February 21, 2012 u vol. 109 u no. 8 u 2685–3190

Cover image: An artistic rendition of combined immunofluorescence and FISH images of a breast tumor shows the antigens CD44 (blue) and CD24 (yellow), chromosome segment 8q24 (red), and the centromere of chromosome 8 (green). Kornelia Polyak and Peter K. Vogt present an overview of progress in major areas of current breast cancer research, including results that might lead to improved treatment outcomes for patients. See the introduction to the Breast Cancer Special Feature on pages 2715–2717. Image courtesy of Vanessa Almendro (Dana-Farber Cancer Institute, Harvard Medical School, Boston). From the Cover

2715 Intra-tumor diversity in breast cancer 2890 Nanoscale modeling and design 3077 microRNAs from RNA viruses 3101 Dopamine signaling and nicotine withdrawal

Contents COMMENTARIES

2691 RNA modeling, naturally Eric Westhof THIS WEEK IN PNAS See companion article on page 2890 2693 Actin bends over backward for directional branching 2685 In This Issue Tatyana M. Svitkina See companion article on page 2913 2695 MicroRNA expression by an oncogenic retrovirus LETTERS (ONLINE ONLY) Bryan R. Cullen See companion article on page 3077 E461 Viruses do replicate in cell-free systems 2697 Shifting pharmacology of nicotine use and withdrawal: Yervand E. Karapetyan Breaking the cycle of drug abuse E462 Reply to Karapetyan: Viral synthesis and assembly is Thibaut Sesia and Anthony A. Grace unlikely to occur under cell-free PMCA conditions See companion article on page 3101 Bruce Chesebro, Mikael Klingeborn, and Brent Race 2699 AgRP neurons: The foes of reproduction in leptin-deficient obese subjects Marcelo O. Dietrich and Tamas L. Horvath QNAS See companion article on page 3155

2687 QnAs with Richard T. Durrett PNAS PLUS (AUTHOR SUMMARIES) Sandeep Ravindran

PHYSICAL SCIENCES PROFILE CHEMISTRY

2688 Profile of Robert B. Goldberg 2705 Unusual macrocyclic lactone sex pheromone of Nicholette Zeliadt Parcoblatta lata, a primary food source of the See Inaugural Article on page 8063 in issue 18 of volume 107 endangered red-cockaded woodpecker Dorit Eliyahu, Satoshi Nojima, Richard G. Santangelo, Shannon Carpenter, Francis X. Webster, David J. Kiemle, Cesar Gemeno, Walter S. Leal, and Coby Schal Free online through the PNAS open access option. See full research article on page E490 of www.pnas.org

PNAS u February 21, 2012 u vol. 109 u no. 8 u iii–ix Downloaded by guest on October 1, 2021 SOCIAL SCIENCES BREAST CANCER SPECIAL FEATURE ANTHROPOLOGY 2701 Heterogeneity of hunting ability and nutritional status INTRODUCTION among domestic dogs in lowland Nicaragua 2715 Progress in breast cancer research Jeremy M. Koster and Kenneth B. Tankersley Kornelia Polyak and Peter K. Vogt See full research article on page E463 of www.pnas.org

RESEARCH ARTICLES BIOLOGICAL SCIENCES 2718 Feedback upregulation of HER3 (ErbB3) expression and CELL BIOLOGY activity attenuates antitumor effect of PI3K inhibitors Anindita Chakrabarty, Violeta Sánchez, María G. Kuba, 2702 Rabenosyn-5 defines the fate of the transferrin receptor Cammie Rinehart, and Carlos L. Arteaga following clathrin-mediated endocytosis Deanna M. Navaroli, Karl D. Bellvé, Clive Standley, Lawrence M. Lifshitz, James Cardia, David Lambright, 2724 Subtype and pathway specific responses to anticancer Deborah Leonard, Kevin E. Fogarty, and Silvia Corvera compounds in breast cancer See full research article on page E471 of www.pnas.org Laura M. Heiser, Anguraj Sadanandam, Wen-Lin Kuo, Stephen C. Benz, Theodore C. Goldstein, Sam Ng, William J. Gibb, Nicholas J. Wang, Safiyyah Ziyad, Frances Tong, DEVELOPMENTAL BIOLOGY Nora Bayani, Zhi Hu, Jessica I. Billig, Andrea Dueregger, 2704 Compensatory functions of histone deacetylase 1 Sophia Lewis, Lakshmi Jakkula, James E. Korkola, Steffen (HDAC1) and HDAC2 regulate transcription and Durinck, François Pepin, Yinghui Guan, Elizabeth Purdom, apoptosis during mouse oocyte development Pierre Neuvial, Henrik Bengtsson, Kenneth W. Wood, Pengpeng Ma, Hua Pan, Rusty L. Montgomery, Peter G. Smith, Lyubomir T. Vassilev, Bryan T. Hennessy, Eric N. Olson, and Richard M. Schultz Joel Greshock, Kurtis E. Bachman, Mary Ann Hardwicke, See full research article on page E481 of www.pnas.org John W. Park, Laurence J. Marton, Denise M. Wolf, Eric A. Collisson, Richard M. Neve, Gordon B. Mills, Terence P. ECOLOGY Speed, Heidi S. Feiler, Richard F. Wooster, David Haussler, Joshua M. Stuart, Joe W. Gray, and Paul T. Spellman 2705 Unusual macrocyclic lactone sex pheromone of Parcoblatta lata, a primary food source of the fi endangered red-cockaded woodpecker 2730 Genome-wide functional screen identi es Dorit Eliyahu, Satoshi Nojima, Richard G. Santangelo, a compendium of genes affecting sensitivity Shannon Carpenter, Francis X. Webster, David J. Kiemle, to tamoxifen Cesar Gemeno, Walter S. Leal, and Coby Schal Ana M. Mendes-Pereira, David Sims, Tim Dexter, See full research article on page E490 of www.pnas.org Kerry Fenwick, Ioannis Assiotis, Iwanka Kozarewa, Costas Mitsopoulos, Jarle Hakas, Marketa Zvelebil, Christopher J. Lord, and Alan Ashworth MICROBIOLOGY 2707 Mevalonate governs interdependency of ergosterol and 2736 The HOXB7 protein renders breast cancer cells resistant siderophore biosyntheses in the fungal pathogen to tamoxifen through activation of the EGFR pathway Aspergillus fumigatus Kideok Jin, Xiangjun Kong, Tariq Shah, Marie-France Penet, Sabiha Yasmin, Laura Alcazar-Fuoli, Mario Gründlinger, Flonne Wildes, Dennis C. Sgroi, Xiao-Jun Ma, Yi Huang, Thomas Puempel, Timothy Cairns, Michael Blatzer, Jordi F. Anne Kallioniemi, Goran Landberg, Ivan Bieche, Xinyan Wu, Lopez, Joan O. Grimalt, Elaine Bignell, and Hubertus Haas Peter E. Lobie, Nancy E. Davidson, Zaver M. Bhujwalla, See full research article on page E497 of www.pnas.org Tao Zhu, and Saraswati Sukumar

