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911.
In healthy cows unaffected by imminent or recent calving the protein in serum can directly bind the overwhelming proportion of the bound calcium. In recent calvers this capacity is considerably less. When adding ammonium sulphate to blood serum to 62 % of total saturation a protein fraction precipitates which is mainly albumin. This fraction has a far greater calcium binding capacity than the soluble fraction, which contains most of the serum globulin, and the lowering of this capacity after calving is entirely referable to the former fraction. No difference has been found in these respects between normal cows after calving and cows with parturient paresis. An analysis of 10 amino acids in the two protein fractions described above showed that the amino acid composition of both exhibits differences between recent calvers and cows outside the calving period, and likewise that each of the two fractions differs in composition between healthy cows after calving and cows with parturient paresis. 相似文献
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916.
Matthew T. Weirauch Ally Yang Mihai Albu Atina G. Cote Alejandro Montenegro-Montero Philipp Drewe Hamed S. Najafabadi Samuel A. Lambert Ishminder Mann Kate Cook Hong Zheng Alejandra Goity Harm van Bakel Jean-Claude Lozano Mary Galli Mathew G. Lewsey Eryong Huang Tuhin Mukherjee Xiaoting Chen John S. Reece-Hoyes Sridhar Govindarajan Gad Shaulsky Albertha J.M. Walhout François-Yves Bouget Gunnar Ratsch Luis F. Larrondo Joseph R. Ecker Timothy R. Hughes 《Cell》2014
917.
Vítězslav K?í? Vendula Pospíchalová Jan Ma?ek Michaela Brita Christina Kilander Josef Slavík Kristina Tanneberger Gunnar Schulte Miroslav Machala Alois Kozubík Juergen Behrens Vítězslav Bryja 《The Journal of biological chemistry》2014,289(2):1128-1141
β-Arrestin is a scaffold protein that regulates signal transduction by seven transmembrane-spanning receptors. Among other functions it is also critically required for Wnt/β-catenin signal transduction. In the present study we provide for the first time a mechanistic basis for the β-arrestin function in Wnt/β-catenin signaling. We demonstrate that β-arrestin is required for efficient Wnt3a-induced Lrp6 phosphorylation, a key event in downstream signaling. β-Arrestin regulates Lrp6 phosphorylation via a novel interaction with phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)-binding protein Amer1/WTX/Fam123b. Amer1 has been shown very recently to bridge Wnt-induced and Dishevelled-associated PtdIns(4,5)P2 production to the phosphorylation of Lrp6. Using fluorescence recovery after photobleaching we show here that β-arrestin is required for the Wnt3a-induced Amer1 membrane dynamics and downstream signaling. Finally, we show that β-arrestin interacts with PtdIns kinases PI4KIIα and PIP5KIβ. Importantly, cells lacking β-arrestin showed higher steady-state levels of the relevant PtdInsP and were unable to increase levels of these PtdInsP in response to Wnt3a. In summary, our data show that β-arrestins regulate Wnt3a-induced Lrp6 phosphorylation by the regulation of the membrane dynamics of Amer1. We propose that β-arrestins via their scaffolding function facilitate Amer1 interaction with PtdIns(4,5)P2, which is produced locally upon Wnt3a stimulation by β-arrestin- and Dishevelled-associated kinases. 相似文献
918.
Pierre M. Daye Lance M. Optican Gunnar Blohm Philippe Lefèvre 《Journal of computational neuroscience》2014,36(3):355-382
Coordinating the movements of different body parts is a challenging process for the central nervous system because of several problems. Four of these main difficulties are: first, moving one part can move others; second, the parts can have different dynamics; third, some parts can have different motor goals; and fourth, some parts may be perturbed by outside forces. Here, we propose a novel approach for the control of linked systems with feedback loops for each part. The proximal parts have separate goals, but critically the most distal part has only the common goal. We apply this new control policy to eye-head coordination in two-dimensions, specifically head-unrestrained gaze saccades. Paradoxically, the hierarchical structure has controllers for the gaze and the head, but not for the eye (the most distal part). Our simulations demonstrate that the proposed control structure reproduces much of the published empirical data about gaze movements, e.g., it compensates for perturbations, accurately reaches goals for gaze and head from arbitrary initial positions, simulates the nine relationships of the head-unrestrained main sequence, and reproduces observations from lesion and single-unit recording experiments. We conclude by showing how our model can be easily extended to control structures with more linked segments, such as the control of coordinated eye on head on trunk movements. 相似文献
919.
