Enzymatic capture of an extrahelical thymine in the search for uracil in DNA

The enzyme uracil DNA glycosylase (UNG) excises unwanted uracil bases in the genome using an extrahelical base recognition mechanism. Efficient removal of uracil is essential for prevention of C-to-T transition mutations arising from cytosine deamination, cytotoxic U*A pairs arising from incorporation of dUTP in DNA, and for increasing immunoglobulin gene diversity during the acquired immune response. A central event in all of these UNG-mediated processes is the singling out of rare U*A or U*G base pairs in a background of approximately 10(9) T*A or C*G base pairs in the human genome. Here we establish for the human and Escherichia coli enzymes that discrimination of thymine and uracil is initiated by thermally induced opening of T*A and U*A base pairs and not by active participation of the enzyme. Thus, base-pair dynamics has a critical role in the genome-wide search for uracil, and may be involved in initial damage recognition by other DNA repair glycosylases.     

Female mate-choice drives the evolution of male-biased dispersal in a social mammal

Dispersal has a significant impact on lifetime reproductive success, and is often more prevalent in one sex than the other. In group-living mammals, dispersal is normally male-biased and in theory this sexual bias could be a response by males to female mate preferences, competition for access to females or resources, or the result of males avoiding inbreeding. There is a lack of studies on social mammals that simultaneously assess these factors and measure the fitness consequences of male dispersal decisions. Here we show that male-biased dispersal in the spotted hyaena (Crocuta crocuta) most probably results from an adaptive response by males to simple female mate-choice rules that have evolved to avoid inbreeding. Microsatellite profiling revealed that females preferred sires that were born into or immigrated into the female's group after the female was born. Furthermore, young females preferred short-tenured sires and older females preferred longer-tenured sires. Males responded to these female mate preferences by initiating their reproductive careers in groups containing the highest number of young females. As a consequence, 11% of males started their reproductive career in their natal group and 89% of males dispersed. Males that started reproduction in groups containing the highest number of young females had a higher long-term reproductive success than males that did not. The female mate-choice rules ensured that females effectively avoided inbreeding without the need to discriminate directly against close kin or males born in their own group, or to favour immigrant males. The extent of male dispersal as a response to such female mate preferences depends on the demographic structure of breeding groups, rather than the genetic relatedness between females and males.     

BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module

Engulfment and subsequent degradation of apoptotic cells is an essential step that occurs throughout life in all multicellular organisms. ELMO/Dock180/Rac proteins are a conserved signalling module for promoting the internalization of apoptotic cell corpses; ELMO and Dock180 function together as a guanine nucleotide exchange factor (GEF) for the small GTPase Rac, and thereby regulate the phagocyte actin cytoskeleton during engulfment. However, the receptor(s) upstream of the ELMO/Dock180/Rac module are still unknown. Here we identify brain-specific angiogenesis inhibitor 1 (BAI1) as a receptor upstream of ELMO and as a receptor that can bind phosphatidylserine on apoptotic cells. BAI1 is a seven-transmembrane protein belonging to the adhesion-type G-protein-coupled receptor family, with an extended extracellular region and no known ligands. We show that BAI1 functions as an engulfment receptor in both the recognition and subsequent internalization of apoptotic cells. Through multiple lines of investigation, we identify phosphatidylserine, a key 'eat-me' signal exposed on apoptotic cells, as a ligand for BAI1. The thrombospondin type 1 repeats within the extracellular region of BAI1 mediate direct binding to phosphatidylserine. As with intracellular signalling, BAI1 forms a trimeric complex with ELMO and Dock180, and functional studies suggest that BAI1 cooperates with ELMO/Dock180/Rac to promote maximal engulfment of apoptotic cells. Last, decreased BAI1 expression or interference with BAI1 function inhibits the engulfment of apoptotic targets ex vivo and in vivo. Thus, BAI1 is a phosphatidylserine recognition receptor that can directly recruit a Rac-GEF complex to mediate the uptake of apoptotic cells.     

Attribution of observed surface humidity changes to human influence

Water vapour is the most important contributor to the natural greenhouse effect, and the amount of water vapour in the atmosphere is expected to increase under conditions of greenhouse-gas-induced warming, leading to a significant feedback on anthropogenic climate change. Theoretical and modelling studies predict that relative humidity will remain approximately constant at the global scale as the climate warms, leading to an increase in specific humidity. Although significant increases in surface specific humidity have been identified in several regions, and on the global scale in non-homogenized data, it has not been shown whether these changes are due to natural or human influences on climate. Here we use a new quality-controlled and homogenized gridded observational data set of surface humidity, with output from a coupled climate model, to identify and explore the causes of changes in surface specific humidity over the late twentieth century. We identify a significant global-scale increase in surface specific humidity that is attributable mainly to human influence. Specific humidity is found to have increased in response to rising temperatures, with relative humidity remaining approximately constant. These changes may have important implications, because atmospheric humidity is a key variable in determining the geographical distribution and maximum intensity of precipitation, the potential maximum intensity of tropical cyclones, and human heat stress, and has important effects on the biosphere and surface hydrology.     

