PubMed

Related Articles Mitochondrial One-Carbon Pathway Supports Cytosolic Folate Integrity in Cancer Cells. Cell. 2018 Nov 29;175(6):1546-1560.e17 Authors: Zheng Y, Lin TY, Lee G, Paddock MN, Momb J, Cheng Z, Li Q, Fei DL, Stein BD, Ramsamooj S, Zhang G, Blenis J, Cantley LC Abstract Mammalian folate metabolism is comprised of cytosolic and mitochondrial pathways with nearly identical core reactions, yet the functional advantages of such an organization are not well understood. Using genome-editing and biochemical approaches, we find that ablating folate metabolism in the mitochondria of mammalian cell lines results in folate degradation in the cytosol. Mechanistically, we show that QDPR, an enzyme in tetrahydrobiopterin metabolism, moonlights to repair oxidative damage to tetrahydrofolate (THF). This repair capacity is overwhelmed when cytosolic THF hyperaccumulates in the absence of mitochondrially produced formate, leading to THF degradation. Unexpectedly, we also find that the classic antifolate methotrexate, by inhibiting its well-known target DHFR, causes even more extensive folate degradation in nearly all tested cancer cell lines. These findings shed light on design features of folate metabolism, provide a biochemical basis for clinically observed folate deficiency in QDPR-deficient patients, and reveal a hitherto unknown and unexplored cellular effect of methotrexate. PMID: 30500537 [PubMed - in process]

Related Articles Disruption of Kidney Metabolism in Rats after Subchronic Combined Exposure to Low-Dose Cadmium and Chlorpyrifos. Chem Res Toxicol. 2018 Nov 30;: Authors: Xu MY, Wang P, Sun YJ, Wu YJ Abstract Cadmium (Cd) and chlorpyrifos (CPF) often coexist in the environment and induce combined toxicity to organisms. Here we studied the combined nephrotoxicity of environmentally relevant low doses of Cd and CPF. We treated the mice for 90 days with different doses of Cd and CPF and their mixtures via oral gavage. Then histopathological evaluation and biochemical analysis for kidney tissues were carried out. The change of metabolites in kidney was detected by using a metabolomics approach using GC-MS. We found that Cd, CPF, and their mixtures caused oxidative damage, as well as disturbance of renal amino acid metabolism. We identified potential metabolite biomarkers in kidney, which included acetic acid for CPF treatment, glycerol and carboxylic acid for Cd treatment, and L-ornithine for the mixture of CPF and Cd treatment, respectively. In addition, we found that Cd promoted the metabolism of CPF in kidney. This may contribute to the result that the toxicity of the mixtures was lower than the sum of the toxicities of Cd and CPF alone. In conclusion, our results indicated that CPF and Cd could disrupt the kidney metabolism in rats even when they were exposed to very low dose of CPF and Cd. PMID: 30500169 [PubMed - as supplied by publisher]

Related Articles MetNet: Metabolite network prediction from high-resolution mass spectrometry data in R aids metabolite annotation. Anal Chem. 2018 Nov 30;: Authors: Naake T, Fernie AR Abstract A major bottleneck of mass spectrometric metabolomic analysis is still the rapid detection and annotation of unknown m/z features across biological matrices. This kind of analysis is especially cumbersome for complex samples with hundreds to thousands of unknown features. Traditionally, the annotation was done manually imposing constraints in reproducibility and automatization. Furthermore, different analysis tools are typically used at different steps which requires parsing of data and changing of environments. We present here MetNet, implemented in the R programming language and available as an open-source package via the Bioconductor project. MetNet that is compatible with the output of the xcms/CAMERA suite uses the data-rich output of mass spectrometry metabolomics to putatively link features on their relation to other features in the data set. MetNet uses both structural and quantitative information of metabolomics data for network inference and enables the annotation of unknown analytes. PMID: 30500168 [PubMed - as supplied by publisher]

