molecular cell biology lab troubleshooting
Home Forums /Molecular /Cell /Genetics /Proteomics /Neuroscience /Immunology /Bioinformatics /Histology /Pharmacology /Jobs /Books /Bioproducts /Blog /Methods
Newest top publications from Science, Nature and Cell 27-Jun-2008 07:34 pm last update
Search biowww:

Nature AOP
Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.
  • Structure of a β1-adrenergic G-protein-coupled receptor


  • Escape from adaptive conflict after duplication in an anthocyanin pathway gene
    Gene duplications have been recognized as an important source of evolutionary innovation and adaptation since at least Haldane, and their varying fates may partly explain the vast disparity in observed genome sizes. The expected fates of most gene duplications involve primarily non-adaptive substitutions leading to either non-functionalization of one duplicate copy or subfunctionalization, neither of which yields novel function. A significant evolutionary problem is thus elucidating the mechanisms of adaptive evolutionary change leading to evolutionary novelty. Currently, the most widely recognized adaptive process involving gene duplication is neo-functionalization (NEO-F), in which one copy undergoes directional selection to perform a novel function after duplication. An alternative, but understudied, adaptive fate that has been proposed is escape from adaptive conflict (EAC), in which a single-copy gene is selected to perform a novel function while maintaining its ancestral function. This gene is constrained from improving either novel or ancestral function because of detrimental pleiotropic effects on the other function. After duplication, one copy is free to improve novel function, whereas the other is selected to improve ancestral function. Here we first present two criteria that can be used to distinguish NEO-F from EAC. Using both tests for positive selection and assays of enzyme function, we then demonstrate that adaptive evolutionary change in a duplicated gene of the anthocyanin biosynthetic pathway in morning glories (Ipomoea) is best interpreted as EAC. Finally, we argue that this phenomenon likely occurs more often than has been previously believed and may thus represent an important mechanism in generating evolutionary novelty.

  • Evidence for the evolutionary nascence of a novel sex determination pathway in honeybees
    Sex determination in honeybees (Apis mellifera) is governed by heterozygosity at a single locus harbouring the complementary sex determiner (csd) gene, in contrast to the well-studied sex chromosome system of Drosophila melanogaster. Bees heterozygous at csd are females, whereas homozygotes and hemizygotes (haploid individuals) are males. Although at least 15 different csd alleles are known among natural bee populations, the mechanisms linking allelic interactions to switching of the sexual development programme are still obscure. Here we report a new component of the sex-determining pathway in honeybees, encoded 12 kilobases upstream of csd. The gene feminizer (fem) is the ancestrally conserved progenitor gene from which csd arose and encodes an SR-type protein, harbouring an Arg/Ser-rich domain. Fem shares the same arrangement of Arg/Ser- and proline-rich-domain with the Drosophila principal sex-determining gene transformer (tra), but lacks conserved motifs except for a 30-amino-acid motif that Fem shares only with Tra of another fly, Ceratitis capitata. Like tra, the fem transcript is alternatively spliced. The male-specific splice variant contains a premature stop codon and yields no functional product, whereas the female-specific splice variant encodes the functional protein. We show that RNA interference (RNAi)-induced knockdowns of the female-specific fem splice variant result in male bees, indicating that the fem product is required for entire female development. Furthermore, RNAi-induced knockdowns of female allelic csd transcripts result in the male-specific fem splice variant, suggesting that the fem gene implements the switch of developmental pathways controlled by heterozygosity at csd. Comparative analysis of fem and csd coding sequences from five bee species indicates a recent origin of csd in the honeybee lineage from the fem progenitor and provides evidence for positive selection at csd accompanied by purifying selection at fem. The fem locus in bees uncovers gene duplication and positive selection as evolutionary mechanisms underlying the origin of a novel sex determination pathway.

  • Essential roles of PI(3)K–p110β in cell growth, metabolism and tumorigenesis
    On activation by receptors, the ubiquitously expressed class IA isoforms (p110α and p110β) of phosphatidylinositol-3-OH kinase (PI(3)K) generate lipid second messengers, which initiate multiple signal transduction cascades. Recent studies have demonstrated specific functions for p110α in growth factor and insulin signalling. To probe for distinct functions of p110β, we constructed conditional knockout mice. Here we show that ablation of p110β in the livers of the resulting mice leads to impaired insulin sensitivity and glucose homeostasis, while having little effect on phosphorylation of Akt, suggesting the involvement of a kinase-independent role of p110β in insulin metabolic action. Using established mouse embryonic fibroblasts, we found that removal of p110β also had little effect on Akt phosphorylation in response to stimulation by insulin and epidermal growth factor, but resulted in retarded cell proliferation. Reconstitution of p110β-null cells with a wild-type or kinase-dead allele of p110β demonstrated that p110β possesses kinase-independent functions in regulating cell proliferation and trafficking. However, the kinase activity of p110β was required for G-protein-coupled receptor signalling triggered by lysophosphatidic acid and had a function in oncogenic transformation. Most strikingly, in an animal model of prostate tumour formation induced by Pten loss, ablation of p110β (also known as Pik3cb), but not that of p110α (also known as Pik3ca), impeded tumorigenesis with a concomitant diminution of Akt phosphorylation. Taken together, our findings demonstrate both kinase-dependent and kinase-independent functions for p110β, and strongly indicate the kinase-dependent functions of p110β as a promising target in cancer therapy.

  • Switch of rhodopsin expression in terminally differentiated Drosophila sensory neurons
    Specificity of sensory neurons requires restricted expression of one sensory receptor gene and the exclusion of all others within a given cell. In the Drosophila retina, functional identity of photoreceptors depends on light-sensitive Rhodopsins (Rhs). The much simpler larval eye (Bolwig organ) is composed of about 12 photoreceptors, eight of which are green-sensitive (Rh6) and four blue-sensitive (Rh5). The larval eye becomes the adult extraretinal ‘eyelet’ composed of four green-sensitive (Rh6) photoreceptors. Here we show that, during metamorphosis, all Rh6 photoreceptors die, whereas the Rh5 photoreceptors switch fate by turning off Rh5 and then turning on Rh6 expression. This switch occurs without apparent changes in the programme of transcription factors that specify larval photoreceptor subtypes. We also show that the transcription factor Senseless (Sens) mediates the very different cellular behaviours of Rh5 and Rh6 photoreceptors. Sens is restricted to Rh5 photoreceptors and must be excluded from Rh6 photoreceptors to allow them to die at metamorphosis. Finally, we show that Ecdysone receptor (EcR) functions autonomously both for the death of larval Rh6 photoreceptors and for the sensory switch of Rh5 photoreceptors to express Rh6. This fate switch of functioning, terminally differentiated neurons provides a novel, unexpected example of hard-wired sensory plasticity.

  • Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation
    Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is a key process in several pathological conditions, including tumour growth and age-related macular degeneration. Vascular endothelial growth factors (VEGFs) stimulate angiogenesis and lymphangiogenesis by activating VEGF receptor (VEGFR) tyrosine kinases in endothelial cells. VEGFR-3 (also known as FLT-4) is present in all endothelia during development, and in the adult it becomes restricted to the lymphatic endothelium. However, VEGFR-3 is upregulated in the microvasculature of tumours and wounds. Here we demonstrate that VEGFR-3 is highly expressed in angiogenic sprouts, and genetic targeting of VEGFR-3 or blocking of VEGFR-3 signalling with monoclonal antibodies results in decreased sprouting, vascular density, vessel branching and endothelial cell proliferation in mouse angiogenesis models. Stimulation of VEGFR-3 augmented VEGF-induced angiogenesis and sustained angiogenesis even in the presence of VEGFR-2 (also known as KDR or FLK-1) inhibitors, whereas antibodies against VEGFR-3 and VEGFR-2 in combination resulted in additive inhibition of angiogenesis and tumour growth. Furthermore, genetic or pharmacological disruption of the Notch signalling pathway led to widespread endothelial VEGFR-3 expression and excessive sprouting, which was inhibited by blocking VEGFR-3 signals. Our results implicate VEGFR-3 as a regulator of vascular network formation. Targeting VEGFR-3 may provide additional efficacy for anti-angiogenic therapies, especially towards vessels that are resistant to VEGF or VEGFR-2 inhibitors.

  • Mouse development with a single E2F activator
    The E2F family is conserved from Caenorhabditis elegans to mammals, with some family members having transcription activation functions and others having repressor functions. Whereas C. elegans and Drosophila melanogaster have a single E2F activator protein and repressor protein, mammals have at least three activator and five repressor proteins. Why such genetic complexity evolved in mammals is not known. To begin to evaluate this genetic complexity, we targeted the inactivation of the entire subset of activators, E2f1, E2f2, E2f3a and E2f3b, singly or in combination in mice. We demonstrate that E2f3a is sufficient to support mouse embryonic and postnatal development. Remarkably, expression of E2f3b or E2f1 from the E2f3a locus (E2f3a3bki or E2f3a1ki, respectively) suppressed all the postnatal phenotypes associated with the inactivation of E2f3a. We conclude that there is significant functional redundancy among activators and that the specific requirement for E2f3a during postnatal development is dictated by regulatory sequences governing its selective spatiotemporal expression and not by its intrinsic protein functions. These findings provide a molecular basis for the observed specificity among E2F activators during development.

  • An Fgf/Gremlin inhibitory feedback loop triggers termination of limb bud outgrowth
    During organ formation and regeneration a proper balance between promoting and restricting growth is critical to achieve stereotypical size. Limb bud outgrowth is driven by signals in a positive feedback loop involving fibroblast growth factor (Fgf) genes, sonic hedgehog (Shh) and Gremlin1 (Grem1). Precise termination of these signals is essential to restrict limb bud size. The current model predicts a sequence of signal termination consistent with that in chick limb buds. Our finding that the sequence in mouse limb buds is different led us to explore alternative mechanisms. Here we show, by analysing compound mouse mutants defective in genes comprising the positive loop, genetic evidence that FGF signalling can repress Grem1 expression, revealing a novel Fgf/Grem1 inhibitory loop. This repression occurs both in mouse and chick limb buds, and is dependent on high FGF activity. These data support a mechanism where the positive Fgf/Shh loop drives outgrowth and an increase in FGF signalling, which triggers the Fgf/Grem1 inhibitory loop. The inhibitory loop then operates to terminate outgrowth signals in the order observed in either mouse or chick limb buds. Our study unveils the concept of a self-promoting and self-terminating circuit that may be used to attain proper tissue size in a broad spectrum of developmental and regenerative settings.

  • IRF4 addiction in multiple myeloma
    The transcription factor IRF4 (interferon regulatory factor 4) is required during an immune response for lymphocyte activation and the generation of immunoglobulin-secreting plasma cells. Multiple myeloma, a malignancy of plasma cells, has a complex molecular aetiology with several subgroups defined by gene expression profiling and recurrent chromosomal translocations. Moreover, the malignant clone can sustain multiple oncogenic lesions, accumulating genetic damage as the disease progresses. Current therapies for myeloma can extend survival but are not curative. Hence, new therapeutic strategies are needed that target molecular pathways shared by all subtypes of myeloma. Here we show, using a loss-of-function, RNA-interference-based genetic screen, that IRF4 inhibition is toxic to myeloma cell lines, regardless of transforming oncogenic mechanism. Gene expression profiling and genome-wide chromatin immunoprecipitation analysis uncovered an extensive network of IRF4 target genes and identified MYC as a direct target of IRF4 in activated B cells and myeloma. Unexpectedly, IRF4 was itself a direct target of MYC transactivation, generating an autoregulatory circuit in myeloma cells. Although IRF4 is not genetically altered in most myelomas, they are nonetheless addicted to an aberrant IRF4 regulatory network that fuses the gene expression programmes of normal plasma cells and activated B cells.

  • Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart
    The heart is formed from cardiogenic progenitors expressing the transcription factors Nkx2-5 and Isl1 (refs 1 and 2). These multipotent progenitors give rise to cardiomyocyte, smooth muscle and endothelial cells, the major lineages of the mature heart. Here we identify a novel cardiogenic precursor marked by expression of the transcription factor Wt1 and located within the epicardium—an epithelial sheet overlying the heart. During normal murine heart development, a subset of these Wt1+ precursors differentiated into fully functional cardiomyocytes. Wt1+ proepicardial cells arose from progenitors that express Nkx2-5 and Isl1, suggesting that they share a developmental origin with multipotent Nkx2-5+ and Isl1+ progenitors. These results identify Wt1+ epicardial cells as previously unrecognized cardiomyocyte progenitors, and lay the foundation for future efforts to harness the cardiogenic potential of these progenitors for cardiac regeneration and repair.

  • Crystal structure of the ligand-free G-protein-coupled receptor opsin


  • A new class of homoserine lactone quorum-sensing signals


  • The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards
    Cues that reliably predict rewards trigger the thoughts and emotions normally evoked by those rewards. Humans and other animals will work, often quite hard, for these cues. This is termed conditioned reinforcement. The ability to use conditioned reinforcers to guide our behaviour is normally beneficial; however, it can go awry. For example, corporate icons, such as McDonald’s Golden Arches, influence consumer behaviour in powerful and sometimes surprising ways, and drug-associated cues trigger relapse to drug seeking in addicts and animals exposed to addictive drugs, even after abstinence or extinction. Yet, despite their prevalence, it is not known how conditioned reinforcers control human or other animal behaviour. One possibility is that they act through the use of the specific rewards they predict; alternatively, they could control behaviour directly by activating emotions that are independent of any specific reward. In other words, the Golden Arches may drive business because they evoke thoughts of hamburgers and fries, or instead, may be effective because they also evoke feelings of hunger or happiness. Moreover, different brain circuits could support conditioned reinforcement mediated by thoughts of specific outcomes versus more general affective information. Here we have attempted to address these questions in rats. Rats were trained to learn that different cues predicted different rewards using specialized conditioning procedures that controlled whether the cues evoked thoughts of specific outcomes or general affective representations common to different outcomes. Subsequently, these rats were given the opportunity to press levers to obtain short and otherwise unrewarded presentations of these cues. We found that rats were willing to work for cues that evoked either outcome-specific or general affective representations. Furthermore the orbitofrontal cortex, a prefrontal region important for adaptive decision-making, was critical for the former but not for the latter form of conditioned reinforcement.

