The insecticidal potential of venom peptides

Pest insect species are a burden to humans as they destroy crops and serve as vectors for a wide range of diseases including malaria and dengue. Chemical insecticides are currently the dominant approach for combating these pests. However, the de-registration of key classes of chemical insecticides due to their perceived ecological and human health risks in combination with the development of insecticide resistance in many pest insect populations has created an urgent need for improved methods of insect pest control. The venoms of arthropod predators such as spiders and scorpions are a promising source of novel insecticidal peptides that often have different modes of action to extant chemical insecticides. These peptides have been optimized via a prey–predator arms race spanning hundreds of millions of years to target specific types of insect ion channels and receptors. Here we review the current literature on insecticidal venom peptides, with a particular focus on their structural and pharmacological diversity, and discuss their potential for deployment as insecticides.     

CREB regulates hepatic gluconeogenesis through the coactivator PGC-1

When mammals fast, glucose homeostasis is achieved by triggering expression of gluconeogenic genes in response to glucagon and glucocorticoids. The pathways act synergistically to induce gluconeogenesis (glucose synthesis), although the underlying mechanism has not been determined. Here we show that mice carrying a targeted disruption of the cyclic AMP (cAMP) response element binding (CREB) protein gene, or overexpressing a dominant-negative CREB inhibitor, exhibit fasting hypoglycaemia [corrected] and reduced expression of gluconeogenic enzymes. CREB was found to induce expression of the gluconeogenic programme through the nuclear receptor coactivator PGC-1, which is shown here to be a direct target for CREB regulation in vivo. Overexpression of PGC-1 in CREB-deficient mice restored glucose homeostasis and rescued expression of gluconeogenic genes. In transient assays, PGC-1 potentiated glucocorticoid induction of the gene for phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme in gluconeogenesis. PGC-1 promotes cooperativity between cyclic AMP and glucocorticoid signalling pathways during hepatic gluconeogenesis. Fasting hyperglycaemia is strongly correlated with type II diabetes, so our results suggest that the activation of PGC-1 by CREB in liver contributes importantly to the pathogenesis of this disease.     

Feeding behavior and performance of a rabbitbrush leaf-beetle ( Trirhabda lewisii ) feeding on Chrysothamnus nauseosus regrwoth after fire

Fire often positively affects the growth and nutrient content of plants regrowing after a burn. These changes have been associated with preferential feeding by herbivores in burned areas. In this study in southeastern Wyoming, Chrysothamnus nauseosus Pursh (rubber rabbitbrush) regrowing after a fire produced new shoots with a distinct growth form. Shoots were longer than those on unburned control sites and had longer leaves with longer internodes between leaves. We conducted feeding trials to detect whether C. nauseosus shoots regrowing after fire were nutritionally superior to shoots from unburned plants for the specialist leaf beetle, Trirhabda lewisii Crotch (Coleoptera: Chrysomelidae). We also measured C:N ratios and nitrogen and water contents of leaves from burned and unburned plants. Trirhabda lewisii adults preferred shoots from burned plants when given a choice. The beetles ate similar amounts of burned and unburned plants when fed only a single type. Females that were fed either burned or unburned plants did not differ in number of eggs laid. Chemical analyses revealed no significant differences in nitrogen or water content of leaves from burned versus unburned plants. Carbon-to-nitrogen ratio of burned plants was marginally lower compared with unburned plants. In contrast to previous studies, which suggest that herbivore attraction to burned areas leads to enhanced performance, our study shows that performance is not necessarily enhanced after fire.     

Evidence for cross bridge slippage in a stretched muscle fibre

Summary Bundles of glycerol-extracted psoas fibres which were contracted by immersion in a saline containing 15 mM MgATP and 12 M free Ca⁺⁺ were subjected to up to 3 stretches (rise time 0.8 msec) each of amplitude 1% L_i at intervals of 10 msec. The elastic tension responses to these stretches were all of comparable size and the peak tensions reached during the stretches were in each case followed by a rapid tension decline almost to the tension values before the stretches. This indicates that stretch-induced detachment and reattachment of cross bridges to the actin filament occurred within 10 msec (slippage).Supported by the Deutsche Forschungsgemeinschaft, grant Ru 154/12. The editorial assistance of Mr D.J. Williams is gratefully acknowledged.     

Cystatin C modulates cerebral beta-amyloidosis

The CST3 Thr25 allele of CST3, which encodes cystatin C, leads to reduced cystatin C secretion and conveys susceptibility to Alzheimer's disease. Here we show that overexpression of human cystatin C in brains of APP-transgenic mice reduces cerebral amyloid-beta deposition and that cystatin C binds amyloid-beta and inhibits its fibril formation. Our results suggest that cystatin C concentrations modulate cerebral amyloidosis risk and provide an opportunity for genetic risk assessment and therapeutic interventions.