Related Articles A metabolomics platform by capillary electrophoresis coupled with a high-resolution mass spectrometry for plasma analysis. Anal Chem. 2018 Nov 30;: Authors: Sasaki K, Sagawa H, Suzuki M, Yamamoto H, Tomita M, Soga T, Ohashi Y Abstract Metabolome analysis using capillary electrophoresis (CE) coupled with high-resolution mass spectrometry (HRMS) has the potential to improve coverage of metabolite detection due to its high selectivity and sensitivity. Configuration of the interface between CE and HRMS to meet the ground connection is essential to enable independent regulation of the electrical currents in the CE and electrospray field. In the present study, we applied an electrospray ionization adapter equipped with a grounded nebulizer to CE-HRMS and tested the analytical performance for 34 charged compounds. The extracted ion electropherograms, consisting of seven sets of isomers, showed reasonable peak shapes and separation for the annotation of each metabolite. The levels of 34 target analytes in a standard mixture were determined with a dynamic range of at least 102, maintaining linearity with r2 >0.9. The repeatability and intermediate precision above the lower limit of quantification showed the relative standard deviation to be lower than 20%. In the spike recovery experiment, 27 of the 34 metabolites in plasma extract were recovered at a rate of 80 to 120%, suggesting high accuracy. Furthermore, we assessed the feasibility of our platform to metabolome analysis using human plasma extract. The results showed successful detection of 270 metabolites, indicating the potential of our platform to yield higher coverage of the metabolome. In addition, analysis of dilution integrity demonstrated the quantitative ability of metabolome analysis with CE-HRMS, although the existence of saturation or matrix effects were seen in the case of 33 of the metabolites. This study indicates that our platform has great potential for large scale metabolome analysis of plasma for biological studies and clinical biomarker screening. PMID: 30500154 [PubMed - as supplied by publisher]

Traditional Tibetan medicinal plants: a highlighted resource for novel therapeutic compounds. Future Med Chem. 2018 Nov 30;: Authors: Hao DC, Xiao PG, Liu C Abstract Around 70-80% of drugs used in traditional Tibetan medicine (TTM) come from Qinghai Tibet Plateau, the majority of which are plants. The biological and medicinal culture diversity on Qinghai Tibet Plateau are amazing and constitute a less tapped resource for innovative drug research and development. Meanwhile, the problem of the exhausting Tibetan medicine resources is worrying. Here, the latest awareness, as well as the gaps of the traditional Tibetan medicinal plant issues in drug development and clinical usage of TTM compounds, was systematically reviewed and highlighted. The TTM resource studies should be enhanced within the context of deeper and more extensive investigations of molecular biology and genomics of TTM plants, phytometabolites and metabolomics and ethnopharmacology-based bioactivity, thus enabling the sustainable conservation and exploitation of Tibetan medicinal resource. PMID: 30499690 [PubMed - as supplied by publisher]

Early metabolic characterization of brain tissuesafter whole body radiation based on gas chromatography-mass spectrometry in a rat model. Biomed Chromatogr. 2018 Nov 30;:e4448 Authors: Yao X, Xu C, Cao Y, Lin L, Wu H, Wang C Abstract Radiation-induced brain injury contains acute, early delayed and late delayed damage based on the time-course and clinical manifestations. The acute symptoms are mostly transient and reversible, whereas the late delayed radiation-induced changes are progressive and irreversible. Therefore, evaluation of the organ specific early response to ionizing radiation exposure is necessary for improving treatment strategies and minimizing possible damages at early stage after radiation exposure. In current study, the gas chromatography-mass spectrometry technique (GC-MS) based on metabolomics coupled with metabolic correlation network was applied to investigate the early metabolic characterization of the rat brain tissues following irradiation. Our findings showed that the metabolic response to irradiation was not just limited to the variations of individual metabolite levels, but also accompanied with the alternations of network correlations among differential metabolites. Metabolite clustering indicated that energy metabolism disorder and inflammation response were induced following radiation exposure. The correlation networks revealed that the strong positive correlations of differential metabolites were highly reduced and significant negative linkages were highlighted in irradiated groups even without statistical changes of metabolic levels. Our findings provided new insights into our understanding of the radiation-induced acute brain injury mechanism and clues to therapy target of clinical applications. PMID: 30499600 [PubMed - as supplied by publisher]

