Estrogen Receptor Alpha (ESR1)-Dependent Regulation of the Mouse Oviductal Transcriptome

Estrogen receptor-α (ESR1) is an important transcriptional regulator in the mammalian oviduct, however ESR1-dependent regulation of the transcriptome of this organ is not well defined, especially at the genomic level. The objective of this study was therefore to investigate estradiol- and ESR1-dependent regulation of the transcriptome of the oviduct using transgenic mice, both with (ESR1KO) and without (wild-type, WT) a global deletion of ESR1. Oviducts were collected from ESR1KO and WT littermates at 23 days of age, or ESR1KO and WT mice were treated with 5 IU PMSG to stimulate follicular development and the production of ovarian estradiol, and the oviducts collected 48 h later. RNA extracted from whole oviducts was hybridized to Affymetrix Genechip Mouse Genome 430–2.0 arrays (n = 3 arrays per genotype and treatment) or reverse transcribed to cDNA for analysis of the expression of selected mRNAs by real-time PCR. Following microarray analysis, a statistical two-way ANOVA and pairwise comparison (LSD test) revealed 2428 differentially expressed transcripts (DEG’s, P \u3c 0.01). Genotype affected the expression of 2215 genes, treatment (PMSG) affected the expression of 465 genes, and genotype x treatment affected the expression of 438 genes. With the goal of determining estradiol/ESR1-regulated function, gene ontology (GO) and bioinformatic pathway analyses were performed on DEG’s in the oviducts of PMSG-treated ESR1KO versus PMSG-treated WT mice. Significantly enriched GO molecular function categories included binding and catalytic activity. Significantly enriched GO cellular component categories indicated the extracellular region. Significantly enriched GO biological process categories involved a single organism, modulation of a measurable attribute and developmental processes. Bioinformatic analysis revealed ESR1-regulation of the immune response within the oviduct as the primary canonical pathway. In summary, a transcriptomal profile of estradiol- and ESR1-regulated gene expression and related bioinformatic analysis is presented to increase our understanding of how estradiol/ESR1 affects function of the oviduct, and to identify genes that may be proven as important regulators of fertility in the future

Effect of Cyclosporin A and Zidovudine on Immune Abnormalities Observed in the Murine Acquired Immunodeficiency Syndrome

Two therapeutic modalities, zidovudine (targeting retroviral replication) and cyclosporin A (targeting immunopathologic consequences of retroviral expression) were evaluated in a murine model of AIDS. In previous studies, cyclosporin A treatment (40 or 60 mg/kg/day) before and after infection with LP-BM5 murine leukemia viruses protected against the development of immunodeficiency disease. The present study extends these findings. First, a low dose of cyclosporin A (20 mg/kg/day) was ineffective, and treatment initiated 5 days after infection did not protect against virus-induced lymphoproliferation and hypergammaglobulinemia. Second, zidovudine added to drinking water (0.1 mg initiated 5 days after infection and continued for 8 weeks) was more effective than 0.2 mg/ml, given day 5–12 after infection. This treatment reduced lymph node size, disease severity as determined histologically, retrovirus-induced gp70 expression, and IgE (but not IgM and IgG) levels. Third, combined treatment had an additive, protective effect on lymphocyte proliferative capacity. This successful dual therapeutic strategy in a mouse model has potential applicability for similar approaches in treating human immunodeficiency virus infection

Van der Waals density functional: Self-consistent potential and the nature of the van der Waals bond

We derive the exchange-correlation potential corresponding to the nonlocal van der Waals density functional [M. Dion, H. Rydberg, E. Schroder, D. C. Langreth, and B. I. Lundqvist, Phys. Rev. Lett. 92, 246401 (2004)]. We use this potential for a self-consistent calculation of the ground state properties of a number of van der Waals complexes as well as crystalline silicon. For the latter, where little or no van der Waals interaction is expected, we find that the results are mostly determined by semilocal exchange and correlation as in standard generalized gradient approximations (GGA), with the fully nonlocal term giving little effect. On the other hand, our results for the van der Waals complexes show that the self-consistency has little effect at equilibrium separations. This finding validates previous calculations with the same functional that treated the fully nonlocal term as a post GGA perturbation. A comparison of our results with wave-function calculations demonstrates the usefulness of our approach. The exchange-correlation potential also allows us to calculate Hellmann-Feynman forces, hence providing the means for efficient geometry relaxations as well as unleashing the potential use of other standard techniques that depend on the self-consistent charge distribution. The nature of the van der Waals bond is discussed in terms of the self-consistent bonding charge.Comment: submitted to Phys. Rev.

RELICS: The Reionization Lensing Cluster Survey and the Brightest High-z Galaxies

Massive foreground galaxy clusters magnify and distort the light of objects behind them, permitting a view into both the extremely distant and intrinsically faint galaxy populations. We present here the z ~ 6-8 candidate high-redshift galaxies from the Reionization Lensing Cluster Survey (RELICS), a Hubble and Spitzer Space Telescope survey of 41 massive galaxy clusters spanning an area of ≈200 arcmin². These clusters were selected to be excellent lenses, and we find similar high-redshift sample sizes and magnitude distributions as the Cluster Lensing And Supernova survey with Hubble (CLASH). We discover 257, 57, and eight candidate galaxies at z ~ 6, 7, and 8 respectively, (322 in total). The observed (lensed) magnitudes of the z ~ 6 candidates are as bright as AB mag ~23, making them among the brightest known at these redshifts, comparable with discoveries from much wider, blank-field surveys. RELICS demonstrates the efficiency of using strong gravitational lenses to produce high-redshift samples in the epoch of reionization. These brightly observed galaxies are excellent targets for follow-up study with current and future observatories, including the James Webb Space Telescope

