In an elaborate form of inter-species exploitation, many insects hijack plant development to induce novel plant organs called galls that provide the insect with a source of nutrition and a temporary ...home. Galls result from dramatic reprogramming of plant cell biology driven by insect molecules, but the roles of specific insect molecules in gall development have not yet been determined. Here, we study the aphid Hormaphis cornu, which makes distinctive “cone” galls on leaves of witch hazel Hamamelis virginiana. We found that derived genetic variants in the aphid gene determinant of gall color (dgc) are associated with strong downregulation of dgc transcription in aphid salivary glands, upregulation in galls of seven genes involved in anthocyanin synthesis, and deposition of two red anthocyanins in galls. We hypothesize that aphids inject DGC protein into galls and that this results in differential expression of a small number of plant genes. dgc is a member of a large, diverse family of novel predicted secreted proteins characterized by a pair of widely spaced cysteine-tyrosine-cysteine (CYC) residues, which we named BICYCLE proteins. bicycle genes are most strongly expressed in the salivary glands specifically of galling aphid generations, suggesting that they may regulate many aspects of gall development. bicycle genes have experienced unusually frequent diversifying selection, consistent with their potential role controlling gall development in a molecular arms race between aphids and their host plants.
•Novel aphid bicycle genes contribute to plant gall development•Variation in a bicycle gene alters plant gene expression and a gall phenotype•bicycle genes encode a large family of diverse, secreted, cysteine-rich proteins•Many bicycle genes have experienced repeated diversifying selection
Korgaonkar et al. report on novel secreted aphid proteins encoded by bicycle genes. Variation in the bicycle gene determinant of gall color alters expression of targeted plant genes, suggesting that BICYCLE proteins modulate gall development.
•Oilseed rape seeds are rich in nutritional bioactives.•Current agronomical traits greatly modulate B. napus seeds bioactive contents.•Such disparities influence health outcomes in a mice nutritional ...trial.•Optimized agronomical conditions may beneficially improve B napus nutritional value.
Beside oil, oilseed rape (Brassica napus) seeds contains nutritional bioactives such as polyphenols and glucosinolates. However, to date their nutritional properties have been overlooked in the new “double zero” breeds.
Seed alcoholic extracts from two B. napus cultivars most contrasting in their phytochemical contents as measured by mass-spectrometry were given to ob-mice. Biological outcomes including clinical metrics, gut and plasma metabolomes, liver transcriptome and metabolome were compared to ob-mice given a similar broccoli extract (Brassica oleracea).
One B. napus extract induced a reduction of the oxidative stress indicated by the decrease of plasma isoprostanoids. This was associated to the regulation of the antioxidant stress defense Nrf2 pathway, to ‘omic’ oxidative stress functions, metabolic and cell process regulations, and the metabolomics microbiota profile.
Extracts of B. napus seeds demonstrated health effects that may be improved by selecting appropriate agronomical traits, highlighting the potential benefits of better utilizing agronomy for improved human and animal nutrition
Chemotherapy-induced cognitive impairment affects ~30% of breast cancer survivors, but the effects on how chemotherapy impacts brain lipids, and how omega-3 polyunsaturated fatty acid supplementation ...may confer protection, is unknown. Ovariectomized mice were randomized to two rounds of injections of doxorubicin + cyclophosphamide or vehicle after consuming a diet supplemented with 2% or 0% EPA+DHA, and sacrificed 4, 7, and 14 days after the last injection (study 1, n = 120) or sacrificed 10 days after the last injection (study 2, n = 40). Study 1 whole brain samples were extracted and analyzed by UHPLC-MS/MS to quantify specialized pro-resolving mediators (SPMs). Lipidomics analyses were performed on hippocampal extracts from study 2 to determine changes in the brain lipidome. Study 1 results: only resolvin D1 was present in all samples, but no differences in concentration were observed (P > 0.05). Study 2 results: chemotherapy was positively correlated with omega-9 fatty acids, and EPA+DHA supplementation helped to maintain levels of plasmalogens. No statistically significant chemotherapy*diet effect was observed. Results demonstrate a limited role of SPMs in the brain post-chemotherapy, but a significant alteration of hippocampal lipids previously associated with other models of cognitive impairment (i.e., Alzheimer’s and Parkinson’s disease).
