SIRT1 is a positive regulator of in vivo bone mass and a therapeutic target for osteoporosis

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Overexpression or pharmacological activation of SIRT1 has been shown to extend the lifespan of mice and protect against aging-related diseases. Here we show that pharmacological activation of SIRT1 protects in two models of osteoporosis. Ovariectomized female mice and aged male mice, models for post-menopausal and aging-related osteoporosis, respectively, show significant improvements in bone mass upon treatment with SIRT1 agonist, SRT1720. Further, we find that calorie restriction (CR) results in a two-fold upregulation of sirt1 mRNA expression in bone tissue that is associated with increased bone mass in CR mice. Reciprocally, SIRT1 whole-body knockout (KO) mice, as well as osteoblast and osteoclast specific KOs, show a low bone mass phenotype; though double knockout mice (containing SIRT1 deleted in both osteoblasts and osteoclasts) do not show a more severe phenotype. Altogether, these findings provide strong evidence that SIRT1 is a positive regulator of bone mass and a promising target for the development of novel therapeutics for osteoporosis

Beliefs about the appropriate degree of directiveness in the management relationship, as related to demographic characteristics, educational background, and organizational position

Correlations between beliefs about management and age, gender, nationality, level of education, education field, functional area, and hierarchical level were examined. Analyses were conducted at the ecological level and focused on beliefs regarding appropriate degree of directiveness in the managerial relationship. Two thousand staff members of an international intergovernmental organization received an electronically distributed written survey. Factor analysis was used to develop summated rating scales for each independent variables. Differences between subgroup means were then examined using ANOVA or t tests. The strength of the association between the independent variables and a common scale was assessed using eta squared. Directiveness was found to relate positively to age, and negatively to education level and hierarchical level. More directive, on average, than members of other groups were males, those educated in academic disciplines classified by Biglan as involving single thought paradigms or focusing on nonlife systems (e.g., physical sciences and economics), those in professional functional areas, and those from Japanese, Latin, and Nordic nationality groups. For all independent variables, differences reached high levels of significance (p \u3c .001). Hypotheses regarding the relative strength of association between independent variables and the common scale were not supported. The results suggest that information about subgroup membership can help managers better meet the needs of a diverse staff. The concept of directiveness proved highly effective in predicting outcomes but requires refinement. Further investigation into those independent variables that have not previously been widely investigated and replication of the study in other venues are recommended

Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells

Reductively metabolized glutamine is a major cellular carbon source for fatty acid synthesis during hypoxia or when mitochondrial respiration is impaired. Yet, a mechanistic understanding of what determines reductive metabolism is missing. Here we identify several cellular conditions where the α-ketoglutarate/citrate ratio is changed due to an altered acetyl-CoA to citrate conversion, and demonstrate that reductive glutamine metabolism is initiated in response to perturbations that result in an increase in the α-ketoglutarate/citrate ratio. Thus, targeting reductive glutamine conversion for a therapeutic benefit might require distinct modulations of metabolite concentrations rather than targeting the upstream signalling, which only indirectly affects the process.German Science Foundation (Grant FE1185)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award Postdoctoral Fellowship F32 CA132358)National Institutes of Health (U.S.) (Grant 5-P30-CA14051-39)Damon Runyon Cancer Research FoundationBurroughs Wellcome FundSmith Family FoundationNational Institutes of Health (U.S.) (Grant 1R01CA160458-01A1

Influence of coal composition on the fate of volatile and char nitrogen during combustion

Journal ArticleFifty coals from North America, Europe, Asia, South Africa and Australia were burned in a 21 kW, refractory-lined tunnel furnace to determine the influence of coal properties on the fate of volatile and char nitrogen. Excess air fuel NO emissions (as determined by combustion in Ar/02/C02) ranged from 415 ppm to 1380 ppm with a premixed burner. These results correlated with total fuel nitrogen, inert pyrolysis HCN yield, and non-volatile nitrogen content, rather than with the geographic origin of the coal. Minimum staged NO emissions (at optimum first stage stoichiometry) ranged from 140 ppm to 380 ppm. Detailed in-flame measurements indicated that as first stage stoichiometry (air/fuel) was reduced, first stage NO formation decreased, but was ultimately offset by increases in oxidizable gaseous nitrogen species and solid phase nitrogen retention. TFN (NH3 + NO + HCN) generally increased with increasing fuel nitrogen and the species distribution was dependent upon coal rank. In general, HCN was greater than NH3 with bituminous coals, but less than NH3 with subbituminous and lignite coals. Second stage TFN conversion to exhaust NO decreased as the TFN distribution was shifted in favor of HCN and NH3. Char nitrogen conversion was generally low (less than 20 percent). Exhaust emissions were correlated in terms of the gas phase TFN and the char nitrogen entering the second stage

