Evolutionary and biomedical insights from the rhesus macaque genome

The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species

NO Dioxygenase Activity in Hemoglobins Is Ubiquitous In Vitro, but Limited by Reduction In Vivo

Genomics has produced hundreds of new hemoglobin sequences with examples in nearly every living organism. Structural and biochemical characterizations of many recombinant proteins reveal reactions, like oxygen binding and NO dioxygenation, that appear general to the hemoglobin superfamily regardless of whether they are related to physiological function. Despite considerable attention to “hexacoordinate” hemoglobins, which are found in nearly every plant and animal, no clear physiological role(s) has been assigned to them in any species. One popular and relevant hypothesis for their function is protection against NO. Here we have tested a comprehensive representation of hexacoordinate hemoglobins from plants (rice hemoglobin), animals (neuroglobin and cytoglobin), and bacteria (Synechocystis hemoglobin) for their abilities to scavenge NO compared to myoglobin. Our experiments include in vitro comparisons of NO dioxygenation, ferric NO binding, NO-induced reduction, NO scavenging with an artificial reduction system, and the ability to substitute for a known NO scavenger (flavohemoglobin) in E. coli. We conclude that none of these tests reveal any distinguishing predisposition toward a role in NO scavenging for the hxHbs, but that any hemoglobin could likely serve this role in the presence of a mechanism for heme iron re-reduction. Hence, future research to test the role of Hbs in NO scavenging would benefit more from the identification of cognate reductases than from in vitro analysis of NO and O2 binding

Expanded encyclopaedias of DNA elements in the human and mouse genomes

All data are available on the ENCODE data portal: www.encodeproject. org. All code is available on GitHub from the links provided in the methods section. Code related to the Registry of cCREs can be found at https:// github.com/weng-lab/ENCODE-cCREs. Code related to SCREEN can be found at https://github.com/weng-lab/SCREEN.© The Author(s) 2020. The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.This work was supported by grants from the NIH under U01HG007019, U01HG007033, U01HG007036, U01HG007037, U41HG006992, U41HG006993, U41HG006994, U41HG006995, U41HG006996, U41HG006997, U41HG006998, U41HG006999, U41HG007000, U41HG007001, U41HG007002, U41HG007003, U54HG006991, U54HG006997, U54HG006998, U54HG007004, U54HG007005, U54HG007010 and UM1HG009442

Conceptualizations of occupation in relation to health: A conversation between theory and experience-near data

Current occupational science theory describes a positive link between occupation and human health. This theory asserts that an essential unit of analysis for understanding health is in every-day human actions (Wilcock, 2006). Indeed, extant literature has identified occupation as a powerful facilitator of health and wellbeing. Consequently, basic theory in occupational science has favored positive implications for health based on engagement in occupations. However, experience-near accounts reveal that engaging in occupation has both positive and negative implications. Recent scholarship in occupational science has recognized this conflict and asserts that further understanding of the occupation-health link is necessary (Durocher, Rappolt, & Gibson, 2014). This panel will advance the discussion between experience-near accounts and basic theory by employing case examples from interdisciplinary research. Presentation #1 will frame the discourse by providing a conceptual map (Feyerabend, 2011) of how occupational science has described the relationship between occupation and health, and identify opportunities for theoretical expansion. We will argue for adopting a dialectic perspective on the occupation-health link. To illustrate the need for expanded theory, a case example will be given employing data from a large mixed-methods ethnographic study (‘Autism in urban context: linking heterogeneity with health and service disparities’, NIMH, R01MH089474, 09/30/2009 - 08/31/2012, Solomon, O., P.I.). These data capture the experiences of a child with ASD and his family related to ways in which his medical and developmental conditions make participation in physical play both transformative and detrimental. Presentation #2 extends this dialogue to the clinical care setting by challenging notions of the health-promoting effects of healthcare providers’ recommendations within chronic disease management. This presenter will provide one exemplar case from a study on diabetes as a lens into the experiences of making agentic choices between maintaining the intensive requirements of diabetes management and engaging in developmentally normative, though potentially risky activities. These choices are further examined using theoretical tools from medical sociology and anthropology combined with concepts introduced within occupational science literature. Presentation #3 will describe the activities of a Latino gang. Drawing from a transactionalism framework and understanding the interrelatedness of contextual conditions to occupation (Dickie, Cutchin & Humphry, 2006). The presenter will discuss the affordances and constraints typical of a gang-inhabited neighborhood, and evaluate both the positive and negative health-related aspects of gangs. Additional excerpts from memoirs and first-hand accounts of former gang members (Rodriguez, 2005) will be analyzed to describe the occupational activities of gangs from a participant perspective. This presentation will critically appraise the limitations of a health-promoting view of occupation by framing culturally grounded information as necessary when describing possible impacts on health. As these presentations will illustrate, occupations lead to flourishing for some aspects of health, but may also lead to some negative impact. The panel will demonstrate the importance of including both the positive and the negative impact into conceptualizations of occupation to better understand how it is linked to human health, wellness and participation. Key Words: Health Promotion, Critical Occupational Science, Experience-Near Research Presenter information Mark E. Hardison, MS, OTR/L¹ Kristine M. Carandang, MS, OTR/L¹ Lucía I. Floríndez, MA¹ Elizabeth A. Pyatak, PhD, OTR/L, CDE² Olga Solomon, PhD² Ruth Zemke, PhD, OTR(Retired), FAOTA³ 1 = Presenter and author, 2 = Author only, 3 = Moderator Affiliation University of Southern California, Mrs. T. H. Chan Division of Occupational Science and Occupational Therapy Acknowledgements Autism in Urban Context: Linking Heterogeneity with Health and Service Disparities (NIMH, R01 MH089474, 2009-2012, O. Solomon, P.I.) Objectives for the Discussion Period 1. Participants will ask questions of the panel to clarify or expand the presentation. 2. Participants will share other experiential examples critically appraising the health-promoting view of occupation. 3. Participants and panel members will explore reconciliation of these observations with basic theory of occupation