  • Control of segment number in vertebrate embryos
    The vertebrate body axis is subdivided into repeated segments, best exemplified by the vertebrae that derive from embryonic somites. The number of somites is precisely defined for any given species but varies widely from one species to another. To determine the mechanism controlling somite number, we have compared somitogenesis in zebrafish, chicken, mouse and corn snake embryos. Here we present evidence that in all of these species a similar ‘clock-and-wavefront’ mechanism operates to control somitogenesis; in all of them, somitogenesis is brought to an end through a process in which the presomitic mesoderm, having first increased in size, gradually shrinks until it is exhausted, terminating somite formation. In snake embryos, however, the segmentation clock rate is much faster relative to developmental rate than in other amniotes, leading to a greatly increased number of smaller-sized somites.

  • A unifying framework for dinitrogen fixation in the terrestrial biosphere
    Dinitrogen (N2) fixation is widely recognized as an important process in controlling ecosystem responses to global environmental change, both today and in the past; however, significant discrepancies exist between theory and observations of patterns of N2 fixation across major sectors of the land biosphere. A question remains as to why symbiotic N2-fixing plants are more abundant in vast areas of the tropics than in many of the mature forests that seem to be nitrogen-limited in the temperate and boreal zones. Here we present a unifying framework for terrestrial N2 fixation that can explain the geographic occurrence of N2 fixers across diverse biomes and at the global scale. By examining trade-offs inherent in plant carbon, nitrogen and phosphorus capture, we find a clear advantage to symbiotic N2 fixers in phosphorus-limited tropical savannas and lowland tropical forests. The ability of N2 fixers to invest nitrogen into phosphorus acquisition seems vital to sustained N2 fixation in phosphorus-limited tropical ecosystems. In contrast, modern-day temperatures seem to constrain N2 fixation rates and N2-fixing species from mature forests in the high latitudes. We propose that an analysis that couples biogeochemical cycling and biophysical mechanisms is sufficient to explain the principal geographical patterns of symbiotic N2 fixation on land, thus providing a basis for predicting the response of nutrient-limited ecosystems to climate change and increasing atmospheric CO2.

  • Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells
    Adult skeletal muscle robustly regenerates throughout an organism’s life, but as the muscle ages, its ability to repair diminishes and eventually fails. Previous work suggests that the regenerative potential of muscle stem cells (satellite cells) is not triggered in the old muscle because of a decline in Notch activation, and that it can be rejuvenated by forced local activation of Notch. Here we report that, in addition to the loss of Notch activation, old muscle produces excessive transforming growth factor (TGF)-β (but not myostatin), which induces unusually high levels of TGF-β pSmad3 in resident satellite cells and interferes with their regenerative capacity. Importantly, endogenous Notch and pSmad3 antagonize each other in the control of satellite-cell proliferation, such that activation of Notch blocks the TGF-β-dependent upregulation of the cyclin-dependent kinase (CDK) inhibitors p15, p16, p21 and p27, whereas inhibition of Notch induces them. Furthermore, in muscle stem cells, Notch activity determines the binding of pSmad3 to the promoters of these negative regulators of cell-cycle progression. Attenuation of TGF-β/pSmad3 in old, injured muscle restores regeneration to satellite cells in vivo. Thus a balance between endogenous pSmad3 and active Notch controls the regenerative competence of muscle stem cells, and deregulation of this balance in the old muscle microniche interferes with regeneration.

  • Positive feedback sharpens the anaphase switch
    At the onset of anaphase, sister-chromatid cohesion is dissolved abruptly and irreversibly, ensuring that all chromosome pairs disjoin almost simultaneously. The regulatory mechanisms that generate this switch-like behaviour are unclear. Anaphase is initiated when a ubiquitin ligase, the anaphase-promoting complex (APC), triggers the destruction of securin, thereby allowing separase, a protease, to disrupt sister-chromatid cohesion. Here we demonstrate that the cyclin-dependent kinase 1 (Cdk1)-dependent phosphorylation of securin near its destruction-box motif inhibits securin ubiquitination by the APC. The phosphatase Cdc14 reverses securin phosphorylation, thereby increasing the rate of securin ubiquitination. Because separase is known to activate Cdc14 (refs 5 and 6), our results support the existence of a positive feedback loop that increases the abruptness of anaphase. Consistent with this model, we show that mutations that disrupt securin phosphoregulation decrease the synchrony of chromosome segregation. Our results also suggest that coupling securin degradation with changes in Cdk1 and Cdc14 activities helps coordinate the initiation of sister-chromatid separation with changes in spindle dynamics.

  • Environmental determinants of extinction selectivity in the fossil record
    The causes of mass extinctions and the nature of biological selectivity during extinction events remain central questions in palaeobiology. Although many different environmental perturbations have been invoked as extinction mechanisms, it has long been recognized that fluctuations in sea level coincide with many episodes of biotic turnover. Recent work supports the hypothesis that changes in the areas of epicontinental seas have influenced the macroevolution of marine animals, but the extent to which differential environmental turnover has contributed to extinction selectivity remains unknown. Here I use a new compilation of the temporal durations of sedimentary rock packages to show that carbonate and terrigenous clastic marine shelf environments have different spatio-temporal dynamics and that these dynamics predict patterns of genus-level extinction, extinction selectivity and diversity among Sepkoski’s Palaeozoic and modern evolutionary faunae. These results do not preclude a role for biological interactions or unusual physical events as drivers of macroevolution, but they do suggest that the turnover of marine shelf habitats and correlated environmental changes have been consistent determinants of extinction, extinction selectivity and the shifting composition of the marine biota during the Phanerozoic eon.

  • SMAD proteins control DROSHA-mediated microRNA maturation


  • Osteoclast size is controlled by Fra-2 through LIF/LIF-receptor signalling and hypoxia
    Osteoclasts are multinucleated haematopoietic cells that resorb bone. Increased osteoclast activity causes osteoporosis, a disorder resulting in a low bone mass and a high risk of fractures. Increased osteoclast size and numbers are also a hallmark of other disorders, such as Paget’s disease and multiple myeloma. The protein c-Fos, a component of the AP-1 transcription factor complex, is essential for osteoclast differentiation. Here we show that the Fos-related protein Fra-2 controls osteoclast survival and size. The bones of Fra-2-deficient newborn mice have giant osteoclasts, and signalling through leukaemia inhibitory factor (LIF) and its receptor is impaired. Similarly, newborn animals lacking LIF have giant osteoclasts, and we show that LIF is a direct transcriptional target of Fra-2 and c-Jun. Moreover, bones deficient in Fra-2 and LIF are hypoxic and express increased levels of hypoxia-induced factor 1α (HIF1α) and Bcl-2. Overexpression of Bcl-2 is sufficient to induce giant osteoclasts in vivo, whereas Fra-2 and LIF affect HIF1α through transcriptional modulation of the HIF prolyl hydroxylase PHD2. This pathway is operative in the placenta, because specific inactivation of Fra-2 in the embryo alone does not cause hypoxia or the giant osteoclast phenotype. Thus placenta-induced hypoxia during embryogenesis leads to the formation of giant osteoclasts in young pups. These findings offer potential targets for the treatment of syndromes associated with increased osteoclastogenesis.