NEUROSCIENCE 2742 Maintenance of hormone responsiveness in luminal 2709 Phoneme and word recognition in the auditory breast cancers by suppression of Notch ventral stream James M. Haughian, Mauricio P. Pinto, J. Chuck Harrell, Iain DeWitt and Josef P. Rauschecker Brian S. Bliesner, Kristiina M. Joensuu, Wendy W. Dye, See full research article on page E505 of www.pnas.org Carol A. Sartorius, Aik Choon Tan, Päivi Heikkilä, Charles M. Perou, and Kathryn B. Horwitz 2711 Reduced release probability prevents vesicle depletion and transmission failure at dynamin mutant synapses 2748 Transducin-like enhancer protein 1 mediates estrogen Xuelin Lou, Fan Fan, Mirko Messa, Andrea Raimondi, receptor binding and transcriptional activity in breast Yumei Wu, Loren L. Looger, Shawn M. Ferguson, cancer cells and Pietro De Camilli Kelly A. Holmes, Antoni Hurtado, Gordon D. Brown, See full research article on page E515 of www.pnas.org Rosalind Launchbury, Caryn S. Ross-Innes, James Hadfield, Duncan T. Odom, and Jason S. Carroll PHYSIOLOGY 2713 Sweet taste receptor signaling in beta cells mediates 2754 Cyclin-dependent kinase subunit (Cks) 1 or Cks2 fructose-induced potentiation of glucose-stimulated overexpression overrides the DNA damage response insulin secretion barrier triggered by activated oncoproteins George A. Kyriazis, Mangala M. Soundarapandian, Vasco Liberal, Hanna-Stina Martinsson-Ahlzén, Jennifer and Björn Tyrberg Liberal, Charles H. Spruck, Martin Widschwendter, See full research article on page E524 of www.pnas.org Clare H. McGowan, and Steven I. Reed

