This month in Science Roundup:
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When you give someone the gift of a AAAS membership, they get a subscription to Science, and so much more. Your gift goes to support real world programs that are making an impact in areas including: science policy, diplomacy, public engagement and dialogue, workforce development and diversity, and education. REPORT: Multi-Input RNAi-Based Logic Circuit for Identification of Specific Cancer Cells Abstract: Engineered biological systems that integrate multi-input sensing, sophisticated information processing, and precisely regulated actuation in living cells could be useful in a variety of applications. For example, anticancer therapies could be engineered to detect and respond to complex cellular conditions in individual cells with high specificity. Here, we show a scalable transcriptional/posttranscriptional synthetic regulatory circuit—a cell—type "classifier"—that senses expression levels of a customizable set of endogenous microRNAs and triggers a cellular response only if the expression levels match a predetermined profile of interest. We demonstrate that a HeLa cancer cell classifier selectively identifies HeLa cells and triggers apoptosis without affecting non-HeLa cell types. This approach also provides a general platform for programmed responses to other complex cell states. Supporting online material EDITORIAL: A Grand Challenge in Biology Summary: Richard Feynman, a brilliant Nobel Prize–winning physicist, is often quoted for his statement that "What I cannot create, I do not understand." The remarkable advances in our knowledge of the chemistry of life achieved in the past few decades, published in Science and many other journals, could lead nonexperts to assume that biologists are coming close to a real understanding of cells. On the contrary, as scientists learn more and more, we have increasingly come to recognize how huge the challenge is that confronts us. In this special issue, we review the progress made in the decade-old field called synthetic biology, which, as Feynman would advocate, creates biological networks in order to help us understand, and in some cases redesign, living systems. Along with its promise for the biotechnology industry, synthetic biology has the potential to become a powerful new tool for the long-term fundamental research needed to more effectively create breakthroughs in improving human health and welfare and the environment. PERSPECTIVE: Demystifying DNA Demethylation Summary: Variability and adaptability are necessary for overcoming the challenges of multicellular life. To address this need, nature has evolved a substantial enzymatic toolbox for altering cytosine within the genome. Methylation of the nucleotide cytosine (C) at the 5-position of the base has profound impacts on gene expression and cellular identity. The reverse of this process, DNA demethylation, is equally important for cleaning the genomic slate during embryogenesis or achieving rapid reactivation of previously silenced genes. Although the mechanism of DNA methylation has been rigorously established, active DNA demethylation in mammals has remained enigmatic, as disparate observations have failed to coalesce into a consistent model. Cytosine deamination, oxidation, and base excision repair enzymes have been proposed in a dizzying variety of combinations (1). Against this backdrop, two reports in this issue, by Ito et al. (2) on page 1300 of the 2 September 2011 issue of Science and He et al. on page 1303 of the 2 September 2011 issue of Science (3), help bring new clarity to the mechanistic model for DNA demethylation. REPORT: The Endocast of MH1, Australopithecus sediba Abstract: The virtual endocast of MH1 (Australopithecus sediba), obtained from high-quality synchrotron scanning, reveals generally australopith-like convolutional patterns on the frontal lobes but also some foreshadowing of features of the human frontal lobes, such as posterior repositioning of the olfactory bulbs. Principal component analysis of orbitofrontal dimensions on australopith endocasts (MH1, Sts 5, and Sts 60) indicates that among these, MH1 orbitofrontal shape and organization align most closely with human endocasts. These results are consistent with gradual neural reorganization of the orbitofrontal region in the transition from Australopithecus to Homo, but given the small volume of the MH1 endocast, they are not consistent with gradual brain enlargement before the transition. Supporting online material REPORT: Australopithecus sediba at 1.977 Ma and Implications for the Origins of the Genus Homo Abstract: Newly exposed cave sediments at the Malapa site include a flowstone layer capping the sedimentary unit containing the Australopithecus sediba fossils. Uranium-lead dating of the flowstone, combined with paleomagnetic and stratigraphic analysis of the flowstone and underlying sediments, provides a tightly constrained date of 1.977 ± 0.002 million years ago (Ma) for these fossils. This refined dating suggests that Au. sediba from Malapa predates the earliest uncontested evidence for Homo in Africa. Supporting online material NEWS FOCUS: Which Way to the Island? Summary: Theories of nuclear structure predict that certain key numbers of protons and neutrons in a nucleus, known as magic numbers, make it more stable and hence longer-lived than would normally be the case. Superheavy-element researchers call this area of the chart of nuclides, around the confluence of proton and neutron magic numbers, the island of stability. The half-lives of some of the heaviest elements made so far do show signs of increased stability, suggesting that those nuclei are on the shores of the island. Moving farther inland is an enticing prospect because the atoms we may find there could be exotic creatures indeed. But for the time being, the summit of the island's peak is out of reach because physicists haven't devised