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To construct an East Asia mitochondrial DNA (mtDNA) phylogeny, we sequenced the complete mitochondrial genomes of 672 Japanese individuals (http://www.giib.or.jp/mtsnp/index_e.html). This allowed us to perform a phylogenetic analysis with a pool of 942 Asiatic sequences. New clades and subclades emerged from the Japanese data. On the basis of this unequivocal phylogeny, we classified 4713 Asian partial mitochondrial sequences, with <10% ambiguity. Applying population and phylogeographic methods, we used these sequences to shed light on the controversial issue of the peopling of Japan. Population-based comparisons confirmed that present-day Japanese have their closest genetic affinity to northern Asian populations, especially to Koreans, which finding is congruent with the proposed Continental gene flow to Japan after the Yayoi period. This phylogeographic approach unraveled a high degree of differentiation in Paleolithic Japanese. Ancient southern and northern migrations were detected based on the existence of basic M and N lineages in Ryukyuans and Ainu. Direct connections with Tibet, parallel to those found for the Y-chromosome, were also apparent. Furthermore, the highest diversity found in Japan for some derived clades suggests that Japan could be included in an area of migratory expansion to Continental Asia. All the theories that have been proposed up to now to explain the peopling of Japan seem insufficient to accommodate fully this complex picture

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During the first hour after a sublethal dose of ionizing radiation, 72 genes were upregulated threefold or higher in D. radiodurans R1. Thirty-three of these loci were also among a set of 73 genes expressed in R1 cultures recovering from desiccation. The five transcripts most highly induced in response to each stress are the same and encode proteins of unknown function. The genes (ddrA, ddrB, ddrC, ddrD, and pprA) corresponding to these transcripts were deleted, both alone and in all possible two-way combinations. Characterization of the mutant strains defines three epistasis groups that reflect different cellular responses to ionizing radiation-induced damage. The ddrA and ddrB gene products have complementary activities and inactivating both loci generates a strain that is more sensitive to ionizing radiation than strains in which either single gene has been deleted. These proteins appear to mediate efficient RecA-independent processes connected to ionizing radiation resistance. The pprA gene product is not necessary for homologous recombination during natural transformation, but nevertheless may participate in a RecA-dependent process during recovery from radiation damage. These characterizations clearly demonstrate that novel mechanisms significantly contribute to the ionizing radiation resistance in D. radiodurans. DEINOCOCCUS radiodurans R1 is the type species tution of ionizing radiation-induced single-strand (Dean et al. 1969) and double-strand DNA breaks (Kitayama of a bacterial family distinguished by its ability to tolerate exposure to ionizing radiation (Battista et al. and Matsuyama 1971). We have made identifying the proteins that mediate ionizing radiation resistance a 1999); exponential phase cultures survive doses to 5 kGy without loss of viability. A 5-kGy dose causes massive priority in our efforts to better explain D. radiodurans's extreme radioresistance. DNA damage, cleaving the genome of every D. radiodurans cell into multiple, subgenomic fragments (Bat-In this report we have described the genomic expression profile of D. radiodurans R1 cultures as they recover tista et al. 1999). For most species, this level of DNA damage is lethal, but D. radiodurans has the capacity to from a sublethal dose of ionizing radiation and compare that profile with R1 cultures recovering from desiccareform its genome from these fragments in what appears to be an error-free process. The biochemical details of tion (Mattimore and Battista 1996) to define the overlap in the D. radiodurans response to these stresses. D. radiodurans's ionizing radiation resistance are poorly understood, but it is clear that proteins needed for cell Mattimore and Battista (1996) established a link between the desiccation resistance and the radiotolerance survival are synthesized in cultures exposed to ionizing radiation. Irradiated cultures cannot recover in the presof D. radiodurans by demonstrating that a collection of ionizing radiation-sensitive strains were also sensitive to ence of chloramphenicol; this antibiotic p...

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Determination of the genotypes of the connexin 37, plasminogen-activator inhibitor type 1, and stromelysin-1 genes may prove reliable in predicting the genetic risk of myocardial infarction and might thus contribute to the primary prevention of this condition.

Objective: The diagnosis of mitochondrial disorders (MDs) is occasionally difficult because patients often present with solitary, or a combination of, symptoms caused by each organ insufficiency, which may be the result of respiratory chain enzyme deficiency. Growth differentiation factor 15 (GDF-15) has been reported to be elevated in serum of patients with MDs. In this study, we investigated whether GDF-15 is a more useful biomarker for MDs than several conventional biomarkers. Methods: We measured the serum levels of GDF-15 and fibroblast growth factor 21 (FGF-21), as well as other biomarkers, in 48 MD patients and in 146 healthy controls in Japan. GDF-15 and FGF-21 concentrations were measured by enzyme-linked immunosorbant assay and compared with lactate, pyruvate, creatine kinase, and the lactate-topyruvate ratio. We calculated sensitivity and specificity and also evaluated the correlation based on two rating scales, including the Newcastle Mitochondrial Disease Rating Scale (NMDAS). Results: Mean GDF-15 concentration was 6-fold higher in MD patients compared to healthy controls (2,711 6 2,459 pg/ml vs 462.5 6 141.0 pg/mL; p < 0.001). Using a receiver operating characteristic curve, the area under the curve was significantly higher for GDF-15 than FGF-21 and other conventional biomarkers. Our date suggest that GDF-15 is the most useful biomarker for MDs of the biomarkers examined, and it is associated with MD severity. Interpretation: Our results suggest that measurement of GDF-15 is the most useful first-line test to indicate the patients who have the mitochondrial respiratory chain deficiency.