A double-hexamer archaeal minichromosome maintenance protein is an ATP-dependent DNA helicase

The minichromosome maintenance (MCM) proteins are essential for DNA replication in eukaryotes. Thus far, all eukaryotes have been shown to contain six highly related MCMs that apparently function together in DNA replication. Sequencing of the entire genome of the thermophilic archaeon Methanobacterium thermoautotrophicum has allowed us to identify only a single MCM-like gene (ORF Mt1770). This gene is most similar to MCM4 in eukaryotic cells. Here we have expressed and purified the M. thermoautotrophicum MCM protein. The purified protein forms a complex that has a molecular mass of ≈850 kDa, consistent with formation of a double hexamer. The protein has an ATP-independent DNA-binding activity, a DNA-stimulated ATPase activity that discriminates between single- and double-stranded DNA, and a strand-displacement (helicase) activity that can unwind up to 500 base pairs. The 3′ to 5′ helicase activity requires both ATP hydrolysis and a functional nucleotide-binding site. Moreover, the double hexamer form is the active helicase. It is therefore likely that an MCM complex acts as the replicative DNA helicase in eukaryotes and archaea. The simplified replication machinery in archaea may provide a simplified model for assembly of the machinery required for initiation of eukaryotic DNA replication

Designing and Evaluating Interventions to Eliminate Racial and Ethnic Disparities in Health Care

A large number of factors contribute to racial and ethnic disparities in health status. Health care professionals, researchers, and policymakers have believed for some time that access to care is the centerpiece in the elimination of these health disparities. The Institute of Medicine's (IOM) model of access to health services includes personal, financial, and structural barriers, health service utilization, and mediators of care. This model can be used to describe the interactions among these factors and their impact on health outcomes and equity of services among racial and ethnic groups. We present a modified version of the IOM model that incorporates the features of other access models and highlights barriers and mediators that are relevant for interventions designed to eliminate disparities in U.S. health care. We also suggest that interventions to eliminate disparities and achieve equity in health care services be considered within the broader context of improving quality of care. Some health service intervention studies have shown improvements in the health of disadvantaged groups. If properly designed and implemented, these interventions could be used to reduce health disparities. Successful features of interventions include the use of multifaceted, intense approaches, culturally and linguistically appropriate methods, improved access to care, tailoring, the establishment of partnerships with stakeholders, and community involvement. However, in order to be effective in reducing disparities in health care and health status, important limitations of previous studies need to be addressed, including the lack of control groups, nonrandom assignment of subjects to experimental interventions, and use of health outcome measures that are not validated. Interventions might be improved by targeting high-risk populations, focusing on the most important contributing factors, including measures of appropriateness and quality of care and health outcomes, and prioritizing dissemination efforts