The progestin receptor interactome in the female mouse hypothalamus: Interactions with synaptic proteins are isoform specific and ligand dependent

Progestins bind to the progestin receptor (PR) isoforms, PR-A and PR-B, in brain to influence development, female reproduction, anxiety, and stress. Hormone-activated PRs associate with multiple proteins to form functional complexes. In the present study, proteins from female mouse hypothalamus that associate with PR were isolated using affinity pull-down assays with glutathione S-transferase–tagged mouse PR-A and PR-B. Using complementary proteomics approaches, reverse phase protein array (RPPA) and mass spectrometry, we identified hypothalamic proteins that interact with PR in a ligand-dependent and isoform-specific manner and were confirmed by Western blot. Synaptic proteins, including synapsin-I and synapsin-II, interacted with agonist-bound PR isoforms, suggesting that both isoforms function in synaptic plasticity. In further support, synaptogyrin-III and synapsin-III associated with PR-A and PR-B, respectively. PR also interacted with kinases, including c-Src, mTOR, and MAPK1, confirming phosphorylation as an integral process in rapid effects of PR in the brain. Consistent with a role in transcriptional regulation, PR associated with transcription factors and coactivators in a ligand-specific and isoform-dependent manner. Interestingly, both PR isoforms associated with a key regulator of energy homeostasis, FoxO1, suggesting a novel role for PR in energy metabolism. Because many identified proteins in this PR interactome are synaptic proteins, we tested the hypothesis that progestins function in synaptic plasticity. Indeed, progesterone enhanced synaptic density, by increasing synapsin-I–positive synapses, in rat primary cortical neuronal cultures. This novel combination of RPPA and mass spectrometry allowed identification of PR action in synaptic remodeling and energy homeostasis and reveals unique roles for progestins in brain function and disease

Photoreactivation of Lethal Damage Induced in Hamster X Xenopus Hybrid Cells and Their Parentals by UV Light

A85 Xenopus cells that exhibited a high level of photoreactivation (PR) and V79B2 hamster cells that exhibited little PR were fused to produce the V79B2 x A85 cell line — a hybrid line which possessed a relatively stable karyotype, with most cells containing the entire V79B2 and A85 genomes. UV and UV plus PR fluence-survival relations were then determined and compared for the hybrid and parental lines in a first attempt to elucidate interactions of the parental PR mechanisms in the hybrid. It was anticipated that the A85 genome in the hybrid would produce PR enzyme in sufficient concentration and of such a nature as to efficiently PR UV-induced lethal damage in both A85 and V79B2 DNA, and little difference would be observed in the levels of PR exhibited by the V79B2 x A85 and A85 lines. To the contrary, the level of PR observed for the hybrid was substantially below that observed for the A85 line. To assist in the interpretation of this unexpected observation, three additional preliminary studies were carried out: 1) Comparison of the optimum PR schemes for the A85 and hybrid lines, 2) examination of relations between the PR and dark UV repair mechanisms possessed by these lines, and 3) comparison of the levels of PR of chromatid deletions induced by UV in selected V79B2 and A85 chromosomes of the hybrid. The results suggested that the relatively low level of PR manifested by the hybrid cells was a consequence of their inability to efficiently PR pyrimidine dimers induced by UV in V79B2 DNA

Structural and magnetic properties of Pr-alloyed MnBi nanostructures

The structural and magnetic properties of Pr-alloyed MnBi (short MnBi-Pr) nanostructures with a range of Pr concentrations have been investigated. The nanostructures include thin films having Pr concentrations 0, 2, 3, 5 and 9 atomic percent and melt-spun ribbons having Pr concentrations 0, 2, 4 and 6 percent respectively. Addition of Pr into the MnBi lattice has produced a significant change in the magnetic properties of these nanostructures including an increase in coercivity and structural phase transition temperature, and a decrease in saturation magnetization and anisotropy energy. The highest value of coercivity measured in the films is 23 kOe and in the ribbons is 5.6 kOe. The observed magnetic properties are explained as the consequences of competing ferromagnetic and antiferromagnetic interactions

Analytical shock solutions at large and small Prandtl number

Exact one-dimensional solutions to the equations of fluid dynamics are derived in the large-Pr and small-Pr limits (where Pr is the Prandtl number). The solutions are analogous to the Pr = 3/4 solution discovered by Becker and analytically capture the profile of shock fronts in ideal gases. The large-Pr solution is very similar to Becker's solution, differing only by a scale factor. The small-Pr solution is qualitatively different, with an embedded isothermal shock occurring above a critical Mach number. Solutions are derived for constant viscosity and conductivity as well as for the case in which conduction is provided by a radiation field. For a completely general density- and temperature-dependent viscosity and conductivity, the system of equations in all three limits can be reduced to quadrature. The maximum error in the analytical solutions when compared to a numerical integration of the finite-Pr equations is O(1/Pr) for large Pr and O(Pr) for small Pr.Comment: 11 pages, 6 figures. Accepted for publication in Journal of Fluid Mechanics Rapid

