A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a relatively common neurodegenerative disease caused by homozygous loss of the survival motor neuron 1 (SMN1) gene. Humans possess a linked, nearly identical gene, SMN2, which produces a functional SMN protein but at levels insufficient to compensate for loss of SMN1 (refs. 1,2). A C/T transition at position +6 in exon 7 is all that differentiates the two genes, but this is sufficient to prevent efficient exon 7 splicing in SMN2 (refs. 2,3). Here we show that the C/T transition functions not to disrupt an exonic splicing enhancer (ESE) in SMN1 (ref. 4), as previously suggested, but rather to create an exonic splicing silencer (ESS) in SMN2. We show that this ESS functions as a binding site for a known repressor protein, hnRNP A1, which binds to SMN2 but not SMN1 exon 7 RNA. We establish the physiological importance of these results by using small interfering RNAs to reduce hnRNP A protein levels in living cells and show that this results in efficient SMN2 exon 7 splicing. Our findings not only define a new mechanism underlying the inefficient splicing of SMN2 exon 7 but also illustrate more generally the remarkable sensitivity and precision that characterizes control of mRNA splicing.     

A gravitationally lensed quasar with quadruple images separated by 14.62 arcseconds

Gravitational lensing is a powerful tool for the study of the distribution of dark matter in the Universe. The cold-dark-matter model of the formation of large-scale structures (that is, clusters of galaxies and even larger assemblies) predicts the existence of quasars gravitationally lensed by concentrations of dark matter so massive that the quasar images would be split by over 7 arcsec. Numerous searches for large-separation lensed quasars have, however, been unsuccessful. All of the roughly 70 lensed quasars known, including the first lensed quasar discovered, have smaller separations that can be explained in terms of galaxy-scale concentrations of baryonic matter. Although gravitationally lensed galaxies with large separations are known, quasars are more useful cosmological probes because of the simplicity of the resulting lens systems. Here we report the discovery of a lensed quasar, SDSS J1004 + 4112, which has a maximum separation between the components of 14.62 arcsec. Such a large separation means that the lensing object must be dominated by dark matter. Our results are fully consistent with theoretical expectations based on the cold-dark-matter model.     

Recent ice ages on Mars

A key pacemaker of ice ages on the Earth is climatic forcing due to variations in planetary orbital parameters. Recent Mars exploration has revealed dusty, water-ice-rich mantling deposits that are layered, metres thick and latitude dependent, occurring in both hemispheres from mid-latitudes to the poles. Here we show evidence that these deposits formed during a geologically recent ice age that occurred from about 2.1 to 0.4 Myr ago. The deposits were emplaced symmetrically down to latitudes of approximately 30 degrees--equivalent to Saudi Arabia and the southern United States on the Earth--in response to the changing stability of water ice and dust during variations in obliquity (the angle between Mars' pole of rotation and the ecliptic plane) reaching 30-35 degrees. Mars is at present in an 'interglacial' period, and the ice-rich deposits are undergoing reworking, degradation and retreat in response to the current instability of near-surface ice. Unlike the Earth, martian ice ages are characterized by warmer polar climates and enhanced equatorward transport of atmospheric water and dust to produce widespread smooth deposits down to mid-latitudes.     

The BLM dissolvasome in DNA replication and repair

RecQ DNA helicases are critical for proper maintenance of genomic stability, and mutations in multiple human RecQ genes are linked with genetic disorders characterized by a predisposition to cancer. RecQ proteins are conserved from prokaryotes to humans and in all cases form higher-order complexes with other proteins to efficiently execute their cellular functions. The focus of this review is a conserved complex that is formed between RecQ helicases and type-I topoisomerases. In humans, this complex is referred to as the BLM dissolvasome or BTR complex, and is comprised of the RecQ helicase BLM, topoisomerase IIIα, and the RMI proteins. The BLM dissolvasome functions to resolve linked DNA intermediates without exchange of genetic material, which is critical in somatic cells. We will review the history of this complex and highlight its roles in DNA replication, recombination, and repair. Additionally, we will review recently established interactions between BLM dissolvasome and a second set of genome maintenance factors (the Fanconi anemia proteins) that appear to allow coordinated genome maintenance efforts between the two systems.     

