A calcium sensor in the sodium channel modulates cardiac excitability.

Sodium channels are principal molecular determinants responsible for myocardial conduction and maintenance of the cardiac rhythm. Calcium ions (Ca2+) have a fundamental role in the coupling of cardiac myocyte excitation and contraction, yet mechanisms whereby intracellular Ca2+ may directly modulate Na channel function have yet to be identified. Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias. Mutations targeted to the IQ domain disrupted CaM binding and eliminated Ca2+/CaM-dependent slow inactivation, whereas the gating effects of Ca2+/CaM were restored by intracellular application of a peptide modelled after the IQ domain. A naturally occurring mutation (A1924T) in the IQ domain altered hH1 function in a manner characteristic of the Brugada arrhythmia syndrome, but at the same time inhibited slow inactivation induced by Ca2+/CaM, yielding a clinically benign (arrhythmia free) phenotype.     

The biological soil crusts of the San Nicolas Island: enigmatic algae from a geographically isolated ecosystem

Composite soil samples from 7 sites on San Nicolas Island were evaluated quantitatively and qualitatively for the presence of cyanobacteria and eukaryotic microalgae. Combined data demonstrated a rich algal flora with 19 cyanobacterial and 19 eukaryotic microalgal genera being identified, for a total of 56 species. Nine new species were identified and described among the cyanobacteria and the eukaryotic microalgae that were isolated: Leibleinia edaphica, Aphanothece maritima, Chroococcidiopsis edaphica, Cyanosarcina atroveneta, Hassallia californica, Hassallia pseudoramosissima, Microchaete terrestre, Palmellopsis californicus, and Pseudotetracystis compactis. Distinct distributional patterns of algal taxa existed among sites on the island and among soil algal floras of western North America. Some algal taxa appeared to be widely distributed across many desert regions, including Microcoleus vaginatus, Nostoc punctiforme, Nostoc paludosum, and Tolypothrix distorta, Chlorella vulgaris, Diplosphaera cf. chodatii, Myrmecia astigmatica, Myrmecia biatorellae, Hantzschia amphioxys, and Luticola mutica. Some taxa share a distinctly southern distribution with soil algae from southern Arizona, southern California, and Baja California (e.g., Scenedesmus deserticola and Eustigmatos magnus ). The data presented herein support the view that the cyanobacterial and microalgal floras of soil crusts possess significant biodiversity, much of it previously undescribed.     

Regional and seasonal diet of the Western Burrowing Owl in south central Nevada

We examined diets of Western Burrowing Owls ( Athene cunicularia hypugaea ) based on contents of pellets and large prey remains collected year-round at burrows in each of the 3 regions in south central Nevada (Mojave Desert, Great Basin Desert, and Transition region). The most common prey items, based on percent frequency of occurrence, were crickets and grasshoppers, beetles, rodents, sun spiders, and scorpions. The most common vertebrate prey was kangaroo rats ( Dipodomys spp.). True bugs (Hemiptera), scorpions, and western harvest mice ( Reithrodontomys megalotis ) occurred most frequently in pellets from the Great Basin Desert region. Kangaroo rats ( Dipodomys spp.) and pocket mice (Perognathinae) were the most important vertebrate prey items in the Transition and Mojave Desert regions, respectively. Frequency of occurrence of any invertebrate prey was high (>80%) in samples year-round but dropped in winter samples, with scorpions and sun spiders exhibiting the steepest declines. Frequency of occurrence of any vertebrate prey peaked in spring samples, was intermediate for winter and summer samples, and was lowest in fall samples. With the possible exception of selecting for western harvest mice in the Great Basin Desert region, Western Burrowing Owls in our study appeared to be opportunistic foragers with a generalist feeding strategy.     

Microbial spatial heterogeneity in microbiotic crusts in Colorado National Monument. I. Algae

Spatial heterogeneity in visually similar sites under Utah juniper canopy in Colorado National Monument was examined. Sample sites were arranged in a transect 24 m long, such that distances between samples were 0.013 m, 0.03 m, 1.0 m, 12 m, and 24 m. Twenty-five taxa of algae were observed, mostly belonging to Cyanophyta. Algal density varied by more than an order of magnitude within the 46 samples examined. The coefficients of variation for each distance class were very similar, demonstrating that algal patchiness can be as significant on a scale less than 0.013 m as it is on a scale of 24 m. Goodall's random pairing analysis of spatial pattern supported this conclusion by indicating that the minimal area for sampling soil algal crust populations at this site was equal to or less than 0.013 m. Because of the microscale heterogeneity in algal communities in this study, we recommend that future researchers take composite samples if they wish to quantify algae of microbiotic crusts.     

