October 16, 2012 u vol. 109 u no. 42 u 16751–17142

Cover image: Pictured is a genome-wide expression quantitative trait loci map of whole blood from West African children infected with Plasmodium falciparum, a parasite that causes malaria. Youssef Idaghdour et al. analyzed gene expression and genome-wide genotyping data to investigate how host genetics influence the immune response to malaria. The authors found that both P. falciparum infection and host genotype alter genome-wide immune gene expression in a highly coordinated, additive, and multiplicative manner. The findings suggest that susceptibility to malaria infection is under host genetic control at the transcriptional level. See the Feature Article by Idaghdour et al. on pages 16786–16793. Image courtesy of Youssef Idaghdour, Philip Awadalla, and Vanessa Bruat.

From the Cover 16786 Determinants of host response to malaria 16764 Subseafloor microbial habitats 16817 Fine-tuning synthetic gene networks 16847 Cyanobacterial circadian oscillators 16934 Overcoming male infertility

Contents

PROFILE 16754

THIS WEEK IN PNAS 16751

In This Issue

COMMENTARIES 16756

Tracking microbial habitats in subseafloor sediments Andreas P. Teske See companion article on pages E2846 and 16764

16758

Making gene circuits sing Arthur Prindle and Jeff Hasty See companion article on page 16817

16760

Orderly wheels of the cyanobacterial clock Michael J. Rust See companion article on page 16847

16762

Making male gametes in culture Michael D. Griswold See companion article on page 16934

LETTERS (ONLINE ONLY) E2842

Inhibitory signaling through signal regulatory protein-α is not sufficient to explain the antitumor activities of CD47 antibodies David R. Soto-Pantoja, Thomas W. Miller, William A. Frazier, and David D. Roberts

E2843

On the mechanism of CD47 targeting in cancer Xi Wen Zhao, Hanke L. Matlung, Taco W. Kuijpers, and Timo K. van den Berg

E2844

Reply to Soto-Pantoja et al. and Zhao et al.: Targeting CD47 on human solid tumors Stephen B. Willingham, Jens-Peter Volkmer, Kipp Weiskopf, Aaron M. Ring, and Irving L. Weissman

Profile of Pamela J. Fraker Tinsley H. Davis See Inaugural Article on page 7622 in issue 20 of volume 109

PNAS PLUS (AUTHOR SUMMARIES) BIOLOGICAL SCIENCES ENVIRONMENTAL SCIENCES 16764

RETROSPECTIVE 16753

Sir Alan Cottrell (1919–2012) A. Lindsay Greer and Frans Spaepen

Free online through the PNAS open access option.

Correlating microbial community profiles with geochemical data in highly stratified sediments from the Arctic Mid-Ocean Ridge Steffen Leth Jorgensen, Bjarte Hannisdal, Anders Lanzén, Tamara Baumberger, Kristin Flesland, Rita Fonseca, Lise Øvreas, Ida H. Steen, Ingunn H. Thorseth, Rolf B. Pedersen, and Christa Schleper See Commentary on page 16756 See full research article on page E2846 of www.pnas.org PNAS u October 16, 2012 u vol. 109 u no. 42 u iii–vii

EVOLUTION 16766

Inhibitory cross-talk upon introduction of a new metabolic pathway into an existing metabolic network Juhan Kim and Shelley D. Copley See full research article on page E2856 of www.pnas.org

PHYSICAL SCIENCES APPLIED MATHEMATICS 17052

IMMUNOLOGY 16768

Requirement for the histone deacetylase Hdac3 for the inflammatory gene expression program in macrophages Xuefen Chen, Iros Barozzi, Alberto Termanini, Elena Prosperini, Antonio Recchiuti, Jesmond Dalli, Flore Mietton, Gianluca Matteoli, Scott Hiebert, and Gioacchino Natoli See full research article on page E2865 of www.pnas.org

APPLIED PHYSICAL SCIENCES 16794

MEDICAL SCIENCES 16770

Aberrant expression of c-Jun in glioblastoma by internal ribosome entry site (IRES)-mediated translational activation Lior Blau, Revital Knirsh, Iris Ben-Dror, Sivan Oren, Silke Kuphal, Peter Hau, Martin Proescholdt, Anja-Katrin Bosserhoff, and Lily Vardimon See full research article on page E2875 of www.pnas.org

