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Year of Publication
1.  Proceedings of the Canadian society of allergy and clinical immunology annual scientific meeting 2015 
Côté, Marie-Ève | Boulay, Marie-Ève | Plante, Sophie | Chakir, Jamila | Boulet, Louis-Philippe | Ahmed, Hanan | Ospina, Maria-Beatriz | Sideri, Kyriaki | Vliagoftis, Harissios | Johnson, Sara F. | Woodgate, Roberta L. | Cros, Guilhem | Teira, Pierre | Cellot, Sonia | Bittencourt, Henrique | Decaluwe, Helene | Vachon, Marie France | Duval, Michel | Haddad, Elie | Kim, Vy H. D. | Pham-Huy, Anne | Grunebaum, Eyal | Oliveria, John-Paul | Phan, Stephanie | Tenn, Mark W. | Tworek, Damian | Smith, Steven G. | Baatjes, Adrian J. | Obminski, Caitlin D. | Munoz, Caroline E. | Scime, Tara X. | Sehmi, Roma | Gauvreau, Gail M. | Salter, Brittany M. | Smith, Steven G. | Obminski, Caitlin D. | Munoz, Caroline E. | Schlatman, Abbey | Scime, Tara X. | Watson, Rick | Sherkat, Roya | Khoshnevisan, Razieh | Sheikhbahaei, Saba | Betschel, Stephen | Warrington, Richard | Schellenberg, Robert | Fein, Michael N. | Pelletier, Jean-Philippe | Kan, Manstein | Labrosse, Roxane | Mak, Raymond | Loh, James | Kanani, Amin | Nowak, Dominik A. | Keith, Paul K. | Pannozzo, Daniel | Lima, Hermenio C. | Pham, Diana | Pham, Hoang | Alvarez, Gonzalo G. | Bencze, Istvan T. | Sharma, Krishna B. | Smith, Mark | Aaron, Shawn | Block, Jennifer | Keays, Tara | Leech, Judith | Schneidermen, David | Cameron, Jodi | Forgie, Jennifer | Ring, Alicia | O’Quinn, John W. | Santucci, Stephanie | Yang, William H. | Gaudet, Ena | Aaron, Shawn | Voisin, Mathew R. | Borici-Mazi, Rozita | Vostretsova, Kateryna | Stark, Donald F. | Yeboah, Elizabeth | Martin-Rhee, Michelle | Gula, Cheryl | Cheng, Clare | Paltser, Geoff | Dery, Alizée | Clarke, Ann | Nadeau, Kari | Harada, Laurie | Weatherall, Kimberley | Greenwood, Celia | Daley, Denise | Asai, Yuka | Ben-Shoshan, Moshe | Ling, Ling | Ospina, Maria B. | Protudjer, Jennifer L. P. | Vetander, Mirja | van Hage, Marianne | Olén, Ola | Wickman, Magnus | Bergström, Anna | Teoh, Timothy | Mill, Christopher | Wong, Tiffany | Baerg, Ingrid | Alexander, Angela | Hildebrand, Kyla J. | Dean, John | Kuzeljevic, Boris | Chan, Edmond S. | Argeny, Jonathan | Gona-Hoepler, Mia | Fucik, Petra | Nachbaur, Edith | Gruber, Saskia | Crameri, Reto | Glaser, Andreas | Szépfalusi, Zsolt | Rhyner, Claudio | Eiwegger, Thomas | Plunkett, Greg | Mire, Brad | Yazicioglu, Mehtap | Can, Ceren | Ciplak, Gokce | Cook, Victoria E. | Portales-Casamar, Elodie | Nashi, Emil P. | Gabrielli, Sofianne | Primeau, Marie-Noel | Lejtenyi, Christine | Netchiporouk, Elena | Dery, Alizee | Shand, Greg | Hoe, Erica | Liem, Joel | Ko, Jason K. | Huang, David J. T. | Mazza, Jorge A. | McHenry, Mary | Otley, Anthony | Watson, Wade | Kraft, John N. | Paina, Mihaela | Darwish Hassan, Ahmed A. | Heroux, Delia | Crawford, Lynn | Gauvreau, Gail | Denburg, Judah | Pedder, Linda | Chad, Zave | Sussman, Gordon | Hébert, Jacques | Frankish, Charles | Olynych, Timothy | Cheema, Amarjit | Del Carpio, Jaime | Harrison, Rachel | Torabi, Bahar | Medoff, Elaine | Mill, Jennifer | Quirt, Jaclyn A. | Wen, Xia | Kim, Jonathan | Herrero, Angel Jimenez | Kim, Harold L. | Grzyb, Magdalena J. | Primeau, Marie-Noël | Azad, Meghan B. | Lu, Zihang | Becker, Allan B. | Subbarao, Padmaja | Mandhane, Piushkumar J. | Turvey, Stuart E. | Sears, Malcolm R. | Boucher-Lafleur, Anne-Marie | Gagné-Ouellet, Valérie | Jacques, Éric | Laprise, Catherine | Chen, Michael | McGovern, Toby | Adner, Mikael | Martin, James G. | Cosic, Nela | Ntanda, Henry | Giesbrecht, Gerald | Kozyrskyj, Anita | Letourneau, Nicole | Dawod, Bassel | Marshall, Jean | De Schryver, Sarah | Halbrich, Michelle | La Vieille, Sebastian | Eisman, Harley | Alizadehfar, Reza | Joseph, Lawrence | Morris, Judy | Feldman, Laura Y. | Thacher, Jesse D. | Kull, Inger | Melén, Erik | Pershagen, Göran | Protudjer, Jennifer L. P. | Hosseini, Ali | Hackett, Tillie L. | Hirota, Jeremy | McNagny, Kelly | Wilson, Susan | Carlsten, Chris | Huq, Saiful | Chooniedass, Rishma | Gerwing, Brenda | Huang, Henry | Lefebvre, Diana | Becker, Allan | Khamis, Mona M. | Awad, Hanan | Allen, Kevin | Adamko, Darryl J. | El-Aneed, Anas | Kim, Young Woong | Gliddon, Daniel R. | Shannon, Casey P. | Singh, Amrit | Hickey, Pascal L. C. | Ellis, Anne K. | Neighbour, Helen | Larche, Mark | Tebbutt, Scott J. | Ladouceur, Erika | Stewart, Miriam | Evans, Josh | Masuda, Jeff | To, Teresa | King, Malcolm | Larouche, Miriam | Liang, Liming | Legere, Stephanie A. | Haidl, Ian D. | Legaré, Jean-Francois | Marshall, Jean S. | Sears, Malcolm | Moraes, Theo J. | Ratjen, Felix | Gustafsson, Per | Lou, Wendy | North, Michelle L. | Lee, Elizabeth | Omana, Vanessa | Thiele, Jenny | Brook, Jeff | Rahman, Tanvir | Lejtenyi, Duncan | Fiter, Ryan | Piccirillo, Ciriaco | Mazer, Bruce | Simons, Elinor | Hildebrand, Kyla | Turvey, Stuart | DeMarco, Mari | Le Cao, Kim-Anh | Gauvreau, Gail M. | Mark FitzGerald, J. | O’Byrne, Paul M. | Stiemsma, Leah T. | Arrieta, Marie-Claire | Cheng, Jasmine | Dimitriu, Pedro A. | Thorson, Lisa | Yurist, Sophie | Lefebvre, Diana L. | Mandhane, Piush | McNagny, Kelly M. | Kollmann, Tobias | Mohn, William W. | Brett Finlay, B. | Tran, Maxwell M. | Lefebvre, Diana L. | Ramasundarahettige, Chinthanie F. | Dai, Wei Hao | Mandhane, Piush J. | Tworek, Damian | O’Byrne, Seamus N. | O’Byrne, Paul M. | Denburg, Judah A. | Walsh, Laura | Soliman, Mena | Steacy, Lisa M. | Adams, Daniel E. | Warner, Linda | Mauro, Mary Ann | Mamonluk, Robby | Yang, ChenXi | Conway, Ed M.
