Substrate-modulated gating dynamics in a Na+-coupled neurotransmitter transporter homologue

Neurotransmitter/Na(+) symporters (NSSs) terminate neuronal signalling by recapturing neurotransmitter released into the synapse in a co-transport (symport) mechanism driven by the Na(+) electrochemical gradient. NSSs for dopamine, noradrenaline and serotonin are targeted by the psychostimulants cocaine and amphetamine, as well as by antidepressants. The crystal structure of LeuT, a prokaryotic NSS homologue, revealed an occluded conformation in which a leucine (Leu) and two Na(+) are bound deep within the protein. This structure has been the basis for extensive structural and computational exploration of the functional mechanisms of proteins with a LeuT-like fold. Subsequently, an 'outward-open' conformation was determined in the presence of the inhibitor tryptophan, and the Na(+)-dependent formation of a dynamic outward-facing intermediate was identified using electron paramagnetic resonance spectroscopy. In addition, single-molecule fluorescence resonance energy transfer imaging has been used to reveal reversible transitions to an inward-open LeuT conformation, which involve the movement of transmembrane helix TM1a away from the transmembrane helical bundle. We investigated how substrate binding is coupled to structural transitions in LeuT during Na(+)-coupled transport. Here we report a process whereby substrate binding from the extracellular side of LeuT facilitates intracellular gate opening and substrate release at the intracellular face of the protein. In the presence of alanine, a substrate that is transported ～10-fold faster than leucine, we observed alanine-induced dynamics in the intracellular gate region of LeuT that directly correlate with transport efficiency. Collectively, our data reveal functionally relevant and previously hidden aspects of the NSS transport mechanism that emphasize the functional importance of a second substrate (S2) binding site within the extracellular vestibule. Substrate binding in this S2 site appears to act cooperatively with the primary substrate (S1) binding site to control intracellular gating more than 30?? away, in a manner that allows the Na(+) gradient to power the transport mechanism.     

Clothing Colour Preferences in A Hospital Environment in Hong Kong:Part Ⅱ-Paediatric Nurses’Preferences of Colour on Their Uniform

The present study investigated nurses'colour prefer-ences on their uniform in paediatric wards.Results ofthe study provided guidelines for the selecting of ap-propriate colours for nurses'uniforms for paediatricwards,and the comparison of nurses'preferences ofcolours on their uniform and child patients'colourpreferences of nurses'uniform was drawn.     

THE DEVELOPMENT OF A MANIKIN TO SIMULATE THE THERMAL PHYSIOLOGY OF PREMATURE INFANTS

This paper describes a manikin (also known as mannequin) to simulate the thermal physiology of premature infants and experiments performed on it.The performance of the manikin is shown to compare well with that a selection of premature infants in terms of their rate of heat loss.     

IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells

On activation, naive T cells differentiate into effector T-cell subsets with specific cytokine phenotypes and specialized effector functions. Recently a subset of T cells, distinct from T helper (T(H))1 and T(H)2 cells, producing interleukin (IL)-17 (T(H)17) was defined and seems to have a crucial role in mediating autoimmunity and inducing tissue inflammation. We and others have shown that transforming growth factor (TGF)-beta and IL-6 together induce the differentiation of T(H)17 cells, in which IL-6 has a pivotal function in dictating whether T cells differentiate into Foxp3+ regulatory T cells (T(reg) cells) or T(H)17 cells. Whereas TGF-beta induces Foxp3 and generates T(reg) cells, IL-6 inhibits the generation of T(reg) cells and induces the production of IL-17, suggesting a reciprocal developmental pathway for T(H)17 and T(reg) cells. Here we show that IL-6-deficient (Il6-/-) mice do not develop a T(H)17 response and their peripheral repertoire is dominated by Foxp3+ T(reg) cells. However, deletion of T(reg) cells leads to the reappearance of T(H)17 cells in Il6-/- mice, suggesting an additional pathway by which T(H)17 cells might be generated in vivo. We show that an IL-2 cytokine family member, IL-21, cooperates with TGF-beta to induce T(H)17 cells in naive Il6-/- T cells and that IL-21-receptor-deficient T cells are defective in generating a T(H)17 response.     

Relation of fish communities to environmental conditions in urban streams of the Wasatch Front, Utah

Twenty-eight sites along the Wasatch Front, north central Utah, representing the range of urban land use intensity for wadeable streams of the area, were sampled in September 2000. Fish communities were assessed by single-pass electrofishing, and physical habitat and water-quality characteristics were measured. On average, nonnative species comprised 54% of species richness and 53% of relative abundance, although only Salmo trutta and Pimephales promelas were very abundant at any 1 site. Salmo trutta and Catostomus platyrhynchus , a native species, were the most widely distributed and abundant species captured. Analysis of fish communities using nonmetric multidimensional scaling (NMDS) revealed a community gradient from sites dominated by Salmo trutta and Cottus species ( C. bairdi , C. beldingi ) to sites dominated by Catostomus platyrhynchus . Sites dominated by C. platyrhynchus were smaller in size and had less habitat cover, smaller average substrate size, higher concentrations of dissolved constituents, and higher water temperature than sites dominated by S. trutta . Sites dominated by C. platyrhynchus were located in more intensely urbanized watersheds at lower elevations. Stream size and associated instream habitat availability appear to limit S. trutta distribution and abundance, while native species appear more tolerant of decreased water quality and increased water temperatures in more urbanized streams. Most of the study sites are affected by development of water infrastructure for human water use (e.g., dams and diversions), and this infrastructure may play a role in dispersal of species.     