16774

16776

Statistical connectivity provides a sufficient foundation for specific functional connectivity in neocortical neural microcircuits Sean L. Hill, Yun Wang, Imad Riachi, Felix Schürmann, and Henry Markram See full research article on page E2885 of www.pnas.org Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer’s disease model Pascal E. Sanchez, Lei Zhu, Laure Verret, Keith A. Vossel, Anna G. Orr, John R. Cirrito, Nino Devidze, Kaitlyn Ho, Gui-Qiu Yu, Jorge J. Palop, and Lennart Mucke See full research article on page E2895 of www.pnas.org

CHEMISTRY Bacillus cereus iron uptake protein fishes out an unstable ferric citrate trimer Tatsuya Fukushima, Allyson K. Sia, Benjamin E. Allred, Rita Nichiporuk, Zhongrui Zhou, Ulla N. Andersen, and Kenneth N. Raymond

16906

Lithocholic acid is an endogenous inhibitor of MDM4 and MDM2 Simon M. Vogel, Matthias R. Bauer, Andreas C. Joerger, Rainer Wilcken, Tobias Brandt, Dmitry B. Veprintsev, Trevor J. Rutherford, Alan R. Fersht, and Frank M. Boeckler

EARTH, ATMOSPHERIC, AND PLANETARY SCIENCES 16957

16817

An accumulator model for spontaneous neural activity prior to self-initiated movement Aaron Schurger, Jacobo D. Sitt, and Stanislas Dehaene See full research article on page E2904 of www.pnas.org

ECONOMIC SCIENCES

FEATURE ARTICLE Evidence for additive and interaction effects of host genotype and infection in malaria Youssef Idaghdour, Jacklyn Quinlan, Jean-Philippe Goulet, Joanne Berghout, Elias Gbeha, Vanessa Bruat, Thibault de Malliard, Jean-Christophe Grenier, Selma Gomez, Philippe Gros, Mohamed Chérif Rahimy, Ambaliou Sanni, and Philip Awadalla

iv u www.pnas.org

Nuclear transport receptor binding avidity triggers a self-healing collapse transition in FG-nucleoporin molecular brushes Rafael L. Schoch, Larisa E. Kapinos, and Roderick Y. H. Lim

SOCIAL SCIENCES

17135

16786

Fine-tuning gene networks using simple sequence repeats Robert G. Egbert and Eric Klavins See Commentary on page 16758

PHYSICS

INAUGURAL ARTICLE Feature attention evokes task-specific pattern selectivity in V4 neurons Anna E. Ipata, Angela L. Gee, and Michael E. Goldberg

Oxygen isotopes in tree rings are a good proxy for Amazon precipitation and El Niño-Southern Oscillation variability Roel J. W. Brienen, Gerd Helle, Thijs L. Pons, Jean-Loup Guyot, and Manuel Gloor

ENGINEERING

16911

16778

3D imaging and mechanical modeling of helical buckling in Medicago truncatula plant roots Jesse L. Silverberg, Roslyn D. Noar, Michael S. Packer, Maria J. Harrison, Christopher L. Henley, Itai Cohen, and Sharon J. Gerbode

16829

NEUROSCIENCE 16772

Heterogeneity of AMPA receptor trafficking and molecular interactions revealed by superresolution analysis of live cell imaging Nathanael Hoze, Deepak Nair, Eric Hosy, Christian Sieben, Suliana Manley, Andreas Herrmann, Jean-Baptiste Sibarita, Daniel Choquet, and David Holcman

Adolescents’ risk-taking behavior is driven by tolerance to ambiguity Agnieszka Tymula, Lior A. Rosenberg Belmaker, Amy K. Roy, Lital Ruderman, Kirk Manson, Paul W. Glimcher, and Ifat Levy

PSYCHOLOGICAL AND COGNITIVE SCIENCES 16800

Mental time travel and default-mode network functional connectivity in the developing brain Ylva Østby, Kristine B. Walhovd, Christian K. Tamnes, Håkon Grydeland, Lars Tjelta Westlye, and Anders M. Fjell

17058

Selectively altering belief formation in the human brain Tali Sharot, Ryota Kanai, David Marston, Christoph W. Korn, Geraint Rees, and Raymond J. Dolan

17063

High-resolution imaging of expertise reveals reliable object selectivity in the fusiform face area related to perceptual performance Rankin Williams McGugin, J. Christopher Gatenby, John C. Gore, and Isabel Gauthier

