Transactivational activity of the tumor suppressor protein p53 is dependent on thioredoxin reductase activity in mammalian cells

Reporter gene transactivation by human p53 is inhibited in budding yeast lacking the TRR1 gene encoding thioredoxin reductase. Thioredoxin reductase specifically catalyzes the NADPH-dependent reduction of thioredoxin. Thioredoxin provides a source of electrons for disulfide reduction in various cellular processes. Reduction of disulfides within the cell can be accomplished by the separate but partially overlapping glutathione reductase - glutathione - glutaredoxin pathway. The basis for p53 inhibition was investigated by measuring the redox state of thioredoxin and glutathione in wild-type and Δtrr1 yeast lacking the gene encoding thioredoxin reductase. The Δtrr1 mutation caused an increased in oxidation in both molecules. Highcopy expression of the GLR1 gene encoding glutathione reductase in Δtrr1 yeast restored the redox state of glutathione to wild-type levels, but did not restore p53 activity. Also, p53 activity was unaffected by be a Δglr1 mutation, even though the mutation was known to result in glutathione oxidation. These results indicate that p53 activity has a specific requirement for an intact thioredoxin system, rather than a general dependence on the intracellular reducing environment. In order to test if p53 activity requires an intact thioredoxin system in mammalian cells, dominant-negative and RNAi approaches designed to suppress thioredoxin reductase activity were used in a breast adenocarcinoma cell which contains an endogenous wild-type p53. In cells stably transformed with a plasmid encoding a dominant-negative form of thioredoxin reductase, thioredoxin reductase activity was inhibited 4.3-fold and p53 reporter gene expression was inhibited by 2-fold. In cells stably transformed with a RNAi plasmid designed to target thioredoxin reductase mRNA, thioredoxin reductase activity was inhibited by 1.7-fold and p53 reporter gene expression was inhibited by 1.6-fold. A decrease in the protein levels of the p53 endogenous target genes p21 and Bax was also observed in both dominant-negative and RNAi transformants. Additionally, thioredoxin was shown to bind p53 in vitro (Kd=0.9 μM), and a LexA-thioredoxin fusion protein was shown to bind p53 in vivo. These results suggest that p53 activity is regulated by thioredoxin reductase in mammalian cells through a direct interaction with thioredoxin

Estimating carbon stock change in agroforestry and family forestry practices

Paper presented at the 11th North American Agroforesty Conference, which was held May 31-June 3, 2009 in Columbia, Missouri.In Gold, M.A. and M.M. Hall, eds. Agroforestry Comes of Age: Putting Science into Practice. Proceedings, 11th North American Agroforestry Conference, Columbia, Mo., May 31-June 3, 2009.The Carbon Management Evaluation Tool for Voluntary Reporting (COMET-VR) is an online tool that estimates short-term carbon stock (CS) changes under different farm or forest land management systems, including temperate agroforestry practices. It was developed by the USDA Natural Resources Conservation Service in conjunction with Colorado State University. The intended audience includes private farm and forest landowners, NRCS field staff, and technical service providers. Through the online interface, users identify their location, parcel size, surface soil texture, crop rotation history and tillage intensity. The user can choose either of two methods to estimate CS change for their agroforestry practice: 1) for new or future plantings, by using standard prescriptions common to their geographic region, or 2) for a more accurate estimate of an existing planting, by using a summary of live-tree stand inventory data collected from their parcel. Above and below-ground individual tree biomass is calculated using diameter-based allometric equations generalized for tree genera groups. For existing agroforestry plantings, growth estimates are based on empirical models developed from forest inventory data specific to species and region. For new or future plantings, growth estimates were derived for standard agroforestry prescriptions using the Forest Vegetation Simulator. COMET-VR uses the Century soil carbon model to estimate CS change in soil. The output of the tool is a report estimating CS changes over the forthcoming 10 years in the above and below-ground portions of live trees and in the soil. Although specifically designed to meet the requirements of the US Dept. of Energy voluntary greenhouse gas reporting program, COMET-VR may also be applicable to other private and public sector carbon offset programs.Miles L. Merwin (1), Mark Easter (2), Lyn R. Townsend (1), Roel C. Vining (1) and Greg L. Johnson (1) ; 1. USDA Natural Resources Conservation Service, 1201 NE Lloyd Blvd., Portland, OR 97232. 2. Natural Resource Ecology Laboratory, Colorado State University, Ft. Collins, CO.Includes bibliographical references

