Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6

Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous disease involving abnormalities of melanosomes, platelet dense granules and lysosomes. Here we have used positional candidate and transgenic rescue approaches to identify the genes mutated in ruby-eye 2 and ruby-eye mice (ru2 and ru, respectively), two 'mimic' mouse models of HPS. We also show that these genes are orthologs of the genes mutated in individuals with HPS types 5 and 6, respectively, and that their protein products directly interact. Both genes are previously unknown and are found only in higher eukaryotes, and together represent a new class of genes that have evolved in higher organisms to govern the synthesis of highly specialized lysosome-related organelles.     

A relocation technique for black-tailed prairie dogs

Relocations of black-tailed prairie dogs have occurred both to save individual prairie dogs from urban development and to reestablish populations that have been extirpated. Unfortunately, however, many past relocation efforts rarely exceeded 40% retention. Many factors have contributed to very low retention rates in past relocation efforts including lack of (1) suitable habitat, (2) proper artificial burrow systems, (3) aboveground acclimation cages or pens, and (4) skilled people conducting the relocations. In an attempt to increase prairie dog relocation success, we developed techniques that are easy to implement, promote high retention, and effectively conserve labor, financial resources, and prairie dog populations. We conducted 3 relocations along the Front Range of Colorado in 2001 and 2002. Relocation techniques we developed resulted in at least 46%-92% retention. Our results suggest that a large percentage of prairie dogs can be retained by (1) ensuring that habitat is suitable, (2) using underground nest chambers modeled after natural nest chambers, (3) acclimating prairie dogs to the release site in large retention pens rather than in retention caps or other small acclimation cages (i.e., rabbit hutch), and (4) providing supplemental feed and water ad libitum to the prairie dogs.     

Structural insights into mRNA recognition from a PIWI domain-siRNA guide complex

RNA interference and related RNA silencing phenomena use short antisense guide RNA molecules to repress the expression of target genes. Argonaute proteins, containing amino-terminal PAZ (for PIWI/Argonaute/Zwille) domains and carboxy-terminal PIWI domains, are core components of these mechanisms. Here we show the crystal structure of a Piwi protein from Archaeoglobus fulgidus (AfPiwi) in complex with a small interfering RNA (siRNA)-like duplex, which mimics the 5' end of a guide RNA strand bound to an overhanging target messenger RNA. The structure contains a highly conserved metal-binding site that anchors the 5' nucleotide of the guide RNA. The first base pair of the duplex is unwound, separating the 5' nucleotide of the guide from the complementary nucleotide on the target strand, which exits with the 3' overhang through a short channel. The remaining base-paired nucleotides assume an A-form helix, accommodated within a channel in the PIWI domain, which can be extended to place the scissile phosphate of the target strand adjacent to the putative slicer catalytic site. This study provides insights into mechanisms of target mRNA recognition and cleavage by an Argonaute-siRNA guide complex.     

The DNA sequence of human chromosome 22

Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.     

Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin,a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1)

Hermansky-Pudlak syndrome (HPS; MIM 203300) is a genetically heterogeneous disorder characterized by oculocutaneous albinism, prolonged bleeding and pulmonary fibrosis due to abnormal vesicle trafficking to lysosomes and related organelles, such as melanosomes and platelet dense granules. In mice, at least 16 loci are associated with HPS, including sandy (sdy; ref. 7). Here we show that the sdy mutant mouse expresses no dysbindin protein owing to a deletion in the gene Dtnbp1 (encoding dysbindin) and that mutation of the human ortholog DTNBP1 causes a novel form of HPS called HPS-7. Dysbindin is a ubiquitously expressed protein that binds to alpha- and beta-dystrobrevins, components of the dystrophin-associated protein complex (DPC) in both muscle and nonmuscle cells. We also show that dysbindin is a component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1; refs. 9-11), which regulates trafficking to lysosome-related organelles and includes the proteins pallidin, muted and cappuccino, which are associated with HPS in mice. These findings show that BLOC-1 is important in producing the HPS phenotype in humans, indicate that dysbindin has a role in the biogenesis of lysosome-related organelles and identify unexpected interactions between components of DPC and BLOC-1.     

No oceans on Titan from the absence of a near-infrared specular reflection

With its substantial atmosphere of nitrogen, hydrocarbons and nitriles, Saturn's moon Titan is a unique planetary satellite. Photochemical processing of the gaseous constituents produces an extended haze that obscures the surface. Soon after the Voyager fly-bys in 1980 and 1981 photochemical models led to the conclusion that there should be enough liquid methane/ethane/nitrogen to cover the surface to a depth of several hundred metres. Recent Earth-based radar echoes imply that surface liquid may be present at a significant fraction of the locations sampled. Here we present ground-based observations (at near-infrared wavelengths) and calculations showing that there is no evidence thus far for surface liquid. Combined with the specular signatures from radar observations, we infer mechanisms that produce very flat solid surfaces, involving a substance that was liquid in the past but is not in liquid form at the locations we studied.