Annotated key to Eriogonum (Polygonaceae) of Nevada

Seventy - three species of Eriogonum (Polygonaceae) are reported for Nevada. A key is provided for the identification of these species along with brief notes on their distribution in the state and elsewhere.         

Conservation, status, and life history of the endangered White River spinedace, Lepidomeda albivallis (Cyprinidae)

Lepidomeda albivallis (White River spinedace), a fish species endemic to the White River, Nevada, appeared headed toward extinction. In 1991 only 1 population remained, and it comprised fewer than 50 individuals in a 70-m stream reach. We monitored population recruitment and distribution and studied life history and habitat use from 1993 through 1998. We determined that L. albivallis was not reproducing and was continuing to decline, and as an emergency measure we relocated the population (14 in spring 1995 and 6 in spring 1996) downstream 200 m to a secure habitat that we judged more favorable for reproduction. The relocated population reproduced, and by September 1998 it had increased to 396 individuals that inhabited more than 1 km of stream including both pond and stream habitats. In streams they oriented near the bottom but frequently moved up in the water column to strike at drift items. Gut analysis of museum specimens indicated L. albivallis is omnivorous but feeds primarily upon aquatic invertebrates. Conservation of L. albivallis will require reestablishing additional populations within its former range.     

Effect of Timing of Grazing on Soil-Surface Crytogamic Communities in a Great Basin Low-Shrub Desert: A Preliminary Report

Cover and species richness of vascular and cryptogamic components of the plant community were inventoried in experimental grazing paddocks at the USDA/FS Desert Range Experimental Station, Millard County, Utah. The grazing treatments considered have been applied continuously for over 50 years. The effects of heavy (ca 17 sheep days/acre) grazing treatment applied in two different seasons (early winter versus a split between early and late winter) differed significantly between seasons. Cryptogamic cover and cryptogamic species richness both showed larger decreases under early-late as opposed to early winter only grazing. Vascular plant cover (relative to controls) was also reduced by early-late winter grazing, but not to a significant degree. Late season grazing, likewise, had no significant effect on number of vascular species per transect.     

Leu-8/TQ1 is the human equivalent of the Mel-14 lymph node homing receptor

The human pan-leukocyte antigen Leu-8 has attracted wide interest because its presence or absence identifies suppressor-inducer and helper-inducer CD4+ T-lymphocyte subsets respectively. We report here that Leu-8 is the human homologue of the mouse Mel-14 homing receptor, a molecule that promotes the initial adhesion of blood-borne lymphocytes to the specialized post-capillary endothelium of peripheral lymph nodes. We also show that Leu-8 can adopt both conventional and phospholipid anchored forms, a finding that may have relevance in the context of antigen shedding following activation or homing. The assignment of lymphocytes to different functional classes based on lymph node homing potential may represent a more general association between lymphocyte function and tissue distribution.     

No evidence for expression of the insulin-regulatable glucose transporter in endothelial cells

A major effect of insulin is to increase glucose transport in muscle and fat. A family of genes encoding distinct mammalian glucose transporters has recently been elucidated. One of these, the insulin-regulatable glucose transporter (IRGT), is primarily expressed in muscle and fat, tissues that exhibit insulin-dependent glucose transport. Insulin promotes glucose transport in these tissues by stimulating movement of the glucose transporter from an intracellular location to the plasma membrane. Recent studies, however, suggest that an additional effect of insulin in these tissues may be the facilitation of glucose transport, presumably across capillary endothelium. This hypothesis is based on the localization of the IRGT in endothelial cells specific to muscle and adipose tissue. We report here, however, on morphological and biochemical studies using several different IRGT-specific antibodies in which we could not reproduce these results.