iv u www.pnas.org Downloaded by guest on October 1, 2021 2760 Homeobox B9 induces epithelial-to-mesenchymal 2820 Altered antisense-to-sense transcript ratios in transition-associated radioresistance by accelerating breast cancer DNA damage responses Reo Maruyama, Michail Shipitsin, Sibgat Choudhury, Naokazu Chiba, Valentine Comaills, Bunsyo Shiotani, Zhenhua Wu, Alexei Protopopov, Jun Yao, Pang-Kuo Lo, Fumiyuki Takahashi, Toshiyuki Shimada, Ken Tajima, Marina Bessarabova, Alex Ishkin, Yuri Nikolsky, X. Shirley Daniel Winokur, Tetsu Hayashida, Henning Willers, Liu, Saraswati Sukumar, and Kornelia Polyak Elena Brachtel, Maria d. M. Vivanco, Daniel A. Haber, Lee Zou, and Shyamala Maheswaran PHYSICAL SCIENCES 2766 Sensitization of BCL-2–expressing breast tumors to chemotherapy by the BH3 mimetic ABT-737 APPLIED PHYSICAL SCIENCES Samantha R. Oakes, François Vaillant, Elgene Lim, Lily Lee, Kelsey Breslin, Frank Feleppa, Siddhartha Deb, Matthew E. 2825 A small world of weak ties provides optimal global Ritchie, Elena Takano, Teresa Ward, Stephen B. Fox, Daniele integration of self-similar modules in functional Generali, Gordon K. Smyth, Andreas Strasser, David C. S. brain networks Huang, Jane E. Visvader, and Geoffrey J. Lindeman Lazaros K. Gallos, Hernán A. Makse, and Mariano Sigman 3059 The heterogeneous motility of the Lyme disease 2772 Defining the cellular precursors to human breast cancer spirochete in gelatin mimics dissemination through tissue Patricia J. Keller, Lisa M. Arendt, Adam Skibinski, Tanya Michael W. Harman, Star M. Dunham-Ems, Melissa J. Logvinenko, Ina Klebba, Shumin Dong, Avi E. Smith, Caimano, Alexia A. Belperron, Linda K. Bockenstedt, Aleix Prat, Charles M. Perou, Hannah Gilmore, Henry C. Fu, Justin D. Radolf, and Charles W. Wolgemuth Stuart Schnitt, Stephen P. Naber, Jonathan A. Garlick, and Charlotte Kuperwasser EARTH, ATMOSPHERIC, AND PLANETARY SCIENCES 2778 Comparative oncogenomics identifies breast tumors 2831 A serpentinite-hosted ecosystem in the Southern enriched in functional tumor-initiating cells Mariana Forearc Jason I. Herschkowitz, Wei Zhao, Mei Zhang, Jerry Yasuhiko Ohara, Mark K. Reagan, Katsunori Fujikura, Usary, George Murrow, David Edwards, Jana Knezevic, Hiromi Watanabe, Katsuyoshi Michibayashi, Teruaki Ishii, Stephanie B. Greene, David Darr, Melissa A. Troester, Robert J. Stern, Ignacio Pujana, Fernando Martinez, Susan G. Hilsenbeck, Daniel Medina, Charles M. Perou, Guillaume Girard, Julia Ribeiro, Maryjo Brounce, and Jeffrey M. Rosen Naoaki Komori, and Masashi Kino 2784 Antiangiogenic agents increase breast cancer stem cells 2836 Nonequilibrium atmospheric secondary organic aerosol via the generation of tumor hypoxia formation and growth Sarah J. Conley, Elizabeth Gheordunescu, Pramod Kakarala, Véronique Perraud, Emily A. Bruns, Michael J. Ezell, Bryan Newman, Hasan Korkaya, Amber N. Heath, Stanley N. Johnson, Yong Yu, M. Lizabeth Alexander, Alla Shawn G. Clouthier, and Max S. Wicha Zelenyuk, Dan Imre, Wayne L. Chang, Donald Dabdub, James F. Pankow, and Barbara J. Finlayson-Pitts 2790 Mechanistic insight into Myc stabilization in breast cancer involving aberrant Axin1 expression MATHEMATICS Xiaoli Zhang, Amy S. Farrell, Colin J. Daniel, 2842 Approximately diagonalizing matrices over C(Y) Hugh Arnold, Charles Scanlan, Bryan J. Laraway, Huaxin Lin Mahnaz Janghorban, Lawrence Lum, Dexi Chen, Megan Troxell, and Rosalie Sears STATISTICS 2796 Leukocyte composition of human breast cancer 2848 Significance analysis of xMap cytokine bead arrays Brian Ruffell, Alfred Au, Hope S. Rugo, Laura J. Esserman, Joong-Ho Won, Ofir Goldberger, Shai S. Shen-Orr, E. Shelley Hwang, and Lisa M. Coussens Mark M. Davis, and Richard A. Olshen

2802 Integrated molecular profiles of invasive breast tumors and ductal carcinoma in situ (DCIS) reveal differential SOCIAL SCIENCES vascular and interleukin signaling Vessela N. Kristensen, Charles J. Vaske, Josie Ursini-Siegel, PSYCHOLOGICAL AND COGNITIVE SCIENCES Peter Van Loo, Silje H. Nordgard, Ravi Sachidanandam, Therese Sørlie, Fredrik Wärnberg, Vilde D. Haakensen, 2854 Maternal support in early childhood predicts larger Åslaug Helland, Bjørn Naume, Charles M. Perou, hippocampal volumes at school age David Haussler, Olga G. Troyanskaya, Joan L. Luby, Deanna M. Barch, Andy Belden, Michael S. and Anne-Lise Børresen-Dale Gaffrey, Rebecca Tillman, Casey Babb, Tomoyuki Nishino, Hideo Suzuki, and Kelly N. Botteron 2808 Mammary epithelial-specific disruption of c-Src impairs cell cycle progression and tumorigenesis Richard Marcotte, Harvey W. Smith, Virginie BIOLOGICAL SCIENCES Sanguin-Gendreau, Rosalie V. McDonough, and William J. Muller APPLIED BIOLOGICAL SCIENCES 2814 Disruption of bone morphogenetic protein receptor 2 2748 Transducin-like enhancer protein 1 mediates estrogen (BMPR2) in mammary tumors promotes metastases receptor binding and transcriptional activity in breast through cell autonomous and paracrine mediators cancer cells Philip Owens, Michael W. Pickup, Sergey V. Novitskiy, Kelly A. Holmes, Antoni Hurtado, Gordon D. Brown, Anna Chytil, Agnieszka E. Gorska, Mary E. Aakre, Rosalind Launchbury, Caryn S. Ross-Innes, James Hadfield, James West, and Harold L. Moses Duncan T. Odom, and Jason S. Carroll

