Impaired TNF-α control of IP3R-mediated Ca2+ release in Alzheimer's disease mouse neurons

The misguided control of inflammatory signaling has been previously implicated in the pathogenesis of several neurological disorders, including Alzheimer's disease (AD). Induction of tumor necrosis factor-alpha (TNF-α), a central mediator of neuroinflammation, occurs commensurate with the onset of early disease in 3xTg-AD mice, which develop both amyloid plaque and neurofibrillary tangle pathologies in an age- and region-dependent pattern. Herein, we describe regulation inherent to 3xTg-AD neurons, which results in the loss of TNF-α mediated enhancement of inositol 1,4,5 trisphosphate (IP₃R)-mediated Ca²⁺ release. This modulation also leads to significant down-regulation of IP₃R signaling following protracted cytokine exposure. Through the experimental isolation of each AD-related transgene, it was determined that expression of the PS1^M146V transgene product is responsible for the loss of the TNF-α effect on IP₃R-mediated Ca²⁺ release. Furthermore, it was determined that the suppression of TNF-α receptor expression occurred in the presence of the presenilin transgene. Our findings attribute this familial AD mutation to suppressing a Ca²⁺-regulated signal cascade potentially intended to “inform” neurons of proximal neuroinflammatory events and trigger compensatory responses for protection of neural transmission.     

Presence of predatory wasps and stinkbugs alters foraging behavior of cryptic and non-cryptic caterpillars on plantain (Plantago lanceolata)

We examined the foraging patterns of two species of caterpillar (Junonia coenia: Nymphalidae and Spilosoma congrua: Arctiidae) that contrast in feeding specialization and crypticity on plantain (Plantago lanceolata) in the absence and presence of two different insect predators [stinkbugs, Podisus maculiventris (Pentatomidae) and wasps, Polistes fuscatus (Vespidae)]. Junonia larvae were quite apparent to human observers, feeding on upper leaf surfaces during daylight, whereas Spilosoma larvae were relatively cryptic, often hiding under leaves and in soil crevices during daylight. In the presence of either predator species, the non-cryptic Junonia caterpillars more quickly left the plant on which they were initially placed and were less apparent than Junonia larvae not exposed to predators. The presence of predators had no detectable influence on where the caterpillars occurred on the plants (new, intermediate-aged or mature leaves, or reproductive stalks). Surprisingly, the predators influenced the behavior of the inherently cryptic Spilosoma: the apparency of these larvae at night increased when wasps had access to the plots during the day. Survivorship of the non-cryptic Junonia was less than 12% when stinkbugs were present compared to 60% in their absence. Although the presence of wasps resulted in a lower relative growth rate for the non-cryptic Junonia larvae, the indirect effect of predators on reduction in survivorship due to alterations in prey growth rate through behavioral changes was less than 3%. After taking into account the decline in caterpillars per plot through predation, we found that both the amount of leaves eaten and the proportion of plants eaten were altered on plots with predators present, which suggests that the caterpillars' increased consumption countered increased maintenance costs due to the presence of predators. Overall, our results indicate that hostplant size, level of predation and type of predator can influence the degree to which these caterpillars react to the presence of insect predators. In contrast, degree of inherent feeding specialization and cryptic behavior seemed to have little effect on the expression of reactive behaviors of these caterpillars to predators.     

Foraging behaviour of caterpillars given a choice of plant genotypes in the presence of insect predators

