Sex differences in the development of airway epithelial tolerance to naphthalene.

Exposure to air pollution has been linked to pulmonary diseases. Naphthalene (NA), an abundant polycyclic aromatic hydrocarbon in tobacco smoke and urban air, is a model toxicant for air pollution effects in the lung. Repeated exposures to NA in male mice result in tolerance, defined as the emergence of a resistant cell phenotype after prior exposure. Tolerance has not been studied in females. Females have sex differences in airway epithelial responses and in the prevalence of certain airway diseases. Male and female mice were exposed to a tolerance-inducing regimen of NA, and lungs were examined by airway level to characterize the cellular changes associated with repeated NA exposure and to assess the expression of genes and proteins involved in NA bioactivation and detoxification. The airway epithelium in treated males resembled that of controls. Females in the tolerant state were characterized by dense populations of ciliated cells in midlevel, distal, and bifurcating airways and a lower abundance of Clara cells at all airway levels. Cytotoxicity following a secondary challenge dose was also greater in females than males. Furthermore, females had decreased gene/protein expression of CYP2F2, a P-450 that metabolizes NA to a toxic epoxide, and glutamate-cysteine ligase, the rate-limiting enzyme in glutathione synthesis, than NA-tolerant males at all airway levels examined. We conclude that, while females develop tolerance, sex differences exist in the tolerant state by airway level, and females remain more susceptible than males to repeated exposures to NA.

Inter-domain horizontal gene transfer of nickel-binding superoxide dismutase.

The ability of aerobic microorganisms to regulate internal and external concentrations of the reactive oxygen species (ROS) superoxide directly influences the health and viability of cells. Superoxide dismutases (SODs) are the primary regulatory enzymes that are used by microorganisms to degrade superoxide. SOD is not one, but three separate, non-homologous enzymes that perform the same function. Thus, the evolutionary history of genes encoding for different SOD enzymes is one of convergent evolution, which reflects environmental selection brought about by an oxygenated atmosphere, changes in metal availability, and opportunistic horizontal gene transfer (HGT). In this study, we examine the phylogenetic history of the protein sequence encoding for the nickel-binding metalloform of the SOD enzyme (SodN). The genomic potential to produce SodN is widespread among bacteria, including Actinobacteriota (Actinobacteria), Chloroflexota (Chloroflexi), Cyanobacteria, Proteobacteria, Patescibacteria, and others. The gene is also present in many archaea, with Thermoplasmatota and Nanoarchaeota representing the vast majority of archaeal sodN diversity. A comparison of organismal and SodN protein phylogenetic trees reveals several instances of HGT, including multiple inter-domain transfers of the sodN gene from the bacterial domain to the archaeal domain. Nearly half of the archaeal members with sodN live in the photic zone of the marine water column. The sodN gene is widespread and characterized by apparent vertical gene transfer in some sediment- or soil-associated lineages within the Actinobacteriota and Chloroflexota phyla, suggesting the ancestral sodN likely originated in one of these clades before expanding its taxonomic and biogeographic distribution to additional microbial groups in the surface ocean in response to decreasing iron availability. In addition to decreasing iron quotas, nickel-binding SOD has the added benefit of withstanding high reactant and product ROS concentrations without damaging the enzyme, making it particularly well suited for the modern surface ocean.

Oxygen isotope analysis of bacterial and fungal manganese oxidation.

The ability of micro-organisms to oxidize manganese (Mn) from Mn(II) to Mn(III/IV) oxides transcends boundaries of biological clade or domain. Many bacteria and fungi oxidize Mn(II) to Mn(III/IV) oxides directly through enzymatic activity or indirectly through the production of reactive oxygen species. Here, we determine the oxygen isotope fractionation factors associated with Mn(II) oxidation via various biotic (bacteria and fungi) and abiotic Mn(II) reaction pathways. As oxygen in Mn(III/IV) oxides may be derived from precursor water and molecular oxygen, we use a twofold approach to determine the isotope fractionation with respect to each oxygen source. Using both 18 O-labeled water and closed-system Rayleigh distillation approaches, we constrain the kinetic isotope fractionation factors associated with O atom incorporation during Mn(II) oxidation to -17.3‰ to -25.9‰ for O2 and -1.9‰ to +1.8‰ for water. Results demonstrate that stable oxygen isotopes of Mn(III/IV) oxides have potential to distinguish between two main classes of biotic Mn(II) oxidation: direct enzymatic oxidation in which O2 is the oxidant and indirect enzymatic oxidation in which superoxide is the oxidant. The fraction of Mn(III/IV) oxide-associated oxygen derived from water varies significantly (38%-62%) among these bio-oxides with only weak relationship to Mn oxidation state, suggesting Mn(III) disproportionation may account for differences in the fraction of mineral-bound oxygen from water and O2 . Additionally, direct incorporation of molecular O2 suggests that Mn(III/IV) oxides contain a yet untapped proxy of δ18OO2 of environmental O2 , a parameter reflecting the integrated influence of global respiration, photorespiration, and several other biogeochemical reactions of global significance.

Estimation of premorbid intellectual status in depression.

The validity of the NART and Vocabulary subtest of the WAIS as measures of premorbid IQ in depression was assessed by comparing a group of depressed patients (n = 39) with matched controls. The Vocabulary performance of the depressed group was significantly poorer than controls but there was no significant difference in NART performance.

Independent control of blood gas PO2 and PCO2 in a bubble oxygenator.

An in-vitro circuit simulating cardiopulmonary bypass has been used to evaluate the gas transfer characteristics, gaseous microemboli production and blood damage of the Bentley-10 Plus bubble oxygenator. This oxygenator incorporates a unique integral gas controller which proportions the gas flow between the gas sparger and heat exchange area. The results of the study indicate that maintenance of a gas flow which ensures adequate CO2 removal can be prevented from inducing over-oxygenation by the manipulation of the gas controller which variably proportions the flow of gas from the oxygenation-efficient conventional gas sparger to the less efficient heat exchange area. Independent control of PaO2 with maintenance of CO2 transfer was demonstrated. Reduction in gaseous microemboli production and red blood cell damage with the use of the gas controller was demonstrated.

Relaxin stimulates expression of vascular endothelial growth factor in normal human endometrial cells in vitro and is associated with menometrorrhagia in women.

Although the role of the reproductive hormone, relaxin, in rodents is well documented, its potential contribution to human reproduction is less well defined. In this study, we examine the effects of relaxin on human endometrial cells in vitro and describe the clinical effects of relaxin on menstrual flow in women. In cultured endometrial cells, relaxin specifically induces the expression of an angiogenic agent, vascular endothelial growth factor (VEGF). cAMP is implicated as a second messenger involved in VEGF stimulation. VEGF expression is temporally regulated in the endometrium, and our results suggest that relaxin, which is secreted by the corpus luteum and is present in the endometrium during the menstrual cycle and pregnancy, may be involved in regulating endometrial VEGF expression. Relaxin was recently tested in a clinical trial for efficacy in the treatment of progressive systemic sclerosis, and was administered at levels up to 10 times higher than that measured during pregnancy. The most frequent relaxin-related adverse event reported during the course of the study was the onset of menometrorrhagia, defined in this study as heavier-than-usual or irregular menstrual bleeding. The intensification of menstrual flow observed in these patients is consistent with the hypothesis that relaxin mediates neovascularization of the endometrial lining.