Table of contents
A1 Role of fibrocytes in allergic rhinitis
Marie-Ève Côté, Marie-Ève Boulay, Sophie Plante, Jamila Chakir, Louis-Philippe Boulet
A2 Patterns of aeroallergens sensitization in Northern Alberta
Hanan Ahmed, Maria-Beatriz Ospina, Kyriaki Sideri, Harissios Vliagoftis
A3 Addressing acceptable risk for adolescents with Food-Induced Anaphylaxis (FIA)
Sara F. Johnson, Roberta L. Woodgate
A4 Outcomes of matched related and unrelated bone marrow transplantation after reduced-toxicity conditioning for children suffering from Chronic Granulomatous Disease
Guilhem Cros, Pierre Teira, Sonia Cellot, Henrique Bittencourt, Helene Decaluwe, Marie France Vachon, Michel Duval, Elie Haddad
A5 Outcomes of patients with severe combined immunodeficiency (SCID) prior to and after initiation of newborn screening for SCID in Ontario
Vy H.D. Kim, Anne Pham-Huy, Eyal Grunebaum
A6 Detection of regulatory B cells in the airways of subjects with asthma
John-Paul Oliveria, Stephanie Phan, Mark W. Tenn, Damian Tworek, Steven G. Smith, Adrian J. Baatjes, Caitlin D. Obminski, Caroline E. Munoz, Tara X. Scime, Roma Sehmi, Gail M Gauvreau
A7 Characterization of IgE-expressing B cells in the airways and peripheral blood of allergic asthmatic subjects
John-Paul Oliveria, Stephanie Phan, Mark W. Tenn, Brittany M Salter, Steven G Smith, Caitlin D Obminski, Caroline E Munoz, Abbey Schlatman, Tara X Scime, Rick Watson, Roma Sehmi, Gail M Gauvreau
A8 Pregnancy: could it be a risk factor for primary immunodeficient patients
Roya Sherkat, Razieh Khoshnevisan, Saba Sheikhbahaei
A9 Clinical experience with Octagam: a Canadian retrospective chart review
Stephen Betschel, Richard Warrington, Robert Schellenberg
A10 Kounis syndrome secondary to contrast media with inferior ST elevations and bilateral ischemic stroke
Michael N Fein, Jean-Philippe Pelletier
A11 Honey bee venom immunotherapy ineffective in bumble bee-induced anaphylaxis: case report and review of literature
Manstein Kan, Robert Schellenberg
A12 Delayed immune reconstitution occurring after multiple immune complications of hematological stem cell transplantation for a leaky SCID
Roxane Labrosse, Guilhem Cros, Pierre Teira, Henrique Bittencourt, Helene Decaluwe, Michel Duval, Elie Haddad
A13 Comparison of Three Case Reports of Acquired Angioedema: presentation, management and outcome
Raymond Mak, James Loh, Amin Kanani
A14 Sitagliptin-associated angioedema not related to concurrent use of ARB or ACE inhibitor
Dominik A. Nowak, Paul K. Keith
A15 Sneddon-Wilkinson subcorneal pustular dermatosis associated with an IgA monoclonal gammopathy
Daniel Pannozzo, Dominik A. Nowak, Hermenio C. Lima
A16 Omalizumab can be effective in patients with allergic bronchopulmonary aspergillosis
Diana Pham, Hoang Pham, Gonzalo G. Alvarez, Istvan T. Bencze, Krishna B. Sharma, Mark Smith, Shawn Aaron, Jennifer Block, Tara Keays, Judith Leech, David Schneidermen, Jodi Cameron, Jennifer Forgie, Alicia Ring, John W. O’Quinn, Stephanie Santucci, William H. Yang
A17 Efficacious use of omalizumab in the treatment of cystic fibrosis
Diana Pham, Hoang Pham, Ena Gaudet, Shawn Aaron, Stephanie Santucci, William H. Yang
A18 HAE with normal C1-INH with inconsistent response to C1 esterase inhibitor infusion but reliably responsive to icatibant
Hoang Pham, Stephanie Santucci, William H. Yang
A19 Anaphylaxis reaction to lactase enzyme
Mathew R. Voisin, Rozita Borici-Mazi
A20 Risk of solid tumor malignancies in patients with primary immune deficiency
Kateryna Vostretsova, Donald F. Stark
A21 Is it time to adopt the chromogenic assay for measuring C1 esterase inhibitor function in patients with HAE Type 2?
