The peptidyl-prolyl isomerase Pin1 facilitates cytokine-induced survival of eosinophils by suppressing Bax activation.

PubWeight™: 1.29‹?› | Rank: Top 10%

🔗 View Article (PMC 2847832)

Published in Nat Immunol on February 01, 2009

Authors

Zhong-Jian Shen1, Stephane Esnault, Anna Schinzel, Christoph Borner, James S Malter

Author Affiliations

1: Waisman Center for Developmental Disabilities, the Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705, USA.

Articles citing this

Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol. Cell (2011) 3.23

Apoptosis and oncogenesis: give and take in the BCL-2 family. Curr Opin Genet Dev (2011) 1.71

The prolyl isomerase Pin1 acts as a novel molecular switch for TNF-alpha-induced priming of the NADPH oxidase in human neutrophils. Blood (2010) 1.68

Bax exists in a dynamic equilibrium between the cytosol and mitochondria to control apoptotic priming. Mol Cell (2013) 1.60

Building blocks of the apoptotic pore: how Bax and Bak are activated and oligomerize during apoptosis. Cell Death Differ (2013) 1.54

Evading apoptosis in cancer. Trends Cell Biol (2013) 1.17

Pin1 catalyzes conformational changes of Thr-187 in p27Kip1 and mediates its stability through a polyubiquitination process. J Biol Chem (2009) 1.03

Prolyl isomerase Pin1 in cancer. Cell Res (2014) 1.01

Pin1 associates with and induces translocation of CRTC2 to the cytosol, thereby suppressing cAMP-responsive element transcriptional activity. J Biol Chem (2010) 0.99

Cytosolic Bax: does it require binding proteins to keep its pro-apoptotic activity in check? J Biol Chem (2012) 0.97

D,L-sulforaphane-induced apoptosis in human breast cancer cells is regulated by the adapter protein p66Shc. J Cell Biochem (2012) 0.95

A distinct role for Pin1 in the induction and maintenance of pluripotency. J Biol Chem (2011) 0.95

ROS-dependent phosphorylation of Bax by wortmannin sensitizes melanoma cells for TRAIL-induced apoptosis. Cell Death Dis (2013) 0.93

p66Shc is indispensable for phenethyl isothiocyanate-induced apoptosis in human prostate cancer cells. Cancer Res (2010) 0.91

Regulation of cardiac hypertrophic signaling by prolyl isomerase Pin1. Circ Res (2013) 0.88

Dusp5 negatively regulates IL-33-mediated eosinophil survival and function. EMBO J (2014) 0.87

Sensitization of melanoma cells for TRAIL-induced apoptosis by BMS-345541 correlates with altered phosphorylation and activation of Bax. Cell Death Dis (2013) 0.86

The peptidyl-prolyl isomerase Pin1 up-regulation and proapoptotic function in dopaminergic neurons: relevance to the pathogenesis of Parkinson disease. J Biol Chem (2013) 0.86

Pin1 protein regulates Smad protein signaling and pulmonary fibrosis. J Biol Chem (2012) 0.85

An Autoinhibited Dimeric Form of BAX Regulates the BAX Activation Pathway. Mol Cell (2016) 0.85

Pin1-FADD interactions regulate Fas-mediated apoptosis in activated eosinophils. J Immunol (2013) 0.84

Regulation of spontaneous eosinophil apoptosis-a neglected area of importance. J Cell Death (2014) 0.83

Pin1-Induced Proline Isomerization in Cytosolic p53 Mediates BAX Activation and Apoptosis. Mol Cell (2015) 0.83

Pin1 null mice exhibit low bone mass and attenuation of BMP signaling. PLoS One (2013) 0.82

Mitochondria in the center of human eosinophil apoptosis and survival. Int J Mol Sci (2014) 0.82

Lipid Mediators of Allergic Disease: Pathways, Treatments, and Emerging Therapeutic Targets. Curr Allergy Asthma Rep (2016) 0.78

Essential role of Pin1 via STAT3 signalling and mitochondria-dependent pathways in restenosis in type 2 diabetes. J Cell Mol Med (2013) 0.77