16858

A fundamental protein property, thermodynamic stability, revealed solely from large-scale measurements of protein function Carlos L. Araya, Douglas M. Fowler, Wentao Chen, Ike Muniez, Jeffery W. Kelly, and Stanley Fields

16864

Structural basis for promiscuity and specificity during Candida glabrata invasion of host epithelia Manuel Maestre-Reyna, Rike Diderrich, Maik Stefan Veelders, Georg Eulenburg, Vitali Kalugin, Stefan Brückner, Petra Keller, Steffen Rupp, Hans-Ulrich Mösch, and Lars-Oliver Essen

16870

Chlamydia trachomatis protein GrgA activates transcription by contacting the nonconserved region of σ66 Xiaofeng Bao, Bryce E. Nickels, and Huizhou Fan

16876

Crystal structure of Enpp1, an extracellular glycoprotein involved in bone mineralization and insulin signaling Kazuki Kato, Hiroshi Nishimasu, Shinichi Okudaira, Emiko Mihara, Ryuichiro Ishitani, Junichi Takagi, Junken Aoki, and Osamu Nureki

16882

Pathogen-Related Yeast (PRY) proteins and members of the CAP superfamily are secreted sterol-binding proteins Vineet Choudhary and Roger Schneiter

16888

Modification of RelA by O-linked N-acetylglucosamine links glucose metabolism to NF-κB acetylation and transcription David F. Allison, J. Jacob Wamsley, Manish Kumar, Duo Li, Lisa G. Gray, Gerald W. Hart, David R. Jones, and Marty W. Mayo

16894

Transforming a drug/H+ antiporter into a polyamine importer by a single mutation Shlomo Brill, Ofir Sade Falk, and Shimon Schuldiner

16900

Structural basis for TetM-mediated tetracycline resistance Alexandra Dönhöfer, Sibylle Franckenberg, Stephan Wickles, Otto Berninghausen, Roland Beckmann, and Daniel N. Wilson

SUSTAINABILITY SCIENCE 16805

Economics of nuclear power and climate change mitigation policies Nico Bauer, Robert J. Brecha, and Gunnar Luderer

BIOLOGICAL SCIENCES AGRICULTURAL SCIENCES 16811

Targeted microRNA expression in dairy cattle directs production of β-lactoglobulin-free, high-casein milk Anower Jabed, Stefan Wagner, Judi McCracken, David N. Wells, and Goetz Laible

APPLIED BIOLOGICAL SCIENCES 16817

Fine-tuning gene networks using simple sequence repeats Robert G. Egbert and Eric Klavins See Commentary on page 16758

16823

Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target Yongyuth Yuthavong, Bongkoch Tarnchompoo, Tirayut Vilaivan, Penchit Chitnumsub, Sumalee Kamchonwongpaisan, Susan A. Charman, Danielle N. McLennan, Karen L. White, Livia Vivas, Emily Bongard, Chawanee Thongphanchang, Supannee Taweechai, Jarunee Vanichtanankul, Roonglawan Rattanajak, Uthai Arwon, Pascal Fantauzzi, Jirundon Yuvaniyama, William N. Charman, and David Matthews

BIOPHYSICS AND COMPUTATIONAL BIOLOGY

BIOCHEMISTRY 16829

Bacillus cereus iron uptake protein fishes out an unstable ferric citrate trimer Tatsuya Fukushima, Allyson K. Sia, Benjamin E. Allred, Rita Nichiporuk, Zhongrui Zhou, Ulla N. Andersen, and Kenneth N. Raymond

16906

Lithocholic acid is an endogenous inhibitor of MDM4 and MDM2 Simon M. Vogel, Matthias R. Bauer, Andreas C. Joerger, Rainer Wilcken, Tobias Brandt, Dmitry B. Veprintsev, Trevor J. Rutherford, Alan R. Fersht, and Frank M. Boeckler

16835

Role of protons in sugar binding to LacY Irina Smirnova, Vladimir Kasho, Junichi Sugihara, José Luis Vázquez-Ibar, and H. Ronald Kaback

16911

16841

Protein kinase WNK3 regulates the neuronal splicing factor Fox-1 A-Young Lee, Wei Chen, Steve Stippec, Jon Self, Fan Yang, Xiaojun Ding, She Chen, Yu-Chi Juang, and Melanie H. Cobb

