scholarly journals Consequences of pharmacophagous uptake from plants and conspecifics in a sawfly elucidated using chemical and molecular techniques

2021 ◽  
Author(s):  
Sarah Catherine Paul ◽  
Alice B. Dennis ◽  
Lisa Johanna Tewes ◽  
Jeanne Friedrichs ◽  
Caroline Müller
Keyword(s):  
Social Interactions ◽  
Metabolic Pathways ◽  
Molecular Techniques ◽  
Food Plants ◽  
Metabolic Phenotype ◽  
Plant Metabolites ◽  
Athalia Rosae ◽  
Ajuga Reptans ◽  
Metabolic Costs ◽  
Summary Statement

AbstractPharmacophagy involves the sequestration of specialised plant metabolites for non-nutritive purposes and commonly occurs in insects. Here we investigate pharmacophagy in the turnip sawfly, Athalia rosae, where adults not only collect specialised metabolites (clerodanoids) from a plant (Ajuga reptans), but also from the exterior of conspecifics via fighting. Using behavioural assays, chemical analytics, and RNAseq we show that when individuals nibble on conspecifics that have already acquired clerodanoids from A. reptans leaves, this nibbling results in the transfer of compounds between individuals. Furthermore, unlike other pharmacophagous insects, the acquisition of clerodanoids by A. rosae from the leaves of A. reptans does not induce the upregulation of known detoxification or sequestration genes and pathways. In contrast, pharmacophagous nibbling on conspecifics results in the upregulation of metabolic pathways associated with elevated metabolic rates and increased energy consumption. It therefore seems that individuals attack conspecifics to acquire clerodanoids despite the apparent metabolic costs of this form of pharmacophagy compared to clerodanoid uptake from a plant. Changes in the metabolic phenotype of A.rosae individuals consequently has profound consequences for social interactions with possible ramifications for their social niche.Summary statementThe turnip sawfly (Athalia rosae) gains potentially beneficial compounds from the leaf surface of non-food plants (e.g. Ajuga reptans), but can also steal these compounds from conspecifics via aggressive nibbling.

scholarly journals Quantifying fluorescent glycan uptake to elucidate strain-level variability in foraging behaviors of rumen bacteria

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Leeann Klassen ◽  
Greta Reintjes ◽  
Jeffrey P. Tingley ◽  
Darryl R. Jones ◽  
Jan-Hendrik Hehemann ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Ex Vivo ◽  
Rapid Assessment ◽  
Vital Role ◽  
Strain Level ◽  
Metabolic Phenotype ◽  
Specific Cell ◽  
Bacterial Cells ◽  
Carbohydrate Utilization

AbstractGut microbiomes, such as the microbial community that colonizes the rumen, have vast catabolic potential and play a vital role in host health and nutrition. By expanding our understanding of metabolic pathways in these ecosystems, we will garner foundational information for manipulating microbiome structure and function to influence host physiology. Currently, our knowledge of metabolic pathways relies heavily on inferences derived from metagenomics or culturing bacteria in vitro. However, novel approaches targeting specific cell physiologies can illuminate the functional potential encoded within microbial (meta)genomes to provide accurate assessments of metabolic abilities. Using fluorescently labeled polysaccharides, we visualized carbohydrate metabolism performed by single bacterial cells in a complex rumen sample, enabling a rapid assessment of their metabolic phenotype. Specifically, we identified bovine-adapted strains of Bacteroides thetaiotaomicron that metabolized yeast mannan in the rumen microbiome ex vivo and discerned the mechanistic differences between two distinct carbohydrate foraging behaviors, referred to as “medium grower” and “high grower.” Using comparative whole-genome sequencing, RNA-seq, and carbohydrate-active enzyme fingerprinting, we could elucidate the strain-level variability in carbohydrate utilization systems of the two foraging behaviors to help predict individual strategies of nutrient acquisition. Here, we present a multi-faceted study using complimentary next-generation physiology and “omics” approaches to characterize microbial adaptation to a prebiotic in the rumen ecosystem.

