Neonatal exposure to xenobiotic estrogen alters the adult immune response and exacerbates endometriosis in mice [abstract]

Faculty Mentor: Dr. Susan C. Nagel, Obstetrics/Gynecology, and Women's HealthAbstract only availableEndometriosis is a common medical condition affecting 5-10% of women worldwide, and results in severe cramps, pelvic pain, and infertility. The cause of the disease is still unknown. Endometriosis occurs when endometrial tissue, which escapes into the peritoneal cavity via retrograde menstruation, adheres to other tissues in the cavity and causes irritated, inflamed lesions. Studies have suggested that the risk of developing endometriosis increases in women who have been exposed to xenobiotic (foreign to the body) estrogens during developmental stages of life. Thus, it is our hypothesis that programming of the immune system by xenoestrogens during development could potentially exacerbate endometriosis. This could occur by altering the peritoneal environment and/or the invading endometrial tissue. Therefore, it is our goal to study the effects of neonatal xenoestrogen exposure on the immune system; and ultimately, on the establishment of endometriosis in adulthood. In order to study this response, we dosed two strains of mice (CD1 and C57) with xenobiotic estrogens on postnatal days 2-14. In experiment A, CD1 mice were dosed with vehicle control (corn oil), 20 µg/kg/day, or 200 µg/kg/day bisphenol A. In experiment B, C57 mice were dosed with a vehicle control (corn oil) or 0.1 µg/kg/day diethylstilbestrol. At 8 weeks of age, endometriosis was induced in each strain via both a surgical induction and an injection technique. At 12 weeks, the endometriotic implants were counted and weighed to determine which mice had a greater susceptibility to the condition. Our next objective will be to analyze peritoneal fluid from the treated mice to identify key immune functions (for example, the release of certain cytokines) that may have been programmed by developmental xenoestrogen exposure.Endometriosis is a common medical condition affecting 5-10% of women worldwide, and results in severe cramps, pelvic pain, and infertility.  The cause of the disease is still unknown.  Endometriosis occurs when endometrial tissue, which escapes into the peritoneal cavity via retrograde menstruation, adheres to other tissues in the cavity and causes irritated, inflamed lesions.  Studies have suggested that the risk of developing endometriosis increases in women who have been exposed to xenobiotic (foreign to the body) estrogens during developmental stages of life.  Thus, it is our hypothesis that programming of the immune system by xenoestrogens during development could potentially exacerbate endometriosis.  This could occur by altering the peritoneal environment and/or the invading endometrial tissue.  Therefore, it is our goal to study the effects of neonatal xenoestrogen exposure on the immune system; and ultimately, on the establishment of endometriosis in adulthood.  In order to study this response, we dosed two strains of mice (CD1 and C57) with xenobiotic estrogens on postnatal days 2-14.  In experiment A, CD1 mice were dosed with vehicle control (corn oil), 20 µg/kg/day, or 200 µg/kg/day bisphenol A.  In experiment B, C57 mice were dosed with a vehicle control (corn oil) or 0.1 µg/kg/day diethylstilbestrol.  At 8 weeks of age, endometriosis was induced in each strain via both a surgical induction and an injection technique.  At 12 weeks, the endometriotic implants were counted and weighed to determine which mice had a greater susceptibility to the condition.  Our next objective will be to analyze peritoneal fluid from the treated mice to identify key immune functions (for example, the release of certain cytokines) that may have been programmed by developmental xenoestrogen exposure

Neonatal exposure to xenobiotic estrogen may alter the adult immune response and exacerbate endometriosis in mice [abstract]

