September 4, 2007 ͉ vol. 104 ͉ no. 36 ͉ 14175–14544 In This Issue Proceedings of the National Academy ofPNAS Sciences of the United States of America www.pnas.org 14266 Global heat flow fluctuates more than previously thought 14283 Modular riboswitches 14383 A royal beckoning 14424 Biomarker identified for Huntington’s disease 14501 Mutant mouse models

molecule ligand, is coupled to a ribozyme. Upon ligand binding, GEOPHYSICS aptamer conformational change is transmitted to the ribozyme, which turns mRNA translation on or off. The authors devel- Global heat flow fluctuates more than oped the concept of modular riboswitch design for bioengi- previously thought neering. They report prototypes in which custom riboswitches Like an oven, office building, or the human body, the Earth function either as sensors or growth triggers. Their model is the loses heat produced in its interior via diffusion through its sur- ‘‘hammerhead ribozyme,’’ a face. Approximately 70% of the Earth’s heat loss flows through T-shaped molecule joined to the oceanic lithosphere (the crust and uppermost mantle), an mRNA by its stem. At the principally through young, hot crust that erupts to the surface end of the T arms are two Present Day during the formation of loops whose integrity is essen- Ribozyme is turned off when the 65 Ma mountainous oceanic ridges. tial for ribozyme function: aptamer binds ligand. Taking advantage of recent self-cleavage, which renders reconstructions of seafloor the mRNA nonfunctional. The authors integrate an aptamer age, Sean Loyd et al. modeled into one of the T-arm loops; on shifting conformation, the [mW/m2] the trends in the Earth’s oce- aptamer disrupts the ribozyme structure and turns it off. (Al- 100 200 300 anic heat flow over the last 65 ternatively, ligand binding can restore ribozyme structure to Inferred heat surface flow in the million years. They found that, turn it on.) The riboswitches function in vivo, inserted within Pacific basin at present and 65 even though the amount of plasmids into Saccharomyces cerevisiae, with aptamers sensitive million years ago. seafloor has increased by 8% to either theophylline or tetracycline. The aptamer role could, during this time, heat flow has in theory, be played by any of a wide range of RNA sequences been decreasing by 0.15% every million years, an order of mag- that bind small molecules. — K.M. nitude faster than typical estimates of cooling trends. This rapid ‘‘A modular and extensible RNA-based -regulatory platform for decrease may be indicative of fluctuations in the way plate tec- engineering cellular function’’ by Maung Nyan Win and Christina D. tonics works over time. The cause for this shrinking heat flow, Smolke (see pages 14283–14288) Loyd et al. say, is a decrease in the surface area of young, ridge-proximal crust due to the merging of oceanic plates in the Pacific basin. The authors also note that these findings provide ECOLOGY evidence of how continents and oceanic plates self-organize to transport heat. — N.Z. A royal beckoning ‘‘Time variability in Cenozoic reconstructions of mantle heat flow: The male honey bee’s sole purpose is to mate with the queen Plate tectonic cycles and implications for Earth’s thermal evolution’’ honey bee, once, after which he dies. Even over long distances, by S. J. Loyd, T. W. Becker, C. P. Conrad, C. Lithgow-Bertelloni, the drone can sense the pheromone 9-oxo-2-decenoic acid (9- and F. A. Corsetti (see pages 14266–14271) ODA), one of several substances the queen emits that control the colony’s hierarchy, including female worker attentiveness APPLIED BIOLOGICAL SCIENCES, ENGINEERING and infertility. Using a functional genomics approach, Kevin Wanner et al. attempted to decipher whether 9-ODA is a purely Modular riboswitches sexual signal or also plays a role in social signaling, by searching for its receptor. The intricate nature of honey bee social behav- Natural riboswitches control in bacteria and ior is controlled by pheromones released by the queen, but eukaryotes. In a synthetic riboswitch engineered by Maung teasing out specific effects of each pheromone has been diffi- Win and Christina Smolke, an aptamer, which binds a small- cult. Functional genomics takes advantage of genome sequence

