Glutamine enhances sucrose taste through a gut microbiota-gut-brain axis in Drosophila.

AIMS: Amino acids (AAs) are known to play important roles in various physiological functions. However, their effect on sweet taste perception remains largely unknown. MAIN METHODS: We used Drosophila to evaluate the effect of each AA on sucrose taste perception. Individual AA was supplemented into diets and male flies were fed on these diets for 6 days. The proboscis extension response (PER) assay was applied to assess the sucrose taste sensitivity of treated flies. We further utilized the RNA-seq and germ-free (GF) flies to reveal the underlying mechanisms of sucrose taste sensitization induced by glutamine (Gln). KEY FINDINGS: We found that supplementation of Gln into diets significantly enhances sucrose taste sensitivity. This sucrose taste sensitization is dependent on gut microbiota and requires a specific gut bacterium Acetobacter tropicalis (A. tropicalis). We further found that CNMamide (CNMa) in the gut and CNMa receptor (CNMaR) in dopaminergic neurons are required for increased sucrose taste sensitivity by Gln diet. Finally, we demonstrated that a gut microbiota-gut-brain axis is required for Gln-induced sucrose taste sensitization. SIGNIFICANCE: These findings can advance understanding of the complex interplay between host physiology, dietary factors, and gut microbiota.

On the origin of appetite: GLWamide in jellyfish represents an ancestral satiety neuropeptide.

Food intake is regulated by internal state. This function is mediated by hormones and neuropeptides, which are best characterized in popular model species. However, the evolutionary origins of such feeding-regulating neuropeptides are poorly understood. We used the jellyfish Cladonema to address this question. Our combined transcriptomic, behavioral, and anatomical approaches identified GLWamide as a feeding-suppressing peptide that selectively inhibits tentacle contraction in this jellyfish. In the fruit fly Drosophila, myoinhibitory peptide (MIP) is a related satiety peptide. Surprisingly, we found that GLWamide and MIP were fully interchangeable in these evolutionarily distant species for feeding suppression. Our results suggest that the satiety signaling systems of diverse animals share an ancient origin.

A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice.

Can limb regeneration be induced? Few have pursued this question, and an evolutionarily conserved strategy has yet to emerge. This study reports a strategy for inducing regenerative response in appendages, which works across three species that span the animal phylogeny. In Cnidaria, the frequency of appendage regeneration in the moon jellyfish Aurelia was increased by feeding with the amino acid L-leucine and the growth hormone insulin. In insects, the same strategy induced tibia regeneration in adult Drosophila. Finally, in mammals, L-leucine and sucrose administration induced digit regeneration in adult mice, including dramatically from mid-phalangeal amputation. The conserved effect of L-leucine and insulin/sugar suggests a key role for energetic parameters in regeneration induction. The simplicity by which nutrient supplementation can induce appendage regeneration provides a testable hypothesis across animals.

The ability of animals to replace damaged or lost tissue (or 'regenerate') is a sliding scale, with some animals able to regenerate whole limbs, while others can only scar. But why some animals can regenerate while others have more limited capabilities has puzzled the scientific community for many years. The likes of Charles Darwin and August Weismann suggested regeneration only evolves in a particular organ. In contrast, Thomas Morgan suggested that all animals are equipped with the tools to regenerate but differ in whether they are able to activate these processes. If the latter were true, it could be possible to 'switch on' regeneration. Animals that keep growing throughout their life and do not regulate their body temperatures are more likely to be able to regenerate. But what do growth and temperature regulation have in common? Both are highly energy-intensive, with temperature regulation potentially diverting energy from other processes. A question therefore presents itself: could limb regeneration be switched on by supplying animals with more energy, either in the form of nutrients like sugars or amino acids, or by giving them growth hormones such as insulin? Abrams, Tan, Li et al. tested this hypothesis by amputating the limbs of jellyfish, flies and mice, and then supplementing their diet with sucrose (a sugar), leucine (an amino acid) and/or insulin for eight weeks while they healed. Typically, jellyfish rearrange their remaining arms when one is lost, while fruit flies are not known to regenerate limbs. House mice are usually only able to regenerate the very tip of an amputated digit. But in Abrams, Tan, Li et al.'s experiments, leucine and insulin supplements stimulated limb regeneration in jellyfish and adult fruit flies, and leucine and sucrose supplements allowed mice to regenerate digits from below the second knuckle. Although regeneration was not observed in all animals, these results demonstrate that regeneration can be induced, and that it can be done relatively easily, by feeding animals extra sugar and amino acids. These findings highlight increasing the energy supplies of different animals by manipulating their diets while they are healing from an amputated limb can aid in regeneration. This could in the future pave the way for new therapeutic approaches to tissue and organ regeneration.