a way of making nuclei with enough neutrons. Podcast Interview RESEARCH ARTICLE: Kepler-16: A Transiting Circumbinary Planet Abstract: We report the detection of a planet whose orbit surrounds a pair of low-mass stars. Data from the Kepler spacecraft reveal transits of the planet across both stars, in addition to the mutual eclipses of the stars, giving precise constraints on the absolute dimensions of all three bodies. The planet is comparable to Saturn in mass and size and is on a nearly circular 229-day orbit around its two parent stars. The eclipsing stars are 20 and 69% as massive as the Sun and have an eccentric 41-day orbit. The motions of all three bodies are confined to within 0.5° of a single plane, suggesting that the planet formed within a circumbinary disk. Supporting online material REPORT: A Diverse Assemblage of Late Cretaceous Dinosaur and Bird Feathers from Canadian Amber Abstract: The fossil record of early feathers has relied on carbonized compressions that lack fine structural detail. Specimens in amber are preserved in greater detail, but they are rare. Late Cretaceous coal-rich strata from western Canada provide the richest and most diverse Mesozoic feather assemblage yet reported from amber. The fossils include primitive structures closely matching the protofeathers of nonavian dinosaurs, offering new insights into their structure and function. Additional derived morphologies confirm that plumage specialized for flight and underwater diving had evolved in Late Cretaceous birds. Because amber preserves feather structure and pigmentation in unmatched detail, these fossils provide novel insights regarding feather evolution. Supporting online material PERSPECTIVE: Converging on an HIV Vaccine Summary: Three decades after the discovery of AIDS we still do not have a vaccine against the causative agent, the human immunodeficiency virus (HIV). Multidrug therapy can extend life and health for those with HIV, but only holds the virus at bay, making treatment a lifetime proposition. Access to treatment or other promising infection prevention measures such as topical microbicides (1) are an economic and social challenge (2). A vaccine would be a simple and direct strategy for prevention. On pages 1593 and 1633 of the 16 September 2011 issue of Science, Wu et al. (3) and Scheid et al. (4) detail the trajectory of an immune response to natural HIV infection that may provide a path to a vaccine. NEWS & ANALYSIS: Aboriginal Genome Shows Two-Wave Settlement of Asia Summary: Almost a century ago, British anthropologist Alfred Cort Haddon traveled the world seeking samples of human hair, among other curios, for his ethnographic studies of native people. The samples, which lay in a museum drawer for 90 years, included hair from a young Australian Aboriginal man. Now in a paper published online from the 23 September 2011 issue of Science, geneticists report that they have extracted enough DNA from that hair to sequence the first complete genome of an Aboriginal. The genome offers the first good look at the origins of Aboriginals, showing that they are one of the oldest continuous populations outside of Africa, the authors say. REPORT: Inbreeding Promotes Female Promiscuity Abstract: The widespread phenomenon of polyandry (mating by females with multiple males) is an evolutionary puzzle, because females can sustain costs from promiscuity, whereas full fertility can be provided by a single male. Using the red flour beetle, Tribolium castaneum, we identify major fitness benefits of polyandry to females under inbreeding, when the risks of fertilization by incompatible male haplotypes are especially high. Fifteen generations after inbred populations had passed through genetic bottlenecks, we recorded increased levels of female promiscuity compared with noninbred controls, most likely due to selection from prospective fitness gains through polyandry. These data illustrate how this common mating pattern can evolve if population genetic bottlenecks increase the risks of fitness depression due to fertilization by sperm carrying genetically incompatible haplotypes. Supporting online material EDUCATION FORUM: The Pseudoscience of Single-Sex Schooling Summary: In attempting to improve schools, it is critical to remember that not all reforms lead to meaningful gains for students. We argue that one change in particular—sex-segregated education—is deeply misguided, and often justified by weak, cherry-picked, or misconstrued scientific claims rather than by valid scientific evidence. There is no well-designed research showing that single-sex (SS) education improves students' academic performance, but there is evidence that sex segregation increases gender stereotyping and legitimizes institutional sexism. Podcast Interview In Science Signaling RESEARCH ARTICLE: Small Molecule–Mediated Activation of the Integrin CD11b/CD18 Reduces Inflammatory Disease
PERSPECTIVE: Met Receptor: A Moving Target
RESEARCH ARTICLE: A Synthetic Biology Approach Reveals a CXCR4-G13-Rho Signaling Axis Driving Transendothelial Migration of Metastatic Breast Cancer Cells
In Science Translational Medicine PERSPECTIVE: Hidden Immunotherapy Targets Challenge Dogma
RESEARCH ARTICLE: Gαs-Biased β2-Adrenergic Receptor Signaling from Restoring Synchronous Contraction in the Failing Heart
RESEARCH ARTICLE: A Plasmablast Biomarker for Nonresponse to Antibody Therapy to CD20 in Rheumatoid Arthritis
IMAGE CREDITS (In order of appearance): HENNING DALHOFF/BONNIER PUBLICATIONS/PHOTO RESEARCHERS, INC, GSI HELMHOLTZZENTRUM FÜR SCHWERIONENFORSCHUNG, A. ZSCHAU, CATHERINE YEULET/ISTOCKPHOTO.COM Sponsored by:
AAAS + U = Δ
When you give someone the gift of a AAAS membership, they get a subscription to Science, and so much more. Your gift goes to support real-world programs that are making an impact in areas including science policy, diplomacy, public engagement and dialogue, workforce development and diversity, and education. |