Diet modifies pioglitazone’s influence on hepatic PPARγ-regulated mitochondrial gene expression

Pioglitazone (Pio) is a thiazolidinedione (TZD) insulin-sensitizing drug whose effects result predominantly from its modulation of the transcriptional activity of peroxisome proliferator-activated-receptor-gamma (PPARγ). Pio is used to treat human insulin-resistant diabetes and also frequently considered for treatment of nonalcoholic steatohepatitis (NASH). In both settings, Pio’s beneficial effects are believed to result primarily from its actions on adipose PPARγ activity, which improves insulin sensitivity and reduces the delivery of fatty acids to the liver. Nevertheless, a recent clinical trial showed variable efficacy of Pio in human NASH. Hepatocytes also express PPARγ, and such expression increases with insulin resistance and in nonalcoholic fatty liver disease (NAFLD). Furthermore, mice that overexpress hepatocellular PPARγ and Pio-treated mice with extrahepatic PPARγ gene disruption develop features of NAFLD. Thus, Pio’s direct impact on hepatocellular gene expression might also be a determinant of this drug’s ultimate influence on insulin resistance and NAFLD. Previous studies have characterized Pio’s PPARγ-dependent effects on hepatic expression of specific adipogenic, lipogenic, and other metabolic genes. However, such transcriptional regulation has not been comprehensively assessed. The studies reported here address that consideration by genome-wide comparisons of Pio’s hepatic transcriptional effects in wildtype (WT) and liver-specific PPARγ-knockout (KO) mice given either control or high-fat (HFD) diets. The results identify a large set of hepatic genes for which Pio’s liver PPARγ-dependent transcriptional effects are concordant with its effects on RXR-DNA binding in WT mice. These data also show that HFD modifies Pio’s influence on a subset of such transcriptional regulation. Finally, our findings reveal a broader influence of Pio on PPARγ-dependent hepatic expression of nuclear genes encoding mitochondrial proteins than previously recognized. Taken together, these studies provide new insights about the tissue-specific mechanisms by which Pio affects hepatic gene expression and the broad scope of this drug’s influence on such regulation

Galaxies Probing Galaxies at High Resolution: Co-Rotating Gas Associated with a Milky Way Analog at z=0.4

We present results on gas flows in the halo of a Milky Way-like galaxy at z=0.413 based on high-resolution spectroscopy of a background galaxy. This is the first study of circumgalactic gas at high spectral resolution towards an extended background source (i.e., a galaxy rather than a quasar). Using longslit spectroscopy of the foreground galaxy, we observe spatially extended H alpha emission with circular rotation velocity v=270 km/s. Using echelle spectroscopy of the background galaxy, we detect Mg II and Fe II absorption lines at impact parameter rho=27 kpc that are blueshifted from systemic in the sense of the foreground galaxy's rotation. The strongest absorber EW(2796) = 0.90 A has an estimated column density (N_H>10^19 cm-2) and line-of-sight velocity dispersion (sigma=17 km/s) that are consistent with the observed properties of extended H I disks in the local universe. Our analysis of the rotation curve also suggests that this r=30 kpc gaseous disk is warped with respect to the stellar disk. In addition, we detect two weak Mg II absorbers in the halo with small velocity dispersions (sigma<10 km/s). While the exact geometry is unclear, one component is consistent with an extraplanar gas cloud near the disk-halo interface that is co-rotating with the disk, and the other is consistent with a tidal feature similar to the Magellanic Stream. We can place lower limits on the cloud sizes (l>0.4 kpc) for these absorbers given the extended nature of the background source. We discuss the implications of these results for models of the geometry and kinematics of gas in the circumgalactic medium.Comment: 14 pages, 6 figures, submitted to ApJ, comments welcom

The Role of Landscape Connectivity in Planning and Implementing Conservation and Restoration Priorities. Issues in Ecology