Current understanding of the potential of proteomics and metabolomics approaches in cancer chemoresistance: A focus on Multiple Myeloma. Curr Top Med Chem. 2018 Nov 29;: Authors: Chanukuppa V, Taware R, Chatterjee T, Sharma S, More TH, Taunk K, Kumar S, Santra MK, Rapole S Abstract Chemoresistance is one of the major hurdles in cancer treatment leading to recurrence of cancer and affects overall survival of patients. Cancer chemoresistance can be associated with various phenomena including modulation of vital cellular pathways. Unrevealing these alterations could provide better understanding of chemoresistance and assist in identification of new targets to overcome it. Recent advances in the field of proteomics and metabolomics have substantially helped in identification of potential targets for chemoresistance in various cancers. This review highlights the potential of proteomics and metabolomics research to explore the putative targets associated with cancer chemoresistance with a special focus on Multiple Myeloma (MM). MM is a type of hematological malignancy which constitutes about 13% of all blood cell cancers. The therapeutic advancements for MM have increased the median overall survival rate to over 3-fold in the last one and half decade. Although, in recent times significant improvements in the overall survival rate of MM is achieved, MM remains an incurable disease with unpredictable refractory mechanisms. In spite of therapeutic advances, chemoresistance thrives to be a major hurdle in the treatment of multiple myeloma which demands better understanding of chemoresitance. In this review, we have attempted to highlight the potential applications of proteomics and metabolomics research in understanding of chemoresistance in MM. PMID: 30499398 [PubMed - as supplied by publisher]

Related Articles Multifaceted Interactions Between Endophytes and Plant: Developments and Prospects. Front Microbiol. 2018;9:2732 Authors: Khare E, Mishra J, Arora NK Abstract Microbial endophytes are present in all known plant species. The ability to enter and thrive in the plant tissues makes endophytes unique, showing multidimensional interactions within the host plant. Several vital activities of the host plant are known to be influenced by the presence of endophytes. They can promote plant growth, elicit defense response against pathogen attack, and can act as remediators of abiotic stresses. To date, most of the research has been done assuming that the interaction of endophytes with the host plant is similar to the plant growth-promoting (PGP) microbes present in the rhizosphere. However, a new appreciation of the difference of the rhizosphere environment from that of internal plant tissues is gaining attention. It would be interesting to explore the impact of endosymbionts on the host's gene expression, metabolism, and other physiological aspects essential in conferring resistance against biotic and abiotic stresses. A more intriguing and inexplicable issue with many endophytes that has to be critically evaluated is their ability to produce host metabolites, which can be harnessed on a large scale for potential use in diverse areas. In this review, we discuss the concept of endophytism, looking into the latest insights related to the multifarious interactions beneficial for the host plant and exploring the importance of these associations in agriculture and the environment and in other vital aspects such as human health. PMID: 30498482 [PubMed]

Related Articles A pathogenic role for cystic fibrosis transmembrane conductance regulator in celiac disease. EMBO J. 2018 Nov 29;: Authors: Villella VR, Venerando A, Cozza G, Esposito S, Ferrari E, Monzani R, Spinella MC, Oikonomou V, Renga G, Tosco A, Rossin F, Guido S, Silano M, Garaci E, Chao YK, Grimm C, Luciani A, Romani L, Piacentini M, Raia V, Kroemer G, Maiuri L Abstract Intestinal handling of dietary proteins usually prevents local inflammatory and immune responses and promotes oral tolerance. However, in ~ 1% of the world population, gluten proteins from wheat and related cereals trigger an HLA DQ2/8-restricted TH1 immune and antibody response leading to celiac disease. Prior epithelial stress and innate immune activation are essential for breaking oral tolerance to the gluten component gliadin. How gliadin subverts host intestinal mucosal defenses remains elusive. Here, we show that the α-gliadin-derived LGQQQPFPPQQPY peptide (P31-43) inhibits the function of cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel pivotal for epithelial adaptation to cell-autonomous or environmental stress. P31-43 binds to, and reduces ATPase activity of, the nucleotide-binding domain-1 (NBD1) of CFTR, thus impairing CFTR function. This generates epithelial stress, tissue transglutaminase and inflammasome activation, NF-κB nuclear translocation and IL-15 production, that all can be prevented by potentiators of CFTR channel gating. The CFTR potentiator VX-770 attenuates gliadin-induced inflammation and promotes a tolerogenic response in gluten-sensitive mice and cells from celiac patients. Our results unveil a primordial role for CFTR as a central hub orchestrating gliadin activities and identify a novel therapeutic option for celiac disease. PMID: 30498130 [PubMed - as supplied by publisher]

26 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/11/30PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/11/28PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

