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Ofcial Journal of the American Society for Investigative Pathology Table of Contents November 2013 Volume 183 Number 5 On the Cover: A novel immunouorescence method quanties HER2 protein expression and heterogeneity at the single-cell level on formalin-xed, parafn-embedded patient samples. The assay utilizes automated image analysisdcomparing samples with a parallel-standard cell pellet arraydto identify and classify nontumor (cyan) versus tumor cells with different HER2 expression on a scale of low (pink) to high (red) HER2. (See page 1446.) 1351 This Month in AJP Reviews 1352 Phenotypic Transitions of Macrophages Orchestrate Tissue Repair Margaret L. Novak and Timothy J. Koh 1364 New Insights into the Pathology of Podocyte Loss: Mitotic Catastrophe Helen Liapis, Paola Romagnani, and Hans-Joachim Anders Commentaries 1375 Cannabinoid Receptor 2 Activation: A Means to Prevent MonocyteeEndothelium Engagement Shilpa J. Buch + Related article appears on page 1548 1378 Asbestos-Induced Mesothelioma: Is Fiber Biopersistence Really a Critical Factor? Elliott Kagan + Related article appears on page 1654 Short Communications 1382 Decrease of Virus Receptors during Highly Pathogenic H5N1 Virus Infection in Humans and Other Mammals Debby van Riel, Lonneke M. Leijten, George Kochs, Ab D.M.E. Osterhaus, and Thijs Kuiken 1390 Resveratrol Exacerbates Both Autoimmune and Viral Models of Multiple Sclerosis Fumitaka Sato, Nicholas E. Martinez, Maira Shahid, John W. Rose, Noel G. Carlson, and Ikuo Tsunoda 1397 IL-10 Restrains IL-17 to Limit Lung Pathology Characteristics following Pulmonary Infection with Francisella tularensis Live Vaccine Strain Samantha R. Slight, Leticia Monin, Radha Gopal, Lyndsay Avery, Marci Davis, Hillary Cleveland, Tim D. Oury, Javier Rangel-Moreno, and Shabaana A. Khader 1405 Comparative Evaluation of miRNA Expression between in Vitro and in Vivo Airway Epithelium Demonstrates Widespread Differences Peter Chen, Jeffrey D. Edelman, and Sina A. Gharib

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Page 1: Table of Contents

Official Journal of the American Society for Investigative Pathology

Table of Contents

November 2013

Volume 183

Number 5

On the Cover: A novel immunofluorescence method quantifies HER2 protein expression and heterogeneity at the single-cell levelon formalin-fixed, paraffin-embedded patient samples. The assay utilizes automated image analysisdcomparing samples witha parallel-standard cell pellet arraydto identify and classify nontumor (cyan) versus tumor cells with different HER2 expression ona scale of low (pink) to high (red) HER2. (See page 1446.)

1351 This Month in AJP

Reviews

1352 Phenotypic Transitions of Macrophages Orchestrate Tissue Repair

Margaret L. Novak and Timothy J. Koh

1364 New Insights into the Pathology of Podocyte Loss: Mitotic Catastrophe

Helen Liapis, Paola Romagnani, and Hans-Joachim Anders

Commentaries

1375 Cannabinoid Receptor 2 Activation: A Means to Prevent MonocyteeEndothelium Engagement

Shilpa J. Buch+ Related article appears on page 1548

1378 Asbestos-Induced Mesothelioma: Is Fiber Biopersistence Really a Critical Factor?

Elliott Kagan+ Related article appears on page 1654

Short Communications

1382 Decrease of Virus Receptors during Highly Pathogenic H5N1 Virus Infection in Humans and Other Mammals

Debby van Riel, Lonneke M. Leijten, George Kochs, Ab D.M.E. Osterhaus, and Thijs Kuiken

1390 Resveratrol Exacerbates Both Autoimmune and Viral Models of Multiple Sclerosis

Fumitaka Sato, Nicholas E. Martinez, Maira Shahid, John W. Rose, Noel G. Carlson, and Ikuo Tsunoda

1397 IL-10 Restrains IL-17 to Limit Lung Pathology Characteristics following Pulmonary Infection withFrancisella tularensis Live Vaccine Strain

