Genetic Encoding of 3-Iodo-l-Tyrosine in Escherichia coli for Single-Wavelength Anomalous Dispersion Phasing in Protein Crystallography

SummaryWe developed an Escherichia coli cell-based system to generate proteins containing 3-iodo-l-tyrosine at desired sites, and we used this system for structure determination by single-wavelength anomalous dispersion (SAD) phasing with the strong iodine signal. Tyrosyl-tRNA synthetase from Methanocaldococcus jannaschii was engineered to specifically recognize 3-iodo-l-tyrosine. The 1.7 Å crystal structure of the engineered variant, iodoTyrRS-mj, bound with 3-iodo-l-tyrosine revealed the structural basis underlying the strict specificity for this nonnatural substrate; the iodine moiety makes van der Waals contacts with 5 residues at the binding pocket. E. coli cells expressing iodoTyrRS-mj and the suppressor tRNA were used to incorporate 3-iodo-l-tyrosine site specifically into the ribosomal protein N-acetyltransferase from Thermus thermophilus. The crystal structure of this enzyme with iodotyrosine was determined at 1.8 and 2.2 Å resolutions by SAD phasing at CuKα and CrKα wavelengths, respectively. The native structure, determined by molecular replacement, revealed no significant structural distortion caused by iodotyrosine incorporation

The Frequency Variations of the Oxytocin Receptor Gene Polymorphisms among Dog Breeds

The domestic dog (Canis familiaris) has been diverged from wolves 15,000–100,000 years ago and certain genetic changes may have enabled them to adapt to the human social niche. In this study, we investigated the polymorphisms of the oxytocin receptor gene in dogs and wolves in order to investigate the possibility of the genetic change in the oxytocin system during dog domestication processes. Genotypes of the oxytocin receptor gene polymorphisms were determined in dogs and wolves. The single nucleotide polymorphisms (SNP; rs22927829, rs8679682, rs22896457) were observed in the sampled dogs. On the other hand, for the SNPs rs22927823 and rs22927826, only homozygous GG genotypes were observed (n=25). The frequencies of the SNPs (rs8679682 and rs22896457) were significantly different among wolves and dogs, and also among dog breed groups (p<0.05, chi-square test). The frequency profile of these SNPs among dog breed groups supports the hypothesis that there were selections on the oxytocin receptor gene during the dog domestication processes

Statistical mechanical analysis of a hierarchical random code ensemble in signal processing

We study a random code ensemble with a hierarchical structure, which is closely related to the generalized random energy model with discrete energy values. Based on this correspondence, we analyze the hierarchical random code ensemble by using the replica method in two situations: lossy data compression and channel coding. For both the situations, the exponents of large deviation analysis characterizing the performance of the ensemble, the distortion rate of lossy data compression and the error exponent of channel coding in Gallager's formalism, are accessible by a generating function of the generalized random energy model. We discuss that the transitions of those exponents observed in the preceding work can be interpreted as phase transitions with respect to the replica number. We also show that the replica symmetry breaking plays an essential role in these transitions.Comment: 24 pages, 4 figure

Statistical mechanics of typical set decoding

The performance of ``typical set (pairs) decoding'' for ensembles of Gallager's linear code is investigated using statistical physics. In this decoding, error happens when the information transmission is corrupted by an untypical noise or two or more typical sequences satisfy the parity check equation provided by the received codeword for which a typical noise is added. We show that the average error rate for the latter case over a given code ensemble can be tightly evaluated using the replica method, including the sensitivity to the message length. Our approach generally improves the existing analysis known in information theory community, which was reintroduced by MacKay (1999) and believed as most accurate to date.Comment: 7 page

Tighter decoding reliability bound for Gallager's error-correcting code

Statistical physics is employed to evaluate the performance of error-correcting codes in the case of finite message length for an ensemble of Gallager's error correcting codes. We follow Gallager's approach of upper-bounding the average decoding error rate, but invoke the replica method to reproduce the tightest general bound to date, and to improve on the most accurate zero-error noise level threshold reported in the literature. The relation between the methods used and those presented in the information theory literature are explored

Verification of the Addiction Severity Index Japanese Version (ASI-J) as a Treatment-Customization, Prediction, and Comparison Tool for Alcohol-Dependent Individuals

Objective: To demonstrate the usefulness of the Addiction Severity Index Japanese Version (ASI-J) in Japanese alcohol-dependent individuals. The ASI is a frequently used clinical and research instrument that measures severities in seven functional domains in people with substance abuse disorders. Methods: A total of 370 male inpatients with a history of alcohol dependence participated in the study. Forty-nine participants were excluded in the final analysis due to lack of reliability (i.e., patient misrepresentation or inability to understand). We used the ASI-J and a series of indexes that determined patient states during and post-treatment. Results: The correlations between ASI Composite Scores (CSs), which were calculated through a weighted formula and indicated the severity of each problem area, were significant but low in eight relations and not significant in 13 relations, indicating substantial independence of the problem areas. Significant differences were found in Family/Social CSs between abstinent and relapsed alcohol-dependent individuals. The questions of undesirable attitude were significantly related to the CSs of Employment, Drug use, Family/Social, and Psychiatric sections. Significant differences were observed in patient demographics, CS, and ASI Severity Rating (SR) and interviewer’s subjective scoring between alcohol-dependent individuals and drug abusers. CSs in Japanese alcohol-dependent individuals were generally similar to corresponding CSs in individuals from other countries, with the exception of The Netherlands. Conclusions: This study demonstrated that the ASI-J is useful for understanding individual profiles of problems for each patient and planning customized treatment. The ASI-J served as a predictive tool for relapse and compliance to treatment afterward and was shown to be useful as a comparison tool in clarifying similarities and differences between substance abuser groups

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction