The DNA sequence and biological annotation of human chromosome 1

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.     

Light adaptation in cone vision involves switching between receptor and post-receptor sites

We see over an enormous range of mean light levels, greater than the range of output signals retinal neurons can produce. Even highlights and shadows within a single visual scene can differ approximately 10,000-fold in intensity-exceeding the range of distinct neural signals by a factor of approximately 100. The effectiveness of daylight vision under these conditions relies on at least two retinal mechanisms that adjust sensitivity in the approximately 200 ms intervals between saccades. One mechanism is in the cone photoreceptors (receptor adaptation) and the other is at a previously unknown location within the retinal circuitry that benefits from convergence of signals from multiple cones (post-receptor adaptation). Here we find that post-receptor adaptation occurs as signals are relayed from cone bipolar cells to ganglion cells. Furthermore, we find that the two adaptive mechanisms are essentially mutually exclusive: as light levels increase the main site of adaptation switches from the circuitry to the cones. These findings help explain how human cone vision encodes everyday scenes, and, more generally, how sensory systems handle the challenges posed by a diverse physical environment.     

Skew of mantle upwelling beneath the East Pacific Rise governs segmentation

Mantle upwelling is essential to the generation of new oceanic crust at mid-ocean ridges, and it is generally assumed that such upwelling is symmetric beneath active ridges. Here, however, we use seismic imaging to show that the isotropic and anisotropic structure of the mantle is rotated beneath the East Pacific Rise. The isotropic structure defines the pattern of magma delivery from the mantle to the crust. We find that the segmentation of the rise crest between transform faults correlates well with the distribution of mantle melt. The azimuth of seismic anisotropy constrains the direction of mantle flow, which is rotated nearly 10 degrees anticlockwise from the plate-spreading direction. The mismatch between the locus of mantle melt delivery and the morphologic ridge axis results in systematic differences between areas of on-axis and off-axis melt supply. We conclude that the skew of asthenospheric upwelling and transport governs segmentation of the East Pacific Rise and variations in the intensity of ridge crest processes.     

New evidence that growth in 3T3 cell cultures is a diffusion-limited process

When a confluent culture of 3T3 cells is wounded, new growth occurs at the wound margins. This indicates that the suppression of growth in the intact confluent sheet is under local control, a phenomenon known as 'topoinhibition', and it has been suggested that intercellular contact is responsible. An alternative explanation for topoinhibition is possible, however, namely that a soluble factor necessary for growth is locally depleted from the medium by cells so that each cell in a confluent sheet normally receives an insufficient supply and its growth is inhibited. Here we show that the pattern of release from topoinhibition in a wounded culture can be distorted simply by inducing a gentle laminar flow of medium across the wound. Growth remains suppressed at the upstream margin of the wound despite the reduced level of intercellular contact at wound edges. We conclude that the signal for topoinhibition is carried by the flow as would be predicted if it were the local depletion of growth factor.     

Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta

The vascular endothelium, in response to pulsatile flow and vasoactive agents including acetylcholine, secretes the endothelium-derived relaxing factor (EDRF), a substance which regulates vascular tone. Recent interest in EDRF has focused on its possible dysfunction in atherosclerosis. In animal models of the disease, endothelium-dependent relaxation is markedly reduced. The continuous exposure of the endothelium in hyperlipidaemia to high concentrations of low-density lipoprotein (LDL), a known atherogenic risk factor, may explain this dysfunction. Here, we demonstrate that pathophysiological concentrations of LDL directly inhibit endothelium-dependent relaxation. Chemically modified LDL, in contrast, is inactive, implying that the inhibition is through a receptor-dependent mechanism.     

Effect of blood sampling methodology on plasma levels of corticosterone,inorganic phosphorus and serum 5-hydroxytryptamine concentrations

Zusammenfassung Nachweis, dass diverse konventionelle Methoden der Blutgewinnung (Herzpunktion, Dekapitieren, Punktion de Jugularvene) zu unterschiedlichen absoluten Werten von Serum Corticosteron, anorganischem Phosphat und 5-Hydroxytryptamin führen, wobei auch eine unterschiedliche Hämolyse resultierte.

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The technical assistance ofLaurel Marschall, Paul Millet andStanley Tsai is gratefully acknowledged.

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Supported by Louisiana Heart Association W. C. Feagel Research Award and U.S. Public Health Service grants No. NS08929 and No. AM12389-03.     

Proestrous gonadotropin levels in thyroparathyroidectomized female rats

Summary Intact and TPTx animals showed the expected afternoon increase in serum LH, FSH and prolactin levels. But the afternoon increase in serum LH levels in TPTx rats was less than that observed for intact animals (p<0.01). Neither serum prolactin nor FSH levels were altered by TPTx.The excellent technical and secretarial assistance ofS. Hemelt andD. Landman is gratefully acknowledged.