Renormalized basal metabolic rate describes the human aging process and longevity.

The question of why we age and finally die has been a central subject in the life, medical, and health sciences. Many aging theories have proposed biomarkers that are related to aging. However, they do not have sufficient power to predict the aging process and longevity.

Mitochondrial determinants of mammalian longevity.

Current ageing theories are far from satisfactory because of the many determinants involved in ageing. The well-known rate-of-living theory assumes that the product (lifetime energy expenditure, LEE) of maximum lifespan (MLS) and mass-specific basal metabolic rate (msBMR) is approximately constant. Although this theory provides a significant inverse correlation between msBMR and MLS as a whole for mammals, it remains problematic for two reasons.

Evolution of mitochondrial power in vertebrate metazoans.

Background: Basal metabolic rate (BMR) has a very strong body-mass (M) dependence in an individual animal group, and BMR per unit mass (msBMR) converges on a markedly narrow range even across major taxonomic groups. However, it is here a basic question in metazoan biology how much BMR per unit mitochondrion (mtBMR) changes, and then whether mtBMR can be related to the original molecular mechanism of action of mt-encoded membrane proteins (MMPs) playing a central role in cellular energy production.

Methodology/principal Findings: Analyzing variations of amino-acid compositions of MMPs across 13 metazoan animal groups, incorporating 2022 sequences, we found a strong inverse correlation between Ser/Thr composition (STC) and hydrophobicity (HYD).

Stability of mitochondrial membrane proteins in terrestrial vertebrates predicts aerobic capacity and longevity.

The cellular energy produced by mitochondria is a fundamental currency of life. However, the extent to which mitochondrial (mt) performance (power and endurance) is adapted to habitats and life strategies of vertebrates is not well understood. A global analysis of mt genomes revealed that hydrophobicity (HYD) of mt membrane proteins (MMPs) is much lower in terrestrial vertebrates than in fishes and shows a strong negative correlation with serine/threonine composition (STC).

Adaptive threonine increase in transmembrane regions of mitochondrial proteins in higher primates.

Background: The mitochondrial (mt) gene tree of placental mammals reveals a very strong acceleration of the amino acid (AA) replacement rate and a change in AA compositional bias in the lineage leading to the higher primates (simians), in contrast to the nuclear gene tree. Whether this acceleration and compositional bias were caused by adaptive evolution at the AA level or directional mutation pressure at the DNA level has been vigorously debated.

Methodology/principal Findings: Our phylogenetic analysis indicates that the rate acceleration in the simian lineage is accompanied by a marked increase in threonine (Thr) residues in the transmembrane helix regions of mt DNA-encoded proteins.

Complex population history of two Anopheles dirus mosquito species in Southeast Asia suggests the influence of Pleistocene climate change rather than human-mediated effects.

Anopheles dirus and Anopheles baimaii are closely related species which feed on primates, particularly humans, and transmit malaria in the tropical forests of mainland Southeast Asia. Here, we report an in-depth phylogeographic picture based on 269 individuals from 21 populations from mainland Southeast Asia. Analysis of 1537 bp of mtDNA sequence revealed that the population history of A.

A likelihood-based index of protein protein binding affinities with application to influenza HA escape from antibodies.

In many biological systems, proteins interact with other organic molecules to produce indispensable functions, in which molecular recognition phenomena are essential. Proteins have kept or gained their functions during molecular evolution. Their functions seem to be flexible, and a few amino acid substitutions sometimes cause drastic changes in function.

Robust time estimation reconciles views of the antiquity of placental mammals.

Background: Molecular studies have reported divergence times of modern placental orders long before the Cretaceous-Tertiary boundary and far older than paleontological data. However, this discrepancy may not be real, but rather appear because of the violation of implicit assumptions in the estimation procedures, such as non-gradual change of evolutionary rate and failure to correct for convergent evolution.

Methodology/principal Findings: New procedures for divergence-time estimation robust to abrupt changes in the rate of molecular evolution are described.

Core set approach to reduce uncertainty of gene trees.

Background: A genealogy based on gene sequences within a species plays an essential role in the estimation of the character, structure, and evolutionary history of that species. Because intraspecific sequences are more closely related than interspecific ones, detailed information on the evolutionary process may be available by determining all the node sequences of trees and provide insight into functional constraints and adaptations. However, strong evolutionary correlations on a few lineages make this determination difficult as a whole, and the maximum parsimony (MP) method frequently allows a number of topologies with a same total branching length.

Fold recognition of the human immunodeficiency virus type 1 V3 loop and flexibility of its crown structure during the course of adaptation to a host.

The third hypervariable (V3) region of the HIV-1 gp120 protein is responsible for many aspects of viral infectivity. The tertiary structure of the V3 loop seems to influence the coreceptor usage of the virus, which is an important determinant of HIV pathogenesis. Hence, the information about preferred conformations of the V3-loop region and its flexibility could be a crucial tool for understanding the mechanisms of progression from an initial infection to AIDS.

Multidimensional vector space representation for convergent evolution and molecular phylogeny.