Nuclear transport receptor binding avidity triggers a self-healing collapse transition in FG-nucleoporin molecular brushes Rafael L. Schoch, Larisa E. Kapinos, and Roderick Y. H. Lim

16917

Tetrameric assembly of KvLm K+ channels with defined numbers of voltage sensors Ruhma Syeda, Jose S. Santos, Mauricio Montal, and Hagan Bayley

16923

Identification of cation-binding sites on actin that drive polymerization and modulate bending stiffness Hyeran Kang, Michael J. Bradley, Brannon R. McCullough, Anaëlle Pierre, Elena E. Grintsevich, Emil Reisler, and Enrique M. De La Cruz

16928

In vitro reconstitution of the ordered assembly of the endosomal sorting complex required for transport at membrane-bound HIV-1 Gag clusters Lars-Anders Carlson and James H. Hurley

16847

16852

Rhythmic ring–ring stacking drives the circadian oscillator clockwise Yong-Gang Chang, Roger Tseng, Nai-Wei Kuo, and Andy LiWang See Commentary on page 16760 Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis Duo Lu, Jan Silhan, James T. MacDonald, Elisabeth P. Carpenter, Kirsten Jensen, Christoph M. Tang, Geoff S. Baldwin, and Paul S. Freemont

PNAS u October 16, 2012 u vol. 109 u no. 42 u v

DEVELOPMENTAL BIOLOGY 16934

16939

Testis tissue explantation cures spermatogenic failure in c-Kit ligand mutant mice Takuya Sato, Tetsuhiro Yokonishi, Mitsuru Komeya, Kumiko Katagiri, Yoshinobu Kubota, Shogo Matoba, Narumi Ogonuki, Atsuo Ogura, Shosei Yoshida, and Takehiko Ogawa See Commentary on page 16762 A noncoding RNA regulates the neurogenin1 gene locus during mouse neocortical development Masahiro Onoguchi, Yusuke Hirabayashi, Haruhiko Koseki, and Yukiko Gotoh

16945

Collective mesendoderm migration relies on an intrinsic directionality signal transmitted through cell contacts Julien G. Dumortier, Sandro Martin, Dirk Meyer, Frederic M. Rosa, and Nicolas B. David

16951

Analysis of human samples reveals impaired SHH-dependent cerebellar development in Joubert syndrome/Meckel syndrome Andrea Aguilar, Alice Meunier, Laetitia Strehl, Jelena Martinovic, Maryse Bonniere, Tania Attie-Bitach, Féréchté Encha-Razavi, and Nathalie Spassky

16992

Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo Chiaki Iwamura, Kenta Shinoda, Yusuke Endo, Yukiko Watanabe, Damon John Tumes, Shinichiro Motohashi, Kazuyoshi Kawahara, Yuki Kinjo, and Toshinori Nakayama

16998

Using intein catalysis to probe the origin of major histocompatibility complex class I-presented peptides Diego J. Farfán-Arribas, Lawrence J. Stern, and Kenneth L. Rock

17004

Noncoding transcription within the Igh distal VH region at PAIR elements affects the 3D structure of the Igh locus in pro-B cells Jiyoti Verma-Gaur, Ali Torkamani, Lana Schaffer, Steven R. Head, Nicholas J. Schork, and Ann J. Feeney

MEDICAL SCIENCES 17010

Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of Parkinson disease Héctor De Jesús-Cortés, Pin Xu, Jordan Drawbridge, Sandi Jo Estill, Paula Huntington, Stephanie Tran, Jeremiah Britt, Rachel Tesla, Lorraine Morlock, Jacinth Naidoo, Lisa M. Melito, Gelin Wang, Noelle S. Williams, Joseph M. Ready, Steven L. McKnight, and Andrew A. Pieper

17016

Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of amyotrophic lateral sclerosis Rachel Tesla, Hamilton Parker Wolf, Pin Xu, Jordan Drawbridge, Sandi Jo Estill, Paula Huntington, LaTisha McDaniel, Whitney Knobbe, Aaron Burket, Stephanie Tran, Ruth Starwalt, Lorraine Morlock, Jacinth Naidoo, Noelle S. Williams, Joseph M. Ready, Steven L. McKnight, and Andrew A. Pieper

17022

Biochemical evidence for superior correction of neuronal storage by chemically modified enzyme in murine mucopolysaccharidosis VII Ha T. Huynh, Jeffrey H. Grubb, Carole Vogler, and William S. Sly

