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.

Evidence suggests that serum brain-derived neurotrophic factor (serum BDNF) can be affected by cardiorespiratory fitness (CRF), but this relationship is far from clear. Recent reports show an inverse relationship between serum BDNF and CRF in healthy individuals, and other studies suggest a possible association between serum BDNF and cardiovascular disease. However, the possible interaction between serum BDNF, CRF, and cardiovascular disease risk has not been studied. The purpose of this study was to examine the association among serum BDNF, CRF, and cardiovascular disease risk factors in healthy men. The investigation involved a large sample of men (n = 995, age range: 20-76 years) who live in the central area of South Korea and were recruited into the Preventive Health Study. Our study showed a significant inverse relationship between serum BDNF and relative VO(2)max (r = -0.412, p < 0.0001) and heart rate reserve (r = -0.194, p < 0.0001). Serum BDNF was positively correlated with body mass index (r = 0.80, p < 0.0001), total cholesterol (r = 0.185, p < 0.0001), and triglyceride (r = 0.320, p < 0.0001). Our data suggest that serum BDNF may be associated with effects of increased CRF on cardiovascular disease. However, more research is clearly needed before a determination of whether, and to what extent, serum BDNF may be responsible for some of the health benefits associated with CRF.

The major utilization pathway for lignin-derived aromatic compounds in microorganisms is the beta-ketoadipate pathway. Through this pathway, the aromatic compounds protocatechuate and catechol are converted to acetyl coenzyme A and succinyl coenzyme A. The enzymes of the protocatechuate branch of this pathway are encoded by the pca genes. Here, we describe a gene cluster in Streptomyces coelicolor containing the pca structural genes and a regulatory gene required for the catabolism of protocatechuate. We found that transcription of the structural genes in S. coelicolor is induced by protocatechuate and p-hydroxybenzoate. We also observed inducible transcription of pca structural genes in the ligninolytic strain Streptomyces viridosporus ATCC 39115. Disruption of a gene encoding a putative MarR family transcription factor that is divergently transcribed from the pca structural genes resulted in constitutive transcription of the structural genes. Thus, the transcription factor encoded by this gene is an apparent negative regulator of pca gene transcription in S. coelicolor. Our findings suggest how Streptomyces bacteria could be engineered for and used in biotechnology for the utilization and degradation of lignin and lignin-derived aromatic compounds.

Because of reticuloendotheliosis virus (REV) contamination in commercial poultry vaccines, polymerase chain reaction (PCR) assays have been described to increase the sensitivity of biological assays used to detect REV in vaccines. The PCR assay designed to amplify the long terminal repeat (LTR) region of REV identified REV LTRs in many of the commercial fowl poxvirus (FPV) vaccines evaluated. These commercial vaccines were not thought to be contaminated with replicating REV because of the lack of REV outbreaks, the lack of in vitro amplification, and lack of a serologic response to REV. As previously described, the FPV S vaccine strain is known to carry infectious integrated proviral REV, whereas FPV M vaccine strain and its derivatives carry integrated LTRs or remnants of REV proviral DNA inserted into the FPV genome. Another PCR assay designed to amplify the envelope gene of REV was used to verify that the envelope proviral gene was not present in REV LTR PCR-positive samples. Southern blot analysis with REV LTR probes hybridized to the 9-kb EcoRI genomic fragment of all FPV and pigeon poxviruses evaluated, whereas the envelope probe did not hybridize to any poxvirus genome. Sequence analysis of the 9-kb EcoRI fragment indicated that an integrated REV LTR exists in the 9-kb EcoRI of some poxvirus genomes. A new PCR assay designed to amplify integrated REV LTRs in the 9-kb EcoRI fragment identified complete and incomplete integrated REV LTRs in all FPV and pigeon poxvirus genomes evaluated.

Background Obstructive sleep apnea (OSA) predisposes individuals to cardiovascular morbidity, and cardiopulmonary exercise test (CPET) markers prognostic for cardiovascular disease have been found to be abnormal in adults with OSA. Due to the persistence of OSA and its cardiovascular consequences, whether the cardiovascular adaptations normally conferred by exercise are blunted in adults not utilizing established OSA treatment is unknown. The aims of this study were to document whether OSA participants have abnormal CPET responses and determine whether exercise modifies these CPET markers in individuals with OSA. Methods The CPET responses of 43 sedentary, overweight adults (body mass index [BMI]>25) with untreated OSA (apnea-hypopnea index [AHI]≥15) were compared against matched non-OSA controls (n=9). OSA participants were then randomized to a 12-week exercise training (n=27) or stretching control treatment (n=16), followed by a post-intervention CPET. Measures of resting, exercise, and post-exercise recovery heart rate (HRR), blood pressure, and ventilation, as well as peak oxygen consumption (VO2peak), were obtained. Results OSA participants had blunted HRR compared to non-OSA controls at 1 (P=.03), 3 (P=.02), and 5 min post-exercise (P=.03). For OSA participants, exercise training improved VO2peak (P=.04) and HRR at 1 (P=.03), 3 (P<.01), and 5 min post-exercise (P<.001) compared to control. AHI change was associated with change in HRR at 5-min post-exercise (r=−.30, P<.05), but no other CPET markers. Conclusions These results suggest that individuals with OSA have autonomic dysfunction, and that exercise training, by increasing HRR and VO2peak, may attenuate autonomic imbalance and improve functional capacity independent of OSA severity reduction.

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