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The plant-infecting Secoviridae family of viruses forms part of the Picornavirales order, an important group of non-enveloped viruses that infect vertebrates, arthropods, plants and algae. The impact of the secovirids on cultivated crops is significant, infecting a wide range of plants from grapevine to rice. The overwhelming majority are transmitted by ecdysozoan vectors such as nematodes, beetles and aphids. In this study, we have applied a variety of computational methods to examine the evolutionary traits of these viruses. Strong purifying selection pressures were calculated for the coat protein (CP) sequences of nine species, although for two species evidence of both codon specific and episodic diversifying selection were found. By using Bayesian phylogenetic reconstruction methods CP nucleotide substitution rates for four species were estimated to range from between 9.29×10−3 to 2.74×10−3 (subs/site/year), values which are comparable with the short-term estimates of other related plant- and animal-infecting virus species. From these data, we were able to construct a time-measured phylogeny of the subfamily Comovirinae that estimated divergence of ninety-four extant sequences occurred less than 1,000 years ago with present virus species diversifying between 50 and 250 years ago; a period coinciding with the intensification of agricultural practices in industrial societies. Although recombination (modularity) was limited to closely related taxa, significant and often unique similarities in the protein domains between secovirid and animal infecting picorna-like viruses, especially for the protease and coat protein, suggested a shared ancestry. We discuss our results in a wider context and find tentative evidence to indicate that some members of the Secoviridae might have their origins in insects, possibly colonizing plants in a number of founding events that have led to speciation. Such a scenario; virus infection between species of different taxonomic kingdoms, has significant implications for virus emergence. 相似文献
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Experimental autoimmune encephalomyelitis (EAE) is a well-established murine model of multiple sclerosis, an immune-mediated demyelinating disorder of the central nervous system (CNS). We have previously shown that CNS-specific CD8+ T cells (CNS-CD8+) ameliorate EAE, at least in part through modulation of CNS-specific CD4+ T cell responses. In this study, we show that CNS-CD8+ also modulate the function of CD11c+ dendritic cells (DC), but not other APCs such as CD11b+ monocytes or B220+ B cells. DC from mice receiving either myelin oligodendrocyte glycoprotein-specific CD8+ (MOG-CD8+) or proteolipid protein-specific CD8+ (PLP-CD8+) T cells were rendered inefficient in priming T cell responses from naïve CD4+ T cells (OT-II) or supporting recall responses from CNS-specific CD4+ T cells. CNS-CD8+ did not alter DC subset distribution or MHC class II and CD86 expression, suggesting that DC maturation was not affected. However, the cytokine profile of DC from CNS-CD8+ recipients showed lower IL-12 and higher IL-10 production. These functions were not modulated in the absence of immunization with CD8-cognate antigen, suggesting an antigen-specific mechanism likely requiring CNS-CD8-DC interaction. Interestingly, blockade of IL-10 in vitro rescued CD4+ proliferation and in vivo expression of IL-10 was necessary for the suppression of EAE by MOG-CD8+. These studies demonstrate a complex interplay between CNS-specific CD8+ T cells, DC and pathogenic CD4+ T cells, with important implications for therapeutic interventions in this disease. 相似文献
96.
Anshuman Mishra Sheikh Nizamuddin Geethika Arekatla Satya Prakash Hemlata Dewangan Abishai Dominic Abhishek Mishra Digumarthi V. S. Sudhakar Narasimha R. Parine Nitin C. Tupperwar Kumarasamy Thangaraj 《PloS one》2015,10(5)
BackgroundVisceral leishmaniasis (VL) is a multifactorial disease, where the host genetics play a significant role in determining the disease outcome. The immunological role of anti-inflammatory cytokine, Interleukin 10 (IL10), has been well-documented in parasite infections and considered as a key regulatory cytokine for VL. Although VL patients in India display high level of IL10 in blood serum, no genetic study has been conducted to assess the VL susceptibility / resistance. Therefore, the aim of this study is to investigate the role of IL10 variations in Indian VL; and to estimate the distribution of disease associated allele in diverse Indian populations.MethodologyAll the exons and exon-intron boundaries of IL10 were sequenced in 184 VL patients along with 172 ethnically matched controls from VL endemic region of India.
Result and Discussion
Our analysis revealed four variations; rs1518111 (2195 A>G, intron), rs1554286 (2607 C>T, intron), rs3024496 (4976 T>C, 3’ UTR) and rs3024498 (5311 A>G, 3’ UTR). Of these, a variant g.5311A is significantly associated with VL (χ2=18.87; p =0.00001). In silico approaches have shown that a putative micro RNA binding site (miR-4321) is lost in rs3024498 mRNA. Further, analysis of the above four variations in 1138 individuals from 34 ethnic populations, representing different social and linguistic groups who are inhabited in different geographical regions of India, showed variable frequency. Interestingly, we have found, majority of the tribal populations have low frequency of VL (‘A’ of rs3024498); and high frequency of leprosy (‘T’ of rs1554286), and Behcet’s (‘A’ of rs1518111) associated alleles, whereas these were vice versa in castes. Our findings suggest that majority of tribal populations of India carry the protected / less severe allele against VL, while risk / more severe allele for leprosy and Behcet’s disease. This study has potential implications in counseling and management of VL and other infectious diseases. 相似文献97.