Metabolomic Signature of Patients With Narcolepsy

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013128
Author(s):  
Dauvilliers Yves ◽  
Lucie Barateau ◽  
Benita Middleton ◽  
Daan Van Der Veen ◽  
Debra J Skene
Keyword(s):  
Arachidonic Acid ◽  
Metabolic Pathways ◽  
Slow Wave Sleep ◽  
Arachidonic Acid Metabolism ◽  
Metabolic Phenotype ◽  
Metabolic Disturbances ◽  
Brain Disorder ◽  
Metabolite Concentrations ◽  
Obese Subjects

Background and Objective:Narcolepsy type 1 (NT1) is an orphan brain disorder caused by the irreversible destruction of orexin neurons. Metabolic disturbances are common in patients with NT1 who have a body mass index (BMI) 10-20% higher than the general population, with one third being obese (BMI>30 kg/m2). Besides the destruction of orexin neurons in NT1, the metabolic alterations in obese and non-obese patients with narcolepsy type 1 remain unknown. The aim of the study was to identify possible differences in plasma metabolic profiles between patients with NT1 and controls as a function of their BMI status.Methods:We used a targeted liquid chromatography-mass spectrometry metabolomics approach to measure 141 circulating, low molecular weight metabolites in drug-free fasted plasma samples from 117 NT1 patients (including 41 obese subjects) compared with 116 BMI-matched controls (including 57 obese subjects).Results:Common metabolites driving the difference between NT1 and controls, irrespective of BMI, were identified, namely sarcosine, glutamate, nonaylcarnitine (C9), 5 long chain lysophosphatidylcholine acyls, one sphingolipid, 12 phosphatidylcholine diacyls and 11 phosphatidylcholine acyl-akyls, all showing increased concentrations in NT1. Metabolite concentrations significantly affected by NT1 (n = 42) and BMI category (n = 40) showed little overlap (n = 5). Quantitative enrichment analysis revealed common metabolic pathways that were implicated in the NT1/control differences, in both normal BMI and obese comparisons, namely glycine and serine, arachidonic acid, and tryptophan metabolisms. The metabolites driving these differences were glutamate, sarcosine and ornithine (glycine and serine metabolism), glutamate and PC aa C34:4 (arachidonic acid metabolism) and glutamate, serotonin and tryptophan (tryptophan metabolism). Linear metabolite-endophenotype regression analyses highlight that as part of the NT1 metabolic phenotype, most of the relationships between the sleep parameters (i.e. slow wave sleep duration, sleep latency and periodic leg movement) and metabolite concentrations seen in the controls were lost.Discussion:These results represented the most comprehensive metabolic profiling of patients with NT1 as a function of BMI and propose some metabolic diagnostic biomarkers for NT1, namely glutamate, sarcosine, serotonin, tryptophan, nonaylcarnitine and some phosphatidylcholines. The metabolic pathways identified offer, if confirmed, possible targets for treatment of obesity in NT1.Classification of Evidence:This study provides Class II evidence that a distinct metabolic profile can differentiate patients with Narcolepsy Type 1 from patients without the disorder.

scholarly journals Metabolomics for Crop Breeding: General Considerations

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1602
Author(s):  
Dmitry Y. Litvinov ◽  
Gennady I. Karlov ◽  
Mikhail G. Divashuk
Keyword(s):  
Metabolic Pathways ◽  
Cellular Localization ◽  
Association Studies ◽  
Genetically Modified Crops ◽  
Genome Wide Association Studies ◽  
Plant Metabolites ◽  
Crop Breeding ◽  
Metabolic Markers ◽  
International Service ◽  
Genome Wide

The development of new, more productive varieties of agricultural crops is becoming an increasingly difficult task. Modern approaches for the identification of beneficial alleles and their use in elite cultivars, such as quantitative trait loci (QTL) mapping and marker-assisted selection (MAS), are effective but insufficient for keeping pace with the improvement of wheat or other crops. Metabolomics is a powerful but underutilized approach that can assist crop breeding. In this review, basic methodological information is summarized, and the current strategies of applications of metabolomics related to crop breeding are explored using recent examples. We briefly describe classes of plant metabolites, cellular localization of metabolic pathways, and the strengths and weaknesses of the main metabolomics technique. Among the commercialized genetically modified crops, about 50 different metabolically altered plants have been identified in the International Service for the Acquisition of Agri-biotech Applications (ISAAA) database. These plants are reviewed as encouraging examples of the application of knowledge of biochemical pathways. Based on the recent examples of metabolomic studies, we discuss the performance of metabolic markers, the integration of metabolic and genomic data in metabolic QTLs (mQTLs) and metabolic genome-wide association studies (mGWAS). The elucidation of metabolic pathways and involved genes will help in crop breeding and the introgression of alleles of wild relatives in a more targeted manner.

scholarly journals Combined Targeting of Estrogen Receptor Alpha and Exportin 1 in Metastatic Breast Cancers

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2397
Author(s):  
Eylem Kulkoyluoglu Cotul ◽  
Qianying Zuo ◽  
Ashlie Santaliz-Casiano ◽  
Ozan Berk Imir ◽  
Ayca Nazli Mogol ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metabolic Pathways ◽  
Nuclear Export ◽  
Tumor Regression ◽  
Critical Role ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Metabolic Phenotype ◽  
Breast Cancers

The majority of breast cancer specific deaths in women with estrogen receptor positive (ER+) tumors occur due to metastases that are resistant to therapy. There is a critical need for novel therapeutic approaches to achieve tumor regression and/or maintain therapy responsiveness in metastatic ER+ tumors. The objective of this study was to elucidate the role of metabolic pathways that undermine therapy efficacy in ER+ breast cancers. Our previous studies identified Exportin 1 (XPO1), a nuclear export protein, as an important player in endocrine resistance progression and showed that combining selinexor (SEL), an FDA-approved XPO1 antagonist, synergized with endocrine agents and provided sustained tumor regression. In the current study, using a combination of transcriptomics, metabolomics and metabolic flux experiments, we identified certain mitochondrial pathways to be upregulated during endocrine resistance. When endocrine resistant cells were treated with single agents in media conditions that mimic a nutrient deprived tumor microenvironment, their glutamine dependence for continuation of mitochondrial respiration increased. The effect of glutamine was dependent on conversion of the glutamine to glutamate, and generation of NAD+. PGC1α, a key regulator of metabolism, was the main driver of the rewired metabolic phenotype. Remodeling metabolic pathways to regenerate new vulnerabilities in endocrine resistant breast tumors is novel, and our findings reveal a critical role that ERα-XPO1 crosstalk plays in reducing cancer recurrences. Combining SEL with current therapies used in clinical management of ER+ metastatic breast cancer shows promise for treating and keeping these cancers responsive to therapies in already metastasized patients.

scholarly journals Engineering Microbial Consortia towards Bioremediation

Water ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 2928
Author(s):  
Xianglong Li ◽  
Shanghua Wu ◽  
Yuzhu Dong ◽  
Haonan Fan ◽  
Zhihui Bai ◽  
...  
Keyword(s):  
Social Interactions ◽  
Metabolic Pathways ◽  
Commercial Production ◽  
Microbial Consortia ◽  
The Past ◽  
Ecological Mechanisms ◽  
Toxic Constituent ◽  
Constituent Elements ◽  
Hazardous Compounds

Bioremediation is a sustainable remediation technology as it utilizes microorganisms to convert hazardous compounds into their less toxic or non-toxic constituent elements. This technology has achieved some success in the past decades; however, factors involving microbial consortia, such as microbial assembly, functional interactions, and the role of member species, hinder its development. Microbial consortia may be engineered to reconfigure metabolic pathways and reprogram social interactions to get the desired function, thereby providing solutions to its inherent problems. The engineering of microbial consortia is commonly applied for the commercial production of biomolecules. However, in the field of bioremediation, the engineering of microbial consortia needs to be emphasized. In this review, we will discuss the molecular and ecological mechanisms of engineering microbial consortia with a particular focus on metabolic cross-feeding within species and the transfer of metabolites. We also discuss the advantages and limitations of top-down and bottom-up approaches of engineering microbial consortia and their applications in bioremediation.

scholarly journals The Systemic and Cellular Metabolic Phenotype of Infection and Immune Response to Listeria monocytogenes

2021 ◽  
Vol 11 ◽  
Author(s):  
Robert M. Johnson ◽  
Adesola C. Olatunde ◽  
Lauren N. Woodie ◽  
Michael W. Greene ◽  
Elizabeth Hiltbold Schwartz
Keyword(s):  
Immune Response ◽  
Listeria Monocytogenes ◽  
T Cell ◽  
Immune Responses ◽  
Metabolic Pathways ◽  
Bacterial Load ◽  
Cellular Level ◽  
Metabolic Phenotype ◽  
Infection Model ◽  
Cell Mediated Immunity