Expanded encyclopaedias of DNA elements in the human and mouse genomes

The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE(1) and Roadmap Epigenomics(2) data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes

Using Patient Experiences of Health Management Occupations to Guide Research on Medical Adherence

Title: Using Patient Experiences of Health Management Occupations to Guide Research on Medical Adherence Topic: Examining the construct of medical adherence through the lens of occupational science Purpose/Aims: Adherence originates from medical science literature and is a revision of the earlier concept of compliance. Modern conceptualization of adherence integrates feedback from patients and expands the patient’s role in directing care. Yet still, medical advice is privileged above patient perspectives maintaining providers in the role of expert. Little is known about how patients’ lived experiences of adherence fit within their occupational experience of health management. In this panel, we will explore the dialogue between the medical perspective of adherence and the lived occupational experiences of patients seeking to heal from an injury or manage a chronic disease. Presentation #1 Methods: Using a review of the literature, Presenter 1 compares the constructs of adherence, compliance, patient-provider communication, and partnership. Result: Evidence in this area remains sparse. We argue that the transactionalism (Cutchin & Dickie, 2012) framework within occupational science is poised to assist in improving patient and provider relationships, and support the occupation of health management through research. Presentation #2 Methods: Presenter 2 reports on emergent qualitative findings from a multi-phase, mixed methods study that explored the impact of rheumatic disease on young adults’ occupational engagement. Young adults (n=12) were individually interviewed using a semi-structured guide. Based on iterative analysis, three participants were then purposively recruited to each complete a series of four additional follow-up narrative interviews. Result: Data revealed diverse experiences when young adults collaborated with rheumatologists to find tailored medication regimens while also exploring strategies to maintain a normal life. Presentation #3 Methods: A mixed-methods, case series was completed with 16 patients receiving care at an outpatient hand therapy clinic. Qualitative data was collected via individual, semi-structured interviews across the patients’ episodes of care, and quantitative survey data was collected after each therapy visit. Result: Quantitative data revealed that therapists rated patients as highly adherent and engaged with little variation. However, patients’ perspectives revealed disparate amounts of engagement in therapy because of the interaction between home life and assigned home exercise. Argument/Importance to Occupational Science: Experience-near accounts of patients provide a contextualized perspective of medical treatment. This reveals how adherence fits as a component of the occupation of health management, and expands current understandings of adherence in order to support patients in future applied occupational science research. (397 Words) Key Words: Transactionalism, Health Management Occupations, Adherence, Engagement Objectives for Discussion: Does the current literature as discussed in presentation 1 on adherence accurately describe the construct as patients experience it as seen in presentations 2 and 3? How so? How do the results of presentation 2 and 3 fit with or contradict frameworks in Occupational Science (e.g. Transactionalism, Systems Theory)? What is the opportunity for applied Occupational Science in reframing the medical research on adherence? What are the next steps with this line of work (e.g., development of a model, development of outcome measures for engagement or adherence)

Perspectives on ENCODE.

The Encylopedia of DNA Elements (ENCODE) Project launched in 2003 with the long-term goal of developing a comprehensive map of functional elements in the human genome. These included genes, biochemical regions associated with gene regulation (for example, transcription factor binding sites, open chromatin, and histone marks) and transcript isoforms. The marks serve as sites for candidate cis-regulatory elements (cCREs) that may serve functional roles in regulating gene expression1. The project has been extended to model organisms, particularly the mouse. In the third phase of ENCODE, nearly a million and more than 300,000 cCRE annotations have been generated for human and mouse, respectively, and these have provided a valuable resource for the scientific community

Author Correction: Perspectives on ENCODE.

In this Article, the authors Rizi Ai (Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA) and Shantao Li (Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA) were mistakenly omitted from the ENCODE Project Consortium author list. The original Article has been corrected online