The role of mitophagy during oocyte aging in human, mouse, and Drosophila: implications for oocyte quality and mitochondrial disease

There is a worldwide trend for women to have their first pregnancy later in life. However, as oocyte quality declines with maternal aging, this trend leads to an increase in subfertility. The cellular mechanisms underlying this decline in oocyte competence are poorly understood. Oocyte mitochondria are the subcellular organelles that supply the energy that drives early embryogenesis, and thus their quality is critical for successful conception. Mitochondria contain their own DNA (mtDNA) and mutations in mtDNA cause mitochondrial diseases with severe symptoms, such as neurodegeneration and heart disease. Since mitochondrial function declines in tissues as humans age accompanied by an accumulation of mtDNA mutations, mtDNA is implicated as a cause of declining oocyte quality in older mothers. While this mutation load could be caused by declining accuracy of the mitochondrial replisome, age-related decline in mitochondrial quality control likely contributes, however knowledge is lacking. Mitophagy, a cellular process which specifically targets and recycles damaged mitochondria may be involved, but studies are scarce. And although assisted reproductive technologies can help older mothers, how these techniques affect the mechanisms that regulate mitochondrial and oocyte quality have not been studied. With the long-term goal of understanding the molecular mechanisms that control mitochondrial quality in the oocyte, model systems including Drosophila and mouse as well as human oocytes have been used. In this review, we explore the contribution of mitophagy to oocyte quality and the need for further systematic investigation in oocytes during maternal aging using different systems

Generating Hot Gas in Simulations of Disk-Galaxy Major Mergers

We report on the merger-induced generation of a shock-heated gas wind and formation of a remnant gas halo in simulations of colliding disk galaxies. The simulations use cosmologically motivated initial conditions and include the effects of radiative cooling, star formation, stellar feedback and the non-adiabatic heating of gas. The non-adiabatic heating, i.e. shocks, generated in the final merger forces gas out of the central region of the merger remnant and into the dark-matter halo. We demonstrate that the amount of heating depends on the size of the progenitor disk galaxy as well as the initial orbit the galaxies are placed on. Based upon these dependencies, we motivate a possible recipe for including this effect in semi-analytic models of galaxy formation.Comment: 4 pages, 2 figures, uses emulateapj.cls, submitted to ApJ Letter

The Relation Between Quasar and Merging Galaxy Luminosity Functions and the Merger-Induced Star Formation Rate of the Universe

Using a model for self-regulated growth of black holes (BHs) in mergers involving gas-rich galaxies, we study the relationship between quasars and the population of merging galaxies and predict the merger-induced star formation rate density of the Universe. Mergers drive nuclear gas inflows, fueling starbursts and 'buried quasars' until accretion feedback expels the gas, rendering a briefly visible optical quasar. Star formation is shut down and accretion declines, leaving a passively evolving remnant with properties typical of red, elliptical galaxies. Based on evolution of these events in our simulations, we demonstrate that the observed statistics of merger rates, luminosity functions (LFs) and mass functions, SFR distributions, specific SFRs, quasar and quasar host galaxy LFs, and elliptical/red galaxy LFs are self-consistent and follow from one another as predicted by the merger hypothesis. We use our simulations to de-convolve both quasar and merging galaxy LFs to determine the birthrate of black holes of a given final mass and merger rates as a function of stellar mass. We use this to predict the merging galaxy LF in several observed wavebands, color-magnitude relations, mass functions, absolute and specific SFR distributions and SFR density, and quasar host galaxy LFs, as a function of redshift from z=0-6. We invert this and predict e.g. quasar LFs from observed merger LFs or SFR distributions. Our results agree well with observations, but idealized models of quasar lightcurves are ruled out by comparison of merger and quasar observations at >99.9% confidence. Using only observations of quasars, we estimate the contribution of mergers to the SFR density of the Universe even to high redshifts z~4.Comment: 26 pages, 15 figures, matches version accepted to Ap

The effect of galaxy mass ratio on merger--driven starbursts

We employ numerical simulations of galaxy mergers to explore the effect of galaxy mass ratio on merger--driven starbursts. Our numerical simulations include radiative cooling of gas, star formation, and stellar feedback to follow the interaction and merger of four disk galaxies. The galaxy models span a factor of 23 in total mass and are designed to be representative of typical galaxies in the local Universe. We find that the merger--driven star formation is a strong function of merger mass ratio, with very little, if any, induced star formation for large mass ratio mergers. We define a burst efficiency that is useful to characterize the merger--driven star formation and test that it is insensitive to uncertainties in the feedback parameterization. In accord with previous work we find that the burst efficiency depends on the structure of the primary galaxy. In particular, the presence of a massive stellar bulge stabilizes the disk and suppresses merger--driven star formation for large mass ratio mergers. Direct, co--planar merging orbits produce the largest tidal disturbance and yield that most intense burst of star formation. Contrary to naive expectations, a more compact distribution of gas or an increased gas fraction both decrease the burst efficiency. Owing to the efficient feedback model and the newer version of SPH employed here, the burst efficiencies of the mergers presented here are smaller than in previous studies.Comment: 26 pages, 21 figures, submitted to MNRA

Simulations of Dust in Interacting Galaxies I: Dust Attenuation

A new Monte-Carlo radiative-transfer code, Sunrise, is used in conjunction with hydrodynamic simulations of major galaxy mergers to calculate the effects of dust in such systems. The simulations are in good agreement with observations of dust absorption in starburst galaxies, and the dust has a profound effect on their appearance. The dust attenuation increases with luminosity such that at peak luminosities ~90% of the bolometric luminosity is absorbed by dust. In general, the detailed appearance of the merging event depends on the stage of the merger and the geometry of the encounter. The fraction of bolometric energy absorbed by the dust, however, is a robust quantity that can be predicted from the intrinsic properties bolometric luminosity, baryonic mass, star-formation rate, and metallicity of the system. This paper presents fitting formulae, valid over a wide range of masses and metallicities, from which the absorbed fraction of luminosity (and consequently also the infrared dust luminosity) can be predicted. The attenuation of the luminosity at specific wavelengths can also be predicted, albeit with a larger scatter due to the variation with viewing angle. These formulae for dust attenuation appear to be valid for both isolated and interacting galaxies, are consistent with earlier studies, and would be suitable for inclusion in theoretical models, e.g. semi-analytic models of galaxy formation.Comment: 12 pages, 10 figures, submitted to Ap

A screen for mutations that suppress the phenotype of Drosophila armadillo, the beta-catenin homolog.

During development signaling pathways coordinate cell fates and regulate the choice between cell survival or programmed cell death. The well-conserved Wingless/Wnt pathway is required for many developmental decisions in all animals. One transducer of the Wingless/Wnt signal is Armadillo/beta-catenin. Drosophila Armadillo not only transduces Wingless signal, but also acts in cell-cell adhesion via its role in the epithelial adherens junction. While many components of both the Wingless/Wnt signaling pathway and adherens junctions are known, both processes are complex, suggesting that unknown components influence signaling and junctions. We carried out a genetic modifier screen to identify some of these components by screening for mutations that can suppress the armadillo mutant phenotype. We identified 12 regions of the genome that have this property. From these regions and from additional candidate genes tested we identified four genes that suppress arm: dTCF, puckered, head involution defective (hid), and Dpresenilin. We further investigated the interaction with hid, a known regulator of programmed cell death. Our data suggest that Wg signaling modulates Hid activity and that Hid regulates programmed cell death in a dose-sensitive fashion

Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration

Background: Stressed and hospitalized goats are at risk of developing abomasal (gastric) ulceration, but there is a paucity of pharmacokinetic studies for proton pump inhibiting drugs, such as, esomeprazole in goats. Objectives: The objectives for this study were to estimate plasma pharmacokinetic parameters for esomeprazole in adult goats after intravenous (IV) and subcutaneous (SQ) administration. A secondary objective was to describe the plasma kinetics of the metabolite esomeprazole sulfone after IV and SC administration in goats. Materials and methods: Esomeprazole was administered to 5 adult goats in a crossover study at doses of 1 mg/kg IV or 2 mg/kg SC. Plasma samples were collected over 36 h and analyzed via reverse phase HPLC to determine concentrations of esomeprazole and esomeprazole sulfone. Pharmacokinetic parameters were derived via non-compartmental analysis. Results: Following IV administration, mean values for plasma clearance (Cl), elimination half-life [T1/2 (λz)], C0, and volume of distribution (Vz) of esomeprazole were estimated at 24.9 mL/min/kg, 6 min, 2.324 μg/mL, and 0.23 L/kg, respectively. After SC administration elimination half-life, maximum concentration (Cmax) and time to maximum concentration (Tmax) of esomeprazole were estimated at 29 min, 1.038 μg/mL, and 22 minutes respectively. Maximum concentrations of the sulfone metabolite were 32 and 18 ng/mL after IV and SC administration. Conclusion: Esomeprazole was rapidly eliminated from plasma after both IV and SC injection in goats. The elimination half-life in goats appears to be shorter than reported in dogs, as well as less than that reported for pantoprazole in goats. The sulfone metabolite was detected and also rapidly eliminated from the plasma after both IV and SC administration. Additional pharmacodynamic investigations are needed to determine the efficacy of esomeprazole on abomasal (gastric) acid suppression in goats and could include larger doses or additional routes of administration

