Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5–20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of d-glucose was lower than d-fructose. However, uptake of d-glucose was higher than d-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection.     

First specimen records for Ruffed Grouse in Colorado

We report the first specimen records for Ruffed Grouse ( Bonasa umbellus ) collected in Colorado, provide the location, describe the habitat, and briefly discuss the rarity of this species within the state. Three Ruffed Grouse were collected, an adult male in September 1988 and a juvenile male and adult female in September 1990, on Hoy Mountain, Moffat County, Colorado, within 0.6 km of Utah. The habitat is primarily open Douglas-fir ( Pseudotsuga menziesii ) forest with scattered clumps of quaking aspen ( Populus tremuloides ) and Utah serviceberry ( Amelanchier utahensis ). Habitats to the north, east, and south are primarily dominated by sagebrush ( Artemisia spp.) steppe and pionjuniper ( Pinus spp.-- Juniperus spp.) woodland. We hypothesize that natural expansion of Ruffed Grouse further east, north, and south is prohibited by unsuitable habitat exacerbated by the limited flight range capability of the species.     

Biological Roles of Neural J Proteins

J proteins are chief regulators of the Hsp70 family, a highly conserved family of ATPases that mediate conformational changes in a broad range of proteins. The J protein family has been the central focus of numerous prokaryote and eukaryote biologists. Common questions that arise include: How does the J protein/Hsp70 machinery support protein folding? What role do J proteins play in protein misfolding and neurodegenerative disorders? Can the J protein/ Hsp70 machinery be harnessed to provide a rational basis for recombinant protein production? The current progress that has resulted from the convergence of biochemistry with Escherichia coli and Saccharomyces cerevisiae genetics has accelerated the pace at which these questions are being elucidated. We are beginning to gain some insights into the neuronal network of J proteins. Here, we highlight recent advances in our understanding of how select J proteins harness Hsp70 s for fundamentally important conformational work in neurons.     

钢管相贯口变参数变结构建库与数据提取方法研究

零件的批处理和零件库的建立是计算机辅助设计的重要内容之一，以钢管相贯口为例应用UG的几种建库方法，通过分析电子表格、零件族、GRIP编程在变参变结构的复杂零件建库时存在的问题，提出了一种将零件族和GRIP编程相结合的建库方法来建立变参变结构的复杂零件的零件库。     

The influence of a new antitumor agent on hemopoietic colony forming cells

The cytostatic and immunsuppressive agent N'-methyl-N'-beta-chloroethylbenzaldehyde hydrazone (B1) in in-vitro experiments has a stimulating effect on colony-forming culture (CFUc) of bone marrow from C57BL mice. This unusual behaviour, which is in contrast to other cytostatics, could also be observed in vitro with CFUc obtained from mice treated with therapeutic doses of B1 for 2 weeks. This stimulation is not a particular effect of B1 alone but seems to depend on a synergistic effect of the combination of B1 and the colony-stimulating activity (CSA) present in the serum from endotoxin-treated mice (MP) in the testing system. The results suggest that the described effect of B1 is due to an interference at the cell membrane of CFUc or their precursor cells.     

Sharply increased mass loss from glaciers and ice caps in the Canadian Arctic Archipelago

Mountain glaciers and ice caps are contributing significantly to present rates of sea level rise and will continue to do so over the next century and beyond. The Canadian Arctic Archipelago, located off the northwestern shore of Greenland, contains one-third of the global volume of land ice outside the ice sheets, but its contribution to sea-level change remains largely unknown. Here we show that the Canadian Arctic Archipelago has recently lost 61?±?7?gigatonnes per year (Gt?yr(-1)) of ice, contributing 0.17?±?0.02 mm?yr(-1) to sea-level rise. Our estimates are of regional mass changes for the ice caps and glaciers of the Canadian Arctic Archipelago referring to the years 2004 to 2009 and are based on three independent approaches: surface mass-budget modelling plus an estimate of ice discharge (SMB+D), repeat satellite laser altimetry (ICESat) and repeat satellite gravimetry (GRACE). All three approaches show consistent and large mass-loss estimates. Between the periods 2004-2006 and 2007-2009, the rate of mass loss sharply increased from 31?±?8?Gt?yr(-1) to 92?±?12?Gt?yr(-1) in direct response to warmer summer temperatures, to which rates of ice loss are highly sensitive (64?±?14?Gt?yr(-1) per 1?K increase). The duration of the study is too short to establish a long-term trend, but for 2007-2009, the increase in the rate of mass loss makes the Canadian Arctic Archipelago the single largest contributor to eustatic sea-level rise outside Greenland and Antarctica.     

New species of Splendidofilaria and Chandlerella (Filarioidea: Nematoda), with keys to the species, from the band-tailed pigeon ( Columba fasciata fasciata ) in the Rocky Mountain Region

One male each of Splendidofilaria columbensis n. sp. and S. hibleri n. sp. was found in the subcutaneous fascia of the thighs of a single band-tailed pigeon. The relationship of female worms could not be correlated with the males. Chandlerella robinsoni n. sp. was recovered from the blood vessels of the liver and the fascia of the thighs of six birds. Keys to the males of the species of both genera, together with drawings of the spicules of each species, when available, are included.     

Discharge pattern analysis suggests existence of a low-threshold calcium channel in cold receptors

Summary The regular periodic activity patterns of mammalian cold receptors have been quantitatively studied. Analysis of the timing of either single impulses or impulse groups demonstrated that the periodic receptor process is maintained independently of impulse generation and continues to operate under conditions when afferent impulses are not initiated. These results imply that the underlying conductances must be operational at threshold potentials related to impulse generation. In addition to temperature, the periodic process is considerably sensitive to calcium, which affects mainly the probability of impulse generation during each cycle. Reduction of external calcium and application of calcium entry blockers with relative selectivity for low-threshold calcium channels are similarly effective in modulating cold receptor activity. The data imply the existence of a low-threshold calcium conductance at the sensory terminal.     

Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia

Craniometaphyseal dysplasia (CMD) is a bone dysplasia characterized by overgrowth and sclerosis of the craniofacial bones and abnormal modeling of the metaphyses of the tubular bones. Hyperostosis and sclerosis of the skull may lead to cranial nerve compressions resulting in hearing loss and facial palsy. An autosomal dominant form of the disorder (MIM 123000) was linked to chromosome 5p15.2-p14.1 (ref. 3) within a region harboring the human homolog (ANKH) of the mouse progressive ankylosis (ank) gene. The ANK protein spans the outer cell membrane and shuttles inorganic pyrophosphate (PPi), a major inhibitor of physiologic and pathologic calcification, bone mineralization and bone resorption. Here we carry out mutation analysis of ANKH, revealing six different mutations in eight of nine families. The mutations predict single amino acid substitutions, deletions or insertions. Using a helix prediction program, we propose for the ANK molecule 12 membrane-spanning helices with an alternate inside/out orientation and a central channel permitting the passage of PPi. The mutations occur at highly conserved amino acid residues presumed to be located in the cytosolic portion of the protein. Our results link the PPi channel ANK with bone formation and remodeling.