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This study aimed to evaluate the effect of hyperbaric oxygen preconditioning (HBO2P) on ischemic metabolites and the glutamate level after permanent middle cerebral artery occlusion (MCAO). HBO2P was administered: five treatments, one treatment per day. The permanent rabbit MCAO models were induced by a modified transorbital approach. The microdialysis procedures were performanced in the right peri-infarct area and contralateral area. MCAO decreased glucose levels while increasing lactate, pyruvate and lactate/pyruvate ratios. Early increase of glycerol and glutamate were also shown. HBO2P stabilized the glucose level and decreased the lactate/pyruvate ratios and glycerol in the peri-infarct area. In addition, it inhibited the increase of the glutamate level. Our study demonstrated that MCAO led to the imbalance of brain energy metabolites and excitatory amino acids. The modulation of energy metabolism and glutamate may be one of the factors contributing to the neuroprotective property of HBO2P.

Human genetic diversity is shaped by both demographic and biological factors and has fundamental implications for understanding the genetic basis of diseases. We studied 938 unrelated individuals from 51 populations of the Human Genome Diversity Panel at 650,000 common single-nucleotide polymorphism loci. Individual ancestry and population substructure were detectable with very high resolution. The relationship between haplotype heterozygosity and geography was consistent with the hypothesis of a serial founder effect with a single origin in sub-Saharan Africa. In addition, we observed a pattern of ancestral allele frequency distributions that reflects variation in population dynamics among geographic regions. This data set allows the most comprehensive characterization to date of human genetic variation.

Background: Gene expression patterns in the brain are strongly influenced by the severity and duration of physiological stress at the time of death. This agonal effect, if not well controlled, can lead to spurious findings and diminished statistical power in case-control comparisons. While some recent studies match samples by tissue pH and clinically recorded agonal conditions, we found that these indicators were sometimes at odds with observed stress-related gene expression patterns, and that matching by these criteria still sometimes results in identifying case-control differences that are primarily driven by residual agonal effects. This problem is analogous to the one encountered in genetic association studies, where self-reported race and ethnicity are often imprecise proxies for an individual's actual genetic ancestry., Results: We developed an Agonal Stress Rating (ASR) system that evaluates each sample's degree of stress based on gene expression data, and used ASRs in post hoc sample matching or covariate analysis. While gene expression patterns are generally correlated across different brain regions, we found strong region-region differences in empirical ASRs in many subjects that likely reflect inter-individual variabilities in local structure or function, resulting in region-specific vulnerability to agonal stress., Conclusion: Variation of agonal stress across different brain regions differs between individuals, revealing a new level of complexity for gene expression studies of brain tissues. The Agonal Stress Ratings quantitatively assess each sample's extent of regulatory response to agonal stress, and allow a strong control of this important confounder.

Expression of the human papillomavirus (HPV) E6 and E7 oncoproteins is responsible for the transforming ability of the virus. The HPV long control region (LCR) and E6/E7 promoter regulate transcription of the E6 and E7 viral oncogenes. However, factors involved in the stimulation of E6/E7 promoter activity in carcinogenesis are unclear. We previously identified a point mutation in an HPV-16 immortalized human oral keratinocyte cell line subsequently exposed to a tobacco-specific carcinogen. This mutation was located in the LCR at nucleotide 7633 and contains binding sites for the transcription activator, AP-1, overlapping with putative binding regions for the transcription factor, C/EBP, which represses the E6/E7 promoter. In this study, this mutation was analyzed by both electrophoretic mobility shift analysis and luciferase assays. We found that the point mutation enhanced the binding affinity of AP-1 to the LCR, thus stimulating the E6/E7 promoter activity. Our results suggest that mutations in binding sites for crucial regulators may be the result of exposure to carcinogens and could induce expression of the E6 and E7 oncogenes.