It is widely accepted that infection and immune response incur significant metabolic demands, yet the respective demands of specific immune responses to live pathogens have not been well delineated. It is also established that upon activation, metabolic pathways undergo shifts at the cellular level. However, most studies exploring these issues at the systemic or cellular level have utilized pathogen associated molecular patterns (PAMPs) that model sepsis, or model antigens at isolated time points. Thus, the dynamics of pathogenesis and immune response to a live infection remain largely undocumented. To better quantitate the metabolic demands induced by infection, we utilized a live pathogenic infection model. Mice infected with Listeria monocytogenes were monitored longitudinally over the course of infection through clearance. We measured systemic metabolic phenotype, bacterial load, innate and adaptive immune responses, and cellular metabolic pathways. To further delineate the role of adaptive immunity in the metabolic phenotype, we utilized two doses of bacteria, one that induced both sickness behavior and protective (T cell mediated) immunity, and the other protective immunity alone. We determined that the greatest impact to systemic metabolism occurred during the early immune response, which coincided with the greatest shift in innate cellular metabolism. In contrast, during the time of maximal T cell expansion, systemic metabolism returned to resting state. Taken together, our findings demonstrate that the timing of maximal metabolic demand overlaps with the innate immune response and that when the adaptive response is maximal, the host has returned to relative metabolic homeostasis.

scholarly journals Combined Targeting of Estrogen Receptor Alpha and XPO1 Prevent Akt Activation, Remodel Metabolic Pathways and Induce Autophagy to Overcome Tamoxifen Resistance

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 479 ◽  
Author(s):  
Eylem Kulkoyluoglu-Cotul ◽  
Brandi Patrice Smith ◽  
Kinga Wrobel ◽  
Yiru Chen Zhao ◽  
Karen Lee Ann Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metabolic Pathways ◽  
Estrogen Receptor Alpha ◽  
Expression Profiles ◽  
Endocrine Resistance ◽  
Tamoxifen Resistance ◽  
Gene Expression Profiles ◽  
Therapy Response ◽  
Metabolic Phenotype ◽  
Great Promise

A majority of breast cancer specific deaths in women with ERα (+) tumors occur due to metastases that are resistant to endocrine therapy. There is a critical need for novel therapeutic approaches to resensitize recurrent ERα (+) tumors to endocrine therapies. The objective of this study was to elucidate mechanisms of improved effectiveness of combined targeting of ERα and the nuclear transport protein XPO1 in overcoming endocrine resistance. Selinexor (SEL), an XPO1 antagonist, has been evaluated in multiple late stage clinical trials in patients with relapsed and /or refractory hematological and solid tumor malignancies. Our transcriptomics analysis showed that 4-Hydroxytamoxifen (4-OHT), SEL alone or their combination induced differential Akt signaling- and metabolism-associated gene expression profiles. Western blot analysis in endocrine resistant cell lines and xenograft models validated differential Akt phosphorylation. Using the Seahorse metabolic profiler, we showed that ERα-XPO1 targeting changed the metabolic phenotype of TAM-resistant breast cancer cells from an energetic to a quiescent profile. This finding demonstrated that combined targeting of XPO1 and ERα rewired the metabolic pathways and shut down both glycolytic and mitochondrial pathways that would eventually lead to autophagy. Remodeling metabolic pathways to regenerate new vulnerabilities in endocrine resistant breast tumors is novel, and given the need for better strategies to improve therapy response in relapsed ERα (+) tumors, our findings show great promise for uncovering the role that ERα-XPO1 crosstalk plays in reducing cancer recurrences.

Feline urine metabolomic signature: characterization of low-molecular-weight substances in urine from domestic cats

2017 ◽  
Vol 20 (2) ◽  
pp. 155-163 ◽  
Author(s):  
Sol-Maiam Rivera-Vélez ◽  
Nicolas F Villarino
Keyword(s):  
Molecular Weight ◽  
Metabolic Pathways ◽  
Metabolic Phenotype ◽  
Low Molecular Weight ◽  
Domestic Cats ◽  
Ultrasound Guided ◽  
Relevant Role ◽  
Mass Spectrometery ◽  
Urine Metabolome

Objectives This aim of this study was to characterize the composition and content of the feline urine metabolome. Methods Eight healthy domestic cats were acclimated at least 10 days before starting the study. Urine samples (~2 ml) were collected by ultrasound-guided cystocentesis. Samples were centrifuged at 1000 × g for 8 mins, and the supernatant was analyzed by gas chromatography/time-of-flight mass spectrometery. The urine metabolome was characterized using an untargeted metabolomics approach. Results Three hundred and eighteen metabolites were detected in the urine of the eight cats. These molecules are key components of at least 100 metabolic pathways. Feline urine appears to be dominated by carbohydrates, carbohydrate conjugates, organic acid and derivatives, and amino acids and analogs. The five most abundant molecules were phenaceturic acid, hippuric acid, pseudouridine phosphate and 3-(4-hydroxyphenyl) propionic acid. Conclusions and relevance This study is the first to characterize the feline urine metabolome. The results of this study revealed the presence of multiple low-molecular-weight substances that were not known to be present in feline urine. As expected, the origin of the metabolites detected in urine was diverse, including endogenous compounds and molecules biosynthesized by microbes. Also, the diet seemed to have had a relevant role on the urine metabolome. Further exploration of the urine metabolic phenotype will open a window for discovering unknown, or poorly understood, metabolic pathways. In turn, this will advance our understanding of feline biology and lead to new insights in feline physiology, nutrition and medicine.

