Download [Science] 10 May 2013 vol 340, issue 6133, pages 653-776

[Science] 10 May 2013 vol 340, issue 6133, pages 653-776
Perspectives - Immunology
Crowdsourcing Immunity
James E. Crowe Jr.
Science 10 May 2013: 692-693.[DOI:10.1126/science.1238628]
Computational methods reveal the nature and diversity of antibodies in HIV-infected individuals.
Reports
Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate
Neutralization
Ivelin S. Georgiev, Nicole A. Doria-Rose, Tongqing Zhou, Young Do Kwon, Ryan P. Staupe, Stephanie Moquin, Gwo-Yu Chuang, Mark K. Louder,
Stephen D. Schmidt, Han R. Altae-Tran, Robert T. Bailer, Krisha McKee, Martha Nason, Sijy O’Dell,
Gilad Ofek, Marie Pancera, Sanjay Srivatsan, Lawrence Shapiro, Mark Connors, Stephen A. Migueles, Lynn Morris, Yoshiaki Nishimura, Malcolm A.
Martin, John R. Mascola, and Peter D. Kwong
Science 10 May 2013: 751-756.[DOI:10.1126/science.1233989]
An algorithm predicts the neutralization specificity of sera from HIV-infected individuals.
Perspectives - Neuroscience
Why Adults Need New Brain Cells
Olaf Bergmann and Jonas Frisén
Science 10 May 2013: 695-696.[DOI:10.1126/science.1237976]
Neurogenesis and gliogenesis shape connectivity in the adult brain, influencing plasticity and repair.
Reports
Emergence of Individuality in Genetically Identical Mice
Julia Freund, Andreas M. Brandmaier, Lars Lewejohann, Imke Kirste, Mareike Kritzler, Antonio Krüger, Norbert Sachser,
Ulman Lindenberger, and Gerd Kempermann
Science 10 May 2013: 756-759.[DOI:10.1126/science.1235294]
Over time, the brains and behaviors of inbred mice diversify.
[Science] 10 May 2013 vol 340, issue 6133, pages 653-776
Reviews
Bacterial Subversion of Host Innate Immune Pathways
Leigh A. Baxt, Anna Cristina Garza-Mayers, and Marcia B. Goldberg
Science 10 May 2013: 697-701.[DOI:10.1126/science.1235771]
Cellular Self-Defense: How Cell-Autonomous Immunity Protects Against Pathogens
Felix Randow, John D. MacMicking, and Leo C. James
Science 10 May 2013: 701-706.[DOI:10.1126/science.1233028]
Research Articles
Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors
Joseph Jardine, Jean-Philippe Julien, Sergey Menis, Takayuki Ota, Oleksandr Kalyuzhniy, Andrew McGuire, Devin Sok,
Po-Ssu Huang, Skye MacPherson, Meaghan Jones, Travis Nieusma, John Mathison, David Baker, Andrew B. Ward, Dennis R. Burton, Leonidas
Stamatatos, David Nemazee, Ian A. Wilson, and William R. Schief
Science 10 May 2013: 711-716. DOI:10.1126/science.1234150]
Structural knowledge of broadly neutralizing antibodies against HIV-1 guides the design of an immunogen to elicit them.
[Science] 10 May 2013 vol 340, issue 6133, pages 653-776
Reports
Robust Circadian Oscillations in Growing Cyanobacteria Require Transcriptional
Feedback
Shu-Wen Teng, Shankar Mukherji, Jeffrey R. Moffitt, Sophie de Buyl, and Erin K. O’Shea
Science 10 May 2013: 737-740.[DOI:10.1126/science.1230996]
The cyanobacterial clock uses one circuit for rhythms and a second circuit for intercellular synchronous oscillations.
Global Leaf Trait Relationships: Mass, Area, and the Leaf Economics Spectrum
Jeanne L. D. Osnas, Jeremy W. Lichstein, Peter B. Reich, and Stephen W. Pacala
Science 10 May 2013: 741-744. [DOI:10.1126/science.1231574]
Leaf traits are distributed in proportion to area; relationships between leaf traits are independent of leaf mass and area.
