Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs) play a central role in innate immunity. TLRs are membrane glycoproteins and contain leucine rich repeat (LRR) motif in the ectodomain. TLRs recognize and respond to molecules such as lipopolysaccharide, peptidoglycan, flagellin, and RNA from bacteria or viruses. The LRR domains in TLRs have been inferred to be responsible for molecular recognition. All LRRs include the highly conserved segment, LxxLxLxxNxL, in which "L" is Leu, Ile, Val, or Phe and "N" is Asn, Thr, Ser, or Cys and "x" is any amino acid. There are seven classes of LRRs including "typical" ("<b><it>T</it></b>") and "bacterial" ("<b><it>S</it></b>"). All known domain structures adopt an arc or horseshoe shape. Vertebrate TLRs form six major families. The repeat numbers of LRRs and their "phasing" in TLRs differ with isoforms and species; they are aligned differently in various databases. We identified and aligned LRRs in TLRs by a new method described here.</p> <p>Results</p> <p>The new method utilizes known LRR structures to recognize and align new LRR motifs in TLRs and incorporates multiple sequence alignments and secondary structure predictions. TLRs from thirty-four vertebrate were analyzed. The repeat numbers of the LRRs ranges from 16 to 28. The LRRs found in TLRs frequently consists of LxxLxLxxNxLxxLxxxxF/LxxLxx ("<b><it>T</it></b>") and sometimes short motifs including LxxLxLxxNxLxxLPx(x)LPxx ("<b>S</b>"). The <it>TLR7 </it>family (TLR7, TLR8, and TLR9) contain 27 LRRs. The LRRs at the N-terminal part have a super-motif of <b><it>STT </it></b>with about 80 residues. The super-repeat is represented by <b><it>STTSTTSTT </it></b>or <b><it>_TTSTTSTT</it></b>. The LRRs in TLRs form one or two horseshoe domains and are mostly flanked by two cysteine clusters including two or four cysteine residue.</p> <p>Conclusion</p> <p>Each of the six major TLR families is characterized by their constituent LRR motifs, their repeat numbers, and their patterns of cysteine clusters. The central parts of the <it>TLR1 </it>and <it>TLR7 </it>families and of TLR4 have more irregular or longer LRR motifs. These central parts are inferred to play a key role in the structure and/or function of their TLRs. Furthermore, the super-repeat in the <it>TLR7 </it>family suggests strongly that "bacterial" and "typical" LRRs evolved from a common precursor.</p

Immediate implant loading following computer-guided surgery

AbstractPurposeThe aim of this study was to develop and apply a new method for easy intraoperative adjustment of a provisional fixed full-arch restoration, in order to allow immediate implant loading following computer-guided surgery, regardless of any implant positioning errors compared to the virtual planning.MethodsIn accordance with the NobelGuide™ protocol, a provisional restoration for immediate loading of six maxillary implants was prepared prior to surgery. Because small shifts between the planned and the actual implant positions were to be expected, the provisional restoration was not fabricated directly on temporary cylinders as a conventional one-piece superstructure, but was divided into two portions: six custom made abutments and a long span fixed restoration which were left unconnected. After implantation, the custom abutments were attached to the six implants to be immediately loaded, and the superstructure was cemented simultaneously to all abutments using dual cure resin cement. After the excess cement was cleaned and polished, the superstructure was then reseated. Passive fit was achieved between implants and the superstructure.ConclusionThe superstructure described in this article can be easily seated and adjusted to accommodate any possible shifts in implant positioning occurring during computer-guided surgery. Through this method uneventful immediate implant loading can be achieved in a reasonable operative time

Treatment with Corticosteroid for Pericardial Effusion in a Patient with Advanced Synchronous Esophageal and Gastric Cancers following Chemoradiotherapy

Severe late toxicity following chemoradiotherapy in esophageal cancer, especially cardiac toxicity, is sometimes difficult to treat and is associated with mortality. However there is little published information with regard to patients with delayed pericardial effusion following chemoradiotherapy and its management. We herein report the case of a 63-year-old man with advanced synchronous esophageal and gastric cancers. This patient presented with pericardial effusion with cardiac tamponade after definitive chemoradiotherapy and was successfully treated with corticosteroid after pericardiocentesis. No instances of pericardial and pleural effusions were observed during the 2-year follow-up period until his death from cancer relapses