Scholars@Duke
Neil J. Freedman

Neil J. Freedman

Professor of Medicine
Medicine, Cardiology
neil.freedman@duke.edu
Duke Box 102150, Durham, NC 27710
447 Clin & Res Labs, Box 102150 Duke University Medical Ctr, Durham, NC 27710

Scholarly Works - Journal articles

Phosphorylation of USP20 on Ser334 by IRAK1 promotes IL-1β-evoked signaling in vascular smooth muscle cells and vascular inflammation.

Journal article J Biol Chem · July 2023 Reversible lysine-63 (K63) polyubiquitination regulates proinflammatory signaling in vascular smooth muscle cells (SMCs) and plays an integral role in atherosclerosis. Ubiquitin-specific peptidase 20 (USP20) reduces NFκB activation triggered by proinflamma ... Full text Open Access Link to item Cite

From Colon to Aortic Aneurysm: Trek of the Treg.

Journal article JACC Basic Transl Sci · September 2022 Full text Link to item Cite

Drebrin attenuates atherosclerosis by limiting smooth muscle cell transdifferentiation.

Journal article Cardiovasc Res · February 21, 2022 AIMS: The F-actin-binding protein Drebrin inhibits smooth muscle cell (SMC) migration, proliferation, and pro-inflammatory signalling. Therefore, we tested the hypothesis that Drebrin constrains atherosclerosis. METHODS AND RESULTS: SM22-Cre+/Dbnflox/flox/ ... Full text Open Access Link to item Cite

Drebrin regulates angiotensin II-induced aortic remodelling.

Journal article Cardiovasc Res · November 1, 2018 AIMS: The actin-binding protein Drebrin is up-regulated in response to arterial injury and reduces smooth muscle cell (SMC) migration and proliferation through its interaction with the actin cytoskeleton. We, therefore, tested the hypothesis that SMC Drebr ... Full text Open Access Link to item Cite

USP20 (Ubiquitin-Specific Protease 20) Inhibits TNF (Tumor Necrosis Factor)-Triggered Smooth Muscle Cell Inflammation and Attenuates Atherosclerosis.

Journal article Arterioscler Thromb Vasc Biol · October 2018 Objective- Signaling that activates NFκB (nuclear factor κB) in smooth muscle cells (SMCs) is integral to atherosclerosis and involves reversible ubiquitination that activates proteins downstream of proatherogenic receptors. Deubiquitination of these prote ... Full text Link to item Cite

Regulation of inflammation by β-arrestins: Not just receptor tales.

Journal article Cell Signal · January 2018 The ubiquitously expressed, multifunctional scaffolding proteins β-arrestin1 and β-arrestin2 each affect inflammatory signaling in a variety of cell lines. In addition to binding the carboxyl-terminal tails of innumerable 7-transmembrane receptors, β-arres ... Full text Link to item Cite

Interleukin-9 mediates chronic kidney disease-dependent vein graft disease: a role for mast cells.

Journal article Cardiovasc Res · November 1, 2017 AIMS: Chronic kidney disease (CKD) is a powerful independent risk factor for cardiovascular events, including vein graft failure. Because CKD impairs the clearance of small proteins, we tested the hypothesis that CKD exacerbates vein graft disease by eleva ... Full text Open Access Link to item Cite

C-X-C Motif Chemokine Receptor 3 Splice Variants Differentially Activate Beta-Arrestins to Regulate Downstream Signaling Pathways.

Journal article Mol Pharmacol · August 2017 Biased agonism, the ability of different ligands for the same receptor to selectively activate some signaling pathways while blocking others, is now an established paradigm for G protein-coupled receptor signaling. One group of receptors in which endogenou ... Full text Link to item Cite

The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia.

Journal article Arterioscler Thromb Vasc Biol · May 2016 OBJECTIVE: Vascular smooth muscle cell (SMC) migration is regulated by cytoskeletal remodeling as well as by certain transient receptor potential (TRP) channels, nonselective cation channels that modulate calcium influx. Proper function of multiple subfami ... Full text Open Access Link to item Cite

Ubiquitin-specific Protease 20 Regulates the Reciprocal Functions of β-Arrestin2 in Toll-like Receptor 4-promoted Nuclear Factor κB (NFκB) Activation.

