Sound-Triggered Production of Antiaggregation Pheromone Limits Overcrowding of Dendroctonus valens Attacking Pine Trees.

For insects that aggregate on host plants, both attraction and antiaggregation among conspecifics can be important mechanisms for overcoming host resistance and avoiding overcrowding, respectively. These mechanisms can involve multiple sensory modalities, such as sound and pheromones. We explored how acoustic and chemical signals are integrated by the bark beetle Dendroctonus valens to limit aggregation in China. In its native North American range, this insect conducts nonlethal attacks on weakened trees at very low densities, but in its introduced zone in China, it uses mixtures of host tree compounds and the pheromone component frontalin to mass attack healthy trees. We found that exo-brevicomin was produced by both female and male D. valens, and that this pheromone functioned as an antiaggregating signal. Moreover, beetles feeding in pairs or in masses were more likely than were beetles feeding alone to produce exo-brevicomin, suggesting a potential role of sound by neighboring beetles in stimulating exo-brevicomin production. Sound playback showed that an agreement sound was produced by both sexes when exposed to the aggregation pheromone frontalin and attracts males, and an aggressive sound was produced only by males behaving territorially. These signals triggered the release of exo-brevicomin by both females and males, indicating an interplay of chemical and sonic communication. This study demonstrates that the bark beetle D. valens uses sounds to regulate the production of an antiaggregation pheromone, which may provide new approaches to pest management of this invasive species.

Patient-specific analysis of co-expression to measure biological network rewiring in individuals.

To effectively understand the underlying mechanisms of disease and inform the development of personalized therapies, it is critical to harness the power of differential co-expression (DCE) network analysis. Despite the promise of DCE network analysis in precision medicine, current approaches have a major limitation: they measure an average differential network across multiple samples, which means the specific etiology of individual patients is often overlooked. To address this, we present Cosinet, a DCE-based single-sample network rewiring degree quantification tool. By analyzing two breast cancer datasets, we demonstrate that Cosinet can identify important differences in gene co-expression patterns between individual patients and generate scores for each individual that are significantly associated with overall survival, recurrence-free interval, and other clinical outcomes, even after adjusting for risk factors such as age, tumor size, HER2 status, and PAM50 subtypes. Cosinet represents a remarkable development toward unlocking the potential of DCE analysis in the context of precision medicine.

Paralog-based synthetic lethality: rationales and applications.

Tumor cells can result from gene mutations and over-expression. Synthetic lethality (SL) offers a desirable setting where cancer cells bearing one mutated gene of an SL gene pair can be specifically targeted by disrupting the function of the other genes, while leaving wide-type normal cells unharmed. Paralogs, a set of homologous genes that have diverged from each other as a consequence of gene duplication, make the concept of SL feasible as the loss of one gene does not affect the cell's survival. Furthermore, homozygous loss of paralogs in tumor cells is more frequent than singletons, making them ideal SL targets. Although high-throughput CRISPR-Cas9 screenings have uncovered numerous paralog-based SL pairs, the unclear mechanisms of targeting these gene pairs and the difficulty in finding specific inhibitors that exclusively target a single but not both paralogs hinder further clinical development. Here, we review the potential mechanisms of paralog-based SL given their function and genetic combination, and discuss the challenge and application prospects of paralog-based SL in cancer therapeutic discovery.

Using graph-based model to identify cell specific synthetic lethal effects.

Synthetic lethal (SL) pairs are pairs of genes whose simultaneous loss-of-function results in cell death, while a damaging mutation of either gene alone does not affect the cell's survival. This makes SL pairs attractive targets for precision cancer therapies, as targeting the unimpaired gene of the SL pair can selectively kill cancer cells that already harbor the impaired gene. Limited by the difficulty of finding true SL pairs, especially on specific cell types, current computational approaches provide only limited insights because of overlooking the crucial aspects of cellular context dependency and mechanistic understanding of SL pairs. As a result, the identification of SL targets still relies on expensive, time-consuming experimental approaches. In this work, we applied cell-line specific multi-omics data to a specially designed deep learning model to predict cell-line specific SL pairs. Through incorporating multiple types of cell-specific omics data with a self-attention module, we represent gene relationships as graphs. Our approach achieves the prediction of SL pairs in a cell-specific manner and demonstrates the potential to facilitate the discovery of cell-specific SL targets for cancer therapeutics, providing a tool to unearth mechanisms underlying the origin of SL in cancer biology. The code and data of our approach can be found at https://github.com/promethiume/SLwise.

