Ubiquitin-mediated proteolysis is the key to cell cycle control. Anaphase-promoting complex/cyclosome (APC) is a ubiquitin ligase that targets cyclin B and factors regulating sister chromatid separation for proteolysis by the proteasome and, consequently, regulates metaphase-anaphase transition and exit from mitosis. Here we report that Cdc2-cyclin B-activated Polo-like kinase (Plk) specifically phosphorylates at least three components of APC and activates APC to ubiquitinate cyclin B in the in vitro-reconstituted system. Conversely, protein kinase A (PKA) phosphorylates two subunits of APC but suppresses APC activity. PKA is superior to Plk in its regulation of APC, and Plk activity peaks whereas PKA activity is falling at metaphase. These results indicate that Plk and PKA regulate mitosis progression by controlling APC activity.

ABSTRACT-We investigated the characteristics of D 9 -tetrahydrocannabinol (THC)-induced impairment of learning and memory using an 8-arm radial maze task, a water maze, a visual discrimination task with 2 figures and a passive avoidance test in rats. THC (6 mg /kg, i.p.) impaired spatial memory in the standard task of the 8-arm radial maze. THC (4 -6 mg /kg, i.p.) selectively impaired working memory in a reference and working memory task of the 8-arm radial maze. Even at a dose of 10 mg /kg, THC did not impair spatial memory in the water maze. In addition, THC at a dose of 6 mg /kg, which had inhibitory effects in the 8-arm radial maze, did not affect performance in the visual discrimination task. These results indicate that at low doses (2 -6 mg/kg), THC may not produce visual function abnormalities. THC impaired retrieval (6 mg /kg, i.p.) as well as acquisition (10 mg /kg, i.p.) in the passive avoidance test. The consolidation process was also impaired by i.c.v. injection (100 m g), but not i.p. injection (6 -10 mg /kg) of THC. These results suggest that THC-induced impairment of spatial memory is based on the selective impairment of working memory through its effects on acquisition and retrieval processes.

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The olfactory acuity of 29 patients receiving laryngectomy was prospectively studied. The olfactory acuity was evaluated by Jet Stream Olfactometer (JSO) and Alinamin test preoperatively and at 3, 6 and 12 months postoperatively. The findings of nasal/olfactory mucosae were also observed by rigid endoscope. Based on the results of JSO, the averages of detection/recognition thresholds tended to increase 3 months postoperatively, then the averaged thresholds tended to decrease thereafter. There were significant differences between preoperative values and those 3 months after surgery, but there were no significant differences between preoperative values and these 6/12 months after surgery. Nasal respiratory mucosae observed 12 months after laryngectomy showed atrophic nasal mucosa in 11/14 patients. However, olfactory mucosae appeared normal in all of the patients observed. These results suggested that the function of the olfactory epithelium remained intact after laryngectomy.

The odor stick identification test (OSIT) is a new test of olfactory function recently developed for Japanese people. The purpose of the present study was to evaluate this test in relation to T&T olfactometry and the cross-cultural smell identification test (CC-SIT) by applying to 110 Japanese patients with olfactory disturbance. The averaged recognition thresholds for five odorants in T&T olfactometry, the number of correct answers in the CC-SIT and the rates of identification of 13 odorants in the OSIT were compared. The visual analogue scale (VAS) was also used to evaluate symptoms. The rate of identification of OSIT showed high and significant correlation coefficients with the averaged recognition thresholds of T&T olfactometry (-0.766, P < 0.001), with the number of correct answers in CC-SIT (0.754, P < 0.001) and with the VAS score (0.591, P < 0.001). In addition, on the identification performance measured by OSIT, we found significant differences between all pairs of four degrees of olfactory dysfunction except for one pair. Thus, we conclude that OSIT is useful for evaluating olfactory dysfunction in Japanese people.

SummaryTo study the adequate intake (AI) for vitamin D in the elderly, we have performed an intervention study with 800 IU/d of vitamin D 3 in the institutionalized elderly. Sixty-two institutionalized elderly were randomly assigned to two groups; receiving either supplements of 200 mg calcium plus 800 IU vitamin .3 ng/mL in the Ca ϩ VD group and to 11.1 ng/mL in the Ca group. Post intervention serum 25OH-D level was significantly higher in the Ca ϩ VD group than in the Ca group ( p Ͻ 0.001). In 53 subjects (85.5%) who took more than 80% of their supplements for 30 d, serum PTH level in the Ca ϩ VD group was significantly lower than in the Ca groups ( p ϭ 0.05). Bone turnover markers were not significantly changed after intervention in either group. Daily supplementation of 800 IU vitamin D 3 was considered effective in the institutionalized elderly with minimal chance of sun exposure, but further studies with longer duration are necessary.

We constructed a model organism to study the physiological role and function of P. falciparum malate-quinone oxidoreductase (PfMQO) in a yeast expression system. PfMQO is actively expressed in yeast mitochondria and functions in place of yeast mitochondrial malate dehydrogenase, which catalyzes the oxidation of malate to oxaloacetate in the TCA cycle.

Propolis is a bee product with various biological properties. C57BL/6 mice were fed a high-fat diet and treated with propolis for 14 weeks. Body weight in mice treated with 2% propolis was less than that in control mice from 3 weeks after the start of treatment until 14 weeks except for the 7th week. Mice treated with propolis showed significantly lower epididymal fat weight and subcutaneous fat weight. Infiltration of epididymal fat by macrophages and T cells was reduced in the propolis group. Supplementation of propolis increased feces weight and fat content in feces, suggesting that mechanisms of weight reduction by propolis partly include a laxative effect and inhibition of fat absorption.