Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma.     

Subcellular trafficking of the substrate transporters GLUT4 and CD36 in cardiomyocytes

Cardiomyocytes use glucose as well as fatty acids for ATP production. These substrates are transported into the cell by glucose transporter 4 (GLUT4) and the fatty acid transporter CD36. Besides being located at the sarcolemma, GLUT4 and CD36 are stored in intracellular compartments. Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well as CD36 to translocate to the sarcolemma. As so far studied, signaling pathways that regulate GLUT4 translocation similarly affect CD36 translocation. During the development of insulin resistance and type 2 diabetes, CD36 becomes permanently localized at the sarcolemma, whereas GLUT4 internalizes. This juxtaposed positioning of GLUT4 and CD36 is important for aberrant substrate uptake in the diabetic heart: chronically increased fatty acid uptake at the expense of glucose. To explain the differences in subcellular localization of GLUT4 and CD36 in type 2 diabetes, recent research has focused on the role of proteins involved in trafficking of cargo between subcellular compartments. Several of these proteins appear to be similarly involved in both GLUT4 and CD36 translocation. Others, however, have different roles in either GLUT4 or CD36 translocation. These trafficking components, which are differently involved in GLUT4 or CD36 translocation, may be considered novel targets for the development of therapies to restore the imbalanced substrate utilization that occurs in obesity, insulin resistance and diabetic cardiomyopathy.     

The ATP-binding cassette family: a structural perspective

The ATP-binding cassette family is one of the largest groupings of membrane proteins, moving allocrites across lipid membranes, using energy from ATP. In bacteria, they reside in the inner membrane and are involved in both uptake and export. In eukaryotes, these transporters reside in the cell’s internal membranes as well as in the plasma membrane and are unidirectional—out of the cytoplasm. The range of substances that these proteins can transport is huge, which makes them interesting for structure–function studies. Moreover, their abundance in nature has made them targets for structural proteomics consortia. There are eight independent structures for ATP-binding cassette transporters, making this one of the best characterised membrane protein families. Our understanding of the mechanism of transport across membranes and membrane protein structure in general has been enhanced by recent developments for this family.     

Impact of bolus volume on small intestinal intra-luminal impedance in healthy subjects

AIM: To assess the impact of bolus volume on the characteristics of small intestinal (SI) impedance signals.METHODS: Concurrent SI manometry-impedance measurements were performed on 12 healthy volunteers to assess the pattern of proximal jejunal fluid bolus movement over a 14 cm-segment.Each subject was given 34 boluses of normal saline (volume from 1 to 30 mL) via the feeding tube placed immediately above the proximal margin of the studied segment.A bolus-induced impedance event occurred if there was > 12%...     

Comparison of two roadside survey procedures for dwarf mistletoes on the Sawtooth National Forest, Idaho

Two roadside surveys were conducted for dwarf mistletoes parasitizing lodgepole pine and Douglas-fir on the Sawtooth National Forest, Idaho. One survey used variable-radius plots located less than 150 m from roads. The 2nd survey used variable-radius plots established at 200-m intervals along 1600-m transects run perpendicular to the same roads. Estimates of the incidence (percentage of trees infected and percentage of plots infested) and severity (average dwarf mistletoe rating) for both lodgepole pine and Douglas-fir dwarf mistletoes were not significantly different for the 2 survey methods. These findings are further evidence that roadside-plot surveys and transect-plot surveys conducted away from roads provide similar estimates of the incidence of dwarf mistletoes for large forested areas.     

Infection of young Douglas-firs and spruces by dwarf mistletoes in the Southwest

Mistletoe infection of Douglas-fir and spruce seedlings increased as the mean dwarf mistletoe rating of the overstory, seedling density, and total age of seedlings increased. Percent of spruce seedlings infected increased more rapidly than for Douglas-fir as overstory dwarf mistletoe ratings increased. However, the intensity of infection as measured by the mean dwarf mistletoe rating of seedlings, increased at about the same rate for spruce and Douglas-fir. Percent infection of seedlings less than 20 years total age was higher for spruce than for Douglas-fir. Douglas-fir and spruce seedling mortality was from two to three times greater in heavily infested stands than in healthy stands.     

Vascular flora of Kane Lake Cirque, Pioneer Mountains, Idaho

Kane Lake Cirque lies in the western Pioneer Mountains of south central Idaho. An inventory of the high elevation flora of the cirque revealed the presence of 180 vascular taxa representing 95 genera and 30 families. Five alpine taxa are here documented from Idaho for the first time: Carex incurviformis Mack., Draba fladnizensis Wilfen., Potentilla nivea L., Ranunculus gelidus Kar. & Kir., and Ranunculus pygmaeus Wahlenb. Kane Lake Cirque also contains populations of four additional alpine taxa considered to be of conservation concern in Idaho: Erigeron humilis Graham, Parnassia kotzebuei Cham., Saxifraga adscendens L., and Saxifraga cernua L.     

Ecological studies of a regulated stream: Huntington River, Emery County, Utah

A 36.9x10 6 m 3 reservoir constructed on Huntington River, Emery County, Utah, resulted in changes in physical habitat, water quality, temperature, and flow regime. The greatest changes in physical habitat resulted from: (1) sediment additions from dam and road construction plus erosion of reservoir basin during filling; and (2) changing stream flow from a spring high runoff regime to a moderated flow regime. Elimination of spring nutrient concentration peaks and overall reduction of total dissolved nutrient availability in the river plus moderate reductions in pH were the most apparent water quality changes below the reservoir. Water temperature changes were an increased diurnal and seasonal constancy, summer depression, and winter elevation, generally limited to a 10–12 km reach below the dam. Physical and chemical changes altered macroinvertebrate community structure, with changes greatest near the dam and progressively less as distance downstream increased. Below the dam: (1) more environmentally tolerant taxa increased their dominance; (2) relative numbers of smaller sized individuals increased in relation to larger individuals; and (3) filter feeding, collector/gatherers, and scrapers gained an advantage over shredders. Insect taxa such as Rhithrogena robusta, Pteronarcella badia, and Ephemerella doddsi were eliminated from stream reaches near the dam, and other taxa such as Arctopsyche grandis, Chironomidae, and Simuliidae increased in numbers. Late spring to early summer egg hatch proved to be a disadvantage to Brachycentrus occidentalis, and B. americanus, with a fall hatch, was less impacted by altered river flow patterns. Macroinvertebrate taxa with small instar larvae present from late summer to early fall were negatively impacted by the unnaturally high July and August flows. The reservoir became a physical barrier to downstream larval drift and upcanyon and downcanyon immigration of adults, resulting in reduced numbers of several species above and below the reservoir.