1. To examine the effects of predators and plant genotype on the behaviour, patterns of herbivory, growth, and survivorship of caterpillars, an experiment was conducted under semi‐natural conditions, with two host plant genotypes (low vs. high iridoid glycosides) of plantain Plantago lanceolata, two kinds of herbivores (noncryptic specialist Junonia coenia vs. cryptic generalist Pyrrharctia isabella), and two levels of caterpillar predation (with and without Podisus maculiventris stinkbugs). 2. Choice tests conducted in the laboratory showed that in three out of four cases, caterpillars preferred leaves from the low iridoid glycoside genotype. 3. In the field experiment, the presence of predators affected the amount of leaf material eaten per plot and the proportion of leaf material eaten by the caterpillars as expected, but it did not affect the use of plant genotypes by Junonia caterpillars within the plots. In contrast, the caterpillar density–predation treatments affected the proportion of leaves eaten by Pyrrharctia caterpillars that were of the low iridoid glycoside genotype, but not entirely as expected. The caterpillars used both genotypes equally when predators were present but the high iridoid glycoside genotype was used more by caterpillars at low density and without predators. 4. The message then is that on the scale that caterpillars could be choosy about intake of iridoid glycosides they were not choosy among plant genotypes; however they were choosy between leaves, which can differ in iridoid glycoside concentration via plant genotype and leaf age.     

Effects of plant phenology, nutrients and herbivory on growth and defensive chemistry of plantain, Plantago lanceolata

To assess the combined effect of herbivory, nutrient availability and plant phenology on plant mass and defensive chemistry, we conducted a field experiment with plantain ( Plantago lanceolata : Plantaginaceae) using three levels of herbivory, three levels of fertilizer and two harvest dates. Shoot mass of the no-herbivory plants showed a nonlinear response to increased fertilizer such that mass with high fertilizer was no greater than that with low fertilizer. In contrast, shoot mass of the low-herbivory plants (12% damage) was not influenced by fertilizer, but for high-herbivory plants (23% damage), there was a positive linear response to increased fertilizer. Increasing nutrient levels caused a decrease in iridoid glycoside concentration. Herbivory did not induce higher iridoid glycoside concentration in leaves of any age. But increasing herbivory resulted in a decrease in the concentration of catalpol in new leaves. Another experiment assessed how leaf age and plant age affected plant defensive chemistry. Total iridoid glycosides increased over 5 weeks, but catalpol only increased in new leaves. Overall, the order of importance in determining variation in iridoid glycoside concentration was plant phenology, nutrient availability and, to a much lesser extent, herbivory.     

Effects of genotype,habitat, and seasonal variation on iridoid glycoside content of Plantago lanceolata (Plantaginaceae) and the implications for insect herbivores

Summary We investigated the effects of genotype, habitat, and seasonal variation on production of the iridoid glycosides, aucubin and catalpol, in leaves of the common weed Plantago lanceolata. Two genotypes, one each from a lawn and an adjacent abandoned hayfield population, were clonally replicated in the greenhouse, and then planted back into the two habitats. One quarter of the plants from each treatment were harvested on each of four dates, at approximately two-week intervals. Over the course of the growing season, and in both habitats, we found a significant increase in the concentration of both aucubin and catalpol in P. lanceolata leaves. The genotypes differed in their response to environmental variation, both in time and between sites, as indicated by significant genotype x date and genotype x site interactions. Early in the season, habitat (lawn or field) had a greater effect on iridoid glycoside concentration than did plant genotype, but later in the season, plant genotype was more influential in determining the iridoid glycoside concentration. Thus, the relative palatability of Plantago genotypes to specialist and generalist herbivores may vary in time and space.     

Indoxyl-beta-D-glucuronide, a novel chromogenic reagent for the specific detection and enumeration of Escherichia coli in environmental samples

About 97% of Escherichia coli strains produce beta-glucuronidase, but almost all other Enterobacteriaceae lack this enzyme. A D-glucopyranosiduronic acid (glucuronide) possessing a readily detectable beta-linked aglycone should, therefore, constitute a specific reagent for the detection of this organism. For this purpose, the title compound has been synthesized for the first time. The synthesis proceeds in eight steps from readily available D-glucuronolactone, anthranilic acid, and chloroacetic acid and can be carried out on a large scale. The compound has the predicted properties: when included in the standard membrane filter test for the analysis of water, indoxyl-beta-D-glucuronide allows specific detection of E. coli through the formation of blue colonies that are the result of rapid conversion of the liberated aglycone to indigo. The recovery of E. coli is easily measured and almost quantitative.