The National Adult Reading Test (NART) is widely used as a measure of premorbid IQ of the English-speaking patients with dementia. The purpose of the present study was to develop a Japanese version of the NART (JART), using 50 Japanese irregular words, all of which are Kanji (ideographic script) compound words. Reading performance based on JART and IQ as measured by the Wechsler Adult Intelligence Scale-Revised (WAIS-R) was examined in a sample of 100 normal elderly (NE) persons and in 70 age-, sex-, and education-matched patients with Alzheimer's disease (AD). The NE group was randomly divided into the NE calculation group ( n = 50) and the NE validation group ( n = 50). Using the NE calculation group, a linear regression equation was obtained in which the observed full-scale IQ (FSIQ) was regressed on the reading errors of the JART. When the regressed equation computed from the NE calculation group was applied to the NE validation group, the predicted FSIQ adequately fit the observed FSIQ ( R 2 = 0.78). Further, independent t -tests showed that the JART-predicted IQs were not significantly different between the NE and AD groups, whereas the AD group performed worse in the observed IQs. The reading ability of Kanji compound words is well-preserved in Japanese patients with AD. The JART is a valid scale for evaluating premorbid IQ in patients with AD.

The two translational release factors of prokaryotes, RF1 and RF2, catalyse the termination of polypeptide synthesis at UAG/UAA and UGA/UAA stop codons, respectively. However, how these polypeptide release factors read both non-identical and identical stop codons is puzzling. Here we describe the basis of this recognition. Swaps of each of the conserved domains between RF1 and RF2 in an RF1-RF2 hybrid led to the identification of a domain that could switch recognition specificity. A genetic selection among clones encoding random variants of this domain showed that the tripeptides Pro-Ala-Thr and Ser-Pro-Phe determine release-factor specificity in vivo in RF1 and RF2, respectively. An in vitro release study of tripeptide variants indicated that the first and third amino acids independently discriminate the second and third purine bases, respectively. Analysis with stop codons containing base analogues indicated that the C2 amino group of purine may be the primary target of discrimination of G from A. These findings show that the discriminator tripeptide of bacterial release factors is functionally equivalent to that of the anticodon of transfer RNA, irrespective of the difference between protein and RNA.

Translation termination requires two codonspecific polypeptide release factors in prokaryotes and one omnipotent factor in eukaryotes. Sequences of 17 different polypeptide release factors from prokaryotes and eukaryotes were compared. The prokaryotic release factors share residues split into seven motifs. Conservation of many discrete, perhaps critical, amino acids is observed in eukaryotic release factors, as well as in the C-terminal portion of elongation factor (EF) G. Given that the C-terminal domains of EF-G interacts with ribosomes by mimicry of a tRNA structure, the pattern of conservation of residues in release factors may reflect requirements for a tRNA-mimicry for binding to the A site of the ribosome. This mimicry would explain why release factors recognize stop codons and suggests that all prokaryotic and eukaryotic release factors evolved from the progenitor of EF-G. domain motifs and is involved in omnipotent suppression of nonsense codons (for a review, see ref. 11).Can the current computer programs used for sequence comparison, as designed, predict conserved amino acids at discrete positions in comparisons of multiple random sequences? It seems unlikely to us that the currently used computer programs would recognize single conserved amino acids when the number and diversity of protein sequences is increased, because the algorithms used are essentially based on one-to-one comparison of letters or words of finite length. Here, we approach this problem by identifying first "by computer" the conserved amino acids in prokaryotic RFs, and then asking "by eye" whether these residues are also present in eukaryotic RFs. This approach provided us with clues that lead to universally conserved motifs in RFs, part of which may reflect requirements for molecular mimicry of a tRNA structure.