Metagenomic and functional analysis of hindgut microbiota of a wood-feeding higher termite

From the standpoints of both basic research and biotechnology, there is considerable interest in reaching a clearer understanding of the diversity of biological mechanisms employed during lignocellulose degradation. Globally, termites are an extremely successful group of wood-degrading organisms and are therefore important both for their roles in carbon turnover in the environment and as potential sources of biochemical catalysts for efforts aimed at converting wood into biofuels. Only recently have data supported any direct role for the symbiotic bacteria in the gut of the termite in cellulose and xylan hydrolysis. Here we use a metagenomic analysis of the bacterial community resident in the hindgut paunch of a wood-feeding 'higher' Nasutitermes species (which do not contain cellulose-fermenting protozoa) to show the presence of a large, diverse set of bacterial genes for cellulose and xylan hydrolysis. Many of these genes were expressed in vivo or had cellulase activity in vitro, and further analyses implicate spirochete and fibrobacter species in gut lignocellulose degradation. New insights into other important symbiotic functions including H2 metabolism, CO2-reductive acetogenesis and N2 fixation are also provided by this first system-wide gene analysis of a microbial community specialized towards plant lignocellulose degradation. Our results underscore how complex even a 1-microl environment can be.     

Coherent zero-state and pi-state in an exciton-polariton condensate array

The effect of quantum statistics in quantum gases and liquids results in observable collective properties among many-particle systems. One prime example is Bose-Einstein condensation, whose onset in a quantum liquid leads to phenomena such as superfluidity and superconductivity. A Bose-Einstein condensate is generally defined as a macroscopic occupation of a single-particle quantum state, a phenomenon technically referred to as off-diagonal long-range order due to non-vanishing off-diagonal components of the single-particle density matrix. The wavefunction of the condensate is an order parameter whose phase is essential in characterizing the coherence and superfluid phenomena. The long-range spatial coherence leads to the existence of phase-locked multiple condensates in an array of superfluid helium, superconducting Josephson junctions or atomic Bose-Einstein condensates. Under certain circumstances, a quantum phase difference of pi is predicted to develop among weakly coupled Josephson junctions. Such a meta-stable pi-state was discovered in a weak link of superfluid 3He, which is characterized by a 'p-wave' order parameter. The possible existence of such a pi-state in weakly coupled atomic Bose-Einstein condensates has also been proposed, but remains undiscovered. Here we report the observation of spontaneous build-up of in-phase ('zero-state') and antiphase ('pi-state') 'superfluid' states in a solid-state system; an array of exciton-polariton condensates connected by weak periodic potential barriers within a semiconductor microcavity. These in-phase and antiphase states reflect the band structure of the one-dimensional polariton array and the dynamic characteristics of metastable exciton-polariton condensates.     

Radio-frequency scanning tunnelling microscopy

The scanning tunnelling microscope (STM) relies on localized electron tunnelling between a sharp probe tip and a conducting sample to attain atomic-scale spatial resolution. In the 25-year period since its invention, the STM has helped uncover a wealth of phenomena in diverse physical systems--ranging from semiconductors to superconductors to atomic and molecular nanosystems. A severe limitation in scanning tunnelling microscopy is the low temporal resolution, originating from the diminished high-frequency response of the tunnel current readout circuitry. Here we overcome this limitation by measuring the reflection from a resonant inductor-capacitor circuit in which the tunnel junction is embedded, and demonstrate electronic bandwidths as high as 10 MHz. This approximately 100-fold bandwidth improvement on the state of the art translates into fast surface topography as well as delicate measurements in mesoscopic electronics and mechanics. Broadband noise measurements across the tunnel junction using this radio-frequency STM have allowed us to perform thermometry at the nanometre scale. Furthermore, we have detected high-frequency mechanical motion with a sensitivity approaching approximately 15 fm Hz(-1/2). This sensitivity is on par with the highest available from nanoscale optical and electrical displacement detection techniques, and the radio-frequency STM is expected to be capable of quantum-limited position measurements.