On vv--domains and star operations

Let $\ast$ be a star operation on an integral domain $D$. Let \f(D) be the set of all nonzero finitely generated fractional ideals of $D$. Call $D$ a $\ast$--Pr\"ufer (respectively, $(\ast, v)$--Pr\"ufer) domain if $(FF^{-1})^{\ast}=D$ (respectively, $(F^vF^{-1})^{\ast}=D$) for all F\in \f(D). We establish that $\ast$--Pr\"ufer domains (and $(\ast, v)$--Pr\"ufer domains) for various star operations $\ast$ span a major portion of the known generalizations of Pr\"{u}fer domains inside the class of $v$--domains. We also use Theorem 6.6 of the Larsen and McCarthy book [Multiplicative Theory of Ideals, Academic Press, New York--London, 1971], which gives several equivalent conditions for an integral domain to be a Pr\"ufer domain, as a model, and we show which statements of that theorem on Pr\"ufer domains can be generalized in a natural way and proved for $\ast$--Pr\"ufer domains, and which cannot be. We also show that in a $\ast$--Pr\"ufer domain, each pair of $\ast$-invertible $\ast$-ideals admits a GCD in the set of $\ast$-invertible $\ast$-ideals, obtaining a remarkable generalization of a property holding for the "classical" class of Pr\"ufer $v$--multiplication domains. We also link $D$ being $\ast$--Pr\"ufer (or $(\ast, v)$--Pr\"ufer) with the group Inv$^{\ast}(D)$ of $\ast$-invertible $\ast$-ideals (under $\ast$-multiplication) being lattice-ordered

Topic-based integrator matching for pull request

Pull Request (PR) is the main method for code contributions from the external contributors in GitHub. PR review is an essential part of open source software developments to maintain the quality of software. Matching a new PR for an appropriate integrator will make the PR reviewing more effective. However, PR and integrator matching are now organized manually in GitHub. To make this process more efficient, we propose a Topic-based Integrator Matching Algorithm (TIMA) to predict highly relevant collaborators(the core developers) as the integrator to incoming PRs . TIMA takes full advantage of the textual semantics of PRs. To define the relationships between topics and collaborators, TIMA builds a relation matrix about topic and collaborators. According to the relevance between topics and collaborators, TIMA matches the suitable collaborators as the PR integrator

Farmers' practices and factors associated with the prevalence of all lameness and lameness attributed to interdigital dermatitis and footrot in sheep flocks in England in 2004

The aim of this study was to investigate whether the risk factors associated with all causes of lameness in sheep differed from those associated with the lesion specific causes of lameness, interdigital dermatitis (ID) and footrot (FR). A total of 809 randomly selected English sheep farmers participated in a postal survey in 2005. Data were requested on their management of lameness in 2004 and whether this had changed from 2003 and the prevalence of all lameness, and lameness caused by ID and FR. The farmer ability to recognise ID and FR was assessed from their responses to a written and pictorial description. On 443 farms where both ID and FR were correctly named by the farmer, the mean prevalence of all lameness, and lameness caused by ID and FR were 10.0% (95% CI: 8.9, 10.8), 6.5% (95% CI: 5.8, 7.3) and 3.1% (95% CI: 2.8, 3.6), respectively. The mean prevalence of all lameness on all 809 farms was not significantly different at 10.2% (95% CI: 9.2, 11.0). The data were analysed using negative binomial regression models with the three outcomes farmer estimated prevalence of all lameness and lameness caused by ID or FR in 2004. Farmers who changed management of sheep between 2003 and 2004 were excluded from the analysis, thus all fixed effects were the farmers’ managements in 2003 and 2004 to ensure that the management was in place for at least one year before the prevalence estimates. Routine foot trimming ≥once/year compared with no routine foot trimming was significantly associated with an increased prevalence of all lameness (prevalence ratio (PR) = 1.34), ID (PR = 1.50) and FR (PR = 1.35). Footbathing was also significantly associated with increased prevalence of all lameness (PR = 1.67), ID (PR = 1.68) and FR (PR = 1.76). A stocking density of >8 ewes/ha was associated with a significantly increased prevalence of all lameness (PR = 1.26) and ID (PR = 1.39). There was a significantly lower prevalence of FR (PR = 0.73; PR = 0.70, respectively) on farms in the North East and South East of England. Separating lame sheep at pasture was associated with a decreased prevalence of all lameness and ID (PR = 0.75; PR = 0.73) and location of the farm in South East England was associated with a lower prevalence of all lameness and ID (PR = 0.75; PR = 0.71, respectively). We conclude that management factors associated with all lameness, and lameness attributed to ID and FR are similar