Insecticidal and oviposition deterrent effects of essential oils of Baccharis spp. and histological assessment against Drosophila suzukii (Diptera: Drosophilidae).

The diverse flora of the Atlantic Forest is fertile ground for discovering new chemical structures with insecticidal activity. The presence of species belonging to the genus Baccharis is of particular interest, as these species have shown promise in pest management applications. The objective of this study is to chemically identify the constituents expressed in the leaves of seven species of Baccharis (B. anomala DC., B. calvescens DC., B. mesoneura DC., B. milleflora DC., B. oblongifolia Pers., B. trimera (Less) DC. and B. uncinella DC.) and to evaluate the toxicological and morphological effects caused by essential oils (EOs) on the larvae and adults of Drosophila suzukii (Diptera: Drosophilidae). Chemical analysis using gas chromatography-mass spectrometry (GC-MS) indicated that limonene was the main common constituent in all Baccharis species. This constituent in isolation, as well as the EOs of B. calvescens, B. mesoneura, and B. oblongifolia, caused mortality in over 80% of adults of D. suzukii at a discriminatory concentration of 80 mg L-1 in bioassays of ingestion and topical application. These results are similar to the effect of spinosyn-based synthetic insecticides (spinetoram 75 mg L-1) 120 h after exposure. Limonene and EOs from all species had the lowest LC50 and LC90 values relative to spinosyn and azadirachtin (12 g L-1) in both bioassays. However, they showed the same time toxicity over time as spinetoram when applied to adults of D. suzukii (LT50 ranging from 4.6 to 8.7 h) in a topical application bioassay. In olfactometry tests, 92% of D. suzukii females showed repellent behavior when exposed to the EOs and limonene. Likewise, the EOs of B. calvescens, B. mesoneura, and B. oblongifolia significantly reduced the number of eggs in artificial fruits (≅ 7.6 eggs fruit-1), differing from the control treatment with water (17.2 eggs fruit-1) and acetone (17.6 eggs fruit-1). According to histological analyses, the L3 larvae of D. suzukii had morphological and physiological alterations and deformations after exposure to treatments containing EOs and limonene, which resulted in high larval, pupal, and adult mortality. In view of the results, Baccharis EOs and their isolated constituent, limonene, proved to be promising alternatives for developing bioinsecticides to manage of D. suzukii.

The attractant, but not the trap design, affects the capture of Drosophila suzukii in berry crops.

Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) is recognized as an invasive pest in Europe and North America. In Mexico, it is one of the main insect pests of soft-skinned fruits such as blueberries, strawberries, raspberries, blackberries, plums, and guava. Previous studies have shown that D. suzukii uses visual and chemical cues during host plant searching. This knowledge has been used to develop traps and attractants for monitoring D. suzukii. In this study, five trap designs were evaluated to monitor D. suzukii under field conditions. Traps were baited with SuzukiiTrap®, Z-Kinol, an attractant based on acetoin and methionol, or apple cider vinegar (ACV) enriched with 10% ethanol (EtOH) with the synergistic action of carbon dioxide (CO2). Our results suggested that the attractant was the determining factor in capturing D. suzukii, while trap design seemed to play a modest role. We found that traps baited with Z-Kinol captured the highest number of D. suzukii compared to that caught by traps baited with SuzukiiTrap®, or ACV + EtOH + CO2. The highest catch numbers occurred in blackberry, followed by strawberry, raspberry, and blueberry. Traps captured more females than males. The results obtained may be useful for monitoring D. suzukii populations in Mexico and elsewhere, particularly in states where soft fruit crops are a component of agricultural activities.

