'Slings' enable neutrophil rolling at high shear

Most leukocytes can roll along the walls of venules at low shear stress (1?dyn?cm?2), but neutrophils have the ability to roll at tenfold higher shear stress in microvessels in vivo. The mechanisms involved in this shear-resistant rolling are known to involve cell flattening and pulling of long membrane tethers at the rear. Here we show that these long tethers do not retract as postulated, but instead persist and appear as 'slings' at the front of rolling cells. We demonstrate slings in a model of acute inflammation in vivo and on P-selectin in vitro, where P-selectin-glycoprotein-ligand-1 (PSGL-1) is found in discrete sticky patches whereas LFA-1 is expressed over the entire length on slings. As neutrophils roll forward, slings wrap around the rolling cells and undergo a step-wise peeling from the P-selectin substrate enabled by the failure of PSGL-1 patches under hydrodynamic forces. The 'step-wise peeling of slings' is distinct from the 'pulling of tethers' reported previously. Each sling effectively lays out a cell-autonomous adhesive substrate in front of neutrophils rolling at high shear stress during inflammation.     

The mechanism of the biochemical activity of acridines

Résumé Les acridines forment avec les nucléoprotéides des levures, des complexes électro-adsorptifs. Le pouvoir bactéricide des acridines s'exerce par une compétition entre les ion H⁺ de ce complexe et l'ion acridine. Différents enzymes activés par des ions métalliques doivent leur activité catalytique au même type de complexes. Les acridines inhibent ces enzymes parce qu'ils déplacent le cathion métallique.     

The influence of dyes on the respiration of baker's yeast

Résumé La respiration de la levure de boulangerie en milieu glucose-phosphate est inhibée par la trypaflavine, le bleu de methylène, le violet de cristal. Cette inhibition disparaît du moins partiellement par addition d'acide nucléique, d'acide adénylique et d'A.T.P.     

论竞技健美操技术创新的概念与分类

该研究以竞技健美操技术创新为研究对象,采用文献资料法、案例分析法,对查阅的文献和案例进行综合的归纳分析,在研究竞技健美操技术创新发展现状基础上,结合其他项目技术创新的特点,对竞技健美操技术创新的概念进行了阐述;对竞技健美操技术创新进行了系统的分类.     

ACTH: Differential effects on avoidance and discrimination

Zusammenfassung Andauernde ACTH-Behandlung beeinflusst sowohl Vermeidungs- als auch Fehlerkomponenten im Zweiwahl-Y-Labyrinthtest. Die Einwirkungen waren von der Intensität des Elektroschocks wie auch von der Reaktionsfähigkeit der Tiere abhängig.

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This work was supported by Medical Research Council Grant No. MA 1746. Some of the work was done while the first author held a pre-doctoral terminal year grant from the USPHS and while the second author held a Research Career Award from the Canadian Association for Retarded Children. We are indebted toSusanna Kertesz for help in running the subjects in these studies. Requests for reprints should be sent to Dr.J. A. Corson, Allan Memorial Institute, 1033 Pine Avenue West, Montreal 112 (P.Q., Canada).     

DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome

Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.     

An obesity-associated gut microbiome with increased capacity for energy harvest

The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.