Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160.

The envelope glycoprotein of human immunodeficiency virus (HIV) initiates infection by mediating fusion of the viral envelope with the cell membrane. Fusion activity requires proteolytic cleavage of the gp160 protein into gp120 and gp41 at a site containing several arginine and lysine residues. Activation at basic cleavage sites is observed with many membrane proteins of cellular and viral origin. We have recently found that the enzyme activating the haemagglutinin of fowl plague virus (FPV), an avian influenza virus, is furin. Furin, a subtilisin-like eukaryotic endoprotease, has a substrate specificity for the consensus amino-acid sequence Arg-X-Lys/Arg-Arg at the cleavage site. We show here that the glycoprotein of HIV-1, which has the same protease recognition motif as the FPV haemagglutinin, is also activated by furin.     

A common model approach to macroeconomics: using panel data to reduce sampling error

Is there a common model inherent in macroeconomic data? Macroeconomic theory suggests that market economies of various nations should share many similar dynamic patterns; as a result, individual country empirical models, for a wide variety of countries, often include the same variables. Yet, empirical studies often find important roles for idiosyncratic shocks in the differing macroeconomic performance of countries. We use forecasting criteria to examine the macrodynamic behaviour of 15 OECD countries in terms of a small set of familiar, widely used core economic variables, omitting country‐specific shocks. We find this small set of variables and a simple VAR ‘common model’ strongly support the hypothesis that many industrialized nations have similar macroeconomic dynamics. Copyright © 2005 John Wiley & Sons, Ltd.     

Knowledge transfer in theoretical ecology: Implications for incommensurability,voluntarism, and pluralism

Well-known epistemologies of science have implications for how best to understand knowledge transfer (KT). Yet, to date, no serious attempt has been made to explicate these particular implications. This paper infers views about KT from two popular epistemologies; what we characterize as incommensurabilitist views (after Devitt, 2001; Bird, 2002, 2008; Sankey and Hoyningen-Huene 2013) and voluntarist views (after Van Fraassen, 1984; Dupré, 2001; Chakravartty, 2015). We argue views of the former sort define the methodological, ontological, and social conditions under which research operates within ‘different worlds’ (to use Kuhn's expression), and entail that genuine KTs under those conditions should be difficult or even impossible. By contrast, more liberal voluntarist views recognize epistemological processes that allow for transfers across different sciences even under such conditions. After outlining these antithetical positions, we identify two kinds of KTs present in well-known episodes in the history of ecology—specifically, successful model transfers from chemical kinetics and thermodynamics into areas of ecological research—which reveal significant limitations of incommensurabilitist views. We conclude by discussing how the selected examples support a pluralistic voluntarism regarding KT.     

The volcanoes of Auvergne

It is with good reason that the name Rutherford is closely linked with the early history of the alpha particle. He discovered them, determined their nature, and from 1909 used them to probe the structure of the atom. From 1898 to 1902 Rutherford construed alpha radiation as a type of non-particulate Röntgen radiation. On his theory of the locomotion of radioactive particles Rutherford proposed that alpha radiation consisted of negatively charged particles. During 1902 he confirmed the particulate nature of alpha radiation but discovered that these alpha particles were positively charged. Although Rutherford suspected from 1903 that these alpha particles were related somehow with helium, the proof required six long years of investigation. By mid-1908 it seemed certain that the alpha particle possessed two units of the elementary charge. Since the e/m ratio had already been determined for alpha particles, this evidence enhanced the suspected connection with helium. However, this gain and loss of charge was still construed as an ionization effect. Since as late as 1908 gaseous ionization was assumed to involve the gain or loss of a single unit of charge, Rutherford's alleged case of doubly ionized alpha particles was presumably an exception. Yet helium was known to be an inert gas and thus hardly a likely candidate for such exceptional ionization behaviour. To establish the connection, therefore, Rutherford resorted to a spectroscopic test. He collected spent alpha particles shot into a thin glass tube and gradually observed the spectrum of helium. Rutherford had thus been correct in his assumption, but a proper explanation was possible only after the confirmation of the nuclear structure of the atom.     

