Early Starvation Contributes to the Adaptive Capacity of Corythucha marmorata (Uhler), an Emerging Pest in China

Food shortages severely reduce the prospects of insect survival in natural settings, including in the case of herbivorous insects. However, the early starvation experience of some insects has positive effects throughout their entire lifespan. It is important to discuss the effects of refeeding and host plants on the capacity of herbivorous insects to adapt to starvation and low temperatures, considering that starvation resistance is expected to show some degree of adaptive phenotypic plasticity. We tested the relationship between host plant, starvation, and the supercooling capacity of the invasive pest Corythucha marmorata. In particular, we highlighted how early starvation affects the refeeding and recovery phases. Among the various range of hosts, the chrysanthemum lace bug has the fastest growth rate on Helianthus annuus, and the strongest supercooling capacity on Symphyotrichum novi-belgii. Especially, starvation for 2 days increases the rates of survival, development, and number of eggs upon refeeding, in comparison to no starvation. A 3-day starvation period in the nymphal stage significantly increased the supercooling capacity of 5th instar nymphs and adults, as observed in our study.

Overexpression of Cystine/Glutamate Antiporter xCT Correlates with Nutrient Flexibility and ZEB1 Expression in Highly Clonogenic Glioblastoma Stem-like Cells (GSCs)

Cancer stem-like cells mediate tumor initiation, progression, and therapy resistance; however, their identification and selective eradication remain challenging. Herein, we analyze the metabolic dependencies of glioblastoma stem-like cells (GSCs) with high-resolution proton nuclear magnetic resonance (1H-NMR) spectroscopy. We stratify our in vitro GSC models into two subtypes primarily based on their relative amount of glutamine in relationship to glutamate (Gln/Glu). Gln/GluHigh GSCs were found to be resistant to glutamine deprivation, whereas Gln/GluLow GSCs respond with significantly decreased in vitro clonogenicity and impaired cell growth. The starvation resistance appeared to be mediated by an increased expression of the glutamate/cystine antiporter SLC7A11/xCT and efficient cellular clearance of reactive oxygen species (ROS). Moreover, we were able to directly correlate xCT-dependent starvation resistance and high Gln/Glu ratios with in vitro clonogenicity, since targeted differentiation of GSCs with bone morphogenic protein 4 (BMP4) impaired xCT expression, decreased the Gln/Glu ratio, and restored the sensitivity to glutamine starvation. Moreover, significantly reduced levels of the oncometabolites lactate (Lac), phosphocholine (PC), total choline (tCho), myo-inositol (Myo-I), and glycine (Gly) were observed in differentiated GSCs. Furthermore, we found a strong association between high Gln/Glu ratios and increased expression of Zinc finger E-box-binding homeobox 1 (ZEB1) and xCT in primary GBM tumor tissues. Our analyses suggest that the inhibition of xCT represents a potential therapeutic target in glioblastoma; thus, we could further extend its importance in GSC biology and stress responses. We also propose that monitoring of the intracellular Gln/Glu ratio can be used to predict nutrient stress resistance.

Jack, Master or Both? The Invasive Ladybird Harmonia Axyridis Outperforms Its Native Counterpart Despite Similar Levels of Plasticity

The plasticity of performance traits is expected to promote the successful invasion of species. Therefore, the comparison of reaction norms of invasive species with native competitors should enhance predictions of alien species establishment. Yet, most studies focus on a reduced set of traits, rarely in combination, or do not include trait variability to make predictions of establishment success. Here, we acclimated individuals to a cold, medium or warm temperature regime and measured critical thermal limits, life-history traits, and starvation resistance of the globally invasive Harmonia axyridis and its native counterpart Cheilomenes lunata. The native C. lunata had higher thermal plasticity of starvation resistance and higher upper thermal tolerance than H. axyridis. By contrast, H. axyridis outperformed C. lunata in most life-history traits. We combined trait responses, transport duration and propagule pressure to simulate the final number of beetles established in the introduced site in cold, medium and warm scenarios, where beetles also experienced a heatwave once established. Although C. lunata initially outcompeted the invasive species during transport, more H. axyridis survived in all environments because of higher life-history trait responses, in particular, higher fecundity. Despite increased starvation mortality in the warm scenario, H. axyridis established successfully given sufficient propagule size. By contrast, in the event of a heatwave, H. axyridis numbers plummeted and higher numbers of the native species established in the cold scenario. This study underscores the importance of considering a combination of traits and respective cascading effects when estimating the establishment potential of species and responses to climate warming.