Elizabeth Yeboah, Paul K. Keith
A22 Emergency department visits for anaphylaxis and allergic reactions
Michelle Martin-Rhee, Cheryl Gula, Clare Cheng, Geoff Paltser
A23 START: Susceptibility To food Allergies in a Registry of Twins
Alizée Dery, Ann Clarke, Kari Nadeau, Laurie Harada, Kimberley Weatherall, Celia Greenwood, Denise Daley, Yuka Asai, Moshe Ben-Shoshan
A24 Qualifying the diagnostic approach employed by allergists when managing patients with self-diagnosed non-celiac gluten sensitivity (NCGS)
Lee Horgan, Teresa Pun
A25 Retrospective analysis on the agreement between skin prick test and serum food specific IgE antibody in adults with suspected food allergy
Ling Ling, Maria B. Ospina, Kyriaki Sideri, Harissios Vliagoftis
A26 Staple food hypersensitivity from infancy to adolescence: a report from the BAMSE cohort
Jennifer L.P. Protudjer, Mirja Vetander, Marianne van Hage, Ola Olén, Magnus Wickman, Anna Bergström
A27 Evaluating the impact of supervised epinephrine autoinjector administration during food challenges on perceived parent confidence
Timothy Teoh, Christopher Mill, Tiffany Wong, Ingrid Baerg, Angela Alexander, Kyla J. Hildebrand, John Dean, Boris Kuzeljevic, Edmond S. Chan
A28 Local immunoglobulin production to Aspergillus fumigatus cystic fibrosis
Jonathan Argeny, Mia Gona-Hoepler, Petra Fucik, Edith Nachbaur, Saskia Gruber, Reto Crameri, Andreas Glaser, Zsolt Szépfalusi, Claudio Rhyner, Thomas Eiwegger
A29 Extract consumption with skin prick test (SPT) devices
Greg. Plunkett, Brad Mire
A30 Evaluation of our cases with nonsteroidal anti-inflammatory drug reactions
Mehtap Yazicioglu, Ceren Can, Gokce Ciplak
A31 Reasons for referral and final diagnoses in a tertiary care pediatric allergy clinic
Victoria E. Cook, Kyla J. Hildebrand, Elodie Portales-Casamar, Christopher Mill, Edmond S. Chan
A32 Internist referral practices for inpatients with self-reported penicillin allergies at a tertiary care teaching hospital
Michael N Fein, Emil P Nashi
A33 Assessing the risk of reactions in children with a negative oral challenge after a subsequent use of amoxicillin
Sofianne Gabrielli, Christopher Mill, Marie-Noel Primeau, Christine Lejtenyi, Elena Netchiporouk, Alizee Dery, Greg Shand, Moshe Ben-Shoshan
A34 Validity of self-reported penicillin allergies
Erica Hoe, Joel Liem
A35 Effectiveness of allergy-test directed elimination diets in eosinophilic esophagitis
Jason K. Ko, David J.T. Huang, Jorge A. Mazza
A36 Allergy testing and dietary management in pediatric eosinophilic esophagitis (EoE): A retrospective review of a tertiary Canadian centre’s experience
Mary McHenry, Anthony Otley,Wade Watson
A37 Visualizing the impact of atopic and allergic skin disease
Dominik A. Nowak, John N. Kraft
A38 Cystic fibrosis with and without nasal polyposis in pediatric patients: a cross-sectional comparative study
Mihaela Paina, Ahmed A. Darwish Hassan, Delia Heroux, Lynn Crawford, Gail Gauvreau, Judah Denburg, Linda Pedder, Paul K. Keith
A39 Evaluation of macrolide antibiotic hypersensitivity: the role of oral challenges in children
Bahar Torabi, Marie-Noel Primeau, Christine Lejtenyi, Elaine Medoff, Jennifer Mill, Moshe Ben-Shoshan
A40 Venom allergy testing: is a graded approach necessary?
Jaclyn A. Quirt, Xia Wen, Jonathan Kim, Angel Jimenez Herrero, Harold L. Kim
A41 The role of oral challenges in evaluating cephalosporin hypersensitivity reactions in children
Magdalena J. Grzyb, Marie-Noël Primeau, Christine Lejtenyi, Elaine Medoff, Jennifer Mill, Moshe Ben-Shoshan
A42 Breastfeeding and infant wheeze, atopy and atopic dermatitis: findings from the Canadian Healthy Infant Longitudinal Development Study
Meghan B. Azad, Zihang Lu, Allan B. Becker, Padmaja Subbarao, Piushkumar J. Mandhane, Stuart E. Turvey, Malcolm R. Sears, the CHILD Study Investigators
A43 IL33 DNA methylation in bronchial epithelial cells is associated to asthma
Anne-Marie Boucher-Lafleur, Valérie Gagné-Ouellet, Éric Jacques, Sophie Plante, Jamila Chakir, Catherine Laprise
A44 NRF2 mediates the antioxidant response to organic dust-induced oxidative stress in bronchial epithelial cells
Michael Chen, Toby McGovern, Mikael Adner, James G. Martin
A45 The effects of perinatal distress, immune biomarkers and mother-infant interaction quality on childhood atopic dermatitis (rash) at 18 months
Nela Cosic, Henry Ntanda, Gerald Giesbrecht, Anita Kozyrskyj, Nicole Letourneau
A46 Examining the immunological mechanisms associated with cow’s milk allergy
Bassel Dawod, Jean Marshall
A47 Tryptase levels in children presenting with anaphylaxis to the Montréal Children’s Hospital
Sarah De Schryver, Michelle Halbrich, Ann Clarke, Sebastian La Vieille, Harley Eisman, Reza Alizadehfar, Lawrence Joseph, Judy Morris, Moshe Ben-Shoshan
A48 Secondhand tobacco smoke exposure in infancy and the development of food hypersensitivity from childhood to adolescence
Laura Y. Feldman, Jesse D. Thacher, Inger Kull, Erik Melén, Göran Pershagen, Magnus Wickman, Jennifer L. P. Protudjer, Anna Bergström
A49 Combined exposure to diesel exhaust and allergen enhances allergic inflammation in the bronchial submucosa of atopic subjects