Journal article J Biol Chem · April 1, 2016 Toll-like receptor 4 (TLR4) promotes vascular inflammatory disorders such as neointimal hyperplasia and atherosclerosis. TLR4 triggers NFκB signaling through the ubiquitin ligase TRAF6 (tumor necrosis factor receptor-associated factor 6). TRAF6 activity ca ... Full text Link to item Cite

Chapter Nine - Cellular Roles of Beta-Arrestins as Substrates and Adaptors of Ubiquitination and Deubiquitination.

Journal article Prog Mol Biol Transl Sci · 2016 β-Arrestin1 and β-arrestin2 are homologous adaptor proteins that are ubiquitously expressed in mammalian cells. They belong to a four-member family of arrestins that regulate the vast family of seven-transmembrane receptors that couple to heterotrimeric G ... Full text Link to item Cite

Kruppel-like factor 15 is critical for vascular inflammation.

Journal article J Clin Invest · October 2013 Activation of cells intrinsic to the vessel wall is central to the initiation and progression of vascular inflammation. As the dominant cellular constituent of the vessel wall, vascular smooth muscle cells (VSMCs) and their functions are critical determina ... Full text Open Access Link to item Cite

Immunoglobulin-like domain containing receptor 1 mediates fat-stimulated cholecystokinin secretion.

Journal article J Clin Invest · August 2013 Cholecystokinin (CCK) is a satiety hormone produced by discrete enteroendocrine cells scattered among absorptive cells of the small intestine. CCK is released into blood following a meal; however, the mechanisms inducing hormone secretion are largely unkno ... Full text Link to item Cite

Kalirin promotes neointimal hyperplasia by activating Rac in smooth muscle cells.

Journal article Arterioscler Thromb Vasc Biol · April 2013 OBJECTIVE: Kalirin is a multifunctional protein that contains 2 guanine nucleotide exchange factor domains for the GTPases Rac1 and RhoA. Variants of KALRN have been associated with atherosclerosis in humans, but Kalirin's activity has been characterized a ... Full text Open Access Link to item Cite

MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound β(2)-adrenergic receptors.

Journal article J Cell Biol · November 26, 2012 Lysosomal degradation of ubiquitinated β(2)-adrenergic receptors (β(2)ARs) serves as a major mechanism of long-term desensitization in response to prolonged agonist stimulation. Surprisingly, the βAR antagonist carvedilol also induced ubiquitination and ly ... Full text Link to item Cite

Vein graft neointimal hyperplasia is exacerbated by CXCR4 signaling in vein graft-extrinsic cells.

Journal article J Vasc Surg · November 2012 OBJECTIVE: Because vein graft neointimal hyperplasia engenders vein graft failure, and because most vein graft neointimal cells derive from outside the vein graft, we sought to determine whether vein graft neointimal hyperplasia is affected by activity of ... Full text Open Access Link to item Cite

G protein-coupled receptor kinase-5 attenuates atherosclerosis by regulating receptor tyrosine kinases and 7-transmembrane receptors.

Journal article Arterioscler Thromb Vasc Biol · February 2012 OBJECTIVE: G protein-coupled receptor kinase-5 (GRK5) is a widely expressed Ser/Thr kinase that regulates several atherogenic receptors and may activate or inhibit nuclear factor-κB (NF-κB). This study sought to determine whether and by what mechanisms GRK ... Full text Open Access Link to item Cite

Human umbilical cord blood-derived endothelial cells reendothelialize vein grafts and prevent thrombosis.

Journal article Arterioscler Thromb Vasc Biol · November 2010 Featured Publication OBJECTIVE: To accelerate vein graft reendothelialization and reduce vein graft thrombosis by infusing human umbilical cord blood-derived endothelial cells (hCB-ECs) because loss of endothelium contributes to vein graft thrombosis and neointimal hyperplasia ... Full text Open Access Link to item Cite

Human umbilical cord blood endothelial progenitor cells decrease vein graft neointimal hyperplasia in SCID mice.

Journal article Atherosclerosis · September 2010 AIMS: Vein graft endothelial damage is a key step in the development of neointimal hyperplasia, leading to vein graft failure. We sought to determine whether exogenous endothelial progenitor cells could promote vein graft re-endothelialization, and thereby ... Full text Open Access Link to item Cite

Aging-related atherosclerosis is exacerbated by arterial expression of tumor necrosis factor receptor-1: evidence from mouse models and human association studies.