RIPK1 regulates starvation resistance by modulating aspartate catabolism

RIPK1 is a crucial regulator of cell death and survival. Ripk1 deficiency promotes mouse survival in the prenatal period while inhibits survival in the early postnatal period without a clear mechanism. Metabolism regulation and autophagy are critical to neonatal survival from severe starvation at birth. However, the mechanism by which RIPK1 regulates starvation resistance and survival remains unclear. Here, we address this question by discovering the metabolic regulatory role of RIPK1. First, metabolomics analysis reveals that Ripk1 deficiency specifically increases aspartate levels in both mouse neonates and mammalian cells under starvation conditions. Increased aspartate in Ripk1−/− cells enhances the TCA flux and ATP production. The energy imbalance causes defective autophagy induction by inhibiting the AMPK/ULK1 pathway. Transcriptional analyses demonstrate that Ripk1−/− deficiency downregulates gene expression in aspartate catabolism by inactivating SP1. To summarize, this study reveals that RIPK1 serves as a metabolic regulator responsible for starvation resistance.

Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster

Chronobiotics are a group of drugs, which are utilized to modify circadian rhythms targeting clock-associated molecular mechanisms. The circadian clock is known as a controller of numerous processes in connection with aging. Hypothesis: KL001 and KS15 targeting CRY, affect lifespan, locomotor activity and circadian rhythm of Drosophila melanogaster. We observed a slight (2%, p < 0.001) geroprotective effect on median lifespan (5 µM solution of KL001 in 0.1% DMSO) and a 14% increase in maximum lifespan in the same group. KS15 10 µM solution extended males’ median lifespan by 8% (p < 0.05). The statistically significant positive effects of KL001 and KS15 on lifespan were not observed in female flies. KL001 5 µM solution improved locomotor activity in young male imagoes (p < 0.05), elevated morning activity peak in aged imagoes and modified robustness of their circadian rhythms, leaving the period intact. KS15 10 µM solution decreased the locomotor activity in constant darkness and minimized the number of rhythmic flies. KL001 5 µM solution improved by 9% the mean starvation resistance in male flies (p < 0.01), while median resistance was elevated by 50% (p < 0.0001). This phenomenon may suggest the presence of the mechanism associated with improvement of fat body glucose depos’ utilization in starvation conditions which is activated by dCRY binding KL001.

Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster

Chronobiotics is a group of drugs utilized to modify circadian rhythms targeting clock-associated molecular mechanisms. The circadian clock is known as a controller of numerous processes standing behind aging. Hypothesis: KL001 and KS15 targeting CRY, affect lifespan, locomotor activity and circadian rhythm of Drosophila melanogaster. We observed a slight (2%, p&lt;0.001) geroprotective effect on median lifespan (5 &micro;M solution of KL001 in 0.1% DMSO) and a 14% increase in maximum lifespan in the same group. KS15 10 &micro;M solution extended males&rsquo; median lifespan by 8% (p &lt;0.05). The statistically significant positive effects of KL001 and KS15 on lifespan were not observed in female flies. KL001 5 &micro;M solution improved locomotor activity in young male imagos (p&lt;0.05) and elevated morning activity peak in aged imagos and modified robustness of circadian rhythms, leaving the period intact. KS15 10 &micro;M solution decreased the locomotor activity in constant darkness and minimized the number of rhythmic flies. KL001 5 &micro;M solution improved by 9% the mean starvation resistance in male flies (p&lt;0.01), while median resistance was elevated by 50% (p&lt;0.0001). This phenomenon may suggest the presence of the mechanism associated with improvement of fat body glucose depos&rsquo; utilization in starvation conditions which is activated by dCRY binding KL001.