Fabio R. Melo Francesca Vita Beata Berent-Maoz Francesca Levi-Schaffer Giuliano Zabucchi Gunnar Pejler 《The Journal of biological chemistry》2014,289(11):7682-7690
A hallmark feature of mast cells is their high content of cytoplasmic secretory granules filled with various preformed compounds, including proteases of tryptase-, chymase-, and carboxypeptidase A3 type that are electrostatically bound to serglycin proteoglycan. Apart from participating in extracellular processes, serglycin proteoglycan and one of its associated proteases, tryptase, are known to regulate cell death by promoting apoptosis over necrosis. Here we sought to outline the underlying mechanism and identify core histones as primary proteolytic targets for the serglycin-tryptase axis. During the cell death process, tryptase was found to relocalize from granules into the cytosol and nucleus, and it was found that the absence of tryptase was associated with a pronounced accumulation of core histones both in the cytosol and in the nucleus. Intriguingly, tryptase deficiency resulted in defective proteolytic modification of core histones even at baseline conditions, i.e. in the absence of cytotoxic agent, suggesting that tryptase has a homeostatic impact on nuclear events. Indeed, tryptase was found in the nucleus of viable cells and was shown to cleave core histones in their N-terminal tail. Moreover, it was shown that the absence of the serglycin-tryptase axis resulted in altered chromatin composition. Together, these findings implicate histone proteolysis through a secretory granule-derived serglycin-tryptase axis as a novel principle for histone modification, during both cell homeostasis and cell death. 相似文献
920.
Uwe Kirchhefer Christiane Brekle John Eskandar Gunnar Isensee Dana Ku?erová Frank U. Müller Florence Pinet Jan S. Schulte Matthias D. Seidl Peter Boknik 《The Journal of biological chemistry》2014,289(49):33862-33873
Dephosphorylation of important myocardial proteins is regulated by protein phosphatase 2A (PP2A), representing a heterotrimer that is comprised of catalytic, scaffolding, and regulatory (B) subunits. There is a multitude of B subunit family members directing the PP2A holoenzyme to different myocellular compartments. To gain a better understanding of how these B subunits contribute to the regulation of cardiac performance, we generated transgenic (TG) mice with cardiomyocyte-directed overexpression of B56α, a phosphoprotein of the PP2A-B56 family. The 2-fold overexpression of B56α was associated with an enhanced PP2A activity that was localized mainly in the cytoplasm and myofilament fraction. Contractility was enhanced both at the whole heart level and in isolated cardiomyocytes of TG compared with WT mice. However, peak amplitude of [Ca]i did not differ between TG and WT cardiomyocytes. The basal phosphorylation of cardiac troponin inhibitor (cTnI) and the myosin-binding protein C was reduced by 26 and 35%, respectively, in TG compared with WT hearts. The stimulation of β-adrenergic receptors by isoproterenol (ISO) resulted in an impaired contractile response of TG hearts. At a depolarizing potential of −5 mV, the ICa,L current density was decreased by 28% after administration of ISO in TG cardiomyocytes. In addition, the ISO-stimulated phosphorylation of phospholamban at Ser16 was reduced by 27% in TG hearts. Thus, the increased PP2A-B56α activity in TG hearts is localized to specific subcellular sites leading to the dephosphorylation of important contractile proteins. This may result in higher myofilament Ca2+ sensitivity and increased basal contractility in TG hearts. These effects were reversed by β-adrenergic stimulation. 相似文献