Ali Hosseini, Tillie L. Hackett, Jeremy Hirota, Kelly McNagny, Susan Wilson, Chris Carlsten
A50 Comparison of skin-prick test measurements by an automated system against the manual method
Saiful Huq, Rishma Chooniedass, Brenda Gerwing, Henry Huang, Diana Lefebvre, Allan Becker
A51 The accurate identification and quantification of urinary biomarkers of asthma and COPD through the use of novel DIL- LC-MS/MS methods
Mona M. Khamis, Hanan Awad, Kevin Allen, Darryl J. Adamko, Anas El-Aneed
A52 Systemic immune pathways associated with the mechanism of Cat-Synthetic Peptide Immuno-Regulatory Epitopes, a novel immunotherapy, in whole blood of cat-allergic people
Young Woong Kim, Daniel R. Gliddon, Casey P. Shannon, Amrit Singh, Pascal L. C. Hickey, Anne K. Ellis, Helen Neighbour, Mark Larche, Scott J. Tebbutt
A53 Reducing the health disparities: online support for children with asthma and allergies from low-income families
Erika Ladouceur, Miriam Stewart, Josh Evans, Jeff Masuda, Nicole Letourneau, Teresa To, Malcolm King
A54 Epigenetic association of PSORS1C1 and asthma in the Saguenay-Lac-Saint-Jean asthma study
Miriam Larouche, Liming Liang, Catherine Laprise
A55 IL-33 induces cytokine and chemokine production in human mast cells
Stephanie A. Legere, Ian D. Haidl, Jean-Francois Legaré, Jean S. Marshall
A56 Reference ranges for lung clearance index from infancy to adolescence for Canadian population
Zihang Lu, Malcolm Sears, Theo J. Moraes, Felix Ratjen, Per Gustafsson, Wendy Lou, Padmaja Subbarao
A57 Kingston Allergy Birth Cohort: cohort profile and mother/child characteristics to age 2
Michelle L. North, Elizabeth Lee, Vanessa Omana, Jenny Thiele, Jeff Brook, Anne K. Ellis
A58 Cow’s milk protein specific IgE, IgA and IgG4 as a predictor of outcome in oral immunotherapy
Tanvir Rahman, Duncan Lejtenyi, Sarah De Schryver, Ryan Fiter, Ciriaco Piccirillo, Moshe Ben-Shoshan, Bruce Mazer
A59 Age of peanut introduction and development of reactions and sensitization to peanut
Elinor Simons, Allan B. Becker, Rishma Chooniedass, Kyla Hildebrand, Edmond S. Chan, Stuart Turvey, Padmaja Subbarao, Malcolm Sears
A60 Multi-omic blood biomarker signatures of the late phase asthmatic response
Amrit Singh, Casey P. Shannon, Young Woong Kim, Mari DeMarco, Kim-Anh Le Cao, Gail M. Gauvreau, J. Mark FitzGerald, Louis-Philippe Boulet, Paul M. O’Byrne, Scott J. Tebbutt
A61 Early life gut microbial alterations in children diagnosed with asthma by three years of age
Leah T. Stiemsma, Marie-Claire Arrieta, Jasmine Cheng, Pedro A. Dimitriu, Lisa Thorson, Sophie Yurist, Boris Kuzeljevic, Diana L. Lefebvre, Padmaja Subbarao, Piush Mandhane, Allan Becker, Malcolm R. Sears, Kelly M. McNagny, Tobias Kollmann, the CHILD Study Investigators, William W. Mohn, B. Brett Finlay, Stuart E. Turvey
A62 The relationship between food sensitization and atopic dermatitis at age 1 year in a Canadian birth cohort
Maxwell M. Tran, Diana L. Lefebvre, Chinthanie F. Ramasundarahettige, Allan B. Becker, Wei Hao Dai, Padmaja Subbarao, Piush J. Mandhane, Stuart E. Turvey, Malcolm R. Sears
A63 Allergen inhalation enhances Toll-like receptor-induced thymic stromal lymphopoietin receptor expression by hematopoietic progenitor cells in mild asthmatics
Damian Tworek, Delia Heroux, Seamus N. O’Byrne, Paul M. O’Byrne, Judah A. Denburg
A64 The Allergic Rhinitis Clinical Investigator Collaborative – replicated eosinophilia on repeated cumulative allergen challenges in nasal lavage samples
Laura Walsh, Mena Soliman, Jenny Thiele, Lisa M. Steacy, Daniel E. Adams, Anne K. Ellis
A65 The CHILD Study: optimizing subject retention in pediatric longitudinal cohort research
Linda Warner, Mary Ann Mauro, Robby Mamonluk, Stuart E. Turvey
A66 Differential expression of C3a and C5a in allergic asthma
ChenXi Yang, Amrit Singh, Casey P. Shannon, Young Woong Kim, Ed M. Conway, Scott J. Tebbutt
doi:10.1186/s13223-016-0118-0
PMCID: PMC5009563
2.  Inflammation and oxidative stress in angiogenesis and vascular disease 
Recent evidence suggests that processes of inflammation and angiogenesis are interconnected, especially in human pathologies. Newly formed blood vessels enable the continuous recruitment of inflammatory cells, which release a variety of proangiogenic cytokines, chemokines, and growth factors and further promote angiogenesis. These series of positive feedback loops ultimately create a vicious cycle that exacerbates inflammation, transforming it into the chronic process. Recently, this concept of reciprocity of angiogenesis and inflammation has been expanded to include oxidative stress as a novel mechanistic connection between inflammation-driven oxidation and neovascularization. Production of reactive oxygen species (ROS) results from activation of immune cells by pro-inflammatory stimuli. As oxidative stress can lead to chronic inflammation by activating a variety of transcription factors including NF-κB, AP-1, and PPAR-γ, inflammation itself has a reciprocal relationship with oxidative stress. This review discusses the recent findings in the area bridging neovascularization and oxidation and highlights novel mechanisms of inflammation and oxidative stress driven angiogenesis.
