Dystrophin deficiency leads to disturbance of LAMP1-vesicle-associated protein secretion

Duchenne muscular dystrophy results from loss of the protein dystrophin, which links the intracellular cytoskeletal network with the extracellular matrix, but deficiency in this function does not fully explain the onset or progression of the disease. While some intracellular events involved in the degeneration of dystrophin-deficient muscle fibers have been well characterized, changes in their secretory profile are undescribed. To analyze the secretome profile of mdx myotubes independently of myonecrosis, we labeled the proteins of mdx and wild-type myotubes with stable isotope-labeled amino acids (SILAC), finding marked enrichment of vesicular markers in the mdx secretome. These included the lysosomal-associated membrane protein, LAMP1, that co-localized in vesicles with an over-secreted cytoskeletal protein, myosin light chain 1. These LAMP1/MLC1-3-positive vesicles accumulated in the cytosol of mdx myotubes and were secreted into the culture medium in a range of abnormal densities. Restitution of dystrophin expression, by exon skipping, to some 30 % of the control value, partially normalized the secretome profile and the excess LAMP1 accumulation. Together, our results suggest that a lack of dystrophin leads to a general dysregulation of vesicle trafficking. We hypothesize that disturbance of the export of proteins through vesicles occurs before, and then concurrently with, the myonecrotic cascade and contributes chronically to the pathophysiology of DMD, thereby presenting us with a range of new potential therapeutic targets.     

Approximating Nonlinear Relations Between Susceptibility and Magnetic Contents in Rocks Using Neural Networks

Correlations between magnetic susceptibility and contents of magnetic minerals in rocks are important in interpreting magnetic anomalies in geophysical exploration and understanding magnetic behaviors of rocks in rock magnetism studies. Previous studies were focused on describing such correlations using a sole expression or a set of expressions through statistical analysis. In this paper, we use neural network techniques to approximate the nonlinear relations between susceptibility and magnetite and/or hematite contents in rocks. This is the first time that neural networks are used for such study in rock magnetism and magnetic petrophysics. Three multilayer perceptrons are trained for producing the best possible estimation on susceptibility based on magnetic contents. These trained models are capable of producing accurate mappings between susceptibility and magnetite and/or hematite contents in rocks. This approach opens a new way of quantitative simulation using neural networks in rock magnetism and petrophysical research and applications.     

Spatial pattern and interference in pi?on-juniper woodlands of northwest Colorado

The local spatial arrangement of the coniferous trees Pinus edulis and Juniperus osteosperma was mapped in two woodland stands and measured in two shrub-dominated stands in the semiarid Piceance Basin of northwest Colorado. In the woodlands, small trees were often clumped, while medium and large trees were either randomly or uniformly dispersed. Significant regressions were obtained between a tree?s basal area or canopy area and the area of its Dirichlet domain (the region closer to it than to any other tree). Both findings from the woodland stands accord with results obtained by other workers in other vegetation. Like earlier workers, we interpret these patterns to indicate density-dependent mortality and density-dependent depression of growth rates among the trees in the woodlands. In contrast, the trees in the shrub-dominated stands are located at random with respect to each other. However, they are strongly associated with shrub cover. Apparently tree seeds arrive in these stands primarily by long-distance dispersal, and the establishment of seedlings is more likely in the shade of shrubs.     

Base excision repair and design of small molecule inhibitors of human DNA polymerase β

Base excision repair (BER) can protect a cell after endogenous or exogenous genotoxic stress, and a deficiency in BER can render a cell hypersensitive to stress-induced apoptotic and necrotic cell death, mutagenesis, and chromosomal rearrangements. However, understanding of the mammalian BER system is not yet complete as it is extraordinarily complex and has many back-up processes that complement a deficiency in any one step. Due of this lack of information, we are unable to make accurate predictions on therapeutic approaches targeting BER. A deeper understanding of BER will eventually allow us to conduct more meaningful clinical interventions. In this review, we will cover historical and recent information on mammalian BER and DNA polymerase β and discuss approaches toward development and use of small molecule inhibitors to manipulate BER. With apologies to others, we will emphasize results obtained in our laboratory and those of our collaborators.     

Oreohelices of Utah, I. Rediscovery of the Uinta mountainsnail, Oreohelix eurekensis uinta Brooks, 1939 (Stylommatophora: Oreohelicidae)

The Brian Head mountainsnail, Oreohelix parawanensis , is reported for the 1st time as a living species, and for the 1st time its habitat is described. Preliminary determination of the very limited distribution of this species (≤ 2.3 ha inhabited in ～ 11 ha overall area) is presented. Morphometric data previously had been reported only for the holotype and for 1 topotype; measurements from 37 new specimens as well as 20 paratypes are provided here, and these data show that the lost holotype was not typical of the species. Sizes of reproductive snails and of embryos are also reported.     

