any diseases have been linked to SVs, most often defined as genomic changes at least 50 bp in size, but SVs are challenging to detect accurately. Conditions linked to SVs include autism 1 , schizophrenia, cardiovascular disease 2 , Huntington's disease and several other disorders 3. Far fewer SVs exist in germline genomes relative to small variants, but SVs affect more base pairs, and each SV might be more likely to affect phenotype 4-6. Although next-generation sequencing technologies can detect many SVs, each technology and analysis method has different strengths and weaknesses. To enable the community to
Context A disaster is indiscriminate in whom it affects. Limited research has shown that the poor and medically underserved, especially in rural areas, bear an inequitable amount of the burden. Objective To review the literature on the combined effects of a disaster and living in an area with existing health or health care disparities on a community’s health, access to health resources, and quality of life. Methods We performed a systematic literature review using the following search terms: disaster, health disparities, health care disparities, medically underserved, and rural. Our inclusion criteria were peer-reviewed, US studies that discussed the delayed or persistent health effects of disasters in medically underserved areas. Results There has been extensive research published on disasters, health disparities, health care disparities, and medically underserved populations individually, but not collectively. Conclusions The current literature does not capture the strain of health and health care disparities before and after a disaster in medically underserved communities. Future disaster studies and policies should account for differences in health profiles and access to care before and after a disaster.
MarR family proteins constitute a group of >12 000 transcriptional regulators encoded in bacterial and archaeal genomes that control gene expression in metabolism, stress responses, virulence and multi-drug resistance. There is much interest in defining the molecular mechanism by which ligand binding attenuates the DNA-binding activities of these proteins. Here, we describe how PcaV, a MarR family regulator in Streptomyces coelicolor, controls transcription of genes encoding β-ketoadipate pathway enzymes through its interaction with the pathway substrate, protocatechuate. This transcriptional repressor is the only MarR protein known to regulate this essential pathway for aromatic catabolism. In in vitro assays, protocatechuate and other phenolic compounds disrupt the PcaV–DNA complex. We show that PcaV binds protocatechuate in a 1:1 stoichiometry with the highest affinity of any MarR family member. Moreover, we report structures of PcaV in its apo form and in complex with protocatechuate. We identify an arginine residue that is critical for ligand coordination and demonstrate that it is also required for binding DNA. We propose that interaction of ligand with this arginine residue dictates conformational changes that modulate DNA binding. Our results provide new insights into the molecular mechanism by which ligands attenuate DNA binding in this large family of transcription factors.
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