Chemotherapy produces long-term cognitive impairment (CICI) in ∼30% of those receiving solid tumor treatment. Our previous results revealed a positive correlation between doxorubicin treatment and ...murine hippocampal concentrations of omega-9 fatty acids, relative to untreated controls. Our objective was to measure these and other structurally analogous fatty acids in human plasma following breast-cancer treatment, to determine if they might serve as biomarkers and/or nutritional targets during treatment.
Serum samples were collected from patients (n = 51) at ≥ 2 of 3 visits: immediately prior to standard adjuvant and neo-adjuvant chemotherapy for breast cancer (baseline), prior to the third cycle of chemotherapy, and 6 months after chemotherapy termination. Lipophilic extracts of serum were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to quantify eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA), linoleic acid, oleic acid, mead acid, gondoic acid, erucic acid, nervonic acid and PE(P-18:0/22:6) (plasmalogen). Linear models assessed the impact of visit on fatty acid concentrations, with a fixed intercept used for each subject. A P < 0.05 for chemotherapy was considered significant.
Chemotherapy significantly increased plasma concentrations of gondoic, erucic, nervonic acids and plasmalogen (with no effect on the other fatty acids tested). Six months following chemotherapy, concentrations of gondoic, erucic, nervonic acids and plasmalogen approached baseline concentrations.
Breast cancer chemotherapy significantly increased plasma concentrations of omega-9 fatty acids previously reported as increased in subjects with increasing severity of cognitive impairment and Alzheimer’s disease. Ongoing work includes correlating the concentrations of these fatty acids with measures of memory and cognition. Future investigations will determine if these compounds may serve as nutritional targets for dietary interventions prior to or during chemotherapy treatment, and/or serve as objective biomarkers of CICI.
The Ohio State University Stefanie Spielman Breast Cancer Center Kroger Fund, Pelotonia, NIH R01CA189947, NIH Award Number Grant P30 CA016058, OSU, and OSUCCC.
Chemotherapy upregulates inflammatory processes as measured by circulating concentrations of pro-inflammatory cytokines and their signaling lipids. Our objective was to observe if breast cancer ...chemotherapy influenced the circulating concentrations of provitamin A and non-provitamin A carotenoids and fat-soluble vitamins (FSVs) in free-living patients.
Serum samples were collected from patients (n = 34) immediately prior to standard adjuvant and neo-adjuvant chemotherapy for breast cancer, and 4 months following chemotherapy commencement. Patient multivitamin and non-steroidal anti-inflammatory (NSAID) drug use was noted at both visits. Lipophilic extracts of serum were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to quantify α- and β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol and phylloquinone. Linear mixed models were developed to assess the relationship between the main factors (i.e., chemotherapy, multivitamin, and NSAID use), and their interaction effects, on serum carotenoid and fat-soluble vitamin concentrations. Random effects included a fixed intercept for each subject.
Chemotherapy was significantly associated with reduced serum concentrations of α-carotene (P = 0.053) and retinol (P = 0.042), with a trend observed for reduced β-carotene (P = 0.076) and phylloquinone (P = 0.082). There was no main effect of multivitamin or NSAID use on any analytes investigated. An interaction effect was observed for chemotherapy * multivitamin use, with increased concentrations of serum retinol (P = 0.004) and lycopene (P = 0.004), and a trend observed for zeaxanthin (P = 0.087) for those who took multivitamins. Chemotherapy * NSAID use was also significantly associated with a trend in increased serum lutein (P = 0.061) for those who consumed NSAIDS.
Our results suggest randomized, controlled trials of multivitamin use and/or provitamin A carotenoid-rich food consumption merit further investigation in patients undergoing chemotherapy treatment.
This research was supported by The Ohio State University Stefanie Spielman Breast Cancer Center Kroger Fund, Pelotonia, NIH R01CA189947, NIH Award Number Grant P30 CA016058, OSU, and OSUCCC.