Landscape connectivity, the extent to which a landscape facilitates the movements of organisms and their genes, faces critical threats from both fragmentation and habitat loss. Many conservation efforts focus on protecting and enhancing connectivity to offset the impacts of habitat loss and fragmentation on biodiversity conservation, and to increase the resilience of reserve networks to potential threats associated with climate change. Loss of connectivity can reduce the size and quality of available habitat, impede and disrupt movement (including dispersal) to new habitats, and affect seasonal migration patterns. These changes can lead, in turn, to detrimental effects for populations and species, including decreased carrying capacity, population declines, loss of genetic variation, and ultimately species extinction. Measuring and mapping connectivity is facilitated by a growing number of quantitative approaches that can integrate large amounts of information about organisms’ life histories, habitat quality, and other features essential to evaluating connectivity for a given population or species. However, identifying effective approaches for maintaining and restoring connectivity poses several challenges, and our understanding of how connectivity should be designed to mitigate the impacts of climate change is, as yet, in its infancy. Scientists and managers must confront and overcome several challenges inherent in evaluating and planning for connectivity, including: •characterizing the biology of focal species; •understanding the strengths and the limitations of the models used to evaluate connectivity; •considering spatial and temporal extent in connectivity planning; •using caution in extrapolating results outside of observed conditions; •considering non-linear relationships that can complicate assumed or expected ecological responses; •accounting and planning for anthropogenic change in the landscape; •using well-defined goals and objectives to drive the selection of methods used for evaluating and planning for connectivity; •and communicating to the general public in clear and meaningful language the importance of connectivity to improve awareness and strengthen policies for ensuring conservation. Several aspects of connectivity science deserve additional attention in order to improve the effectiveness of design and implementation. Research on species persistence, behavioral ecology, and community structure is needed to reduce the uncertainty associated with connectivity models. Evaluating and testing connectivity responses to climate change will be critical to achieving conservation goals in the face of the rapid changes that will confront many communities and ecosystems. All of these potential areas of advancement will fall short of conservation goals if we do not effectively incorporate human activities into connectivity planning. While this Issue identifies substantial uncertainties in mapping connectivity and evaluating resilience to climate change, it is also clear that integrating human and natural landscape conservation planning to enhance habitat connectivity is essential for biodiversity conservation

The Color Magnitude Distribution of Field Galaxies to z~3: the evolution and modeling of the blue sequence

Using deep NIR VLT/ISAAC and optical HST/WFPC2 imaging in the fields of the HDFS and MS1054-03, we study the rest-frame UV-to-optical colors and magnitudes of galaxies to z~3. While there is no evidence for a red sequence at z~3, there does appear to be a well-defined color-magnitude relation (CMR) for blue galaxies at all redshifts, with more luminous galaxies having redder U-V colors. The slope of the blue CMR is independent of redshift d(U-V)/dMV = -0.09 (0.01) and can be explained by a correlation of dust-reddening with luminosity. The average color at fixed luminosity reddens strongly \Delta(U-V) = 0.75 from z~3 to z=0, much of which can be attributed to aging of the stars. The color scatter of the blue sequence is relatively small sigma(U-V) = 0.25 (0.03) and constant to z~3, but notably asymmetrical with a sharp blue ridge and a wing towards redder colors. We explore sets of star formation histories to study the constraints placed by the shape of the scatter at z=2-3. One particular set of models, episodic star formation, reproduces the detailed properties very well. For a two-state model with high and low star formation, the duty cycle is constrained to be > 40% and the contrast between the states must be a factor > 5 (or a scatter in log(SFR) of > 0.35 dex around the mean). However, episodic models do not explain the observed tail of very red galaxies, primarily Distant Red Galaxies (DRGs), which may have ceased star formation altogether or are more heavily obscured. Finally, the relative number density of red, luminous MV < -20.5 galaxies increases by a factor of ~ 6 from z = 2.7 to z = 0.5, as does their contribution to the total rest-frame V-band luminosity density. We are likely viewing the progressive formation of red, passively evolving galaxies.Comment: 29 pages, 24 figures, in emulateapj style. Abstract is abridged. Some postscript figures are compressed. accepted for publication in ApJ (scheduled for August 20, 2007, v665n 2 issue

The Origin of Line Emission in Massive z~2.3 Galaxies: Evidence for Cosmic Downsizing of AGN Host Galaxies

Using the Gemini Near-InfraRed Spectrograph (GNIRS), we have assembled a complete sample of 20 K-selected galaxies at 2.0<z<2.7 with high quality near-infrared spectra. As described in a previous paper, 9 of these 20 galaxies have strongly suppressed star formation and no detected emission lines. The present paper concerns the 11 galaxies with detected Halpha emission, and studies the origin of the line emission using the GNIRS spectra and follow-up observations with SINFONI on the VLT. Based on their [NII]/Halpha ratios, the spatial extent of the line emission and several other diagnostics, we infer that four of the eleven emission-line galaxies host narrow line active galactic nuclei (AGNs). The AGN host galaxies have stellar populations ranging from evolved to star-forming. Combining our sample with a UV-selected galaxy sample at the same redshift that spans a broader range in stellar mass, we find that black-hole accretion is more effective at the high-mass end of the galaxy distribution (~2.9x10^11 Msun) at z~2.3. Furthermore, by comparing our results with SDSS data, we show that the AGN activity in massive galaxies has decreased significantly between z~2.3 and z~0. AGNs with similar normalized accretion rates as those detected in our K-selected galaxies reside in less massive galaxies (~4.0x10^10 Msun) at low redshift. This is direct evidence for downsizing of AGN host galaxies. Finally, we speculate that the typical stellar mass-scale of the actively accreting AGN host galaxies, both at low and at high redshift, might be similar to the mass-scale at which star-forming galaxies seem to transform into red, passive systems.Comment: Accepted for publication in the Astrophysical Journa