Samantha R. Slight, Leticia Monin, Radha Gopal, Lyndsay Avery, Marci Davis, Hillary Cleveland, Tim D. Oury,

Javier Rangel-Moreno, and Shabaana A. Khader

1405 Comparative Evaluation of miRNA Expression between in Vitro and in Vivo Airway Epithelium DemonstratesWidespread Differences

Peter Chen, Jeffrey D. Edelman, and Sina A. Gharib
Page 2: Table of Contents

The American Journal of PATHOLOGY, Vol. 183, No. 5, November 2013

Regular Articles

Animal Models

1411 Sparing of the Dystrophin-Deficient Cranial Sartorius Muscle Is Associated with Classical and NovelHypertrophy Pathways in GRMD Dogs

Peter P. Nghiem, Eric P. Hoffman, Priya Mittal, Kristy J. Brown, Scott J. Schatzberg, Svetlana Ghimbovschi,

Zuyi Wang, and Joe N. Kornegay

1425 Transthyretin Is Dysregulated in Preeclampsia, and Its Native Form Prevents the Onset of Disease in a PreclinicalMouse Model

Satyan S. Kalkunte, Stefan Neubeck, Wendy E. Norris, Shi-Bin Cheng, Stefan Kostadinov, Dang Vu Hoang, Aftab Ahmed,

Ferdinand von Eggeling, Zahir Shaikh, James Padbury, Goran Berg, Anders Olofsson, Udo R. Markert, and Surendra Sharma

Biomarkers, Genomics, Proteomics, and Gene Regulation

1437 miR-210 Inhibits Trophoblast Invasion and Is a Serum Biomarker for Preeclampsia

Lauren Anton, Anthony O. Olarerin-George, Nadav Schwartz, Sindhu Srinivas, Jamie Bastek, John B. Hogenesch, and Michal A. Elovitz

1446 Single-Cell Quantitative HER2 Measurement Identifies Heterogeneity and Distinct Subgroups within TraditionallyDefined HER2-Positive Patients

Matthew D. Onsum, Elena Geretti, Violette Paragas, Arthur J. Kudla, Sharon P. Moulis, Lia Luus, Thomas J. Wickham,

Charlotte F. McDonagh, Gavin MacBeath, and Bart S. Hendriks

Cardiovascular, Pulmonary, and Renal Pathology

1461 Treatment with AntieGremlin 1 Antibody Ameliorates Chronic Hypoxia/SU5416eInduced PulmonaryArterial Hypertension in Mice

Loredana Ciuclan, KellyAnn Sheppard, Liqun Dong, Daniel Sutton, Nicholas Duggan, Martin Hussey, Jenny Simmons,

Nicholas W. Morrell, Gabor Jarai, Matthew Edwards, Gerald DuBois, Matthew Thomas, Gino Van Heeke, and Karen England

1474 Epithelial Calreticulin Up-Regulation Promotes Profibrotic Responses and Tubulointerstitial Fibrosis Development

Niki Prakoura, Panagiotis K. Politis, Yoshito Ihara, Marek Michalak, and Aristidis S. Charonis

1488 The Selective A3AR Antagonist LJ-1888 Ameliorates UUO-Induced Tubulointerstitial Fibrosis

Jiyoun Lee, Inah Hwang, Jung H. Lee, Hyuk W. Lee, Lak-Shin Jeong, and Hunjoo Ha

Gastrointestinal, Hepatobiliary, and Pancreatic Pathology

1498 IL-17A Synergistically Enhances Bile AcideInduced Inflammation during Obstructive Cholestasis

Kate M. O’Brien, Katryn M. Allen, Cheryl E. Rockwell, Keara Towery, James P. Luyendyk, and Bryan L. Copple

1508 Alcohol Exacerbates LPS-Induced Fibrosis in Subclinical Acute Pancreatitis

Haitao Gu, Franco Fortunato, Frank Bergmann, Markus W. Büchler, David C. Whitcomb, and Jens Werner

1518 Role of Bile Acids in Liver Injury and Regeneration following Acetaminophen Overdose

Bharat Bhushan, Prachi Borude, Genea Edwards, Chad Walesky, Joshua Cleveland, Feng Li, Xiaochao Ma, and Udayan Apte