PNAS u February 21, 2012 u vol. 109 u no. 8 u v Downloaded by guest on October 1, 2021 BIOCHEMISTRY 2760 Homeobox B9 induces epithelial-to-mesenchymal 2860 STK33 kinase inhibitor BRD-8899 has no effect on transition-associated radioresistance by accelerating KRAS-dependent cancer cell viability DNA damage responses Tuoping Luo, Kristina Masson, Jacob D. Jaffe, Whitney Naokazu Chiba, Valentine Comaills, Bunsyo Shiotani, Silkworth, Nathan T. Ross, Christina A. Scherer, Claudia Fumiyuki Takahashi, Toshiyuki Shimada, Ken Tajima, Scholl, Stefan Fröhling, Steven A. Carr, Andrew M. Stern, Daniel Winokur, Tetsu Hayashida, Henning Willers, Stuart L. Schreiber, and Todd R. Golub Elena Brachtel, Maria d. M. Vivanco, Daniel A. Haber, Lee Zou, and Shyamala Maheswaran 2866 Surprising complexity of the Asf1 histone chaperone-Rad53 kinase interaction 2790 Mechanistic insight into Myc stabilization in breast Yue Jiao, Karsten Seeger, Aurelie Lautrette, Albane Gaubert, cancer involving aberrant Axin1 expression Florence Mousson, Raphael Guerois, Carl Mann, Xiaoli Zhang, Amy S. Farrell, Colin J. Daniel, and Françoise Ochsenbein Hugh Arnold, Charles Scanlan, Bryan J. Laraway, Mahnaz Janghorban, Lawrence Lum, Dexi Chen, 2872 Interdomain dynamics and coactivation of the mRNA Megan Troxell, and Rosalie Sears decapping enzyme Dcp2 are mediated by a gatekeeper tryptophan 2814 Disruption of bone morphogenetic protein receptor 2 Stephen N. Floor, Mark S. Borja, and John D. Gross (BMPR2) in mammary tumors promotes metastases through cell autonomous and paracrine mediators 2878 Tropoelastin bridge region positions the cell-interactive Philip Owens, Michael W. Pickup, Sergey V. Novitskiy, C terminus and contributes to elastic fiber assembly Anna Chytil, Agnieszka E. Gorska, Mary E. Aakre, Giselle C. Yeo, Clair Baldock, Anne Tuukkanen, Manfred James West, and Harold L. Moses Roessle, Leanne B. Dyksterhuis, Steven G. Wise, Jacqueline α Matthews, Suzanne M. Mithieux, and Anthony S. Weiss 2931 Skeletal muscle transcriptional coactivator PGC-1 mediates mitochondrial, but not metabolic, changes during calorie restriction BIOPHYSICS AND COMPUTATIONAL BIOLOGY Lydia W. S. Finley, Jaewon Lee, Amanda Souza, Valérie 2884 Subunit order of eukaryotic TRiC/CCT chaperonin by Desquiret-Dumas, Kevin Bullock, Glenn C. Rowe, cross-linking, mass spectrometry, and combinatorial Vincent Procaccio, Clary B. Clish, Zoltan Arany, homology modeling and Marcia C. Haigis Nir Kalisman, Christopher M. Adams, and Michael Levitt 2937 Charged linker sequence modulates eukaryotic heat 2890 Modeling and design by hierarchical natural moves shock protein 90 (Hsp90) chaperone activity Adelene Y. L. Sim, Michael Levitt, and Peter Minary Shinji Tsutsumi, Mehdi Mollapour, Chrisostomos Prodromou, See Commentary on page 2691 Chung-Tien Lee, Barry Panaretou, Soichiro Yoshida, Matthias P. Mayer, and Leonard M. Neckers 2896 Anomalous Brownian motion discloses viscoelasticity in fi the ear’s mechanoelectrical-transduction apparatus 2943 Hydrogen sul de (H2S) metabolism in mitochondria Andrei S. Kozlov, Daniel Andor-Ardó, and A. J. Hudspeth and its regulatory role in energy production Ming Fu, Weihua Zhang, Lingyun Wu, Guangdong Yang, 2+ 2902 Entropic origin of Mg -facilitated RNA folding Hongzhu Li, and Rui Wang Julie L. Fiore, Erik D. Holmstrom, and David J. Nesbitt 2908 Structure of saposin A lipoprotein discs DEVELOPMENTAL BIOLOGY Konstantin Popovic, John Holyoake, Régis Pomès, 2949 Control of target gene specificity during metamorphosis and Gilbert G. Privé by the steroid response gene E93 2913 Actin filament curvature biases branching direction Xiaochun Mou, Dianne M. Duncan, Eric H. Baehrecke, Viviana I. Risca, Evan B. Wang, Ovijit Chaudhuri, and Ian Duncan Jia Jun Chia, Phillip L. Geissler, and Daniel A. Fletcher 2955 A Y-linked anti-Müllerian hormone duplication takes See Commentary on page 2693 over a critical role in sex determination 2919 Aberration-free three-dimensional multiphoton imaging Ricardo S. Hattori, Yu Murai, Miho Oura, Shuji of neuronal activity at kHz rates Masuda, Sullip K. Majhi, Takashi Sakamoto, Juan I. Edward J. Botcherby, Christopher W. Smith, Michael M. Fernandino, Gustavo M. Somoza, Masashi Yokota, Kohl, Delphine Débarre, Martin J. Booth, Rimas Juškaitis, and Carlos A. Strüssmann Ole Paulsen, and Tony Wilson 2925 DNA cleavage and opening reactions of human ECOLOGY topoisomerase IIα are regulated via Mg2+-mediated 2831 A serpentinite-hosted ecosystem in the Southern dynamic bending of gate-DNA Mariana Forearc Sanghwa Lee, Seung-Ryoung Jung, Kang Heo, Jo Ann W. Byl, Yasuhiko Ohara, Mark K. Reagan, Katsunori Fujikura, Joseph E. Deweese, Neil Osheroff, and Sungchul Hohng Hiromi Watanabe, Katsuyoshi Michibayashi, Teruaki Ishii, Robert J. Stern, Ignacio Pujana, Fernando Martinez, Guillaume Girard, Julia Ribeiro, Maryjo Brounce, CELL BIOLOGY Naoaki Komori, and Masashi Kino 2754 Cyclin-dependent kinase subunit (Cks) 1 or Cks2 overexpression overrides the DNA damage response barrier triggered by activated oncoproteins EVOLUTION Vasco Liberal, Hanna-Stina Martinsson-Ahlzén, Jennifer 2960 “Evolution Canyon,” a potential microscale monitor of Liberal, Charles H. Spruck, Martin Widschwendter, global warming across life Clare H. McGowan, and Steven I. Reed Eviatar Nevo

