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41.
Patients with systemic autoimmune diseases usually produce high levels of antibodies to self-antigens (autoantigens). The
repertoire of common autoantigens is remarkably limited, yet no readily understandable shared thread links these apparently
diverse proteins. Using computer prediction algorithms, we have found that most nuclear systemic autoantigens are predicted
to contain long regions of extreme structural disorder. Such disordered regions would generally make poor B cell epitopes
and are predicted to be under-represented as potential T cell epitopes. Consideration of the potential role of protein disorder
may give novel insights into the possible role of molecular mimicry in the pathogenesis of autoimmunity. The recognition of
extreme autoantigen protein disorder has led us to an explicit model of epitope spreading that explains many of the paradoxical
aspects of autoimmunity – in particular, the difficulty in identifying autoantigen-specific helper T cells that might collaborate
with the B cells activated in systemic autoimmunity. The model also explains the experimentally observed breakdown of major
histocompatibility complex (MHC) class specificity in peptides associated with the MHC II proteins of activated autoimmune
B cells, and sheds light on the selection of particular T cell epitopes in autoimmunity. Finally, the model helps to rationalize
the relative rarity of clinically significant autoimmunity despite the prevalence of low specificity/low avidity autoantibodies
in normal individuals. 相似文献
42.
Tarfa FD Obodozie OO Mshelia E Ibrahim K Temple VJ 《Indian journal of experimental biology》2004,42(3):326-329
Leaf extracts of T. sessilifolius growing on five different host plants (Psidium guajava, Citrus lemon, Vernonia amygdalina, Persea americana and Jatropa curcas) were evaluated for antimicrobial activity of the plant. Powdered leaves of T. sessilifolius collected from each host plant was divided into two portions. One portion was used for aqueous infusion and the other portion was successively extracted with hexane, ethylacetate and methanol. Infusion of aqueous extract of powdered leaves did not show antimicrobial effect even at the concentration of 1000 and 2000 microg/ml on test microorganisms (Staph. aureus, E. coli, Bacillus subtilis, Pseudomonas aeruginosa and Candida albicans). However in broth culture, methanolic and hexane extract had MIC range of 62.5-500 microg/ml and ethylacetate extract had 250-500 microg/ml. Phytochemical screening of leaf samples of T. sessilifolius collected from different host plants showed positive test for hydrolysable tannins, saponins, flavonoids, terpenes, cardiac glycoside, reducing sugars and proteins. LD50 concentration was found to be > 1.500 mg/kg for samples from P. guajava; 489.89 mg/kg for J. curcas and C. lemon; and 692 mg/kg for V. amydalina in mice. 相似文献
43.
44.
Mackay DJ Hahnemann JM Boonen SE Poerksen S Bunyan DJ White HE Durston VJ Thomas NS Robinson DO Shield JP Clayton-Smith J Temple IK 《Human genetics》2006,119(1-2):179-184
Transient neonatal diabetes mellitus (TNDM) is characterised by intra-uterine growth retardation, while Beckwith–Wiedemann
syndrome (BWS) is a clinically heterogeneous overgrowth syndrome. Both TNDM and BWS may be caused by aberrant loss of methylation
(LOM) at imprinted loci on chromosomes 6q24 and 11p15.5 respectively. Here we describe two patients with a clinical diagnosis
of TNDM caused by LOM at the maternally methylated imprinted domain on 6q24; in addition, these patients had LOM at the centromeric
differentially methylated region of 11p15.5. This shows that imprinting anomalies can affect more than one imprinted locus
and may alter the clinical presentation of imprinted disease. 相似文献
45.
Temple CL Tse R Bettger-Hahn M MacDermid J Gan BS Ross DC 《Plastic and reconstructive surgery》2006,117(7):2119-27; discussion 2128-30
46.