Preparedness for nuclear accident responsiveness includes interventions to protect pregnancies against prolonged exposure to radioactive iodine. The aim of this study was to investigate a new design ...consisting of repeated administration of potassium iodide (KI, 1 mg/kg) for 8 days in late pregnancy gestational day 9-16 (GD9-GD16) in rats. The later-life effects of this early-life iodine thyroid blocking (ITB) strategy were assessed in offspring two months afterbirth. Functional behavioral tests including forced swimming test (FST) and rotarod test (RRT) in rats of both genders showed lower FST performance in KI-treated females and lower RRT performance in KI-treated male pups. This performance decline was associated with metabolic disruptions in cortex involving amino acid metabolism, tyrosine metabolism, as well as docosahexaenoic acid (DHA) lipids and signaling lipids in males and females. Beyond these behavior-associated metabolic changes, a portion of the captured metabolome (17-25%) and lipidome (3.7-7.35%) remained sensitive to in utero KI prophylactic treatment in both cortex and plasma of post-weaning rats, with some gender-related variance. Only part of these disruptions was attributed to lower levels of TSH and T4 (males only). The KI-induced metabolic shifts involved a broad spectrum of functions encompassing metabolic and cell homeostasis and cell signaling functions. Irrespective Regardless of gender and tissues, the predominant effects of KI affected neurotransmitters, amino acid metabolism, and omega-3 DHA metabolism. Taken together, data demonstrated that repeated daily KI administration at 1 mg/kg/day for 8 days during late pregnancy failed to protect the mother-fetus against nuclear accident radiation.
Abbreviations: CV-ANOVA: Cross-validation analysis of variance; DHA: Docosahexaenoic acid; FST: Forced swimming test; FT3: plasma free triiodothyronine; FT4: plasma free thyroxine; GD: Gestational day; ITB: Iodine thyroid blocking; KI: potassium iodide; LC/MS: Liquid chromatography coupled with mass spectrometry; MTBE: Methyl tert-butyl ether; m/z: mass-to-charge ratio; PLS-DA: Partial least squares-discriminant analysis; PRIODAC: Repeated stable iodide prophylaxis in accidental radioactive releases; RRT: Rotarod test; TSH: Thyroid-stimulating hormone; VIP: Variable importance in projection.
To determine how omega-3 (n3-FA) supplementation may confer protection against lipid modifications following doxorubicin-based chemotherapy (DOX).
Ovariectomized C57BL/6 mice consumed a diet with 0% ...or 2% kcal supplemental EPA + DHA for 4 weeks, followed by two injections of either DOX (9 mg/kg) + cyclophosphamide (90 mg/kg), or vehicle. In study 1, animals were sacrificed at 4, 7, and 14 days after the last injection (n = 120) and in study 2, at 10 days after the last injection (n = 40). Whole brain from study 1 were analyzed by targeted methods (UHPLC-MS/MS), to quantify specialized pro-resolving mediators resolvin D1 (RvD1), resolvin D2 (RvD2), resolvin D3 (RvD3), resolvin D5 (RvD5), resolvin E1 (RvE1), maresin (MaR1), and protectin (PD1). In study 2, lipidomics analyses were performed on hippocampus to determine changes in the lipidome after n3-FA supplementation and chemotherapy injection.
Study 1 results: RvD1 was present in all samples, but no significant differences in concentration were observed regardless of treatment or dietary group. RvD3, PD1 and MaR1 were detected in a subset of samples. Study 2 results: EPA + DHA (2%) supplementation favorably altered lipids associated with cognitive function (i.e., PE (P-16:0/20:5), PE (P-18:0/22:6, with adjusted p-value equal to 0.003 and 0.04 respectively), which have been previously negatively correlated with Alzheimer’s and Parkinson’s disease. Chemotherapy treatment increases omega-9 fatty acids (i.e., nervonic, gadoleic and mead acid) previously positively correlated with diseases of cognitive decline (e.g., Alzheimer’s, Parkinson’s). No chemo*n3-FA interaction was observed (p-value > 0.05).
N3-FA supplementation favorably altered lipids associated with cognitive function. DOX increased lipids associated with diseases of cognitive decline. Future investigations will determine if the same biomarkers of n-3 FA consumption and chemotherapy are observed in human breast cancer patients.
This research was supported by a Foods for Health Discovery Themes Initiative SEEDS grant, NIH R01CA189947, NIH Award Number Grant P30 CA016058, OSU, and OSUCCC.
Solid tumor chemotherapy produces long-term cognitive side effects well beyond treatment, but the structural changes on brain chemistry are unknown. A diet supplemented with omega-3 fatty acids (EPA ...+ DHA) before and during chemotherapy partially protects the cerebral tissue against some of the chemo-induced modifications. We hypothesize that EPA + DHA supplementation results in a greater neuroinflammation-resolving response mediated by specialized pro-resolving mediators (SPMs i.e., omega-3 derived metabolites which attenuate inflammation), and reduces oxidation of structural brain lipids.