doi:10.1007/s00109-013-1007-3
PMCID: PMC3656485  PMID: 23430240
Angiogenesis; Inflammation; Oxidative stress
3.  Canadian Society of Allergy and Clinical Immunology annual scientific meeting 2016 
Alsayegh, Mohammad A. | Alshamali, Hanan | Khadada, Mousa | Ciccolini, Amanda | Ellis, Anne K. | Quint, Diana | Powley, William | Lee, Laurie | Fiteih, Yahya | Baksh, Shairaz | Vliagoftis, Harissios | Gerega, Sebastien K. | Millson, Brad | Charland, Katia | Barakat, Stephane | Sun, Xichun | Jimenez, Ricardo | Waserman, Susan | FitzGerald, Mark J. | Hébert, Jacques | Cognet-Sicé, Josiane | Renahan, Kevin E. | Huq, Saiful | Chooniedass, Rishma | Sawyer, Scott | Pasterkamp, Hans | Becker, Allan | Smith, Steven G. | Zhang, Shiyuan | Jayasundara, Kavisha | Tacon, Claire | Simidchiev, Alex | Nadeau, Gilbert | Gunsoy, Necdet | Mullerova, Hana | Albers, Frank | Kim, Young Woong | Shannon, Casey P. | Singh, Amrit | Neighbour, Helen | Larché, Mark | Tebbutt, Scott J. | Klopp, Annika | Vehling, Lorena | Becker, Allan B. | Subbarao, Padmaja | Mandhane, Piushkumar J. | Turvey, Stuart E. | Sears, Malcolm R. | Azad, Meghan B. | Loewen, Keely | Monchka, Barret | Mahmud, Salaheddin M. | Jong, Geert ‘t | Longo, Cristina | Bartlett, Gillian | Ducharme, Francine M. | Schuster, Tibor | MacGibbon, Brenda | Barnett, Tracie | North, Michelle L. | Brook, Jeff | Lee, Elizabeth | Omana, Vanessa | Thiele, Jenny | Steacy, Lisa M. | Evans, Greg | Diamond, Miriam | Sussman, Gordon L. | Amistani, Yann | Abiteboul, Kathy | Tenn, Mark W. | Yang, ChenXi | Carlsten, Christopher | Conway, Edward M. | Mack, Douglas | Othman, Yasmin | Barber, Colin M. | Kalicinsky, Chrystyna | Burke, Andrea E. | Messieh, Mary | Nair, Parameswaran | Che, Chun T. | Douglas, Lindsay | Liem, Joel | Duan, Lucy | Miller, Charlotte | Dupuis, Pascale | Connors, Lori A. | Fein, Michael N. | Shuster, Joseph | Hadi, Hani | Polk, Brooke | Raje, Nikita | Labrosse, Roxane | Bégin, Philippe | Paradis, Louis | Roches, Anne Des | Lacombe-Barrios, Jonathan | Mishra, Sanju | Lacuesta, Gina | Chiasson, Meredith | Haroon, Babar | Robertson, Kara | Issekutz, Thomas | Leddin, Desmond | Couban, Stephen | Connors, Lori | Roos, Adrienne | Kanani, Amin | Chan, Edmond S. | Schellenberg, Robert | Rosenfield, Lana | Cvetkovic, Anna | Woodward, Kevin | Quirt, Jaclyn | Watson, Wade T. A. | Castilho, Edson | Sullivan, Jennifer A. | Temple, Beverley | Martin, Donna | Cook, Victoria E. | Mills, Christopher | Portales-Casamar, Elodie | Fu, Lisa W. | Ho, Alexander | Zaltzman, Jeffrey | Chen, Lucy | Vadas, Peter | Gabrielli, Sofianne | Clarke, Ann | Eisman, Harley | Morris, Judy | Joseph, Lawrence | LaVieille, Sebastien | Ben-Shoshan, Moshe | Graham, François | Barnes, Charles | Portnoy, Jay | Stagg, Vincent | Simons, Elinor | Lefebvre, Diana | Dai, David | Mandhane, Piushkumar | Sears, Malcolm | Tam, Herman | Simons, F. Estelle R. | Alotaibi, Dhaifallah | Dawod, Bassel | Tunis, Matthew C. | Marshall, Jean | Desjardins, Marylin | Béland, Marianne | Lejtenyi, Duncan | Drolet, Jean-Phillipe | Lemire, Martine | Tsoukas, Christos | Noya, Francisco J.D. | Alizadehfar, Reza | McCusker, Christine T. | Mazer, Bruce D. | Maestre-Batlle, Danay | Gunawan, Evelyn | Rider, Christopher F. | Bølling, Anette K. | Pena, Olga M. | Suez, Daniel | Melamed, Isaac | Hussain, Iftikhar | Stein, Mark | Gupta, Sudhir | Paris, Kenneth | Fritsch, Sandor | Bourgeois, Christelle | Leibl, Heinz | McCoy, Barbara | Noel, Martin | Yel, Leman | Scott, Ori | Reid, Brenda | Atkinson, Adelle | Kim, Vy Hong-Diep | Roifman, Chaim M. | Grunebaum, Eyal | AlSelahi, Eiman | Aleman, Fernando | Oberle, Amber | Trus, Mike | Sussman, Gordon | Kanani, Amin S. | Chambenoi, Olivier | Chiva-Razavi, Sima | Grodecki, Savannah | Joshi, Nikhil | Menikefs, Peter | Holt, David | Pun, Teresa | Tworek, Damian | Hanna, Raphael | Heroux, Delia | Rosenberg, Elli | Stiemsma, Leah | Turvey, Stuart | Denburg, Judah | Mill, Christopher | Teoh, Timothy | Zimmer, Preeti | Avinashi, Vishal | Paina, Mihaela | Darwish Hassan, Ahmed A. | Oliveria, John Paul | Olesovsky, Chris | Gauvreau, Gail | Pedder, Linda | Keith, Paul K. | Plunkett, Greg | Bolner, Michelle | Pourshahnazari, Persia | Stark, Donald | Vostretsova, Kateryna | Moses, Andrew | Wakeman, Andrew | Singer, Alexander | Gerstner, Thomas | Abrams, Elissa | Johnson, Sara F. | Woodgate, Roberta L.