Insulin-dependent diabetes mellitus is characterized by the infiltration of lymphocytes into the islets of Langerhans of the pancreas (insulitis) followed by destruction of insulin-secreting beta-cells leading to overt diabetes. The best model for the disease is the non-obese diabetic (NOD) mouse. Two unusual features of the class II major histocompatibility complex (MHC) of the NOD mouse are the absence of I-E and the presence of unique I-A molecules (I-ANOD), in which aspartic acid at position 57 of the beta-chain is replaced by serine. This feature is also found in the HLA-DQ chain of many Caucasians with insulin-dependent diabetes mellitus. We have previously reported that the expression of I-E prevents the development of insulitis in NOD mouse. Here we report that the expression of I-Ak (A alpha kA beta k) in transgenic NOD mice can also prevent insulitis, and that this protection is seen not only when the I-A beta-chain has aspartic acid as residue 57, but also when this residue is serine. These results show that the single amino-acid substitution at position 57 of the I-A beta-chain from aspartic acid to serine is not sufficient for the development of the disease.

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Our results suggest that FA reflects progression of AD-related histopathological changes in the UF of the white matter and may represent a useful biological index in monitoring AD. Diffusion tensor tract-specific analysis with voxelized tract shape processing to measure the core of the tract may be a sensitive tool for evaluation of diffusion abnormalities of white matter tracts in AD.

Prokaryotic translational release factors, RF1 and RF2, catalyze polypeptide release at UAG͞UAA and UGA͞UAA stop codons, respectively. In this study, we isolated a bacterial RF2 mutant (RF2*) containing an E167K substitution that restored the growth of a temperature-sensitive RF1 strain of Escherichia coli and the viability of a chromosomal RF1͞RF2 double knockout. In both in vivo and in vitro polypeptide termination assays, RF2* catalyzed UAG͞UAA termination, as does RF1, as well as UGA termination, showing that RF2* acquired omnipotent release activity. This result suggests that the E167K mutation abolished the putative third-base discriminator function of RF2. These findings are interpreted as indicating that prokaryotic and eukaryotic release factors share the same anticodon moiety and that only one omnipotent release factor is sufficient for bacterial growth, similar to the eukaryotic single omnipotent factor.The termination of protein synthesis takes place on the ribosomes as a response to a stop, rather than a sense, codon in the ''decoding'' site (A site). Translation termination generally requires two codon-specific polypeptide release factors (RFs), RF1 (for UAG͞UAA) and RF2 (for UGA͞UAA), in prokaryotes (1, 2) and one factor, eRF1 (omnipotent for the three stop codons), in eukaryotes (2-4) (Fig. 1A). However, the mechanism of stop codon recognition by release factors is unknown and represents a long-standing coding problem of considerable interest. It entails protein-RNA recognition rather than the well understood mRNA-tRNA interaction in codon-anticodon pairing (2, 5, 6).The fact that two RFs from prokaryotes exhibit codon specificity suggests that they must interact directly with the codon. On accumulation of RF sequences from different organisms, the conservation of protein motifs has emerged in prokaryotic and eukaryotic RFs, as well as in the C-terminal portion of elongation factor EF-G, a translocase protein that forwards peptidyl tRNA from the A site to the P site on the ribosome (7). The three-dimensional structure of Thermus thermophilus EF-G comprises five subdomains; the C-terminal part, domains III-V, appears to mimic the shapes of the acceptor stem, the anticodon helix, and the T stem of tRNA, respectively (8-10). Furthermore, it appears that an RF region shares homology with domain IV of EF-G, thus constituting a putative ''tRNA-mimicry'' domain necessary for RF binding to the ribosomal A site (7). This mimicry model would explain why RFs recognize stop codons by assuming an anticodonmimicry element in the protein and further suggest that all prokaryotic and eukaryotic RFs evolved from the progenitor of EF-G. RF1 and RF2 are known to be structurally similar, and both read the UAA codon. It might be possible, therefore, to alter mutationally either factor so that its stop codon specificity is altered. In the present study, we mutationally altered RF2 and show that a single amino acid substitution permits it to terminate translation at the UAG stop codon as well as the UGA and UAA ...

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