Comparison of the genome sequence of the poultry pathogen Bordetella avium with those of B. bronchiseptica, B. pertussis, and B. parapertussis reveals extensive diversity in surface structures associated with host interaction 总被引:2,自引:0,他引:2
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Sebaihia M Preston A Maskell DJ Kuzmiak H Connell TD King ND Orndorff PE Miyamoto DM Thomson NR Harris D Goble A Lord A Murphy L Quail MA Rutter S Squares R Squares S Woodward J Parkhill J Temple LM 《Journal of bacteriology》2006,188(16):6002-6015
Bordetella avium is a pathogen of poultry and is phylogenetically distinct from Bordetella bronchiseptica, Bordetella pertussis, and Bordetella parapertussis, which are other species in the Bordetella genus that infect mammals. In order to understand the evolutionary relatedness of Bordetella species and further the understanding of pathogenesis, we obtained the complete genome sequence of B. avium strain 197N, a pathogenic strain that has been extensively studied. With 3,732,255 base pairs of DNA and 3,417 predicted coding sequences, it has the smallest genome and gene complement of the sequenced bordetellae. In this study, the presence or absence of previously reported virulence factors from B. avium was confirmed, and the genetic bases for growth characteristics were elucidated. Over 1,100 genes present in B. avium but not in B. bronchiseptica were identified, and most were predicted to encode surface or secreted proteins that are likely to define an organism adapted to the avian rather than the mammalian respiratory tracts. These include genes coding for the synthesis of a polysaccharide capsule, hemagglutinins, a type I secretion system adjacent to two very large genes for secreted proteins, and unique genes for both lipopolysaccharide and fimbrial biogenesis. Three apparently complete prophages are also present. The BvgAS virulence regulatory system appears to have polymorphisms at a poly(C) tract that is involved in phase variation in other bordetellae. A number of putative iron-regulated outer membrane proteins were predicted from the sequence, and this regulation was confirmed experimentally for five of these. 相似文献
47.
The archaeal origins of the eukaryotic translational system 总被引:1,自引:0,他引:1
Among the 78 eukaryotic ribosomal proteins, eleven are specific to Eukarya, 33 are common only to Archaea and Eukarya and 34 are homologous (at least in part) to those of both Bacteria and Archaea. Several other translational proteins are common only to Eukarya and Archaea (e.g., IF2a, SRP19, etc.), whereas others are shared by the three phyla (e.g., EFTu/EF1A and SRP54). Although this and other analyses strongly support an archaeal origin for a substantial fraction of the eukaryotic translational machinery, especially the ribosomal proteins, there have been numerous unique and ubiquitous additions to the eukaryotic translational system besides the 11 unique eukaryotic ribosomal proteins. These include peptide additions to most of the 67 archaeal homolog proteins, rRNA insertions, the 5.8S RNA and the Alu extension to the SRP RNA. Our comparative analysis of these and other eukaryotic features among the three different cellular phylodomains supports the idea that an archaeal translational system was most likely incorporated by means of endosymbiosis into a host cell that was neither bacterial nor archaeal in any modern sense. Phylogenetic analyses provide support for the timing of this acquisition coinciding with an ancient bottleneck in prokaryotic diversity. 相似文献
48.
Christopher Talbot Thomas M. Jordan Nicholas W. Roberts Shaun P. Collin N. Justin Marshall Shelby E. Temple 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2012,198(12):849-856
The cornea is the first optical element in the path of light entering the eye, playing a role in image formation and protection. Corneas of vertebrate simple camera-type eyes possess microprojections on the outer surface in the form of microridges, microvilli, and microplicae. Corneas of invertebrates, which have simple or compound eyes, or both, may be featureless or may possess microprojections in the form of nipples. It was previously unknown whether cephalopods (invertebrates with camera-type eyes like vertebrates) possess corneal microprojections and, if so, of what form. Using scanning electron microscopy, we examined corneas of a range of cephalopods and discovered nipple-like microprojections in all species. In some species, nipples were like those described on arthropod compound eyes, with a regular hexagonal arrangement and sizes ranging from 75 to 103?nm in diameter. In others, nipples were nodule shaped and irregularly distributed. Although terrestrial invertebrate nipples create an antireflective surface that may play a role in camouflage, no such optical function can be assigned to cephalopod nipples due to refractive index similarities of corneas and water. Their function may be to increase surface-area-to-volume ratio of corneal epithelial cells to increase nutrient, gas, and metabolite exchange, and/or stabilize the corneal mucous layer, as proposed for corneal microprojections of vertebrates. 相似文献
49.
Skidmore J Atcha Z Boucherat E Castelletti L Chen DW Coppo FT Cutler L Dunsdon RM Heath BM Hutchings R Hurst DN Javed S Martin S Maskell ES Norton D Pemberton DJ Redshaw S Rutter R Sehmi SS Scoccitti T Temple HE Theobald P Ward RW Wilson DM 《Bioorganic & medicinal chemistry letters》2012,22(10):3560-3563
A series of α7 nicotinic acetylcholine receptor full-agonists with a 1,3,4-oxadiazol-2-amine core has been discovered. Systematic exploration of the structure-activity relationships for both α7 potency and selectivity with respect to interaction with the hERG channel are described. Further profiling led to the identification of compound 22, a potent full agonist showing efficacy in the novel object recognition model of cognition enhancement. 相似文献
50.
Lorien Radmer Mesfin Tesfaye David A. Somers Stephen J. Temple Carroll P. Vance Deborah A. Samac 《Plant and Soil》2012,351(1-2):121-134