The Protein Ontology (PRO) provides a formal, logically-based classification of specific protein classes including structured representations of protein isoforms, variants and modified forms. Initially focused on proteins found in human, mouse and Escherichia coli, PRO now includes representations of protein complexes. The PRO Consortium works in concert with the developers of other biomedical ontologies and protein knowledge bases to provide the ability to formally organize and integrate representations of precise protein forms so as to enhance accessibility to results of protein (...) research. PRO (http://pir.georgetown.edu/pro) is part of the Open Biomedical Ontologies (OBO) Foundry. (shrink)

Biomedical ontologies are emerging as critical tools in genomic and proteomic research where complex data in disparate resources need to be integrated. A number of ontologies exist that describe the properties that can be attributed to proteins; for example, protein functions are described by Gene Ontology, while human diseases are described by Disease Ontology. There is, however, a gap in the current set of ontologies—one that describes the protein entities themselves and their relationships. We have designed a PRotein Ontology (PRO) (...) to facilitate protein annotation and to guide new experiments. The components of PRO extend from the classification of proteins on the basis of evolutionary relationships to the representation of the multiple protein forms of a gene (products generated by genetic variation, alternative splicing, proteolytic cleavage, and other post-translational modification). PRO will allow the specification of relationships between PRO, GO and other OBO Foundry ontologies. Here we describe the initial development of PRO, illustrated using human proteins from the TGF-beta signaling pathway. (shrink)

The Protein Ontology provides terms for and supports annotation of species-specific protein complexes in an ontology framework that relates them both to their components and to species-independent families of complexes. Comprehensive curation of experimentally known forms and annotations thereof is expected to expose discrepancies, differences, and gaps in our knowledge. We have annotated the early events of innate immune signaling mediated by Toll-Like Receptor 3 and 4 complexes in human, mouse, and chicken. The resulting ontology and annotation data set has (...) allowed us to identify species-specific gaps in experimental data and possible functional differences between species, and to employ inferred structural and functional relationships to suggest plausible resolutions of these discrepancies and gaps. (shrink)

Representing species-specific proteins and protein complexes in ontologies that are both human and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because (...) proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. (shrink)

The Protein Ontology (PRO) is designed as a formal and principled Open Biomedical Ontologies (OBO) Foundry ontology for proteins. The components of PRO extend from a classification of proteins on the basis of evolutionary relationships at the homeomorphic level to the representation of the multiple protein forms of a gene, including those resulting from alternative splicing, cleavage and/or posttranslational modifications. Focusing specifically on the TGF-beta signaling proteins, we describe the building, curation, usage and dissemination of PRO. PRO provides a framework (...) for the formal representation of protein classes and protein forms in the OBO Foundry. It is designed to enable data retrieval and integration and machine reasoning at the molecular level of proteins, thereby facilitating cross-species comparisons, pathway analysis, disease modeling and the generation of new hypotheses. (shrink)

Research investigating the underlying mechanisms and boundary conditions under which leader humility influences employee voice remains underdeveloped. Drawing from approach–inhibition theory of power and leader humility literature, we developed a moderated-mediation model in which personal sense of power (i.e., employees’ ability to influence other individuals such as their leader) was theorized as a unique mechanism underlining why employees feel motivated to speak up under the supervision of humble leaders. Additionally, the cultural value of power distance was proposed to be a (...) relevant boundary condition to influence such relationship. We tested the model using time-lagged supervisor–subordinate matched data. Results of mixed models analyses provided support for our hypotheses confirming that employees’ personal sense of power mediates the relationship between leader humility and employee voice, and such relationship was found to be stronger when employees’ power distance was lower rather than higher. (shrink)

IPCC SPECIAL REPORT ON CLIMATE CHANGE AND LAND (SRCCL) -/- Chapter 3: Climate Change and Land: An IPCC special report on climate change, desertification, land degradation, sustainable land management, food security, and greenhouse gas fluxes in terrestrial ecosystems.