A screen for sleep and starvation resistance identifies a wake-promoting role for the auxiliary channel unc79

The regulation of sleep and metabolism are highly interconnected, and dysregulation of sleep is linked to metabolic diseases that include obesity, diabetes, and heart disease. Further, both acute and long-term changes in diet potently impact sleep duration and quality. To identify novel factors that modulate interactions between sleep and metabolic state, we performed a genetic screen for their roles in regulating sleep duration, starvation resistance, and starvation-dependent modulation of sleep. This screen identified a number of genes with potential roles in regulating sleep, metabolism or both processes. One such gene encodes the auxiliary ion channel UNC79, which was implicated in both the regulation of sleep and starvation resistance. Genetic knockdown or mutation of unc79 results in flies with increased sleep duration, as well as increased starvation resistance. Previous findings have shown that unc79 is required in pacemaker for 24-hour circadian rhythms. Here, we find that unc79 functions in the mushroom body, but not pacemaker neurons, to regulate sleep duration and starvation resistance. Together, these findings reveal spatially localized separable functions of unc79 in the regulation of circadian behavior, sleep, and metabolic function.

Natural variation in the irld gene family affects insulin/IGF signaling and starvation resistance

Starvation resistance is a fundamental, disease-relevant trait, but the genetic basis of its natural variation is unknown. We developed a synthetic population-sequencing approach to measure starvation resistance for many wild C. elegans strains simultaneously. We identified three quantitative trait loci with variants in 16 insulin/EGF receptor-like domain (irld) family members. We show that four irld genes affect starvation resistance by regulating insulin/IGF signaling. We propose that IRLD proteins bind insulin-like peptides to modify signaling in the sensory nervous system thereby affecting organismal physiology. This work demonstrates efficacy of using population sequencing to dissect a complex trait, identifies irld genes that regulate insulin/IGF signaling, and shows that an expanded gene family modifies a deeply conserved signaling pathway to affect a fitness-proximal trait.

Genome wide analysis in Drosophila reveals diet by gene interactions and uncovers diet-responsive genes

Genetic and environmental factors play a major role in metabolic health. However, they do not act in isolation, as a change in an environmental factor such as diet may exert different effects based on an individual’s genotype. Here, we sought to understand how such gene-diet interactions influenced nutrient storage and utilization, a major determinant of metabolic disease. We subjected 178 inbred strains from the Drosophila Genetic Reference Panel (DGRP), to diets varying in sugar, fat and protein. We assessed starvation resistance, a holistic phenotype of nutrient storage and utilization that can be robustly measured. Diet influenced the starvation resistance of most strains, but the effect varied markedly between strains such that some displayed better survival on a high carbohydrate diet compared to a high fat diet while others had opposing responses, illustrating a considerable gene x diet interaction. This demonstrates that genetics plays a major role in diet responses. Furthermore, heritability analysis revealed that the greatest genetic variability arose from diets either high in sugar or high in protein. To uncover the genetic variants that contribute to the heterogeneity in starvation resistance, we mapped 566 diet-responsive SNPs in 293 genes, 174 of which have human orthologues. Using whole-body knockdown, we identified two genes that were required for glucose tolerance, storage and utilization. Strikingly, flies in which the expression of one of these genes, CG4607 a putative homolog of a mammalian glucose transporter, was reduced at the whole-body level, displayed lethality on a high carbohydrate diet. This study provides evidence that there is a strong interplay between diet and genetics in governing survival in response to starvation, a surrogate measure of nutrient storage efficiency and obesity. It is likely that a similar principle applies to higher organisms thus supporting the case for nutrigenomics as an important health strategy.

Activation of innate immune signalling during development predisposes to inflammatory intestine and shortened lifespan

Early-life inflammatory response is associated with risks of age-related pathologies. How transient immune signalling activity during animal development influences life-long fitness is not well understood. Using Drosophila as a model, we find that activation of innate immune pathway IMD signalling in the developing larvae increases adult starvation resistance, decreases food intake, and shortens organismal lifespan. Interestingly, lifespan is shortened by the IMD activation in the larval gut and fat body, while starvation resistance and food intake are altered by that in neurons. The adult flies developed with IMD activation show sustained IMD activity in the gut, despite complete tissue renewal during metamorphosis. The inflammatory adult gut is associated with a greater amount of Gluconobacter sp., characteristic gut microbiota increased in response to immune activation. Removing gut microbiota by antibiotics attenuates the increase of IMD activity and rescues the shortened lifespan. This study demonstrates a tissue-specific programming effect of early-life immune activation on the adult physiology and organismal lifespan.