CYP4G8 is responsible for the synthesis of methyl-branched hydrocarbons in the polyphagous caterpillar of Helicoverpa armigera.

Insect cuticular hydrocarbons (CHCs) have dual functions as physical barrier and chemical signals. The last step of CHC biosynthesis is known to be catalyzed by cytochrome P450 CYP4G in a number of insects. Until recently, studies on CYP4Gs in the context of functional evolution are rare. In this study, we analyzed sequence similarity and temporal-spatial expression patterns of the five CYP4G genes in the cotton bollworm Helicoverpa armigera, an important agricultural pest and also typical representative of lepidopteran insects. Moreover, the CRISPR/Cas9-induced knockout was used to clarify the roles of the five CYP4Gs in CHC biosynthesis. Temporal-spatial expression patterns revealed that CYP4G8 was highly expressed at all developmental stages and in most tissues examined. Larvae with CYP4G8 knocked out could not produce methyl-branched CHCs and failed to pupate, while larvae with the other four CYP4G genes knocked out (4G1-type-KO) showed no significant changes in their CHC profiles, weight gain and survival. Comparative transcriptomics revealed that knocking out CYP4G8 affected the global gene expression in larvae, especially down-regulated the expression of genes in the fatty acid biosynthetic pathway, while no significant change in 4G1-type-KO transcriptome was observed. These findings indicate that the five members of the CYP4G subfamily have undergone functional divergence: CYP4G8 maintains the essential function in CHC biosynthesis, while the function of the other four CYP4G genes remains unclear. Intriguingly, CYP4G8 has evolved to be a P450 enzyme responsible for the synthesis of larval methyl-branched hydrocarbons. The observation that CYP4G8 knockout is lethal strongly suggest that CYP4G8 may serve as a candidate target for the development of insecticidal agents for the control of cotton bollworms.

Functional characterization of a novel, highly expressed ion-driven sugar antiporter in the thoracic muscles of Helicoverpa armigera.

Sugar transporters (STs), which mainly mediate cellular sugar exchanges, play critical physiological roles in living organisms, and they may be responsible for sugar exchanges among various insect tissues. However, the molecular and physiological functions of insect STs are largely unknown. Here, 16 STs of Helicoverpa armigera were identified. A phylogenetic analysis classified the putative HaSTs into 12 sub-families, and those identified in this study were distributed into 6 sub-families. Real-time polymerase chain reaction indicated that the 16 HaSTs had diverse tissue-specific expression levels. One transporter, HaST10, was highly expressed in thoracic muscles. A functional study using a Xenopus oocyte expression system revealed that HaST10 mediated both H+ -driven trehalose and Na+ -driven glucose antiport activities with high transport efficiency and low affinity levels. A HaST10 knockout clearly impaired the performance of H. armigera. Thus, HaST10 may participate in sugar-supply regulation and have essential physiological roles in H. armigera.

Summer diapause induced by high temperatures in the oriental tobacco budworm: ecological adaptation to hot summers.

Summer diapause in Helicoverpa assulta (Hübner), which prolongs the pupal stage, particularly in males, is induced by high temperatures. In the laboratory, 3(rd)-, 4(th)-, 6(th)-instar and prepupal larvae were exposed to high temperatures - 33 and 35 °C with a photoperiod of LD16:8 - until pupation to induce summer diapause. The results showed that the incidence of summer diapause was influenced by temperature, stage exposed, and sex. The higher the temperature, the more often summer diapause was attained. Sixth-instar and prepupal larvae were the sensitive stages for summer diapause induction. H. assulta summer-diapausing pupae needed diapause development to resume development when temperatures became favorable. Furthermore, both body mass and energy storage capacity (lipid and glycogen) were significantly affected by diapause rather than sex, and were significantly higher in summer-diapausing pupae than in non-diapausing pupae. In addition, the body mass loss and respiration rate showed that the rate of metabolism in the summer-diapausing pupae was consistently lower than in non-diapausing pupae, which were significantly affected by diapause and pupal age. We conclude that summer diapause in H. assulta is a true diapause, and H. assulta has evolved mechanisms to accumulate energy storage and to lower its metabolism to adapt to hot summers.