17028

Misconduct accounts for the majority of retracted scientific publications Ferric C. Fang, R. Grant Steen, and Arturo Casadevall

17034

A framework for identification of actionable cancer genome dependencies in small cell lung cancer Martin L. Sos, Felix Dietlein, Martin Peifer, Jakob Schöttle, Hyatt Balke-Want, Christian Müller, Mirjam Koker, André Richters, Stefanie Heynck, Florian Malchers, Johannes M. Heuckmann, Danila Seidel, Patrick A. Eyers, Roland T. Ullrich, Andrey P. Antonchick, Viktor V. Vintonyak, Peter M. Schneider, Takashi Ninomiya, Herbert Waldmann, Reinhard Büttner, Daniel Rauh, Lukas C. Heukamp, and Roman K. Thomas

ENVIRONMENTAL SCIENCES 16957

16963

Oxygen isotopes in tree rings are a good proxy for Amazon precipitation and El Niño-Southern Oscillation variability Roel J. W. Brienen, Gerd Helle, Thijs L. Pons, Jean-Loup Guyot, and Manuel Gloor Evidence for the respiration of ancient terrestrial organic C in northern temperate lakes and streams S. Leigh McCallister and Paul A. del Giorgio

EVOLUTION 16969

Tibet is one of the centers of domestication of cultivated barley Fei Dai, Eviatar Nevo, Dezhi Wu, Jordi Comadran, Meixue Zhou, Long Qiu, Zhonghua Chen, Avigdor Beiles, Guoxiong Chen, and Guoping Zhang

16974

Cell-type homologies and the origins of the neocortex Jennifer Dugas-Ford, Joanna J. Rowell, and Clifton W. Ragsdale

16980

Variation in personality and fitness in wild female baboons Robert M. Seyfarth, Joan B. Silk, and Dorothy L. Cheney

GENETICS 16786

Evidence for additive and interaction effects of host genotype and infection in malaria Youssef Idaghdour, Jacklyn Quinlan, Jean-Philippe Goulet, Joanne Berghout, Elias Gbeha, Vanessa Bruat, Thibault de Malliard, Jean-Christophe Grenier, Selma Gomez, Philippe Gros, Mohamed Chérif Rahimy, Ambaliou Sanni, and Philip Awadalla

IMMUNOLOGY 16986

Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages Kristopher Clark, Kirsty F. MacKenzie, Kasparas Petkevicius, Yosua Kristariyanto, Jiazhen Zhang, Hwan Geun Choi, Mark Peggie, Lorna Plater, Patrick G. A. Pedrioli, Ed McIver, Nathanael S. Gray, J. Simon C. Arthur, and Philip Cohen

vi u www.pnas.org

MICROBIOLOGY 17040

Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity Peter S. Lee, Reiko Yoshida, Damian C. Ekiert, Naoki Sakai, Yasuhiko Suzuki, Ayato Takada, and Ian A. Wilson

17046

Alphaherpesvirus axon-to-cell spread involves limited virion transmission Matthew P. Taylor, Oren Kobiler, and Lynn W. Enquist

NEUROSCIENCE 16778

Feature attention evokes task-specific pattern selectivity in V4 neurons Anna E. Ipata, Angela L. Gee, and Michael E. Goldberg

17052

17058

17063

PLANT BIOLOGY 17117

Heterogeneity of AMPA receptor trafficking and molecular interactions revealed by superresolution analysis of live cell imaging Nathanael Hoze, Deepak Nair, Eric Hosy, Christian Sieben, Suliana Manley, Andreas Herrmann, Jean-Baptiste Sibarita, Daniel Choquet, and David Holcman

XAX1 from glycosyltransferase family 61 mediates xylosyltransfer to rice xylan Dawn Chiniquy, Vaishali Sharma, Alex Schultink, Edward E. Baidoo, Carsten Rautengarten, Kun Cheng, Andrew Carroll, Peter Ulvskov, Jesper Harholt, Jay D. Keasling, Markus Pauly, Henrik V. Scheller, and Pamela C. Ronald

17123

Selectively altering belief formation in the human brain Tali Sharot, Ryota Kanai, David Marston, Christoph W. Korn, Geraint Rees, and Raymond J. Dolan