For four weeks, ovariectomized mice were fed a 2% kcal EPA + DHA supplemented (n = 60) or control diet (n = 60), followed by two treatments with vehicle (n = 30 per dietary group) or doxorubicin (n = 30 per dietary group). Animals were sacrificed at 4, 7, and 14 days post-treatment, and samples extracted and purified with SPE. Targeted analyses (LC-MS/MS) were performed on extracts, using stable isotope internal standards for SPM quantitation (i.e., resolvin E1, D1, D2, D3, D5, maresin 1, protectin D1). Untargeted LC-HRMS metabolomics analyses were performed on the hippocampal extracts of follow-up set of animals, to determine changes in the brain lipidome.
Resolvin D1 was quantifiable in all samples regardless of dietary or treatment group, and correlations were observed with orthogonal measures of inflammation in chemo-treated animals. Resolvin D3, maresin 1, and protectin D1 were detected in a subset of animals. A cluster of lipid-based metabolites differentiated animals receiving chemotherapy with omega-3 fatty acid supplementation from those not receiving the supplementation.
The protective effects of EPA + DHA supplementation on chemo-induced cerebral damage appear to be only partially correlated with SPM synthesis over the time course observed.
This research was supported by an OSU Foods for Health Discovery Themes Initiative SEEDS grant. The mouse samples were collected under NIH R01CA189947. The sample analyses were partially supported by NIH Award Number Grant P30 CA016058, OSU, and OSUCCC.
Le colza (Brassica napus) est cultivée pour la richesse de ses graines en lipides et protéines. Cette plante possède aussi des métabolites secondaires bioactifs pouvant moduler la santé du ...consommateur. Ainsi différentes actions ont été mises en place par les industries agroalimentaires pour réduire le taux de métabolites antinutritionnels. A l’inverse peu sont consacrés à l’exploitation des métabolites favorables à la santé. L’une des pistes est d’identifier les conditions de culture en interaction avec les génotypes pour générer des graines de qualité nutritionnelle optimale. D’une manière générale, les résultats ont montré que certaines variétés sont résilientes à l’environnement. D’autres au contraire se sont montrées plus sensibles. L'impact des IGEC observé a été évaluée sur un modèle préclinique de souris ob/ob par une approche multi-omique, et comparée à celle d’un extrait de référence issu de Brassica oleracea (Brocoli) commercialisé pour ces vertus santé. Les résultats ont montré que la réponse biologique « omique » mesurée dans l’intestin, le foie et le plasma présentait une forte proximité entre l’un des extraits de colza (ES-Mambo) avec l’extrait de référence (Brocoli). Nous pensons que cela résulte de la présence de composés bioactifs communs et minoritaires entre les deux plantes et dont nous avons pu identifier la nature de certains (composés phénoliques et glucosinolates). L’approche métabolomique a démontré que les conditions de culture et le génotype du colza ayant modifié leur contenu bioactif induisaient une réponse biologique différentielle chez le consommateur. Cette preuve de concept pourrait s’appliquer à d’autres plantes de grande consommation.
Rapeseed (Brassica napus) is the first oleaginous crop in France. It is cultivated for the abundance of its seeds in lipids, proteins as wellas for its richness in secondary metabolites that can modulate the health of the consumer. For instance, different actions have beenimplemented by food and feed industries to reduce the rate of anti-nutritional metabolites. Conversely few are devoted to theexploitation of health promoting molecules. A strategy is to identify the genotype x environment x agronomic management interactions(GEAI) to generate seeds of optimal nutritional quality.The results showed that some varieties are resilient to the environment. On the other hand, others appeared more sensitive. The environment and genetic impact was evaluated on a preclinical model ob/ob mouse by a multi-omic approach, and compared to a reference extract from Brassica oleracea (Broccoli), marketed for its health benefits. The results showed that the "omic" biological response measured in the intestine, liver and plasma showed a strong proximity between one of the rapeseed extract (ES-Mambo) and the reference extract (Broccoli). We believe that these results occured from the presence of common bioactive compounds between the two plants (rapeseed and broccoli), that some of them were identified (phenolic compounds and glucosinolates). The metabolomic approach was efficient to estimate the health impact of phytochemical extracts that have never been evaluated before. We demonstrated that the GEAI of rapeseed that modified their bioactive contents induced a differential biological response in the consumer. This proof of concept study could be applied to other food plant products.
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