  • An internal thermal sensor controlling temperature preference in Drosophila
    Animals from flies to humans are able to distinguish subtle gradations in temperature and show strong temperature preferences. Animals move to environments of optimal temperature and some manipulate the temperature of their surroundings, as humans do using clothing and shelter. Despite the ubiquitous influence of environmental temperature on animal behaviour, the neural circuits and strategies through which animals select a preferred temperature remain largely unknown. Here we identify a small set of warmth-activated anterior cell (AC) neurons located in the Drosophila brain, the function of which is critical for preferred temperature selection. AC neuron activation occurs just above the fly’s preferred temperature and depends on dTrpA1, an ion channel that functions as a molecular sensor of warmth. Flies that selectively express dTrpA1 in the AC neurons select normal temperatures, whereas flies in which dTrpA1 function is reduced or eliminated choose warmer temperatures. This internal warmth-sensing pathway promotes avoidance of slightly elevated temperatures and acts together with a distinct pathway for cold avoidance to set the fly’s preferred temperature. Thus, flies select a preferred temperature by using a thermal sensing pathway tuned to trigger avoidance of temperatures that deviate even slightly from the preferred temperature. This provides a potentially general strategy for robustly selecting a narrow temperature range optimal for survival.

  • Subtropical to boreal convergence of tree-leaf temperatures
    The oxygen isotope ratio (δ18O) of cellulose is thought to provide a record of ambient temperature and relative humidity during periods of carbon assimilation. Here we introduce a method to resolve tree-canopy leaf temperature with the use of δ18O of cellulose in 39 tree species. We show a remarkably constant leaf temperature of 21.4 ± 2.2 °C across 50° of latitude, from subtropical to boreal biomes. This means that when carbon assimilation is maximal, the physiological and morphological properties of tree branches serve to raise leaf temperature above air temperature to a much greater extent in more northern latitudes. A main assumption underlying the use of δ18O to reconstruct climate history is that the temperature and relative humidity of an actively photosynthesizing leaf are the same as those of the surrounding air. Our data are contrary to that assumption and show that plant physiological ecology must be considered when reconstructing climate through isotope analysis. Furthermore, our results may explain why climate has only a modest effect on leaf economic traits in general.

  • Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA
    Innate immune defences are essential for the control of virus infection and are triggered through host recognition of viral macromolecular motifs known as pathogen-associated molecular patterns (PAMPs). Hepatitis C virus (HCV) is an RNA virus that replicates in the liver, and infects 200 million people worldwide. Infection is regulated by hepatic immune defences triggered by the cellular RIG-I helicase. RIG-I binds PAMP RNA and signals interferon regulatory factor 3 activation to induce the expression of interferon-α/β and antiviral/interferon-stimulated genes (ISGs) that limit infection. Here we identify the polyuridine motif of the HCV genome 3′ non-translated region and its replication intermediate as the PAMP substrate of RIG-I, and show that this and similar homopolyuridine or homopolyriboadenine motifs present in the genomes of RNA viruses are the chief feature of RIG-I recognition and immune triggering in human and murine cells. 5′ terminal triphosphate on the PAMP RNA was necessary but not sufficient for RIG-I binding, which was primarily dependent on homopolymeric ribonucleotide composition, linear structure and length. The HCV PAMP RNA stimulated RIG-I-dependent signalling to induce a hepatic innate immune response in vivo, and triggered interferon and ISG expression to suppress HCV infection in vitro. These results provide a conceptual advance by defining specific homopolymeric RNA motifs within the genome of HCV and other RNA viruses as the PAMP substrate of RIG-I, and demonstrate immunogenic features of the PAMP–RIG-I interaction that could be used as an immune adjuvant for vaccine and immunotherapy approaches.

  • Structural basis of specific tRNA aminoacylation by a small in vitro selected ribozyme
    In modern organisms, protein enzymes are solely responsible for the aminoacylation of transfer RNA. However, the evolution of protein synthesis in the RNA world required RNAs capable of catalysing this reaction. Ribozymes that aminoacylate RNA by using activated amino acids have been discovered through selection in vitro. Flexizyme is a 45-nucleotide ribozyme capable of charging tRNA in trans with various activated l-phenylalanine derivatives. In addition to a more than 105 rate enhancement and more than 104-fold discrimination against some non-cognate amino acids, this ribozyme achieves good regioselectivity: of all the hydroxyl groups of a tRNA, it exclusively aminoacylates the terminal 3′-OH. Here we report the 2.8-Å resolution structure of flexizyme fused to a substrate RNA. Together with randomization of ribozyme core residues and reselection, this structure shows that very few nucleotides are needed for the aminoacylation of specific tRNAs. Although it primarily recognizes tRNA through base-pairing with the CCA terminus of the tRNA molecule, flexizyme makes numerous local interactions to position the acceptor end of tRNA precisely. A comparison of two crystallographically independent flexizyme conformations, only one of which appears capable of binding activated phenylalanine, suggests that this ribozyme may achieve enhanced specificity by coupling active-site folding to tRNA docking. Such a mechanism would be reminiscent of the mutually induced fit of tRNA and protein employed by some aminoacyl-tRNA synthetases to increase specificity.

  • Volcanic carbon dioxide vents show ecosystem effects of ocean acidification
    The atmospheric partial pressure of carbon dioxide (pCO2) will almost certainly be double that of pre-industrial levels by 2100 and will be considerably higher than at any time during the past few million years. The oceans are a principal sink for anthropogenic CO2 where it is estimated to have caused a 30% increase in the concentration of H+ in ocean surface waters since the early 1900s and may lead to a drop in seawater pH of up to 0.5 units by 2100 (refs 2, 3). Our understanding of how increased ocean acidity may affect marine ecosystems is at present very limited as almost all studies have been in vitro, short-term, rapid perturbation experiments on isolated elements of the ecosystem. Here we show the effects of acidification on benthic ecosystems at shallow coastal sites where volcanic CO2 vents lower the pH of the water column. Along gradients of normal pH (8.1–8.2) to lowered pH (mean 7.8–7.9, minimum 7.4–7.5), typical rocky shore communities with abundant calcareous organisms shifted to communities lacking scleractinian corals with significant reductions in sea urchin and coralline algal abundance. To our knowledge, this is the first ecosystem-scale validation of predictions that these important groups of organisms are susceptible to elevated amounts of pCO2. Sea-grass production was highest in an area at mean pH 7.6 (1,827 μatm pCO2) where coralline algal biomass was significantly reduced and gastropod shells were dissolving due to periods of carbonate sub-saturation. The species populating the vent sites comprise a suite of organisms that are resilient to naturally high concentrations of pCO2 and indicate that ocean acidification may benefit highly invasive non-native algal species. Our results provide the first in situ insights into how shallow water marine communities might change when susceptible organisms are removed owing to ocean acidification.

  • Template-directed synthesis of a genetic polymer in a model protocell
    Contemporary phospholipid-based cell membranes are formidable barriers to the uptake of polar and charged molecules ranging from metal ions to complex nutrients. Modern cells therefore require sophisticated protein channels and pumps to mediate the exchange of molecules with their environment. The strong barrier function of membranes has made it difficult to understand the origin of cellular life and has been thought to preclude a heterotrophic lifestyle for primitive cells. Although nucleotides can cross dimyristoyl phosphatidylcholine membranes through defects formed at the gel-to-liquid transition temperature, phospholipid membranes lack the dynamic properties required for membrane growth. Fatty acids and their corresponding alcohols and glycerol monoesters are attractive candidates for the components of protocell membranes because they are simple amphiphiles that form bilayer membrane vesicles that retain encapsulated oligonucleotides and are capable of growth and division. Here we show that such membranes allow the passage of charged molecules such as nucleotides, so that activated nucleotides added to the outside of a model protocell spontaneously cross the membrane and take part in efficient template copying in the protocell interior. The permeability properties of prebiotically plausible membranes suggest that primitive protocells could have acquired complex nutrients from their environment in the absence of any macromolecular transport machinery; that is, they could have been obligate heterotrophs.