A P-type ATPase required for rice blast disease and induction of host resistance

To cause diseases in plants, pathogenic microorganisms have evolved mechanisms to deliver proteins directly into plant cells, where they suppress plant defences and facilitate tissue invasion. How plant pathogenic fungi, which cause many of the world's most serious plant diseases, deliver proteins during plant infection is currently unknown. Here we report the characterization of a P-type ATPase-encoding gene, MgAPT2, in the economically important rice blast pathogen Magnaporthe grisea, which is required for exocytosis during plant infection. Targeted gene replacement showed that MgAPT2 is required for both foliar and root infection by the fungus, and for the rapid induction of host defence responses in an incompatible reaction. DeltaMgapt2 mutants are impaired in the secretion of a range of extracellular enzymes and accumulate abnormal Golgi-like cisternae. However, the loss of MgAPT2 does not significantly affect hyphal growth or sporulation, indicating that the establishment of rice blast disease involves the use of MgApt2-dependent exocytotic processes that operate during plant infection.     

Human immunodeficiency viruses: SIV infection in wild gorillas

Chimpanzees (Pan troglodytes troglodytes) from west central Africa are recognized as the reservoir of simian immunodeficiency viruses (SIVcpzPtt) that have crossed at least twice to humans: this resulted in the AIDS pandemic (from human immunodeficiency virus HIV-1 group M) in one instance and infection of just a few individuals in Cameroon (by HIV-1 group N) in another. A third HIV-1 lineage (group O) from west central Africa also falls within the SIVcpzPtt radiation, but the primate reservoir of this virus has not been identified. Here we report the discovery of HIV-1 group O-like viruses in wild gorillas.     

Proteome survey reveals modularity of the yeast cell machinery

Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry. Through systematic tagging of open reading frames (ORFs), the majority of complexes were purified several times, suggesting screen saturation. The richness of the data set enabled a de novo characterization of the composition and organization of the cellular machinery. The ensemble of cellular proteins partitions into 491 complexes, of which 257 are novel, that differentially combine with additional attachment proteins or protein modules to enable a diversification of potential functions. Support for this modular organization of the proteome comes from integration with available data on expression, localization, function, evolutionary conservation, protein structure and binary interactions. This study provides the largest collection of physically determined eukaryotic cellular machines so far and a platform for biological data integration and modelling.     

Immunology: Toll-like receptors and antibody responses

Microbial components, such as lipopolysaccharides, augment immune responses by activating Toll-like receptors (TLRs). Some have interpreted this to mean that TLR signalling might not only help to initiate the adaptive immune response, but may also be required for it. The expanded view is shared by Pasare and Medzhitov, who conclude from an analysis of mice deficient in MyD88 (a TLR-signalling adaptor protein) that the generation of T-dependent antigen-specific antibody responses requires activation of TLRs in B cells. However, we show here that robust antibody responses can be elicited even in the absence of TLR signals. This appreciable TLR-independence of immune responses should be taken into account in the rational design of immunogenic and toleragenic vaccines.     

An exceptional Devonian fish from Australia sheds light on tetrapod origins

The transition from fishes to tetrapods was one of the most dramatic events in the evolution of vertebrates, but many pivotal fossils are incomplete, resulting in gaps in the data that are used for phylogenetic reconstruction. Here we present new observations from the most complete, acid-prepared Devonian tetrapodomorph fish yet discovered, Gogonasus, which was previously placed just crownward of Kenichthys and rhizodontids, the most primitive taxa on the tetrapod lineage. Unexpectedly, Gogonasus shows a mosaic of plesiomorphic and derived tetrapod-like features. Whereas the braincase and dermal cranial skeleton exhibit generalized morphologies with respect to Eusthenopteron or Panderichthys, taxa that are traditionally considered to be phyletically close to tetrapods, the presence of a deeply invaginated, wide spiracle, advanced internal spiracular architecture and near-horizontal hyomandibula are specialized features that are absent from Eusthenopteron. Furthermore, the pectoral fin skeleton of Gogonasus shares several features with that of Tiktaalik, the most tetrapod-like fish. A new phylogenetic analysis places Gogonasus crownward of Eusthenopteron as the sister taxon to the Elpistostegalia. Aspects of the basic tetrapod limb skeleton and middle ear architecture can now be traced further back within the tetrapodomorph radiation.