Comprehensive DNA methylation profiling in a human cancer genome identifies novel epigenetic targets

Using a unique microarray platform for cytosine methylation profiling, the DNA methylation landscape of the human genome was monitored at more than 21,000 sites, including 79% of the annotated transcriptional start sites (TSS). Analysis of an oligodendroglioma derived cell line LN-18 revealed more than 4000 methylated TSS. The gene-centric analysis indicated a complex pattern of DNA methylation exists along each autosome, with a trend of increasing density approaching the telomeres. Remarkably, 2% of CpG islands (CGI) were densely methylated, and 17% had significant levels of 5 mC, whether or not they corresponded to a TSS. Substantial independent verification, obtained from 95 loci, suggested that this approach is capable of large scale detection of cytosine methylation with an accuracy approaching 90%. In addition, we detected large genomic domains that are also susceptible to DNA methylation reinforced inactivation, such as the HOX cluster on chromosome 7 (CH7). Extrapolation from the data suggests that more than 2000 genomic loci may be susceptible to methylation and associated inactivation, and most have yet to be identified. Finally, we report six new targets of epigenetic inactivation (IRX3, WNT10A, WNT6, RARalpha, BMP7 and ZGPAT). These targets displayed cell line and tumor specific differential methylation when compared with normal brain samples, suggesting they may have utility as biomarkers. Uniquely, hypermethylation of the CGI within an IRX3 exon was correlated with over-expression of IRX3 in tumor tissues and cell lines relative to normal brain samples

Decellularization reduces the immune response to aortic valve allografts in the rat

ObjectivesCryopreserved valve allografts used in congenital cardiac surgery are associated with a significant cellular and humoral immune response. This might be reduced by removal of antigenic cellular elements (decellularization). The aim of this study was to determine the immunologic effect of decellularization in a rat allograft valve model.MethodsBrown Norway and Lewis rat aortic valves were decellularized with a series of hypotonic and hypertonic buffers, protease inhibitors, gentle detergents (Triton X-100), and phosphate-buffered saline. Valves were implanted into Lewis rats in syngeneic and allogeneic combinations. Cellular (CD3 and CD8) infiltrates were assessed with morphometric analysis, and the humoral response was assessed with flow cytometry.ResultsMorphometric analysis identified a significant reduction in CD3+ cell infiltrates (cells per square millimeter of leaflet tissue) in decellularized allografts compared with that seen in nondecellularized allografts at 1 (79 ± 29 vs 3310 ± 223, P < .001), 2 (26 ± 11 vs 109 ± 20, P = .004), and 4 weeks (283 ± 122 vs 984 ± 145, P < .001). Anti-CD8 staining confirmed the majority of infiltrates were cytotoxic T cells. Flow cytometric mean channel fluorescence intensity identified a negative shift (abrogated antibody formation) for decellularized allografts compared with nondecellularized allografts at 2 (19 ± 1 vs 27 ± 3, P = .033), 4 (35 ± 2 vs 133 ± 29, P = .001), and 16 weeks (28 ± 2 vs 166 ± 54, P = .017).ConclusionsDecellularization significantly reduces the cellular and humoral immune response to allograft tissue. This could prolong the durability of valve allografts and might prevent immunologic sensitization of allograft recipients

An accurate in vitro model of the E. coli envelope

Gram-negative bacteria are an increasingly serious source of antibiotic-resistant infections, partly owing to their characteristic protective envelope. This complex, 20 nm thick barrier includes a highly impermeable, asymmetric bilayer outer membrane (OM), which plays a pivotal role in resisting antibacterial chemotherapy. Nevertheless, the OM molecular structure and its dynamics are poorly understood because the structure is difficult to recreate or study in vitro. The successful formation and characterization of a fully asymmetric model envelope using Langmuir-Blodgett and Langmuir-Schaefer methods is now reported. Neutron reflectivity and isotopic labeling confirmed the expected structure and asymmetry and showed that experiments with antibacterial proteins reproduced published in vivo behavior. By closely recreating natural OM behavior, this model provides a much needed robust system for antibiotic development

The effects of perceived and received support on objective performance outcome.