The prolyl isomerase Pin1 modulates development of CD8+ cDC in mice. PLoS One (2012) 0.75

Transforming Growth Factor-β1 Antagonizes Interleukin-5 Pro-Survival Signaling by Activating Calpain-1 in Primary Human Eosinophils. J Clin Cell Immunol (2011) 0.75

Microarray Analysis Reveals Increased Transcriptional Repression and Reduced Metabolic Activity but Not Major Changes in the Core Apoptotic Machinery during Maturation of Sympathetic Neurons. Front Cell Neurosci (2016) 0.75

Combination of endogenous neural stem cell mobilization and lithium chloride treatment for hydrocephalus following intraventricular hemorrhage. Exp Ther Med (2016) 0.75

Epstein-Barr Virus Induced Gene 2 (EBI2) Mediates Allergen-induced, Leukocyte Migration into Airways. Am J Respir Crit Care Med (2017) 0.75

Protein Translation and Signaling in Human Eosinophils. Front Med (Lausanne) (2017) 0.75

Articles cited by this

The Bcl-2 protein family: arbiters of cell survival. Science (1998) 16.08

Structure of Bax: coregulation of dimer formation and intracellular localization. Cell (2000) 7.00

A critical role for eosinophils in allergic airways remodeling. Science (2004) 5.53

Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism. Science (1997) 5.40

Bax in murine thymus is a soluble monomeric protein that displays differential detergent-induced conformations. J Biol Chem (1998) 4.71

The prolyl isomerase PIN1: a pivotal new twist in phosphorylation signalling and disease. Nat Rev Mol Cell Biol (2007) 4.49

The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein. Nature (1999) 3.96

Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J Clin Invest (2003) 3.16

An improved immunomagnetic procedure for the isolation of highly purified human blood eosinophils. J Immunol Methods (1991) 2.96

Treatment strategies for allergy and asthma. Nat Rev Immunol (2008) 2.92

JNK- and p38 kinase-mediated phosphorylation of Bax leads to its activation and mitochondrial translocation and to apoptosis of human hepatoma HepG2 cells. J Biol Chem (2006) 2.71

Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature (2003) 2.66

Control of apoptosis in the immune system: Bcl-2, BH3-only proteins and more. Annu Rev Immunol (2001) 2.65

Clusterin inhibits apoptosis by interacting with activated Bax. Nat Cell Biol (2005) 2.30

Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophils. J Biol Chem (2004) 2.30

Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol (2007) 2.27

Pinning down proline-directed phosphorylation signaling. Trends Cell Biol (2002) 2.17

Epidermal growth factor activates m-calpain (calpain II), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation. Mol Cell Biol (2004) 2.08

Phosphorylation-specific prolyl isomerization: is there an underlying theme? Nat Cell Biol (2005) 2.06

Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression. Proc Natl Acad Sci U S A (2000) 2.04

The peptidyl-prolyl isomerase Pin1 regulates the stability of granulocyte-macrophage colony-stimulating factor mRNA in activated eosinophils. Nat Immunol (2005) 1.99

Differential expression of bcl-2 and susceptibility to anti-Fas-mediated cell death in peripheral blood lymphocytes, monocytes, and neutrophils. Blood (1994) 1.94

Selective inactivation of parvulin-like peptidyl-prolyl cis/trans isomerases by juglone. Biochemistry (1998) 1.80

Conformational control of Bax localization and apoptotic activity by Pro168. J Cell Biol (2004) 1.80

Bax cleavage is mediated by calpain during drug-induced apoptosis. Oncogene (1998) 1.79

Comparison of airway immunopathology of eosinophilic bronchitis and asthma. Thorax (2003) 1.75

Nicotine inactivation of the proapoptotic function of Bax through phosphorylation. J Biol Chem (2005) 1.59

A critical role for Pin1 in allergic pulmonary eosinophilia in rats. J Allergy Clin Immunol (2007) 1.58