A mixed pollination system in Penstemon pseudospectabilis M. E. Jones (Scrophulariaceae)

A population of Penstemon pseudospectabilis M. E. Jones (Scrophulariaceae) on Cave Creek in Cochise County, Arizona, was used in an experimental test of reproductive fitness with three caging treatments: all flying pollinators excluded, hummingbirds excluded, and no exclusion. Twenty plants were chosen and three shoots on each used in the experiment. The flowers were 25.6 (s.d. = 1.5) mm long, the end diameter was 8.5 (s.d. = 1.0) mm, the tube opening was 6.5 (s.d. = 1.0) mm, and the greatest diameter, 75% distal from the receptacle, was 10.1 (s.d. = 0.8) mm (N= 59). Floral nectar contained 11.7% (s.d. = 2.9%) fructose, 13.8% (s.d. = 2.7%) glucose, and 74.5% (s.d. = 5.4%) sucrose (N = 74). There was some evidence, significant only for fructose, that nectar-sugar composition varies between morning and evening. Larger floral dimensions were correlated with lower sucrose and higher hexoses. Casual observation showed Xylocopa sp., small bees, flies, and hummingbirds to be visitors. There was no sign of nectar robbing. Five percent of flowers set seed with all pollen vectors excluded, 44% with hummingbirds excluded, and 63%with no exclusion. Seed set per fruit was 2 with all excluded, 23 with hummingbirds excluded, and 46 with no exclusion. Mean seed set on pollinated flowers was 60, with a range of 2 to 192. Multiple linear regression showed the fraction of fruit setting seed when hummingbirds were excluded to be related to larger flower diameters and shorter flowers. With no pollinator exclusion, fruits setting seed were related to larger diameters and nectar fructose. For seeds per fruit, multiple regression gave similar, but less clear, results. We conclude that P. pseudospectabilis is pollinated by both bees and hummingbirds, with other pollinators not to be excluded as possible contributors. We found no hard evidence of selective forces currently at work.     

Dam-site selection by beavers in an eastern Oregon basin

We compared physical and vegetative habitat characteristics at 14 dam sites occupied by beaver ( Castor Canadensis ) with those at 41 random unoccupied reaches to identify features important to dam-site selection in the Long Creek basin, Grant County, Oregon. Stream reaches with dams were shallower and had a lower gradient than unoccupied reaches. Beaver did not build dams at sites with a rock substrate. Bank slopes at occupied reaches were not as steep as those at unoccupied reaches; and occupied stream reaches had greater tree canopy cover, especially of thinleaf alder ( Alnus tenuifolia ), than did unused reaches. A discriminant model using transformations of bank slope, stream gradient, and hardwood cover classified all beaver dam sites correctly and 35 of 41 random sites as unoccupied sites. The 6 misclassified sites had rock substrates. We also tested four habitat suitability models for beaver in this basin. Three models produced significantly different ( P < .05) scores between occupied and random unoccupied reaches, suggesting that they might have some utility for this region.     

Two new species of Aurealcaulis (Osmundaceae) from northwestern New Mexico

Two new osmundaceous species, Aurealcaulis moorei and A. bransonii , are described from the San Juan Basin of northwestern New Mexico. The area from which they were collected is uncertain, but it is presumed they came from the Lower Eocene San Jose Formation near Angel Peak, southeast of Bloomfield, New Mexico. The species are characterized by having a heterogeneous ( A. moorei ) to homogeneous ( A. bransonii ) pith, non- or partial closure of their leaf gaps, exarch protoxylem clusters, formation of their C-shaped leaf traces by fusion of two segments from adjacent xylem strands in their inner cortices, relatively low numbers of traces in their cortices (16-22 in A. moorei , 15-19 in A. bransonii ), roots arising from lateral margins of these segments, sclerenchymatous outer cortex that connects with the sclerotic ring of the petiolar vascular strand, crenate ( A. moorei ) or interrupted ( A. bransonii ) sclerenchyma lining the adaxial concavity of their petiole strands, and leaf bases that may or may not contain one, occasionally two, sclerotic cellular masses in their stipular wings in A. moorei and 6-8 more or less aligned masses in A. bransonii . They are compared with other osmundaceous taxa, particularly A. crossii Tidwell & Parker of Paleocene age. Because of variations in these new species, Aurealcaulis Tidwell & Parker is slightly emended to accept species of this genus with heterogeneous or homogeneous piths, protoxylem becoming endarch in the leaf traces, petiolar vascular strands formed by fusion of segments from the xylem strands in the inner cortex, outer cortex, or outside the stem, and the occurrence or nonoccurrence of sclerenchyma in the adaxial concavity of their petiolar vascular stands and in their stipular wings. The paleoecological conditions under which these species of Aurealcaulis grew are also considered.     

Classification of the riparian vegetation of the montane and subalpine zones in western Colorado

A classification of the riparian vegetation of part of western Colorado was developed by cluster analysis and ordination of 115 samples of relatively undisturbed vegetation. The classification of plant associations contains five montane riparian forests, three subalpine riparian forests, four lower subalpine willow carrs, three upper subalpine willow carrs, and one subalpine wetland.