Fatty acid ß-oxidation is required for the differentiation of larval hematopoietic progenitors in Drosophila.

Cell-intrinsic and extrinsic signals regulate the state and fate of stem and progenitor cells. Recent advances in metabolomics illustrate that various metabolic pathways are also important in regulating stem cell fate. However, our understanding of the metabolic control of the state and fate of progenitor cells is in its infancy. Using Drosophila hematopoietic organ: lymph gland, we demonstrate that Fatty Acid Oxidation (FAO) is essential for the differentiation of blood cell progenitors. In the absence of FAO, the progenitors are unable to differentiate and exhibit altered histone acetylation. Interestingly, acetate supplementation rescues both histone acetylation and the differentiation defects. We further show that the CPT1/whd (withered), the rate-limiting enzyme of FAO, is transcriptionally regulated by Jun-Kinase (JNK), which has been previously implicated in progenitor differentiation. Our study thus reveals how the cellular signaling machinery integrates with the metabolic cue to facilitate the differentiation program.

Stem cells are special precursor cells, found in all animals from flies to humans, that can give rise to all the mature cell types in the body. Their job is to generate supplies of new cells wherever these are needed. This is important because it allows damaged or worn-out tissues to be repaired and replaced by fresh, healthy cells. As part of this renewal process, stem cells generate pools of more specialized cells, called progenitor cells. These can be thought of as half-way to maturation and can only develop in a more restricted number of ways. For example, so-called myeloid progenitor cells from humans can only develop into a specific group of blood cell types, collectively termed the myeloid lineage. Fruit flies, like many other animals, also have several different types of blood cells. The fly's repertoire of blood cells is very similar to the human myeloid lineage, and these cells also develop from the fly equivalent of myeloid progenitor cells. These progenitors are found in a specialized organ in fruit fly larvae called the lymph gland, where the blood forms. These similarities between fruit flies and humans mean that flies are a good model to study how myeloid progenitor cells mature. A lot is already known about the molecules that signal to progenitor cells how and when to mature. However, the role of metabolism ­ the chemical reactions that process nutrients and provide energy inside cells ­ is still poorly understood. Tiwari et al. set out to identify which metabolic reactions myeloid progenitor cells require and how these reactions might shape the progenitors' development into mature blood cells. The experiments in this study used fruit fly larvae that had been genetically altered so that they could no longer perform key chemical reactions needed for the breakdown of fats. In these mutant larvae, the progenitors within the lymph gland could not give rise to mature blood cells. This showed that myeloid progenitor cells need to be able to break down fats in order to develop properly. These results highlight a previously unappreciated role for metabolism in controlling the development of progenitor cells. If this effect also occurs in humans, this knowledge could one day help medical researchers engineer replacement tissues in the lab, or even increase our own bodies' ability to regenerate blood, and potentially other organs.

Protection against oxidative stress and anti-aging effect in Drosophila of royal jelly-collagen peptide.

Dietary peptide has been of great interest because of its perspective in nutrition and health of human body. The aim of this study was to develop a dietary nutritional supplement exerting both antioxidant and anti-aging effects. Peptide, named as ERJ-CP, was prepared by mixing enzyme-treated royal jelly (ERJ) with collagen peptide (CP), showing stronger antioxidant activity in vitro. Drosophila was used as model animal to investigate anti-aging effect of ERJ-CP in vivo. ERJ-CP significantly prolonged the average life span of Drosophila treated with H2O2 and paraquat, reducing malondialdehyde (MDA) and protein carbonyl (PCO) levels in Drosophila. In addition, 3 mg/mL of ERJ-CP could prolong the lifespan of natural aging Drosophila by 11.16%. ERJ-CP could up-regulate the levels of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and down-regulate the contents of MDA and PCO. Moreover, the intake of ERJ-CP increased the food consumption, weight gain and exercise capacity of Drosophila. The results showed that ERJ-CP played a protective role in both antioxidant and anti-aging effects on Drosophila, and the anti-aging effect may be achieved by alleviating oxidative damage. It suggests that ERJ-CP could be developed as a health-promoting ingredient with antioxidant and anti-aging effects for human body.