Decreased expression of membrane IL-5 receptor alpha on human eosinophils: I. Loss of membrane IL-5 receptor alpha on airway eosinophils and increased soluble IL-5 receptor alpha in the airway after allergen challenge. J Immunol (2002) 1.46

Homeostatic control of lymphocyte survival: potential origins and implications. Nat Immunol (2002) 1.40

The pathobiology of bronchial asthma. Adv Immunol (1992) 1.32

Complexes of plasmid DNA with basic domain 47-57 of the HIV-1 Tat protein are transferred to mammalian cells by endocytosis-mediated pathways. J Biol Chem (2003) 1.30

Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation. Cell Death Differ (2007) 1.29

Pin1 regulates TGF-beta1 production by activated human and murine eosinophils and contributes to allergic lung fibrosis. J Clin Invest (2008) 1.28

Pin1 mediates neural-specific activation of the mitochondrial apoptotic machinery. Neuron (2006) 1.25

Requirement of Lyn and Syk tyrosine kinases for the prevention of apoptosis by cytokines in human eosinophils. J Exp Med (1996) 1.24

Activation of ERK1/2 protects melanoma cells from TRAIL-induced apoptosis by inhibiting Smac/DIABLO release from mitochondria. Oncogene (2003) 1.16

Lyn, Jak2, and Raf-1 kinases are critical for the antiapoptotic effect of interleukin 5, whereas only Raf-1 kinase is essential for eosinophil activation and degranulation. J Exp Med (1998) 1.12

Airway mast cells and eosinophils correlate with clinical severity and airway hyperresponsiveness in corticosteroid-treated asthma. J Allergy Clin Immunol (2000) 1.09

The peptidyl-prolyl isomerase Pin1 regulates granulocyte-macrophage colony-stimulating factor mRNA stability in T lymphocytes. J Immunol (2006) 1.07

Role for Bcl-xL in delayed eosinophil apoptosis mediated by granulocyte-macrophage colony-stimulating factor and interleukin-5. Blood (1998) 1.02

Expression of the death gene Bik/Nbk promotes sensitivity to drug-induced apoptosis in corticosteroid-resistant T-cell lymphoma and prevents tumor growth in severe combined immunodeficient mice. Blood (1999) 1.00

Fatal liaisons of p53 with Bax and Bak. Nat Cell Biol (2004) 0.99

Interleukin-5 inhibits translocation of Bax to the mitochondria, cytochrome c release, and activation of caspases in human eosinophils. Blood (2001) 0.98

Bcl-2 is required for cranial sensory neuron survival at defined stages of embryonic development. Development (1997) 0.88

Molecules involved in the regulation of eosinophil apoptosis. Chem Immunol Allergy (2006) 0.88

Extracellular signal-regulated kinase mediates granulocyte-macrophage colony-stimulating factor messenger RNA stabilization in tumor necrosis factor-alpha plus fibronectin-activated peripheral blood eosinophils. Blood (2002) 0.88

Bax is crucial for IFN-gamma-induced resolution of allergen-induced mucus cell metaplasia. J Immunol (2002) 0.87

Expression of the proapoptotic protein Bax is reduced in bronchial mucous cells of asthmatic subjects. Am J Physiol Lung Cell Mol Physiol (2008) 0.85

Regulation of the function of eosinophils and basophils. Crit Rev Immunol (1997) 0.80

Articles by these authors

Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha. Science (2006) 4.46

Characterization of the signal that directs Bcl-x(L), but not Bcl-2, to the mitochondrial outer membrane. J Cell Biol (2003) 3.01

XIAP discriminates between type I and type II FAS-induced apoptosis. Nature (2009) 3.00

Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Arch Toxicol (2013) 3.00

An activated ErbB3/NRG1 autocrine loop supports in vivo proliferation in ovarian cancer cells. Cancer Cell (2010) 2.85

The fragile X mental retardation protein is required for type-I metabotropic glutamate receptor-dependent translation of PSD-95. Proc Natl Acad Sci U S A (2003) 2.82

FMRP mediates mGluR5-dependent translation of amyloid precursor protein. PLoS Biol (2007) 2.75

Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling. Mol Cell Biol (2003) 2.69

Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study. Blood (2008) 2.00

The peptidyl-prolyl isomerase Pin1 regulates the stability of granulocyte-macrophage colony-stimulating factor mRNA in activated eosinophils. Nat Immunol (2005) 1.99

Incoming RNA virus nucleocapsids containing a 5'-triphosphorylated genome activate RIG-I and antiviral signaling. Cell Host Microbe (2013) 1.95

Phosphorylation of Tip60 by GSK-3 determines the induction of PUMA and apoptosis by p53. Mol Cell (2011) 1.87

Conformational control of Bax localization and apoptotic activity by Pro168. J Cell Biol (2004) 1.80

The prolyl isomerase Pin1 acts as a novel molecular switch for TNF-alpha-induced priming of the NADPH oxidase in human neutrophils. Blood (2010) 1.68

A critical role for Pin1 in allergic pulmonary eosinophilia in rats. J Allergy Clin Immunol (2007) 1.58

Volatile anesthetics induce caspase-dependent, mitochondria-mediated apoptosis in human T lymphocytes in vitro. Anesthesiology (2005) 1.55

ON/OFF and beyond--a boolean model of apoptosis. PLoS Comput Biol (2009) 1.53

beta-Amyloid degradation and Alzheimer's disease. J Biomed Biotechnol (2006) 1.35

Cell death provoked by loss of interleukin-3 signaling is independent of Bad, Bim, and PI3 kinase, but depends in part on Puma. Blood (2006) 1.31

Pin1 regulates TGF-beta1 production by activated human and murine eosinophils and contributes to allergic lung fibrosis. J Clin Invest (2008) 1.28

The mitochondrial protein Bak is pivotal for gliotoxin-induced apoptosis and a critical host factor of Aspergillus fumigatus virulence in mice. J Cell Biol (2006) 1.28

Bcl-2 family members: integrators of survival and death signals in physiology and pathology [corrected]. Biochim Biophys Acta (2004) 1.27

The biology of cytotoxic cell granule exocytosis pathway: granzymes have evolved to induce cell death and inflammation. Microbes Infect (2009) 1.19

Reversal of fragile X phenotypes by manipulation of AβPP/Aβ levels in Fmr1KO mice. PLoS One (2011) 1.15

Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis. Oncogene (2002) 1.08

The peptidyl-prolyl isomerase Pin1 regulates granulocyte-macrophage colony-stimulating factor mRNA stability in T lymphocytes. J Immunol (2006) 1.07

Switch from type II to I Fas/CD95 death signaling on in vitro culturing of primary hepatocytes. Hepatology (2008) 1.07

RIP death domain structural interactions implicated in TNF-mediated proliferation and survival. Proteins (2006) 1.06

Caspase-3 mediates hippocampal apoptosis in pneumococcal meningitis. Acta Neuropathol (2003) 1.01

Pin1 and PKMzeta sequentially control dendritic protein synthesis. Sci Signal (2010) 1.00

Seizure susceptibility and mortality in mice that over-express amyloid precursor protein. Int J Clin Exp Pathol (2008) 1.00

RhoB mRNA is stabilized by HuR after UV light. Oncogene (2005) 0.99

Caspase-3 feeds back on caspase-8, Bid and XIAP in type I Fas signaling in primary mouse hepatocytes. Apoptosis (2012) 0.99

Expression of interleukin-5- and granulocyte macrophage-colony-stimulating factor-responsive genes in blood and airway eosinophils. Am J Respir Cell Mol Biol (2003) 0.98

Decoy mRNAs reduce beta-amyloid precursor protein mRNA in neuronal cells. Neurobiol Aging (2006) 0.97

Hyaluronic acid or TNF-alpha plus fibronectin triggers granulocyte macrophage-colony-stimulating factor mRNA stabilization in eosinophils yet engages differential intracellular pathways and mRNA binding proteins. J Immunol (2003) 0.97

Cytosolic Bax: does it require binding proteins to keep its pro-apoptotic activity in check? J Biol Chem (2012) 0.97

