The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo

Comparison of the histological and immunohistochemical features of the thymus in young- and elderly-onset myasthenia gravis without thymoma

ArticleJOURNAL OF CLINICAL NEUROSCIENCE. 14(2): 110-115 (2007)journal articl

Frequentist Coverage Properties of Uncertainty Intervals for Weak Poisson Signals in the Presence of Background

We construct uncertainty intervals for weak Poisson signals in the presence of background. We consider the case where a primary experiment yields a realization of the signal plus background, and a second experiment yields a realization of the background. The data acquisitions times for the background-only experiment,T_bg, and the primary experiment,T, are selected so that their ratio varies from 1 to 25. The expected number of background counts in the primary experiment varies from 0.2 to 2. We construct 90 and 95 percent confidence intervals based on a propagation-of-errors method as well as two implementations of a Neyman procedure where acceptance regions are constructed based on a likelihood-ratio criterion that automatically determines whether the resulting confidence interval is one-sided or two-sided. The first Neyman procedure (due to Feldman and Cousins) neglects uncertainty in the background. In the other Neyman procedure, we account for uncertainty in the background with a parametric bootstrap method. We also construct minimum length Bayesian credibility intervals. For each method, we test for the presence of a signal based on the value of the lower endpoint of the uncertainty interval. When T_bg/T is 5 or more and the expected background is 2 or less, the Feldman Cousins method outperforms the other methods considered.Comment: 12 pages,12 tables, 10 figures. This is the final version of a manuscript that has been accepted for publication by Measurement Science and Technolog

Left atrial volume predicts adverse cardiac and cerebrovascular events in patients with hypertrophic cardiomyopathy

<p>Abstract</p> <p>Aims</p> <p>To prospectively evaluate the relationship between left atrial volume (LAV) and the risk of clinical events in patients with hypertrophic cardiomyopathy (HCM).</p> <p>Methods</p> <p>We enrolled a total of 141 HCM patients with sinus rhythm and normal pump function, and 102 patients (73 men; mean age, 61 ± 13 years) who met inclusion criteria were followed for 30.8 ± 10.0 months. The patients were divided into two groups with or without major adverse cardiac and cerebrovascular events (MACCE), a composite of stroke, sudden death, and congestive heart failure. Detailed clinical and echocardiographic data were obtained.</p> <p>Results</p> <p>MACCE occurred in 24 patients (18 strokes, 4 congestive heart failure and 2 sudden deaths). Maximum LAV, minimum LAV, and LAV index (LAVI) corrected for body surface area (BSA) were significantly greater in patients with MACCE than those without MACCE (maximum LAV: 64.3 ± 25.0 vs. 51.9 ± 16.0 ml, p = 0.005; minimum LAV: 33.9 ± 15.1 vs. 26.2 ± 10.9 ml, p = 0.008; LAVI: 40.1 ± 15.4 vs. 31.5 ± 8.7 ml/mm², p = 0.0009), while there were no differences in the other echocardiographic parameters.</p> <p>LAV/BSA of ≥ 40.4 ml/m²to identify patients with cardiovascular complications with a sensitivity of 73% and a specificity of 88%.</p> <p>Conclusion</p> <p>LAVI may be an effective marker for detecting the risk of MACCE in patients with HCM and normal pump function.</p