Actin-Based Motility of Intracellular Microbial Pathogens

A diverse group of intracellular microorganisms, including Listeria monocytogenes, Shigella spp., Rickettsia spp., and vaccinia virus, utilize actin-based motility to move within and spread between mammalian host cells. These organisms have in common a pathogenic life cycle that involves a stage within the cytoplasm of mammalian host cells. Within the cytoplasm of host cells, these organisms activate components of the cellular actin assembly machinery to induce the formation of actin tails on the microbial surface. The assembly of these actin tails provides force that propels the organisms through the cell cytoplasm to the cell periphery or into adjacent cells. Each of these organisms utilizes preexisting mammalian pathways of actin rearrangement to induce its own actin-based motility. Particularly remarkable is that while all of these microbes use the same or overlapping pathways, each intercepts the pathway at a different step. In addition, the microbial molecules involved are each distinctly different from the others. Taken together, these observations suggest that each of these microbes separately and convergently evolved a mechanism to utilize the cellular actin assembly machinery. The current understanding of the molecular mechanisms of microbial actin-based motility is the subject of this review.     

Boron adsorption by maize cell walls

Boron adsorption by cell walls isolated from corn (Zea mays) roots was investigated as a function of solution pH and ionic strength. Adsorption increased with increasing solution pH from pH 4.5 to 10, exhibited an adsorption maximum at pH 10–10.5, and decreased with increases in pH above 10.5. Boron adsorption increased with increasing solution ionic strength indicating the formation of strong inner-sphere surface complexes. A surface complexation model, the constant capacitance model was well able to describe the B adsorption data, optimizing two B surface complexes and the dissociation constant for the surface functional group, XOH. The large absolute value of the dissociation constant is consistent with phenolic functional groups.     

Effect of high boron application on boron content and growth of melons

Synthetic chelates, such as ethylene diamine tetraacetic acid (EDTA), have been shown to enhance phytoextraction of Pb from contaminated soil but also cause leaching of heavy metal-chelate complexes, posing a groundwater contamination threat. In a soil column study, we examined the effect of EDTA and a biodegradable chelate [S,S] isomere of ethylene diamine disuccinate ([S,S]-EDDS), newly introduced in phytoextraction research, on the uptake of Pb by the Chinese cabbage (Brassica rapa) and Pb leaching through the soil profile. Soil water sorption characteristics were modified by acrylamide hydrogel. The addition of 0.1 and 0.2% (w/w) of hydrogel amendments increased soil field water capacity from initial 24.6% to 28.5% and 31.3%, respectively. The additions of 2.5, 5 and 10 mmol EDTA kg^–1 soil were more effective in enhancing Pb plant uptake than comparable [S,S]-EDDS treatments, but caused (as also 10 mmol kg^–1 [S,S]-EDDS additions) unacceptably high Pb leaching in treatments with any soil water sorption conditions tested. The most efficient level of EDTA (10 mmol kg^–1) enhanced plant Pb uptake by 97 times compared to the control. Shoots Pb concentrations reached 500 mg kg^–1 of dry biomass. However, in this treatment 36.2% of total initial Pb was leached from the soil during the first four weeks after chelate addition. Hydrogel soil amendments were more effective in treatments with [S,S]-EDDS than with EDTA. In treatments with 10 mmol kg^–1[S,S]-EDDS hydrogel amended soils, plant Pb uptake was significantly reduced and Pb leach was as high as 44.2% of total initial soil Pb. At lower [S,S]-EDDS concentrations, the effect of hydrogel soil amendment on Pb leaching was the opposite. The addition of 5 mmol kg^–1 [S,S]-EDDS soil to the soil amended with 0.2% hydrogel increased Pb uptake by 18 times while only 0.2% of total initial Pb was leached. In all treatments, the concentrations of Pb in dry plant biomass were far from concentrations required for efficient soil remediation within a reasonable time span.     

Differential drift and parasitism in invading and native Gammarus spp. (Crustacea: Amphipoda)

Invading and native species often interact directly, such as by predation, producing patterns of exclusion and coexistence. Less direct factors, such as interactions with the broader abiotic and biotic environment, may also contribute to such patterns, but these have received less recognition. In Northern Ireland, the North American Gammarus tigrinus has invaded freshwaters populated with the native Gammarus duebeni celticus , with intraguild predation between the two implicated in their relative success. However, these species also engage in day and night "drifting", an activity that subjects amphipods to intense predation from fish and wildfowl. Sampling of two rivers where the invader and native co-occur showed that, compared with the benthos, G. tigrinus was underrepresented and G. d. celticus overrepresented in the drift. In addition, G. tigrinus were free from parasites, whereas some G. d. celticus harboured the acanthocephalans Polymorphus minutus and Echinorhynchus truttae and the muscle wasting microsporidian Pleistophora sp. (new species). Compared with the benthos, G. d. celticus parasitized with P. minutus were overrepresented and unparasitized individuals underrepresented in the drift. The opposite pattern was found with Pleistophora sp . In laboratory experiments, G. tigrinus were less positively phototropic and less "active" than G. d. celticus (unparasitized animals). Polymorphus minutus increased G. d. celticus positive phototropism and activity, while Pleistophora sp. increased positive phototropism but decreased activity. Previous studies show that the invader G. tigrinus is more disadvantaged by intraguild predation from the native G. d. celticus than vice versa. However, the native appears more disadvantaged with respect to drift, parasitism and the interaction of the two. These factors may mitigate direct interactions and help explain complex patterns of coexistence between these invader and native species.     