Myeloid progenitor cells lacking p53 exhibit delayed up-regulation of Puma and prolonged survival after cytokine deprivation. Blood (2009) 0.96

Pin1 modulates the type 1 immune response. PLoS One (2007) 0.95

Mixed-lineage kinase 3 phosphorylates prolyl-isomerase Pin1 to regulate its nuclear translocation and cellular function. Proc Natl Acad Sci U S A (2012) 0.94

Whisker stimulation-dependent translation of FMRP in the barrel cortex requires activation of type I metabotropic glutamate receptors. Brain Res Mol Brain Res (2003) 0.93

Tumor necrosis factor α sensitizes primary murine hepatocytes to Fas/CD95-induced apoptosis in a Bim- and Bid-dependent manner. Hepatology (2010) 0.90

Alzheimer's disease and Down syndrome rodent models exhibit audiogenic seizures. J Alzheimers Dis (2010) 0.90

Tissue transglutaminase, protein cross-linking and Alzheimer's disease: review and views. Int J Clin Exp Pathol (2008) 0.90

Identification of genes expressed by human airway eosinophils after an in vivo allergen challenge. PLoS One (2013) 0.90

Potent synergistic effect of IL-3 and TNF on matrix metalloproteinase 9 generation by human eosinophils. Cytokine (2012) 0.90

Nuclear proteins acting on mitochondria. Biochim Biophys Acta (2010) 0.90

Ets-1 regulates TNF-alpha-induced matrix metalloproteinase-9 and tenascin expression in primary bronchial fibroblasts. J Immunol (2004) 0.89

Integration of Boolean models exemplified on hepatocyte signal transduction. Brief Bioinform (2011) 0.89

Pinning down signaling in the immune system: the role of the peptidyl-prolyl isomerase Pin1 in immune cell function. Crit Rev Immunol (2008) 0.89

The significance of Pin1 in the development of Alzheimer's disease. J Alzheimers Dis (2007) 0.88

Extracellular signal-regulated kinase mediates granulocyte-macrophage colony-stimulating factor messenger RNA stabilization in tumor necrosis factor-alpha plus fibronectin-activated peripheral blood eosinophils. Blood (2002) 0.88

Effects of HNE-modification induced by Abeta on neprilysin expression and activity in SH-SY5Y cells. J Neurochem (2009) 0.87

MPEP reduces seizure severity in Fmr-1 KO mice over expressing human Abeta. Int J Clin Exp Pathol (2009) 0.87

Low perforin expression of early differentiated HCV-specific CD8+ T cells limits their hepatotoxic potential. J Hepatol (2012) 0.86

TNFα-induced lysosomal membrane permeability is downstream of MOMP and triggered by caspase-mediated NDUFS1 cleavage and ROS formation. J Cell Sci (2013) 0.86

A novel mitochondrial MAVS/Caspase-8 platform links RNA virus-induced innate antiviral signaling to Bax/Bak-independent apoptosis. J Immunol (2014) 0.85

Pin1 protein regulates Smad protein signaling and pulmonary fibrosis. J Biol Chem (2012) 0.85

Thymic stromal lymphopoietin (TSLP) as a bridge between infection and atopy. Int J Clin Exp Pathol (2008) 0.85

Modeling system states in liver cells: survival, apoptosis and their modifications in response to viral infection. BMC Syst Biol (2009) 0.85

Non-caspase proteases: triggers or amplifiers of apoptosis? Cell Mol Life Sci (2010) 0.85

Antisense targeting of TGF-beta1 augments BMP-induced upregulation of osteopontin, type I collagen and Cbfa1 in human Saos-2 cells. Exp Cell Res (2007) 0.84

Pin1-FADD interactions regulate Fas-mediated apoptosis in activated eosinophils. J Immunol (2013) 0.84

Bcl-w(edding) with mitochondria. Trends Cell Biol (2004) 0.84

The Pin 1 inhibitor juglone attenuates kidney fibrogenesis via Pin 1-independent mechanisms in the unilateral ureteral occlusion model. Fibrogenesis Tissue Repair (2010) 0.83