doi:10.1186/s13223-017-0192-y
PMCID: PMC5390240
4.  AllerGen’s 8th research conference 
Arrieta, Marie-Claire | Arevalos, Andrea | Stiemsma, Leah | Chico, Marta E. | Sandoval, Carlos | Jin, Minglian | Walter, Jens | Cooper, Phil | Finlay, Brett | Bernatchez, Emilie | Gold, Matthew J. | Langlois, Anick | Blais-Lecours, Pascale | Duchaine, Caroline | Marsolais, David | McNagny, Kelly M. | Blanchet, Marie-Renée | Brubacher, Jordan | Chhetri, Bimal | Sabaliauskas, Kelly | Bassil, Kate | Kwong, Jeff | Coates, Frances | Takaro, Tim K. | Chow, Angela | Miller, Gregory E. | Chen, Edith | Mandhane, Piushkumar J. | Turvey, Stuart E. | Elliott, Susan J. | Becker, Allan B. | Subbarao, Padmaja | Sears, Malcolm R. | Kozyrskyj, Anita L. | Dubeau, Aimée | Lu, Zihang | Balkovec, Susan | Kowalik, Krzysztof | Gustafsson, Per | Ratjen, Felix | Edgar, Rachel D. | Bush, Nicole R. | MacIssac, Julie L. | McEwen, Lisa M. | Boyce, Thomas W. | Kobor, Michael S. | Emmerson, Melanie | Dubeau, Aimée | Lu, Zihang | Shen, Bingqing | Kowalik, Krzysztof | Ratjen, Felix | Moraes, Theo J. | Gabrielli, Sofianne | Clarke, Ann | Eisman, Harley | Morris, Judy | Joseph, Lawrence | LaVieille, Sebastien | Ben-Shoshan, Moshe | Islam, Sumaiya A. | Brückmann, Christof | Nieratschker, Vanessa | Jamieson, Kyla C. | Proud, David | Kanagaratham, Cynthia | Camateros, Pierre | Kopriva, Frantisek | Henri, Jennifer | Hajduch, Marian | Radzioch, Danuta | Kang, Liane J. | Koleva, Petya T. | Field, Catherine J. | Konya, Tedd | Scott, James A. | Konya, Theodore | Azad, Meghan B. | Brook, Jeff | Guttman, David | Kumari, Manjeet | Bridgman, Sarah L. | Tun, Mon H. | Mandal, Rupasri | Wishart, David S. | Lee, Amy H. Y. | Xia, Jeff | Gill, Erin | Hancock, Bob | Maestre, Danay | Sutherland, Darren | Hirota, Jeremy | Pena, Olga | Carlsten, Christopher | McEwen, Lisa M. | Jones, Meaghan J. | MacIsaac, Julia L. | Dow, William H. | Rosero-Bixby, Luis | Rehkopf, David H. | Morimoto, Takeshi | Smith, Steven G. | Oliveria, John-Paul | Beaudin, Suzanne | Schlatman, Abbey | Howie, Karen | Obminski, Caitlin | Nusca, Graeme | Sehmi, Roma | Gauvreau, Gail M. | O’Byrne, Paul M. | North, Michelle | Peng, Cheng | Sanchez-Guerra, Marco | Byun, Hyang-Min | Ellis, Anne K. | Baccarelli, Andrea A. | Okeme, Joseph O. | Dhal, Suman | Saini, Aman | Diamond, Miriam L. | Olesovsky, Christopher J. | Salter, Brittany M. | Wang, Michael | Lacy, Paige | O’Sullivan, Michael J. | Park, Chan Y. | Fredberg, Jeffrey J. | Lauzon, Anne-Marie | Martin, James G. | Ryu, Min Hyung | Mookherjee, Neeloffer | Carlsten, Christopher | Simons, Elinor | Lefebvre, Diana | Dai, David | Singh, Amrit | Shannon, Casey P. | Kim, Young Woong | Yang, Chen Xi | Mark FitzGerald, J. | Boulet, Louis-Philippe | Tebbutt, Scott J. | Singhera, Gurpreet K. | JasemineYang, S. | Dorscheid, Delbert R. | Sinnock, Hasantha | Goruk, Susan | Tavakoli, Hamid | Lynd, Larry D. | Sadatsafavi, Mohsen | Tenn, Mark W. | Thiele, Jenny | Adams, Daniel E. | Steacy, Lisa M. | Ellis, Anne K. | Torabi, Bahar | De Schryver, Sarah | Lejtenyi, Duncan | Baerg, Ingrid | Chan, Edmond S. | Mazer, Bruce D. | Tran, Maxwell M. | Dai, Wei Hao | Lou, Wendy | Chari, Radha S. | Conway, Edward M. | Neighbour, Helen | Larché, Mark | Tebbutt, Scott J
doi:10.1186/s13223-016-0164-7
PMCID: PMC5260783
5.  Receptor-Mediated Mechanism Controlling Tissue Levels of Bioactive Lipid Oxidation Products 
Circulation research  2015;117(4):321-332.
Rationale
Oxidative stress is an important contributing factor in a number of human pathologies ranging from atherosclerosis to cancer progression; however, the mechanisms underlying tissue protection from oxidation products are poorly understood. Oxidation of membrane phospholipids, containing the polyunsaturated fatty acid DHA, results in the accumulation of an end product, 2-(ω-carboxyethyl)pyrrole (CEP), which was shown to have pro-angiogenic and pro-inflammatory functions. While CEP is continuously accumulated during chronic processes such as tumor progression and atherosclerosis, its levels during wound healing return to normal when the wound is healed, suggesting the existence of a specific clearance mechanism.
Objective
To identify the cellular and molecular mechanism for CEP clearance.
Methods and Results
Here we show that macrophages are able to bind, scavenge, and metabolize carboxyethylpyrrole derivatives of proteins but not structurally similar ethylpyrrole derivatives, demonstrating the high specificity of the process. F4/80hi and M2-skewed macrophages are much more efficient at CEP binding and scavenging compared to F4/80lo and M1-skewed macrophages. Depletion of macrophages leads to increased CEP accumulation in vivo. CEP binding and clearance are dependent on two receptors expressed by macrophages, CD36 and TLR2. While knockout of each individual receptor results in diminished CEP clearance, the lack of both receptors almost completely abrogates macrophages’ ability to scavenge CEP derivatives of proteins.
Conclusions
Our study demonstrates the mechanisms of recognition, scavenging, and clearance of pathophysiologically active products of lipid oxidation in vivo, thereby contributing to tissue protection against products of oxidative stress.
doi:10.1161/CIRCRESAHA.117.305925
PMCID: PMC4522201  PMID: 25966710
Oxidized lipids; CEP; macrophage; wound healing; angiogenesis; CD36; TLR2
6.  Stability and function of adult vasculature is sustained by Akt/Jagged1 signalling axis in endothelium 
Nature Communications  2016;7:10960.
The signalling pathways operational in quiescent, post-development vasculature remain enigmatic. Here we show that unlike neovascularization, endothelial Akt signalling in established vasculature is crucial not for endothelial cell (EC) survival, but for sustained interactions with pericytes and vascular smooth muscle cells (VSMCs) regulating vascular stability and function. Inducible endothelial-specific Akt1 deletion in adult global Akt2KO mice triggers progressive VSMC apoptosis. In hearts, this causes a loss of arteries and arterioles and, despite a high capillary density, diminished vascular patency and severe cardiac dysfunction. Similarly, endothelial Akt deletion induces retinal VSMC loss and basement membrane deterioration resulting in vascular regression and retinal atrophy. Mechanistically, the Akt/mTOR axis controls endothelial Jagged1 expression and, thereby, Notch signalling regulating VSMC maintenance. Jagged1 peptide treatment of Akt1ΔEC;Akt2KO mice and Jagged1 re-expression in Akt-deficient endothelium restores VSMC coverage. Thus, sustained endothelial Akt1/2 signalling is critical in maintaining vascular stability and homeostasis, thereby preserving tissue and organ function.