Quantum heuristic algorithm for traveling salesman problem

We propose a quantum heuristic algorithm to solve a traveling salesman problem by generalizing Grover search. Sufficient conditions are derived to greatly enhance the probability of finding the tours with extremal costs, reaching almost to unity and they are shown characterized by statistical properties of tour costs. In particular for a Gaussian distribution of the tours along the cost we show that the quantum algorithm exhibits the quadratic speedup of its classical counterpart, similarly to Grover search.Comment: Published versio

Transport and superconducting properties of Fe-based superconductors: SmFeAs(O1-x Fx) versus Fe1+y (Te1-x, Sex)

We present transport and superconducting properties - namely resistivity, magnetoresistivity, Hall effect, Seebeck effect, thermal conductivity, upper critical field - of two different families of Fe-based superconductors, which can be viewed in many respects as end members: SmFeAs(O1-xFx) with the largest Tc and the largest anisotropy and Fe1+y(Te1-x,Sex), with the largest Hc2, the lowest Tc and the lowest anisotropy. In the case of the SmFeAs(O1-xFx) series, we find that a single band description allows to extract an approximated estimation of band parameters such as carrier density and mobility from experimental data, although the behaviour of Seebeck effect as a function of doping demonstrates that a multiband description would be more appropriate. On the contrary, experimental data of the Fe1+y(Te1-x,Sex) series exhibit a strongly compensated behaviour, which can be described only within a multiband model. In the Fe1+y(Te1-x,Sex) series, the role of the excess Fe, tuned by Se stoichiometry, is found to be twofold: it dopes electrons in the system and it introduces localized magnetic moments, responsible for Kondo like scattering and likely pair-breaking of Cooper pairs. Hence, excess Fe plays a crucial role also in determining superconducting properties such as the Tc and the upper critical field Bc2. The huge Bc2 values of the Fe1+y(Te1-x,Sex) samples are described by a dirty limit law, opposed to the clean limit behaviour of the SmFeAs(O1-xFx) samples. Hence, magnetic scattering by excess Fe seems to drive the system in the dirty regime, but its detrimental pairbreaking role seems not to be as severe as predicted by theory. This issue has yet to be clarified, addressing the more fundamental issue of the interplay between magnetism and superconductivity

Statistical mechanics of a single particle in a multiscale random potential: Parisi landscapes in finite dimensional Euclidean spaces

We construct a N-dimensional Gaussian landscape with multiscale, translation invariant, logarithmic correlations and investigate the statistical mechanics of a single particle in this environment. In the limit of high dimension N>>1 the free energy of the system and overlap function are calculated exactly using the replica trick and Parisi's hierarchical ansatz. In the thermodynamic limit, we recover the most general version of the Derrida's Generalized Random Energy Model (GREM). The low-temperature behaviour depends essentially on the spectrum of length scales involved in the construction of the landscape. If the latter consists of K discrete values, the system is characterized by a K-step Replica Symmetry Breaking solution. We argue that our construction is in fact valid in any finite spatial dimensions $N\ge 1$. We discuss implications of our results for the singularity spectrum describing multifractality of the associated Boltzmann-Gibbs measure. Finally we discuss several generalisations and open problems, the dynamics in such a landscape and the construction of a Generalized Multifractal Random Walk.Comment: 25 pages, published version with a few misprints correcte

The Salmonella effector SteD mediates MARCH8-1 dependent ubiquitination of MHC II molecules and inhibits T cell activation

The SPI-2 type III secretion system (T3SS) of intracellular Salmonella enterica translocates effector proteins into mammalian cells. Infection of antigen-presenting cells results in SPI-2 T3SS-dependent ubiquitination and reduction of surface-localized mature MHC class II (mMHCII). We identify the effector SteD as required and sufficient for this process. In Mel Juso cells, SteD localized to the Golgi network and vesicles containing the E3 ubiquitin ligase MARCH8 and mMHCII. SteD caused MARCH8-dependent ubiquitination and depletion of surface mMHCII. One of two transmembrane domains and the C-terminal cytoplasmic region of SteD mediated binding to MARCH8 and mMHCII, respectively. Infection of dendritic cells resulted in SteD-dependent depletion of surface MHCII, the co-stimulatory molecule B7.2, and suppression of T cell activation. SteD also accounted for suppression of T cell activation during Salmonella infection of mice. We propose that SteD is an adaptor, forcing inappropriate ubiquitination of mMHCII by MARCH8 and thereby suppressing T cell activation

Dual Superconductor Scenario of Confinement: A Systematic Study of Gribov Copy Effects

We perform a study of the effects from maximal abelian gauge Gribov copies in the context of the dual superconductor scenario of confinement, on the basis of a novel approach for estimation of systematic uncertainties from incomplete gauge fixing. We present numerical results, in SU(2) lattice gauge theory, using the overrelaxed simulated annealing gauge fixing algorithm. We find abelian and non-abelian string tensions to differ significantly, their ratio being 0.92(4) at BETA = 2.5115. An approximate factorization of the abelian potential into monopole and photon contributions has been confirmed, the former giving rise to the abelian string tension.Comment: 35 pages uucompressed LaTeX with 10 encapsuled postscript figure