  • Mei-P26 regulates microRNAs and cell growth in the Drosophila ovarian stem cell lineage
    Drosophila neuroblasts and ovarian stem cells are well characterized models for stem cell biology. In both cell types, one daughter cell self-renews continuously while the other undergoes a limited number of divisions, stops to proliferate mitotically and differentiates. Whereas neuroblasts segregate the Trim–NHL (tripartite motif and Ncl-1, HT2A and Lin-41 domain)-containing protein Brain tumour (Brat) into one of the two daughter cells, ovarian stem cells are regulated by an extracellular signal from the surrounding stem cell niche. After division, one daughter cell looses niche contact. It undergoes 4 transit-amplifying divisions to form a cyst of 16 interconnected cells that reduce their rate of growth and stop to proliferate mitotically. Here we show that the Trim–NHL protein Mei-P26 (refs 7, 8) restricts growth and proliferation in the ovarian stem cell lineage. Mei-P26 expression is low in stem cells but is strongly induced in 16-cell cysts. In mei-P26 mutants, transit-amplifying cells are larger and proliferate indefinitely leading to the formation of an ovarian tumour. Like brat, mei-P26 regulates nucleolar size and can induce differentiation in Drosophila neuroblasts, suggesting that these genes act through the same pathway. We identify Argonaute-1, a component of the RISC complex, as a common binding partner of Brat and Mei-P26, and show that Mei-P26 acts by inhibiting the microRNA pathway. Mei-P26 and Brat have a similar domain composition that is also found in other tumour suppressors and might be a defining property of a new family of microRNA regulators that act specifically in stem cell lineages.

  • IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis
    Insulin-like growth-factor-binding proteins (IGFBPs) bind to and modulate the actions of insulin-like growth factors (IGFs). Although some of the actions of IGFBPs have been reported to be independent of IGFs, the precise mechanisms of IGF-independent actions of IGFBPs are largely unknown. Here we report a previously unknown function for IGFBP-4 as a cardiogenic growth factor. IGFBP-4 enhanced cardiomyocyte differentiation in vitro, and knockdown of Igfbp4 attenuated cardiomyogenesis both in vitro and in vivo. The cardiogenic effect of IGFBP-4 was independent of its IGF-binding activity but was mediated by the inhibitory effect on canonical Wnt signalling. IGFBP-4 physically interacted with a Wnt receptor, Frizzled 8 (Frz8), and a Wnt co-receptor, low-density lipoprotein receptor-related protein 6 (LRP6), and inhibited the binding of Wnt3A to Frz8 and LRP6. Although IGF-independent, the cardiogenic effect of IGFBP-4 was attenuated by IGFs through IGFBP-4 sequestration. IGFBP-4 is therefore an inhibitor of the canonical Wnt signalling required for cardiogenesis and provides a molecular link between IGF signalling and Wnt signalling.

  • Dissecting direct reprogramming through integrative genomic analysis


  • Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription
    With the recent recognition of non-coding RNAs (ncRNAs) flanking many genes, a central issue is to obtain a full understanding of their potential roles in regulated gene transcription programmes, possibly through different mechanisms. Here we show that an RNA-binding protein, TLS (for translocated in liposarcoma), serves as a key transcriptional regulatory sensor of DNA damage signals that, on the basis of its allosteric modulation by RNA, specifically binds to and inhibits CREB-binding protein (CBP) and p300 histone acetyltransferase activities on a repressed gene target, cyclin D1 (CCND1) in human cell lines. Recruitment of TLS to the CCND1 promoter to cause gene-specific repression is directed by single-stranded, low-copy-number ncRNA transcripts tethered to the 5′ regulatory regions of CCND1 that are induced in response to DNA damage signals. Our data suggest that signal-induced ncRNAs localized to regulatory regions of transcription units can act cooperatively as selective ligands, recruiting and modulating the activities of distinct classes of RNA-binding co-regulators in response to specific signals, providing an unexpected ncRNA/RNA-binding protein-based strategy to integrate transcriptional programmes.

  • Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving
    Relapse to cocaine use after prolonged abstinence is an important clinical problem. This relapse is often induced by exposure to cues associated with cocaine use. To account for the persistent propensity for relapse, it has been suggested that cue-induced cocaine craving increases over the first several weeks of abstinence and remains high for extended periods. We and others identified an analogous phenomenon in rats that was termed ‘incubation of cocaine craving’: time-dependent increases in cue-induced cocaine-seeking over the first months after withdrawal from self-administered cocaine. Cocaine-seeking requires the activation of glutamate projections that excite receptors for α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in the nucleus accumbens. Here we show that the number of synaptic AMPA receptors in the accumbens is increased after prolonged withdrawal from cocaine self-administration by the addition of new AMPA receptors lacking glutamate receptor 2 (GluR2). Furthermore, we show that these new receptors mediate the incubation of cocaine craving. Our results indicate that GluR2-lacking AMPA receptors could be a new target for drug development for the treatment of cocaine addiction. We propose that after prolonged withdrawal from cocaine, increased numbers of synaptic AMPA receptors combined with the higher conductance of GluR2-lacking AMPA receptors causes increased reactivity of accumbens neurons to cocaine-related cues, leading to an intensification of drug craving and relapse.

  • Imaging the biogenesis of individual HIV-1 virions in live cells
    Observations of individual virions in live cells have led to the characterization of their attachment, entry and intracellular transport. However, the assembly of individual virions has never been observed in real time. Insights into this process have come primarily from biochemical analyses of populations of virions or from microscopic studies of fixed infected cells. Thus, some assembly properties, such as kinetics and location, are either unknown or controversial. Here we describe quantitatively the genesis of individual virions in real time, from initiation of assembly to budding and release. We studied fluorescently tagged derivatives of Gag, the major structural component of HIV-1—which is sufficient to drive the assembly of virus-like particles—with the use of fluorescence resonance energy transfer, fluorescence recovery after photobleaching and total-internal-reflection fluorescent microscopy in living cells. Virions appeared individually at the plasma membrane, their assembly rate accelerated as Gag protein accumulated in cells, and typically 5–6 min was required to complete the assembly of a single virion. These approaches allow a previously unobserved view of the genesis of individual virions and the determination of parameters of viral assembly that are inaccessible with conventional techniques.

  • A myocardial lineage derives from Tbx18 epicardial cells
    Understanding the origins and roles of cardiac progenitor cells is important for elucidating the pathogenesis of congenital and acquired heart diseases. Moreover, manipulation of cardiac myocyte progenitors has potential for cell-based repair strategies for various myocardial disorders. Here we report the identification in mouse of a previously unknown cardiac myocyte lineage that derives from the proepicardial organ. These progenitor cells, which express the T-box transcription factor Tbx18, migrate onto the outer cardiac surface to form the epicardium, and then make a substantial contribution to myocytes in the ventricular septum and the atrial and ventricular walls. Tbx18-expressing cardiac progenitors also give rise to cardiac fibroblasts and coronary smooth muscle cells. The pluripotency of Tbx18 proepicardial cells provides a theoretical framework for applying these progenitors to effect cardiac repair and regeneration.

