Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer

Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylation in vitro and in vivo. Immunofluorescence microscopy and ATAC-See revealed the association of this modification with active chromatin. Brpf1 deletion obliterates the acylation in mouse embryos and fibroblasts. Moreover, we identify BRPF1 variants in 12 previously unidentified cases of syndromic intellectual disability and demonstrate that these cases and known BRPF1 variants impair H3K23 propionylation. Cardiac anomalies are present in a subset of the cases. H3K23 acylation is also impaired by cancer-derived somatic BRPF1 mutations. Valproate, vorinostat, propionate and butyrate promote H3K23 acylation. These results reveal the dual functionality of BRPF1-KAT6 complexes, shed light on mechanisms underlying related developmental disorders and various cancers, and suggest mutation-based therapy for medical conditions with deficient histone acylation

Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer

Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylati

Schwäbisches Kriegskochbuch

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Elm Street community survey : an honors thesis (HONRS 499)

During the Spring and Summer of 2003 a survey was conducted of residents on Elm Street in the Old McKinley Neighborhood, North of Wysor Street and South of the White River. The purpose of the survey was to find the self-reported needs and assets of this community. The composition of this neighborhood is primarily Caucasian and 70% of households make under $30,000 per year. The community reported many assets such as the value of education and the role of religion as well as the availability of public transportation and expressed desire to see change come to the community. Respondents expressed a desire to reduce crime, restore the physical conditions of the neighborhood, build relationships with neighbors, and provide meaningful activities for children.Honors CollegeThesis (B.?.

"Saint Anthony's Sanitarium, Las Vegas, New Mexico"

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The process of politics: a study of the political process leading to the establishment of the Minnesota Center for Arts Education.

University of Minnesota Ph.D. dissertation. Major: Educational Policy and Administration. Advisor: Dr. Neal Nickerson. 1 computer file (PDF); vi, 387 pages, appendices A-O.The purpose of this study was to investigate the political process that resulted in the establishment of the Minnesota Center for Arts Education as a state funded educational policy option. This research identified the interest group actors who initiated the idea and the key actors who guided it through the policy arena, and analyzed the interactions of the participants from the political perspective of actors, goals, motivations, resources, strategies, arenas, critical interactions, and outcomes. This study focused on the executive and legislative arenas in Minnesota government. The study was bounded in time by the initial policy proposal set forth to the members of the Minnesota Alliance for the Arts in Education in 1976, and the final enabling legislation passed in 1989. The research methodology was single case study with qualitative data gathered from interviews with 27 significant informants, archival sources, and the public record. The research found that human agency and personalization of policy were key elements in the policy making process and a constant factor in the dynamic interaction between Governor Perpich and state legislators. The concept of a state financed arts high school originated outside the K-12 policy subsystems and gained crucial support when the Governor attached himself and the resources of his position to the idea in 1984. The findings are significant for proponents of educational reform who believe that education policy options ought to be enacted on the merits of the idea and underestimate the importance of the complex interplay of human behavior: power, motivation, advocacy, executive leadership, and political strategy. This research concluded that the legislation for the Minnesota Center for Arts Education was enacted because of the effective use of resources controlled by the Governor and his staff, and a pragmatic understanding and implementation of political strategies during critical interactions in the legislative arena

Fenfluramine: An Uncommon Cause of False Positive Urine Drug Testing: A Case Report

ABSTRACT Background Fenfluramine is an antiseizure medication approved by the Food and Drug Administration for the treatment of Dravet syndrome in patients older than 2 years. Fenfluramine is an amphetamine derivative. It cross‐reacts with amphetamines in urine drug screen immunoassays. Patient Presentation A 2‐year‐old patient with Dravet syndrome had a cardiorespiratory arrest and tested positive for amphetamines in a urine drug screen, raising concerns of child abuse. Liquid chromatography–mass spectrometry confirmed the presence of fenfluramine but did not detect amphetamines. Conclusion Fenfluramine can result in a false‐positive amphetamine urine drug screen at the recommended dose for Dravet syndrome. Awareness of this potential cross‐reactivity can prevent undue child protective services reports, especially in patients at high risk for sudden death