Messages are received both near and far, they show, to create transient and sustained responses. The cone presynaptic terminal is highly invaginated, with ribbons of glutamate-containing vesicles above each invagination. Cones respond to changes in light with graded changes in membrane potential. Decreases in light intensity depolarize cones and increase glutamate release, which then activates a class of cells known as Off bipolar cells. In the new report, DeVries et al. show that Off bipolar cell dendrites contact cone terminals at two sites. Most subtypes of Off bipolar cells contact the base of the cone terminal, 300 nm away from the vesicle fusion sites. The group found, however, that one Off cell subtype extended its dendrites up into each invagination to end close to fusion sites. These contacts within invaginations experienced large, rapid fl uctuations in glutamate levels when a cone was depolarized. Glutamate then spilled out of the invaginations to the basal contacts. In spite of their distance from release sites, even a single vesicle's worth of glutamate was able to reach and activate these cells. Distance exacted a toll, however, as the glutamate concentrations sensed by these cells fl uctuated more slowly and at much lower levels. The invaginating cell senses glutamate via AMPA receptors, which recover rapidly from glutamate-induced desensitization and can thus decode rapid consecutive pulses. Basal cells instead use kainate receptors, which have much slower recovery times and produce responses that average over rapid fl uctuations in glutamate concentration. The basally located Off bipolar cells thus generate more sustained responses. The steady signal conveys the basic sight information of change magnitude and duration. The transient signal saying just that there was a change "is probably very important," says DeVries, "because it can help an animal avoid predators or moving objects."

Nutrient limitaton is a critical signal in Salmonela virulence gene regulation. The katF (rpoS) gene mediates the expression of the Salkionella spy p i virulence genes during bacterial starvation. A katF Salmonella mutant has Increased su bilit to nutrient deprivation, oxidative stress, acid stress, and DNA damage, conditions which are relevant to the intraphagnal environment of host macrophages. Moreover, the katF mutant has g ntly reduced virulence in mice. katF encodes an alternative a factor of RNA polymerase which coordinately regulates Sabnonela viruence.

Summary Host inflammation alters the availability of nutrients such as iron to limit microbial growth. However, Salmonella enterica serovar Typhimurium thrives in the inflamed gut by scavenging for iron with siderophores. By administering Escherichia coli strain Nissle 1917, which assimilates iron by similar mechanisms, we show that this non-pathogenic bacterium can outcompete and reduce S. Typhimurium colonization in mouse models of acute colitis and chronic persistent infection. This probiotic activity depends on E. coli Nissle iron acquisition as mutants deficient in iron uptake colonize the intestine but do not reduce S. Typhimurium colonization. Additionally, the ability of E. coli Nissle to overcome iron restriction by the host protein lipocalin-2, which counteracts some siderophores, is essential as S. Typhimurium is unaffected by E. coli Nissle in lipocalin-2-deficient mice. Thus, iron availability impacts S. Typhimurium growth and E. coli Nissle reduces S. Typhimurium intestinal colonization by competing for this limiting nutrient.

Superoxide dismutase (SOD) catalyzes the conversion of superoxide radical to hydrogen peroxide. Periplasmic localization of bacterial Cu,Zn-SOD has suggested a role of this enzyme in defense against extracellular phagocyte-derived reactive oxygen species. Sequence analysis of regions f lanking the Salmonella typhimurium sodC gene encoding Cu,Zn-SOD demonstrates significant homology to phage proteins, ref lecting possible bacteriophage-mediated horizontal gene transfer of this determinant among pathogenic bacteria. Salmonella deficient in Cu,Zn-SOD has reduced survival in macrophages and attenuated virulence in mice, which can be restored by abrogation of either the phagocyte respiratory burst or inducible nitric oxide synthase. Moreover, a sodC mutant is extremely susceptible to the combination of superoxide and nitric oxide. These observations suggest that SOD protects periplasmic or inner membrane targets by diverting superoxide and limiting peroxynitrite formation, and they demonstrate the ability of the respiratory burst and nitric oxide synthase to synergistically kill microbial pathogens in vivo.