The Akt pathway integrates multiple signals, but whether it affects vasculature function is debatable. Here the authors show that Akt pathway shutdown in adult mouse endothelium causes destabilization of vasculature leading to cardiac and retinal dysfunction, due to decreased levels of Jagged1 and impaired Notch signaling.
doi:10.1038/ncomms10960
PMCID: PMC4793084  PMID: 26971877
7.  Management of Recurrent Paravalvular Leakage in a Very High-Risk Patient: A Case Report 
Interventional device closure has emerged as a less invasive alternative to surgery in the management of paravalvular leakage. However, this procedure involves various problems such as a high probability of residual leakage or hemolysis. Here, we report a case of residual paravalvular leakage despite two attempts at interventional closure in a patient with a history of four previous mitral valve replacements. The fifth operation for the primary repair of paravalvular leakage was performed successfully. Careful evaluation before the procedure and specially designed devices are essential for the interventional treatment of paravalvular leakage. Surgery can be performed adequately in the management of paravalvular leakage even in high-risk patients.
doi:10.5090/kjtcs.2015.48.1.59
PMCID: PMC4333853  PMID: 25705600
Mitral valve; Mitral valve, replacement; Reoperation; Recurrence; Regurgitation
9.  Patterns of isotope uptake in sequential postoperative bone scan in undisplaced femoral-neck fractures 
International Orthopaedics  2013;37(8):1541-1545.
Purpose
We aimed to investigate the changing pattern of isotope uptake in the sequential bone scan test for the prediction of osteonecrosis of the femoral head in patients with an undisplaced femoral-neck fracture.
Methods
Fifty-four cases of sequential bone scan for nondisplaced femoral-neck fracture treated by internal fixation with cannulated screws between 2000 and 2009 were retrospectively studied. The mean follow-up period was 4.2 years. The first postoperative bone scan was performed two weeks postoperatively in all patients. Second, third, and fourth follow-up bone scans were performed at one to six months, 12–18 months, and 18–24 months postoperatively.
Results
Mean femoral-head ratio (FHR) in the first postoperative bone scan was 0.99. Although it was under 1.0 in 38 patients (70.4 % of the 54 patients), only one patient developed osteonecrosis of the femoral head. The others showed hot uptake in their second follow-up bone scan. Mean FHRs in the second, third, and fourth postoperative bone scans were 1.69, 1.29, and 1.05, respectively, and there were significant statistical differences in each follow-up period (P = 0.035). In addition, there were unique patterns of isotope uptake with the passage of time, such as cold uptake in the early stage, hot uptake in a couple of months, and iso-uptake in the late stage.
Conclusions
Early postoperative bone scan results should not be over interpreted when predicting osteonecrosis of the femoral head.
doi:10.1007/s00264-013-1983-5
PMCID: PMC3728394  PMID: 23812576
10.  Glucosamine hydrochloride exerts a protective effect against unilateral ureteral obstruction-induced renal fibrosis by attenuating TGF-β signaling 
Abstract
Renal fibrosis is a common consequence of unilateral ureteral obstruction, which provides a useful model to investigate the pathogenesis of obstructive nephropathy and progressive renal fibrosis. Transforming growth factor (TGF-β1) has been recognized as a key mediator in renal fibrosis by stimulating matrix-producing fibrogenic cells and promoting extracellular matrix deposition. Therefore, considerable efforts have been made to regulate TGF-β signaling for antifibrotic therapy. Here, we investigated the mode of action of glucosamine hydrochloride (GS-HCl) on TGF-β1-induced renal fibrosis. In the obstructed kidneys and TGF-β1-treated renal cells, GS-HCl significantly decreased renal expression of α-smooth muscle actin, collagen I, and fibronectin. By investigating the inhibitory mechanism of GS-HCl on renal fibrosis, we found that GS-HCl suppressed TGF-β signaling by inhibiting N-linked glycosylation of the type II TGF-β receptor (TβRII), leading to an inefficient trafficking of TβRII to the membrane surface. Defective N-glycosylation of TβRII further suppressed the TGF-β1-binding to TβRII, thereby decreasing TGF-β signaling. Notably, GS-HCl treatment significantly reduced TGF-β1-induced up-regulation of Smad2/3 phosphorylation and transcriptional activity in vivo and in vitro. Taken together, GS-HCl-mediated regulation of TGF-β signaling exerted an antifibrotic effect, thereby ameliorating renal fibrosis. Our study suggests that GS-HCl would be a promising agent for therapeutic intervention for preventing TGF-β1-induced renal fibrosis in kidney diseases.
Key message
Glucosamine-mediated attenuation of TGF-β signaling ameliorates renal fibrosis in vivoTGF-β1-induced fibrogenic action is reduced by glucosamine in vitroN-glycosylation of the type II TGF-β receptor is suppressed by glucosamineGlucosamine-induced defective N-glycosylation of TβRII decreases TGF-β signaling.
Electronic supplementary material
The online version of this article (doi:10.1007/s00109-013-1086-1) contains supplementary material, which is available to authorized users.
doi:10.1007/s00109-013-1086-1
PMCID: PMC3825548  PMID: 24072041
Renal fibrosis; Glucosamine hydrochloride; TGF-β signaling; N-glycosylation; Type II TGF-β receptor
11.  TGF-β sensitivity is determined by N-linked glycosylation of the type II TGF-β receptor 
Biochemical Journal  2012;445(Pt 3):403-411.