vi u www.pnas.org Downloaded by guest on October 1, 2021 2966 Enzyme functional evolution through improved catalysis 3012 Plasmacytoid dendritic cells control T-cell response to of ancestrally nonpreferred substrates chronic viral infection Ruiqi Huang, Frank Hippauf, Diana Rohrbeck, Maria Luisa Cervantes-Barragan, Kanako L. Lewis, Sonja Firner, Haustein, Katrin Wenke, Janie Feike, Noah Sorrelle, Volker Thiel, Stephanie Hugues, Walter Reith, Birgit Piechulla, and Todd J. Barkman Burkhard Ludewig, and Boris Reizis

GENETICS MEDICAL SCIENCES 2778 Comparative oncogenomics identifies breast tumors 2718 Feedback upregulation of HER3 (ErbB3) expression and enriched in functional tumor-initiating cells activity attenuates antitumor effect of PI3K inhibitors Jason I. Herschkowitz, Wei Zhao, Mei Zhang, Jerry Anindita Chakrabarty, Violeta Sánchez, María G. Kuba, Usary, George Murrow, David Edwards, Jana Knezevic, Cammie Rinehart, and Carlos L. Arteaga Stephanie B. Greene, David Darr, Melissa A. Troester, fi Susan G. Hilsenbeck, Daniel Medina, Charles M. Perou, 2730 Genome-wide functional screen identi es and Jeffrey M. Rosen a compendium of genes affecting sensitivity to tamoxifen 2972 Human genetic variation altering anthrax Ana M. Mendes-Pereira, David Sims, Tim Dexter, toxin sensitivity Kerry Fenwick, Ioannis Assiotis, Iwanka Kozarewa, Mikhail Martchenko, Sophie I. Candille, Hua Tang, Costas Mitsopoulos, Jarle Hakas, Marketa Zvelebil, and Stanley N. Cohen Christopher J. Lord, and Alan Ashworth 2978 Congenital diaphragmatic hernia candidate genes 2736 The HOXB7 protein renders breast cancer cells resistant derived from embryonic transcriptomes to tamoxifen through activation of the EGFR pathway Meaghan K. Russell, Mauro Longoni, Julie Wells, Kideok Jin, Xiangjun Kong, Tariq Shah, Marie-France Penet, Faouzi I. Maalouf, Adam A. Tracy, Maria Loscertales, Flonne Wildes, Dennis C. Sgroi, Xiao-Jun Ma, Yi Huang, Kate G. Ackerman, Barbara R. Pober, Kasper Lage, Anne Kallioniemi, Goran Landberg, Ivan Bieche, Xinyan Wu, Carol J. Bult, and Patricia K. Donahoe Peter E. Lobie, Nancy E. Davidson, Zaver M. Bhujwalla, 2984 Exposure to anticancer drugs can result in Tao Zhu, and Saraswati Sukumar transgenerational genomic instability in mice 2742 Maintenance of hormone responsiveness in luminal Colin D. Glen and Yuri E. Dubrova breast cancers by suppression of Notch 2989 Mutation of A677 in histone methyltransferase EZH2 in James M. Haughian, Mauricio P. Pinto, J. Chuck Harrell, human B-cell lymphoma promotes hypertrimethylation Brian S. Bliesner, Kristiina M. Joensuu, Wendy W. Dye, of histone H3 on lysine 27 (H3K27) Carol A. Sartorius, Aik Choon Tan, Päivi Heikkilä, Michael T. McCabe, Alan P. Graves, Gopinath Ganji, Elsie Charles M. Perou, and Kathryn B. Horwitz Diaz, Wendy S. Halsey, Yong Jiang, Kimberly N. Smitheman, 2766 Sensitization of BCL-2–expressing breast tumors to Heidi M. Ott, Melissa B. Pappalardi, Kimberly