The zebrafish kidney mutant zeppelin reveals that brca2/fancd1 is essential for pronephros development.

The zebrafish kidney is conserved with other vertebrates, making it an excellent genetic model to study renal development. The kidney collects metabolic waste using a blood filter with specialized epithelial cells known as podocytes. Podocyte formation is poorly understood but relevant to many kidney diseases, as podocyte injury leads to progressive scarring and organ failure. zeppelin (zep) was isolated in a forward screen for kidney mutants and identified as a homozygous recessive lethal allele that causes reduced podocyte numbers, deficient filtration, and fluid imbalance. Interestingly, zep mutants had a larger interrenal gland, the teleostean counterpart of the mammalian adrenal gland, which suggested a fate switch with the related podocyte lineage since cell proliferation and cell death were unchanged within the shared progenitor field from which these two identities arise. Cloning of zep by whole genome sequencing (WGS) identified a splicing mutation in breast cancer 2, early onset (brca2)/fancd1, which was confirmed by sequencing of individual fish. Several independent brca2 morpholinos (MOs) phenocopied zep, causing edema, reduced podocyte number, and increased interrenal cell number. Complementation analysis between zep and brca2ZM_00057434 -/- zebrafish, which have an insertional mutation, revealed that the interrenal lineage was expanded. Importantly, overexpression of brca2 rescued podocyte formation in zep mutants, providing critical evidence that the brca2 lesion encoded by zep specifically disrupts the balance of nephrogenesis. Taken together, these data suggest for the first time that brca2/fancd1 is essential for vertebrate kidney ontogeny. Thus, our findings impart novel insights into the genetic components that impact renal development, and because BRCA2/FANCD1 mutations in humans cause Fanconi anemia and several common cancers, this work has identified a new zebrafish model to further study brca2/fancd1 in disease.

Diagnosis and Management of Subcoracoid Impingement.

Impingement of the subcoracoid space is a poorly understood pathologic cause of anterior shoulder pain. Because of its relative rarity in isolation and nonspecific presentation, diagnosis and management are often challenging for orthopaedic surgeons and their patients. Stenosis of the subcoracoid space between the lesser tuberosity and the coracoid process <6 mm can lead to anterior shoulder pain and associated rotator cuff and biceps pathology. Multiple imaging modalities are available to assess narrowing of the coracohumeral interval, each with its strengths and limitations. If the patient can be accurately diagnosed with subcoracoid impingement, both conservative and surgical management options are available. Despite earlier case series demonstrating promising results with arthroscopic treatment, comparative studies have yet to support these initial claims.

Teaching the Genome Generation: Bringing Modern Human Genetics into the Classroom Through Teacher Professional Development.

Teaching the Genome Generation (TtGG) is a teacher professional development program and set of high school biology lessons that support interwoven classroom instruction of molecular genetics, bioinformatics, and bioethics. Participating teachers from across New England implement the modular elements of program at a high rate in a variety of biology classrooms. Evaluation data collected over three academic years (2014/15 to 2016/17) indicate that TtGG has increased teachers' abilities to integrate complex concepts of genomics and bioethics into their high school classes.

From hagfish to humans: teaching comparative physiology to internal medicine residents.

With more clinical information for trainees to master in the face of increasing time pressures, discussions about underlying physiology and the mechanisms of disease seem to have been de-emphasized during residency training. This reduced focus on pathophysiology and basic science may weaken trainees' clinical effectiveness and reduce their interest in pursuing research careers.In response, the authors helped to develop in 2006 a one-week immersive comparative physiology course for second- and third-year internal medicine residents at Beth Israel Deaconess Medical Center. The course, held at the Mount Desert Island Biological Laboratory, includes four modules (hematology, vascular physiology, secretory physiology, and salt and water homeostasis), each composed of basic science experiments using aquatic species and accompanied by clinical correlation discussions and group presentations.From 2007 to 2010, 72 residents rotated through the course. Most reported that it enhanced their understanding of the mechanisms of disease in their patients. After the course, residents reported that physiology played a more prominent role in their teaching and clinical decision making during both ward and intensive care unit rotations. They also reported being more likely than before the course to read about the pathophysiology of disease when faced with a clinical problem.Although cost-intensive and geographically unique, this model for teaching the mechanisms of disease could be applied elsewhere with the help of physician-scientists and clinician-educators. In this article, the authors describe the development of the course, share preliminary data evaluating progress toward its goals, and discuss future directions and lessons learned.