Effects of rangefire on soil algal crusts in semiarid shrub-steppe of the Lower Columbia Basin and their subsequent recovery

Effects of rangefire on soil algae in sagebrush steppe in the Lower Columbia Basin were studied. Dynamics of recovery of the soil algal community in the first two years following the fire were also documented. The study site was on the Arid Lands Ecology Reserve managed by Battelle Pacific Northwest Laboratory. Fire decreased the numbers of algae by more than an order of magnitude. Species composition in burned plots was similar to that in unburned plots, although some cyanophyte algae, particularly Nostoc commune , were decimated by the fire. Algal recovery took place in the winter months of the second year. Ninety taxa of algae were identified during the course of the study, over half of which were chlorophytes. Seasonal changes in the algal flora were also noted.     

Lichens of soil crust communities in the Intermountain Area of the western United States

Lichens are common components of microbiotic soil crusts. A total of 34 species from 17 genera are reported from soil crust communities throughout the Intermountain Area. Distribution of terricolous lichens is determined by various physical and biological factors: physical and chemical characteristics of the soil, moisture regimes, temperature, insolation, and development and composition of the vascular plant community. Some species demonstrate a broad ecological amplitude while others have a more restricted distribution. All growth forms are represented; however, the vast majority of soil crust lichens are squamulose (minutely foliose). Fruticose species are least abundant. In exposed, middle-elevation sites vagrant (detached) species are common. This paper describes and discusses terricolous lichen communities of desert habitats of the intermountain western United States. Effects of various human-related activities including grazing, wildfire, air pollution, and recreation vehicles on soil crust lichens are discussed. Gypsoplaca macrophylla (Zahlbr.) Timdal, a rare squamulose lichen which occurs on gypsifersous soils, was recently collected in Emery County, Utah, and is reported as new to the state.     

Timing, distribution, and abundance of kokanees spawning in a Lake Tahoe tributary

We counted kokanee spawners and carcasses every 1-7 days from mid-September through mid-November in 1991 and 1992 in Taylor Creek, a tributary to Lake Tahoe, California-Nevada. Less than 1% of the spawning run entered Taylor Creek before flow from Fallen Leaf Lake was increased on 2 October 1991; in 1992 the peak occurred on 30 September or 1 October after flows increased on 29 September. In both years spawners concentrated in the middle three of five stream reaches below the impassable Fallen Leaf Lake dam. From tab-and-recovery experiments, the average longevity of male spawners in the stream was 3.5 days in 1991 and 2.8 days in 1992, whereas the average female longevity was 2.0 days in 1991 and 2.3 days in 1992. Observed carcasses accounted for less than 10% of spawners counted, suggesting removal by scavengers or high predation on prespawners. An estimated 1928 males and 1309 females spawned in 1991, and 8021 males and 8712 females spawned in 1992. Our estimate of 3237 spawners in 1991 compared favorably to our estimate of 3520 ± 1474 prespawners staging in Lake Tahoe in mid-September. An index of kokanee abundance in Lake Tahoe has historically been based on 1-day surveys every 1 November since 1960; however, estimated total spawner abundance was 19 times higher than the annual index of 158 spawners in 1991, 141 times higher than the index count of 100 spawners in 1992. The index count and mean fork lengths of spawners (278 ± 10 mm [2 SE] for males, and 248 ± 3 mm for females) in 1991 and 1992 were the lowest on record.     

PTC124 targets genetic disorders caused by nonsense mutations

Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.     

Heparan sulphate proteoglycans fine-tune mammalian physiology

Heparan sulphate proteoglycans reside on the plasma membrane of all animal cells studied so far and are a major component of extracellular matrices. Studies of model organisms and human diseases have demonstrated their importance in development and normal physiology. A recurrent theme is the electrostatic interaction of the heparan sulphate chains with protein ligands, which affects metabolism, transport, information transfer, support and regulation in all organ systems. The importance of these interactions is exemplified by phenotypic studies of mice and humans bearing mutations in the core proteins or the biosynthetic enzymes responsible for assembling the heparan sulphate chains.