  • IL-21 and TGF-β are required for differentiation of human TH17 cells
    The recent discovery of CD4+ T cells characterized by secretion of interleukin (IL)-17 (TH17 cells) and the naturally occurring regulatory FOXP3+ CD4 T cell (nTreg) has had a major impact on our understanding of immune processes not readily explained by the TH1/TH2 paradigm. TH17 and nTreg cells have been implicated in the pathogenesis of human autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and psoriasis. Our recent data and the work of others demonstrated that transforming growth factor-β (TGF-β) and IL-6 are responsible for the differentiation of naive mouse T cells into TH17 cells, and it has been proposed that IL-23 may have a critical role in stabilization of the TH17 phenotype. A second pathway has been discovered in which a combination of TGF-β and IL-21 is capable of inducing differentiation of mouse TH17 cells in the absence of IL-6 (refs 6–8). However, TGF-β and IL-6 are not capable of differentiating human TH17 cells and it has been suggested that TGF-β may in fact suppress the generation of human TH17 cells. Instead, it has been recently shown that the cytokines IL-1β, IL-6 and IL-23 are capable of driving IL-17 secretion in short-term CD4+ T cell lines isolated from human peripheral blood, although the factors required for differentiation of naive human CD4 to TH17 cells are still unknown. Here we confirm that whereas IL-1β and IL-6 induce IL-17A secretion from human central memory CD4+ T cells, TGF-β and IL-21 uniquely promote the differentiation of human naive CD4+ T cells into TH17 cells accompanied by expression of the transcription factor RORC2. These data will allow the investigation of this new population of TH17 cells in human inflammatory disease.

  • Essential role for Nix in autophagic maturation of erythroid cells
    Erythroid cells undergo enucleation and the removal of organelles during terminal differentiation. Although autophagy has been suggested to mediate the elimination of organelles for erythroid maturation, the molecular mechanisms underlying this process remain undefined. Here we report a role for a Bcl-2 family member, Nix (also called Bnip3L), in the regulation of erythroid maturation through mitochondrial autophagy. Nix-/- mice developed anaemia with reduced mature erythrocytes and compensatory expansion of erythroid precursors. Erythrocytes in the peripheral blood of Nix-/- mice exhibited mitochondrial retention and reduced lifespan in vivo. Although the clearance of ribosomes proceeded normally in the absence of Nix, the entry of mitochondria into autophagosomes for clearance was defective. Deficiency in Nix inhibited the loss of mitochondrial membrane potential (ΔΨm), and treatment with uncoupling chemicals or a BH3 mimetic induced the loss of ΔΨm and restored the sequestration of mitochondria into autophagosomes in Nix-/- erythroid cells. These results suggest that Nix-dependent loss of ΔΨm is important for targeting the mitochondria into autophagosomes for clearance during erythroid maturation, and interference with this function impairs erythroid maturation and results in anaemia. Our study may also provide insights into molecular mechanisms underlying mitochondrial quality control involving mitochondrial autophagy.

Science: Current Issue
The best in science news, commentary, and research
  • This Week in Science
    Mesoporous Metal Composites from Nanoparticles | After the Asteroid | Let There Be Light | Birds, Birds, Birds | Electron Relay Station | Linking Cell Contact and Polarity | Developing the Lateral Line | Expanding β-Arrestin's Remit | Dissecting Spliceosome Functions | Same But Different | Human Migration Unraveled | Getting the Measure of Trapped Atoms | From Microscopic to Macroscopic Properties | Reassessing Defects on Titania Surfaces | Mountain Forest Ecosystem Change

  • Editors' Choice
    IMMUNOLOGY: AID-ing Up MicroRNA Functions | BIOMEDICINE: A Brush with Infection | CHEMISTRY: Sensors with Sparkle | CLIMATE SCIENCE: Charting Global Runoff | CELL BIOLOGY: Not So Identical Twins | GEOLOGY: Crust on the Move | SCIENCE SIGNALING: Receptor Rendezvous

  • Science Scope
    Hungary: Where Europe Will Be EITing | Council: Machine Won't Destroy Earth | New Woes for NPOESS | Canada-CIRM Cancer Deal

  • Random Samples
    PI FROM THE SKY? | PARACELSUS, EAT YOUR HEART OUT | HOMER AND THE ECLIPSE | GET ONLINE, LITTLE DOGIES

  • Newsmakers
    IN THE NEWS | MOVERS | MOVERS | AWARDS

  • [EDITORIAL] Long Road to Reform in France
    Authors: Edouard Brézin, Antoine Triller

  • [NEWS] ARCHAEOLOGY: Early Stonehenge Pilgrims Came From Afar, With Cattle in Tow
    Isotopic studies of teeth from six cattle found at a nearby earthen henge, coming on the heels of new dates for human remains at Stonehenge, are fueling ongoing debates about whether the 5000-year-old monument served chiefly as a "place of the dead" or whether its stones were valued for their healing properties.

    Author: Michael Balter

  • [NEWS] FRANCE: Despite Protest, CNRS Moves Toward Major Shakeup
    Researchers and science labor unions last week stopped a proposed reform of one of Europe's biggest research agencies with their bodies. But their victory may be short-lived, as France's science ministry says the makeover of the National Center for Scientific Research (CNRS) will proceed.

    Author: Martin Enserink

  • [NEWS] U.S. OCEAN POLICY: Proposed Rule Would Limit Fish Catch but Faces Data Gaps
    Environmentalists are welcoming the U.S. government's first-ever annual catch limits on fish. But experts caution that it will be difficult--and hugely expensive--for the agency to regulate the many marine species about which little is known.

    Author: Erik Stokstad

  • [NEWS] 2008 U.S. BUDGET: House Gives $400 Million to Four Science Agencies
    The $186 billion supplemental spending bill to continue funding the U.S. war effort in Iraq and Afghanistan approved by the House of Representatives last week includes a welcome bump-up of $400 million for four agencies whose research budgets were flattened late last year by legislators.

    Author: Jeffrey Mervis

  • [NEWS] FUSION REACTOR: ITER Costs Give Partners Pause
    Last week, ITER scientists revealed a new cost estimate for the multibillion-dollar fusion reactor that was 30% higher than earlier calculations. Now the project's seven international partners must decide whether they can afford it.

    Author: Daniel Clery

  • [NEWS] ETHICS: Senate Inquiry on Research Conflicts Shifts to Grantees
    In the wake of an ongoing Senate investigation, universities are scrambling to tighten procedures to track financial conflicts of interest among their faculty members, hoping to reassure the public and stave off more stringent measures that they say could stifle cooperation with industry.

    Author: Jocelyn Kaiser

  • [NEWS] VIROLOGY: 'Biased' Viruses Suggest New Vaccine Strategy for Polio and Other Diseases
    Introducing hundreds of seemingly inconsequential mutations into a poliovirus can cripple the virus enough to make it work as a live vaccine in mice, scientists report on page 1784 of this week's issue of Science. The technology might lead to safer polio vaccines and perhaps to so-called live attenuated vaccines against other diseases.

