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A bioinformatic approach to the identification of bacterial proteins interacting with Toll–interleukin 1 receptor–resistance (TIR) homology domains (2003)

Turner, Jonathan D

Oxford, UK : Blackwell Publishing Ltd

FEMS immunology and medical microbiology 37 (2003), S. 0

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ISSN: 1574-695X

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Biology , Medicine

Notes: Members of the Toll-like receptor (TLR) family are currently under intense scrutiny for their role in the sampling and recognition of pathogens. It has already been reported that both vaccinia virus and Yersinia spp. express proteins that help them evade the TLR mediated immune response, acting through the Toll–interleukin-1 receptor–resistance (TIR) domain and leucine-rich repeat region of the host TLRs respectively. The TIR domain is involved in the dimerisation of the TLRs and their complexation with their adapter molecules. We tested here the hypothesis that bacteria have the ability to secrete proteins containing similar motifs to the intracellular TIR domains that are involved in the TIR–TIR interaction necessary for the subsequent signal transmission. Based upon their sequence homology, proteins expressing TIRs have been divided into three sub-classes, based around the TLRs, the TLR adapter proteins, and the interleukin-1 and -18 adapter proteins. The highly conserved regions from these separate sub-families were then used to identify similar bacterial proteins. The bacterial proteins identified were then included in an iterative MEME-BLAST process to broaden the search. Tollip, a known TLR antagonist and adapter protein, was included in this investigation although it does not fit into any of the three sub-classes outlined above. If suitable bacterial proteins had been identified, it would signify that certain bacteria had evolved a mechanism to aid them in avoiding detection by the innate immune system acting through the TIR domains. At this stage one has to conclude that there is no evidence currently available suggesting such a mechanism, when using the strategy applied here.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1016/S0928-8244(03)00095-6

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5-HT1A receptor agonists improve the performance of normal and scopolamine-impaired rats in an operant delayed matching to position task (1994)

Cole, Belinda J. ; Jones, Graham H. ; Turner, Jonathan D.

Springer

Psychopharmacology 116 (1994), S. 135-142

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ISSN: 1432-2072

Keywords: Short term memory ; Delayed matching to position ; 5-HT ; 5-HT1A receptor ; 8-OH DPAT ; Ipsapirone ; Rat

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Abstract A series of experiments examined the effects of 5-HT1A ligands alone and in combination with the muscarinic antagonist scopolamine on short term working memory in the rat. The behavioural paradigm was a discrete trial, operant delayed matching to position task, with delays of 0, 5, 15 and 30 s. The 5-HT1A ligands tested were the full agonist, 8-OH DPAT (0, 0.1, 0.3 and 1 mg/kg), the partial agonist, ipsapirone (0, 1, 3 and 10 mg/kg), and the purported antagonist, NAN 190 (0, 1, 2, and 4 mg/kg). 1-PP (0, 0.1, 0.3, 1 mg/kg), the major metabolite of ipsapirone, was also tested. The lowest dose of 8-OH DPAT significantly improved matching accuracy at the longest delay, whereas the highest dose impaired matching accuracy and increased the latency to respond. Ipsapirone also significantly improved the accuracy of performance at a dose of 3 mg/kg, but the doses of 1 and 10 mg/kg did not significantly affect performance. NAN-190, at the highest dose tested (4 mg/kg), impaired matching accuracy, whereas the two lower doses did not significantly affect performance. The highest dose also increased the latency to respond. 1-PP had no effect on performance. Scopolamine HBr (0.14 mg/kg) caused a delay dependent impairment in matching accuracy, and had no effect on missed trials or the latency to respond. Low doses of 8-OH DPAT (0.1 and 0.3 mg/kg) significantly attenuated the scopolamine induced accuracy impairment, whereas 1 mg/kg 8-OH DPAT potentiated the impairment. Ipsapirone (3 mg/kg) also significantly improved the performance of scopolamine impaired rats. NAN-190 increased the latency to respond and reduced the number of nose pokes made during the delays in scopolamine-treated rats, and tended to potentiate the scopolamine-induced accuracy impairment. 1-PP did not affect the performance of scopolamine treated rats. Taken together, these results suggest that modulation of 5-HT1A receptors influences short term spatial working memory in the rat.