Journal article Hum Mol Genet · July 15, 2010 Featured Publication Aging is believed to be among the most important contributors to atherosclerosis, through mechanisms that remain largely obscure. Serum levels of tumor necrosis factor (TNF) rise with aging and have been correlated with the incidence of myocardial infarcti ... Full text Open Access Link to item Cite

Reciprocal regulation of the platelet-derived growth factor receptor-beta and G protein-coupled receptor kinase 5 by cross-phosphorylation: effects on catalysis.

Journal article Mol Pharmacol · March 2009 Featured Publication Signaling by the platelet-derived growth factor receptor-beta (PDGFRbeta) is diminished when the PDGFRbeta is phosphorylated on seryl residues by G protein-coupled receptor kinase-5 (GRK5), but mechanisms for GRK5 activation by the PDGFRbeta remain obscure ... Full text Link to item Cite

Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis.

Journal article PLoS Genet · January 2009 Featured Publication Neuropeptide Y (NPY) is a strong candidate gene for coronary artery disease (CAD). We have previously identified genetic linkage to familial CAD in the genomic region of NPY. We performed follow-up genetic, biostatistical, and functional analysis of NPY in ... Full text Open Access Link to item Cite

Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor.

Journal article J Biol Chem · August 8, 2008 Agonist-stimulated beta(2)-adrenergic receptor (beta(2)AR) ubiquitination is a major factor that governs both lysosomal trafficking and degradation of internalized receptors, but the identity of the E3 ubiquitin ligase regulating this process was unknown. ... Full text Link to item Cite

Beta-arrestins regulate atherosclerosis and neointimal hyperplasia by controlling smooth muscle cell proliferation and migration.

Journal article Circ Res · July 3, 2008 Featured Publication Atherosclerosis and arterial injury-induced neointimal hyperplasia involve medial smooth muscle cell (SMC) proliferation and migration into the arterial intima. Because many 7-transmembrane and growth factor receptors promote atherosclerosis, we hypothesiz ... Full text Open Access Link to item Cite

Polymorphisms of the tumor suppressor gene LSAMP are associated with left main coronary artery disease.

Journal article Ann Hum Genet · July 2008 Previous association mapping on chromosome 3q13-21 detected evidence for association at the limbic system-associated membrane protein (LSAMP) gene in individuals with late-onset coronary artery disease (CAD). LSAMP has never been implicated in the pathogen ... Full text Link to item Cite

Tumor necrosis factor receptor-2 signaling attenuates vein graft neointima formation by promoting endothelial recovery.

Journal article Arterioscler Thromb Vasc Biol · February 2008 Featured Publication OBJECTIVE: Inflammation appears intricately linked to vein graft arterialization. We have previously shown that tumor necrosis factor (TNF) receptor-1 (TNFR1, p55) signaling augments vein graft neointimal hyperplasia (NH) and remodeling through its effects ... Full text Link to item Cite

Substrate specificities of g protein-coupled receptor kinase-2 and -3 at cardiac myocyte receptors provide basis for distinct roles in regulation of myocardial function.

Journal article Mol Pharmacol · September 2007 The closely related G protein-coupled receptor kinases GRK2 and GRK3 are both expressed in cardiac myocytes. Although GRK2 has been extensively investigated in terms of regulation of cardiac beta-adrenergic receptors, the substrate specificities of the two ... Full text Link to item Cite

Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis.

Journal article Arterioscler Thromb Vasc Biol · May 2007 Featured Publication OBJECTIVE: Mechanisms by which tumor necrosis factor-alpha (TNF) contributes to atherosclerosis remain largely obscure. We therefore sought to determine the role of the arterial wall TNF receptor-1 (TNFR1) in atherogenesis. METHODS AND RESULTS: Carotid art ... Full text Link to item Cite

Regulation of the platelet-derived growth factor receptor-beta by G protein-coupled receptor kinase-5 in vascular smooth muscle cells involves the phosphatase Shp2.

