Three chemosensory proteins enriched in antennae and tarsi of Rhaphuma horsfieldi differentially contribute to the binding of insecticides.

Antennae and legs (primarily the tarsal segments) of insects are the foremost sensory organs that contact a diverse range of toxic chemicals including insecticides. Binding proteins expressed in the two tissues are potential molecular candidates serving as the binding and sequestering of insecticides, like chemosensory proteins (CSPs). Insect CSPs endowed with multiple roles have been suggested to participate in insecticide resistance, focusing mainly on moths, aphids and mosquitos. Yet, the molecular underpinnings underlying the interactions of cerambycid CSPs and insecticides remain unexplored. Here, we present binding properties of three antenna- and tarsus-enriched RhorCSPs (RhorCSP1, CSP2 and CSP3) in Rhaphuma horsfieldi to eight insecticide classes totaling 15 chemicals. From the transcriptome of this beetle, totally 16 CSP-coding genes were found, with seven full-length sequences. In phylogeny, these RhorCSPs were distributed dispersedly in different clades. Expression profiles revealed the abundant expression of RhorCSP1, CSP2 and CSP3 in antennae and tarsi, thus as representatives for studying the protein-insecticide interactions. Binding assays showed that the three RhorCSPs were tuned differentially to insecticides but exhibited the highest affinities with hexaflumuron, chlorpyrifos and rotenone (dissociation constants <13 µM). In particular, RhorCSP3 could interact strongly with 10 of tested insecticides, of which four residues (Tyr25, Phe42, Val65 and Phe68) contributed significantly to the binding of six, four, three and four ligands, respectively. Of these, the binding of four mutated RhorCSP3s to a botanical insecticide rotenone was significantly weakened compared to the wildtype protein. Furthermore, we also evidenced that RhorCSP3 was a broadly-tuned carrier protein in response to a wide variety of plant odorants outside insecticides. Altogether, our findings shed light on different binding mechanisms and odorant-tuning profiles of three RhorCSPs in R. horsfieldi and identify key residues of the RhorCSP3-insecticide interactions.

A Meta-Analysis of 5-Hydroxytryptamine Receptor 1B Polymorphisms With Risk of Major Depressive Disorder and Suicidal Behavior.

Purpose: Previous association studies have investigated whether genetic polymorphisms in HTR1B influenced individuals' susceptibility to major depressive disorder (MDD), anti-depressant response (ADR) and suicidal behavior. However, equivocal evidence was obtained. In this meta-analysis, we aimed to examine the association of HTR1B polymorphisms with risk of MDD, ADR and suicidal behavior. Materials and Methods: Studies evaluating the association between HTR1B polymorphisms and risk of MDD, ADR and suicidal behavior were searched in Pubmed, Ovid Medline, web of science and China National Knowledge Infrastructure databases. Summary odds ratios (ORs), 95 % confidence intervals (CIs) and p-values were calculated using a fixed or random effects model. Results: Meta-analysis findings revealed a significantly increased risk of MDD with rs6296 GC and GC/CC genotypes (GC vs. GG: OR = 1.26, 95% CI, 1.07-1.48; GC/CC vs. GG: OR = 1.22, 95% CI, 1.04-1.43, respectively). Moreover, rs6298 CT genotype was significantly associated with an increased risk of suicidal behavior (CT vs. CC: OR = 1.48, 95% CI, 1.16-1.88). However, both rs6296 and rs130058 were not significant risk factors for lethal suicidal behavior. Conclusion: This meta-analysis identified that rs6296 and rs6298 in HTR1B may be significantly related to the risk of MDD and lethality of suicide attempts, respectively. Further studies are required to assess the markers in larger cohorts.