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目次: 特異な主要キャラクターのキャラクター言語に見られる過剰性と逸脱性―アーニャ（『SPYxFAMILY』）とナカタさん（『海辺のカフカ』）の日英対照― pp.1－48 / 『1Q84』のふかえりによる日瑞訳の話し方について pp.49－62 / 『騎士団長殺し』におけるキャラクターの言語表現及び中国語訳の分析について pp.63－77 / 村上春樹と関西方言について―遠心的／求心的な移動とポリフォニー― pp.79－90

目次: 『騎士団長殺し』のキャラクターのスウェーデン語への翻訳の仕方について pp.1-11 / 日本のロールプレイングゲーム(JRPG)の英語翻訳における役割語・キャラクター言語の表現手法ー「古い英語表現」に着目してー pp.13-24 / 『1084』における役割語とキャラクターの機能に関する一考察ーコレスポンデンス分析を用いてー pp.25-38 / 村上春樹作品と日本語史の「共鳴」ー『騎士団長殺し』騎士団長の「あらない」再考— pp.39-47

Ameloblastoma of the jaws remains the top difficult to treat odontogenic tumour and has a high recurrence rate. New evidence suggests that non-coding RNAs (ncRNAs) play a critical role in tumourgenesis and prognosis of cancer. However, ameloblastoma ncRNA expression data is lacking. Here we present the first report of ameloblastoma ncRNA signatures. A total of 95 ameloblastoma cases and a global array transcriptome technology covering > 285.000 full-length transcripts were used in this two-step analysis. The analysis first identified in a test cohort 31 upregulated ameloblastoma-associated ncRNAs accompanied by signalling pathways of cancer, spliceosome, mRNA surveillance and Wnt. Further validation in an independent cohort points out the long non-coding (lncRNAs) and small nucleolar RNA (snoRNAs): LINC340, SNORD116-25, SNORA11, SNORA21, SNORA47 and SNORA65 as a distinct ncRNA signature of ameloblastoma. Importantly, the presence of these ncRNAs was independent of BRAFV600E and SMO-L412F mutations, histology type or tumour location, but was positively correlated with the tumour size. Taken together, this study shows a systematic investigation of ncRNA expression of ameloblastoma, and illuminates new diagnostic and therapeutic targets for this invasive odontogenic tumour.

Background: The American Academy of Periodontology has recently stated that, ‘‘[risk assessment will become] increasingly important in periodontal treatment planning and should be part of every comprehensive dental and periodontal evaluation.’’ (J Periodontol 2006;77:1608). Unaided risk assessment and prognostication show significant variability because chronic periodontitis is a multifactorial disease. This report summarizes the clinical validation of an algorithm for chronic periodontitis risk assessment and prognostication. The algorithm is a Web-based analytic tool that integrates some 20 risk predictors and calculates scores indicating levels of risk for chronic periodontitis for the dentition (Level I) and, if an elevated risk is found, prognosticates disease progression tooth by tooth (Level II). Methods: An independent clinical validation sample was generated in an open, prospective clinical trial and analyzed in a predetermined validation plan. Results: The analyses identified two threshold scores above which significant progression of periodontitis was found. Based on these scores, sufficiently high explanatory values with significant and increasing parameter estimates for increasing risk were established in Level I, justifying detailed analysis tooth by tooth in Level II. Subsequent prognostication of chronic periodontitis in Level II was found to be accompanied by clinically relevant measures of quality in relation to rates of disease progression. Three score intervals representing increasing levels of periodontitis progression were identified corresponding to increasing levels of significant annual marginal bone loss. Conclusions: The predictors included in the algorithm reflect a relevant selection for periodontitis risk assessment. Risk assessment and prognostication with the algorithm provides the clinician with a validated, reliable, consistent, and objective tool supporting treatment planning

Background: Patients with severe forms of chronic periodontitis present with varying degrees of decreased inflammatory reactivity. A previously reported algorithm for chronic periodontitis risk assessment and prognostication is based on the analysis of some 20 risk predictors. One of these predictors is a skin provocation test that assesses the individual patient’s reactivity to a lipid A challenge. The aim of this report was to analyze results from validation data for the algorithm with respect to the contribution of results of the skin provocation test as a risk predictor for the progression of chronic periodontitis and to compare these results with the contribution from other predictors, namely smoking, angular bony destruction, furcation involvement, abutment teeth, and endodontic pathology. Methods: Data from a previously reported clinical validation sample were used for the analysis, including the calculation of quality measures and explanatory values using different types of regression analysis and non-parametric testing. Results: Smoking, endodontic pathology, abutment teeth, angular bony destruction, and furcation involvement presented with individual explanatory values for periodontitis progression between 4% and 13% and highly significant parameter estimates. Explanatory values for the results of the skin provocation test ranged between 2.6% and 5.1% depending on the disease severity group, with a positive predictive value of 82% for the identification of high-risk patients. Conclusion: The skin provocation test provided a clinically significant contribution to the quality of analysis with the periodontitis risk and prognostication algorithm, in particular in the selection of high-risk patients for in-depth individual tooth analysis.

Helicobacter pylori, the causative agent of peptic ulcer disease, expresses two different forms of the zinc-containing enzyme carbonic anhydrase (CA) (α and β), catalyzing the reversible hydration of CO2. Presumably, the high CO2 requirement of H. pylori implies an important role for this enzyme in the bacterial physiology. In this paper, expression of the CAs has been analyzed in three different strains of the bacterium, 26695, J99 and 17.1, and appears to be independent of CO2 concentration in the investigated range (0.1–10%). Presence of the potent and highly specific CA inhibitor, acetazolamide, in the medium does not seem to inhibit bacterial growth at the given sulfonamide concentration. Moreover, the localization and distribution of the α-CA was analyzed by immunonegative staining, while SDS-digested freeze-fracture immunogold labelling was used for the β-form of the enzyme. The latter method has the advantage of allowing assessment of protein localization to distinct cell compartments and membrane structures. The resulting electron microscopy images indicate a localization of the β-CA in the cytosol, on the cytosolic side of the inner membrane and on the outer membrane facing the periplasmic space. The α-enzyme was found attached to the surface of the bacterium.

