Bladder-cancer-associated mutations in RXRA activate peroxisome proliferator-activated receptors to drive urothelial proliferation

RXRA regulates transcription as part of a heterodimer with 14 other nuclear receptors, including the peroxisome proliferator-activated receptors (PPARs). Analysis from TCGA raised the possibility that hyperactive PPAR signaling, either due to PPAR gamma gene amplification or RXRA hot-spot mutation (S427F/Y) drives 20–25% of human bladder cancers. Here, we characterize mutant RXRA, demonstrating it induces enhancer/promoter activity in the context of RXRA/PPAR heterodimers in human bladder cancer cells. Structure-function studies indicate that the RXRA substitution allosterically regulates the PPAR AF2 domain via an aromatic interaction with the terminal tyrosine found in PPARs. In mouse urothelial organoids, PPAR agonism is sufficient to drive growth-factor-independent growth in the context of concurrent tumor suppressor loss. Similarly, mutant RXRA stimulates growth-factor-independent growth of Trp53/Kdm6a null bladder organoids. Mutant RXRA-driven growth of urothelium is reversible by PPAR inhibition, supporting PPARs as targetable drivers of bladder cancer.</jats:p

Forecasting temporal dynamics of cutaneous leishmaniasis in Northeast Brazil.

IntroductionCutaneous leishmaniasis (CL) is a vector-borne disease of increasing importance in northeastern Brazil. It is known that sandflies, which spread the causative parasites, have weather-dependent population dynamics. Routinely-gathered weather data may be useful for anticipating disease risk and planning interventions.Methodology/principal findingsWe fit time series models using meteorological covariates to predict CL cases in a rural region of Bahía, Brazil from 1994 to 2004. We used the models to forecast CL cases for the period 2005 to 2008. Models accounting for meteorological predictors reduced mean squared error in one, two, and three month-ahead forecasts by up to 16% relative to forecasts from a null model accounting only for temporal autocorrelation.SignificanceThese outcomes suggest CL risk in northeastern Brazil might be partially dependent on weather. Responses to forecasted CL epidemics may include bolstering clinical capacity and disease surveillance in at-risk areas. Ecological mechanisms by which weather influences CL risk merit future research attention as public health intervention targets

Interpretation of the in-plane infrared response of the high-Tc cuprate superconductors involving spin fluctuations revisited

The in-plane infrared response of the high-Tc cuprate superconductors was studied using the spin-fermion model, where charged quasiparticles of the copper-oxygen planes are coupled to spin fluctuations. First, we analyzed structures of the superconducting-state conductivity reflecting the coupling of the quasiparticles to the resonance mode observed by neutron scattering. The conductivity computed with the input spin susceptibility in the simple form of the mode exhibits two prominent features: an onset of the real part of the conductivity starting around the frequency of the mode omega_{0} and a maximum of a related function W(omega), roughly proportional to the second derivative of the scattering rate, centered approximately at omega=omega_{0}+Delta_{0}/hbar, where Delta_{0} is the maximum value of the superconducting gap. The two structures are well known from earlier studies. Their physical meaning, however, has not been sufficiently elucidated thus far. Our analysis involving quasiparticle spectral functions provides a clear interpretation. Second, we explored the role played by the spin-fluctuation continuum. Third, we investigated the temperature dependence of the conductivity, of the intraband spectral weight, and of the effective kinetic energy. The changes of the latter two quantities below Tc are determined by the formation of the gap, by a feedback effect of the spin fluctuations on the quasiparticles, and by a significant shift of the chemical potential.Comment: 20 pages, 18 figures, submitted to Physical Review

Thermodynamics of the half-filled Kondo lattice model around the atomic limit

We present a perturbation theory for studying thermodynamic properties of the Kondo spin liquid phase of the half-filled Kondo lattice model. The grand partition function is derived to calculate chemical potential, spin and charge susceptibilities and specific heat. The treatment is applicable to the model with strong couplings in any dimensions (one, two and three dimensions). The chemical potential equals zero at any temperatures, satisfying the requirement of the particle-hole symmetry. Thermally activated behaviors of the spin(charge) susceptibility due to the spin(quasiparticle) gap can be seen and the two-peak structure of the specific heat is obtained. The same treatment to the periodic Anderson model around atomic limit is also briefly discussed.Comment: 5 pages, 3 figures, to appear in Phys. Rev.