Retrofit Installation Of A Boiler Feed Pump Hydraulic Coupling.

LecturePg. 101-110The application of main turbine-generator shaft drive for boiler feed pumps is generally accepted as a method to increase unit efficiency. The use of shaft drive eliminates the power requirement of an auxiliary motor or turbine drives. The addition of variable speed to this shaft drive provides economic advantages at lower unit loads. During the installation of any equipment, it is necessary to pay particular attention to all facets of the design. It is especially important when dealing with an operating facility for which many design details are not readily available. A case history of a utility's experience in installing variable speed hydraulic couplings for main boiler feed pump drive service is presented

Self-reported interoceptive deficits in eating disorders: A meta-analysis of studies using the eating disorder inventory

This document is the Accepted Manuscript version of the following article: Paul M. Jenkinson, Lauren Taylor, Keith R. Laws, ‘Self-reported interoceptive deficits in eating disorders: A meta-analysis of studies using the eating disorder inventory’, Journal of Psychosomatic Research, Vol. 110: 38-45, July 2018, under embargo until 19 April 2019. The Version of Record is available online at DOI: https://doi.org/10.1016/j.jpsychores.2018.04.005Objective: An impairment of the ability to sense the physiological condition of the body – interoception – has long been proposed as central to the onset and maintenance of eating disorders. More recent attention to this topic has generally indicated the presence of interoceptive deficits in individuals with an eating disorder diagnosis; however, possible links with specific diagnosis, BMI, age, illness duration, depression, and alexithymia remain unclear from individual studies. This meta-analysis aimed to provide a necessary quantitative overview of self-reported interoceptive deficits in eating disorder populations, and the relationship between these deficits and the previously mentioned factors. Methods: Using a random effects model, our meta-analysis assessed the magnitude of differences in interoceptive abilities as measured using the Eating Disorder Inventory in 41 samples comparing people with eating disorders (n=4308) and healthy controls (n=3459). Follow-up and moderator analysis was conducted, using group comparisons and meta-regressions. Results: We report a large pooled effect size of 1.62 for eating disorders with some variation between diagnostic groups. Further moderator analysis showed that BMI, age and alexithymia were significant predictors of overall effect size. Conclusion: This meta-analysis is the first to confirm that large interoceptive deficits occur in a variety of eating disorders and crucially, in those who have recovered. These deficits may be useful in identifying and distinguishing eating disorders. Future research needs to consider both objective and subjective measures of interoception across different types of eating disorders and may fruitfully examine interoception as a possible endophenotype and target for treatment.Peer reviewe

Report of the ACBS Task Force on the Strategies and Tactics of Contextual Behavioral Science Research

Throughout its history the strategy and tactics of contextual behavioral science (CBS) research have had distinctive features as compared to traditional behavioral science approaches. Continued progress in CBS research can be facilitated by greater clarity about how its strategy and tactics can be brought to bear on current challenges. The present white paper is the result of a 2 1/2-year long process designed to foster consensus among representative producers and consumers of CBS research about the best strategic pathway forward. The Task Force agreed that CBS research should be multilevel, process-based, multidimensional, prosocial, and pragmatic, and provided 33 recommendations to the CBS community arranged across these characteristics. In effect, this report provides a detailed research agenda designed to maximize the impact of CBS as a field. Scientists and practitioners are encouraged to mount this ambitious agenda