Journal article J Biol Chem · December 8, 2006 Featured Publication Smooth muscle cell (SMC) proliferation and migration are substantially controlled by the platelet-derived growth factor receptor-beta (PDGFRbeta), which can be regulated by the Ser/Thr kinase G protein-coupled receptor kinase-2 (GRK2). In mouse aortic SMCs ... Full text Link to item Cite

New therapeutic possibilities for vein graft disease in the post-edifoligide era.

Journal article Future Cardiol · July 2006 Vein graft neointimal hyperplasia involves proliferation and migration of vascular smooth muscle cells into the vessel intima, and ultimately engenders accelerated atherosclerosis and vein graft failure. Since a myriad of stimuli provoke smooth muscle cell ... Full text Link to item Cite

The platelet-derived growth factor receptor-beta phosphorylates and activates G protein-coupled receptor kinase-2. A mechanism for feedback inhibition.

Journal article J Biol Chem · September 2, 2005 Featured Publication G protein-coupled receptor kinase-2 (GRK2) serine-phosphorylates the platelet-derived growth factor receptor-beta (PDGFRbeta), and thereby diminishes signaling by the receptor. Because activation of GRK2 may involve phosphorylation of its N-terminal tyrosi ... Full text Link to item Cite

Activation of vascular smooth muscle cells by TNF and PDGF: overlapping and complementary signal transduction mechanisms.

Journal article Cardiovasc Res · February 15, 2005 Featured Publication OBJECTIVE: Because tumor necrosis factor-alpha (TNF) has been implicated in the pathogenesis of vein graft neointimal hyperplasia, we sought to determine mechanisms by which TNF could induce proliferative and migratory responses in smooth muscle cells (SMC ... Full text Link to item Cite

Vein graft neointimal hyperplasia is exacerbated by tumor necrosis factor receptor-1 signaling in graft-intrinsic cells.

Journal article Arterioscler Thromb Vasc Biol · December 2004 Featured Publication OBJECTIVE: Vein graft remodeling and neointimal hyperplasia involve inflammation, graft-intrinsic cells, and recruitment of vascular progenitor cells. We sought to examine if the inflammatory cytokine tumor necrosis factor (TNF) affects vein graft remodeli ... Full text Link to item Cite

Phosphorylation of the platelet-derived growth factor receptor-beta by G protein-coupled receptor kinase-2 reduces receptor signaling and interaction with the Na(+)/H(+) exchanger regulatory factor.

Journal article J Biol Chem · October 1, 2004 Featured Publication G protein-coupled receptor kinase-2 (GRK2) can phosphorylate and desensitize the platelet-derived growth factor receptor-beta (PDGFRbeta) in heterologous cellular systems. To determine whether GRK2 regulates the PDGFRbeta in physiologic systems, we examine ... Full text Link to item Cite

Anti-beta(1)-adrenergic receptor antibodies and heart failure: causation, not just correlation.

Journal article J Clin Invest · May 2004 Antibodies specific for the beta(1)-adrenergic receptor are found in patients with chronic heart failure of various etiologies. From work presented in this issue of the JCI, we can now infer that these antibodies actually contribute to the pathogenesis of ... Full text Open Access Link to item Cite

Anti-beta(1)-adrenergic receptor antibodies and heart failure: causation, not just correlation.

Journal article The Journal of clinical investigation · May 1, 2004 Antibodies specific for the beta(1)-adrenergic receptor are found in patients with chronic heart failure of various etiologies. From work presented in this issue of the JCI, we can now infer that these antibodies actually contribute to the pathogenesis of ... Cite

Graft-extrinsic cells predominate in vein graft arterialization.

Journal article Arterioscler Thromb Vasc Biol · March 2004 Featured Publication OBJECTIVE: Vein graft disease involves neointimal smooth muscle cells, the origins of which are unclear. This study sought to characterize and quantitate vein graft infiltration by cells extrinsic to the graft in a mouse model of vein graft disease. METHOD ... Full text Link to item Cite

The adaptor protein beta-arrestin2 enhances endocytosis of the low density lipoprotein receptor.