Early Mesodermal Cues Assign Avian Cardiac Pacemaker Fate Potential in a Tertiary
Heart Field
Michael Bressan, Gary Liu, and Takashi Mikawa
Science 10 May 2013: 744-748. [DOI:10.1126/science.1232877]
A region of the lateral plate mesoderm gives rise to the cardiac pacemaker cell lineage prior to the onset of heart
formation.
Wolbachia Invades Anopheles stephensi Populations and Induces Refractoriness to
Plasmodium Infection
Guowu Bian, Deepak Joshi, Yuemei Dong, Peng Lu, Guoli Zhou, Xiaoling Pan, Yao Xu, George Dimopoulos, and Zhiyong Xi
Science 10 May 2013: 748-751.[DOI:10.1126/science.1236192]
Stable inheritance of a symbiotic bacterium suppresses malaria parasites in mosquitoes.
Compartmentalization of GABAergic Inhibition by Dendritic Spines
Chiayu Q. Chiu, Gyorgy Lur, Thomas M. Morse, Nicholas T. Carnevale, Graham C. R. Ellis-Davies, and Michael J. Higley
Science 10 May 2013: 759-762.[DOI:10.1126/science.1234274]
Inhibitory synapses can control individual dendritic spines independently from their neighbors.
[Science Sig] 7 May 2013 Vol 6, Issue 274
Gene network reconstruction reveals cell cycle and antiviral genes as major
drivers of cervical cancer
Karina L. Mine,1, 2, 12Natalia Shulzhenko,1, 3, 4, 12Anatoly Yambartsev,5Mark Rochman,6, 13
Gerdine F. O. Sanson,1, 13Malin Lando,7Sudhir Varma,8Jeff Skinner,8Natalia Volfovsky,9
Tao Deng,6Sylvia M. F. Brenna,10Carmen R. N. Carvalho,11Julisa C. L. Ribalta,11Michael Bustin,6Polly
Matzinger,3Ismael D. C. G. Silva,11Heidi Lyng,7Maria Gerbase-DeLima1, 2
& Andrey Morgun1, 3, 4
Instituto de Imunogenética—Associação Fundo de Incentivo à Pesquisa (IGEN-AFIP), São Paulo, São
Paulo, Brazil
Although human papillomavirus was identified as an aetiological factor in cervical
cancer, the key human gene drivers of this disease remain unknown. Here we apply
an unbiased approach integrating gene expression and chromosomal aberration data.
In an independent group of patients, we reconstruct and validate a gene regulatory
meta-network, and identify cell cycle and antiviral genes that constitute two major
subnetworks upregulated in tumour samples. These genes are located within the
same regions as chromosomal amplifications, most frequently on 3q. We propose a
model in which selected chromosomal gains drive activation of antiviral genes
contributing to episomal virus elimination, which synergizes with cell cycle
dysregulation. These findings may help to explain the paradox of episomal human
papillomavirus decline in women with invasive cancer who were previously unable to
clear the virus.
Table of Contents
May 1, 2013; 27 (9)
The mechanisms by which the p53 tumor suppressor acts remain
incompletely understood. To gain new insights into p53 biology, we used
high-throughput sequencing to analyze global p53 transcriptional
networks in primary mouse embryo fibroblasts in response to DNA
damage. Chromatin immunoprecipitation sequencing reveals 4785 p53bound sites in the genome located near 3193 genes involved in diverse
biological processes. RNA sequencing analysis shows that only a subset
of p53-bound genes is transcriptionally regulated, yielding a list of 432
p53-bound and regulated genes. Interestingly, we identify a host of
autophagy genes as direct p53 target genes. While the autophagy
program is regulated predominantly by p53, the p53 family members p63
and p73 contribute to activation of this autophagy gene network.
Induction of autophagy genes in response to p53 activation is associated
with enhanced autophagy in diverse settings and depends on p53
transcriptional activity. While p53-induced autophagy does not affect cell
cycle arrest in response to DNA damage, it is important for both robust
p53-dependent apoptosis triggered by DNA damage and transformation
suppression by p53. Together, our data highlight an intimate connection
between p53 and autophagy through a vast transcriptional network and
indicate that autophagy contributes to p53-dependent apoptosis and
cancer suppression.
KJ
The Novel Gene tank, a Tumor Suppressor Homolog, Regulates Ethanol
Sensitivity in Drosophila
Anita V. Devineni, Mark Eddison, and Ulrike Heberlein
Abstract
In both mammalian and insect models of ethanol intoxication, high doses of ethanol induce motor impairment and
eventually sedation. Sensitivity to the sedative effects of ethanol is inversely correlated with risk for alcoholism.