Dong Hyun Kim Nitin Puri Komal Sodhi John R. Falck Nader G. Abraham Joseph Shapiro Michal L. Schwartzman 《Journal of lipid research》2013,54(3):786-793
20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a product of the cytochrome
P450 (CYP)-catalyzed ω-hydroxylation of arachidonic acid, induces
oxidative stress and, in clinical studies, is associated with increased body
mass index (BMI) and the metabolic syndrome. This study was designed to examine
the effects of exogenous 20-HETE on mesenchymal stem cell (MSC)-derived
adipocytes. The expression levels of CYP4A11 and CYP4F2 (major 20-HETE synthases
in humans) in MSCs decreased during adipocyte differentiation; however,
exogenous administration of 20-HETE (0.1–1 μM) increased adipogenesis
in a dose-dependent manner in these cells (P < 0.05). The
inability of a 20-HETE analog to reproduce these effects suggested the
involvement of a metabolic product of 20-HETE in mediating its pro-adipogenic
effects. A cyclooxygenase (COX)-1 selective inhibitor enhanced, whereas a COX-2
selective or a dual COX-1/2 inhibitor attenuated adipogenesis induced by
20-HETE. The COX-derived metabolite of 20-HETE, 20-OH-PGE2, enhanced
adipogenesis and lipid accumulation in MSCs. The pro-adipogenic effects of
20-HETE and 20-OH-PGE2 resulted in the increased expression of the
adipogenic regulators PPARγ and β-catenin in MSC-derived adipocytes.
Taken together we show for the first time that 20-HETE-derived COX-2-dependent
20-OH-PGE2 enhances mature inflamed adipocyte hypertrophy in MSC
undergoing adipogenic differentiation. 相似文献
98.
Cell polarization and cell division are two fundamental cellular processes. The mechanisms that establish and maintain cell polarity and the mechanisms by which cells progress through the cell cycle are now fairly well understood following decades of experimental work. There is also increasing evidence that the polarization state of a cell affects its proliferative properties. The challenge now is to understand how these two phenomena are mechanistically connected. The aim of the present chapter is to provide an overview of the evidence of cross-talk between apicobasal polarity and proliferation, and the current state of knowledge of the precise mechanism by which this cross-talk is achieved. 相似文献
99.
We measured the immunoreactivity of the neuropeptide gastrin cholecystokinin 8 (gastrin/CCK 8) in neurons of the terrestrial slug Semperula maculata following acute treatment with mercuric chloride (HgCl2). The distribution of gastrin/CCK 8 was analyzed in neurons of different regions, specifically from cerebral ganglia (procerebrum (pro-c), mesocerebrum (meso-c) and metacerebrum (meta-c). In the control group, neurons of pedal, pleural, parietal and visceral ganglia showed positive immunoreactivity using vertebrate antiserum against gastrin/CCK 8. Gastrin/CCK 8 immunoreactivity was also seen in the fibers and neuropil region of all ganglia. In the cerebral ganglion, 10, 12 and 8 % of the neurons from pro-c, meso-c and meta-c, respectively, were stained with the antibody. The immunostaining was increased in neurons (giant, large, medium and small) after HgCl2 treatment. The treatment greatly increased the mucin content within the neurons. Exposure to HgCl2 enhanced gastrin immunoreactivity in the neurons and this increased with time. Results are discussed in the context of neuropathology in cerebral ganglia associated with the feeding behavior of Semperula maculata. 相似文献
100.
Sublocalization of an Ataxia-Telangiectasia Gene Distal to D11S384 by Ancestral Haplotyping In Costa Rican Families 总被引:4,自引:4,他引:4 下载免费PDF全文
Nancy Uhrhammer Ethan Lange Oscar Porras Arash Naeim Xiaoguang Chen Sepideh Sheikhavandi Sujata Chiplunkar Lan Yang Sugandha Dandekar Teresa Liang Nima Patel Sharon Teraoka Nitin Udar Nidia Calvo Patrick Concannon Kenneth Lange Richard A. Gatti 《American journal of human genetics》1995,57(1):103-111
In an effort to localize a gene for ataxia-telangiectasia (A-T), we have genotyped 27 affected Costa Rican families, with 13 markers, in the chromosome 11q22-23 region. Significant linkage disequilibrium was detected for 9/13 markers between D11S1816 and D11S1391. Recombination events observed in these pedigrees places A-T between D11S1819 and D11S1960. One ancestral haplotype is common to 24/54 affected chromosomes and roughly two-thirds of the families. Inferred (ancestral) recombination events involving this common haplotype in earlier generations suggest that A-T is distal to D11S384 and proximal to D11S1960. Several other common haplotypes were identified, consistent with multiple mutations in a single gene. When considered together with all other evidence, this study further sublocalizes the major A-T locus to ≈200 kb, between markers S384 and S535. 相似文献