30 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/11/27PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Oxidosqualene cyclase and CYP716 enzymes contribute to the triterpene structural diversity in the medicinal tree banaba. New Phytol. 2018 Nov 24;: Authors: Sandeep, Misra RC, Chanotiya CS, Mukhopadhyay P, Ghosh S Abstract Pentacyclic triterpenes (PCTs) represent a major class of bioactive metabolites in banaba (Lagerstroemia speciosa) leaves; however, biosynthetic enzymes and their involvement in temporal accumulation of PCTs are still not studied. We employed an integrated approach involving transcriptomics, metabolomics and gene function analysis to identify oxidosqualene cyclases (OSCs) and cytochrome P450 monooxygenases (P450s) that catalyzed sequential cyclization and oxidative reactions towards PCT scaffold diversification. Four monofunctional OSCs (LsOSC1,3-5) converted triterpene precursor 2,3-oxidosqualene to either of lupeol, β-amyrin and cycloartenol, and a multifunctional LsOSC2 formed α-amyrin as a major product along with β-amyrin. Two CYP716 family P450s (CYP716A265, CYP716A266) catalyzed C-28 oxidation of α-amyrin, β-amyrin and lupeol to form ursolic acid, oleanolic acid and betulinic acid, respectively. However, CYP716C55 catalyzed C-2α hydroxylation of ursolic acid and oleanolic acid to produce corosolic acid and maslinic acid, respectively. Besides, combined transcript and metabolite analysis suggested major roles for the LsOSC2, CYP716A265 and CYP716C55 in determining leaf ursane and oleanane profiles. Combinatorial expression of OSCs and CYP716s in Saccharomyces cerevisiae and Nicotiana benthamiana led to PCT pathway reconstruction, signifying the utility of banaba enzymes for bioactive PCT production in alternate plant/microbial hosts that are easily tractable than the tree species. This article is protected by copyright. All rights reserved. PMID: 30472753 [PubMed - as supplied by publisher]

Phosphatidylcholine could protect the defect of zearalenone exposure on follicular development and oocyte maturation. Aging (Albany NY). 2018 Nov 25;: Authors: Lai FN, Liu XL, Li N, Zhang RQ, Zhao Y, Feng YZ, Nyachoti CM, Shen W, Li L Abstract Zearalenone (ZEA) is a well-known exogenous endocrine disruptor and can lead to severe negative effects on the human and animal reproductive process. Using a follicle culture model, we have previously shown that ZEA exposure significantly affected the follicular development and antrum formation but the underlying mechanisms are not well known. Therefore, in this study, we explored the metabolomic changes of granulosa cell (GC) culture media with or without ZEA exposure. The results showed that ZEA significantly increased phosphatidylcholine or phosphatidyl ethanolamine adducts in culture medium. A comprehensive analysis with the metabolome data from follicular fluid of small and large antral follicles showed that lyso phosphatidylcholine (LPC) was accumulated during follicle growth, but was depleted by ZEA exposure. Exogenous supplement with LPC to the follicle growth media or oocyte maturation media can partly protect the defect of ZEA exposure on follicular antrum formation and oocyte maturation. Taken together, our results demonstrate that ZEA exposure hinders the follicular growth and exogenous LPC can practically protect the defect of ZEA on follicular development and oocyte maturation. PMID: 30472698 [PubMed - as supplied by publisher]

Ancestral Transcriptome Inference Based on RNA-Seq and ChIP-seq Data. Methods. 2018 Nov 22;: Authors: Yang J, Ruan H, Zou Y, Su Z, Gu X Abstract With the help of high-throughput NGS (next-generation sequencing) technologies, ancestral transcriptome reconstruction is helpful to understand the complexity of transcriptional regulatory systems that underlies the evolution of multiple cellular metazoans with sophisticated functions and distinctive morphologies. To this end, we report a new method of ancestral state inference. The new method used Ornstein-Uhlenbeck (OU) model, which is more biologically realistic, to replace the Brownian motion (BM) model and is suitable for multi-transcriptome data. Implemented in the free R package, AnceTran is specially designed for RNA-seq and ChIP-seq data, which is feasible. It should be noticed that our work will be integrated to a unified, statistically-sound phylogenetic framework to study the evolution of many other molecular phenomes such as proteomics, chromatin accessibility, methylation status, and metabolomics. We exemplify our method by a case study, using the ChIP-seq binding data of three liver-specific transcription factors and the RNA-seq liver expression data in four closely related mice species, and some technical issues are discussed. PMID: 30472248 [PubMed - as supplied by publisher]

