Nature advance online publication 01 November 2009. doi:10.1038/nature08557

Authors:

Although Galactic cosmic rays (protons and nuclei) are widely believed to be mainly accelerated by the winds and supernovae of massive stars, definitive evidence of this origin remains elusive nearly a century after their discovery. The active regions of starburst galaxies have exceptionally high rates of star formation, and their large size—more than 50 times the diameter of similar Galactic regions—uniquely enables reliable calorimetric measurements of their potentially high cosmic-ray density. The cosmic rays produced in the formation, life and death of massive stars in these regions are expected to produce diffuse γ-ray emission through interactions with interstellar gas and radiation. M82, the prototype small starburst galaxy, is predicted to be the brightest starburst galaxy in terms of γ-ray emission. Here we report the detection of >700-GeV γ-rays from M82. From these data we determine a cosmic-ray density of 250 eV cm-3 in the starburst core, which is about 500 times the average Galactic density. This links cosmic-ray acceleration to star formation activity, and suggests that supernovae and massive-star winds are the dominant accelerators.

Nature advance online publication 01 November 2009. doi:10.1038/nature08582

Authors: Kirill I. Bolotin, Fereshte Ghahari, Michael D. Shulman, Horst L. Stormer & Philip Kim

When electrons are confined in two dimensions and subject to strong magnetic fields, the Coulomb interactions between them can become very strong, leading to the formation of correlated states of matter, such as the fractional quantum Hall liquid. In this strong quantum regime, electrons and magnetic flux quanta bind to form complex composite quasiparticles with fractional electronic charge; these are manifest in transport measurements of the Hall conductivity as rational fractions of the elementary conductance quantum. The experimental discovery of an anomalous integer quantum Hall effect in graphene has enabled the study of a correlated two-dimensional electronic system, in which the interacting electrons behave like massless chiral fermions. However, owing to the prevailing disorder, graphene has so far exhibited only weak signatures of correlated electron phenomena, despite intense experimental and theoretical efforts. Here we report the observation of the fractional quantum Hall effect in ultraclean, suspended graphene. In addition, we show that at low carrier density graphene becomes an insulator with a magnetic-field-tunable energy gap. These newly discovered quantum states offer the opportunity to study correlated Dirac fermions in graphene in the presence of large magnetic fields.

