Maximal aerobic power was measured for 5-6 successive years in 50 Japanese schoolboys starting from the age of 9 or 13 yr. and for 2-3 yr in 6 superior junior runners from the age of 14 yr. A large increase in aerobic power was observed during the adolescent growth spurt for 7 schoolboys who trained between the ages of 9 and 14 yr. Aerobic power for 43 average schoolboys increased from 45.0 to 52.2 ml/kg.min between the ages of 13 and 17 yr. The aerobic power of 6 superior junior runners increased from 63.4 to 73.4 ml/kg.min between the ages of 14 and 17 yr. A remarkable increase in aerobic power was not observed in trained boys before the age of peak height growth velocity (PHV). Beginning approximately 1 yr prior to the age of PHV and thereafter, training effectively increased aerobic power above the normal increase attributable to age and growth. The highly developed aerobic power found in superior junior runners may have been derived from strenuous training and partially by genetically superior endowment.

Purpose: Oncolytic adenoviruses (Ad) have been actively pursued as potential agents for cancer treatment. Among the various types of oncolytic Ads, the telomerase-specific replication-competent Ad (TRAD), which possesses an E1 gene expression cassette driven by the human telomerase reverse transcriptase promoter, has shown promising results in human clinical trials; however, the E1 gene is also slightly expressed in normal cells, leading to replication of TRAD and cellular toxicity in normal cells.Experimental Design: To overcome this problem, we utilized a microRNA (miRNA)-regulated gene expression system. Four copies of complementary sequences for miR-143, -145, -199a, or let-7a, which have been reported to be exclusively downregulated in tumor cells, were incorporated into the 3 0 -untranslated region of the E1 gene expression cassette.Results: Among the TRAD variants (herein called TRADs) constructed, TRADs containing the sequences complementary to miR-143, -145, or -199a showed efficient oncolytic activity comparable to the parental TRAD in the tumor cells. On the other hand, replication of the TRADs containing the miRNA complementary sequences was at most 1,000-fold suppressed in the normal cells, including primary normal cells. In addition, to suppress the replication of the TRADs in hepatocytes as well as other normal cells, we constructed a TRAD containing 2 distinct complementary sequences for miR-199a and liver-specific miR122a (TRAD-122a/199aT). TRAD-122a/199aT exhibited more than 10-fold reduction in viral replication in all the normal cells examined, including primary hepatocytes.Conclusions: This study showed that oncolytic Ads containing the sequences complementary to normal cell-specific miRNAs showed significantly improved safety profiles without altering tumor cell lysis activity.

Luciferases are widely used as sensitive reporters in various fields ranging from basic biology to medical diagnosis, public health, and food inspection. Scientists have isolated novel luciferases from bioluminescent organisms and concentrated on improving their brightness and thermostability. Recently, small bright luciferases such as artificial luciferase (ALuc) (21 kDa), NanoLuc (19 kDa), GLuc (18 kDa), and TurboLuc (16 kDa) have been reported. However, smaller, brighter, and more stable luciferases are desired for further applications. Here, we constructed the smallest and bright mutant of ALuc, named "picALuc" (13 kDa). picALuc retained the luminescence activity of the full-length ALuc; moreover, its brightness and thermostability were at the same levels as NanoLuc. Furthermore, we showed the advantage of picALuc for the bioluminescence resonance energy transfer-based assay due to its smallness. Our development has opened the door for wider and more practical applications of luciferases.