Seasonal Reproductive Biology of Drosophila suzukii (Diptera: Drosophilidae) in Temperate Climates.

Drosophila suzukii (Matsumura; Diptera: Drosophilidae) is a key pest of sweet cherry and small fruits worldwide. The present studies were designed to describe the reproductive physiology in both sexes, through dissections of their reproductive organs. We extensively dissected female D. suzukii throughout the season from 2013 to 2016 and classified the reproductive status flies based on five recognizable ovarian maturation stages: 1) no ovaries; 2) unripe ovaries 3) ripening eggs in ovarioles; 4) mature eggs in ovarioles; and 5) mature eggs in the abdomen. Development was examined as a function of calendar days as well as degree-days (DD). Results obtained from winter collections revealed that females collected from November to March contained a lower percentage of mature eggs than females collected from April to September. These data suggest that environmental conditions during the dormant period induce reproductive diapause. Oogenesis likely increased with an increase in mean monthly temperatures and DD. The first overwintered females with mature eggs were dissected as early as 21 February 2014 in Trento (7 DD). Additionally, we found that a low proportion of males (less than 50%) had sperm in their testes between January and March, yet during the same period females already have sperm stored in their spermathecal. Ivy berries was an alternative but unfavorable non-crop host during the late dormant period, as evidenced by emergence of smaller adults when compared to individuals emerging from cherry fruits. This study showed that D. suzukii females have great potential for oviposition early in the season, posing a risk to early season maturing crop hosts.

Drosophila divalent metal ion transporter Malvolio is required in dopaminergic neurons for feeding decisions.

Members of the natural resistance-associated macrophage protein (NRAMP) family are evolutionarily conserved metal ion transporters that play an essential role in regulating intracellular divalent cation homeostasis in both prokaryotes and eukaryotes. Malvolio (Mvl), the sole NRAMP family member in insects, plays a role in food choice behaviors in Drosophila and other species. However, the specific physiological and cellular processes that require the action of Mvl for appropriate feeding decisions remain elusive. Here, we show that normal food choice requires Mvl function specifically in the dopaminergic system, and can be rescued by supplementing food with manganese. Collectively, our data indicate that the action of the Mvl transporter affects food choice behavior via the regulation of dopaminergic innervation of the mushroom bodies, a principle brain region associated with decision-making in insects. Our studies suggest that the homeostatic regulation of the intraneuronal levels of divalent cations plays an important role in the development and function of the dopaminergic system and associated behaviors.

Modeling Human Cancers in Drosophila.

Cancer is a complex disease that affects multiple organs. Whole-body animal models provide important insights into oncology that can lead to clinical impact. Here, we review novel concepts that Drosophila studies have established for cancer biology, drug discovery, and patient therapy. Genetic studies using Drosophila have explored the roles of oncogenes and tumor-suppressor genes that when dysregulated promote cancer formation, making Drosophila a useful model to study multiple aspects of transformation. Not limited to mechanism analyses, Drosophila has recently been showing its value in facilitating drug development. Flies offer rapid, efficient platforms by which novel classes of drugs can be identified as candidate anticancer leads. Further, we discuss the use of Drosophila as a platform to develop therapies for individual patients by modeling the tumor's genetic complexity. Drosophila provides both a classical and a novel tool to identify new therapeutics, complementing other more traditional cancer tools.

Identification of excitatory premotor interneurons which regulate local muscle contraction during Drosophila larval locomotion.