    Author: Martin Enserink

  • [NEWS FOCUS] INFECTIOUS DISEASE: An Ill Wind, Bringing Meningitis
    Crippling epidemics of meningococcal meningitis sweep across Africa with the onset of the dry season and harsh harmattan winds. An affordable, effective vaccine in the works could change that.

    Author: Leslie Roberts

  • [NEWS FOCUS] INFECTIOUS DISEASE: Costs of Meningitis Outbreaks Are Crippling, Too
    One illness in a family can exact a huge toll on household income, not only in direct costs but indirect ones as well, including loss of income and property such as cattle and crops.

    Author: Leslie Roberts

  • [NEWS FOCUS] INFECTIOUS DISEASE: Clinical Trials: Dispelling Suspicions, Building Trust in Mali
    Across West Africa, suspicions of Western medicine--and in particular the fear of being used as a guinea pig in clinical trials--run high. So winning the trust of the local community to enlist participants in clinical trials and ensure that consent is truly informed is a task that can't be undertaken lightly.

    Author: Leslie Roberts

  • [NEWS FOCUS] EVOLUTION: Building the Tree of Life, Genome by Genome
    Cheaper sequencing has put many more genes into the hands of researchers trying to sort out the degree of relatedness of a menagerie of organisms. Thanks to one such "phylogenomic" analysis reported on page 1763 of this week's issue of Science, bird guides may never be the same.

    Author: Elizabeth Pennisi

  • [LETTERS] The Verbosity Epidemic


    Authors: Rebecca F. Grais, E. A. Ashley, N. J. White

  • [LETTERS] The Future of the CMJ


    Authors: Matko Marušić, Ana Marušić

  • [LETTERS] The Case Against the CMJ's Editors


    Author: Nada Čikeš

  • [LETTERS] Making Memories, Again


    Authors: Nathaniel Lasry, Emmanuelle Levy, Jacques Tremblay

  • [LETTERS] Don't Forget the Fungi


    Author: Susan Goldhor

  • [LETTERS] Corrections and Clarifications


  • [BOOKS ET AL.] COMMUNICATING SCIENCE: Peaks of 20th-Century Presentation
    These selections from writings by researchers over the past century cover such topics as what scientists study, who they are, what they think, and what they find delight in.

    Author: Hanne Andersen

  • [BOOKS ET AL.] SCIENCE AND THE LAW: Compelling Cases for Change
    Discussing a number of high-profile cases, the author argues that current forensic practices fall far short of the field's public perceptions and potential.

    Author: C. Michael Bowers

  • [BOOKS ET AL.] Books Received


  • [EDUCATION FORUM] THE EARLY YEARS: Preschool Programs Can Boost School Readiness
    Preschool programs in Oklahoma help children to succeed in school.

    Authors: William T. Gormley Jr., Deborah Phillips, Ted Gayer

  • [PERSPECTIVES] BIOCHEMISTRY: Metamorphic Proteins
    Proteins that can adopt more than one native folded conformation may be more common than previously thought.

    Author: Alexey G. Murzin

  • [PERSPECTIVES] CELL BIOLOGY: Arrestin' Movement in Cilia
    A signaling protein localizes to primary cilia through its interaction with a complex that contains a motor protein.

    Authors: Rajat Rohatgi, Matthew P. Scott

  • [PERSPECTIVES] ATMOSPHERIC SCIENCE: Himalaya--Carbon Sink or Source?
    Chemical analysis of hot springs in the Himalaya suggest that the carbon released from mountain forming regions may warm Earth.

    Authors: Jerome Gaillardet, Albert Galy

  • [PERSPECTIVES] MATERIALS SCIENCE: The Statistical Mechanics of Strain-Hardened Metals
    The average distance that dislocations in crystals travel before freezing into place is a key quantity in describing how metals harden when strained.

    Author: Anter El-Azab

  • [PERSPECTIVES] BIOCHEMISTRY: Electron Relay in Proteins
    Electron transfer in proteins can be accelerated by electron relay along a chain of residues.

    Author: J. Martin Bollinger Jr.

  • [AAAS AFFAIRS] AAAS News and Notes
    A monthly roundup of recent news and projects of Science's publisher, the American Association for the Advancement of Science.

    Author:

  • [REVIEWS] Quantum State Engineering and Precision Metrology Using State-Insensitive Light Traps


    Authors: Jun Ye, H. J. Kimble, Hidetoshi Katori

  • [BREVIA] Serotonin Modulates Behavioral Reactions to Unfairness
    Individuals with low levels of brain serotonin are less likely to accept an unfair offer of money from other players in a laboratory game.

    Authors: Molly J. Crockett, Luke Clark, Golnaz Tabibnia, Matthew D. Lieberman, Trevor W. Robbins

  • [RESEARCH ARTICLES] Deep Drilling into the Chesapeake Bay Impact Structure
    Drill cores from the Chesapeake Bay impact crater reveal that the impact moved huge blocks of country rock, trapped salty pore water, and still affects microbial communities.

    Authors: G. S. Gohn, C. Koeberl, K. G. Miller, W. U. Reimold, J. V. Browning, C. S. Cockell, J. W. Horton Jr., T. Kenkmann, A. A. Kulpecz, D. S. Powars, W. E. Sanford, M. A. Voytek

  • [REPORTS] Dislocation Mean Free Paths and Strain Hardening of Crystals
    Simulations of the motions of atomic dislocations in a face-centered cubic metal allow these dynamics to be related to the metal's bulk strength and deformation.

    Authors: B. Devincre, T. Hoc, L. Kubin

  • [REPORTS] Ordered Mesoporous Materials from Metal Nanoparticle–Block Copolymer Self-Assembly
    A polymer and platinum nanoparticles stabilized with a ligand form large lamellar or inverse hexagonal structures that can be fused to create porous platinum-carbon composites.

    Authors: Scott C. Warren, Lauren C. Messina, Liane S. Slaughter, Marleen Kamperman, Qin Zhou, Sol M. Gruner, Francis J. DiSalvo, Ulrich Wiesner

  • [REPORTS] Very-High-Energy gamma rays from a Distant Quasar: How Transparent Is the Universe?
    Observation of gamma rays from a quasar 5 billion light-years away implies that the background light in the universe is consistent with surveys of stars and galaxies.