Nutrient relationships between Orobanche fasciculata Nutt. and its host Artemisia pygmaea Gray in the Uinta Basin of Utah, USA

Patterns of mineral nutrient uptake and distribution within the roots, stems, and leaves of Artemisia pygmaea and in the vascular parasite Orobanche fasciculata were investigated. All nutrients studied were magnified over concentrations found in the soil into the host and parasite. Nitrogen, phosphorus, potassium, and zinc were magnified along the flow gradient of soil-roots-stems-leaves of the host. All others increased in the roots and then decreased in the stems and leaves. Orobanche fasciculata concentrated phosphorus, potassium, and sodium over soil and root concentrations while excluding to some degree all others.     

Density, distribution, and habitat of Flammulated Owls in Idaho

From 1990 to 1992 we surveyed for Flammulated Owls ( Otus flammeolus ) in 3 areas in Idaho: Salmon National Forest (SNF), Payette National Forest and adjacent Hells Canyon National Recreation Area (PNF-HCNRA), and Nez Perce National Forest (NPNF). We also collected and summarized information on all historic and modern records of Flammulated Owls in Idaho. Flammulated Owls were detected on 65% of 68 routes (2-16 km in length) surveyed at densities ranging from 0.04 to 1.25 singing males/40 ha. Owls were detected on survey routes as early as 10 May and as late as 23 July. Mean percent canopy cover estimated at owl locations on the PNF-HCNRA and NPNF study sites ranged from 52% to 64%, while shrub cover ranged from 16% to 21% and ground cover was 39% to 49%. Our surveys and summary of distributional records indicated that Flammulated Owls occur throughout the montane forests of Idaho in old or mature stands of open ponderosa pine ( Pinus ponderosa ), Douglas-fir ( Pseudotsuga menziesii ), and stands co-dominated by those 2 species. Fire suppression and timber harvest activity in ponderosa pine forests represent 2 main threats to the species' future security in Idaho. More research on the effects of various silvicultural treatments on Flammulated Owl populations is warranted.     

Ruffed grouse ( Bonasa umbellus ) foraging in aspen stands during winter in northern Utah

Ruffed Grouse ( Bonasa umbellus ) population densities are lower in the Intermountain West than elsewhere in the species' range. Throughout much of its range, the Ruffed Grouse is closely associated with quaking aspen ( Populus tremuloides ), in part because aspen buds are an important winter food. Because population fluctuations of Ruffed Grouse have been associated with changes in aspen abundance or chemical composition, we studied winter foraging of the species in the Intermountain West where it has received little attention. Aspen buds were the most prominent forage in the bird's diet, although in contrast to other Ruffed Grouse food habits studies, reproductive buds were not eaten more than vegetative buds, and buds of other deciduous plants were also important (>20% of the diet). Excretion of high concentrations of ammonium nitrogen suggests that grouse in northern Utah are ingesting higher levels of secondary plant compounds than reported elsewhere. Our results show aspen is important in the winter ecology of Ruffed Grouse in northern Utah and suggest that continued loss of aspen may impact grouse populations.     

Current status of cutthroat trout subspecies in the western Bonneville Basin

Recent discoveries of native cutthroat trout populations in desert mountain ranges on the western fringe of the Bonneville Basin have prompted intensified management efforts by state and federal agencies. Analysis of Snake Valley cutthroat specimens in Trout Creek, Deep Creek Mountain Range, Utah, indicate this is a pure strain of the trout which once inhabited Pleistocene Lake Bonneville and which was thought to be extinct in Utah. The Snake Valley cutthroat is similar to Salmo clarki utah of the eastern Bonneville Basin; however, electrophoretic and morphomeristic analysis show unique genetic differences brought about by long - term isolation (8,000 years) from the remainder of the Bonneville Basin cutthroat. This cutthroat is a common ancestor to several other limited cutthroat populations within the basin in Nevada. In May 1977 the BLM withdrew from mineral entry about 27,000 acres within the Deep Creek Mountains for protection of this salmonid cutthroat and other unique resources on the range. Results of 1977 stream surveys on the Pilot Peak Mountain Range, Utah, indicate the presence of the threatened Lahontan cutthroat, Salmo clarki henshawi, in one isolated stream.