scholarly journals NMR-Based Metabolomics Analysis Predicts Response to Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiangming He ◽  
Jinping Gu ◽  
Dehong Zou ◽  
Hongjian Yang ◽  
Yongfang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Metabolic Pathways ◽  
Triple Negative ◽  
Metabolic Phenotype ◽  
Roc Curve Analysis ◽  
Metabolic Pathway Analysis ◽  
Discriminative Ability ◽  
Metabolic Phenotypes

Triple-negative breast cancer (TNBC) is the most fatal type of breast cancer (BC). Due to the lack of relevant targeted drug therapy, in addition to surgery, chemotherapy is still the most common treatment option for TNBC. TNBC is heterogeneous, and different patients have an unusual sensitivity to chemotherapy. Only part of the patients will benefit from chemotherapy, so neoadjuvant chemotherapy (NAC) is controversial in the treatment of TNBC. Here, we performed an NMR spectroscopy–based metabolomics study to analyze the relationship between the patients’ metabolic phenotypes and chemotherapy sensitivity in the serum samples. Metabolic phenotypes from patients with pathological partial response, pathological complete response, and pathological stable disease (pPR, pCR, and pSD) could be distinguished. Furthermore, we conducted metabolic pathway analysis based on identified significant metabolites and revealed significantly disturbed metabolic pathways closely associated with three groups of TNBC patients. We evaluated the discriminative ability of metabolites related to significantly disturbed metabolic pathways by using the multi-receiver–operating characteristic (ROC) curve analysis. Three significantly disturbed metabolic pathways of glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, and alanine, aspartate, and glutamate metabolism could be used as potential predictive models to distinguish three types of TNBC patients. These results indicate that a metabolic phenotype could be used to predict whether a patient is suitable for NAC. Metabolomics research could provide data in support of metabolic phenotypes for personalized treatment of TNBC.

scholarly journals Elucidating cancer metabolic plasticity by coupling gene regulation with metabolic pathways

2019 ◽  
Vol 116 (9) ◽  
pp. 3909-3918 ◽  
Author(s):  
Dongya Jia ◽  
Mingyang Lu ◽  
Kwang Hwa Jung ◽  
Jun Hyoung Park ◽  
Linglin Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Regulation ◽  
Cancer Cells ◽  
Model Prediction ◽  
Metabolic Pathways ◽  
Cancer Metabolism ◽  
The Cancer Genome Atlas ◽  
Metabolic Phenotype ◽  
Metabolic State ◽  
Metabolic Plasticity

Metabolic plasticity enables cancer cells to switch their metabolism phenotypes between glycolysis and oxidative phosphorylation (OXPHOS) during tumorigenesis and metastasis. However, it is still largely unknown how cancer cells orchestrate gene regulation to balance their glycolysis and OXPHOS activities. Previously, by modeling the gene regulation of cancer metabolism we have reported that cancer cells can acquire a stable hybrid metabolic state in which both glycolysis and OXPHOS can be used. Here, to comprehensively characterize cancer metabolic activity, we establish a theoretical framework by coupling gene regulation with metabolic pathways. Our modeling results demonstrate a direct association between the activities of AMPK and HIF-1, master regulators of OXPHOS and glycolysis, respectively, with the activities of three major metabolic pathways: glucose oxidation, glycolysis, and fatty acid oxidation. Our model further characterizes the hybrid metabolic state and a metabolically inactive state where cells have low activity of both glycolysis and OXPHOS. We verify the model prediction using metabolomics and transcriptomics data from paired tumor and adjacent benign tissue samples from a cohort of breast cancer patients and RNA-sequencing data from The Cancer Genome Atlas. We further validate the model prediction by in vitro studies of aggressive triple-negative breast cancer (TNBC) cells. The experimental results confirm that TNBC cells can maintain a hybrid metabolic phenotype and targeting both glycolysis and OXPHOS is necessary to eliminate their metabolic plasticity. In summary, our work serves as a platform to symmetrically study how tuning gene activity modulates metabolic pathway activity, and vice versa.

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