1,339 research outputs found

    The sheep conceptus modulates proteome profiles in caruncular endometrium during early pregnancy

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    This project was funded by NHS Grampian R&D project number RG05/019Peer reviewedPostprin

    Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: pharmacological and behavioral genetics evidence.

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    Considerable evidence suggests that transmission at hypocretin-1 (orexin-1) receptors (Hcrt-R1) plays an important role in the reinstatement of extinguished cocaine-seeking behaviors in rodents. However, far less is known about the role for hypocretin transmission in regulating ongoing cocaine-taking behavior. Here, we investigated the effects of the selective Hcrt-R1 antagonist SB-334867 on cocaine intake, as measured by intravenous (IV) cocaine self-administration in rats. The stimulatory effects of cocaine on brain reward systems contribute to the establishment and maintenance of cocaine-taking behaviors. Therefore, we also assessed the effects of SB-334867 on the reward-enhancing properties of cocaine, as measured by cocaine-induced lowering of intracranial self-stimulation (ICSS) thresholds. Finally, to definitively establish a role for Hcrt-R1 in regulating cocaine intake, we assessed IV cocaine self-administration in Hcrt-R1 knockout mice. We found that SB-334867 (1-4 mg/kg) dose-dependently decreased cocaine (0.5 mg/kg/infusion) self-administration in rats but did not alter responding for food rewards under the same schedule of reinforcement. This suggests that SB-334867 decreased cocaine reinforcement without negatively impacting operant performance. SB-334867 (1-4 mg/kg) also dose-dependently attenuated the stimulatory effects of cocaine (10 mg/kg) on brain reward systems, as measured by reversal of cocaine-induced lowering of ICSS thresholds in rats. Finally, we found that Hcrt-R1 knockout mice self-administered far less cocaine than wildtype mice across the entire dose-response function. These data demonstrate that Hcrt-R1 play an important role in regulating the reinforcing and reward-enhancing properties of cocaine and suggest that hypocretin transmission is likely essential for establishing and maintaining the cocaine habit in human addicts

    DevA, a GntR-like transcriptional regulator required for development in streptomyces coelicolor

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    The gram-positive filamentous bacterium Streptomyces coelicolor has a complex developmental cycle with three distinct phases: growth of the substrate mycelium, development of reproductive structures called aerial hyphae, and differentiation of these aerial filaments into long chains of exospores. During a transposon mutagenesis screen, we identified a novel gene (devA) required for proper development. The devA mutant produced only rare aerial hyphae, and those that were produced developed aberrant spore chains that were much shorter than wild-type chains and had misplaced septa. devA encodes a member of the GntR superfamily, a class of transcriptional regulators that typically respond to metabolite effector molecules. devA forms an operon with the downstream gene devB, which encodes a putative hydrolase that is also required for aerial mycelium formation on R5 medium. S1 nuclease protection analysis showed that transcription from the single devA promoter was temporally associated with vegetative growth, and enhanced green fluorescent protein transcriptional fusions showed that transcription was spatially confined to the substrate hyphae in the wild type. In contrast, devAB transcript levels were dramatically upregulated in a devA mutant and the devA promoter was also active in aerial hyphae and spores in this background, suggesting that DevA might negatively regulate its own production. This suggestion was confirmed by gel mobility shift assays that showed that DevA binds its own promoter region in vitro

    Controlling Marangoni induced instabilities in spin-cast polymer films: how to prepare uniform films

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    In both research and industrial settings spin coating is extensively used to prepare highly uniform thin polymer films. However, under certain conditions, spin coating results in films with non-uniform surface morphologies. Although the spin coating process has been extensively studied, the origin of these morphologies is not fully understood and the formation of non-uniform spincast films remains a practical problem. Here we report on experiments demonstrating that the formation of surface instabilities during spin coating is dependent on temperature. Our results suggest that non-uniform spincast films form as a result of the Marangoni effect, which describes flow due to surface tension gradients. We find that both the wavelength and amplitude of the pattern increase with temperature. Finally, and most important from a practical viewpoint, the non-uniformities in the film thickness can be entirely avoided simply by lowering the spin coating temperature.Comment: 8 pages, 6 figures. electronic supplementary material: 3 pages, 4 figure

    The insulin-like growth factor system : a target for endocrine disruptors?

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    Acknowledgments: Figures were created with BioRender.com Funding: This work was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie project PROTECTED (grant agreement No. 722634) and FREIA project (grant agreement No. 825100). The authors declare no conflicts of interest regarding this studyPeer reviewedPublisher PD

    Effects of maternal smoking on offspring reproductive outcomes : an intergenerational study in the North East of Scotland

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    The authors thank Dr Amalraj Raja (University of Aberdeen) for his expertise in planning the data analysis and the custodians of the Aberdeen Maternity and Neonatal Databank for granting access to the required data. Thanks also to the course leaders of the University of Aberdeen BSc MedSci course for enabling the research project.Peer reviewedPublisher PD

    Testing the twin testosterone transfer hypothesis : Intergenerational analysis of 317 dizygotic twins born in Aberdeen, Scotland

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    Corriegendum: The authors would like to apologise for errors in Table IV and Supplementary Table SI of the above article. ACKNOWLEDGMENTS The authors thank the custodians of Aberdeen Maternal and Neonatal Databank for granting access to the required dataset. FUNDING This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 722634.Peer reviewedPublisher PD
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