E. Allen, chemotherapy by the BH3 mimetic ABT-737 Stephanie B. Chen, Anthony Della Pietra III, Edward Dul, Samantha R. Oakes, François Vaillant, Elgene Lim, Lily Lee, Ashley M. Hughes, Seth A. Gilbert, Sara H. Thrall, Kelsey Breslin, Frank Feleppa, Siddhartha Deb, Matthew E. Peter J. Tummino, Ryan G. Kruger, Martin Brandt, Ritchie, Elena Takano, Teresa Ward, Stephen B. Fox, Daniele Benjamin Schwartz, and Caretha L. Creasy Generali, Gordon K. Smyth, Andreas Strasser, David C. S. 2995 Defective transcription initiation causes postnatal Huang, Jane E. Visvader, and Geoffrey J. Lindeman growth failure in a mouse model of nucleotide fi excision repair (NER) progeria 2772 De ning the cellular precursors to human breast cancer Irene Kamileri, Ismene Karakasilioti, Aria Sideri, Patricia J. Keller, Lisa M. Arendt, Adam Skibinski, Tanya Theodoros Kosteas, Antonis Tatarakis, Iannis Talianidis, Logvinenko, Ina Klebba, Shumin Dong, Avi E. Smith, and George A. Garinis Aleix Prat, Charles M. Perou, Hannah Gilmore, Stuart Schnitt, Stephen P. Naber, Jonathan A. Garlick, IMMUNOLOGY and Charlotte Kuperwasser 2796 Leukocyte composition of human breast cancer 2784 Antiangiogenic agents increase breast cancer stem cells Brian Ruffell, Alfred Au, Hope S. Rugo, Laura J. Esserman, via the generation of tumor hypoxia E. Shelley Hwang, and Lisa M. Coussens Sarah J. Conley, Elizabeth Gheordunescu, Pramod Kakarala, 2848 Significance analysis of xMap cytokine bead arrays Bryan Newman, Hasan Korkaya, Amber N. Heath, Joong-Ho Won, Ofir Goldberger, Shai S. Shen-Orr, Shawn G. Clouthier, and Max S. Wicha Mark M. Davis, and Richard A. Olshen 2802 Integrated molecular profiles of invasive breast tumors 3001 IL-38 binds to the IL-36 receptor and has biological effects and ductal carcinoma in situ (DCIS) reveal differential on immune cells similar to IL-36 receptor antagonist vascular and interleukin signaling Frank L. van de Veerdonk, Angela K. Stoeckman, Gouping Vessela N. Kristensen, Charles J. Vaske, Josie Ursini-Siegel, Wu, Aaron N. Boeckermann, Tania Azam, Mihai G. Netea, Peter Van Loo, Silje H. Nordgard, Ravi Sachidanandam, Leo A. B. Joosten, Jos W. M. van der Meer, Ruyi Hao, Therese Sørlie, Fredrik Wärnberg, Vilde D. Haakensen, Vassili Kalabokis, and Charles A. Dinarello Åslaug Helland, Bjørn Naume, Charles M. Perou, David Haussler, Olga G. Troyanskaya, 3006 Protein phosphatase 1 subunit Ppp1r15a/GADD34 and Anne-Lise Børresen-Dale regulates cytokine production in polyinosinic: polycytidylic acid-stimulated dendritic cells 2808 Mammary epithelial-specific disruption of c-Src impairs Giovanna Clavarino, Nuno Cláudio, Alexandre Dalet, cell cycle progression and tumorigenesis Seigo Terawaki, Thérèse Couderc, Lionel Chasson, Richard Marcotte, Harvey W. Smith, Virginie Maurizio Ceppi, Enrico K. Schmidt, Till Wenger, Sanguin-Gendreau, Rosalie V. McDonough, Marc Lecuit, Evelina Gatti, and Philippe Pierre and William J. Muller