Nature advance online publication 28 October 2009. doi:10.1038/nature08574

Authors: A. A. Abdo, M. Ackermann, M. Ajello, K. Asano, W. B. Atwood, M. Axelsson, L. Baldini, J. Ballet, G. Barbiellini, M. G. Baring, D. Bastieri, K. Bechtol, R. Bellazzini, B. Berenji, P. N. Bhat, E. Bissaldi, E. D. Bloom, E. Bonamente, J. Bonnell, A. W. Borgland, A. Bouvier, J. Bregeon, A. Brez, M. S. Briggs, M. Brigida, P. Bruel, J. M. Burgess, T. H. Burnett, G. A. Caliandro, R. A. Cameron, P. A. Caraveo, J. M. Casandjian, C. Cecchi, Ö. Çelik, V. Chaplin, E. Charles, C. C. Cheung, J. Chiang, S. Ciprini, R. Claus, J. Cohen-Tanugi, L. R. Cominsky, V. Connaughton, J. Conrad, S. Cutini, C. D. Dermer, A. de Angelis, F. de Palma, S. W. Digel, B. L. Dingus, E. do Couto e Silva, P. S. Drell, R. Dubois, D. Dumora, C. Farnier, C. Favuzzi, S. J. Fegan, J. Finke, G. Fishman, W. B. Focke, L. Foschini, Y. Fukazawa, S. Funk, P. Fusco, F. Gargano, D. Gasparrini, N. Gehrels, S. Germani, L. Gibby, B. Giebels, N. Giglietto, F. Giordano, T. Glanzman, G. Godfrey, J. Granot, J. Greiner, I. A. Grenier, M.-H. Grondin, J. E. Grove, D. Grupe, L. Guillemot, S. Guiriec, Y. Hanabata, A. K. Harding, M. Hayashida, E. Hays, E. A. Hoversten, R. E. Hughes, G. Jóhannesson, A. S. Johnson, R. P. Johnson, W. N. Johnson, T. Kamae, H. Katagiri, J. Kataoka, N. Kawai, M. Kerr, R. M. Kippen, J. Knödlseder, D. Kocevski, C. Kouveliotou, F. Kuehn, M. Kuss, J. Lande, L. Latronico, M. Lemoine-Goumard, F. Longo, F. Loparco, B. Lott, M. N. Lovellette, P. Lubrano, G. M. Madejski, A. Makeev, M. N. Mazziotta, S. McBreen, J. E. McEnery, S. McGlynn, P. Mészáros, C. Meurer, P. F. Michelson, W. Mitthumsiri, T. Mizuno, A. A. Moiseev, C. Monte, M. E. Monzani, E. Moretti, A. Morselli, I. V. Moskalenko, S. Murgia, T. Nakamori, P. L. Nolan, J. P. Norris, E. Nuss, M. Ohno, T. Ohsugi, N. Omodei, E. Orlando, J. F. Ormes, M. Ozaki, W. S. Paciesas, D. Paneque, J. H. Panetta, D. Parent, V. Pelassa, M. Pepe, M. Pesce-Rollins, V. Petrosian, F. Piron, T. A. Porter, R. Preece, S. Rainò, E. Ramirez-Ruiz, R. Rando, M. Razzano, S. Razzaque, A. Reimer, O. Reimer, T. Reposeur, S. Ritz, L. S. Rochester, A. Y. Rodriguez, M. Roth, F. Ryde, H. F.-W. Sadrozinski, D. Sanchez, A. Sander, P. M. Saz Parkinson, J. D. Scargle, T. L. Schalk, C. Sgrò, E. J. Siskind, D. A. Smith, P. D. Smith, G. Spandre, P. Spinelli, M. Stamatikos, F. W. Stecker, M. S. Strickman, D. J. Suson, H. Tajima, H. Takahashi, T. Takahashi, T. Tanaka, J. B. Thayer, J. G. Thayer, D. J. Thompson, L. Tibaldo, K. Toma, D. F. Torres, G. Tosti, E. Troja, Y. Uchiyama, T. Uehara, T. L. Usher, A. J. van der Horst, V. Vasileiou, N. Vilchez, V. Vitale, A. von Kienlin, A. P. Waite, P. Wang, C. Wilson-Hodge, B. L. Winer, K. S. Wood, X. F. Wu, R. Yamazaki, T. Ylinen & M. Ziegler

A cornerstone of Einstein’s special relativity is Lorentz invariance—the postulate that all observers measure exactly the same speed of light in vacuum, independent of photon-energy. While special relativity assumes that there is no fundamental length-scale associated with such invariance, there is a fundamental scale (the Planck scale, lPlanck ≈ 1.62 × 10-33 cm or EPlanck = MPlanckc2 ≈ 1.22 × 1019 GeV), at which quantum effects are expected to strongly affect the nature of space–time. There is great interest in the (not yet validated) idea that Lorentz invariance might break near the Planck scale. A key test of such violation of Lorentz invariance is a possible variation of photon speed with energy. Even a tiny variation in photon speed, when accumulated over cosmological light-travel times, may be revealed by observing sharp features in γ-ray burst (GRB) light-curves. Here we report the detection of emission up to ∼31 GeV from the distant and short GRB 090510. We find no evidence for the violation of Lorentz invariance, and place a lower limit of 1.2EPlanck on the scale of a linear energy dependence (or an inverse wavelength dependence), subject to reasonable assumptions about the emission (equivalently we have an upper limit of lPlanck/1.2 on the length scale of the effect). Our results disfavour quantum-gravity theories in which the quantum nature of space–time on a very small scale linearly alters the speed of light.

Nature advance online publication 28 October 2009. doi:10.1038/nature08562

Authors: Kehkooi Kee, Vanessa T. Angeles, Martha Flores, Ha Nam Nguyen & Renee A. Reijo Pera

The leading cause of infertility in men and women is quantitative and qualitative defects in human germ-cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ-cell formation and differentiation owing to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages. Here we used a germ-cell reporter to quantify and isolate primordial germ cells derived from both male and female human embryonic stem cells. By silencing and overexpressing genes that encode germ-cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ-cell formation and developmental progression. We observed that human DAZL (deleted in azoospermia-like) functions in primordial germ-cell formation, whereas closely related genes DAZ and BOULE (also called BOLL) promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications.