Perception of affect in biological motion cues in anorexia nervosa

Nonverbal motion cues (a clenched fist) convey essential information about the intentions of the actor. Individuals with anorexia nervosa (AN) have demonstrated impairment in deciphering intention from facial affective cues but it is unknown whether such deficits extend to deciphering affect from body motion cues

'Correction:' Serum transforming growth factor beta-1 (TGF-beta-1) levels in diabetic patients are not associated with pre-existent coronary artery disease

<p>Abstract</p> <p>Background</p> <p>The association between TGF-β1 levels and long-term major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD) is controversial. No study specifically addressed patients with CAD and diabetes mellitus (DM). The association between TGF-β1 levels and long-term major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD) is controversial. No study specifically addressed patients with CAD and diabetes mellitus (DM).</p> <p>Methods</p> <p>Patients (n = 135, 30–80 years) referred for coronary angiography were submitted to clinical and laboratory evaluation, and the coronary angiograms were evaluated by two operators blinded to clinical characteristics. CAD was defined as the presence of a 70% stenosis in one major coronary artery, and DM was characterized as a fasting glycemia > 126 mg/dl or known diabetics (personal history of diabetes or previous use of anti-hyperglycemic drugs or insulin). Based on these criteria, study patients were classified into four groups: no DM and no CAD (controls, C n = 61), DM without CAD (D n = 23), CAD without DM (C-CAD n = 28), and CAD with DM (D-CAD n = 23). Baseline differences between the 4 groups were evaluated by the χ²test for trend (categorical variables) and by ANOVA (continuous variables, post-hoc Tukey). Patients were then followed-up during two years for the occurrence of MACE (cardiac death, stroke, myocardial infarction or myocardial revascularization). The association of candidate variables with the occurrence of 2-year MACE was assessed by univariate analysis.</p> <p>Results</p> <p>The mean age was 58.2 ± 0.9 years, and 51% were men. Patients with CAD had a higher mean age (p = 0.011) and a higher percentage were male (p = 0.040). There were no significant baseline differences between the 4 groups regarding hypertension, smoking status, blood pressure levels, lipid levels or inflammatory markers. TGF-β1 was similar between patients with or without CAD or DM (35.1 ×/÷ 1.3, 33.6 ×/÷ 1.6, 33.9 ×/÷ 1.4 and 31.8 ×/÷ 1.4 ng/ml in C, D, C-CAD and D-CAD, respectively, p = 0.547). In the 2-year follow-ip, independent predictors of 2-year MACE were age (p = 0.007), C-reactive protein (p = 0.048) and systolic blood pressure (p = 0.008), but not TGF-β1.</p> <p>Conclusion</p> <p>Serum TGF-β1 was not associated with CAD or MACE occurrence in patients with or without DM.</p

Patterns of psychological responses among the public during the early phase of COVID-19: A cross-regional analysis

This study aimed to compare the mediation of psychological flexibility, prosociality and coping in the impacts of illness perceptions toward COVID-19 on mental health among seven regions. Convenience sampled online survey was conducted between April and June 2020 from 9130 citizens in 21 countries. Illness perceptions toward COVID-19, psychological flexibility, prosociality, coping and mental health, socio-demographics, lockdown-related variables and COVID-19 status were assessed. Results showed that psychological flexibility was the only significant mediator in the relationship between illness perceptions toward COVID-19 and mental health across all regions (all ps = 0.001–0.021). Seeking social support was the significant mediator across subgroups (all ps range = <0.001–0.005) except from the Hong Kong sample (p = 0.06) and the North and South American sample (p = 0.53). No mediation was found for problem-solving (except from the Northern European sample, p = 0.009). Prosociality was the significant mediator in the Hong Kong sample (p =0.016) and the Eastern European sample (p = 0.008). These findings indicate that fostering psychological flexibility may help to mitigate the adverse mental impacts of COVID-19 across regions. Roles of seeking social support, problem-solving and prosociality vary across regions. © 2021 by the authors. Licensee MDPI, Basel, Switzerland