We use Drosophila larval locomotion as a model to elucidate the working principles of motor circuits. Larval locomotion is generated by rhythmic and sequential contractions of body-wall muscles from the posterior to anterior segments, which in turn are regulated by motor neurons present in the corresponding neuromeres. Motor neurons are known to receive both excitatory and inhibitory inputs, combined action of which likely regulates patterned motor activity during locomotion. Although recent studies identified candidate inhibitory premotor interneurons, the identity of premotor interneurons that provide excitatory drive to motor neurons during locomotion remains unknown. In this study, we searched for and identified two putative excitatory premotor interneurons in this system, termed CLI1 and CLI2 (cholinergic lateral interneuron 1 and 2). These neurons were segmentally arrayed and activated sequentially from the posterior to anterior segments during peristalsis. Consistent with their being excitatory premotor interneurons, the CLIs formed GRASP- and ChAT-positive putative synapses with motoneurons and were active just prior to motoneuronal firing in each segment. Moreover, local activation of CLI1s induced contraction of muscles in the corresponding body segments. Taken together, our results suggest that the CLIs directly activate motoneurons sequentially along the segments during larval locomotion.

Supplementation with Major Royal-Jelly Proteins Increases Lifespan, Feeding, and Fecundity in Drosophila.

The major royal-jelly proteins (MRJPs) are the main constituents responsible for the specific physiological role of royal jelly (RJ) in honeybees. Male and female Drosophila flies were fed diets containing either no MRJPs (A) or casein (B) at 1.25% (w/w) of diet or MRJPs at 1.25% (C), 2.50% (D), or 5.00% (E). Diets B, C, D, and E increased mean lifespan by 4.3%, 9.0%, 12.4%, and 13.9% in males and by 5.8%, 9.7%, 20.0%, and 11.8% in females in comparison to results from diet A, respectively. The diet supplemented with 2.50% MRJPs seems to have the optimal dose to improve both physiological and biochemical measures related to aging in both sexes. Interestingly, lifespan extension by MRJPs in Drosophila was positively associated with feeding and fecundity and up-regulation of copper and zinc-superoxide dismutase (CuZn-SOD) and the Egfr-mediated signaling pathway. This study provides strong evidence that MRJPs are important components of RJ for prolonging lifespan in Drosophila.

Behavioral and Antennal Responses of Drosophila suzukii (Diptera: Drosophilidae) to Volatiles From Fruit Extracts.

Native to Southeast Asia, the spotted wing drosophila, Drosophila suzukii Matsumura (Diptera: Drosophilidae), has become a serious pest of soft-skinned fruit crops since its introduction into North America and Europe in 2008. Current monitoring strategies use baits based on fermentation products; however, to date, no fruit-based volatile blends attractive to this fly have been identified. This is particularly important because females are able to cut into the epicarp of ripening fruit for oviposition. Thus, we conducted studies to: 1) investigate the behavioral responses of adult D. suzukii to volatiles from blueberry, cherry, raspberry, and strawberry fruit extracts; 2) identify the antennally active compounds from the most attractive among the tested extracts (raspberry) using gas chromatography (GC)-mass spectrometry and coupled gas chromatography -electroantennographic detection (GC-EAD); and 3) test a synthetic blend containing the EAD-active compounds identified from raspberry extract on adult attraction. In olfactometer studies, both female and male D. suzukii were attracted to all four fruit extracts. The attractiveness of the fruit extracts ranks as: raspberry ≥ strawberry > blueberry ≥ cherry. GC analyses showed that the fruit extracts emit distinct volatile compounds. In GC-EAD experiments, 11 raspberry extract volatiles consistently elicited antennal responses in D. suzukii. In choice test bioassays, a synthetic EAD-active blend attracted more D. suzukii than a blank control, but was not as attractive as the raspberry extract. To our knowledge, this is the first report of a behaviorally and antennally active blend of host fruit volatiles attractive to D. suzukii, offering promising opportunities for the development of improved monitoring and behaviourally based management tools.

Antioxidant activity, antitumor effect, and antiaging property of proanthocyanidins extracted from Kunlun Chrysanthemum flowers.