PNAS u February 21, 2012 u vol. 109 u no. 8 u vii Downloaded by guest on October 1, 2021 2820 Altered antisense-to-sense transcript ratios in 3065 Genomic epidemiology of the Escherichia coli O104:H4 breast cancer outbreaks in Europe, 2011 Reo Maruyama, Michail Shipitsin, Sibgat Choudhury, Yonatan H. Grad, Marc Lipsitch, Michael Feldgarden, Zhenhua Wu, Alexei Protopopov, Jun Yao, Pang-Kuo Lo, Harindra M. Arachchi, Gustavo C. Cerqueira, Michael Marina Bessarabova, Alex Ishkin, Yuri Nikolsky, X. Shirley FitzGerald, Paul Godfrey, Brian J. Haas, Cheryl I. Murphy, Liu, Saraswati Sukumar, and Kornelia Polyak Carsten Russ, Sean Sykes, Bruce J. Walker, Jennifer R. Wortman, Sarah Young, Qiandong Zeng, Amr Abouelleil, 3018 Phosphorylation of dedicator of cytokinesis 1 (Dock180) James Bochicchio, Sara Chauvin, Timothy DeSmet, Sharvari at tyrosine residue Y722 by Src family kinases mediates Gujja, Caryn McCowan, Anna Montmayeur, Scott Steelman, EGFRvIII-driven glioblastoma tumorigenesis Jakob Frimodt-Møller, Andreas M. Petersen, Carsten Struve, Haizhong Feng, Bo Hu, Michael J. Jarzynka, Yanxin Li, Susan Karen A. Krogfelt, Edouard Bingen, François-Xavier Weill, Keezer, Terrance G. Johns, Careen K. Tang, Ronald L. Eric S. Lander, Chad Nusbaum, Bruce W. Birren, Hamilton, Kristiina Vuori, Ryo Nishikawa, Jann N. Deborah T. Hung, and William P. Hanage Sarkaria, Tim Fenton, Tao Cheng, Frank B. Furnari, Webster K. Cavenee, and Shi-Yuan Cheng 3071 Human kinome profiling identifies a requirement for AMP-activated protein kinase during human 3024 Breast cancer signatures for invasiveness and prognosis cytomegalovirus infection fi de ned by deep sequencing of microRNA Laura J. Terry, Livia Vastag, Joshua D. Rabinowitz, Stefano Volinia, Marco Galasso, Maria Elena Sana, and Thomas Shenk Timothy F. Wise, Jeff Palatini, Kay Huebner, and Carlo M. Croce 3077 RNA virus microRNA that mimics a B-cell oncomiR Rodney P. Kincaid, James M. Burke, 3030 Central diabetes insipidus associated with impaired and Christopher S. Sullivan renal aquaporin-1 expression in mice lacking liver X See Commentary on page 2695 receptor β Chiara Gabbi, Xiaomu Kong, Hitoshi Suzuki, Hyun-Jin Kim, 3083 Pulmonary infection by Yersinia pestis rapidly establishes Min Gao, Xiao Jia, Hideo Ohnishi, Yoichi Ueta, Margaret a permissive environment for microbial proliferation Warner, Youfei Guan, and Jan-Åke Gustafsson Paul A. Price, Jianping Jin, and William E. Goldman 3035 Role of retroviral restriction factors in the interferon-α– 3089 Neutralizing antibodies against the preactive form of mediated suppression of HIV-1 in vivo respiratory syncytial virus fusion protein offer Satish K. Pillai, Mohamed Abdel-Mohsen, John Guatelli, unique possibilities for clinical intervention Mark Skasko, Alexander Monto, Katsuya Fujimoto, Margarita Magro, Vicente Mas, Keith Chappell, Mónica Steven Yukl, Warner C. Greene, Helen Kovari, Andri Rauch, Vázquez, Olga Cano, Daniel Luque, María C. Terrón, Jacques Fellay, Manuel Battegay, Bernard Hirschel, José A. Melero, and Concepción Palomo Andrea Witteck, Enos Bernasconi, Bruno Ledergerber, NEUROSCIENCE Huldrych F. Günthard, Joseph K. Wong, and the Swiss HIV Cohort Study 3095 A neurophysiological–metabolic model for burst suppression 3041 Intratumoral heterogeneity of receptor tyrosine kinases ShiNung Ching, Patrick L. Purdon, Sujith Vijayan, fi EGFR and PDGFRA ampli cation in glioblastoma Nancy J. Kopell, and Emery N. Brown defines subpopulations with distinct growth factor response 3101 Phasic D1 and tonic D2 dopamine receptor signaling Nicholas J. Szerlip, Alicia Pedraza, Debyani Chakravarty, double dissociate the motivational effects of acute Mohammad Azim, Jeremy McGuire, Yuqiang Fang, nicotine and chronic nicotine withdrawal Tatsuya Ozawa, Eric C. Holland, Jason T. Huse, Taryn E. Grieder, Olivier George, Huibing Tan, Susan R. Suresh Jhanwar, Margaret A. Leversha, Tom Mikkelsen, George, Bernard Le Foll, Steven R. Laviolette, and Cameron W. Brennan and Derek van der Kooy See Commentary on page 2697 3047 Essential requirement for β-arrestin2 in mouse intestinal tumors with elevated Wnt signaling 3107 Cortical topography of intracortical inhibition influences Caroline Bonnans, Maud Flacelière, Fanny Grillet, Christelle the speed of decision making Dantec, Jean-Pierre Desvignes, Julie Pannequin, Dany Claudia Wilimzig, Patrick Ragert, and Hubert R. Dinse Severac, Emeric Dubois, Frédéric Bibeau, Virginie Escriou, 3113 Highly neurotoxic monomeric α-helical prion protein Philippe Crespy, Laurent Journot, Frédéric Hollande, Minghai Zhou, Gregory Ottenberg, Gian Franco Sferrazza, and Dominique Joubert and Corinne Ida Lasmézas 3053 Inactivation of androgen-induced regulator ARD1 3119 Transcription factor LIM homeobox 7 (Lhx7) maintains inhibits androgen receptor acetylation and subtype identity of cholinergic interneurons in prostate tumorigenesis the mammalian striatum Zehua Wang, Zemin Wang, Jianhui Guo, Yingchun Li, Rita Lopes, Nicole Verhey van Wijk, Guilherme Neves, Jasmin H. Bavarva, Chiping Qian, M. Christiane and Vassilis Pachnis Brahimi-Horn, Deyong Tan, and Wanguo Liu 3125 MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and MICROBIOLOGY adult brain function 3059 The heterogeneous motility of the Lyme disease Brooke H. Miller, Zane Zeier, Li Xi, Thomas A. Lanz, spirochete in gelatin mimics dissemination through tissue Shibing Deng, Julia Strathmann, David Willoughby, Michael W. Harman, Star M. Dunham-Ems, Melissa J. Paul J. Kenny, John D. Elsworth, Matthew S. Lawrence, Caimano, Alexia A. Belperron, Linda K. Bockenstedt, Robert H. Roth, Dieter Edbauer, Robin J. Kleiman, Henry C. Fu, Justin D. Radolf, and Charles W. Wolgemuth and Claes Wahlestedt