Abstract only availableEndometriosis is a common medical condition affecting 5-10% of women worldwide and often results in severe cramps, pelvic pain, and infertility. The condition occurs when endometrial tissue, which escapes into the peritoneal cavity via retrograde menstruation, adheres to peritoneal cavity tissues and causes irritated, inflamed lesions. Studies have suggested that the risk of developing endometriosis increases in women who have been exposed to xenobiotic (foreign to the body) estrogens during development. This could be due to developmental programming of the peritoneal environment, and specifically, an altered immune function within this environment. Therefore, it is our hypothesis that developmental programming by xenoestrogens alters the immune response to shed endometrial tissue and exacerbates endometriosis. To better understand the role of xenoestrogens in immune programming, we are conducting our studies using a mouse model of surgically induced endometriosis. In particular, we are concentrating on two major aspects of immunity: 1) the presence of immune cells and 2) the function of those cells. Our study of the former is being largely performed using methods of immunohistochemistry (IHC). IHC allows us to quantify the macrophages present in the peritoneal fluid of experimental mice (exposed to diethylstilbestrol) versus control mice (no xenoestrogen exposure). In order to study our second focus, immune cell function, we are using a cytokine antibody array to determine the relative cytokine concentrations in the peritoneal fluid samples. By identifying the degree to which certain cytokine concentrations differ, we hope to better understand the effect of xenoestrogen exposure on immune cell function.Life Sciences Undergraduate Research Opportunity Progra

From Bare Metal Powders to Colloidally Stable TCO Dispersions and Transparent Nanoporous Conducting Metal Oxide Thin Films

Cataloged from PDF version of article.A simple, green, robust, widely applicable, multi-gram and cost-effective 'one-pot' synthesis of aqueous dispersions of colloidally stable 3-6 nm TCO NPs using bare metal powder precursors is described, and their utilization for making TCO high surface area nanoporous films is also demonstrated, which speaks well for their usage in a wide range of possible processes and devices. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Influence of Short Carbon-Chain Alcohol (Ethanol and 1-Propanol)/Diesel Fuel Blends over Diesel Engine Emissions

Oxygenated fuels, in this case short carbon-chain alcohols, have been investigated as alternative fuels to power compression ignition engines. A major advantage of short-chain alcohols is that they can be produced from renewable resources, i.e., cultivated commodities or biomass-based biorefineries. However, before entering the market, the effects of short-chain alcohols on engine performance, exhaust emissions, noise and sound quality need to be understood. This work sheds light on the relationship between the physicochemical properties of the alcohol/diesel fuel blends (ethanol and 1-propanol) on engine performance, exhaust emissions and, for the first time, on noise and sound quality. It has been demonstrated that when the content of alcohol in blends increased, soot and soluble organic material emissions drastically decreased, mainly due to the increase of oxygen content in the fuel. Reduction in soot emissions combined with higher thermodynamic efficiency of alcohol fuels, with respect to diesel fuel, enable their utilization on compression ignition engines. There is also an improvement in the soot-NOx trade off, leading to large reductions on soot with a small effect on NOx emissions. The oxygen content within the fuel reduces CO and THC emissions at extra-urban driving operation conditions. However, hydrocarbons and CO emissions increased at urban driving conditions, due to the high heat of vaporization of the alcohol fuels which reduces cylinder temperature worsening fuel atomization, vaporization and mixing with air being more significant at lower cylinder temperature conditions (low engine loads and speeds). Similarly, the higher the presence of alcohol in the blend, the higher the noise emitted by the engine due to their low tendency to auto-ignition. The optimization of alcohol quantity and the calibration of engine control parameters (e.g., injection settings) which is out of the scope of this work, will be required to overcome noise emission penalty. Furthermore, under similar alcohol content in the blend (10% v/v), the use of propanol is preferred over ethanol, as it exhibits lower exhaust emissions and better sound quality than ethanol

DULIP: A dual luminescence-based co-immunoprecipitation assay for interactome mapping in mammalian cells

Mapping of protein-protein interactions (PPIs) is critical for understanding protein function and complex biological processes. Here, we present DULIP, a dual luminescence-based co-immunoprecipitation assay, for systematic PPI mapping in mammalian cells. DULIP is a second-generation luminescence-based PPI screening method for the systematic and quantitative analysis of co-immunoprecipitations using two different luciferase tags. Benchmarking studies with positive and negative PPI reference sets revealed that DULIP allows the detection of interactions with high sensitivity and specificity. Furthermore, the analysis of a PPI reference set with known binding affinities demonstrated that both low- and high-affinity interactions can be detected with DULIP assays. Finally, using the well-characterized interaction between Syntaxin-1 and Munc18, we found that DULIP is capable of detecting the effects of point mutations on interaction strength. Taken together, our studies demonstrate that DULIP is a sensitive and reliable method of great utility for systematic interactome research. It can be applied for interaction screening as well as for the validation of PPIs in mammalian cells. Moreover, DULIP permits the specific analysis of mutation-dependent binding patterns