The objective of the present study was to evaluate the antioxidant activity, antitumor effect, and antiaging property of proanthocyanidins from Kunlun Chrysanthemum flowers (PKCF) grown in Xinjiang. In vitro antioxidant experiments results showed that the total antioxidant activity and the scavenging capacity of hydroxyl radicals ((•)OH) and 1,1-diphenyl-2-picrylhydrazyl (DPPH(•)) radicals increased in a concentration-dependent manner and were stronger than those of vitamin C. To investigate the antioxidant activity of PKCF in vivo, we used serum, liver, and kidney from mouse for the measurement of superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (T-AOC). Results indicated that PKCF had antioxidative effect in vivo which significantly improved the activity of SOD and T-AOC and decreased MDA content. To investigate the antitumor activity of PKCF, we used H22 cells, HeLa cells, and Eca-109 cells with Vero cells as control. Inhibition ratio and IC50 values were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; PKCF showed great inhibitory activity on H22 cells and HeLa cells. We also used fruit flies as a model for analyzing the anti-aging property of PKCF. Results showed that PKCF has antiaging effect on Drosophila. Results of the present study demonstrated that PKCF could be a promising agent that may find applications in health care, medicine, and cosmetics.

Nordihydroguaiaretic Acid Extends the Lifespan of Drosophila and Mice, Increases Mortality-Related Tumors and Hemorrhagic Diathesis, and Alters Energy Homeostasis in Mice.

Mesonordihydroguaiaretic acid (NDGA) extends murine lifespan. The studies reported here describe its dose dependence, effects on body weight, toxicity-related clinical chemistries, and mortality-related pathologies. In flies, we characterized its effects on lifespan, food consumption, body weight, and locomotion. B6C3F1 mice were fed AIN-93M diet supplemented with 1.5, 2.5, 3.5, or 4.5 g NDGA/kg diet (1.59, 2.65, 3.71 and 4.77 mg/kg body weight/day) beginning at 12 months of age. Only the 3.5 mg/kg diet produced a highly significant increase in lifespan, as judged by either the Mantel-Cox log-rank test (p = .008) or the Gehan-Breslow-Wilcoxon test (p = .009). NDGA did not alter food intake, but dose-responsively reduced weight, suggesting it decreased the absorption or increased the utilization of calories. NDGA significantly increased the incidence of liver, lung, and thymus tumors, and peritoneal hemorrhagic diathesis found at necropsy. However, clinical chemistries found little evidence for overt toxicity. While NDGA was not overtly toxic at its therapeutic dosage, its association with severe end of life pathologies does not support the idea that NDGA consumption will increase human lifespan or health-span. The less toxic derivatives of NDGA which are under development should be explored as anti-aging therapeutics.

Characterization of volatiles of necrotic Stenocereus thurberi and Opuntia littoralis and toxicity and olfactory preference of Drosophila melanogster, D. mojavensis wrigleyi, and D. mojavensis sonorensis to necrotic cactus volatiles.

Drosophila mojavensis wrigleyi and D. mojavensis sonorensis are geographically separated races of cactophilic fruit flies. D. mojavensis sonorensis inhabits the Sonoran Desert and utilizes necrotic rots of Stenocereus thurberi Engelm. as a food source and to oviposit while D. mojavensis wrigleyi inhabits Santa Catalina Island, California and utilizes the necrotic rots of Opuntia littoralis (Engelm.) Cockerell. The objectives of this study were to determine the volatile compositions of the necrotic cacti and to determine if the volatile components show either selective toxicity or attraction toward the fruit flies. The volatile chemical compositions of field-rot specimens of both necrotic cacti were obtained by dynamic headspace (purge-and-trap) and hydrodistillation techniques and analyzed by gas chromatography - mass spectrometry. The volatile fraction of necrotic S. thurberi early rot was dominated by carboxylic acids (84.8%) and the late rot by p-cresol (32.6% in the dynamic headspace sample and 55.9% in the hydrodistilled sample). O. littoralis volatiles were dominated by carboxylic acids (86% in the dynamic headspace sample and 89.1% in the hydrodistilled sample). Fifteen compounds that were identified in the necrotic rot volatiles were used to test insecticidal activity and olfactory preference on the cactophilic Drosophila species, as well as D. melanogaster. Differences in toxicity and olfactory preference were observed between the different taxa. Both races of D. mojavensis exhibited toxicity to benzaldehyde and 2-nonanone, while butanoic acid and palmitic acid were tolerated at high concentrations. D. m. wrigleyi demonstrated a greater olfactory preference for anisole, butanoic acid, 2-heptanone, and palmitic acid than did D. m. sonorensis, while D. m. sonorensis demonstrated a greater preference for hexadecane, octanoic acid, and oleic acid than did D. m. wrigleyi.

