ABSTRACT
BACKGROUND: Congenital forms of hearing impairment can be caused by mutations in the estrogen related receptor beta (ESRRB) gene. Our initial linkage studies suggested the ESRRB locus is linked to high caries experience in humans. METHODS: We tested for association between the ESRRB locus and dental caries in 1,731 subjects, if ESRRB was expressed in whole saliva, if ESRRB was associated with the microhardness of the dental enamel, and if ESRRB was expressed during enamel development of mice. RESULTS: Two families with recessive ESRRB mutations and DFNB35 hearing impairment showed more extensive dental destruction by caries. Expression levels of ESRRB in whole saliva samples showed differences depending on sex and dental caries experience. CONCLUSIONS: The common etiology of dental caries and hearing impairment provides a venue to assist in the identification of individuals at risk to either condition and provides options for the development of new caries prevention strategies, if the associated ESRRB genetic variants are correlated with efficacy.
Subject(s)
Dental Caries/genetics , Hearing Loss, Sensorineural/pathology , Receptors, Estrogen/genetics , Tooth Demineralization/genetics , Adolescent , Adult , Animals , Cell Line, Tumor , Child , Child, Preschool , Chromosomes, Human, Pair 14 , Dental Enamel/growth & development , Female , Genetic Association Studies , Hearing Loss, Sensorineural/genetics , Humans , Linkage Disequilibrium , Male , Mice , Pedigree , Polymorphism, Single Nucleotide , Receptors, Estrogen/physiology , Young AdultABSTRACT
Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This bioinspired microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and inflammatory responses of the lung to silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticulates and stimulates their transport into the underlying microvascular channel. Similar effects of physiological breathing on nanoparticle absorption are observed in whole mouse lung. Mechanically active "organ-on-a-chip" microdevices that reconstitute tissue-tissue interfaces critical to organ function may therefore expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications.
Subject(s)
Alveolar Epithelial Cells/physiology , Biomimetic Materials , Capillaries/physiology , Endothelial Cells/physiology , Microfluidic Analytical Techniques , Pulmonary Alveoli/blood supply , Pulmonary Alveoli/physiology , Air , Animals , Blood-Air Barrier , Capillary Permeability , Cells, Cultured , Escherichia coli/immunology , Humans , Immunity, Innate , Inflammation , Lung/blood supply , Lung/physiology , Mice , Microtechnology , Nanoparticles/toxicity , Neutrophil Infiltration , Oxidative Stress , Pulmonary Alveoli/cytology , Pulmonary Alveoli/immunology , Respiration , Silicon Dioxide/toxicity , Stress, MechanicalABSTRACT
IR and Raman spectra are reported for 1,1-difluorocyclopropane-d0, -d2, and -d4, and complete assignments of vibrational fundamentals are given for these species. These assignments are consistent with predictions of frequencies, intensities, and Raman depolarization ratios computed with the B3LYP/cc-pVTZ quantum chemical (QC) model. Ground state rotational constants for five 13C and deuterium isotopomers, obtained from published microwave spectra, were "corrected" into equilibrium rotational constants. The needed vibration-rotation interaction constants were computed with QC models after scaling the force constants. A semi-experimental equilibrium structure, fitted to the equilibrium moments of inertia, is rC1C = 1.470(1) A, rCC = 1.546(1) A, rCF = 1.343(1) A, rCH = 1.078(1) A, alphaFCF = 109.5(1), alphaFCC = 119.4(1) degrees, alphaHCH = 116.7(1) degrees, alphaC1CH = 117.4(1) degrees, and alphaCCH = 117.1(1) degrees. This structure agrees within the indicated uncertainties with the ab initio structure obtained from an extrapolated set of CCSD(T)/aug-cc-pVnZ calculations except for rCC = 1.548 A. The F2C-CH2 bonds are significantly shortened and strengthened; the H2C-CH2 bond is significantly lengthened and weakened.
ABSTRACT
The overall rate constants of the reactions of NO with hydroxy- and chloroalkylperoxy radicals, derived from the OH- and Cl-initiated oxidation of methacrolein and methyl vinyl ketone, respectively, were directly determined for the first time using the turbulent-flow technique and pseudo-first-order kinetics conditions with high-pressure chemical ionization mass spectrometry for the direct detection of peroxy radical reactants. The individual 100 Torr, 298 K hydroxyalkylperoxy + NO rate constants for the methacrolein [(0.93 +/- 0.12) (2sigma) x 10(-11) cm3 molecule(-1) s(-1)] and methyl vinyl ketone [(0.84 +/- 0.10) x 10(-11) cm3 molecule(-1) s(-1)] systems were found to be identical within the 95% confidence interval associated with each separate measurement, as were the chloroalkylperoxy + NO rate constants for both methacrolein [(1.17 +/- 0.11) x 10(-11) cm3 molecule(-1) s(-1)] and methyl vinyl ketone [(1.14 +/- 0.14) x 10(-11) cm3 molecule(-1) s(-1)]. However, the difference in the rate constants between the hydroxyperoxy + NO and chloroalkylperoxy + NO systems was found to be statistically significant, with the chloroalkylperoxy + NO rate constants about 30% higher than the corresponding hydroxyalkylperoxy + NO rate constants. This substituent effect was rationalized via a frontier molecular orbital model approach.
