67 research outputs found

    Regulator of G Protein Signaling 3 Modulates Wnt5b Calcium Dynamics and Somite Patterning

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    Vertebrate development requires communication among cells of the embryo in order to define the body axis, and the Wnt-signaling network plays a key role in axis formation as well as in a vast array of other cellular processes. One arm of the Wnt-signaling network, the non-canonical Wnt pathway, mediates intracellular calcium release via activation of heterotrimeric G proteins. Regulator of G protein Signaling (RGS) proteins can accelerate inactivation of G proteins by acting as G protein GTPase-activating proteins (GAPs), however, the possible role of RGS proteins in non-canonical Wnt signaling and development is not known. Here, we identify rgs3 as having an overlapping expression pattern with wnt5b in zebrafish and reveal that individual knockdown of either rgs3 or wnt5b gene function produces similar somite patterning defects. Additionally, we describe endogenous calcium release dynamics in developing zebrafish somites and determine that both rgs3 and wnt5b function are required for appropriate frequency and amplitude of calcium release activity. Using rescue of gene knockdown and in vivo calcium imaging assays, we demonstrate that the activity of Rgs3 requires its ability to interact with Gα subunits and function as a G protein GAP. Thus, Rgs3 function is necessary for appropriate frequency and amplitude of calcium release during somitogenesis and is downstream of Wnt5 activity. These results provide the first evidence for an essential developmental role of RGS proteins in modulating the duration of non-canonical Wnt signaling

    Measured greenhouse gas budgets challenge emission savings from palm-oil biodiesel

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    Special thanks to our field assistants in Indonesia (Basri, Bayu and Darwis) and to Frank Tiedemann, Edgar Tunsch, Dietmar Fellert and Malte Puhan for technical assistance. We thank PTPN VI and the owner of the plantation at Pompa Air for allowing us to conduct our research at their plantation. We would also like to thank the Spanish national project GEISpain (CGL2014-52838-C2-1-R) and the DAAD (scholarship from the programme ‘Research Stays for University Academics and Scientist 2018, ref. no. 91687130)' for partly financing A. Meijide during the preparation of this paper.The potential of palm-oil biofuels to reduce greenhouse gas (GHG) emissions compared with fossil fuels is increasingly questioned. So far, no measurement-based GHG budgets were available, and plantation age was ignored in Life Cycle Analyses (LCA). Here, we conduct LCA based on measured CO2, CH4 and N2O fluxes in young and mature Indonesian oil palm plantations. CO2 dominates the on-site GHG budgets. The young plantation is a carbon source (1012 ± 51 gC m−2 yr−1), the mature plantation a sink (−754 ± 38 gC m−2 yr−1). LCA considering the measured fluxes shows higher GHG emissions for palm-oil biodiesel than traditional LCA assuming carbon neutrality. Plantation rotation-cycle extension and earlier-yielding varieties potentially decrease GHG emissions. Due to the high emissions associated with forest conversion to oil palm, our results indicate that only biodiesel from second rotation-cycle plantations or plantations established on degraded land has the potential for pronounced GHG emission savings.This study was financed by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)— Project-ID 192626868—in the framework of the collaborative German-Indonesian research project CRC990 (subprojects A03, A04 and A05).Spanish national project GEISpain (CGL2014-52838-C2-1-R) and the DAAD (scholarship from the programme ‘Research Stays for University Academics and Scientist 2018, ref. no. 91687130

    Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

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    OBJECTIVE: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. METHODS: Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype. RESULTS: Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3). CONCLUSIONS: This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials

    Epidemiologic and clinical updates on impulse control disorders: a critical review

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    The article reviews the current knowledge about the impulse control disorders (ICDs) with specific emphasis on epidemiological and pharmacological advances. In addition to the traditional ICDs present in the DSM-IV—pathological gambling, trichotillomania, kleptomania, pyromania and intermittent explosive disorder—a brief description of the new proposed ICDs—compulsive–impulsive (C–I) Internet usage disorder, C–I sexual behaviors, C–I skin picking and C–I shopping—is provided. Specifically, the article summarizes the phenomenology, epidemiology and comorbidity of the ICDs. Particular attention is paid to the relationship between ICDs and obsessive–compulsive disorder (OCD). Finally, current pharmacological options for treating ICDs are presented and discussed

    Calcium orthophosphate-based biocomposites and hybrid biomaterials

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    Carbon metabolism of the terrestrial biosphere: A multitechnique approach for improved understanding

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    Understanding terrestrial carbon metabolism is critical because terrestrial ecosystems play a major role in the global carbon cycle. Furthermore, humans have severely disrupted the carbon cycle in ways that will alter the climate system and directly affect terrestrial metabolism. Changes in terrestrial metabolism may well be as important an indicator of global change as the changing temperature signal. Improving our understanding of the carbon cycle at various spatial and temporal scales will require the integration of multiple, complementary and independent methods that are used by different research communities. Tools such as air sampling networks, inverse numerical methods, and satellite data (top-down approaches) allow us to study the strength and location of the global- and continental-scale carbon sources and sinks. Bottom-up studies provide estimates of carbon fluxes at finer spatial scales and examine the mechanisms that control fluxes at the ecosystem, landscape, and regional scales. Bottom-up approaches include comparative and process studies (for example, ecosystem manipulative experiments) that provide the necessary mechanistic information to develop and validate terrestrial biospheric models. An iteration and reiteration of top-down and bottom-up approaches will be necessary to help constrain measurements at various scales. We propose a major international effort to coordinate and lead research programs of global scope of the carbon cycle
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