MYC Induces a Hybrid Energetics Program Early in Cell Reprogramming. Stem Cell Reports. 2018 Nov 09;: Authors: Prieto J, Seo AY, León M, Santacatterina F, Torresano L, Palomino-Schätzlein M, Giménez K, Vallet-Sánchez A, Ponsoda X, Pineda-Lucena A, Cuezva JM, Lippincott-Schwartz J, Torres J Abstract Cell reprogramming is thought to be associated with a full metabolic switch from an oxidative- to a glycolytic-based metabolism. However, neither the dynamics nor the factors controlling this metabolic switch are fully understood. By using cellular, biochemical, protein array, metabolomic, and respirometry analyses, we found that c-MYC establishes a robust bivalent energetics program early in cell reprogramming. Cells prone to undergo reprogramming exhibit high mitochondrial membrane potential and display a hybrid metabolism. We conclude that MYC proteins orchestrate a rewiring of somatic cell metabolism early in cell reprogramming, whereby somatic cells acquire the phenotypic plasticity necessary for their transition to pluripotency in response to either intrinsic or external cues. PMID: 30472011 [PubMed - as supplied by publisher]

Modified metabolites mapping by liquid chromatography-high resolution mass spectrometry using full scan/all ion fragmentation/neutral loss acquisition. J Chromatogr A. 2018 Nov 11;: Authors: Li H, Qin Q, Shi X, He J, Xu G Abstract Modified metabolites play important roles in diagnostic monitoring, oxidative response and physiological regulation. Comprehensive analytical methods are greatly needed for improving the coverage of modified metabolites and studying their physiological function. Here, a novel nontargeted profiling method for mapping modified metabolites was developed by liquid chromatography-high resolution mass spectrometry with full scan/all ion fragmentation/neutral loss (FS/AIF/NL) data acquisition. Modified metabolites were unbiasedly defined with less false positive results by mixed standards verification. Thirteen types of modified metabolites in urine were analyzed at the same time, and 198 of 307 modified metabolites at positive mode and 166 of 366 modified metabolites at negative mode were putatively identified. The modified metabolites profiling method was applied for investigating the metabolic differences between the patients with breast cancer and health controls. As a result, many modified metabolites with glucuronidation, ribosylation and indole acetylation modification were significantly up-regulated in breast cancer and four modified metabolites including 7-methylguanosine, N4-acetylcytidine, dihyroxy-1H-indole glucuronide I and indole-3-acetic acid-O-glucuronide were identified as potential biomarkers for the diagnose of breast cancer. PMID: 30471789 [PubMed - as supplied by publisher]

Related Articles Asymmetrical flow field-flow fractionation for improved characterization of human plasma lipoproteins. Anal Bioanal Chem. 2018 Nov 23;: Authors: Bria CRM, Afshinnia F, Skelly PW, Rajendiran TM, Kayampilly P, Thomas TP, Andreev VP, Pennathur S, Kim Ratanathanawongs Williams S Abstract High- and low-density lipoproteins (HDL and LDL) are attractive targets for biomarker discovery. However, ultracentrifugation (UC), the current methodology of choice for isolating HDL and LDL, is tedious, requires large sample volume, results in sample loss, and does not readily provide information on particle size. In this work, human plasma HDL and LDL are separated and collected using semi-preparative asymmetrical flow field-flow fractionation (SP-AF4) and UC. The SP-AF4 and UC separation conditions, sample throughput, and liquid chromatography/mass spectrometry (LC/MS) lipidomic results are compared. Over 600 μg of total proteins is recovered in a single SP-AF4 run, and Western blot results confirm apoA1 pure and apoB100 pure fractions, consistent with HDL and LDL, respectively. The SP-AF4 separation requires ~ 60 min per sample, thus providing a marked improvement over UC which can span hours to days. Lipidome analysis of SP-AF4-prepared HDL and LDL fractions is compared to UC-prepared HDL and LDL samples. Over 270 lipids in positive MS mode and over 140 lipids in negative MS mode are identified by both sample preparation techniques with over 98% overlap between the lipidome. Additionally, lipoprotein size distributions are determined using analytical scale AF4 coupled with multiangle light scattering (MALS) and dynamic light scattering (DLS) detectors. These developments position SP-AF4 as a sample preparation method of choice for lipoprotein biomarker characterization and identification. Graphical abstract ᅟ. PMID: 30470915 [PubMed - as supplied by publisher]

