28 research outputs found

    Polymeric Schiff bases. 17 - Azomethine copolymers

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    Chemical synthesis of azomethine copolymers by melt polymerization techniques - polymeric Schiff base

    Differential Roles for L-Type Calcium Channel Subtypes in Alcohol Dependence

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    It has previously been shown that the inhibition of L-type calcium channels (LTCCs) decreases alcohol consumption, although the contribution of the central LTCC subtypes Cav1.2 and Cav1.3 remains unknown. Here, we determined changes in Cav1.2 (Cacna1c) and Cav1.3 (Cacna1d) mRNA and protein expression in alcohol-dependent rats during protracted abstinence and naive controls using in situ hybridization and western blot analysis. Functional validation was obtained by electrophysiological recordings of calcium currents in dissociated hippocampal pyramidal neurons. We then measured alcohol self-administration and cue-induced reinstatement of alcohol seeking in dependent and nondependent rats after intracerebroventricular (i.c.v.) injection of the LTCC antagonist verapamil, as well as in mice with an inducible knockout (KO) of Cav1.2 in Ca2+/calmodulin-dependent protein kinase parallel to alpha (CaMKII alpha)-expressing neurons. Our results show that Cacna1c mRNA concentration was increased in the amygdala and hippocampus of alcohol-dependent rats after 21 days of abstinence, with no changes in Cacna1d mRNA. This was associated with increased Cav1.2 protein concentration and L-type calcium current amplitudes. Further analysis of Cacna1c mRNA in the CA1, basolateral amygdala (BLA), and central amygdala (CeA) revealed a dynamic regulation over time during the development of alcohol dependence. The inhibition of central LTCCs via i. c. v. administration of verapamil prevented cue-induced reinstatement of alcohol seeking in alcohol-dependent rats. Further studies in conditional Cav1.2-KO mice showed a lack of dependence-induced increase of alcohol-seeking behavior. Together, our data indicate that central Cav1.2 channels, rather than Cav1.3, mediate alcohol-seeking behavior. This finding may be of interest for the development of new antirelapse medications

    A previously functional tetracycline-regulated transactivator fails to target gene expression to the bone

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    <p>Abstract</p> <p>Background</p> <p>The tetracycline-controlled transactivator system is a powerful tool to control gene expression <it>in vitro </it>and to generate consistent and conditional transgenic <it>in vivo </it>model organisms. It has been widely used to study gene function and to explore pathological mechanisms involved in human diseases. The system permits the regulation of the expression of a target gene, both temporally and quantitatively, by the application of tetracycline or its derivative, doxycycline. In addition, it offers the possibility to restrict gene expression in a spatial fashion by utilizing tissue-specific promoters to drive the transactivator.</p> <p>Findings</p> <p>In this study, we report our problems using a reverse tetracycline-regulated transactivator (rtTA) in a transgenic mouse model system for the bone-specific expression of the Hutchinson-Gilford progeria syndrome mutation. Even though prior studies have been successful utilizing the same rtTA, expression analysis of the transactivator revealed insufficient activity for regulating the transgene expression in our system. The absence of transactivator could not be ascribed to differences in genetic background because mice in a mixed genetic background and in congenic mouse lines showed similar results.</p> <p>Conclusions</p> <p>The purpose of this study is to report our negative experience with previously functional transactivator mice, to raise caution in the use of tet-based transgenic mouse lines and to reinforce the need for controls to ensure the stable functionality of generated tetracycline-controlled transactivators over time.</p

    Parton distribution functions at LO, NLO and NNLO with correlated uncertainties between orders

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    Sets of parton distribution functions (PDFs) of the proton are reported for the leading (LO), next-to-leading (NLO) and next-to-next-to leading order (NNLO) QCD calculations. The parton distribution functions are determined with the HERAFitter program using the data from the HERA experiments and preserving correlations between uncertainties for the LO, NLO and NNLO PDF sets. The sets are used to study cross-section ratios and their uncertainties when calculated at different orders in QCD. A reduction of the overall theoretical uncertainty is observed if correlations between the PDF sets are taken into account for the ratio of WWWW di-boson to ZZ boson production cross sections at the LHC

    Patterns of Freshwater Species Richness, Endemism, and Vulnerability in California.

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    The ranges and abundances of species that depend on freshwater habitats are declining worldwide. Efforts to counteract those trends are often hampered by a lack of information about species distribution and conservation status and are often strongly biased toward a few well-studied groups. We identified the 3,906 vascular plants, macroinvertebrates, and vertebrates native to California, USA, that depend on fresh water for at least one stage of their life history. We evaluated the conservation status for these taxa using existing government and non-governmental organization assessments (e.g., endangered species act, NatureServe), created a spatial database of locality observations or distribution information from ~400 data sources, and mapped patterns of richness, endemism, and vulnerability. Although nearly half of all taxa with conservation status (n = 1,939) are vulnerable to extinction, only 114 (6%) of those vulnerable taxa have a legal mandate for protection in the form of formal inclusion on a state or federal endangered species list. Endemic taxa are at greater risk than non-endemics, with 90% of the 927 endemic taxa vulnerable to extinction. Records with spatial data were available for a total of 2,276 species (61%). The patterns of species richness differ depending on the taxonomic group analyzed, but are similar across taxonomic level. No particular taxonomic group represents an umbrella for all species, but hotspots of high richness for listed species cover 40% of the hotspots for all other species and 58% of the hotspots for vulnerable freshwater species. By mapping freshwater species hotspots we show locations that represent the top priority for conservation action in the state. This study identifies opportunities to fill gaps in the evaluation of conservation status for freshwater taxa in California, to address the lack of occurrence information for nearly 40% of freshwater taxa and nearly 40% of watersheds in the state, and to implement adequate protections for freshwater taxa where they are currently lacking
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