Transcriptional repressor PRR5 directly regulates clock-output pathways Norihito Nakamichi, Takatoshi Kiba, Mari Kamioka, Takamasa Suzuki, Takafumi Yamashino, Tetsuya Higashiyama, Hitoshi Sakakibara, and Takeshi Mizuno

17129

CIRCADIAN CLOCK-ASSOCIATED 1 regulates ROS homeostasis and oxidative stress responses Alvina Grace Lai, Colleen J. Doherty, Bernd Mueller-Roeber, Steve A. Kay, Jos H. M. Schippers, and Paul P. Dijkwel

High-resolution imaging of expertise reveals reliable object selectivity in the fusiform face area related to perceptual performance Rankin Williams McGugin, J. Christopher Gatenby, John C. Gore, and Isabel Gauthier

17069

Fine-tuning synaptic plasticity by modulation of CaV2.1 channels with Ca2+ sensor proteins Karina Leal, Sumiko Mochida, Todd Scheuer, and William A. Catterall

17075

Cognitive signals for brain–machine interfaces in posterior parietal cortex include continuous 3D trajectory commands Markus Hauschild, Grant H. Mulliken, Igor Fineman, Gerald E. Loeb, and Richard A. Andersen

PSYCHOLOGICAL AND COGNITIVE SCIENCES 17135

CORRECTIONS APPLIED BIOLOGICAL SCIENCES 17141

17081

DBL-1, a TGF-β, is essential for Caenorhabditis elegans aversive olfactory learning Xiaodong Zhang and Yun Zhang

17087

Activity-dependent BDNF release and TRPC signaling is impaired in hippocampal neurons of Mecp2 mutant mice Wei Li, Gaston Calfa, Jennifer Larimore, and Lucas Pozzo-Miller

17093

Functional anatomy of neural circuits regulating fear and extinction Ewelina Knapska, Matylda Macias, Marta Mikosz, Aleksandra Nowak, Dorota Owczarek, Marcin Wawrzyniak, Marcelina Pieprzyk, Iwona A. Cymerman, Tomasz Werka, Morgan Sheng, Stephen Maren, Jacek Jaworski, and Leszek Kaczmarek

17105

17111

Cardiomyocytes from AKAP7 knockout mice respond normally to adrenergic stimulation Brian W. Jones, Sylvain Brunet, Merle L. Gilbert, C. Blake Nichols, Thomas Su, Ruth E. Westenbroek, John D. Scott, William A. Catterall, and G. Stanley McKnight Assessment of morphometry of pulmonary acini in mouse lungs by nondestructive imaging using multiscale microcomputed tomography Dragos¸ M. Vasilescu, Zhiyun Gao, Punam K. Saha, Leilei Yin, Ge Wang, Beatrice Haefeli-Bleuer, Matthias Ochs, Ewald R. Weibel, and Eric A. Hoffman Solar UV radiation reduces the barrier function of human skin Krysta Biniek, Kemal Levi, and Reinhold H. Dauskardt

In vivo fluorescence imaging of exogenous enzyme activity in the gastrointestinal tract Gregor Fuhrmann and Jean-Christophe Leroux

DEVELOPMENTAL BIOLOGY 17141

Transcriptional network controlled by the trithorax-group gene ash2 in Drosophila melanogaster Sergi Beltran, Enrique Blanco, Florenci Serras, Beatriz Pérez-Villamil, Roderic Guigó, Spyros Artavanis-Tsakonas, and Montserrat Corominas

PHARMACOLOGY 17141

PHYSIOLOGY 17099

Adolescents’ risk-taking behavior is driven by tolerance to ambiguity Agnieszka Tymula, Lior A. Rosenberg Belmaker, Amy K. Roy, Lital Ruderman, Kirk Manson, Paul W. Glimcher, and Ifat Levy

Chemical and genetic evidence for the involvement of Wnt antagonist Dickkopf2 in regulation of glucose metabolism Xiaofeng Li, Jufang Shan, Woochul Chang, Ingyu Kim, Ju Bao, Ho-Jin Lee, Xinxin Zhang, Varman T. Samuel, Gerald I. Shulman, Dakai Liu, Jie J. Zheng, and Dianqing Wu

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Supplement 2 ARTHUR M. SACKLER COLLOQUIUM OF THE NATIONAL ACADEMY OF SCIENCES 17143–17308

Biological Embedding of Early Social Adversity: From Fruit Flies to Kindergartners

PNAS u October 16, 2012 u vol. 109 u no. 42 u vii