N-linked glycosylation is a critical determinant of protein structure and function, regulating processes such as protein folding, stability and localization, ligand–receptor binding and intracellular signalling. TβRII [type II TGF-β (transforming growth factor β) receptor] plays a crucial role in the TGF-β signalling pathway. Although N-linked glycosylation of TβRII was first demonstrated over a decade ago, it was unclear how this modification influenced TβRII biology. In the present study, we show that inhibiting the N-linked glycosylation process successfully hinders binding of TGF-β1 to TβRII and subsequently renders cells resistant to TGF-β signalling. The lung cancer cell line A549, the gastric carcinoma cell line MKN1 and the immortal cell line HEK (human embryonic kidney)-293 exhibit reduced TGF-β signalling when either treated with two inhibitors, including tunicamycin (a potent N-linked glycosylation inhibitor) and kifunensine [an inhibitor of ER (endoplasmic reticulum) and Golgi mannosidase I family members], or introduced with a non-glycosylated mutant version of TβRII. We demonstrate that defective N-linked glycosylation prevents TβRII proteins from being transported to the cell surface. Moreover, we clearly show that not only the complex type, but also a high-mannose type, of TβRII can be localized on the cell surface. Collectively, these findings demonstrate that N-linked glycosylation is essentially required for the successful cell surface transportation of TβRII, suggesting a novel mechanism by which the TGF-β sensitivity can be regulated by N-linked glycosylation levels of TβRII.
doi:10.1042/BJ20111923
PMCID: PMC3462611  PMID: 22571197
cell surface transport; N-linked glycosylation; transforming growth factor β sensitivity (TGF-β sensitivity); transforming growth factor β signalling (TGF-β signalling); type II transforming growth factor β receptor (TβRII); DAPI, 4′,6-diamidino-2-phenylindole; dNG, deficient N-linked glycosylation; Endo H, endoglycosidase H; ER, endoplasmic reticulum; FBS, fetal bovine serum; GlcNAc, N-acetylglucosamine; HEK, human embryonic kidney; KIF, kifunensine; PDI, protein disulfide-isomerase; PEI, polyethyleneimine; PNGase F, peptide N-glycosidase F; RT, room temperature; TGF-β, transforming growth factor β; TβRI, type I TGF-β receptor; TβRII, type II TGF-β receptor; Tun, tunicamycin; WT, wild-type
12.  Mind bomb 1 in the lymphopoietic niches is essential for T and marginal zone B cell development 
The Journal of Experimental Medicine  2008;205(11):2525-2536.
Notch signaling regulates lineage decisions at multiple stages of lymphocyte development, and Notch activation requires the endocytosis of Notch ligands in the signal-sending cells. Four E3 ubiquitin ligases, Mind bomb (Mib) 1, Mib2, Neuralized (Neur) 1, and Neur2, regulate the Notch ligands to activate Notch signaling, but their roles in lymphocyte development have not been defined. We show that Mib1 regulates T and marginal zone B (MZB) cell development in the lymphopoietic niches. Inactivation of the Mib1 gene, but not the other E3 ligases, Mib2, Neur1, and Neur2, abrogated T and MZB cell development. Reciprocal bone marrow (BM) transplantation experiments revealed that Mib1 in the thymic and splenic niches is essential for T and MZB cell development. Interestingly, when BM cells from transgenic Notch reporter mice were transplanted into Mib1-null mice, the Notch signaling was abolished in the double-negative thymocytes. In addition, the endocytosis of Dll1 was impaired in the Mib1-null microenvironment. Moreover, the block in T cell development and the failure of Dll1 endocytosis were also observed in coculture system by Mib1 knockdown. Our study reveals that Mib1 is the essential E3 ligase in T and MZB cell development, through the regulation of Notch ligands in the thymic and splenic microenvironments.
doi:10.1084/jem.20081344
PMCID: PMC2571928  PMID: 18824586
13.  Mind bomb-1 Is Essential for Intraembryonic Hematopoiesis in the Aortic Endothelium and the Subaortic Patches▿ †  
Molecular and Cellular Biology  2008;28(15):4794-4804.
Intraembryonic hematopoiesis occurs at two different sites, the floor of the aorta and subaortic patches (SAPs) of the para-aortic splanchnopleura (P-Sp)/aorta-gonad-mesonephros (AGM) region. Notch1 and RBP-jκ are critical for the specification of hematopoietic stem cells (HSCs) in Notch signal-receiving cells. However, the mechanism by which Notch signaling is triggered from the Notch signal-sending cells to support embryonic hematopoiesis remains to be determined. We previously reported that Mind bomb-1 (Mib1) regulates Notch ligands in the Notch signal-sending cells (B. K. Koo, M. J. Yoon, K. J. Yoon, S. K. Im, Y. Y. Kim, C. H. Kim, P. G. Suh, Y. N. Jan, and Y. Y. Kong, PLoS ONE 2:e1221, 2007). Here, we show that intraembryonic hematopoietic progenitors were absent in the P-Sp of Mib1−/− embryos, whereas they were partly preserved in the Tie2-cre; Mib1f/f P-Sps, suggesting that Mib1 plays a role in the endothelium and the SAPs. Interestingly, dll1 and dll4/Jag1 are expressed in the SAPs and the endothelium of the AGM, respectively, where mib1 is detected. Indeed, Notch signaling was activated in the nascent HSCs at both sites. In the P-Sp explant culture, the overexpression of Dll1 in OP9 stromal cells rescued the failed production of hematopoietic progenitors in the Mib1−/− P-Sp, while its activity was abolished by Mib1 knockdown. These results suggest that Mib1 is important for intraembryonic hematopoiesis not only in the aortic endothelium but also in the SAPs.
doi:10.1128/MCB.00436-08
PMCID: PMC2493361  PMID: 18505817
14.  Receptor Activator of NF-κB Ligand Regulates the Proliferation of Mammary Epithelial Cells via Id2 
Molecular and Cellular Biology  2006;26(3):1002-1013.
Receptor activator of NF-κB ligand (RANKL) is a key regulator for mammary gland development during pregnancy. RANKL-deficient mice display impaired development of lobulo-alveolar mammary structures. Similar mammary gland defects have been reported in mice lacking Id2. Here we report that RANKL induces the proliferation of mammary epithelial cells via Id2. RANKL triggers marked nuclear translocation of Id2 in mammary epithelial cells. In vivo studies further demonstrated the defective nuclear translocation of Id2, but the normal expression of cyclin D1, in the mammary epithelial cells of rankl−/− mice. In vitro studies with nuclear localization sequence-tagged Id2 revealed that the nuclear localization of Id2 itself is critical for the downregulation of p21 promoter activity. Moreover, RANKL stimulation failed to induce cell growth and to downregulate p21 expression in Id2−/− mammary epithelial cells. Our results indicate that the inhibitor of helix-loop-helix protein, Id2, is critical to control the proliferation of mammary epithelial cells in response to RANKL stimulation.
doi:10.1128/MCB.26.3.1002-1013.2006
PMCID: PMC1347028  PMID: 16428453

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