Structural basis of tropism of Escherichia coli to the bladder during urinary tract infection

The first step in the colonization of the human urinary tract by pathogenic Escherichia coli is the mannose-sensitive binding of FimH, the adhesin present at the tip of type 1 pili, to the bladder epithelium. We elucidated crystallographically the interactions of FimH with D-mannose. The unique site binding pocket occupied by D-mannose was probed using site-directed mutagenesis. All but one of the mutants examined had greatly diminished mannose-binding activity and had also lost the ability to bind human bladder cells. The binding activity of the mono-saccharide D-mannose was delineated from this of mannotriose (Man(alpha 1-3)[Man(alpha 1-6)]Man) by generating mutants that abolished D-mannose binding but retained mannotriose binding activity. Our structure/function analysis demonstrated that the binding of the monosaccharide alpha-D-mannose is the primary bladder cell receptor for uropathogenic E. coli and that this event requires a highly conserved FimH binding pocket. The residues in the FimH mannose-binding pocket were sequenced and found to be invariant in over 200 uropathogenic strains of E. coli. Only enterohaemorrhagic E. coli (EHEC) possess a sequence variation within the mannose-binding pocket of FimH, suggesting a naturally occurring mechanism of attenuation in EHEC bacteria that would prevent them from being targeted to the urinary tract.     

The effects of training history, player position, and body composition on exercise performance in collegiate football players

Performance data for 261 NCAA Division 1A collegiate football players were analyzed to determine if player position, body weight, body fat, and training time were correlated with changes in performance in the following events: power clean (PC), bench press (BP), squat (SQ), vertical jump (VJ), 40-yd dash (40yd), and 20-yd shuttle (20yd). Individual positions were combined into the following groups: (A) wide receivers, defensive backs, and running backs, (B) linebackers, kickers, tight ends, quarterbacks, and specialists, and (C) linemen. Increases in body weight were positively correlated with increases in BP and PC performance for all groups. Increases in body fat were negatively correlated with performance in the PC and VJ for all groups. For group C, increases in body fat were also negatively correlated with performance in the 40yd and 20yd. Group and training time exhibited no linear relationship with performance in any of the tested events. No linear relationships were observed between the independent variables and performance in the SQ. When individual training data were analyzed longitudinally, a nonlinear increase in performance in the PC, BP, and SQ was observed as training time increased, with the greatest rate of change occurring between the first and second semesters of training.     

Morals,suicide, and psychiatry: a view from Japan

In this paper, I argue that within the Japanese social context, the act of suicide is a positive moral act because the values underpinning it are directly related to a socially pervasive moral belief that any act of self–sacrifice is a worthy pursuit. The philosophical basis for this view of the self and its relation to society goes back to the writings of Confucius who advocated a life of propriety in which being dutiful, obedient, and loyal to one's group takes precedence over the desires of the individual selves that make up the group. I argue that this philosophical perspective poses formidable challenges to Japanese psychiatry (which accepts a contrary western perspective) because, as western psychiatry is based on the concept of autonomous individuality, the Japanese conceive of the self as socially embedded. Because suicide in Japan is viewed as a potentially honorable, virtuous, and even beautiful act of self–sacrifice expressing one's duty to one's group, the western perspective is quite foreign to the Japanese self–conceptual framework. Therefore, since Japanese psychiatry and law have embraced the western medical tradition of viewing suicide as a non–rational response to mental illness, which runs counter to the cultural view that suicide is a moral (and rational) act, I argue that western explanations of suicide present significant cross–cultural problems for Japanese psychiatry.     

Identification of a dantrolene-binding sequence on the skeletal muscle ryanodine receptor

Dantrolene is a drug that suppresses intracellular Ca(2+) release from sarcoplasmic reticulum (SR) in skeletal muscle and is used as a therapeutic agent in individuals susceptible to malignant hyperthermia. Although its precise mechanism of action has not been elucidated, we have identified the N-terminal region (amino acids 1-1400) of the skeletal muscle isoform of the ryanodine receptor (RyR1), the primary Ca(2+) release channel in SR, as a molecular target for dantrolene using the photoaffinity analog [(3)H]azidodantrolene. Here, we demonstrate that heterologously expressed RyR1 retains its capacity to be specifically labeled with [(3)H]azidodantrolene, indicating that muscle specific factors are not required for this ligand-receptor interaction. Synthetic domain peptides of RyR1 previously shown to affect RyR1 function in vitro and in vivo were exploited as potential drug binding site mimics and used in photoaffinity labeling experiments. Only DP1 and DP1-2s, peptides containing the amino acid sequence corresponding to RyR1 residues 590-609, were specifically labeled by [(3)H]azidodantrolene. A monoclonal anti-RyR1 antibody that recognizes RyR1 and its 1400-amino acid N-terminal fragment recognizes DP1 and DP1-2s in both Western blots and immunoprecipitation assays and specifically inhibits [(3)H]azidodantrolene photolabeling of RyR1 and its N-terminal fragment in SR. Our results indicate that synthetic domain peptides can mimic a native, ligand-binding conformation in vitro and that the dantrolene-binding site and the epitope for the monoclonal antibody on RyR1 are equivalent and composed of amino acids 590-609.     

Managing Brachycaudis persicae (Homoptera: Aphididae) during peach orchard establishment

We investigated whether preplant root dips or postplant sprays or drenches could be used to control the black peach aphid, Brachycaudus persicae (Passerini), on young peach trees. In greenhouse trials, B. persicae died after being placed on peach trees that had their roots dipped in imidacloprid before planting. All rates (0.8, 1.6, and 3.2 ml/liter of water) tested controlled this aphid. B. persicae died faster on trees dipped in imidacloprid (1.6 ml/liter of water) for 5 min before planting than on trees dipped for 2 s. Aphids eventually died on all treated trees. Approximately 50% of untreated trees died from B. persicae infestations in greenhouse studies. Results from afield experiment show that peach trees root-dipped in imidacloprid before planting or drenched with imidacloprid after planting eliminate B. persicae infestations and prevent root colonization for at least 1 yr.     

Development of Hydrotaea aenescens (Diptera: Muscidae) in manure of unweaned dairy calves and lactating cows

In laboratory studies performed in the United States and Hungary, the dump fly Hydrotaea aenescens (Wiedemann) was reared successfully in manure of 1- to 8-wk-old dairy calves, and in manure from adult lactating dairy cows. Survival in manure collected from 1-wk-old calves was poor (7.2%), better in manure collected from 2- and 3-wk-old calves (53.5%), and best in manure collected from 4- to 8-wk-old calves (71.4%). Survival in cow manure was slightly lower (47.4%) than that in calf manure. Reasons for different rates of development in the United States and in Hungary, and by calf age are discussed as are implications for biological control.