Publications

Gene trapping is a method of generating murine embryonic stem (ES) cell lines containing insertional mutations in known and novel genes. A number of international groups have used this approach to create sizeable public cell line repositories available to the scientific community for the generation of mutant mouse strains. The major gene trapping groups worldwide have recently joined together to centralize access to all publicly available gene trap lines by developing a user-oriented Website for the International Gene Trap Consortium (IGTC). This collaboration provides an impressive public informatics resource comprising approximately 45 000 well-characterized ES cell lines which currently represent approximately 40% of known mouse genes, all freely available for the creation of knockout mice on a non-collaborative basis. To standardize annotation and provide high confidence data for gene trap lines, a rigorous identification and annotation pipeline has been developed combining genomic localization and transcript alignment of gene trap sequence tags to identify trapped loci. This information is stored in a new bioinformatics database accessible through the IGTC Website interface. The IGTC Website (www.genetrap.org) allows users to browse and search the database for trapped genes, BLAST sequences against gene trap sequence tags, and view trapped genes within biological pathways. In addition, IGTC data have been integrated into major genome browsers and bioinformatics sites to provide users with outside portals for viewing this data. The development of the IGTC Website marks a major advance by providing the research community with the data and tools necessary to effectively use public gene trap resources for the large-scale characterization of mammalian gene function.

Many U.S. residents who speak little English may face language barriers when seeking health care. This article describes what is currently known about language barriers in health care and outlines a research agenda based on mismatches between the current state of knowledge of language barriers and what health care stakeholders need to know. Three broad areas needing more research are discussed: the ways in which language barriers affect health and health care, the efficacy of linguistic access service interventions, and the costs of language barriers and efforts to overcome them. In each of these areas, we outline specific research questions and recommendations.

The Rho family of small GTPases plays a key role in the dynamic regulation of the actin cytoskeleton that underlies various important cellular functions such as shape changes, migration, and polarity. We found that Smurf1, a HECT domain E3 ubiquitin ligase, could specifically target RhoA but not Cdc42 or Rac1 for degradation. Smurf1 interacts with the dominant inactive form of RhoA, RhoA N19, which binds constitutively to guanine nucleotide exchange factors (GEFs) in vivo. Smurf1 also interacts directly with either nucleotide-free or GDP-bound RhoA in vitro; however, loading with GTPgammaS inhibits the interaction. RhoA is ubiquitinated by wild-type Smurf1 but not the catalytic mutant of Smurf1 (C699A) in vivo and in vitro, indicating that RhoA is a direct substrate of Smurf1. In this chapter, we summarize the systems and methods used in the analyses of Smurf1-regulated RhoA ubiquitination and degradation.

BACKGROUND

With recent advances in breast cancer risk reduction practices, it is increasingly important to assess both the breadth of and disparities in use across different racial/ethnic groups.

METHODS

We conducted telephone interviews with 1,700 women ages 40 to 74, from four racial/ethnic groups, without prior history of breast cancer, who received mammograms at one of five mammography facilities in San Francisco. Main outcomes measured included recognition of tamoxifen, raloxifene, genetic testing, and prophylactic surgery. Global indicators (recognition of any therapy, discussion of breast cancer risk) were developed from original outcome measures and analyzed using logistic regression.

RESULTS

Multivariate analyses indicate that race/ethnicity and interview language affected recognition of therapies and discussion of risk. White women were more likely than all other women to recognize any therapy and more likely than Asian-Americans to discuss risk. Women at high risk, who had a prior abnormal mammogram, who perceived themselves to be at high risk, or who were exposed to breast health information were more likely to discuss risk.

CONCLUSIONS

Women are aware of preventive therapies, although discussion and use is limited. Interventions to increase use of therapies should focus on those at high risk.