Biomedical subjects
Karen M May
Publications and source records attributed to Karen M May.
In vivo dynamics of Swi6 in yeast: evidence for a stochastic model of heterochromatin.
The mechanism for transcriptional silencing of pericentric heterochromatin is conserved from fission yeast to mammals. Silenced genome regions are marked by epigenetic methylation of histone H3, which serves as a binding site for structural heterochromatin proteins. In the fission yeast Schizosaccharomyces pombe, the major structural heterochromatin protein is Swi6. To gain insight into Swi6 function in vivo, we have studied its dynamics in the nucleus of living yeast. We demonstrate that, in contrast to mammalian cells, yeast heterochromatin domains undergo rapid, large-scale motions within the nucleus. Similar to the situation in mammalian cells, Swi6 does not permanently associate with these chromatin domains but binds only transiently to euchromatin and heterochromatin. Swi6 binding dynamics are dependent on growth status and on the silencing factors Clr4 and Rik1, but not Clr1, Clr2, or Clr3. By comparing the kinetics of mutant Swi6 proteins in swi6(-) and swi6(+) strains, we demonstrate that homotypic protein-protein interactions via the chromoshadow domain stabilize Swi6 binding to chromatin in vivo. Kinetic modeling allowed quantitative estimation of residence times and indicated the existence of at least two kinetically distinct populations of Swi6 in heterochromatin. The observed dynamics of Swi6 binding are consistent with a stochastic model of heterochromatin and indicate evolutionary conservation of heterochromatin protein binding properties from mammals to yeast.
Specialist management and coordination of "out-of-domain care".
BACKGROUND AND OBJECTIVES: Fifteen percent of Medicare patients receive care only from specialists. This has led to the supposition that there might be a "hidden system of primary care," where specialists provide comprehensive care to their patients, including care traditionally outside their specialty domain. This study explores the perspectives of specialists at an academic medical center on their decisions to provide "out-of-domain" care and how it is coordinated. METHODS: We used grounded theory methodology and a constant comparative process with 13 specialist interviews. RESULTS: Patient requests drive the provision of out-of-domain care. Specialist comfort with this care and desire to perform it are involved with their decision to provide out-of-domain care. Coordination of out-of-domain care performed by specialists can be difficult and time consuming but is important and is facilitated by electronic medical records. CONCLUSIONS: The results suggest that there is no hidden system of primary care. Coordination among all providers of medical care for a patient is needed to prevent medical errors, especially when specialists provide out-of-domain care.
Polo boxes and Cut23 (Apc8) mediate an interaction between polo kinase and the anaphase-promoting complex for fission yeast mitosis.
The fission yeast plo1(+) gene encodes a polo-like kinase, a member of a conserved family of kinases which play multiple roles during the cell cycle. We show that Plo1 kinase physically interacts with the anaphase-promoting complex (APC)/cyclosome through the noncatalytic domain of Plo1 and the tetratricopeptide repeat domain of the subunit, Cut23. A new cut23 mutation, which specifically disrupts the interaction with Plo1, results in a metaphase arrest. This arrest can be rescued by high expression of Plo1 kinase. We suggest that this physical interaction is crucial for mitotic progression by targeting polo kinase activity toward the APC.