Bibliometric studies on emissions from diesel engines running on alcohol/diesel fuel blends. A case study about noise emissions

The growing demand for fossil fuels, the rise in their price and many environmental concerns strengthen the incessant search for fuel alternatives. Recently, traffic noise has been described as a threat to human health and the environment, being responsible for premature deaths. In this context, the usage of alcohol/diesel fuel blends in diesel engines has gained increasing impact as a substitute fuel for use in internal combustion engines. Moreover, alcohol can be derived from environmentally friendly processes, i.e., fermentation. Furthermore, alcohols can enhance combustion characteristics due to a rise of the oxygen concentration, thus decreasing major emissions such as soot and reducing knock. The commonly used alcohols blended with diesel fuel are methanol and ethanol, recently followed by butanol. In contrast, there are very few studies about propanol blends; however, emissions reduction (including noise) could be remarkable. In the present work, an analytical literature review about noise and exhaust emissions from alcohol/diesel fuel blends was performed. The literature review analysis revealed a continuous increase in the number of publications about alcohol/diesel fuel blend exhaust emissions since 2000, confirming the growing interest in this field. However, only few publications about noise emission were found. Then, an experimental case study of noise emitted by an engine running on different alcohol (ethanol, butanol and propanol)/diesel fuel blends was presented. Experimental results showed that although diesel fuel provided the best results regarding noise emissions, butanol displayed the least deviation from that of diesel fuel among all tested alcohol blends. It may be concluded that tested alcohol/diesel fuel blends in general, and butanol blends in particular, could be a promising alternative to diesel fuel, considering noise behavior

Hybridization from Guest-Host Interactions Reduces the Thermal Conductivity of Metal-Organic Frameworks

We experimentally and theoretically investigate the thermal conductivity and mechanical properties of polycrystalline HKUST-1 metal–organic frameworks (MOFs) infiltrated with three guest molecules: tetracyanoquinodimethane (TCNQ), 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F$_{4}$-TCNQ), and (cyclohexane-1,4-diylidene)dimalononitrile (H$_{4}$-TCNQ). This allows for modification of the interaction strength between the guest and host, presenting an opportunity to study the fundamental atomic scale mechanisms of how guest molecules impact the thermal conductivity of large unit cell porous crystals. The thermal conductivities of the guest@MOF systems decrease significantly, by on average a factor of 4, for all infiltrated samples as compared to the uninfiltrated, pristine HKUST-1. This reduction in thermal conductivity goes in tandem with an increase in density of 38% and corresponding increase in heat capacity of ∼48%, defying conventional effective medium scaling of thermal properties of porous materials. We explore the origin of this reduction by experimentally investigating the guest molecules’ effects on the mechanical properties of the MOF and performing atomistic simulations to elucidate the roles of the mass and bonding environments on thermal conductivity. The reduction in thermal conductivity can be ascribed to an increase in vibrational scattering introduced by extrinsic guest-MOF collisions as well as guest molecule-induced modifications to the intrinsic vibrational structure of the MOF in the form of hybridization of low frequency modes that is concomitant with an enhanced population of localized modes. The concentration of localized modes and resulting reduction in thermal conductivity do not seem to be significantly affected by the mass or bonding strength of the guest species

OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors.

MYC genes have both essential roles during normal development and exert oncogenic functions during tumorigenesis. Expression of a dominant-negative allele of MYC, termed OmoMYC, can induce rapid tumor regression in mouse models with little toxicity for normal tissues. How OmoMYC discriminates between physiological and oncogenic functions of MYC is unclear. We have solved the crystal structure of OmoMYC and show that it forms a stable homodimer and as such recognizes DNA in the same manner as the MYC/MAX heterodimer. OmoMYC attenuates both MYC-dependent activation and repression by competing with MYC/MAX for binding to chromatin, effectively lowering MYC/MAX occupancy at its cognate binding sites. OmoMYC causes the largest decreases in promoter occupancy and changes in expression on genes that are invaded by oncogenic MYC levels. A signature of OmoMYC-regulated genes defines subgroups with high MYC levels in multiple tumor entities and identifies novel targets for the eradication of MYC-driven tumors