Interplay of Protein and DNA Structure Revealed in Simulations of the lac Operon

The E. coli Lac repressor is the classic textbook example of a protein that attaches to widely spaced sites along a genome and forces the intervening DNA into a loop. The short loops implicated in the regulation of the lac operon suggest the involvement of factors other than DNA and repressor in gene control. The molecular simulations presented here examine two likely structural contributions to the in-vivo looping of bacterial DNA: the distortions of the double helix introduced upon association of the highly abundant, nonspecific nucleoid protein HU and the large-scale deformations of the repressor detected in low-resolution experiments. The computations take account of the three-dimensional arrangements of nucleotides and amino acids found in crystal structures of DNA with the two proteins, the natural rest state and deformational properties of protein-free DNA, and the constraints on looping imposed by the conformation of the repressor and the orientation of bound DNA. The predicted looping propensities capture the complex, chain-length-dependent variation in repression efficacy extracted from gene expression studies and in vitro experiments and reveal unexpected chain-length-dependent variations in the uptake of HU, the deformation of repressor, and the folding of DNA. Both the opening of repressor and the presence of HU, at levels approximating those found in vivo, enhance the probability of loop formation. HU affects the global organization of the repressor and the opening of repressor influences the levels of HU binding to DNA. The length of the loop determines whether the DNA adopts antiparallel or parallel orientations on the repressor, whether the repressor is opened or closed, and how many HU molecules bind to the loop. The collective behavior of proteins and DNA is greater than the sum of the parts and hints of ways in which multiple proteins may coordinate the packaging and processing of genetic information. © 2013 Czapla et al

Health Care for Homeless Women: Unmet Needs and Barriers to Care

OBJECTIVE: Homelessness is a significant and growing problem in the United States. Women and families are the fastest growing segments of the homeless population. Homelessness increases the risk of having health problems and encountering barriers to care. This study determines how much perceived unmet need for medical care there is among homeless women, what homeless women perceive to be barriers to health care, and how barriers and other factors are associated with unmet needs. DESIGN: Cross-sectional study of homeless women, utilizing structured interviews. SETTING AND PARTICIPANTS: Community-based probability sample of 974 homeless women aged 15 to 44 years. MAIN OUTCOME MEASURES: Perceived unmet need for medical care in the past 60 days. Relationship between unmet need and demographic variables, place of stay, source of health care, insurance, and perceived barriers to care. RESULTS: Of the 974 women, 37% reported unmet need for medical care. Controlling for other factors, the odds of unmet need were lower among those with a regular source of care (odds ratio [OR] to .35, 95% confidence interval [CI], .21 to 58), while having health insurance was not significantly associated. The odds of unmet need were higher among those who experienced the barriers: not knowing where to go (OR 2.27, 95% CI, 1.40 to 3.69), long office waiting times (OR 1.89, 95% CI 1.27 to 2.83) and being too sick to seek care (OR 2.03, 95% CI, 1.14 to 3.62). CONCLUSIONS: There is significant unmet need for medical care among homeless women. Having a regular source of care was more important than health insurance in lowering the odds of unmet need. Homeless women must be educated regarding sources of care, and clinics serving the homeless must decrease waiting times