Lateral presynaptic inhibition mediates gain control in an olfactory circuit

Olfactory signals are transduced by a large family of odorant receptor proteins, each of which corresponds to a unique glomerulus in the first olfactory relay of the brain. Crosstalk between glomeruli has been proposed to be important in olfactory processing, but it is not clear how these interactions shape the odour responses of second-order neurons. In the Drosophila antennal lobe (a region analogous to the vertebrate olfactory bulb), we selectively removed most interglomerular input to genetically identified second-order olfactory neurons. Here we show that this broadens the odour tuning of these neurons, implying that interglomerular inhibition dominates over interglomerular excitation. The strength of this inhibitory signal scales with total feedforward input to the entire antennal lobe, and has similar tuning in different glomeruli. A substantial portion of this interglomerular inhibition acts at a presynaptic locus, and our results imply that this is mediated by both ionotropic and metabotropic receptors on the same nerve terminal.     

Observed and modelled stability of overflow across the Greenland-Scotland ridge

Across the Greenland-Scotland ridge there is a continuous flow of cold dense water, termed 'overflow', from the Nordic seas to the Atlantic Ocean. This is a main contributor to the production of North Atlantic Deep Water that feeds the lower limb of the Atlantic meridional overturning circulation, which has been predicted to weaken as a consequence of climate change. The two main overflow branches pass the Denmark Strait and the Faroe Bank channel. Here we combine results from direct current measurements in the Faroe Bank channel for 1995-2005 with an ensemble hindcast experiment for 1948-2005 using an ocean general circulation model. For the overlapping period we find a convincing agreement between model simulations and observations on monthly to interannual timescales. Both observations and model data show no significant trend in volume transport. In addition, for the whole 1948-2005 period, the model indicates no persistent trend in the Faroe Bank channel overflow or in the total overflow transport, in agreement with the few available historical observations. Deepening isopycnals in the Norwegian Sea have tended to decrease the pressure difference across the Greenland-Scotland ridge, but this has been compensated for by the effect of changes in sea level. In contrast with earlier studies, we therefore conclude that the Faroe Bank channel overflow, and also the total overflow, did not decrease consistently from 1950 to 2005, although the model does show a weakening total Atlantic meridional overturning circulation as a result of changes south of the Greenland-Scotland ridge.     

Structure and function of human perforin

Perforin (P1) is a cytolytic protein with similarity to complement component C9. P1 has been described as a unique component of murine cytolytic T-cell and rat natural killer cell granules Previous studies indicated that human granules and P1 differed from murine granules and P1 in that they appeared to be cytolytically less active and lacked the haemolytic activity characteristic of P1. It has been suggested that P1, like C9, is under the control of the homologous restriction factor. Here we determine the primary structure of human P1, re-examine its functional properties, and address the question of homologous restriction.     

N″-cyano-N-4-pyridyl-N′-1,2,2-trimethylpropylguanidine,monohydrate (P 1134): A new,potent vasodilator

Summary N-cyano-N-4-pyridyl-N-1,2,2-trimethylpropylguanidine, monohydrate (P 1134) is a new agent which induces a marked and sustained hypotensive response in normotensive and renal, neurogenic, and spontaneously hypertensive rats, as well as in normotensive and renal hypertensive dogs. The overall potency of this compound is 2–3 times greater than that of hydralazine. The fall of blood pressure is accompanied by an increase in heart rate and cardiac output and a decrease in total peripheral resistance. The hypotensive effect appears to be due primarily to a direct relaxant effect on vascular smooth muscle.Acknowledgment. The helpful comments and advice of Dr W.O. Godtfredsen are greatefully acknowledged.     

Behaviour of intrinsically disordered proteins in protein–protein complexes with an emphasis on fuzziness

Intrinsically disordered proteins (IDPs) do not, by themselves, fold into a compact globular structure. They are extremely dynamic and flexible, and are typically involved in signalling and transduction of information through binding to other macromolecules. The reason for their existence may lie in their malleability, which enables them to bind several different partners with high specificity. In addition, their interactions with other macromolecules can be regulated by a variable amount of chemically diverse post-translational modifications. Four kinetically and energetically different types of complexes between an IDP and another macromolecule are reviewed: (1) simple two-state binding involving a single binding site, (2) avidity, (3) allovalency and (4) fuzzy binding; the last three involving more than one site. Finally, a qualitative definition of fuzzy binding is suggested, examples are provided, and its distinction to allovalency and avidity is highlighted and discussed.     

The native architecture of a photosynthetic membrane

In photosynthesis, the harvesting of solar energy and its subsequent conversion into a stable charge separation are dependent upon an interconnected macromolecular network of membrane-associated chlorophyll-protein complexes. Although the detailed structure of each complex has been determined, the size and organization of this network are unknown. Here we show the use of atomic force microscopy to directly reveal a native bacterial photosynthetic membrane. This first view of any multi-component membrane shows the relative positions and associations of the photosynthetic complexes and reveals crucial new features of the organization of the network: we found that the membrane is divided into specialized domains each with a different network organization and in which one type of complex predominates. Two types of organization were found for the peripheral light-harvesting LH2 complex. In the first, groups of 10-20 molecules of LH2 form light-capture domains that interconnect linear arrays of dimers of core reaction centre (RC)-light-harvesting 1 (RC-LH1-PufX) complexes; in the second they were found outside these arrays in larger clusters. The LH1 complex is ideally positioned to function as an energy collection hub, temporarily storing it before transfer to the RC where photochemistry occurs: the elegant economy of the photosynthetic membrane is demonstrated by the close packing of these linear arrays, which are often only separated by narrow 'energy conduits' of LH2 just two or three complexes wide.     

120-150 ka human tooth and ivory engravings from Xinglongdong Cave, Three Gorges Region, South China

Rich paleoanthropological materials were unearthed in primary context from the Xinglongdong Cave in Fengjie County, Chongqing, South China, including a human tooth, numerous mammalian fossils, some stone artifacts and a Stegodon tusk exhibiting intentional engravings.Based on biostratigraphic data and uranium series dating,the cave was utilized as a human shelter about 120000-150000 years ago. It is the first time that an archaic Homo sapiens fossil has been unearthed from the Three Gorges Region. Engravings on the Stegodon tusk appear in groups,making up simple and abstract images. It is the earliest known engravings created by human beings; it exhibits great potential for the study of the origin of art and the development of ancient cultures in south China and bears important implications for the origin of modern humans in East Asia.     

The genome of the social amoeba Dictyostelium discoideum

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.     

The roles of collagen genes in skeletal development and morphogenesis

Molecular genetic analyses of osteochondrodysplasias in mice and humans have recently led to the identification of mutations in genes encoding structural proteins growth factor receptors and sulphate transporters. Further analyses of such inherited disorders, using rapid techniques for gene mapping, positional cloning and mutation detection, will undoubtedly uncover other genes that are important for skeletal development. Together with studies of transgenic mice, in which specific genes that are expressed in the skeleton are mutated, these analyses will provide insight into genes that are essential for skeletal morphogenesis.