The Yin and Yang of Wnt/Ryk axon guidance in development and regeneration.

In the developing embryo, nascent axons navigate towards their specific targets to establish the intricate network of axonal connections linking neurons within the mature nervous system. Molecular navigational systems comprising repulsive and attractive guidance cues form chemotactic gradients along the pathway of the exploring growth cone. Axon-bound receptors detect these gradients and determine the trajectory of the migrating growth cone. In contrast to their benevolent role in the developing nervous system, repulsive guidance receptors are detrimental to the axon's ability to regenerate after injury in the adult. In this review we explore the essential and beneficial role played by the chemorepulsive Wnt receptor, Ryk/Derailed in axon navigation in the embryonic nervous system (the Yin function). Specifically, we focus on the role of Wnt5a/Rykmediated guidance in the establishment of two major axon tracts in the mammalian central nervous system, the corticospinal tract and the corpus callosum. Recent studies have also identified Ryk as a major suppressor of axonal regeneration after spinal cord injury. Thus, we also discuss this opposing aspect of Ryk function in axonal regeneration where its activity is a major impediment to axon regrowth (the Yang function).

Lifespan extension by cranberry supplementation partially requires SOD2 and is life stage independent.

Many nutraceuticals and pharmaceuticals have been shown to promote healthspan and lifespan. However, the mechanisms underlying the beneficial effects of prolongevity interventions and the time points at which interventions should be implemented to achieve beneficial effects are not well characterized. We have previously shown that a cranberry-containing nutraceutical can promote lifespan in worms and flies and delay age-related functional decline of pancreatic cells in rats. Here we investigated the mechanism underlying lifespan extension induced by cranberry and the effects of short-term or life stage-specific interventions with cranberry on lifespan in Drosophila. We found that lifespan extension induced by cranberry was associated with reduced phosphorylation of ERK, a component of oxidative stress response MAPK signaling, and slightly increased phosphorylation of AKT, a component of insulin-like signaling. Lifespan extension was also associated with a reduced level of 4-hydroxynonenal protein adducts, a biomarker of lipid oxidation. Moreover, lifespan extension induced by cranberry was partially suppressed by knockdown of SOD2, a major mitochondrial superoxide scavenger. Furthermore, cranberry supplementation was administered in three life stages of adult flies, health span (3-30 days), transition span (31-60 days) and senescence span (61 days to the end when all flies died). Cranberry supplementation during any of these life stages extended the remaining lifespan relative to the non-supplemented and life stage-matched controls. These findings suggest that cranberry supplementation is sufficient to promote longevity when implemented during any life stage, likely through reducing oxidative damage.

Carotenoid supplementation enhances reproductive success in captive strawberry poison frogs (Oophaga pumilio).

Amphibians are currently experiencing the most severe declines in biodiversity of any vertebrate, and their requirements for successful reproduction are poorly understood. Here, we show that supplementing the diet of prey items (fruit flies) with carotenoids has strong positive effects on the reproduction of captive strawberry poison frogs (Oophaga pumilio), substantially increasing the number of metamorphs produced by pairs. This improved reproduction most likely arose via increases in the quality of both the fertilized eggs from which tadpoles develop and trophic eggs that are fed to tadpoles by mothers. Frogs in this colony had previously been diagnosed with a Vitamin A deficiency, and this supplementation may have resolved this issue. These results support growing evidence of the importance of carotenoids in vertebrate reproduction and highlight the nuanced ways in which nutrition constrains captive populations.