A physiological correlate of disuse-induced sprouting at the neuromuscular junction.

Recent investigations have established that many of the normal properties of muscle fibres are maintained, at least in part, by muscle activity. Thus, a fall in resting membrane potential, an increase in input resistance, and spread of acetylcholine receptors to extrajunctional sites can all be induced by abolishing muscle activity and prevented by direct stimulation of denervated muscle fibres. Muscle activity also exerts a trophic influence on the innervating motoneurones; furthermore it may be a factor in the regulation of sprouting. Brown and Ironton found fine, "ultra-terminal sprouts" emanating from the endplates of muscles rendered inactive by chronic conduction block of the muscle nerve. Pestronk and Drachman saw increased branching of the motor nerve terminal and a consequent increase in endplate size in similar conditions. If these sprouts at the endplates of inactive muscles were functional, one might expect more transmitter to be released in response to nerve stimulation. We report here that both quantum content and spontaneous miniature endplate potential (m.e.p.p) frequency are increased at the terminals of inactive (disused) muscles.     

Protein-folding location can regulate manganese-binding versus copper- or zinc-binding

Metals are needed by at least one-quarter of all proteins. Although metallochaperones insert the correct metal into some proteins, they have not been found for the vast majority, and the view is that most metalloproteins acquire their metals directly from cellular pools. However, some metals form more stable complexes with proteins than do others. For instance, as described in the Irving-Williams series, Cu(2+) and Zn(2+) typically form more stable complexes than Mn(2+). Thus it is unclear what cellular mechanisms manage metal acquisition by most nascent proteins. To investigate this question, we identified the most abundant Cu(2+)-protein, CucA (Cu(2+)-cupin A), and the most abundant Mn(2+)-protein, MncA (Mn(2+)-cupin A), in the periplasm of the cyanobacterium Synechocystis PCC 6803. Each of these newly identified proteins binds its respective metal via identical ligands within a cupin fold. Consistent with the Irving-Williams series, MncA only binds Mn(2+) after folding in solutions containing at least a 10(4) times molar excess of Mn(2+) over Cu(2+) or Zn(2+). However once MncA has bound Mn(2+), the metal does not exchange with Cu(2+). MncA and CucA have signal peptides for different export pathways into the periplasm, Tat and Sec respectively. Export by the Tat pathway allows MncA to fold in the cytoplasm, which contains only tightly bound copper or Zn(2+) (refs 10-12) but micromolar Mn(2+) (ref. 13). In contrast, CucA folds in the periplasm to acquire Cu(2+). These results reveal a mechanism whereby the compartment in which a protein folds overrides its binding preference to control its metal content. They explain why the cytoplasm must contain only tightly bound and buffered copper and Zn(2+).     

Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G

The human APOBEC3G (apolipoprotein B messenger-RNA-editing enzyme, catalytic polypeptide-like 3G) protein is a single-strand DNA deaminase that inhibits the replication of human immunodeficiency virus-1 (HIV-1), other retroviruses and retrotransposons. APOBEC3G anti-viral activity is circumvented by most retroelements, such as through degradation by HIV-1 Vif. APOBEC3G is a member of a family of polynucleotide cytosine deaminases, several of which also target distinct physiological substrates. For instance, APOBEC1 edits APOB mRNA and AID deaminates antibody gene DNA. Although structures of other family members exist, none of these proteins has elicited polynucleotide cytosine deaminase or anti-viral activity. Here we report a solution structure of the human APOBEC3G catalytic domain. Five alpha-helices, including two that form the zinc-coordinating active site, are arranged over a hydrophobic platform consisting of five beta-strands. NMR DNA titration experiments, computational modelling, phylogenetic conservation and Escherichia coli-based activity assays combine to suggest a DNA-binding model in which a brim of positively charged residues positions the target cytosine for catalysis. The structure of the APOBEC3G catalytic domain will help us to understand functions of other family members and interactions that occur with pathogenic proteins such as HIV-1 Vif.     

Increasing risk of Amazonian drought due to decreasing aerosol pollution

The Amazon rainforest plays a crucial role in the climate system, helping to drive atmospheric circulations in the tropics by absorbing energy and recycling about half of the rainfall that falls on it. This region (Amazonia) is also estimated to contain about one-tenth of the total carbon stored in land ecosystems, and to account for one-tenth of global, net primary productivity. The resilience of the forest to the combined pressures of deforestation and global warming is therefore of great concern, especially as some general circulation models (GCMs) predict a severe drying of Amazonia in the twenty-first century. Here we analyse these climate projections with reference to the 2005 drought in western Amazonia, which was associated with unusually warm North Atlantic sea surface temperatures (SSTs). We show that reduction of dry-season (July-October) rainfall in western Amazonia correlates well with an index of the north-south SST gradient across the equatorial Atlantic (the 'Atlantic N-S gradient'). Our climate model is unusual among current GCMs in that it is able to reproduce this relationship and also the observed twentieth-century multidecadal variability in the Atlantic N-S gradient, provided that the effects of aerosols are included in the model. Simulations for the twenty-first century using the same model show a strong tendency for the SST conditions associated with the 2005 drought to become much more common, owing to continuing reductions in reflective aerosol pollution in the Northern Hemisphere.     

Type IV collagens regulate BMP signalling in Drosophila

Dorsal-ventral patterning in vertebrate and invertebrate embryos is mediated by a conserved system of secreted proteins that establishes a bone morphogenetic protein (BMP) gradient. Although the Drosophila embryonic Decapentaplegic (Dpp) gradient has served as a model to understand how morphogen gradients are established, no role for the extracellular matrix has been previously described. Here we show that type IV collagen extracellular matrix proteins bind Dpp and regulate its signalling in both the Drosophila embryo and ovary. We provide evidence that the interaction between Dpp and type IV collagen augments Dpp signalling in the embryo by promoting gradient formation, yet it restricts the signalling range in the ovary through sequestration of the Dpp ligand. Together, these results identify a critical function of type IV collagens in modulating Dpp in the extracellular space during Drosophila development. On the basis of our findings that human type IV collagen binds BMP4, we predict that this role of type IV collagens will be conserved.     

An extraordinary new genus and species of spider wasps (Insecta: Hymenoptera: Pompilidae) from Southeast Asia

The new genus Aberropompilus Shimizu & Wahis, family Pompilidae, is described from Southeast Asia (Malaysia, Thailand) based on the new species A. dayi Shimizu & Wahis. Its peculiar morphological characteristics and taxonomic position within the family are discussed and the genus is tentatively placed in the subfamily Pepsinae.