Nature advance online publication 21 October 2009. doi:10.1038/nature08460

Authors: David A. Barbie, Pablo Tamayo, Jesse S. Boehm, So Young Kim, Susan E. Moody, Ian F. Dunn, Anna C. Schinzel, Peter Sandy, Etienne Meylan, Claudia Scholl, Stefan Fröhling, Edmond M. Chan, Martin L. Sos, Kathrin Michel, Craig Mermel, Serena J. Silver, Barbara A. Weir, Jan H. Reiling, Qing Sheng, Piyush B. Gupta, Raymond C. Wadlow, Hanh Le, Sebastian Hoersch, Ben S. Wittner, Sridhar Ramaswamy, David M. Livingston, David M. Sabatini, Matthew Meyerson, Roman K. Thomas, Eric S. Lander, Jill P. Mesirov, David E. Root, D. Gary Gilliland, Tyler Jacks & William C. Hahn

The proto-oncogene KRAS is mutated in a wide array of human cancers, most of which are aggressive and respond poorly to standard therapies. Although the identification of specific oncogenes has led to the development of clinically effective, molecularly targeted therapies in some cases, KRAS has remained refractory to this approach. A complementary strategy for targeting KRAS is to identify gene products that, when inhibited, result in cell death only in the presence of an oncogenic allele. Here we have used systematic RNA interference to detect synthetic lethal partners of oncogenic KRAS and found that the non-canonical IκB kinase TBK1 was selectively essential in cells that contain mutant KRAS. Suppression of TBK1 induced apoptosis specifically in human cancer cell lines that depend on oncogenic KRAS expression. In these cells, TBK1 activated NF-κB anti-apoptotic signals involving c-Rel and BCL-XL (also known as BCL2L1) that were essential for survival, providing mechanistic insights into this synthetic lethal interaction. These observations indicate that TBK1 and NF-κB signalling are essential in KRAS mutant tumours, and establish a general approach for the rational identification of co-dependent pathways in cancer.

Nature advance online publication 21 October 2009. doi:10.1038/nature08462

Authors: Etienne Meylan, Alison L. Dooley, David M. Feldser, Lynn Shen, Erin Turk, Chensi Ouyang & Tyler Jacks

NF-κB transcription factors function as crucial regulators of inflammatory and immune responses as well as of cell survival. They have also been implicated in cellular transformation and tumorigenesis. However, despite extensive biochemical characterization of NF-κB signalling during the past twenty years, the requirement for NF-κB in tumour development in vivo, particularly in solid tumours, is not completely understood. Here we show that the NF-κB pathway is required for the development of tumours in a mouse model of lung adenocarcinoma. Concomitant loss of p53 (also known as Trp53) and expression of oncogenic Kras(G12D) resulted in NF-κB activation in primary mouse embryonic fibroblasts. Conversely, in lung tumour cell lines expressing Kras(G12D) and lacking p53, p53 restoration led to NF-κB inhibition. Furthermore, the inhibition of NF-κB signalling induced apoptosis in p53-null lung cancer cell lines. Inhibition of the pathway in lung tumours in vivo, from the time of tumour initiation or after tumour progression, resulted in significantly reduced tumour development. Together, these results indicate a critical function for NF-κB signalling in lung tumour development and, further, that this requirement depends on p53 status. These findings also provide support for the development of NF-κB inhibitory drugs as targeted therapies for the treatment of patients with defined mutations in Kras and p53.

Nature advance online publication 21 October 2009. doi:10.1038/nature08496

Authors: Levi T. Morran, Michelle D. Parmenter & Patrick C. Phillips

The tendency of organisms to reproduce by cross-fertilization despite numerous disadvantages relative to self-fertilization is one of the oldest puzzles in evolutionary biology. For many species, the primary obstacle to the evolution of outcrossing is the cost of production of males, individuals that do not directly contribute offspring and thus diminish the long-term reproductive output of a lineage. Self-fertilizing (‘selfing’) organisms do not incur the cost of males and therefore should possess at least a twofold numerical advantage over most outcrossing organisms. Two competing explanations for the widespread prevalence of outcrossing in nature despite this inherent disadvantage are the avoidance of inbreeding depression generated by selfing and the ability of outcrossing populations to adapt more rapidly to environmental change. Here we show that outcrossing is favoured in populations of Caenorhabditis elegans subject to experimental evolution both under conditions of increased mutation rate and during adaptation to a novel environment. In general, fitness increased with increasing rates of outcrossing. Thus, each of the standard explanations for the maintenance of outcrossing are correct, and it is likely that outcrossing is the predominant mode of reproduction in most species because it is favoured under ecological conditions that are ubiquitous in natural environments.

