virus, by altering the phenotype and function of local APCs. 相似文献
3.
J W Ludlow C L Glendening D M Livingston J A DeCarprio 《Molecular and cellular biology》1993,13(1):367-372
The retinoblastoma gene product (RB) undergoes cell cycle-dependent phosphorylation and dephosphorylation. Pulse-chase experiments revealed that the change in RB gel electrophoretic migration which occurs near mitosis is due to enzymatic dephosphorylation (J. W. Ludlow, J. Shon, J. M. Pipas, D. M. Livingston, and J. A. DeCaprio, Cell 60:387-396, 1990). To determine the precise timing of RB dephosphorylation and whether a specific phosphatase is active in this process, we have utilized a nocodazole block and release protocol which allows a large population of cells to progress synchronously through mitosis. In such experiments, RB dephosphorylation began during anaphase and continued until complete dephosphorylation was apparent in the ensuing G1 period. In addition, late mitotic cell extracts were capable of dephosphorylating RB in vitro. This RB-specific mitotic phosphatase activity was more active in anaphase extracts than in pro- or metaphase extracts, which is consistent with the results obtained in vivo. Okadaic acid and protein phosphatase inhibitors 1 and 2 inhibited this specific RB phosphatase activity. These results suggest a role for serine and threonine phosphoprotein phosphatase type 1 in the late mitotic dephosphorylation of RB. 相似文献
4.
Vasant Chellappa Kendra N. Taylor Kathryn Pedrick Carlos Donado Ilka Arun Netravali Khaleda Haider Annaiah Cariappa Natasha F. Dalomba Shiv Pillai 《PloS one》2013,8(1)
Catalytically defective rare variants of Sialic acid Acetyl Esterase (SIAE) have previously been linked to autoimmunity. Studies presented here confirm that the M89V SIAE protein and all other products of common variant alleles of SIAE are catalytically normal. Although overexpressing transfected non-lymphoid cells secrete small amounts of SIAE that can associate with the cell surface, normal human lymphocytes do not exhibit cell surface SIAE, supporting genetic evidence in mice that indicates that this protein functions in a lymphocyte intrinsic manner. Analyses of the plasma proteome also indicate that SIAE is not secreted in vivo. A re-analysis exclusively of catalytically defective rare variant alleles of SIAE in subjects in which this gene was completely sequenced confirmed an association of SIAE with autoimmunity. A subset of catalytically defective rare variant SIAE alleles has previously been typed in a large genotyping study comparing a diverse group of disease subjects and controls; our re-analysis of this data shows that catalytically defective alleles are enriched in disease subjects. These data suggest that SIAE may be associated with autoimmunity and that further study of catalytically defective rare variant SIAE alleles in terms of autoimmune disease susceptibility is strongly warranted. 相似文献
5.
The relationship between actual and perceived profitability was investigated by quantifying choice behavior of foraging honey bees (Apis mellifera).Rate of net energy gain was used as a measure of profitability. Individual bees repeatedly chose between a yellow and a blue tubular artificial flower which had different associated profitabilities. Handling costs were manipulated by using flowers of different depth;energy gains were manipulated by using different volumes of a 20% (w/w) sucrose solution. Bees' discrimination between the two flowers increased as the absolute difference in profitabilities increased and discrimination decreased as profitabilities of both flowers increased. Therefore, discrimination depended on the relative difference in profitability between flowers, and therefore, perception was a nonlinear function of actual rates of net energy gain. The results also suggested that motivation to choose between flowers depended on the level of profitability. We suggest that nonlinear perceptual scales and motivation should be incorporated into models of food choice as constraints and should be considered in the design of experiments used to test predictions of models and in the interpretation of experimental results. 相似文献
6.
