In an effort to identify novel genes involved in recombination repair, we isolated fission yeast Schizosaccharomyces pombe mutants sensitive to methyl methanesulfonate (MMS) and a synthetic lethal with rad2. A gene that complements such mutations was isolated from the S. pombe genomic library, and subsequent analysis identified it as the fbh1 gene encoding the F-box DNA helicase, which is conserved in mammals but not conserved in Saccharomyces cerevisiae. An fbh1 deletion mutant is moderately sensitive to UV, MMS, and ␥ rays. The rhp51 (RAD51 ortholog) mutation is epistatic to fbh1. fbh1 is essential for viability in stationary-phase cells and in the absence of either Srs2 or Rqh1 DNA helicase. In each case, lethality is suppressed by deletion of the recombination gene rhp57. These results suggested that fbh1 acts downstream of rhp51 and rhp57. Following UV irradiation or entry into the stationary phase, nuclear chromosomal domains of the fbh1⌬ mutant shrank, and accumulation of some recombination intermediates was suggested by pulsed-field gel electrophoresis. Focus formation of Fbh1 protein was induced by treatment that damages DNA. Thus, the F-box DNA helicase appears to process toxic recombination intermediates, the formation of which is dependent on the function of Rhp51.Homologous recombination not only shuffles genetic information upon sexual reproduction but also repairs damaged DNA by use of the homologous information. Furthermore, it can regenerate replication forks when they become stalled or collapsed.Molecular mechanisms of homologous recombination in eukaryotes have been most extensively studied in the budding yeast Saccharomyces cerevisiae (reviewed in references3, 27, 42, 46, and 48). In this yeast, the MRX (Mre11 Rad50 Xrs2) complex is required for the processing of double-strand break ends to generate 3Ј-protruding ends. The resulting singlestrand regions are coated by single-strand-binding protein RPA (replication protein A). Rad52 stimulates loading of Rad51 on RPA-coated single-strand DNA to form Rad51 nucleoprotein filament. A complex of Rad55 and Rad57, which are Rad51 paralogs, is also implicated in the assembly and stabilization of Rad51 nucleoprotein filament. Rad51 nucleoprotein filament searches homologous sequences and catalyzes the exchange of strands to form a heteroduplex joint called a D loop. Rad54 facilitates D-loop formation by remodeling chromatin structures. The annealed 3Ј ends are then used as primers for repair DNA synthesis. The resulting junction molecules are resolved either by dissociation of the crossed strands or by cutting of the junction point. The Rad52 group proteins (Rad50, Rad51, Rad52, Rad54, Rad55, Rad57, Mre11, and Xrs2) are conserved throughout eukaryotes, indicating a conservation of the molecular mechanisms pertaining to homologous recombination.In addition to the aforementioned recombination factors,

The present study aims to identify the effects of systematic walking on exercise energy expenditure (EEE) and blood profiles in middle-aged women. Fifty-two female nurse managers, aged 32 to 57 years (42.0 +/- 6.2), were randomly assigned to an intervention group (IG) and a control group (CG) for a 12-week study of the walking program. EEE was measured using a microelectronic device. Blood profiles were assessed before and after the walking program. The mean EEE (kcal/kg/d) in the IG and CG was 4.73 +/- 1.02 and 3.88 +/- 0.81 (P = 0.01), indicating an increase of 1.17 +/- 0.98 and 0.46 +/- 0.68 from baseline (P = 0.01), respectively. The mean change in high-density lipoprotein cholesterol in the IG and CG was 1.8 +/- 8.3 mg/dL and -2.9 +/- 7.0 mg/dL (P = 0.051); that in insulin was -4.5 +/- 7.5 microU/dL and -0.6 +/- 4.3 microU/dL (P = 0.046), respectively. These results show that systematic walking increases EEE and improves blood profiles.

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EEE increased significantly, but fibrinogen levels did not decrease significantly. The effects of a 12-week off-site walking program on fibrinogen levels were inconclusive. As implications for nursing practice, our findings have suggested fibrinogen levels are not a novel cardiovascular risk factor any more, and provide important information on safe exercise to minimize adverse effects from fibrinogen arising from exercise intensity, especially in women with advanced atherosclerosis when nurses increase exercise intensity levels. Further studies with larger sample sizes in women to confirm the effect of exercise on reducing fibrinogen levels are necessary.

Although colocalization of amyloid β (Aβ) with prion protein (PrP) in the kuru plaque has previously been observed in the brain of prion diseases patients, the participating Aβ species has not been identified. Here, we present an immunohistochemical assessment of the brain and spinal cord of a 69-year-old Japanese female patient with Gerstmann-Sträussler-Scheinker disease with a P105L mutation on the PRNP gene (GSS-P105L). Immunohistochemical assessment of serial brain sections was performed using anti-PrP and -Aβ antibodies in the hippocampus, frontal and occipital lobes. She died 69 years after a 21-year clinical course. Immunohistochemistorical examination revealed that~50% of the kuru plaques in the cerebrum were colocalized with Aβ, and Aβ42 was predominantly observed to be colocalized with PrP-plaques. The Aβ deposition patterns were unique, and distinct from diffuse plaques observed in the normal aging brain or Alzheimer's disease brain. The spinal cord exhibited degeneration in the lateral corticospinal tract, posterior horn, and fasciculus gracilis. We have demonstrated for the first time that Aβ42, rather than Aβ40, is the main Aβ component associated with PrP-plaques, and also the degeneration of the fasciculus gracilis in the spinal cord in GSS-P105L, which could be associated with specific clinical features of GSS-P105L.