This is a postprint of an article published in European Journal of Sport Science, 2008, Vol. 8, Issue 6, pp. 359 – 368 © 2008 copyright Taylor & Francis. European Journal of Sport Science is available online at: http://www.tandfonline.com/loi/tejs20In this study, we examined the main and stress-buffering effects of perceived and received support upon objective performance outcome. The sample consisted of 123 male British high performance golfers, mean age 25.3 years (SD = 5.4). Participants completed measures of perceived support, stressors, stress, and received support before competitions. After the competitions, performance outcome (number of shots) was recorded. When both types of support were considered separately, there were significant main effects for perceived (ΔR2 = .08, b = -.81, p < .01) and received support (ΔR2 = .05, b = -.68, p < .01) on performance. There were also significant stress-buffering effects for perceived (ΔR2 = .03, b = -.48, p = .02) and received support (ΔR2 = .06, b = -.61, p < .01). When both types of support were considered simultaneously, the significant main effect (DR2 = .09, p < .01) was primarily attributable to perceived support (b = -.63, p = .02). The significant stress-buffering effect (DR2 = .06, p = .01) was primarily attributable to received support (b = -.56, p = .04). These results demonstrate the beneficial influence of social support on performance. The findings highlight the need to recognise the distinction between perceived and received support, both in terms of theory and the design of social support interventions with athletes

Comparison of selected foreign plans and practices for spent fuel and high-level waste management

This report describes the major parameters for management of spent nuclear fuel and high-level radioactive wastes in selected foreign countries as of December 1989 and compares them with those in the United States. The foreign countries included in this study are Belgium, Canada, France, the Federal Republic of Germany, Japan, Sweden, Switzerland, and the United Kingdom. All the countries are planning for disposal of spent fuel and/or high-level wastes in deep geologic repositories. Most countries (except Canada and Sweden) plan to reprocess their spent fuel and vitrify the resultant high-level liquid wastes; in comparison, the US plans direct disposal of spent fuel. The US is planning to use a container for spent fuel as the primary engineered barrier. The US has the most developed repository concept and has one of the earliest scheduled repository startup dates. The repository environment presently being considered in the US is unique, being located in tuff above the water table. The US also has the most prescriptive regulations and performance requirements for the repository system and its components. 135 refs., 8 tabs

Comparison of Selected Foreign Plans and Practices for Spent Fuel and High-Level Waste Management

This report describes the major parameters for management of spent nuclear fuel and high-level radioactive wastes in selected foreign countries as of December 1989 and compares them with those in the United States. The foreign countries included in this study are Belgium, Canada, France, the Federal Republic of Germany, Japan, Sweden, Switzerland, and the United Kingdom. All the countries are planning for disposal of spent fuel and/or high-level wastes in deep geologic repositories. Most countries (except Canada and Sweden) plan to reprocess their spent fuel and vitrify the resultant high-level liquid wastes; in comparison, the US plans direct disposal of spent fuel. The US is planning to use a container for spent fuel as the primary engineered barrier. The US has the most developed repository concept and has one of the earliest scheduled repository startup dates. The repository environment presently being considered in the US is unique, being located in tuff above the water table. The US also has the most prescriptive regulations and performance requirements for the repository system and its components. 135 refs., 8 tabs

Calculus Volume 2

Calculus is designed for the typical two- or three-semester general calculus course, incorporating innovative features to enhance student learning. The book guides students through the core concepts of calculus and helps them understand how those concepts apply to their lives and the world around them. Due to the comprehensive nature of the material, we are offering the book in three volumes for flexibility and efficiency. Volume 2 covers integration, differential equations, sequences and series, and parametric equations and polar coordinates.https://commons.erau.edu/oer-textbook/1001/thumbnail.jp

Antibody Duration after infection From Sars-Cov-2 in the Texas Coronavirus antibody Response Survey

Understanding the duration of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes COVID-19 is important to controlling the current pandemic. Participants from the Texas Coronavirus Antibody Response Survey (Texas CARES) with at least 1 nucleocapsid protein antibody test were selected for a longitudinal analysis of antibody duration. A linear mixed model was fit to data from participants (n = 4553) with 1 to 3 antibody tests over 11 months (1 October 2020 to 16 September 2021), and models fit showed that expected antibody response after COVID-19 infection robustly increases for 100 days postinfection, and predicts individuals may remain antibody positive from natural infection beyond 500 days depending on age, body mass index, smoking or vaping use, and disease severity (hospitalized or not; symptomatic or not)

How Does Perceived Support Lead to Better Performance? An Examination of Potential Mechanisms

This is a postprint of an article published in Journal of Applied Sport Psychology, 2009, Vol. 21, pp. 421 – 429 © 2009 copyright Taylor & Francis. Journal of Applied Sport Psychology is available online at: http://www.tandfonline.com/toc/uasp20/currentUsing a high-performance sample of 118 golfers, we examined the relationship between perceived support and performance. Observed variable path analysis revealed that the beneficial effects of perceived support were primarily attributable to esteem support. High levels of esteem support were associated with appraising a competition as less of a threat. Esteem support was also positively associated with situational control, which was positively associated with challenge appraisals and negatively associated with threat appraisals. Challenge appraisals were associated with better performance and threat appraisals with poorer performance. These results highlight possible mechanisms underlying the relationship between esteem support and performance