Leadership-Focused Coaching in Action: An Approach to Continuous Improvement and Supporting Public Schools

This article details the efforts of one program’s collaborative efforts toward continuous improvement and strengthening partnerships with local school districts using Leadership-Focused Coaching, a research-based model for principal preparation programs. Practical experiences and lessons learned from the ongoing online program improvement and redesign initiative are shared. In advance of two accreditation visits, data and feedback were gathered from partner districts, recent graduates, current students, and employers, which helped to identify ways in which the program could better prepare instructional leaders. This article describes the efforts, successes, setbacks, and future plans of a group of professors working to improve a program while preparing for accreditation visits and strengthening district partnerships. Résumé Cet article détaille les efforts d’un programme spécifique de collaboration afin d’assurer une amélioration continue et un renforcement des partenariats avec des districts scolaires locaux au moyen du Leadership-Focused Coaching (coaching axé sur le leadership), lequel est un modèle basé sur la recherche pour les programmes visant à mieux former les directeurs d'école. Cet article partage les expériences et les leçons pratiques tirées d’une initiative en cours qui consiste à améliorer et reconcevoir le programme en ligne dont il est question dans l’article. Avant deux visites d'accréditation, des données et des commentaires ont été recueillis auprès de districts partenaires, de diplômés récents, d’étudiants actuels et d’employeurs, ce qui a permis d’identifier les moyens par lesquels le programme pourrait mieux préparer les leaders pédagogiques. En somme, cet article décrit les efforts, les succès, les revers et les projets d'un groupe de professeurs travaillant à l'amélioration d’un programme tout en se préparant aux visites d’accréditation et en renforçant les partenariats avec les districts. Keywords / Mots clés : leadership preparation, university-school partnerships, leadership field experience, leadership-focused coaching, leadership mentoring / préparation au leadership, partenariats université-école, expérience de terrain en matière de leadership, coaching axé sur le leadership, mentorat en matière de leadershi

Taking Responsibility to Create a Trauma and Social Justice-Informed Workforce

This conceptual paper describes the efforts to address curriculum deficits related to the preparation of graduates across multiple service fields for their work in high-poverty communities. Faculty members from various programs jointly facilitated a high-impact simulation designed to ascertain its impact on students’ perceptions and personal biases toward disadvantaged community members. This mixed methods study used Yun and Weaver’s (2010) Short Form of the Attitude Toward Poverty Scale, as well as focus groups. Quantitative data indicated that participants held more positive attitudes towards individuals struggling with poverty after completing the simulation. The overarching themes concerning college students’ attitudes about poverty indicated paradigm shifts in their personal thinking and professional behavior in the workforce, as well as empathy regarding the cycle of poverty and the extremely hard decisions that are necessary when experiencing poverty. These findings are important for facilitating learning about the social injustices that can ensue from poverty. The study comes at a time of a pandemic when online learning is at its height and poverty is intensifying

High-resolution simulations of chromatin folding at genomic rearrangements in malignant B cells provide mechanistic insights into proto-oncogene deregulation

Genomic rearrangements are known to result in proto-oncogene deregulation in many cancers, but the link to 3D genome structure remains poorly understood. Here, we used the highly predictive heteromorphic polymer (HiP-HoP) model to predict chromatin conformations at the proto-oncogene CCND1 in healthy and malignant B cells. After confirming that the model gives good predictions of Hi-C data for the nonmalignant human B cell–derived cell line GM12878, we generated predictions for two cancer cell lines, U266 and Z-138. These possess genome rearrangements involving CCND1 and the immunoglobulin heavy locus (IGH), which we mapped using targeted genome sequencing. Our simulations showed that a rearrangement in U266 cells where a single IGH super-enhancer is inserted next to CCND1 leaves the local topologically associated domain (TAD) structure intact. We also observed extensive changes in enhancer-promoter interactions within the TAD, suggesting that it is the downstream chromatin remodeling which gives rise to the oncogene activation, rather than the presence of the inserted super-enhancer DNA sequence per se. Simulations of the IGH-CCND1 reciprocal translocation in Z-138 cells revealed that an oncogenic fusion TAD is created, encompassing CCND1 and the IGH super-enhancers. We predicted how the structure and expression of CCND1 changes in these different cell lines, validating this using qPCR and fluorescence in situ hybridization microscopy. Our work demonstrates the power of polymer simulations to predict differences in chromatin interactions and gene expression for different translocation breakpoints

Evolutionary fitness as a function of pubertal age in 22 subsistence-based traditional societies

<p>Abstract</p> <p>Context</p> <p>The age of puberty has fallen over the past 130 years in industrialized, western countries, and this fall is widely referred to as the secular trend for earlier puberty. The current study was undertaken to test two evolutionary theories: (a) the reproductive system maximizes the number of offspring in response to positive environmental cues in terms of energy balance, and (b) early puberty is a trade-off response for high mortality rate and reduced resource availability.</p> <p>Methods</p> <p>Using a sample of 22 natural-fertility societies of mostly tropical foragers, horticulturalists, and pastoralists from Africa, South America, Australia, and Southeastern Asia, this study compares indices of adolescence growth and menarche with those of fertility fitness in these non-industrial, traditional societies.</p> <p>Results</p> <p>The average age at menarche correlated with the first reproduction, but did not correlate with the total fertility rate TFR or reproductive fitness. The age at menarche correlated negatively with their average adult body mass, and the average adult body weight positively correlated with reproductive fitness. Survivorship did not correlate with the age at menarche or age indices of the adolescent growth spurt. The population density correlated positively with the age at first reproduction, but not with menarche age, TFR, or reproductive fitness.</p> <p>Conclusions</p> <p>Based on our analyses, we reject the working hypotheses that reproductive fitness is enhanced in societies with early puberty or that early menarche is an adaptive response to greater mortality risk. Whereas body mass is a measure of resources is tightly associated with fitness, the age of menarche is not.</p

Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers

Chromosomal translocations are important drivers of hematological malignancies whereby proto-oncogenes are activated by juxtaposition with super-enhancers, often called enhancer hijacking. We analysed the epigenomic consequences of rearrangements between the super-enhancers of the immunoglobulin heavy locus (IGH) and proto-oncogene CCND1 that are common in B cell malignancies. By integrating BLUEPRINT epigenomic data with DNA breakpoint detection, we characterised the normal chromatin landscape of the human IGH locus and its dynamics after pathological genomic rearrangement. We detected an H3K4me3 broad domain (BD) within the IGH locus of healthy B cells that was absent in samples with IGH-CCND1 translocations. The appearance of H3K4me3-BD over CCND1 in the latter was associated with overexpression and extensive chromatin accessibility of its gene body. We observed similar cancer-specific H3K4me3-BDs associated with super-enhancer hijacking of other common oncogenes in B cell (MAF, MYC and FGFR3/NSD2) and in T-cell malignancies (LMO2, TLX3 and TAL1). Our analysis suggests that H3K4me3-BDs can be created by super-enhancers and supports the new concept of epigenomic translocation, where the relocation of H3K4me3-BDs from cell identity genes to oncogenes accompanies the translocation of super-enhancers

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk