Exposure to ultraviolet-B radiation increases the susceptibility of mosquitoes to infection with dengue virus

By 2100, greenhouse gases are predicted to reduce ozone and cloud cover over the tropics causing increased exposure of organisms to harmful ultraviolet-B radiation (UVBR). UVBR damages DNA and is an important modulator of immune function and disease susceptibility in humans and other vertebrates. The effect of UVBR on invertebrate immune function is largely unknown, but UVBR together with ultraviolet-A radiation impairs an insect immune response that utilizes melanin, a pigment that also protects against UVBR-induced DNA damage. If UVBR weakens insect immunity, then it may make insect disease vectors more susceptible to infection with pathogens of socioeconomic and public health importance. In the tropics, where UVBR is predicted to increase, the mosquito-borne dengue virus (DENV), is prevalent and a growing threat to humans. We therefore examined the effect of UVBR on the mosquito Aedes aegypti, the primary vector for DENV, to better understand the potential implications of increased tropical UVBR for mosquito-borne disease risk. We found that exposure to a UVBR dose that caused significant larval mortality approximately doubled the probability that surviving females would become infected with DENV, despite this UVBR dose having no effect on the expression of an effector gene involved in antiviral immunity. We also found that females exposed to a lower UVBR dose were more likely to have low fecundity even though this UVBR dose had no effect on larval size or activity, pupal cuticular melanin content, or adult mass, metabolic rate, or flight capacity. We conclude that future increases in tropical UVBR associated with anthropogenic global change may have the benefit of reducing mosquito-borne disease risk for humans by reducing mosquito fitness, but this benefit may be eroded if it also makes mosquitoes more likely to be infected with deadly pathogens.     

Depression of voltage-activated Ca2+ release in skeletal muscle by activation of a voltage-sensing phosphatase

Phosphoinositides act as signaling molecules in numerous cellular transduction processes, and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P₂) regulates the function of several types of plasma membrane ion channels. We investigated the potential role of PtdIns(4,5)P₂ in Ca²⁺ homeostasis and excitation–contraction (E-C) coupling of mouse muscle fibers using in vivo expression of the voltage-sensing phosphatases (VSPs) Ciona intestinalis VSP (Ci-VSP) or Danio rerio VSP (Dr-VSP). Confocal images of enhanced green fluorescent protein–tagged Dr-VSP revealed a banded pattern consistent with VSP localization within the transverse tubule membrane. Rhod-2 Ca²⁺ transients generated by 0.5-s-long voltage-clamp depolarizing pulses sufficient to elicit Ca²⁺ release from the sarcoplasmic reticulum (SR) but below the range at which VSPs are activated were unaffected by the presence of the VSPs. However, in Ci-VSP–expressing fibers challenged by 5-s-long depolarizing pulses, the Ca²⁺ level late in the pulse (3 s after initiation) was significantly lower at 120 mV than at 20 mV. Furthermore, Ci-VSP–expressing fibers showed a reversible depression of Ca²⁺ release during trains, with the peak Ca²⁺ transient being reduced by ∼30% after the application of 10 200-ms-long pulses to 100 mV. A similar depression was observed in Dr-VSP–expressing fibers. Cav1.1 Ca²⁺ channel–mediated current was unaffected by Ci-VSP activation. In fibers expressing Ci-VSP and a pleckstrin homology domain fused with monomeric red fluorescent protein (PLCδ₁PH-mRFP), depolarizing pulses elicited transient changes in mRFP fluorescence consistent with release of transverse tubule–bound PLCδ₁PH domain into the cytosol; the voltage sensitivity of these changes was consistent with that of Ci-VSP activation, and recovery occurred with a time constant in the 10-s range. Our results indicate that the PtdIns(4,5)P₂ level is tightly maintained in the transverse tubule membrane of the muscle fibers, and that VSP-induced depletion of PtdIns(4,5)P₂ impairs voltage-activated Ca²⁺ release from the SR. Because Ca²⁺ release is thought to be independent from InsP₃ signaling, the effect likely results from an interaction between PtdIns(4,5)P₂ and a protein partner of the E-C coupling machinery.     

Focus: Allergic Diseases and Type II Immunity: Allergy Prevention: An Overview of Current Evidence

Background: There has been a rapid rise in allergic disorders across the globe. This has increased research into the determinants of allergy development, to identify factors that may be manipulated to mitigate risk. An opportune window in immunological development appears to exist in early life whereby certain exposures may promote or prevent the development of an allergic disposition. Furthermore, factors that affect the composition and diversity of the microbiome in early life have been explored. In this review, we discuss current literature and recommendations relating to exposures that may prevent allergy development or promote tolerance. Risk factors and recommendations: Delivery by caesarean section, omission of breastfeeding, vitamin D insufficiency, and environmental exposures, such as cigarette smoke exposure, all increase the risk of an allergic predisposition. Dietary diversity during pregnancy, lactation, and in infancy is protective. Breastfeeding for at least 4 months reduces the risk of eczema. Recommendations for food-allergen exposure has shifted from delayed introduction to early introduction as a tolerance-inducing strategy. Supplements such as probiotics and vitamins during pregnancy and infancy have yet to produce conclusive results for allergy prevention. Emollient use in infancy has not been shown to be protective against eczema or food allergy.