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Proceedings of the National Academy of Sciences

In This Issue [This Week in PNAS]
Extraterrestrial quasicrystalpnas;109/5/1355/UNFIG01F1unfig01Rock sample from the mineral collection of the Museo di Storia Naturale in Florence, previously unearthed in the Koryak Mountains in Russia.Unlike crystalline solids, quasicrystals contain a near-periodic arrangement of atoms and symmetrie...

Femtosecond laser vaporization that preserves protein-folded structure: An un...
Electrospray ionization (ESI) made the transfer of nonvolatile molecules, such as proteins, from solution into the gas phase without covalent bond dissociation possible, revolutionizing MS for biological applications. However, whether the gaseous ions from ESI can preserve their biologically active ...

Travels in time: Assessing the functional complexity of T cells [Commentary]
When the host encounters a pathogen, the ensuing immune response involves a complex set of cellular responses distributed across many different types of cells. In T and B lymphocytes of the adaptive immune system, these responses include irreversible differentiation events that generate functionally...

Evolution of patterns on Conus shells [Evolution]
The pigmentation patterns of shells in the genus Conus can be generated by a neural-network model of the mantle. We fit model parameters to the shell pigmentation patterns of 19 living Conus species for which a well resolved phylogeny is available. We infer the evolutionary history of these paramete...

GluN2B subunit deletion reveals key role in acute and chronic ethanol sensiti...
The bed nucleus of the stria terminalis (BNST) is a critical region for alcohol/drug-induced negative affect and stress-induced reinstatement. NMDA receptor (NMDAR)-dependent plasticity, such as long-term potentiation (LTP), has been postulated to play key roles in alcohol and drug addiction; yet, t...

Evidence for the extraterrestrial origin of a natural quasicrystal [Applied P...
We present evidence that a rock sample found in the Koryak Mountains in Russia and containing icosahedrite, an icosahedral quasicrystalline phase with composition Al63Cu24Fe13, is part of a meteorite, likely formed in the early solar system about 4.5 Gya. The quasicrystal grains are intergrown with ...

Soluble factors produced by activated CD4+ T cells modulate EBV latency [Cell...
Following infection with Epstein?Barr virus (EBV), the virus is carried for life in the memory B-cell compartment in a silent state (latency I/0). These cells do not resemble the proliferating lymphoblastoid cells (LCLs) (latency III) that are generated after infection. It is of fundamental signific...

Mitochondrial hexokinase II (HKII) and phosphoprotein enriched in astrocytes ...
The metabolic state of a cell is a key determinant in the decision to live and proliferate or to die. Consequently, balanced energy metabolism and the regulation of apoptosis are critical for the development and maintenance of differentiated organisms. Hypoxia occurs physiologically during developme...

Plasma membrane recruitment and activation of the AGC kinase Ypk1 is mediated...
The yeast AGC kinase orthologs Ypk1 and Ypk2 control several important cellular processes, including actin polarization, endocytosis, and sphingolipid metabolism. Activation of Ypk1/2 requires phosphorylation by kinases localized at the plasma membrane (PM), including the 3-phosphoinositide-dependen...

Nematode sperm maturation triggered by protease involves sperm-secreted serin...
Spermiogenesis is a series of poorly understood morphological, physiological and biochemical processes that occur during the transition of immotile spermatids into motile, fertilization-competent spermatozoa. Here, we identified a Serpin (serine protease inhibitor) family protein (As_SRP-1) that is ...

Carnivorous dinocephalian from the Middle Permian of Brazil and tetrapod disp...
The medial Permian (?270?260 Ma: Guadalupian) was a time of important tetrapod faunal changes, in particular reflecting a turnover from pelycosaurian- to therapsid-grade synapsids. Until now, most knowledge on tetrapod distribution during the medial Permian has come from fossils found in the South A...

Commodity durability, trader specialization, and market performance [Economic...
The original double auction studies of supply and demand markets established their strong efficiency and equilibrium convergence behavior using economically unsophisticated and untrained subjects. The results were unexpected because all individual costs and values were private and dependent entirely...

Polyfunctional responses by human T cells result from sequential release of c...
The release of cytokines by T cells defines a significant part of their functional activity in vivo, and their ability to produce multiple cytokines has been associated with beneficial immune responses. To date, time-integrated end-point measurements have obscured whether these polyfunctional states...