The size evolution of galaxies since z~3: combining SDSS, GEMS and FIRES

We present the evolution of the luminosity-size and stellar mass-size relations of luminous (L_V>3.4x10^10h_70^-2L_sun) and of massive (M_*>3x10^10h_70^-2M_sun) galaxies in the last ~11 Gyr. We use very deep near-infrared images of the Hubble Deep Field-South and the MS1054-03 field in the J_s, H and K_s bands from FIRES to retrieve the sizes in the optical rest-frame for galaxies with z>1. We combine our results with those from GEMS at 0.2<z<1 and SDSS at z~0.1 to achieve a comprehensive picture of the optical rest-frame size evolution from z=0 to z=3. Galaxies are differentiated according to their light concentration using the Sersic index n. For less concentrated objects, the galaxies at a given luminosity were typically ~3+-0.5 (+-2 sigma) times smaller at z~2.5 than those we see today. The stellar mass-size relation has evolved less: the mean size at a given stellar mass was \~2+-0.5 times smaller at z~2.5, evolving proportional to (1+z)^{-0.40+-0.06}. Simple scaling relations between dark matter halos and baryons in a hierarchical cosmogony predict a stronger (although consistent within the error bars) than observed evolution of the stellar mass-size relation. The observed luminosity-size evolution out to z~2.5 matches well recent infall model predictions for Milky-Way type objects. For low-n galaxies, the evolution of the stellar mass-size relation would follow naturally if the individual galaxies grow inside-out. For highly concentrated objects, the situation is as follows: at a given luminosity, these galaxies were ~2.7+-1.1 times smaller at z~2.5 (or put differently, were typically ~2.2+-0.7 mag brighter at a given size than they are today), and at a given stellar mass the size has evolved proportional to (1+z)^{-0.45+-0.10}.Comment: Accepted for publication in ApJ. The new version includes several improvements: much accurate size estimations and a better completeness and robustness analysis. Tables of data are included. 29 pages and 14 figures (one low resolution

Mass equidistribution of Hilbert modular eigenforms

Let F be a totally real number field, and let f traverse a sequence of non-dihedral holomorphic eigencuspforms on GL(2)/F of weight (k_1,...,k_n), trivial central character and full level. We show that the mass of f equidistributes on the Hilbert modular variety as max(k_1,...,k_n) tends to infinity. Our result answers affirmatively a natural analogue of a conjecture of Rudnick and Sarnak (1994). Our proof generalizes the argument of Holowinsky-Soundararajan (2008) who established the case F = Q. The essential difficulty in doing so is to adapt Holowinsky's bounds for the Weyl periods of the equidistribution problem in terms of manageable shifted convolution sums of Fourier coefficients to the case of a number field with nontrivial unit group.Comment: 40 pages; typos corrected, nearly accepted for

Ionized Gas Extended Over 40 kpc in an Odd Radio Circle Host Galaxy

A new class of extragalactic astronomical sources discovered in 2021, named Odd Radio Circles (ORCs, Norris et al. 2021), are large rings of faint, diffuse radio continuum emission spanning ~1 arcminute on the sky. Galaxies at the centers of several ORCs have photometric redshifts of z~0.3-0.6, implying physical scales of several 100 kiloparsecs in diameter for the radio emission, the origin of which is unknown. Here we report spectroscopic data on an ORC including strong [OII] emission tracing ionized gas in the central galaxy of ORC4 at z=0.4512. The physical extent of the [OII] emission is ~40 kpc in diameter, larger than expected for a typical early-type galaxy (Pandya et al, 2017) but an order of magnitude smaller than the large-scale radio continuum emission. We detect a ~200 km/s velocity gradient across the [OII] nebula, as well as a high velocity dispersion of ~180 km/s. The [OII] equivalent width (EW, ~50 Ang) is extremely high for a quiescent galaxy. The morphology, kinematics, and strength of the [OII] emission are consistent with the infall of shock ionized gas near the galaxy, following a larger-scale, outward moving shock driven by a galactic wind. Both the extended optical and radio emission, while observed on very different scales, may therefore result from the same dramatic event.Comment: 7 figures, accepted to Natur

Perturbative calculation of the scaled factorial moments in second-order quark-hadron phase transition within the Ginzburg-Landau description

The scaled factorial moments $F_q$ are studied for a second-order quark-hadron phase transition within the Ginzburg-Landau description. The role played by the ground state of the system under low temperature is emphasized. After a local shift of the order parameter the fluctuations are around the ground state, and a perturbative calculation for $F_q$ can be carried out. Power scaling between $F_q$'s is shown, and a universal scaling exponent $\nu\simeq 1.75$ is given for the case with weak correlations and weak self-interactions.Comment: 12 pages in RevTeX, 12 eps figure