The effects of a hot gaseous halo on disc thickening in galaxy minor mergers

We employ hydrodynamical simulations to study the effects of dissipational gas physics on the vertical heating and thickening of disc galaxies during minor mergers. For the first time we present a suite of simulations that includes a diffuse, rotating, cooling, hot gaseous halo, as predicted by cosmological hydrodynamical simulations as well as models of galaxy formation. We study the effect of this new gaseous component on the vertical structure of a Milky Way-like stellar disc during 1:10 and 1:5 mergers. For 1:10 mergers we find no increased final thin disc scale height compared to the isolated simulation, leading to the conclusion that thin discs can be present even after a 1:10 merger if a reasonable amount of hot gas is present. The reason for this is the accretion of new cold gas, leading to the formation of a massive new thin stellar disc that dominates the surface brightness profile. In a previous study, in which we included only cold gas in the disk, we showed that the presence of cold gas decreased the thickening by a minor merger relative to the no-gas case. Here, we show that the evolution of the scale height in the presences of a cooling hot halo is dominated by the formation of the new stellar disc. In this scenario, the thick disc is the old stellar disc that has been thickened in a minor merger at z>1, while the thin disc is the new stellar disc that reforms after this merger. In addition, we study the evolution of the scale height during a 1:5 merger and find that a thin disc can be present even after this merger, provided enough hot gas is available. The final scale height in our simulations depends on the mass of the hot gaseous halo, the efficiency of the winds and the merger mass ratio. We find post-merger values in the range 0.5<z0<1.0 kpc in good agreement with observational constraints by local galaxies.Comment: 14 pages, 10 figures, 2 tables, submitted to MNRA

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: common genetic variants in GCK and TCF7L2 are associated with fasting and postchallenge glucose levels in pregnancy and with the new consensus definition of gestational diabetes mellitus from the International Association of Diabetes and Pregnancy Study Groups.

OBJECTIVE: Common genetic variants in GCK and TCF7L2 are associated with higher fasting glucose and type 2 diabetes in nonpregnant populations. However, their associations with glucose levels from oral glucose tolerance tests (OGTTs) in pregnancy have not been assessed in a large sample. We hypothesized that these variants are associated with quantitative measures of glycemia in pregnancy. RESEARCH DESIGN AND METHODS: We analyzed the associations between variants rs1799884 (GCK) and rs7903146 (TCF7L2) and OGTT outcomes at 24-32 weeks' gestation in 3,811 mothers of European (U.K. and Australia) and 1,706 mothers of Asian (Thailand) ancestry from the HAPO cohort. We also tested associations with offspring birth anthropometrics. RESULTS: The maternal GCK variant was associated with higher fasting glucose in Europeans (P = 0.001) and Thais (P 0.05). In both populations, both variants were associated with higher odds of gestational diabetes mellitus according to the new International Association of Diabetes and Pregnancy Study Groups recommendations (P = 0.001-0.08). CONCLUSIONS: Maternal GCK and TCF7L2 variants are associated with glucose levels known to carry an increased risk of adverse pregnancy outcome in women without overt diabetes. Further studies will be important to determine the variance in maternal glucose explained by all known genetic variants

Advancing the human right to housing in post-Katrina New Orleans: discursive opportunity structures in housing and community development

In post-Katrina New Orleans, housing and community development (HCD) advocates clashed over the future of public housing. This case study examines the evolution of and limits to a human right to housing frame introduced by one nongovernmental organization (NGO). Ferree’s concept of the discursive opportunity structure and Bourdieu’s social field ground this NGO’s failure to advance a radical economic human rights frame, given its choice of a political inside strategy that opened up for HCD NGOs after Hurricane Katrina. Strategic and ideological differences within the field limited the efficacy of this rights-based frame, which was seen as politically radical and risky compared with more resonant frames for seeking affordable housing resources and development opportunities. These divides flowed from the position of the movement-born HCD field within a neoliberal political economy, especially its current institutionalization in the finance and real estate sector, and its dependence on the state for funding and political legitimacy