Nature advance online publication 18 October 2009. doi:10.1038/nature08524

Authors: Matt Eichenfield, Jasper Chan, Ryan M. Camacho, Kerry J. Vahala & Oskar Painter

Periodicity in materials yields interesting and useful phenomena. Applied to the propagation of light, periodicity gives rise to photonic crystals, which can be precisely engineered for such applications as guiding and dispersing optical beams, tightly confining and trapping light resonantly, and enhancing nonlinear optical interactions. Photonic crystals can also be formed into planar lightwave circuits for the integration of optical and electrical microsystems. In a photonic crystal, the periodicity of the host medium is used to manipulate the properties of light, whereas a phononic crystal uses periodicity to manipulate mechanical vibrations. As has been demonstrated in studies of Raman-like scattering in epitaxially grown vertical cavity structures and photonic crystal fibres, the simultaneous confinement of mechanical and optical modes in periodic structures can lead to greatly enhanced light–matter interactions. A logical next step is thus to create planar circuits that act as both photonic and phononic crystals: optomechanical crystals. Here we describe the design, fabrication and characterization of a planar, silicon-chip-based optomechanical crystal capable of co-localizing and strongly coupling 200-terahertz photons and 2-gigahertz phonons. These planar optomechanical crystals bring the powerful techniques of optics and photonic crystals to bear on phononic crystals, providing exquisitely sensitive (near quantum-limited), optical measurements of mechanical vibrations, while simultaneously providing strong nonlinear interactions for optics in a large and technologically relevant range of frequencies.

Nature advance online publication 14 October 2009. doi:10.1038/nature08478

Authors: Ingo Bartholomäus, Naoto Kawakami, Francesca Odoardi, Christian Schläger, Djordje Miljkovic, Joachim W. Ellwart, Wolfgang E. F. Klinkert, Cassandra Flügel-Koch, Thomas B. Issekutz, Hartmut Wekerle & Alexander Flügel

The tissues of the central nervous system are effectively shielded from the blood circulation by specialized vessels that are impermeable not only to cells, but also to most macromolecules circulating in the blood. Despite this seemingly absolute seclusion, central nervous system tissues are subject to immune surveillance and are vulnerable to autoimmune attacks. Using intravital two-photon imaging in a Lewis rat model of experimental autoimmune encephalomyelitis, here we present in real-time the interactive processes between effector T cells and cerebral structures from their first arrival to manifest autoimmune disease. We observed that incoming effector T cells successively scanned three planes. The T cells got arrested to leptomeningeal vessels and immediately monitored the luminal surface, crawling preferentially against the blood flow. After diapedesis, the cells continued their scan on the abluminal vascular surface and the underlying leptomeningeal (pial) membrane. There, the T cells encountered phagocytes that effectively present antigens, foreign as well as myelin proteins. These contacts stimulated the effector T cells to produce pro-inflammatory mediators, and provided a trigger to tissue invasion and the formation of inflammatory infiltrations.

Nature advance online publication 14 October 2009. doi:10.1038/nature08522

Authors: Xu Du, Ivan Skachko, Fabian Duerr, Adina Luican & Eva Y. Andrei

In graphene, which is an atomic layer of crystalline carbon, two of the distinguishing properties of the material are the charge carriers’ two-dimensional and relativistic character. The first experimental evidence of the two-dimensional nature of graphene came from the observation of a sequence of plateaus in measurements of its transport properties in the presence of an applied magnetic field. These are signatures of the so-called integer quantum Hall effect. However, as a consequence of the relativistic character of the charge carriers, the integer quantum Hall effect observed in graphene is qualitatively different from its semiconductor analogue. As a third distinguishing feature of graphene, it has been conjectured that interactions and correlations should be important in this material, but surprisingly, evidence of collective behaviour in graphene is lacking. In particular, the quintessential collective quantum behaviour in two dimensions, the fractional quantum Hall effect (FQHE), has so far resisted observation in graphene despite intense efforts and theoretical predictions of its existence. Here we report the observation of the FQHE in graphene. Our observations are made possible by using suspended graphene devices probed by two-terminal charge transport measurements. This allows us to isolate the sample from substrate-induced perturbations that usually obscure the effects of interactions in this system and to avoid effects of finite geometry. At low carrier density, we find a field-induced transition to an insulator that competes with the FQHE, allowing its observation only in the highest quality samples. We believe that these results will open the door to the physics of FQHE and other collective behaviour in graphene.