1527 Islet Transplantation and Insulin Administration Relieve Long-Term Complications and Rescue the ResidualEndogenous Pancreatic b Cells

Marina Figliuzzi, Roberto Bianchi, Cristina Cavagnini, Raffaella Lombardi, Carla Porretta-Serapiglia, Giuseppe Lauria,

Federica Avezza, Annalisa Canta, Valentina Carozzi, Alessia Chiorazzi, Paola Marmiroli, Cristina Meregalli, Norberto Oggioni,

Barbara Sala, Guido Cavaletti, and Andrea Remuzzi

Immunopathology and Infectious Diseases

1539 Atypical and Classical Forms of the Disease-Associated State of the Prion Protein Exhibit Distinct Neuronal Tropism,Deposition Patterns, and Lesion Profiles

Gabor G. Kovacs, Natallia Makarava, Regina Savtchenko, and Ilia V. Baskakov
Page 3: Table of Contents

The American Journal of PATHOLOGY, Vol. 183, No. 5, November 2013

1548 Selective Activation of Cannabinoid Receptor 2 in Leukocytes Suppresses Their Engagement of the BrainEndothelium and Protects the BloodeBrain Barrier

Slava Rom, Viviana Zuluaga-Ramirez, Holly Dykstra, Nancy L. Reichenbach, Pal Pacher, and Yuri Persidsky+ Related Commentary appears on page 1375

Matrix Pathobiology

1559 Activated Alveolar Epithelial Cells Initiate Fibrosis through Secretion of Mesenchymal Proteins

Jibing Yang, Sarah E. Wheeler, Miranda Velikoff, Kathryn R. Kleaveland, Michael J. LaFemina, James A. Frank,

Harold A. Chapman, Paul J. Christensen, and Kevin K. Kim

1571 Renal Heparan Sulfate Proteoglycans Modulate Fibroblast Growth Factor 2 Signaling in Experimental ChronicTransplant Dysfunction

Kirankumar Katta, Miriam Boersema, Saritha Adepu, Heleen Rienstra, Johanna W.A.M. Celie, Rik Mencke, Grietje Molema,

Harry van Goor, Jo H.M. Berden, Gerjan Navis, Jan-Luuk Hillebrands, and Jacob van den Born

Metabolic, Endocrine, and Genitourinary Pathobiology

1585 Age-Related Alterations in Regeneration of the Urinary Bladder after Subtotal Cystectomy

David M. Burmeister, Tamer AbouShwareb, Christopher R. Bergman, Karl-Erik Andersson, and George J. Christ

1596 VEGFR-3 Neutralization Inhibits Ovarian Lymphangiogenesis, Follicle Maturation, and Murine Pregnancy

Joseph M. Rutkowski, Jong Eun Ihm, Seung Tae Lee, Witold W. Kilarski, Veronique I. Greenwood, Miriella C. Pasquier,

Alexandra Quazzola, Didier Trono, Jeffrey A. Hubbell, and Melody A. Swartz

Stem Cells, Tissue Engineering, and Hematopoietic Elements

1608 CNS Inflammation and Bone Marrow Neuropathy in Type 1 Diabetes

Ping Hu, Jeffrey S. Thinschmidt, Yuanqing Yan, Sugata Hazra, Ashay Bhatwadekar, Sergio Caballero, Tatiana Salazar,

Jaleel A. Miyan, Wencheng Li, Andrei Derbenev, Andrea Zsombok, Maria Tikhonenko, James M. Dominguez II,

Susan P. McGorray, Daniel R. Saban, Michael E. Boulton, Julia V. Busik, Mohan K. Raizada, Tailoi Chan-Ling, and Maria B. Grant

1621 Reactivation of NCAM1 Defines a Subpopulation of Human Adult Kidney Epithelial Cells with Clonogenicand Stem/Progenitor Properties

Ella Buzhor, Dorit Omer, Orit Harari-Steinberg, Zohar Dotan, Einav Vax, Sara Pri-Chen, Sally Metsuyanim, Oren Pleniceanu,

Ronald S. Goldstein, and Benjamin Dekel

Tumorigenesis and Neoplastic Progression

1634 PPAPDC1B and WHSC1L1 Are Common Drivers of the 8p11-12 Amplicon, Not Only in Breast TumorsBut Also in Pancreatic Adenocarcinomas and Lung Tumors