Related Articles QTL mapping of insect resistance components of Solanum galapagense. Theor Appl Genet. 2018 Nov 23;: Authors: Vosman B, Kashaninia A, Van't Westende W, Meijer-Dekens F, van Eekelen H, Visser RGF, de Vos RCH, Voorrips RE Abstract KEY MESSAGE: QTLs for insect resistance parameters, trichome type IV development, and more than 200 non-volatile metabolites, including 76 acyl sugars, all co-locate at the end of Chromosome 2 of Solanum galapagense. Host plant resistance is gaining importance as more and more insecticides are being banned due to environmental concerns. In tomato, resistance towards insects is found in wild relatives and has been attributed to the presence of glandular trichomes and their specific phytochemical composition. In this paper, we describe the results from a large-scale QTL mapping of data from whitefly resistance tests, trichome phenotyping and a comprehensive metabolomics analysis in a recombinant inbred line population derived from a cross between the cultivated Solanum lycopersicum and the wild relative S. galapagense, which is resistant to a range of pest insects. One major QTL (Wf-1) was found to govern the resistance against two different whitefly species. This QTL co-localizes with QTLs for the presence of trichomes type IV and V, as well as all 76 acyl sugars detected and about 150 other non-volatile phytochemicals, including methyl esters of the flavonols myricetin and quercetin. Based on these results, we hypothesize that Wf-1 is regulating the formation of glandular trichome type IV on the leaf epidermis, enabling the production and accumulation of bioactive metabolites in this type of trichomes. PMID: 30470858 [PubMed - as supplied by publisher]

Related Articles Symbiotic microbes affect the expression of male reproductive genes in Glossina m. morsitans. BMC Microbiol. 2018 Nov 23;18(Suppl 1):169 Authors: Scolari F, Attardo GM, Aksoy E, Weiss B, Savini G, Takac P, Abd-Alla A, Parker AG, Aksoy S, Malacrida AR Abstract BACKGROUND: Tsetse flies (Diptera, Glossinidae) display unique reproductive biology traits. Females reproduce through adenotrophic viviparity, nourishing the growing larva into their modified uterus until parturition. Males transfer their sperm and seminal fluid, produced by both testes and male accessory glands, in a spermatophore capsule transiently formed within the female reproductive tract upon mating. Both sexes are obligate blood feeders and have evolved tight relationships with endosymbionts, already shown to provide essential nutrients lacking in their diet. However, the partnership between tsetse and its symbionts has so far been investigated, at the molecular, genomic and metabolomics level, only in females, whereas the roles of microbiota in male reproduction are still unexplored. RESULTS: Here we begin unravelling the impact of microbiota on Glossina m. morsitans (G. morsitans) male reproductive biology by generating transcriptomes from the reproductive tissues of males deprived of their endosymbionts (aposymbiotic) via maternal antibiotic treatment and dietary supplementation. We then compared the transcriptional profiles of genes expressed in the male reproductive tract of normal and these aposymbiotic flies. We showed that microbiota removal impacts several male reproductive genes by depressing the activity of genes in the male accessory glands (MAGs), including sequences encoding seminal fluid proteins, and increasing expression of genes in the testes. In the MAGs, in particular, the expression of genes related to mating, immunity and seminal fluid components' synthesis is reduced. In the testes, the absence of symbionts activates genes involved in the metabolic apparatus at the basis of male reproduction, including sperm production, motility and function. CONCLUSIONS: Our findings mirrored the complementary roles male accessory glands and testes play in supporting male reproduction and open new avenues for disentangling the interplay between male insects and endosymbionts. From an applied perspective, unravelling the metabolic and functional relationships between tsetse symbionts and male reproductive physiology will provide fundamental information useful to understanding the biology underlying improved male reproductive success in tsetse. This information is of particular importance in the context of tsetse population control via Sterile Insect Technique (SIT) and its impact on trypanosomiasis transmission. PMID: 30470198 [PubMed - in process]