RANKL directly induces bone morphogenetic protein-2 expression in RANK-expressing POS-1 osteosarcoma cells

International audienceThe POS-1 murine model of osteolytic osteosarcoma was used to elucidate the molecular and cellular mechanisms involved in the development of primary bone tumors and associated lung metastasis. The POS-1 cell line is derived from an osteosarcoma tumor which develops spontaneously in C3H mice. The POS-1 cell line was characterized in vitro by mineralization capacity and expression of bone markers by semi-quantitative RT-PCR, compared to primary osteoblasts and bone marrow cells. POS-1 cells showed no mineralization capacity and exhibited an undifferentiated phenotype, expressing both osteoblastic and unexpected osteoclastic markers (TRAP, cathepsin K and RANK). Thereby, experiments were performed to determine whether RANK was functional, by studying the biological activity of murine RANKL through the receptor RANK expressed on POS-1 cells. Results revealed a RANKL-induced increase in ERK phosphorylation, as well as BMP-2 induction at the mRNA and protein levels, and a decrease of POS-1 cell proliferation in the presence of 10 ng/ml RANKL. BMP-2 induction is dependent on the ERK 1/2 signal transduction pathway, as its expression is abolished in the presence of UO126, a specific synthetic inhibitor of the ERK 1/2 pathway. Moreover, a 2-fold molar excess of soluble RANK blocks the RANKL-induced BMP-2 expression, demonstrating that the biological effects of RANKL observed in POS-1 cells are mediated by RANK. This is the first report describing a functional RANK expressed on osteosarcoma cells, as shown by its ability to induce signal transduction pathways and biological activity when stimulated by RANKL

On Ultrasmall Silicate Grains in the Diffuse Interstellar Medium

The abundance of both amorphous and crystalline silicates in very small grains is limited by the fact that the 10 micron silicate emission feature is not detected in the diffuse ISM. On the basis of the observed IR emission spectrum for the diffuse ISM, the observed ultraviolet extinction curve, and the 10 micron silicate absorption profile, we obtain upper limits on the abundances of ultrasmall (a < 15 Angstrom) amorphous and crystalline silicate grains. Contrary to previous work, as much as ~20% of interstellar Si could be in a < 15 Angstrom silicate grains without violating observational constraints. Not more than ~5% of the Si can be in crystalline silicates (of any size).Comment: Submitted to ApJ Letters, 11 pages, 4 figures, Late

Project Update of 500 TPD Demonstration Plant for Coal-fired Power Plant

AbstractSouthern Company and MHI successfully started the world's largest 500 TPD carbon capture plant for a coal-fired power plant in June 2011 at Alabama Power's Plant Barry and achieved full load operation. These operation experience and lessons & learned of the actual plants would help facilitate scale-up CO2 capture plant for coal fired power plant. This paper gives updated operation results of the demonstration plant along with MHI's R&D Activities for the commercial applicatio

A Case of Mycobacterial Skin Disease Caused by Mycobacterium peregrinum, and a Review of Cutaneous Infection

An 83-year-old Japanese man presented with a 2-month history of symptomatic nodules on the left hand. He was not in an immunocompromised condition and reported no causal events. A biopsy specimen demonstrated granulomatous tissue with mixed cell infiltration consisting of neutrophils, histiocytes, lymphocytes, and multinuclear giant cells. No bacillus was detected by PAS, acid-fast stain, immunofluorescent stain or polymerase chain reaction analysis. The isolate was found to be a rapidly growing mycobacterium after 4 weeks of incubation at 25°C on an Ogawa egg slant. Mycobacterium peregrinum was isolated by DNA-DNA hybridization analysis, 16S rRNA gene sequence, and by its production of 3-day arylsulfatase. The patient received 200 mg oral minocycline for 28 weeks. The lesion disappeared after 10 weeks of this treatment

Improved Enamel Acid Resistance by Highly Concentrated Acidulated Phosphate Sodium Monofluorophosphate Solution

Sodium monofluorophosphate (MFP) is a component of fluoride-containing dentifrices and is more biosafe than the conventional sodium fluoride (NaF). MFP can respond not only on the tooth surface layer but also deep into the enamel. We aim to confirm that high concentrations of acid phosphate MFP (AP-MFP, 9000 ppmF), used in professional care, could lead to a highly biosafe fluoride application method that acts through the deep enamel layers. Sample groups were respectively treated in vitro with NaF, acidulated phosphate fluoride (APF), MFP, and AP-MFP, and the samples were compared against an untreated group. Characterizations after fluoride application confirmed that MFP and AP-MFP treatments improved the acid resistance of enamel compared to that of conventional methods. Furthermore, the acid resistance of highly concentrated MFPs improved by using phosphoric acid. Although the acid resistance from the AP-MFP method is not as good as that using APF, AP-MFP can act both on the surface layer and deep into the enamel. Moreover, AP-MFP retains fluoride ions as much as APF does on the tooth surface. The proposed fluoride application method using AP-MFP introduces a dental treatment for acid resistance that is highly biosafe and penetrates deep layers of the enamel

