Water-soluble ferulic acid derivatives improve amyloid-β-induced neuronal cell death and dysmnesia through inhibition of amyloid-β aggregation

Ferulic acid (FA) has been reported to exhibit protective effects against amyloid-β (Aβ)-induced neurodegeneration in vitro and in vivo. Recently, we developed two water-soluble FA derivatives: 1-feruloyl glycerol and 1-feruloyl diglycerol. In this study, we examined the neuroprotective effects of these water-soluble FA derivatives on Aβ-induced neurodegeneration both in vitro and in vivo. FA and water-soluble FA derivatives inhibited Aβ aggregation and destabilized pre-aggregated Aβ to a similar extent. Furthermore, water-soluble FA derivatives, as well as FA, inhibited Aβ-induced neuronal cell death in cultured neuronal cells. In in vivo experiments, oral administration of water-soluble FA derivatives to mice improved Aβ-induced dysmnesia assessed by contextual fear conditioning test and protected hippocampal neurons against Aβ-induced neurotoxicity. This study provides useful evidence suggesting that water-soluble FA derivatives are expected to be effective neuroprotective agents.     

STT3B-dependent posttranslational N-glycosylation as a surveillance system for secretory protein

The chemical identity and integrity of the genome is challenged by the incorporation of ribonucleoside triphosphates (rNTPs) in place of deoxyribonucleoside triphosphates (dNTPs) during replication. Misincorporation is limited by the selectivity of DNA replicases. We show that accumulation of ribonucleoside monophosphates (rNMPs) in the genome causes replication stress and has toxic consequences, particularly in the absence of RNase H1 and RNase H2, which remove rNMPs. We demonstrate that postreplication repair (PRR) pathways-MMS2-dependent template switch and Pol ζ-dependent bypass-are crucial for tolerating the presence of rNMPs in the chromosomes; indeed, we show that Pol ζ efficiently replicates over 1-4 rNMPs. Moreover, cells lacking RNase H accumulate mono- and polyubiquitylated PCNA and have a constitutively activated PRR. Our findings describe a crucial function for RNase H1, RNase H2, template switch, and translesion DNA synthesis in overcoming rNTPs misincorporated during DNA replication, and may be relevant for the pathogenesis of Aicardi-Goutières syndrome.     

Changes in the amounts of two kinds of reserve glucose-containing polysaccharides during germination of the Easter lity bulb

A demonstration of two kinds of reserve glucose-containing polysaccharidesdigesing in different modes during germination of the Easterlily bulb, and a discussion of the physiological role of bothpolysaccharides. ¹Present address: Department of Horticulture, Kagoshima University,Kagoshima, Japan. (Received November 27, 1973; )     

Growth of the hydrocarbon-rich microalga Botryococcus braunii in secondarily treated sewage

Summary A hydrocarbon-rich green microalga, Botryococcus braunii, was able to grow well in secondarily treated sewage (STS) from domestic waste-water in a batch system. The growth in STS from domestic waste-water was as good as in the common artificial medium of modified Chu 13 and its hydrocarbon contents were high enough at 53% and 40% compared with 58% in the case of the modified Chu 13 medium. B. braunii utilized nitrate from 7.67 or 4.48 mg/l to a level below detection of < 0.01 mg/l in STS. After this consumption of nitrate, nitrite was consumed, and ammonium was not. Phosphate, even at an extremely low concentration, was also consumed by B. braunii. These results show the possibility of using STS as a medium to grow B. braunii and for removal of nitrogen and phosphorus by algal consumption in STS.Correspondence to: S. Yokoyama     

Bacterial lipopolysaccharide induces osteoclast formation in RAW 264.7 macrophage cells

Lipopolysaccharide (LPS) is a potent bone resorbing factor. The effect of LPS on osteoclast formation was examined by using murine RAW 264.7 macrophage cells. LPS-induced the formation of multinucleated giant cells (MGC) in RAW 264.7 cells 3 days after the exposure. MGCs were positive for tartrate-resistant acid phosphatase (TRAP) activity. Further, MGC formed resorption pits on calcium-phosphate thin film that is a substrate for osteoclasts. Therefore, LPS was suggested to induce osteoclast formation in RAW 264.7 cells. LPS-induced osteoclast formation was abolished by anti-tumor necrosis factor (TNF)-alpha antibody, but not antibodies to macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-kappaB ligand (RANKL). TNF-alpha might play a critical role in LPS-induced osteoclast formation in RAW 264.7 cells. Inhibitors of NF-kappaB and stress activated protein kinase (SAPK/JNK) prevented the LPS-induced osteoclast formation. The detailed mechanism of LPS-induced osteoclast formation is discussed.     

Incidence of symptomatic vertebral fractures in women of childbearing age newly treated with high-dose glucocorticoid

Background: The treatment and prevention of glucocorticoid (GC)-induced osteoporosis have been controversial in premenopausal women during their childbearing years.Objective: This study assessed the incidence and risk factors for symptomatic vertebral fracture in women of childbearing age newly treated with high-dose GC.Methods: An observational cohort study was conducted at the rheumatic center of Shimoshizu National Hospital in Chiba, Japan, from 1986 to 2006. The prevalence of symptomatic vertebral fractures, as determined by x-rays, was assessed in premenopausal (aged <50 years) women with collagen vascular disease newly treated with high-dose GC (≥20 mg/d prednisolone equivalent) compared with their counterparts who did not receive GC. Differences in the incidences of vertebral fractures were compared between groups by the Kaplan-Meier method and evaluated by the log-rank test. Hazard ratios (HRs) with 95% CIs were estimated using the Cox proportional hazards regression model.Results: A total of 373 women were assessed: 292 patients in the high-dose GC treatment group (mean [SD] initial age, 32.4 [8.2] years; initial dose, 43.8 [14.9] mg/d; follow-up time, 124.2 [75.4] months) and 81 patients in the non-GC control group (initial age, 39.3 [7.8] years; follow-up time, 106.5 [79.7] months). Symptomatic vertebral fractures occurred more frequently in the high-dose GC group (11.3%) than in the non-GC group (1.2%). Using the Cox model, the adjusted HR for the high-dose GC group was 13.96 (95% CI, 1.87–104.22) relative to the non-GC group. In the high-dose GC group, Kaplan-Meier analyses revealed that the incidence of fractures in women in their forties was significantly higher in comparison with those in their twenties (P < 0.001) and thirties (P < 0.05), and that the incidence of fractures in those who consumed alcohol (>80 g/wk of pure alcohol) was significantly higher than in those who did not (P < 0.05). The Cox model also revealed that the risk was independently higher with every 10-year increment of initial age (HR = 2.27; 95% CI, 1.46–3.53), with every GC dose increase (HR = 2.28; 95% CI, 1.58–3.31), and with each 1-gram decrease of cumulative GC dose (HR = 0.95; 95% CI, 0.93–0.98).Conclusions: In this study, high-dose GC use was associated with a significantly high prevalence of symptomatic vertebral fractures in premenopausal women with collagen vascular disease during their childbearing years. However, the fracture risk was relatively low in women of childbearing age, especially those in their twenties and thirties during the early years of treatment.