The aim of this paper is to explore the conditions under which generalisation from single case studies, in the sense of making inferences concerning a wider class of phenomena beyond a case, is reasonable. Two sets of conditions, in particular, provide the basis for our consideration of this issue. The first is an exploration of the impressive amount of empirical knowledge that is contained within the theories that are used to make observations, to classify phenomena, and to understand and interpret (...) cases. The second is recognition of the role of a pattern of inference known as abduction, or inference to the best explanation, in drawing conclusions from case studies. It is argued that these two conditions, when applied to the procedures for conducting case studies, can be used to defend, as reasonable, the making of certain provisional generalisations from single cases. An epistemological procedure for testing and further justifying these generalisations, with a particular emphasis on dealing with the problem of confirmation bias, is then discussed and recommended. (shrink)

Alzheimer's disease is characterized by plaques of amyloid-beta peptide, cleaved from amyloid-beta protein precursor . Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 , and the beta amyloid precursor (...) cleaving enzyme . In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. (shrink)

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

Wisdom is a multi-component trait that is important for mental health and well-being. In this study, we sought to understand gender differences in relative strengths in wisdom. A total of 659 individuals aged 27–103 years completed surveys including the 3-Dimensional Wisdom Scale and the San Diego Wisdom Scale. Analyses assessed gender differences in wisdom and gender’s moderating effect on the relationship between wisdom and associated constructs including depression, loneliness, well-being, optimism, and resilience. Women scored higher on average on the 3D-WS (...) but not on the SD-WISE. Women scored higher on compassion-related domains and on SD-WISE Self-Reflection. Men scored higher on cognitive-related domains and on SD-WISE Emotion Regulation. There was no impact of gender on the relationships between wisdom and associated constructs. Women and men have different relative strengths in wisdom, likely driven by sociocultural and biological factors. Tailoring wisdom interventions to individuals based on their profiles is an important next step. (shrink)

Objectives The objective of this research was to develop ethics accreditation standards for hospitals. Research design Our research methods included a literature review, an expert focus group, the Delphi technique and a hospital survey. The entire process was separated into two stages: (1) the development of a draft of hospital ethics accreditation standards; and (2) conducting a nationwide hospital survey of the proposed standards. Results This study produced a tentative draft of hospital ethics accreditation standards comprised of six chapters and (...) 62 standards based on the expert focus group and Delphi technique. The six chapters are: Medical ethics policies, regulations and leadership; The establishment and operation of a medical ethics committee; The establishment and operation of research-related ethics committees; Medical ethics education; Organisational ethical climate; and Respect for patients' rights and establishment of good hospital-patient relationships. The hospital survey indicated that the concept of an organisational ethical climate was new to most hospital managers, most hospitals disliked the idea of having a separate hospital ethics accreditation system, and small hospitals were concerned about their ability to comply with all of the standards. Conclusions Regardless of whether hospital ethics accreditation can be a stand-alone accreditation or just part of existing hospital accreditation programmes, we hope this draft can serve as a good reference for future endeavours by hospital accreditation authorities. (shrink)

“Looking for Asian America shows real people engaged in the full range of human activity. This is no small accomplishment for the photographer or his subjects. For Asian Americans it is extraordinary to be merely ordinary. To others, even if not to themselves, Asian Americans appear to be contradictions of identity—a Chinese-Yankee is a knockoff.” —Frank H. Wu, from the Foreword In search of contemporary Asian America, celebrated photographer Wing Young Huie—the only member of his family not born in China—traveled (...) with his wife Tara through nearly forty states to explore and document the funny, touching, and sometimes strange intersection of Asian American and American cultures. Looking for Asian America illustrates their rich and surprising journey across the United States. Through Huie’s eyes, keenly aware of his own Midwestern roots and perspective, we witness such images as a Vietnamese Elvis, Miss Congeniality on her cell phone in San Francisco’s Chinatown, a Hmong street sign in rural North Carolina, a meditating Falun Gong protestor in Washington, D.C., a bubble tea Valley Girl, and a Chinese theme park in Orlando. Huie’s camera captures ABCs, FOAs, and a self-described “redneck” Chinese restaurant owner near the Okefenokee Swamp. Taken together the photographs reveal a complex portrait of the U.S. cultural landscape, and their dignified elegance invites a closer, deeper look. Accompanied by the personal reflections of both Wing and Tara Huie, the nearly one hundred spectacular photos tell a story that both mirrors and contradicts stereotypes of Asian Americans, ultimately questioning what it means to be ethnic and American in the twenty-first century. Wing Young Huie has received widespread acclaim for his works, including Lake Street USA, documenting the cultural landscape of his native Minnesota. He is a recipient of a Bush Artist Fellowship and two-time recipient of the McKnight Photography Fellowship. He lives in Minneapolis. Frank H. Wu is dean of Wayne State University Law School and the author of Yellow: Race in America Beyond Black and White. Anita Gonzalez teaches in the Master of Liberal Studies Program at the University of Minnesota. (shrink)