Anti-Abeta: The good, the bad, and the unforeseen. J Neurosci Res (2004) 0.83

Role of Bcl-2 expression for productive herpes simplex virus 2 replication. Virology (2006) 0.83

Soy-based diet exacerbates seizures in mouse models of neurological disease. J Alzheimers Dis (2013) 0.83

Pin1 null mice exhibit low bone mass and attenuation of BMP signaling. PLoS One (2013) 0.82

Serum and low-density lipoprotein enhance interleukin-8 secretion by airway epithelial cells. Am J Respir Cell Mol Biol (2003) 0.82

Interleukin-1R signaling is essential for induction of proapoptotic CD8 T cells, viral clearance, and pathology during lymphocytic choriomeningitis virus infection in mice. J Virol (2012) 0.82

Effects of 4-hydroxy-nonenal and Amyloid-beta on expression and activity of endothelin converting enzyme and insulin degrading enzyme in SH-SY5Y cells. J Alzheimers Dis (2009) 0.81

The regulation of AβPP expression by RNA-binding proteins. Ageing Res Rev (2012) 0.81

N-acetylcysteine prevents 4-hydroxynonenal- and amyloid-beta-induced modification and inactivation of neprilysin in SH-SY5Y cells. J Alzheimers Dis (2010) 0.81

GM-CSF regulation in eosinophils. Arch Immunol Ther Exp (Warsz) (2002) 0.81

Dendritic cell-based immunotherapy for cancer and relevant challenges for transfusion medicine. Transfus Med Rev (2004) 0.80

Preprotein transport machineries of yeast mitochondrial outer membrane are not required for Bax-induced release of intermembrane space proteins. J Mol Biol (2007) 0.80

Effect of Anticoagulants on Amyloid β-Protein Precursor and Amyloid Beta Levels in Plasma. J Alzheimers Dis Parkinsonism (2011) 0.80

Rck/p54 interacts with APP mRNA as part of a multi-protein complex and enhances APP mRNA and protein expression in neuronal cell lines. Neurobiol Aging (2008) 0.79

Human airway eosinophils exhibit preferential reduction in STAT signaling capacity and increased CISH expression. J Immunol (2013) 0.79

HuR mRNA ligands expressed after seizure. J Neuropathol Exp Neurol (2005) 0.78

Fragile X mental retardation protein in plasticity and disease. J Neurosci Res (2002) 0.78

Determinants of eosinophil survival and apoptotic cell death. Apoptosis (2015) 0.77

Circadian changes in granulocyte-macrophage colony-stimulating factor message in circulating eosinophils. Ann Allergy Asthma Immunol (2007) 0.77

Preparation of synaptoneurosomes from mouse cortex using a discontinuous percoll-sucrose density gradient. J Vis Exp (2011) 0.77

Thymic stromal lymphopoietin expression in allergic pulmonary inflammation is Pin1-dependent. J Allergy Clin Immunol (2008) 0.77

Non-canonical function of Bax in stress-induced nuclear protein redistribution. Cell Mol Life Sci (2013) 0.77

Cellular stress induces Bax-regulated nuclear bubble budding and rupture followed by nuclear protein release. Nucleus (2014) 0.77

Role of caspases and non-caspase proteases in cell death. F1000 Biol Rep (2010) 0.76

Bcl-x(S) induces an NGF-inhibitable cytochrome c release. Exp Cell Res (2004) 0.76

Transforming Growth Factor-β1 Antagonizes Interleukin-5 Pro-Survival Signaling by Activating Calpain-1 in Primary Human Eosinophils. J Clin Cell Immunol (2011) 0.75

Interleukin-33: a potential link between rhinovirus infections and asthma exacerbation. Am J Respir Crit Care Med (2014) 0.75

Plasma exchange after initial intravenous immunoglobulin treatment in Guillain-Barré syndrome: critical reassessment of effectiveness and cost-efficiency. J Clin Neuromuscul Dis (2010) 0.75