The viability of a thermoelectric fuel conditioning system for a diesel engine utilizing biodiesel

Certain internal combustion engines, which run on hydrocarbon fuels, experience difficulty upon engine start-up in extreme cold weather. As ambient temperature decreases below the fuel cloud point and beyond, paraffin form in the fuel and eventually clog the fuel filter causing the engine to fail to start. This problem becomes more pronounced when the engine in question is a Diesel and the fuel utilized is biodiesel. As an alternative fuel source, biodiesel has many advantages; however, its cold weather performance is worse than even conventional diesel fuel. As biodiesel becomes more integrated into the world’s energy usage scenario, one of the systems within a Diesel engine that requires further investigation is its fuel conditioning system. This thesis describes research aimed at the development of a fuel conditioning system that utilizes several emerging technologies while decreasing the amount of electrical energy required for operation. The system utilizes a eutectic - thermoelectric (E-TE) combination which consists of a eutectic compound based latent heat storage device with adjacent thermoelectric elements to transfer waste heat stored in the eutectic reservoir into the fuel filter, thus diminishing the amount of electrical energy typically required for the fuel conditioning process. Simulations of the E-TE system are conducted while operating within three different modes (start-up, heat storage, and electrical energy generation) depending on fuel and ambient temperature conditions, while a supervisory controller distinguishes between desired operational status. The research activities and findings reported contained herein include development of E-TE system models which each consist of several components. The first of which is a set of control laws, implemented in Simulink, which control system performance using various temperature related variables. The second component is a supervisory control law, implemented in Matlab®, which controls the switching between various modes of operation. With system model developed, the viability of the system is examined

Economics of marginal corn ground compared to seeding to pasture or hay

High commodity grain prices from 2008-2013 attracted marginal ground in to row crop production at the expense of pasture, hay and wooded acres in the Driftless Region. CBO, USDA and FAPRI forecast till 2018 and beyond is for average grain prices to be at or below costs of production. In some cases the marginal, lower productive ground may not make economic sense to continue in grain production

Vitellogenesis in \u3ci\u3eHyalomma dromedarii\u3c/i\u3e (Acari: Ixodidae): A Model for Analysis of Endocrine Regulation in Ixodid Ticks

The egg yolk proteins, vitellins, and their hemolymph precursors, vitellogenins, were characterized in the ixodid tick Hyalomma dromedarii. Three vitellins were identified. The high molecular weight vitellins, VN A and VN B, were composed of seven homologous molecular weight subunit polypeptides, VN 1-7. VN A appears to be a dimeric form of VN B. VN C was composed of single polypeptide. Low levels of vitellogenin, were identified in western immunoblots utilizing antibody raised against purified vitellin. Adult protein and polypeptide profiles, including vitellin and vitellogenin, were characterized as a function of sex, tissue and reproductive development. Quantitative assessment of the vitellin and vitellogenin was accomplished by ELISA. By this method, a rise in the level of vitellogenin from 0.15 to 11.19 % of the hemolymph protein between the stages of fed virgin and repletion in females was observed. Similarly, fat body levels rose from 0.15 to 3.0% during these physiological stages. The level of ovarian vitellin rose rapidly from 0.39 to over 50% of the tissue protein during the four days after repletion. The level of vitellogenin in midgut, salivary gland and muscle, increased slowly during repletion, and never exceeded 1.1% of its respective tissue protein. Tissue specific synthesis of vitellogenin and vitellin was monitored in vitro. Continuous synthesis of vitellogenin was demonstrated with replete fat body tissue over an eight day culture period. Other tissues, including ovary, midgut, muscle and salivary gland, did not synthesize vitellin or vitellogenin in vitro. Stimulation of vitellogenin synthesis by various authentic hormones and tissue extracts was tested both in vitro and in vivo. Vitellogenin synthesis by cultured fed virgin fat body was stimulated 35 fold by treatment with synganglion extracts from replete females. Similar stimulation of vitellogenesis with synganglion extracts was observed in vivo. Although Juvenile hormone bis-epoxide and 20 hydroxyecdysone treatment did not affect vitellogenin synthesis in cultured fed virgin fat body, they did demonstrate stimulatory activity in vivo. Multihormonal regulation of vitellogenesis, involving a synganglion factor, a juvenoid and 20 hydroxyecdysone is considered

Influence of Dietary Modification With and Without Exercise on Physical Performance in Male Rats

This study examined if specific dietary plan, with and without exercise, can positively impact physical performance in male rats. The present research examined three aspects of physical performance in relation to the Daniel Fast diet (DF) compared to a Western diet (WD). Long-Evans rats (n=56, aged 3-4 weeks) were on a 12 week diet and exercise intervention. Results demonstrated that treadmill run time to exhaustion increased in both exercise groups, with a greater increase in the DF+E group. Wire hang and slant board performance decreased from pre to post in all groups at a similar rate. Body weight gain was greater in WD vs. all groups. Body composition demonstrated a lower fat mass in DF groups vs. WD groups. Improved performance in DF compared to WD for treadmill run may be due to the favorable composition of the DF diet (lower glycemic carbohydrate; poly-unsaturated fatty acids) and the resultant lower fat mass