Experimental evolution of multicellularity [Evolution]
Multicellularity was one of the most significant innovations in the history of life, but its initial evolution remains poorly understood. Using experimental evolution, we show that key steps in this transition could have occurred quickly. We subjected the unicellular yeast Saccharomyces cerevisiae t...

Complementary costimulation of human T-cell subpopulations by cluster of diff...
Cluster of differentiation 81 (CD81) is a widely expressed tetraspanin molecule that physically associates with CD4 and CD8 on the surface of human T cells. Coengagement of CD81 and CD3 results in the activation and proliferation of T cells. CD81 also costimulated mouse T cells that lack CD28, sugge...

Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced...
Ischemia of the myocardium and lower limbs is a common consequence of arterial disease and a major source of morbidity and mortality in modernized countries. Inducing neovascularization for the treatment of ischemia is an appealing therapeutic strategy for patients for whom traditional treatment mod...

Dissociable neural representations of reinforcement and belief prediction err...
Decision-making in the presence of other competitive intelligent agents is fundamental for social and economic behavior. Such decisions require agents to behave strategically, where in addition to learning about the rewards and punishments available in the environment, they also need to anticipate a...

3{beta}-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach ...
Emerging evidence suggests that the pathogenesis of depressive disorders (DDs) is associated with neuronal abnormalities in brain microtubule function, including changes in ?-tubulin isoforms. Currently available antidepressant drugs may act by rescuing these alterations, but only after long-term tr...

Striatum processes reward differently in adolescents versus adults [Neuroscie...
Adolescents often respond differently than adults to the same salient motivating contexts, such as peer interactions and pleasurable stimuli. Delineating the neural processing differences of adolescents is critical to understanding this phenomenon, as well as the bases of serious behavioral and psyc...

Telomere length in early life predicts lifespan [Physiology]
The attrition of telomeres, the ends of eukaryote chromosomes, is thought to play an important role in cell deterioration with advancing age. The observed variation in telomere length among individuals of the same age is therefore thought to be related to variation in potential longevity. Studies of...

Retinotopic memory is more precise than spatiotopic memory [Psychological and...
Successful visually guided behavior requires information about spatiotopic (i.e., world-centered) locations, but how accurately is this information actually derived from initial retinotopic (i.e., eye-centered) visual input? We conducted a spatial working memory task in which subjects remembered a c...

Noninvasive inference of the molecular chemotactic response using bacterial t...
The quality of sensing and response to external stimuli constitutes a basic element in the selective performance of living organisms. Here we consider the response of Escherichia coli to chemical stimuli. For moderate amplitudes, the bacterial response to generic profiles of sensed chemicals is reco...

Gut bacteria and brain function: The challenges of a growing field [Letters (...
In a recent article, Bravo et al. (1) demonstrated antidepressant and anxiolytic-like properties of a probiotic Lactobacillus rhamnosus in mice. Evidence for an involvement of the vagus nerve and the central gamma-aminobutyric acid (GABA) system in the modulation of emotional behavior by these bacte...

Illuminating neuromyelitis optica pathogenesis [Commentary]
What is the most important moment in the history of a disease? Let us consider neuromyelitis optica (NMO), which was coined by French neurologist Eugene Devic in 1894 for a disease believed until recently to be a subtype of multiple sclerosis (MS). The discovery (in 2004) of a disease-specific bioma...

Phylogeny and beyond: Scientific, historical, and conceptual significance of ...
In 1977, Carl Woese and George Fox published a brief paper in PNAS that established, for the first time, that the overall phylogenetic structure of the living world is tripartite. We describe the way in which this monumental discovery was made, its context within the historical development of evolut...

Liquid crystal self-assembly of random-sequence DNA oligomers [Applied Physic...
In biological systems and nanoscale assemblies, the self-association of DNA is typically studied and applied in the context of the evolved or directed design of base sequences that give complementary pairing, duplex formation, and specific structural motifs. Here we consider the collective behavior ...

Detecting anthrax in the mail by coherent Raman microspectroscopy [Applied Ph...
In this report, we show the collection of spatial information through a turbid medium by coherent Raman microspectroscopic imaging. In particular, the technique is capable of identifying anthrax endospores inside a sealed paper envelope.

Uric acid stones in the urinary bladder of aryl hydrocarbon receptor (AhR) kn...
The aryl hydrocarbon receptor (AhR) knockout mice raised in the laboratory of Fujii-Kuriyama have been under investigation for several years because of the presence in their urinary bladder of large, yellowish stones. The stones are composed of uric acid and become apparent in the bladders as tiny s...

