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1.
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
2.
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
3.
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
4.
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
5.
6.
An efficient synthesis of novel 1,2,3-1H-triazolyl glycohybrids with two or more than two sugar units or a chromenone moiety via copper-catalysed azide–alkyne cycloaddition (CuAAC), a 1,3-dipolar cycloaddition of glycosyl azides to 2,3-unsaturated alkynyl glycosides or propargyloxy coumarins is described. The synthesised glycohybrids were screened for their α-glucosidase, glycogen phosphorylase and glucose-6-phosphatase inhibitory activities. A few of the glycohybrids showed promising inhibitory activities against these enzymes. 相似文献
7.
Natasha Solovyova Peter R. Moult Bogdan Milojkovic Jeremy J. Lambert Jenni Harvey 《Journal of neurochemistry》2009,108(1):190-201
The hormone leptin has widespread actions in the CNS. Indeed, leptin markedly influences hippocampal excitatory synaptic transmission and synaptic plasticity. However, the effects of leptin on fast inhibitory synaptic transmission in the hippocampus have not been evaluated. Here, we show that leptin modulates GABAA receptor-mediated synaptic transmission onto hippocampal CA1 pyramidal cells. Leptin promotes a rapid and reversible increase in the amplitude of evoked GABAA receptor-mediated inhibitory synaptic currents (IPSCs); an effect that was paralleled by increases in the frequency and amplitude of miniature IPSCs, but with no change in paired pulse ratio or coefficient of variation, suggesting a post-synaptic expression mechanism. Following washout of leptin, a persistent depression (inhibitory long-lasting depression) of evoked IPSCs was observed. Whole-cell dialysis or bath application of inhibitors of phosphoinositide 3 (PI 3)-kinase or Akt prevented leptin-induced enhancement of IPSCs indicating involvement of a post-synaptic PI 3-kinase/Akt-dependent pathway. In contrast, blockade of PI 3-kinase or Akt activity failed to alter the ability of leptin to induce inhibitory long-lasting depression, suggesting that this process is independent of PI 3-kinase/Akt. In conclusion these data indicate that the hormone leptin bi-directionally modulates GABAA receptor-mediated synaptic transmission in the hippocampus. These findings have important implications for the role of this hormone in regulating hippocampal pyramidal neuron excitability. 相似文献
8.
Hyungjun Yang Hong B. Yu Ganive Bhinder Natasha R. Ryz Julia Lee Hong Yang Abbas Fotovati Deanna L. Gibson Stuart E. Turvey Gregor S. Reid Bruce A. Vallance 《Cellular microbiology》2019,21(7)
Mammalian cells express an array of toll‐like receptors to detect and respond to microbial pathogens, including enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC). These clinically important attaching and effacing (A/E) pathogens infect the apical surface of intestinal epithelial cells, causing inflammation as well as severe diarrheal disease. Because EPEC and EHEC are human‐specific, the related murine pathogen Citrobacter rodentium has been widely used to define how hosts defend against A/E pathogens. This study explored the role of TLR9, a receptor that recognises unmethylated CpG dinucleotides present in bacterial DNA, in promoting host defence against C. rodentium. Infected Tlr9?/? mice suffered exaggerated intestinal damage and carried significantly higher (10–100 fold) pathogen burdens in their intestinal tissues as compared with wild type (WT) mice. C. rodentium infection also induced increased antimicrobial responses, as well as hyperactivation of NF‐κB signalling in the intestines of Tlr9?/? mice. These changes were associated with accelerated depletion of the intestinal microbiota in Tlr9?/? mice as compared with WT mice. Notably, antibiotic‐based depletion of the gut microbiota in WT mice prior to infection increased their susceptibility to the levels seen in Tlr9?/? mice. Our results therefore indicate that TLR9 signalling suppresses intestinal antimicrobial responses, thereby promoting microbiota‐mediated colonisation resistance against C. rodentium infection. 相似文献
9.
Sophie A Harrington James M Connorton Natasha I M Nyangoma Rose McNelly Yvie M L Morgan Mohamad F Aslam Paul A Sharp Alexander A T Johnson Cristobal Uauy Janneke Balk 《Plant physiology》2023,191(1):528
Dietary deficiencies of iron and zinc cause human malnutrition that can be mitigated by biofortified staple crops. Conventional breeding approaches to increase grain mineral concentrations in wheat (Triticum aestivum L.) have had only limited success, and our understanding of the genetic and physiological barriers to altering this trait is incomplete. Here we demonstrate that a transgenic approach combining endosperm-specific expression of the wheat VACUOLAR IRON TRANSPORTER gene TaVIT2-D with constitutive expression of the rice (Oryza sativa) NICOTIANAMINE SYNTHASE gene OsNAS2 significantly increases the total concentration of zinc and relocates iron to white-flour fractions. In two distinct bread wheat cultivars, we show that the so called VIT-NAS construct led to a two-fold increase in zinc in wholemeal flour, to ∼50 µg g−1. Total iron was not significantly increased, but redistribution within the grain resulted in a three-fold increase in iron in highly pure, roller-milled white flour, to ∼25 µg g−1. Interestingly, expression of OsNAS2 partially restored iron translocation to the aleurone, which is iron depleted in grain overexpressing TaVIT2 alone. A greater than three-fold increase in the level of the natural plant metal chelator nicotianamine in the grain of VIT-NAS lines corresponded with improved iron and zinc bioaccessibility in white flour. The growth of VIT-NAS plants in the greenhouse was indistinguishable from untransformed controls. Our results provide insights into mineral translocation and distribution in wheat grain and demonstrate that the individual and combined effects of the two transgenes can enhance the nutritional quality of wheat beyond what is possible by conventional breeding.Targeted expression of a vacuolar iron transporter and increased nicotianamine levels have combinatorial effects on iron and zinc levels and their distribution in wheat grain. 相似文献
10.