CRHSP-24 phosphorylation is regulated by multiple signaling pathways in pancreatic acinar cells

Ca2+-regulated heat-stable protein of 24 kDa (CRHSP-24) is a serine phosphoprotein originally identified as a physiological substrate for the Ca2+-calmodulin regulated protein phosphatase calcineurin (PP2B). CRHSP-24 is a paralog of the brain-specific mRNA-binding protein PIPPin and was recently shown to interact with the STYX/dead phosphatase protein in developing spermatids (Wishart MJ and Dixon JE. Proc Natl Acad Sci USA 99: 2112-2117, 2002). Investigation of the effects of phorbol ester (12-o-tetradecanoylphorbol-13-acetate; TPA) and cAMP analogs in 32P-labeled pancreatic acini revealed that these agents acutely dephosphorylated CRHSP-24 by a Ca2+-independent mechanism. Indeed, cAMP- and TPA-mediated dephosphorylation of CRHSP-24 was fully inhibited by the PP1/PP2A inhibitor calyculin A, indicating that the protein is regulated by an additional phosphatase other than PP2B. Supporting this, CRHSP-24 dephosphorylation in response to the Ca2+-mobilizing hormone cholecystokinin was differentially inhibited by calyculin A and the PP2B-selective inhibitor cyclosporin A. Stimulation of acini with secretin, a secretagogue that signals through the cAMP pathway in acini, induced CRHSP-24 dephosphorylation in a concentration-dependent manner. Isoelectric focusing and immunoblotting indicated that elevated cellular Ca2+ dephosphorylated CRHSP-24 on at least three serine sites, whereas cAMP and TPA partially dephosphorylated the protein on at least two sites. The cAMP-mediated dephosphorylation of CRHSP-24 was inhibited by low concentrations of okadaic acid (10 nM) and fostriecin (1 microM), suggesting that CRHSP-24 is regulated by PP2A or PP4. Collectively, these data indicate that CRHSP-24 is regulated by diverse and physiologically relevant signaling pathways in acinar cells, including Ca2+, cAMP, and diacylglycerol.     

Removal of Ca2+ channel beta3 subunit enhances Ca2+ oscillation frequency and insulin exocytosis

An oscillatory increase in pancreatic beta cell cytoplasmic free Ca2+ concentration, [Ca2+]i, is a key feature in glucose-induced insulin release. The role of the voltage-gated Ca2+ channel beta3 subunit in the molecular regulation of these [Ca2+]i oscillations has now been clarified by using beta3 subunit-deficient beta cells. beta3 knockout mice showed a more efficient glucose homeostasis compared to wild-type mice due to increased glucose-stimulated insulin secretion. This resulted from an increased glucose-induced [Ca2+]i oscillation frequency in beta cells lacking the beta3 subunit, an effect accounted for by enhanced formation of inositol 1,4,5-trisphosphate (InsP3) and increased Ca2+ mobilization from intracellular stores. Hence, the beta3 subunit negatively modulated InsP3-induced Ca2+ release, which is not paralleled by any effect on the voltage-gated L type Ca2+ channel. Since the increase in insulin release was manifested only at high glucose concentrations, blocking the beta3 subunit in the beta cell may constitute the basis for a novel diabetes therapy.     

GENETIC AND SOCIAL INHERITANCE OF BODY AND EGG SIZE IN THE BARNACLE GOOSE (BRANTA LEUCOPSIS)

We present heritability estimates for final size of body traits and egg size as well as phenotypic and genetic correlations between body and egg traits in a recently established population of the barnacle goose (Branta leucopsis) in the Baltic area. Body traits as well as egg size were heritable and, hence, could respond evolutionarily to phenotypic selection. Genetic correlations between body size traits were significantly positive and of similar magnitude or higher than the corresponding phenotypic correlations. Heritability estimates for tarsus length obtained from full-sib analyses were higher than those obtained from midoffspring-midparent regressions, and this indicates common environment effects on siblings. Heritabilities for tarsus length obtained from midoffspring-mother regressions were significantly higher than estimates from midoffspring-father regressions. The results suggest that this discrepancy is not caused by maternal effects through egg size, nor by extra-pair fertilizations, but by a socially inherited foraging site fidelity in females.     