Bench and pilot scale process evaluation of reburning for in-furnace NOx reduction

Journal ArticleThis paper describes a combined experimental and theoretical study which was undertaken to quantify the impact of fuel and process parameters on reburning effectiveness and provide the scaling information required for commercial application of reburning under highly varied industrial conditions. Initially parametric screening studies were conducted in a 25 KW refractory- lined tunnel furnace. These studies were supported by large scale testing in a 3.0 MW pilot scale facility. The work at both scales focused on the importance and the fate of the reactive nitrogen species within the reburning zone

Literature-based language arts integrated into the social studies area: A unit on Japan for grade three

The process of instructional development was engaged in to extend the literature base of a unit on Japan for third grade. The goal of this process was to provide a rich learning environment and to integrate the curricular areas through the genres of literature. Learning centers as well as teacher-directed sessions were developed. Two types of centers--sustaining and ones specific to the unit--were offered. Sustaining centers assisted in maintaining a secure, predictable environment as well as extending the literature base. The learning centers specific to the unit on Japan focused on many aspects of the Japanese culture and provided many options for literature-based expressive activity

Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism

Metformin inhibits cancer cell proliferation, and epidemiology studies suggest an association with increased survival in patients with cancer taking metformin; however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation, whereas increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer.German Science Foundation (Grant FE1185)National Institutes of Health (U.S.)Glenn Foundation for Medical ResearchNational Institutes of Health (U.S.) (Grant 5-P50-090381-09)National Institutes of Health (U.S.) (Grant 5-P30-CA14051-39)Burroughs Wellcome FundSmith Family FoundationDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.) (Grant 1R01DK075850-01)National Institutes of Health (U.S.) (Grant 1R01CA160458-01A1

Pulverized Coal Combustion: The Influence of Flame Temperature

A laboratory combustor was used to investigate the factors that influence the conversion of fuel nitrogen in coal during coal combustion. Fuel NO was isolated by experimentation utilizing Argon/Oxygen/Carbon Dioxide mixtures as the oxidant, and care was taken to compare cases with air at matched conditions. For both well mixed and slowly mixed flame types, fuel NO contributed over 75% of the total NO emissions for all conditions examined. Fuel NO was insensitive to temperature changes except when the adiabatic flame temperatures were above 2480 0 K (4000°F). At the highest adiabatic flame temperature, 2580 0 K (4200°F), a 10% increase in fuel NO was observed. Four different coals and one coal char were investigated. Fuel NO could not be correlated with fuel nitrogen content alone, even though aerodynamic conditions were kept constant. Fuel nitrogen conversion to NO during pulverized char combustion was 12-16% at a stoichiometric ratio of 1.15 compared to 28% for a pulverized coal of the same nitrogen content. Furthermore, in contrast to the coal results, NO emissions from char combustion were not greatly influenced by changes in injector design. The implication is that although conversion of fuel nitrogen to NO may be relatively low during the char burnout regime of coal combustion, the residual "char NO" may be especially resistant to abatement by modifications of the burner aerodynamics

The Impact of Error-Management Climate, Error Type and Error Originator on Auditors’ Reporting Errors Discovered on Audit Work Papers

We examine factors affecting the auditor’s willingness to report their own or their peers’ self-discovered errors in working papers subsequent to detailed working paper review. Prior research has shown that errors in working papers are detected in the review process; however, such detection rates only rarely exceed 50% of the seeded errors. Hence, measures that encourage auditors to be alert to their own (or their peers’) potential errors any time they revisit the audit working papers may be valuable in detecting such residual errors and potentially correcting them before damage occurs to the audit firm or its client. We hypothesize that three factors affect the auditor’s willingness to report post detailed review discovered errors: the local office error-management climate (open versus blame), the type of error (mechanical versus conceptual) and who committed the error (the individual who committed the error (self) or a peer). Local office error-management climate is said to be open and supportive where errors and mistakes are accepted as part of everyday life as long as they are learned from and not repeated. In alternative, a blame error-management climate focuses on a “get it right the first time” culture where mistakes are not tolerated and blame gets attached to those admitting to or found committing such errors. We find that error-management climate has a significant overall effect on auditor willingness to report errors, as does who committed the error originally. We find both predicted and unpredicted significant interactions among the three factors that qualify these observed significant main effects. We discuss implications for audit practice and further research