A morphologically specialized soldier caste improves colony defense in a neot...
Division of labor among workers is common in insect societies and is thought to be important in their ecological success. In most species, division of labor is based on age (temporal castes), but workers in some ants and termites show morphological specialization for particular tasks (physical caste...

Divergence of duplicate genes in exon-intron structure [Evolution]
Gene duplication plays key roles in organismal evolution. Duplicate genes, if they survive, tend to diverge in regulatory and coding regions. Divergences in coding regions, especially those that can change the function of the gene, can be caused by amino acid-altering substitutions and/or alteration...

Deciphering the genetic architecture of variation in the immune response to M...
Tuberculosis (TB) is a major public health problem. One-third of the world's population is estimated to be infected with Mycobacterium tuberculosis (MTB), the etiological agent causing TB, and active disease kills nearly 2 million individuals worldwide every year. Several lines of evidence indicate ...

Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 i...
The astrocytic aquaporin-4 (AQP4) water channel is the target of pathogenic antibodies in a spectrum of relapsing autoimmune inflammatory central nervous system disorders of varying severity that is unified by detection of the serum biomarker neuromyelitis optica (NMO)-IgG. Neuromyelitis optica is t...

Critical role for phosphoinositide 3-kinase gamma in parasite invasion and di...
Obligate intracellular pathogens such as Leishmania specifically target host phagocytes for survival and replication. Phosphoinositide 3-kinase ? (PI3K?), a member of the class I PI3Ks that is highly expressed by leukocytes, controls cell migration by initiating actin polymerization and cytoskeletal...

Hypoxic regulation of the cerebral microcirculation is mediated by a carbon m...
Enhancement of cerebral blood flow by hypoxia is critical for brain function, but signaling systems underlying its regulation have been unclear. We report a pathway mediating hypoxia-induced cerebral vasodilation in studies monitoring vascular disposition in cerebellar slices and in intact mouse bra...

Homeostatic plasticity mechanisms are required for juvenile, but not adult, o...
Ocular dominance (OD) plasticity in the visual cortex is a classic model system for understanding developmental plasticity, but the visual cortex also shows plasticity in adulthood. Whether the plasticity mechanisms are similar or different at the two ages is not clear. Several plasticity mechanisms...

Betacellulin promotes cell proliferation in the neural stem cell niche and st...
Neural stem cells (NSCs) reside in specialized niches in the adult mammalian brain, including the subventricular zone and the dentate gyrus, which act to control NSC behavior. Among other cell types within these niches, NSCs are found in close proximity to blood vessels. We carried out an analysis o...

The mystery of missing heritability: Genetic interactions create phantom heri...
Human genetics has been haunted by the mystery of ?missing heritability? of common traits. Although studies have discovered >1,200 variants associated with common diseases and traits, these variants typically appear to explain only a minority of the heritability. The proportion of heritability expla...

Correction for Zhang et al., Duplication and partitioning in evolution and fu...
EVOLUTION Correction for ?Duplication and partitioning in evolution and function of homoeologous Q loci governing domestication characters in polyploid wheat,? by Zengcui Zhang, Harry Belcram, Piotr Gornicki, Mathieu Charles, Jérémy Just, Cécile Huneau, Ghislaine Magdelenat, Arnaud Couloux, Sylvie S...

Rosalyn Sussman Yalow (1921-2011) [Retrospectives]
Rosalyn S. Yalow, a member of the National Academy of Sciences and the second woman to win a Nobel Prize in Physiology or Medicine, died on May 30, 2011, at the age of 89, having suffered recurrent strokes and a prolonged period of decline. She was awarded the Nobel Prize in 1977 for creation of the...

Lethal arrhythmias in Tbx3-deficient mice reveal extreme dosage sensitivity o...
TBX3 is critical for human development: mutations in TBX3 cause congenital anomalies in patients with ulnar-mammary syndrome. Data from mice and humans suggest multiple roles for Tbx3 in development and function of the cardiac conduction system. The mechanisms underlying the functional development, ...

Evolutionary conservation of the habenular nuclei and their circuitry control...
The medial (MHb) and lateral (LHb) habenulae are a small group of nuclei that regulate the activity of monoaminergic neurons. Disruptions to these nuclei lead to deficits in a range of cognitive and motor functions from sleep to decision making. Interestingly, the habenular nuclei are present in all...