An Assessment of a Small Urban Stream Restoration Project in Northern California

Stream restoration projects have become increasingly common, and the need for systematic post‐project evaluation, particularly for small‐scale projects, is evident. This study describes how a 70‐m restored reach of a small urban stream, Baxter Creek (in Poinsett Park, El Cerrito, California), was quickly and inexpensively evaluated using habitat, biological, and resident‐attitude assessments. The restoration involved opening a previously culverted channel, planting riparian vegetation, and adding in‐stream step‐pool sequences and sinuosity. Replicated benthic macroinvertebrate samples from the restored site and an upstream unrestored site were compared using several metrics, including taxa richness and a biotic index. Both biological and habitat quality improved in the restored compared with the unrestored section. However, when compared with a creek restored 12 years before, habitat condition was of lower quality in the recently restored creek. A survey of the neighborhood residents indicated that, overall, they were pleased with the restored creek site. The approach used in this demonstration project may be applicable to other small‐scale evaluations of urban stream restorations.     

ENU mutagenesis in the mouse: application to human genetic disease.

Genetic approaches in model organisms provide a powerful means by which to examine the biological basis of human diseases as well as the physiological processes that are affected by them. Although not without its drawbacks, the mouse has become the mammalian species of choice in studying the molecular basis of disease. Targeted mutagenesis approaches in the mouse have led to dramatic increases in our understanding of human disease processes. As a complement to these gene-driven studies, three developments have led to the reassessment of a phenotype-driven approach in the mouse--the accumulation of information that has emerged from human and mouse genome sequencing projects, the use of high-efficiency point mutagens such as N-ethyl-N-nitrosourea (ENU) and the application of systematic hierarchical screening protocols for the mouse. In this paper, progress with existing phenotypic screening programmes is discussed and opportunities for the development of new mouse disease models are presented.     

Collagen-induced arthritis is exacerbated in IL-10-deficient mice

IL-10 is a potent immunoregulatory cytokine attenuating a wide range of immune effector and inflammatory responses. In the present study, we assess whether endogenous levels of IL-10 function to regulate the incidence and severity of collagen-induced arthritis. DBA/1 wildtype (WT), heterozygous (IL-10^+/-) and homozygous (IL-10^-/-) IL-10-deficient mice were immunized with type II collagen. Development of arthritis was monitored over time, and collagen-specific cytokine production and anticollagen antibodies were assessed. Arthritis developed progressively in mice immunized with collagen, and 100% of the WT, IL-10^+/-, and IL-10^-/- mice were arthritic at 35 days. However, the severity of arthritis in the IL-10^-/- mice was significantly greater than that in WT or IL-1^+/- animals. Disease severity was associated with reduced IFN-γ levels and a dramatic increase in CD11b-positive macrophages. Paradoxically, both the IgG₁ and IgG_2a anticollagen antibody responses were also significantly reduced. These data demonstrate that IL-10 is capable of controlling disease severity through a mechanism that involves IFN-γ. Since IL-10 levels are elevated in rheumatoid arthritis synovial fluid, these findings may have relevance to rheumatoid arthritis.     

Differential effects of the pharmacological manipulation of serotonin systems on cocaine and amphetamine self-administration in rats

The effects of the administration of serotonergic drugs on infusion rates of rats self-administering cocaine and amphetamine on an FR-10 schedule of reinforcement in daily 4 hour sessions were compared. Pretreatment with fluoxetine (2.5, 5, and 10 mg/kg), an inhibitor of serotonin reuptake, significantly decreased rates of responding maintained by amphetamine, but had no effect on responding maintained by cocaine at any of the doses tested. Pretreatment with cinanserin (3, 10, and 17.5 mg/kg), a serotonergic receptor antagonist, decreased rates of amphetamine self-administration at the highest dose tested, and also had no effect on cocaine self-administration. These data suggest a differential sensitivity of cocaine and amphetamine self-administration to pharmacological manipulation of central serotonin systems. They are consistent with biochemical data which demonstrates a negative correlation between the reinforcing potency of amphetamine-like drugs, but not cocaine-like drugs and their potency at serotonin binding sites.     

Disentangling the Association between Statins,Cholesterol, and Colorectal Cancer: A Nested Case-Control Study

BackgroundSeveral prior studies have found an association between statin use and reduced risk of colorectal cancer. We hypothesized that these findings may be due to systematic bias and examined the independent association of colorectal cancer risk with statin use, serum cholesterol, and change in cholesterol concentration.ConclusionsAlthough the risk of colorectal cancer was lower in statin users versus nonusers, no difference was observed among those who continued versus discontinued statin therapy, suggesting the potential for indication bias. The association between decreased serum cholesterol and colorectal cancer risk suggests a cholesterol-lowering effect of undiagnosed malignancy. Clinical judgment should be used when considering causes of cholesterol reduction in patients, including those on statin therapy.