viii u www.pnas.org Downloaded by guest on October 1, 2021 3131 Temporally-independent functional modes of PSYCHOLOGICAL AND COGNITIVE SCIENCES spontaneous brain activity 3178 Optimal inference of sameness Stephen M. Smith, Karla L. Miller, Steen Moeller, Ronald van den Berg, Michael Vogel, Krešimir Josic, Junqian Xu, Edward J. Auerbach, Mark W. Woolrich, and Wei Ji Ma Christian F. Beckmann, Mark Jenkinson, Jesper Andersson, Matthew F. Glasser, David C. Van Essen, David A. Feinberg, Essa S. Yacoub, and Kamil Ugurbil SYSTEMS BIOLOGY 2724 Subtype and pathway specific responses to anticancer compounds in breast cancer PHARMACOLOGY Laura M. Heiser, Anguraj Sadanandam, Wen-Lin Kuo, 3137 Polycation-siRNA nanoparticles can disassemble at Stephen C. Benz, Theodore C. Goldstein, Sam Ng, William J. fi the kidney glomerular basement membrane Gibb, Nicholas J. Wang, Sa yyah Ziyad, Frances Tong, Jonathan E. Zuckerman, Chung Hang J. Choi, Han Han, Nora Bayani, Zhi Hu, Jessica I. Billig, Andrea Dueregger, and Mark E. Davis Sophia Lewis, Lakshmi Jakkula, James E. Korkola, Steffen Durinck, François Pepin, Yinghui Guan, Elizabeth Purdom, 3143 Fibroblast growth factor 21 promotes bone loss Pierre Neuvial, Henrik Bengtsson, Kenneth W. Wood, by potentiating the effects of peroxisome Peter G. Smith, Lyubomir T. Vassilev, Bryan T. Hennessy, proliferator-activated receptor γ Joel Greshock, Kurtis E. Bachman, Mary Ann Hardwicke, Wei Wei, Paul A. Dutchak, Xunde Wang, Xunshan Ding, John W. Park, Laurence J. Marton, Denise M. Wolf, Eric A. Xueqian Wang, Angie L. Bookout, Regina Goetz, Collisson, Richard M. Neve, Gordon B. Mills, Terence P. Moosa Mohammadi, Robert D. Gerard, Paul C. Speed, Heidi S. Feiler, Richard F. Wooster, David Haussler, Dechow, David J. Mangelsdorf, Steven A. Kliewer, Joshua M. Stuart, Joe W. Gray, and Paul T. Spellman and Yihong Wan 3184 Integrated cross-species transcriptional network analysis 3149 Small molecule antagonist reveals seizure-induced of metastatic susceptibility mediation of neuronal injury by prostaglandin E2 Ying Hu, Gang Wu, Michael Rusch, Luanne Lukes, receptor subtype EP2 Kenneth H. Buetow, Jinghui Zhang, and Kent W. Hunter Jianxiong Jiang, Thota Ganesh, Yuhong Du, Yi Quan, Geidy Serrano, Min Qui, Iris Speigel, Asheebo Rojas, Nadia Lelutiu, and Raymond Dingledine CORRECTIONS

PHYSIOLOGY CHEMISTRY 3155 Ablation of neurons expressing agouti-related protein, 3190 Elucidating the mechanism of selective ion adsorption to but not melanin concentrating hormone, in leptin- the liquid water surface deficient mice restores metabolic functions and fertility Dale E. Otten, Patrick R. Shaffer, Phillip L. Geissler, Qi Wu, Benjamin B. Whiddon, and Richard D. Palmiter and Richard J. Saykally See Commentary on page 2699

3161 Membrane-localized β-subunits alter the PIP2 regulation ECOLOGY 2+ of high-voltage activated Ca channels 3190 Dynamic model of flexible phytoplankton Byung-Chang Suh, Dong-Il Kim, Björn H. Falkenburger, nutrient uptake and Bertil Hille Juan A. Bonachela, Michael Raghib, and Simon A. Levin

PLANT BIOLOGY GENETICS, STATISTICS 3167 Arabidopsis circadian clock protein, TOC1, is 3190 Completely phased genome sequencing through a DNA-binding transcription factor chromosome sorting Joshua M. Gendron, José L. Pruneda-Paz, Hong Yang, Xi Chen, and Wing Hung Wong Colleen J. Doherty, Andrew M. Gross, S. Earl Kang, and Steve A. Kay MICROBIOLOGY 3190 Polar growth in the Alphaproteobacterial POPULATION BIOLOGY order Rhizobiales Pamela J. B. Brown, Miguel A. de Pedro, David T. Kysela, 3173 Impact of cross-protective vaccines on epidemiological Charles Van der Henst, Jinwoo Kim, Xavier De Bolle, fl and evolutionary dynamics of in uenza Clay Fuqua, and Yves V. Brun Nimalan Arinaminpathy, Oliver Ratmann, Katia Koelle, Suzanne L. Epstein, Graeme E. Price, Cecile Viboud, Mark A. Miller, and Bryan T. Grenfell xi Subscription Form

PNAS u February 21, 2012 u vol. 109 u no. 8 u ix Downloaded by guest on October 1, 2021