    Authors: The MAGIC Collaboration, The MAGIC Collaboration, J. Albert, E. Aliu, H. Anderhub, L. A. Antonelli, P. Antoranz, M. Backes, C. Baixeras, J. A. Barrio, H. Bartko, D. Bastieri, J. K. Becker, W. Bednarek, K. Berger, E. Bernardini, C. Bigongiari, A. Biland, R. K. Bock, G. Bonnoli, P. Bordas, V. Bosch-Ramon, T. Bretz, I. Britvitch, M. Camara, E. Carmona, A. Chilingarian, S. Commichau, J. L. Contreras, J. Cortina, M. T. Costado, S. Covino, V. Curtef, F. Dazzi, A. De Angelis, E. De Cea del Pozo, R. de los Reyes, B. De Lotto, M. De Maria, F. De Sabata, C. Delgado Mendez, A. Dominguez, D. Dorner, M. Doro, M. Errando, M. Fagiolini, D. Ferenc, E. Fernández, R. Firpo, M. V. Fonseca, L. Font, N. Galante, R. J. García López, M. Garczarczyk, M. Gaug, F. Goebel, M. Hayashida, A. Herrero, D. Höhne, J. Hose, C. C. Hsu, S. Huber, T. Jogler, T. M. Kneiske, D. Kranich, A. La Barbera, A. Laille, E. Leonardo, E. Lindfors, S. Lombardi, F. Longo, M. López, E. Lorenz, P. Majumdar, G. Maneva, N. Mankuzhiyil, K. Mannheim, L. Maraschi, M. Mariotti, M. Martínez, D. Mazin, M. Meucci, M. Meyer, J. M. Miranda, R. Mirzoyan, S. Mizobuchi, M. Moles, A. Moralejo, D. Nieto, K. Nilsson, J. Ninkovic, N. Otte, I. Oya, M. Panniello, R. Paoletti, J. M. Paredes, M. Pasanen, D. Pascoli, F. Pauss, R. G. Pegna, M. A. Perez-Torres, M. Persic, L. Peruzzo, A. Piccioli, F. Prada, E. Prandini, N. Puchades, A. Raymers, W. Rhode, M. Ribó, J. Rico, M. Rissi, A. Robert, S. Rügamer, A. Saggion, T. Y. Saito, M. Salvati, M. Sanchez-Conde, P. Sartori, K. Satalecka, V. Scalzotto, V. Scapin, R. Schmitt, T. Schweizer, M. Shayduk, K. Shinozaki, S. N. Shore, N. Sidro, A. Sierpowska-Bartosik, A. Sillanpää, D. Sobczynska, F. Spanier, A. Stamerra, L. S. Stark, L. Takalo, F. Tavecchio, P. Temnikov, D. Tescaro, M. Teshima, M. Tluczykont, D. F. Torres, N. Turini, H. Vankov, A. Venturini, V. Vitale, R. M. Wagner, W. Wittek, V. Zabalza, F. Zandanel, R. Zanin, J. Zapatero

  • [REPORTS] The Role of Interstitial Sites in the Ti3d Defect State in the Band Gap of Titania
    Scanning tunneling microscope data and calculations show that near-surface titanium sites, not bridging oxygen vacancies, determine the useful electronic properties of TiO2.

    Authors: Stefan Wendt, Phillip T. Sprunger, Estephania Lira, Georg K. H. Madsen, Zheshen Li, Jonas Ø. Hansen, Jesper Matthiesen, Asger Blekinge-Rasmussen, Erik Lægsgaard, Bjørk Hammer, Flemming Besenbacher

  • [REPORTS] Tryptophan-Accelerated Electron Flow Through Proteins
    A tryptophan residue placed between a donor and acceptor in a protein acts as a relay and accelerates long-distance electron transfer by more than a factor of 100.

    Authors: Crystal Shih, Anna Katrine Museth, Malin Abrahamsson, Ana Maria Blanco-Rodriguez, Angel J. Di Bilio, Jawahar Sudhamsu, Brian R. Crane, Kate L. Ronayne, Mike Towrie, Antonín Vlček Jr., John H. Richards, Jay R. Winkler, Harry B. Gray

  • [REPORTS] A Phylogenomic Study of Birds Reveals Their Evolutionary History
    Nuclear DNA sequences of 19 loci from 169 bird species lead to a revised phylogenetic tree of avian evolution, in which several well-accepted orders are not monophyletic.

    Authors: Shannon J. Hackett, Rebecca T. Kimball, Sushma Reddy, Rauri C. K. Bowie, Edward L. Braun, Michael J. Braun, Jena L. Chojnowski, W. Andrew Cox, Kin-Lan Han, John Harshman, Christopher J. Huddleston, Ben D. Marks, Kathleen J. Miglia, William S. Moore, Frederick H. Sheldon, David W. Steadman, Christopher C. Witt, Tamaki Yuri

  • [REPORTS] A Significant Upward Shift in Plant Species Optimum Elevation During the 20th Century
    A 100-year survey shows that the optimal elevations for growth of plant species in European temperate forests have shifted upward by about 30 meters per decade.

    Authors: J. Lenoir, J. C. Gégout, P. A. Marquet, P. de Ruffray, H. Brisse

  • [REPORTS] Polarization of the C. elegans Embryo by RhoGAP-Mediated Exclusion of PAR-6 from Cell Contacts
    Exclusion of a regulatory protein from cell-cell contacts in the developing worm allows it to direct the assembly of an asymmetrical cytoskeleton in preparation for gastrulation.

    Authors: Dorian C. Anderson, Jason S. Gill, Ryan M. Cinalli, Jeremy Nance

  • [REPORTS] FGF-Dependent Mechanosensory Organ Patterning in Zebrafish
    A fish sensory organ develops when a wave of migrating primordial cells cyclically deposits rosettes of differentiated cells under the influence of fibroblast growth factor.

    Authors: Alex Nechiporuk, David W. Raible

  • [REPORTS] β-Arrestin–Mediated Localization of Smoothened to the Primary Cilium
    β-arrestin, which has several known roles in signaling systems, also links a key receptor to a motor protein so that the receptor can be transported to cilia for sensing environmental cues.

    Authors: Jeffrey J. Kovacs, Erin J. Whalen, Renshui Liu, Kunhong Xiao, Jihee Kim, Minyong Chen, Jiangbo Wang, Wei Chen, Robert J. Lefkowitz

  • [REPORTS] Both Catalytic Steps of Nuclear Pre-mRNA Splicing Are Reversible
    The transesterification splicing reactions performed on RNA by the spliceosome protein complex in eukaryotic cells are reversible.

    Authors: Chi-Kang Tseng, Soo-Chen Cheng

  • [REPORTS] Virus Attenuation by Genome-Scale Changes in Codon Pair Bias
    Altering the frequency of the adjacent codons in the poliovirus genome results in an attenuated virus that could form the basis of a vaccine.

    Authors: J. Robert Coleman, Dimitris Papamichail, Steven Skiena, Bruce Futcher, Eckard Wimmer, Steffen Mueller

  • [REPORTS] Paleo-Eskimo mtDNA Genome Reveals Matrilineal Discontinuity in Greenland
    Ancient human DNA sequences from Greenland suggest that the earliest inhabitants of the far north were from a lineage distinct from extant Native Americans and Eskimos.

    Authors: M. Thomas P. Gilbert, Toomas Kivisild, Bjarne Grønnow, Pernille K. Andersen, Ene Metspalu, Maere Reidla, Erika Tamm, Erik Axelsson, Anders Götherström, Paula F. Campos, Morten Rasmussen, Mait Metspalu, Thomas F. G. Higham, Jean-Luc Schwenninger, Roger Nathan, Cees-Jan De Hoog, Anders Koch, Lone Nukaaraq Møller, Claus Andreasen, Morten Meldgaard, Richard Villems, Christian Bendixen, Eske Willerslev

  • NEW PRODUCTS


  • [PODCASTS] Science Podcast
    Author:

Cell
Volume 133, Issue 7
About the site | Terms of service | Privacy policy | Ad Sponsorship | Contact us

Copyright 2000-2008 Biowww.net, All rights reserved