www.pnas.org͞cgi͞doi͞10.1073͞iti3607104 PNAS ͉ September 4, 2007 ͉ vol. 104 ͉ no. 36 ͉ 14175–14176 Downloaded by guest on September 29, 2021 data to identify molecular in- ‘‘Analysis of potential transcriptomic biomarkers for Huntington’s teractions. Wanner et al. disease in peripheral blood’’ by Heike Runne, Alexandre Kuhn, found candidate pheromone Edward J. Wild, Wirahpati Pratyaksha, Mark Kristiansen, Jeremy D. receptors by looking for Isaacs, Etienne Re´gulier, Mauro Delorenzi, Sarah J. Tabrizi, and more highly expressed in Ruth Luthi-Carter (see pages 14424–14429) drone antennae. The authors found that AmOr11 responds specifically to 9-ODA, showing NEUROSCIENCE that it is the likely receptor. The high degree of specificity Mutant mouse models schizophrenia suggests that AmOr11 is a Frontal view of queen honey pheromone receptor that Mice may be suitable model organisms for the study of physical bee head. mediates more than one disorders such as cardiovascular disease, but modeling of psy- behavioral effect, including chiatric diseases in rodents has proven much more difficult. influencing sexual and social behaviors. — T.H.D. Advances in the genetics of diseases such as schizophrenia ‘‘A honey bee odorant receptor for the queen substance 9-oxo-2- decenoic acid’’ by Kevin W. Wanner, Andrew S. Nichols, Kimberly have provided some promising K. O. Walden, Axel Brockmann, Charles W. Luetje, and Hugh M. candidate genes for such dis- Robertson (see pages 14383–14388) orders, for example, the Disrupted-In-Schizophrenia MEDICAL SCIENCES gene DISC1. Takatoshi Hikida et al. describe their develop- Biomarker identified for Huntington’s ment and characterization of disease mice having a deficient ver- 3D construction of changes in sion of this gene. DISC1 mu- DISC1 transgenic mice. Huntington’s disease (HD), a hereditary neurodegenerative disor- tant mice had enlarged lateral der, causes a progressive decline in mental and motor abilities, ventricles, a feature frequently seen in patients with schizophre- leading to abnormal involuntary movements, cognitive difficulties, nia. The mice also displayed several behavioral abnormalities, and eventually death. Although it was one of the first inherited including hyperactivity, disturbance in information processing, disorders to have an accurate genetic test, there are few reliable and depression-like symptoms, as well as a decrease in the pro- biomarkers for HD, which makes it difficult to predict disease on- tein marker associated with the abnormal electrical patterns set or accurately measure progression. Current therapies for HD observed in schizophrenia patients. Given the phenotypes of the have been ineffective, and although many candidate treatments are DISC1 mutant mice and the converging genetic evidence link- in development, clinical trials of these agents require validated bi- ing DISC1 to a variety of psychiatric disorders, Hikida et al. omarkers. Toward this goal, Heike Runne et al. analyzed the suggest that these mice provide an important tool for further up-regulation of neuroinflammatory genes in the blood of Hun- study of the combinations of factors that underlie major mental tington’s patients. Neuroinflammation has been shown to be inte- illnesses such as schizophrenia and mood disorders. — M.M. gral to the pathogenic process in the brain, and the tested genes ‘‘Dominant-negative DISC1 transgenic mice display schizophrenia- included those involved in immune response and cell cycle and cell associated phenotypes detected by measures translatable to humans’’ death pathways. One gene, immediate early response 3 (IER3), by Takatoshi Hikida, Hanna Jaaro-Peled, Saurav Seshadri, Kenichi showed a significant increase in expression in patients’ peripheral Oishi, Caroline Hookway, Stephanie Kong, Di Wu, Rong Xue, blood cells. The authors suggest that longitudinal studies may aid Manuella Andrade´, Stephanie Tankou, Susumu Mori, Michela Gal- in the detection of additional HD biomarkers from readily avail- lagher, Koko Ishizuka, Mikhail Pletnikov, Satoshi Kida, and Akira able patient tissues and fluids, such as blood. — F.A. Sawa (see pages 14501–14506)

14176 ͉ www.pnas.org͞cgi͞doi͞10.1073͞iti3607104 Downloaded by guest on September 29, 2021