With growing amounts of genome data and constant improvement of models of molecular evolution, phylogenetic reconstruction became more reliable. However, our knowledge of the real process of molecular evolution is still limited. When enough large-sized data sets are analyzed, any subtle biases in statistical models can support incorrect topologies significantly because of the high signal-to-noise ratio.

Economic analysis of a filmless system based on the hospital information system.

A filmless system (FLS) based on a picture archiving and communication system (PACS) equipped with UNIX work- stations and a local area network (LAN) specialized for viewing radiographs has not been deemed acceptable, for reasons of economics. However, personal computers (PCs) have recently become more powerful, to the point where PCs approach UNIX workstations in terms of capabilities. As a result, a PC-based image viewing workstation (IVW) has sufficient functions for practical use.

A new theory of phylogeny inference through construction of multidimensional vector space.

Here, a new theory of molecular phylogeny is developed in a multidimensional vector space (MVS). The molecular evolution is represented as a successive splitting of branch vectors in the MVS. The end points of these vectors are the extant species and indicate the specific directions reflected by their individual histories of evolution in the past.

Problems regarding the integration of medical images into the total hospital information system.

Since 1989, the integration of medical images into the total hospital information system (HIS) has been investigated and developed at Kochi Medical School. The basic concept of the integration is that, in the same way they can view text based data, doctors can retrieve and view images using the PC terminals of the total HIS. The possibility of utilizing the PC terminals of the total HIS as image viewing stations was investigated.

New approach to the medical information system for quality management in patient care: development of Problem Mapping System.

A new type of medical information system named Problem Mapping System (P-Map) has been developed, which aids physicians with solving patients' problems. With this system, physicians can define the problems of in-patients, monitor their progress clearly, and share information efficiently. In P-map, a list of problems, such as disease names, can be set for each inpatient easily.

Fast image accessing based on an analysis of the picture archiving and communications system in Kochi Medical School.

A large-scale picture archiving and communication system was developed by Kochi Medical School. Using JPEG to achieve 90% compression, this system was capable of storing several years worth of CT and MR examination records and eliminated the bottleneck in conventional systems caused by slow data access in the filing system. Under the new system, access of image files from client PCs was checked for bottlenecks.

Increase or decrease of HDL-cholesterol concentrations during pravastatin treatment depending on the pre-treatment HDL cholesterol levels.

Objective: The effect of pravastatin was evaluated using patient data accumulated in the data base of a hospital information system (HIS).

Methods: We selected 130 patients treated with pravastatin 10 mg per day, for a minimum period of 4 weeks.

Results: In the t test analysis, the reduction rates of total cholesterol (TC) and low-density lipoprotein (LDL) levels for pravastatin administration were 18%, and 27%, respectively.

Longitudinal characteristic curve of liver disease.

A longitudinal characteristic curve of chronic liver disease (LCC-LD) is derived for the first time by a new method of time series data analysis, where a hospital information system is utilized as a clinical research application of the database. It describes a typical pattern of development of disease from the beginning of chronic hepatitis to the final stage of cirrhosis. The LCC-LD is obtained by effectively using patient data with various stages of developments of liver disease and the present method is applicable to derive the LCC of other diseases.

Dynamical monitoring network system for perinatal care.

A new type of monitoring network system for perinatal care is proposed and has been developed. The patient monitoring system and data analyzing system are connected by a local area network (LAN). The doctor can retrieve past sampled data and results of data analysis, and make a detailed analysis at the same time that the patient is being monitored.

Development of a diagnostic and therapeutic simulation system based on patient data and specialist's knowledge. I. Simulation of diagnostic process.

A new simulation system of diagnostic and therapeutic processes is developed. The aim is to train medical students for the practical use of their knowledge, utilizing patient data in a total hospital information system. The knowledge in the system is presented by the specialists for every case.

Online support functions of prescription order system and prescription audit in an integrated hospital information system.

The role of the online prescription support functions of a prescription order entry system was analysed and the results of the prescription audit by pharmacists were examined. In the Kochi Medical School Hospital, an online prescription order system has been developed as part of an integrated hospital information system named IMIS (the Integrated Medical Information System), in which all the physicians enter their prescription orders into online display terminals. The prescription order entry system is provided with prescription support functions, which check the entered prescription data, issue warnings, and offer information about drugs or patients.

New control chart for multivariate data with missing values.

A new multivariate statistical quality control method has been developed. It is an extension of the method developed by Kume, which is able to find abnormal values in multivariate biochemical data of a clinical laboratory. The present method makes use of the difference between two sets of data measured from the samples of the same patient obtained on different days.

Efficacy of a computerized system applied to central operating theatre for medical records collection.

A computer system operation is introduced, which has been in use since October 1981 at Kochi medical school as one of the integral sub-systems of the total hospital information system called IMIS. The system was designed from the beginning with the main purposes of obtaining better management of operations, and detailed medical records are included for before, during and after operations. It is shown that almost all operations except emergencies were managed using the computer system rather than the paper system.