Climate–ecosystem modelling made easy: The Land Sites Platform

Dynamic Global Vegetation Models (DGVMs) provide a state-of-the-art process-based approach to study the complex interplay between vegetation and its physical environment. For example, they help to predict how terrestrial plants interact with climate, soils, disturbance and competition for resources. We argue that there is untapped potential for the use of DGVMs in ecological and ecophysiological research. One fundamental barrier to realize this potential is that many researchers with relevant expertize (ecology, plant physiology, soil science, etc.) lack access to the technical resources or awareness of the research potential of DGVMs. Here we present the Land Sites Platform (LSP): new software that facilitates single-site simulations with the Functionally Assembled Terrestrial Ecosystem Simulator, an advanced DGVM coupled with the Community Land Model. The LSP includes a Graphical User Interface and an Application Programming Interface, which improve the user experience and lower the technical thresholds for installing these model architectures and setting up model experiments. The software is distributed via version-controlled containers; researchers and students can run simulations directly on their personal computers or servers, with relatively low hardware requirements, and on different operating systems. Version 1.0 of the LSP supports site-level simulations. We provide input data for 20 established geo-ecological observation sites in Norway and workflows to add generic sites from public global datasets. The LSP makes standard model experiments with default data easily achievable (e.g., for educational or introductory purposes) while retaining flexibility for more advanced scientific uses. We further provide tools to visualize the model input and output, including simple examples to relate predictions to local observations. The LSP improves access to land surface and DGVM modelling as a building block of community cyberinfrastructure that may inspire new avenues for mechanistic ecosystem research across disciplines.     

Somatic progenitor cell vulnerability to mitochondrial DNA mutagenesis underlies progeroid phenotypes in Polg mutator mice

Somatic stem cell (SSC) dysfunction is typical for different progeroid phenotypes in mice with genomic DNA repair defects. MtDNA mutagenesis in mice with defective Polg exonuclease activity also leads to progeroid symptoms, by an unknown mechanism. We found that Polg-Mutator mice had neural (NSC) and hematopoietic progenitor (HPC) dysfunction already from embryogenesis. NSC self-renewal was decreased in vitro, and quiescent NSC amounts were reduced in vivo. HPCs showed abnormal lineage differentiation leading to anemia and lymphopenia. N-acetyl-L-cysteine treatment rescued both NSC and HPC abnormalities, suggesting that subtle ROS/redox changes, induced by mtDNA mutagenesis, modulate SSC function. Our results show that mtDNA mutagenesis affected SSC function early but manifested as respiratory chain deficiency in nondividing tissues in old age. Deletor mice, having mtDNA deletions in postmitotic cells and no progeria, had normal SSCs. We propose that SSC compartment is sensitive to mtDNA mutagenesis, and that mitochondrial dysfunction in SSCs can underlie progeroid manifestations.     

Stipitate stereoid basidiocarps have evolved multiple times

Stipitate stereoid fungi are Basidiomycetes with a stipe, a spathulate-to funnel-shaped pileus, a smooth hymenophore, and hyaline, smooth spores. Representatives of the genera Cotylidia, Cymatoderma, Muscinupta, Podoscypha and Stereopsis were subjected to molecular phylogenetic analyses based on nuclear ribosomal large subunit, 5.8S and ITS sequences. For four of the genera the type species was included in analyses. Stereopsis radicans, the type species of Stereopsis, forms a lineage with the corticioid species Clavulicium globosum but could not be placed in any of the presently accepted orders within Agaricomycotina. Stereopsis vitellina falls within the Atheliales, making it the first pileus- and stipe-forming fungus recovered in this order. Cotylidia and Muscinupta again are shown to be members of the Hymenochaetales, whereas Cymatoderma and Podoscypha belong in the Polyporales. Cymatoderma is polyphyletic and Cymatoderma sensu stricto is separated from other stipitate stereoid fungi in the Polyporales, whereas the remaining Cymatoderma species are nested within a well supported clade holding all Podoscypha species but also Abortiporus biennis.