Journal article J Biol Chem · November 7, 2003 Featured Publication Endocytosis of the low density lipoprotein (LDL) receptor (LDLR) in coated pits employs the clathrin adaptor protein ARH. Similarly, agonist-dependent endocytosis of heptahelical receptors in coated pits employs the clathrin adaptor beta-arrestin proteins. ... Full text Link to item Cite

Phosphorylation of the platelet-derived growth factor receptor-beta and epidermal growth factor receptor by G protein-coupled receptor kinase-2. Mechanisms for selectivity of desensitization.

Journal article J Biol Chem · December 13, 2002 Featured Publication Accumulating evidence suggests that receptor protein-tyrosine kinases, like the platelet-derived growth factor receptor-beta (PDGFRbeta) and epidermal growth factor receptor (EGFR), may be desensitized by serine/threonine kinases. One such kinase, G protei ... Full text Link to item Cite

Neointimal hyperplasia rapidly reaches steady state in a novel murine vein graft model.

Journal article J Vasc Surg · October 2002 Featured Publication OBJECTIVE: Neointimal hyperplasia remains a principal cause of vein graft failure. Genetic contributions to vein graft neointimal hyperplasia could be well studied in the mouse; however, surgical approaches to vein bypass surgery in the mouse have yet to r ... Link to item Cite

Overexpression of G protein-coupled receptor kinase-2 in smooth muscle cells reduces neointimal hyperplasia.

Journal article J Mol Cell Cardiol · October 2002 Featured Publication The activation of vascular smooth muscle cells (SMCs) in neointimal hyperplasia involves signaling through receptor tyrosine kinases as well as G protein-coupled receptors. Overexpression of G protein-coupled receptor kinase-2 (GRK2) in SMCs can attenuate ... Full text Link to item Cite

Serine 232 of the alpha(2A)-adrenergic receptor is a protein kinase C-sensitive effector coupling switch.

Journal article Biochemistry · December 11, 2001 alpha(2)-adrenergic receptors (alpha(2)AR) couple to multiple effectors including adenylyl cyclase and phospholipase C. We hypothesized that signaling selectivity to these effectors is dynamically directed by kinase-sensitive domains within the third intra ... Full text Link to item Cite

Overexpression of G protein-coupled receptor kinase-2 in smooth muscle cells attenuates mitogenic signaling via G protein-coupled and platelet-derived growth factor receptors.

Journal article Circulation · August 15, 2000 Featured Publication BACKGROUND: Neointimal hyperplasia involves activation of smooth muscle cells (SMCs) by several G protein-coupled receptor (GPCR) agonists, including endothelin-1, angiotensin II, thrombin, and thromboxane A(2). Signaling of many GPCRs is diminished by GPC ... Full text Link to item Cite

G protein-coupled receptor kinases.

Journal article Annu Rev Biochem · 1998 G protein-coupled receptor kinases (GRKs) constitute a family of six mammalian serine/threonine protein kinases that phosphorylate agonist-bound, or activated, G protein-coupled receptors (GPCRs) as their primary substrates. GRK-mediated receptor phosphory ... Full text Link to item Cite

Phosphorylation and desensitization of human endothelin A and B receptors. Evidence for G protein-coupled receptor kinase specificity.

Journal article J Biol Chem · July 11, 1997 Although endothelin-1 can elicit prolonged physiologic responses, accumulating evidence suggests that rapid desensitization affects the primary G protein-coupled receptors mediating these responses, the endothelin A and B receptors (ETA-R and ETB-R). The m ... Full text Link to item Cite

Monoclonal antibodies reveal receptor specificity among G-protein-coupled receptor kinases.

Journal article Proc Natl Acad Sci U S A · July 23, 1996 Guanine nucleotide-binding regulatory protein (G protein)-coupled receptor kinases (GRKs) constitute a family of serine/threonine kinases that play a major role in the agonist-induced phosphorylation and desensitization of G-protein-coupled receptors. Here ... Full text Open Access Link to item Cite

Phosphorylation of the type 1A angiotensin II receptor by G protein-coupled receptor kinases and protein kinase C.

Journal article J Biol Chem · May 31, 1996 The type 1A angiotensin II receptor (AT1A-R), which mediates cardiovascular effects of angiotensin II, has been shown to undergo rapid agonist-induced desensitization. We investigated the potential role of second messenger-activated kinases and G protein-c ... Full text Link to item Cite

Desensitization of G protein-coupled receptors.