Optimal 3D single-molecule localization for superresolution microscopy with a...
Photo-activation localization microscopy is a far-field superresolution imaging technique based on the localization of single molecules with subdiffraction limit precision. Known under acronyms such as PALM (photo-activated localization microscopy) or STORM (stochastic optical reconstruction microsc...

Nanoscale buckling deformation in layered copolymer materials [Applied Physic...
In layered materials, a common mode of deformation involves buckling of the layers under tensile deformation in the direction perpendicular to the layers. The instability mechanism, which operates in elastic materials from geological to nanometer scales, involves the elastic contrast between differe...

Global risk of big earthquakes has not recently increased [Earth, Atmospheric...
The recent elevated rate of large earthquakes has fueled concern that the underlying global rate of earthquake activity has increased, which would have important implications for assessments of seismic hazard and our understanding of how faults interact. We examine the timing of large (magnitude M?7...

The spread of a transposon insertion in Rec8 is associated with obligate asex...
Although transitions from sexual to asexual reproduction are thought to have important evolutionary consequences, little is known about the mechanistic underpinnings of these changes. The cyclical parthenogen Daphnia pulex is a powerful model in which to address these issues because female-limited m...

Historical contingency affects signaling strategies and competitive abilities...
One of the key innovations during the evolution of life on earth has been the emergence of efficient communication systems, yet little is known about the causes and consequences of the great diversity within and between species. By conducting experimental evolution in 20 independently evolving popul...

Tiling genomes of pathogenic viruses identifies potent antiviral shRNAs and r...
shRNAs can trigger effective silencing of gene expression in mammalian cells, thereby providing powerful tools for genetic studies, as well as potential therapeutic strategies. Specific shRNAs can interfere with the replication of pathogenic viruses and are currently being tested as antiviral therap...

Cenozoic climate change influences mammalian evolutionary dynamics [Geology]
Global climate change is having profound impacts on the natural world. However, climate influence on faunal dynamics at macroevolutionary scales remains poorly understood. In this paper we investigate the influence of climate over deep time on the diversity patterns of Cenozoic North American mammal...

End-Cretaceous marine mass extinction not caused by productivity collapse [Ge...
An asteroid impact at the end of the Cretaceous caused mass extinction, but extinction mechanisms are not well-understood. The collapse of sea surface to sea floor carbon isotope gradients has been interpreted as reflecting a global collapse of primary productivity (Strangelove Ocean) or export prod...

Micro-chemical synthesis of molecular probes on an electronic microfluidic de...
We have developed an all-electronic digital microfluidic device for microscale chemical synthesis in organic solvents, operated by electrowetting-on-dielectric (EWOD). As an example of the principles, we demonstrate the multistep synthesis of [18F]FDG, the most common radiotracer for positron emissi...

Novelty exposure overcomes foot shock-induced spatial-memory impairment by pr...
Novelty processing can transform short-term into long-term memory. We propose that this memory-reinforcing effect of novelty could be explained by mechanisms outlined in the ?synaptic tagging hypothesis.? Initial short-term memory is sustained by a transient plasticity change at activated synapses a...

Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcemen...
People attend not only to their own experiences, but also to the experiences of those around them. Such social awareness profoundly influences human behavior by enabling observational learning, as well as by motivating cooperation, charity, empathy, and spite. Oxytocin (OT), a neurosecretory hormone...

Behavioral study of whisker-mediated vibration sensation in rats [Neuroscience]
Rats use their vibrissal sensory system to collect information about the nearby environment. They can accurately and rapidly identify object location, shape, and surface texture. Which features of whisker motion does the sensory system extract to construct sensations? We addressed this question by t...

Human medial gastrocnemius force-velocity behavior shifts with locomotion spe...
Humans walk and run over a wide range of speeds with remarkable efficiency. For steady locomotion, moving at different speeds requires the muscle?tendon units of the leg to modulate the amount of mechanical power the limb absorbs and outputs in each step. How individual muscles adapt their behavior ...

Variation in cognitive functioning as a refined approach to comparing aging a...
Comparing the burden of aging across countries hinges on the availability of valid and comparable indicators. The Old Age Dependency Ratio allows only a limited assessment of the challenges of aging, because it does not include information on any individual characteristics except age itself. Existin...