The -carbonic anhydrase gene from Helicobacter pylori strain 26695 has been cloned and sequenced. The full-length protein appears to be toxic to Escherichia coli, so we prepared a modified form of the gene lacking a part that presumably encodes a cleavable signal peptide. This truncated gene could be expressed in E. coli yielding an active enzyme comprising 229 amino acid residues. The amino acid sequence shows 36% identity with that of the enzyme from Neisseria gonorrhoeae and 28% with that of human carbonic anhydrase II. The H. pylori enzyme was purified by sulfonamide affinity chromatography and its circular dichroism spectrum and denaturation profile in guanidine hydrochloride have been measured. Kinetic parameters for CO2 hydration catalyzed by the H. pylori enzyme at pH 8.9 and 25oC are kcat=2.4x105 s-1, KM=17 mM and kcat/KM=1.4x107 M-1 s-1. The pH dependence of kcat/KM fits with a simple titration curve with pKa=7.5. Thiocyanate yields an uncompetitive inhibition pattern at pH 9 indicating that the maximal rate of CO2 hydration is limited by proton transfer between a zinc-bound water molecule and the reaction medium in analogy to other forms of the enzyme. The 4-nitrophenyl acetate hydrolase activity of the H. pylori enzyme is quite low with an apparent catalytic second-order rate constant, kenz, of 24 M-1 s-1 at pH 8.8 and 25oC. However, with 2-nitrophenyl acetate as substrate a kenz value of 665 M-1 s-1 was obtained under similar conditions.

A single mutation, involving the replacement of an arginine residue with histidine to reconstruct a zinc-binding site, suffices to change a catalytically inactive murine carbonic anhydrase-related protein (CARP) to an active carbonic anhydrase with a CO2-hydration turnover number of 1.2 × 104 s−1. Further mutations, leading to a more ‘carbonic anhydrase-like’ active-site cavity, results in increased activity. A quintuple mutant having His94, Gln92, Val121, Val143, and Thr200 (human carbonic anhydrase I numbering system) shows kcat = 4 × 104 s−1 and kcat/Km = 2 × 107 m−1·s−1, greatly exceeding the corresponding values for carbonic anhydrase isozyme III and approaching those characterizing carbonic anhydrase I. In addition, a buffer change from 50 mm Taps/NaOH to 50 mm 1,2-dimethylimidazole/H2SO4 at pH 9 results in a 14-fold increase in kcat for this quintuple mutant. The CO2-hydrating activity of a double mutant with His94 and Gln92 shows complex pH-dependence, but the other mutants investigated behave as if the activity (kcat/Km) is controlled by the basic form of a single group with pKa near 7.7. In a similar way to human carbonic anhydrase II, the buffer behaves formally as a second substrate in a ping-pong pattern, suggesting that proton transfer between a zinc-bound water molecule and buffer limits the maximal rate of catalysis in both systems at low buffer concentrations. However, the results of isotope-exchange kinetic studies suggest that proton shuttling via His64 is insignificant in the CARP mutant in contrast with carbonic anhydrase II. The replacement of Ile residues with Val in positions 121 or 143 results in measurable 4-nitrophenyl acetate hydrolase activity. The pH–rate profile for this activity has a similar shape to those of carbonic anhydrase I and II. CD spectra of the double mutant with His94 and Gln92 are variable, indicating an equilibrium between a compact form of the protein and a ‘molten globule’-like form. The introduction of Thr200 seems t

The crystal structure of carbonic anhydrase from Neisseria gonorrhoeae has been solved to a resolution of 1.78 A by molecular replacement using human carbonic anhydrase II as a template. After refinement the R factor was 17.8% (Rfree=23.2%). There are two molecules per asymmetric unit (space group P21), but they have essentially identical structures. The fold of the N. gonorrhoeae enzyme is very similar to that of human isozyme II; 192 residues, 74 of which are identical in the two enzymes, have equivalent positions in the three-dimensional structures. This corresponds to 85% of the entire polypeptide chain of the bacterial enzyme. The only two cysteine residues in the bacterial enzyme, which has a periplasmic location in the cell, are connected by a disulfide bond. Most of the secondary structure elements present in human isozyme II are retained in N. gonorrhoeae carbonic anhydrase, but there are also differences, particularly in the few helical regions. Long deletions in the bacterial enzyme relative to human isozyme II have resulted in a considerable shortening of three surface loops. One of these deletions, corresponding to residues 128 to 139 in the human enzyme, leads to a widening of the entrance to the hydrophobic part of the active site cavity. Practically all the amino acid residues in the active site of human isozyme II are conserved in the N. gonorrhoeae enzyme and have similar structural positions. However, the imidazole ring of a histidine residue, which has been shown to function as a proton shuttle in the catalytic mechanism of the human enzyme, interacts with an extraneous entity, which has tentatively been identified as a 2-mercaptoethanol molecule from the crystallization medium. When this entity is removed by soaking the crystal in a different medium, the side-chain of His66 becomes quite mobile. The structure of a complex with the sulfonamide inhibitor, acetazolamide, has also been determined. Its position in the active site is very similar to t