Journal article Recent Prog Horm Res · 1996 Waning responsiveness to continuous or repeated stimulation constitutes the phenomenon of desensitization, which pervades biological systems. Over the last several years, molecular mechanisms for desensitization of cellular signaling through G protein-coup ... Link to item Cite

Agonist-dependent phosphorylation of the mouse delta-opioid receptor: involvement of G protein-coupled receptor kinases but not protein kinase C.

Journal article Mol Pharmacol · August 1995 With chronic opiate use, opioid receptor desensitization may be one of the important mechanisms underlying the development of opiate tolerance and addiction. Opioid receptors belong to the G protein-coupled receptor superfamily. In this study, the mouse de ... Link to item Cite

Phosphorylation and desensitization of the human beta 1-adrenergic receptor. Involvement of G protein-coupled receptor kinases and cAMP-dependent protein kinase.

Journal article J Biol Chem · July 28, 1995 Persistent stimulation of the beta 1-adrenergic receptor (beta 1AR) engenders, within minutes, diminished responsiveness of the beta 1 AR/adenylyl cyclase signal transduction system. This desensitization remains incompletely defined mechanistically, howeve ... Full text Link to item Cite

A highly conserved tyrosine residue in G protein-coupled receptors is required for agonist-mediated beta 2-adrenergic receptor sequestration.

Journal article J Biol Chem · January 28, 1994 An aromatic residue, tyrosine 326 in the prototypical human beta 2-adrenergic receptor, exists in a highly conserved sequence motif in virtually all members of the G protein-coupled receptor family. The potential role of this conserved aromatic amino acid ... Link to item Cite

Inhibition of thrombin receptor signaling by a G-protein coupled receptor kinase. Functional specificity among G-protein coupled receptor kinases.

Journal article J Biol Chem · January 14, 1994 The thrombin receptor, a member of the seven membrane-spanning superfamily of G-protein coupled receptors, is activated by an irreversible proteolytic mechanism, but signaling by activated thrombin receptors shuts off soon after receptor activation. This s ... Link to item Cite

Effects of ocular carteolol and timolol on plasma high-density lipoprotein cholesterol level.

Journal article Am J Ophthalmol · November 15, 1993 Fifty-eight healthy, normolipidemic adult men participated in a prospective, masked, randomized crossover study designed to compare the effects of two topical nonselective beta-adrenergic antagonists, carteolol and timolol, on plasma high-density lipoprote ... Full text Link to item Cite

Structural basis for receptor subtype-specific regulation revealed by a chimeric beta 3/beta 2-adrenergic receptor.

Journal article Proc Natl Acad Sci U S A · April 15, 1993 The physiological significance of multiple G-protein-coupled receptor subtypes, such as the beta-adrenergic receptors (beta ARs), remains obscure, since in many cases several subtypes activate the same effector and utilize the same physiological agonists. ... Full text Open Access Link to item Cite

Secreted extracellular domains of macrophage scavenger receptors form elongated trimers which specifically bind crocidolite asbestos.

Journal article J Biol Chem · February 15, 1993 Macrophage scavenger receptors, which have been implicated in the development of atherosclerosis and other macrophage-mediated events, are trimeric integral membrane glycoproteins whose extracellular domains have been predicted to include alpha-helical coi ... Link to item Cite

The type I and type II bovine scavenger receptors expressed in Chinese hamster ovary cells are trimeric proteins with collagenous triple helical domains comprising noncovalently associated monomers and Cys83-disulfide-linked dimers.

Journal article J Biol Chem · December 15, 1991 Scavenger receptors have been implicated in the development of atherosclerosis and other macrophage-associated functions. The structures and processing of type I and type II bovine macrophage scavenger receptors were examined using polyclonal anti-receptor ... Link to item Cite

Expression of type I and type II bovine scavenger receptors in Chinese hamster ovary cells: lipid droplet accumulation and nonreciprocal cross competition by acetylated and oxidized low density lipoprotein.

Journal article Proc Natl Acad Sci U S A · June 1, 1991 Type I and type II scavenger receptors, which have been implicated in the development of atherosclerosis and other macrophage-associated functions, differ only by the presence in the type I receptor of an extracellular cysteine-rich C-terminal domain. Stab ... Full text Link to item Cite