COVID-19-Related Factors Delaying Dental Visits of Workers in Japan

BACKGROUND: The aim of this research was to investigate the factors associated with postponing dental attendance amongst Japanese workers during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted an internet-based survey in Japan from November 24 to 29, 2021. The participants were selected from people registered with an online research company. The inclusion criteria for this study were full-time or part-time workers aged 20 to 69 years. Participants filled out a questionnaire about their oral health, behaviour, and working conditions. RESULTS: A total of 1840 participants were included in the analysis. Three hundred ninety-eight participants (21.5%) answered that they postponed dental attendance due to COVID-19. Multiple logistic regression showed that women were more likely to postpone dental attendance (odds ratio [OR], 1.74; 95% confidence interval, 1.33–2.26). Moreover, employment status, household income, changes in income, working at home, interdental cleaning device use, regular dental attendance, awareness of untreated teeth, and dental pain were also associated with postponing dental attendance. The results of decision tree analysis showed that regular dental attenders with dental pain were the most likely to postpone dental attendance. CONCLUSIONS: The characteristics of postponed dental visits for Japanese workers differ depending on whether one is a regular dental attender or not. Amongst regular dental attenders, worsening oral health due to interruptions in dental attendance is concerning. Meanwhile, untreated teeth might be neglected amongst nonregular dental attenders. Preventing patients from refraining from dental attendance, regardless of whether or not they are regular dental attenders, is important during the COVID-19 pandemic

Galactosemia produces ARI-preventable nodal changes similar to those of diabetic neuropathy

The present study was designed to examine the development of structural changes, characteristic of diabetic neuropathy, in chronic galactosemia and their responsiveness to inhibition of the polyol-pathway. Sprague-Dawley rats weighing 70-90 g were given a 50% galactose diet continued for 4 or 8 months. Half of these animals were simultaneously given the aldose reductase inhibitor (ARI) WAY 121-509. ARI-treatment normalized galactitol and myoinositol levels in the sciatic nerve. At 4 months, sciatic nerve conduction velocity (NCV) in galactosemic rats was reduced by 30% which was prevented in ARI-treated rats. At 8 months galactosemia reduced NCV to 58% of control values, while ARI-treatment for 8 months improved NCV to 71% of control values. ARI-treatment prevented in galactosemic rats nodal structural changes characteristic of diabetic neuropathy, whereas axonal atrophy was not affected by ARI-treatment, which may in part account for the only partial prevention of the NCV slowing at 8 months. Nerve fiber regeneration was increased 4-fold in ARI-treated rats compared with untreated galactosemic rats. These data suggest that chronic galactosemia produces a neuropathy structurally similar to diabetic neuropathy. The lack of an ARI-treatment effect on axonal atrophy suggests that this defect is not polyol related in galactosemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31346/1/0000256.pd

Radical-mediated dehydrogenation of bile acids by means of hydrogen atom transfer to triplet carbonyls

The aim of the present paper is to explore the potential of radical-mediated dehydrogenation of bile salts (BSs), which is reminiscent of the enzymatic action of hydroxysteroid dehydrogenase enzymes (HSDH). The concept has been demonstrated using triplet carbonyls that can be efficiently generated upon selective UVA-excitation. Hydrogen atom transfer (HAT) from BSs to triplet benzophenone (BP) derivatives gave rise to radicals, ultimately leading to reduction of the BP chromophore with concomitant formation of the oxo-analogs of the corresponding BSs. The direct reactivity of triplet BP with BSs in the initial step was evaluated by determining the kinetic rate constants using laser flash photolysis (LFP). The BP triplet decay was monitored (lambda(max) = 520 nm) upon addition of increasing BS concentrations, and the obtained rate constant values indicated a reactivity of the methine hydrogen atoms in the order of C-3 < C-12 < C-7. The steady-state kinetics of the overall process, monitored through the disappearance of the typical BP absorption band at 260 nm, was much faster under N-2 than under O-2, also supporting the role of the oxygen-quenchable triplet in the dehydrogenation process. Furthermore, irradiation of deaerated aqueous solutions of sodium cholate in the presence of KPMe provided the oxo-analogs, 3[O], 7[O]-CA, 3[O]-CA and 7[O]-CA, arising from the HAT process.Financial support from the Spanish Government (Grants SEV-2012-0267 and CTQ2012-38754-C03-03), Generalitat Valenciana (Prometeo Program) and the Technical University of Valencia (Predoctoral FPI fellowship for P. Miro) is gratefully acknowledged.Miró Richart, P.; Marín García, ML.; Miranda Alonso, MÁ. (2016). Radical-mediated dehydrogenation of bile acids by means of hydrogen atom transfer to triplet carbonyls. Organic and Biomolecular Chemistry. 14(9):2679-2683. https://doi.org/10.1039/c5ob02561cS2679268314