dTo elucidate the biological functions of the ribosomal protein L34, which is encoded by the rpmH gene, the rpmH deletion mutant of Bacillus subtilis and two suppressor mutants were characterized. Although the ⌬rpmH mutant exhibited a severe slowgrowth phenotype, additional mutations in the yhdP or mgtE gene restored the growth rate of the ⌬rpmH strain. Either the disruption of yhdP, which is thought to be involved in the efflux of Mg 2؉ , or overexpression of mgtE, which plays a major role in the import of Mg 2؉ , could suppress defects in both the formation of the 70S ribosome and growth caused by the absence of L34. Interestingly, the Mg 2؉ content was lower in the ⌬rpmH cells than in the wild type, and the Mg 2؉ content in the ⌬rpmH cells was restored by either the disruption of yhdP or overexpression of mgtE. In vitro experiments on subunit association demonstrated that 50S subunits that lacked L34 could form 70S ribosomes only at a high concentration of Mg 2؉ . These results showed that L34 is required for efficient 70S ribosome formation and that L34 function can be restored partially by Mg 2؉ . In addition, the Mg 2؉ content was consistently lower in mutants that contained significantly reduced amounts of the 70S ribosome, such as the ⌬rplA (L1) and ⌬rplW (L23) strains and mutant strains with a reduced number of copies of the rrn operon. Thus, the results indicated that the cellular Mg 2؉ content is influenced by the amount of 70S ribosomes.T he eubacterial ribosome (70S), which plays a central role in protein synthesis, is composed of a small (30S) subunit and a large (50S) subunit. The small subunit is comprised of the 16S rRNA and more than 20 proteins, whereas the large subunit is comprised of the 23S and 5S rRNAs and more than 30 proteins (1, 2). The molecular mechanisms of translation have been elucidated in detail by the convergence of various approaches, including crystal structure analysis (3-8). The individual functions of several ribosomal proteins have also been elucidated by biochemical and genetic analyses, including reconstitution and mutational analysis. For example, ribosomal protein L2 plays important roles in the assembly of the ribosomal subunits, binding of the tRNA to the A and P sites, peptidyltransferase activity, and formation of the peptide bond (9-13). However, in general, disruption of the genes that encode the ribosomal proteins has been avoided as a means of identifying protein function, because these genes, which are highly conserved in bacteria, have been considered essential for cell proliferation (14). Nonetheless, recently, it was found that 22 of the 54 Escherichia coli genes for ribosomal proteins could be deleted on an individual basis (15,16). We have also shown that out of the 57 ribosomal-protein-encoding genes that have been annotated in the Gram-positive bacterium Bacillus subtilis, at least 22 genes are not individually essential for cell proliferation (17). The rpmH gene encoding ribosomal protein L34, which is a component of the large subunit, is one of the...

Chronic circadian disruption due to shift work or frequent travel across time zones leads to jet‐lag and an increased risk of diabetes, cardiovascular disease, and cancer. The development of new pharmaceuticals to treat circadian disorders, however, is costly and hugely time‐consuming. We therefore performed a high‐throughput chemical screen of existing drugs for circadian clock modulators in human U2OS cells, with the aim of repurposing known bioactive compounds. Approximately 5% of the drugs screened altered circadian period, including the period‐shortening compound dehydroepiandrosterone (DHEA; also known as prasterone). DHEA is one of the most abundant circulating steroid hormones in humans and is available as a dietary supplement in the USA. Dietary administration of DHEA to mice shortened free‐running circadian period and accelerated re‐entrainment to advanced light–dark (LD) cycles, thereby reducing jet‐lag. Our drug screen also revealed the involvement of tyrosine kinases, ABL1 and ABL2, and the BCR serine/threonine kinase in regulating circadian period. Thus, drug repurposing is a useful approach to identify new circadian clock modulators and potential therapies for circadian disorders.

Oxygen embrittlement in Zr-based bulk amorphous alloys is an important problem, which must be solved before the application of the bulk amorphous alloys to industrial materials. In the Zr-Cu-Al ternary system, the cast bulk amorphous Zr 50 Cu 40 Al 10 alloy near the ternary eutectic composition shows good ductility, in the case of the restriction of crystalline inclusions. Furthermore, the addition of Ni element brings about much higher ductility because of the proof ability against oxygen embrittlement. As a result, the Zr 50 Cu 30 Ni 10 Al 10 bulk amorphous alloy exhibits good ductility and proof ability against oxidization.

To help us investigate the time course of mandibular enlargement in acromegaly or acrogiantism to determine the most suitable period for occlusal treatment in this disease, our aim was to develop a rat model of acromegaly (acrogiantism). In this study, prominent mandibular enlargement was induced by continuous subcutaneous infusion of human recombinant insulin-like growth factor-I (IGF-I) (640 microg/day) in 10-week-old male rats for 4 weeks (n = 6); the control sham-operated group was injected with saline alone (n = 6). Circulating human IGF-I was clearly detectable in the IGF-I group during the four-week administration period, while endogenous rat IGF-I levels decreased. Total IGF-I (human + rat) increased significantly during administration, returning to control levels afterwards. The length of every bone examined (mandible, maxilla, and femur) showed a significant increase compared to control rats, especially the mandible. Although the mandible did not continue to grow after discontinuation of IGF-I administration, it did not return to control size, unlike the maxilla and femur, and disharmonious jaw size (between maxilla and mandible) persisted even after circulating IGF-I levels normalized. These findings in our rat model suggest that mandibular occlusal treatment should only be considered for acromegalic (acrogiantic) patients after serum IGF-I levels have normalized and bone growth has ceased.

The world's smallest (0.36 mm 2 ) solid-state CMOS-compatible glucose fuel cell, which exhibits an open-circuit voltage (OCV) of 228 mV and a power generation density of 1.32 µW/cm 2 with a 30 mM glucose solution, is reported in this paper. Compared with conventional wet etching, dry etching (reactive ion etching) for patterning minimizes damage to the anode and cathode, resulting in a cell with a small size and a high OCV, sufficient for CMOS circuit operation.