Ana Buchadas Martin Jung Mercedes Bustamante Álvaro Fernández-Llamazares Stephen T. Garnett Ana Sofía Nanni Natasha Ribeiro Patrick Meyfroidt Tobias Kuemmerle 《Global Change Biology》2023,29(17):4880-4897
Tropical and subtropical dry woodlands are rich in biodiversity and carbon. Yet, many of these woodlands are under high deforestation pressure and remain weakly protected. Here, we assessed how deforestation dynamics relate to areas of woodland protection and to conservation priorities across the world's tropical dry woodlands. Specifically, we characterized different types of deforestation frontier from 2000 to 2020 and compared them to protected areas (PAs), Indigenous Peoples' lands and conservation areas for biodiversity, carbon and water. We found that global conservation priorities were always overrepresented in tropical dry woodlands compared to the rest of the globe (between 4% and 96% more than expected, depending on the type of conservation priority). Moreover, about 41% of all dry woodlands were characterized as deforestation frontiers, and these frontiers have been falling disproportionately in areas with important regional (i.e. tropical dry woodland) conservation assets. While deforestation frontiers were identified within all tropical dry woodland classes of woodland protection, they were lower than the average within protected areas coinciding with Indigenous Peoples' lands (23%), and within other PAs (28%). However, within PAs, deforestation frontiers have also been disproportionately affecting regional conservation assets. Many emerging deforestation frontiers were identified outside but close to PAs, highlighting a growing threat that the conserved areas of dry woodland will become isolated. Understanding how deforestation frontiers coincide with major types of current woodland protection can help target context-specific conservation policies and interventions to tropical dry woodland conservation assets (e.g. PAs in which deforestation is rampant require stronger enforcement, inactive deforestation frontiers could benefit from restoration). Our analyses also identify recurring patterns that can be used to test the transferability of governance approaches and promote learning across social–ecological contexts. 相似文献
7.
Natasha B. Kotliar 《Plant Ecology》1996,127(2):117-128
Hierarchy theory has provided a valuable conceptual framework for studies of heterogeneity. However, there have been few empirical studies of hierarchical structure and little is known about how hierarchical structure originates or varies among systems. Here, I explore how scale dependency can influence the detection of hierarchical structure. Specifically, I compared how heterogeneity changed with scale in patches of larkspur (Delphinium spp). The distribution of Delphinium nelsonii inflorescences was quite uniform over the range of measured scales (1 m2-2500 m2) and only a single level of patchiness was observed. Aggregations of D. barbeyi inflorescences were much more pronounced and this patchiness was evident at many scales. The number of hierarchical levels and the scales at which patchiness occurred varied both within and between plots of D. barbeyi. Because patchiness was not strongly scale-dependent for either species, discrete patch boundaries and well-defined hierarchical levels were not usually apparent even when multiple scales of patchiness were present. In several cases, the scales of detected patchiness depended on the difference in scale between grain (resolution) and extent. I predict that because of the lack of dominant and strongly scale-dependent processes, microlandscapes such as Delphinium meadows, may be less likely to exhibit well-defined hierarchical structure than larger-scale landscapes, especially those heavily altered by human activities. 相似文献
8.
Damage to primary photosynthetic reactions by drought, excess light and heat in leaves of Macroptilium atropurpureum Dc. cv. Siratro was assessed by measurements of chlorophyll fluorescence emission kinetics at 77 K (-196°C). Paraheliotropic leaf movement protected waterstressed Siratro leaves from damage by excess light (photoinhibition), by heat, and by the interactive effects of excess light and high leaf temperatures. When the leaves were restrained to a horizontal position, photoinhibition occurred and the degree of photoinhibitory damage increased with the time of exposure to high levels of solar radiation. Severe inhibition was followed by leaf death, but leaves gradually recovered from moderate damage. This drought-induced photoinhibitory damage seemed more closely related to low leaf water potential than to low leaf conductance. Exposure to leaf temperatures above 42°C caused damage to the photosynthetic system even in the dark and leaves died at 48°C. Between 42 and 48°C the degree of heat damage increased with the time of exposure, but recovery from moderate heat damage occurred over several days. The threshold temperature for direct heat damage increased with the growth temperature regime, but was unaffected by water-stress history or by current leaf water status. No direct heat damage occurred below 42°C, but in water-stressed plants photoinhibition increased with increasing leaf temperature in the range 31–42°C and with increasing photon flux density up to full sunglight values. Thus, water stress evidently predisposes the photosynthetic system to photoinhibition and high leaf temperature exacerbates this photoinhibitory damage. It seems probable that, under the climatic conditions where Siratro occurs in nature, but in the absence of paraheliotropic leaf movement, photoinhibitory damage would occur more frequently during drought than would direct heat damage.Abbreviations and symbols PFD
photon flux area density
- PSI, PSII
photosyntem I, II
-
F
M, F
O, F
V
maximum, instantaneous, variable fluorescence emission
- PLM
paraheliotropic leaf movement; all data of parameter of variation are mean ± standard error 相似文献
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