Variation in Vector Competence for Dengue Viruses Does Not Depend on Mosquito Midgut Binding Affinity

Several factors, such as mosquito and virus genetics and environmental variables, determine the ability of mosquitoes to transmit dengue viruses. In this report, we describe new and important information that in some ways contradicts what is in the literature. Midgut infection barriers have been described as important determinants of virus transmission in mosquitoes but we found that virus binding to these midgut cells does not vary. When we compared binding of 8 different, low passage dengue viruses to mosquito midguts that were dissected out of Aedes aegypti mosquitoes (the main vectors of dengue) from Mexico and Texas, we found that there were no differences. Previously, we (and others) had shown that these same viruses differed significantly in replication and dissemination throughout the rest of the mosquito body, including the salivary glands, and therefore they differed greatly in their potential to be transmitted to humans. Thus, the data presented here are important considerations for future studies of vector competence and in determining strategies for control of dengue viruses in the vector

Extensive Crosstalk between O-GlcNAcylation and Phosphorylation Regulates Akt Signaling

O-linked N-acetylglucosamine glycosylations (O-GlcNAc) and O-linked phosphorylations (O-phosphate), as two important types of post-translational modifications, often occur on the same protein and bear a reciprocal relationship. In addition to the well documented phosphorylations that control Akt activity, Akt also undergoes O-GlcNAcylation, but the interplay between these two modifications and the biological significance remain unclear, largely due to the technique challenges. Here, we applied a two-step analytic approach composed of the O-GlcNAc immunoenrichment and subsequent O-phosphate immunodetection. Such an easy method enabled us to visualize endogenous glycosylated and phosphorylated Akt subpopulations in parallel and observed the inhibitory effect of Akt O-GlcNAcylations on its phosphorylation. Further studies utilizing mass spectrometry and mutagenesis approaches showed that O-GlcNAcylations at Thr 305 and Thr 312 inhibited Akt phosphorylation at Thr 308 via disrupting the interaction between Akt and PDK1. The impaired Akt activation in turn resulted in the compromised biological functions of Akt, as evidenced by suppressed cell proliferation and migration capabilities. Together, this study revealed an extensive crosstalk between O-GlcNAcylations and phosphorylations of Akt and demonstrated O-GlcNAcylation as a new regulatory modification for Akt signaling

Soil-Transmitted Helminth Reinfection after Drug Treatment: A Systematic Review and Meta-Analysis

Infections with soil-transmitted helminths (the roundworm Ascaris lumbricoides, the whipworm Trichuris trichiura, and hookworm) affect over 1 billion people, particularly rural communities in the developing world. The global strategy to control soil-transmitted helminth infections is ‘preventive chemotherapy’, which means large-scale administration of anthelmintic drugs to at-risk populations. However, because reinfection occurs after treatment, ‘preventive chemotherapy’ must be repeated regularly. Our systematic review and meta-analysis found that at 3, 6, and 12 months after treatment, A. lumbricoides prevalence reached 26% (95% confidence interval (CI): 16–43%), 68% (95% CI: 60–76%) and 94% (95% CI: 88–100%) of pretreatment levels, respectively. For T. trichiura, respective reinfection prevalence at these time points were 36% (95% CI: 28–47%), 67% (95% CI: 42–100%), and 82% (95% CI: 62–100%); and for hookworm, 30% (95% CI: 26–34%), 55% (95% CI: 34–87%), and 57% (95% CI: 49–67%). Prevalence and intensity of reinfection were positively correlated with pretreatment infection status. Our results suggest a frequent anthelmintic drug administration to maximize the benefit of preventive chemotherapy. Moreover, an integrated control strategy, consisting of preventive chemotherapy combined with health education and environmental sanitation is needed to interrupt transmission of soil-transmitted helminths