However, the genes regulating ethanol sensitivity are largely unknown. Based on a previous genetic screen in
Drosophila for ethanol sedation mutants, we identified a novel gene, tank (CG15626), the homolog of the mammalian
tumor suppressor EI24/PIG8, which has a strong role in regulating ethanol sedation sensitivity. Genetic and behavioral
analyses revealed that tank acts in the adult nervous system to promote ethanol sensitivity. We localized the function
of tank in regulating ethanol sensitivity to neurons within the pars intercerebralis that have not been implicated
previously in ethanol responses. We show that acutely manipulating the activity of all tank-expressing neurons, or of
pars intercerebralis neurons in particular, alters ethanol sensitivity in a sexually dimorphic manner, since neuronal
activation enhanced ethanol sedation in males, but not females. Finally, we provide anatomical evidence that tankexpressing neurons form likely synaptic connections with neurons expressing the neural sex determination factor
fruitless (fru), which have been implicated recently in the regulation of ethanol sensitivity. We suggest that a
functional interaction with fru neurons, many of which are sexually dimorphic, may account for the sex-specific effect
induced by activating tank neurons. Overall, we have characterized a novel gene and corresponding set of neurons
that regulate ethanol sensitivity in Drosophila.
KJ
KJ
KJ
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA.
How hematopoietic stem cells (HSCs) coordinate the regulation of opposing cellular mechanisms such as self-renewal
and differentiation commitment remains unclear. Here we identified the transcription factor and chromatin remodeler
Satb1 as a critical regulator of HSC fate. HSCs lacking Satb1 had defective self-renewal, were less quiescent and
showed accelerated lineage commitment, which resulted in progressive depletion of functional HSCs. The enhanced
commitment was caused by less symmetric self-renewal and more symmetric differentiation divisions of Satb1deficient HSCs. Satb1 simultaneously repressed sets of genes encoding molecules involved in HSC activation and
cellular polarity, including Numb and Myc, which encode two key factors for the specification of stem-cell fate. Thus,
Satb1 is a regulator that promotes HSC quiescence and represses lineage commitment.
Laboratory of Host Defense, World Premier International Research Center Immunology Frontier Research Center,
Osaka University, Osaka, Japan.
NLRP3 forms an inflammasome with its adaptor ASC, and its excessive activation can cause inflammatory diseases.
However, little is known about the mechanisms that control assembly of the inflammasome complex. Here we show
that microtubules mediated assembly of the NLRP3 inflammasome. Inducers of the NLRP3 inflammasome caused
aberrant mitochondrial homeostasis to diminish the concentration of the coenzyme NAD+, which in turn inactivated
the NAD+-dependent α-tubulin deacetylase sirtuin 2; this resulted in the accumulation of acetylated α-tubulin.
Acetylated α-tubulin mediated the dynein-dependent transport of mitochondria and subsequent apposition of ASC
on mitochondria to NLRP3 on the endoplasmic reticulum. Therefore, in addition to direct activation of NLRP3, the
creation of optimal sites for signal transduction by microtubules is required for activation of the entire NLRP3
inflammasome.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
NOD2 receptor and the cytosolic protein kinase RIPK2 regulate NF-κB and MAP kinase signaling during bacterial
infections, but the role of this immune axis during viral infections has not been addressed. We demonstrate that
Nod2−/− and Ripk2−/− mice are hypersusceptible to infection with influenza A virus. Ripk2−/− cells exhibited defective
autophagy of mitochondria (mitophagy), leading to enhanced mitochondrial production of superoxide and
accumulation of damaged mitochondria, which resulted in greater activation of the NLRP3 inflammasome and
production of IL-18. RIPK2 regulated mitophagy in a kinase-dependent manner by phosphorylating the mitophagy
inducer ULK1. Accordingly, Ulk1−/− cells exhibited enhanced mitochondrial production of superoxide and activation of
caspase-1. These results demonstrate a role for NOD2-RIPK2 signaling in protection against virally triggered
immunopathology by negatively regulating activation of the NLRP3 inflammasome and production of IL-18 via ULK1dependent mitophagy.