Medical Education From a Theory-Practice-Philosophy Perspective.

Medical schooling, at least as structured in the United States and Canada, is commonly assembled intuitively or empirically to meet concrete goals. Despite a long history of scholarship in educational theory to address how people learn, this is rarely examined during medical curriculum design. We provide a historical perspective on educational theory-practice-philosophy and a tool to aid faculty in learning how to identify and use theory-practice-philosophy for the design of curriculum and instruction.

Benign Papilloma of the Breast.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.

National standards in pathology education: developing competencies for integrated medical school curricula.

Context: Medical school education has evolved from department-specific memorization of facts to an integrated curriculum presenting knowledge in a contextual manner across traditional disciplines, integrating information, improving retention, and facilitating application to clinical practice. Integration occurs throughout medical school using live data-sharing technologies, thereby providing the student with a framework for lifelong active learning. Incorporation of educational teams during medical school prepares students for team-based patient care, which is also required for pay-for-performance models used in accountable care organizations.

A WW-like module in the RAG1 N-terminal domain contributes to previously unidentified protein-protein interactions.

More than one-third of the RAG1 protein can be truncated from the N-terminus with only subtle effects on the products of V(D)J recombination in vitro or in a mouse. What, then, is the function of the N-terminal domain? We believe it to be regulatory. We determined, several years ago, that an included RING motif could function as an ubiquitin E3 ligase.

Regulation of host cell cyclin D1 by Trypanosoma cruzi in myoblasts.

Infection with the parasite Trypanosoma cruzi causes Chagas disease. In this study we demonstrated that there was an increase in cyclin D1 expression in T. cruzi (Tulahuen strain)-infected myoblasts.

PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing.

Tandem PHD and bromodomains are often found in chromatin-associated proteins and have been shown to cooperate in gene silencing. Each domain can bind specifically modified histones: the mechanisms of cooperation between these domains are unknown. We show that the PHD domain of the KAP1 corepressor functions as an intramolecular E3 ligase for sumoylation of the adjacent bromodomain.

Ku70 is stabilized by increased cellular SUMO.

Ku70 is a protein that finds itself at the heart of several important cellular processes. It is essential to the non-homologous end joining pathway as a part of the DNA-end binding complex, required for proper maintenance of telomeres and contributes to DNA damage recognition and regulation of apoptosis. Forces that regulate Ku70 are therefore likely to have large consequences on the physiologic state of the cell.

SUMO modification of human XRCC4 regulates its localization and function in DNA double-strand break repair.

The nonhomologous end-joining (NHEJ) pathway is responsible for rejoining the majority of double-strand breaks in mammalian cells, including the programmed breaks introduced by V(D)J recombination. The regulation of the enzymatic activities associated with this recombination pathway is still largely unknown. Here we report that human XRCC4 (for X-ray cross-complementation group 4), a protein essential for NHEJ, is subject to posttranslational protein modification.

Recombination-activating gene proteins: more regulation, please.

Developing B and T cells assemble gene segments in order to create the variable regions of immunoglobulin and T-cell receptors required by our adaptive immune response. The chemistry of this recombination pathway requires a specific nuclease and a more general repair pathway for double-strand breaks. A complex of the recombination-activating gene 1 (RAG1) and RAG2 proteins provides the nuclease activity.

Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing mice.

RAG1 and RAG2 are the lymphocyte-specific components of the V(D)J recombinase. In vitro analyses of RAG function have relied on soluble, highly truncated "core" RAG proteins. To identify potential functions for noncore regions and assess functionality of core RAG1 in vivo, we generated core RAG1 knockin (RAG1(c/c)) mice.

The RAG1 N-terminal domain is an E3 ubiquitin ligase.

RAG1 and RAG2 initiate V(D)J recombination, which is the assembly of immunoglobulin and T cell receptor genes. The N-terminal region of RAG1 can be deleted, leaving an enzymatic "core" able to catalyze the complete reaction. Here we report that the N-terminal portion of RAG1 has a distinct enzymatic role separate from the rest of the protein.