Sardar F. Mahmood, Nadège Gruel, Rémy Nicolle, Elodie Chapeaublanc, Olivier Delattre, François Radvanyi,

and Isabelle Bernard-Pierrot

1645 The Regulation of SOX7 and Its Tumor Suppressive Role in Breast Cancer

Daniel B. Stovall, Meimei Wan, Lance D. Miller, Paul Cao, Dejan Maglic, Qiang Zhang, Martha R. Stampfer, Wennuan Liu,

Jianfeng Xu, and Guangchao Sui

1654 Continuous Exposure to Chrysotile Asbestos Can Cause Transformation of Human Mesothelial Cells viaHMGB1 and TNF-a Signaling

Fang Qi, Gordon Okimoto, Sandro Jube, Andrea Napolitano, Harvey I. Pass, Rozalia Laczko, Richard M. DeMay,

Ghazal Khan, Maarit Tiirikainen, Caterina Rinaudo, Alessandro Croce, Haining Yang, Giovanni Gaudino, and

Michele Carbone+ Related Commentary appears on page 1378

1667 Src Plays a Key Role in ADAM28 Expression in v-srceTransformed Epithelial Cells and Human Carcinoma Cells

Hitoshi Abe, Satsuki Mochizuki, Kentaro Ohara, Mari Ueno, Hiroki Ochiai, Yuko Kitagawa, Okio Hino, Hiroshi Sato,

and Yasunori Okada

1679 Progesterone Signaling Inhibits Cervical Carcinogenesis in Mice

Young A Yoo, Jieun Son, Fabiola F. Mehta, Francesco J. DeMayo, John P. Lydon, and Sang-Hyuk Chung
Page 4: Table of Contents

The American Journal of PATHOLOGY, Vol. 183, No. 5, November 2013

1688 Slug/b-CatenineDependent Proinflammatory Phenotype in Hypoxic Breast Cancer Stem Cells

Gianluca Storci, Sara Bertoni, Sabrina De Carolis, Alessio Papi, Marina Nati, Claudio Ceccarelli, Chiara Pirazzini, Paolo Garagnani,

Alberto Ferrarini, Genny Buson, Massimo Delledonne, Michelangelo Fiorentino, Elisa Capizzi, Elisa Gruppioni, Mario Taffurelli,

Donatella Santini, Claudio Franceschi, Giuseppe Bandini, Francesca Bonifazi, and Massimiliano Bonafé

1698 Corrections

ASIP 2013 AJP CME Program in Pathogenesis appears online. For details about objectives, educational goals, registration,and required examination, see http://www.asip.org/CME/index.cfm. The planning committee members and staff have no relevantfinancial relationships with commercial interest to disclose. Financial relationships (including the name of the commercial entity andthe nature of the relationship) of the authors of selected articles in this journal-based CME activity will be disclosed in the publishedarticle and in each journal CME examination. See below for CME accreditation statement.

Objectives: Upon completion of this journal-based CME activity you will be able to:- discuss the research underway and/or current molecular approaches to decipher the pathogenesis of disease.- demonstrate a gained level of knowledge of the methods and techniques being used by researchers and practitioners.- understand the link between pathogenesis and the development of new diagnostic, prognostic, and therapeutic approaches to

infectious diseases, inherited diseases and syndromes, and to acquired diseases and syndromes spanning systems biology.

The ASIP 2013 AJP CME Program in Pathogenesis qualifies as an American Board of Pathology Maintenance of Certification Part IISelf-Assessment Module (SAM). For details, see http://www.asip.org/CME/index.cfm.

denotes participating articles in this issue

CME Accreditation Statement: This activity (“ASIP 2013 AJP CME Program in Pathogenesis”) has been planned and implementedin accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through thejoint sponsorship of the American Society for Clinical Pathology (ASCP) and the American Society for Investigative Pathology (ASIP).ASCP is accredited by the ACCME to provide continuing medical education for physicians.

The ASCP designates this journal-based CME activity (“ASIP 2013 AJP CME Program in Pathogenesis”) for a maximum of 48 AMA PRACategory 1 Credit(s)�. Physicians should only claim credit commensurate with the extent of their participation in the activity.