Exosome-Mediated Impact on Systemic Metabolism

Annual Review of Physiology, Journal Year: 2024, Volume and Issue: 86(1), P. 225 - 253

Published: Feb. 12, 2024

Exosomes are small extracellular vesicles that carry lipids, proteins, and microRNAs (miRNAs). They released by all cell types can be found not only in circulation but many biological fluids. essential for interorgan communication because they transfer their contents from donor to recipient cells, modulating cellular functions. The miRNA content of exosomes is responsible most effects, changes exosomal levels contribute the progression or regression metabolic diseases. As miRNAs selectively sorted packaged into exosomes, useful as biomarkers diagnosing field metabolism expanding rapidly, researchers consistently making new discoveries this area. a result, have great potential next-generation drug delivery platform

Language: Английский

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Unveiling the Wonders of Bacteria-Derived Extracellular Vesicles: From Fundamental Functions to Beneficial Applications

Heliyon, Journal Year: 2025, Volume and Issue: 11(4), P. e42509 - e42509

Published: Feb. 1, 2025

:Extracellular vesicles (EVs), are critical mediators of intercellular communication and exhibit significant potential across various biomedical domains. These nano-sized, membrane-encapsulated entities have captured substantial interest due to their diverse roles in pathogenesis promising therapeutic applications. EVs manage numerous physiological processes by transferring bioactive molecules, including proteins, lipids, nucleic acids, between cells. This review delves into the factors influencing properties EVs, such as temperature stress conditions, which collectively influence size, composition, functional attributes. We also describe emerging emphasizing involvement microbial interactions, immune modulation, antimicrobial resistance spread innovative diagnostic instruments. Despite applications, advancement EV-based therapies faces several challenges, will be discussed. By elucidating these elements, we aim provide a comprehensive overview transformative revolutionizing diagnostics therapeutics medicine.

Language: Английский

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Extracellular vesicles of Limosilactobacillus fermentum SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism

Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)

Published: March 3, 2025

Atopic dermatitis (AD) is a globally prevalent chronic inflammatory skin disorder. Its pathogenesis remains incompletely understood, resulting in considerable therapeutic challenges. Recent studies have highlighted the significance of interaction between AD and gut microbiome. In this study, we investigated effects probiotic-derived extracellular vesicles on AD. Initially, isolated characterized from Limosilactobacillus fermentum SLAM 216 (LF216EV) their composition through multi-omics analysis. Gene ontology (GO) pathway analysis classified LF216EV proteins into biological processes, molecular functions, cellular components. Importantly, specific abundance linoleic, oleic, palmitic, sebacic, stearic acids indicating upregulated fatty acid metabolism were observed by metabolomic Furthermore, featured lipid profiling including AcylGlcADG ceramide LF216EV. an atopic dermatitis-like cell model induced TNFα/IFNγ, significantly modulated expression immune regulatory genes (TSLP, TNFα, IL-6, IL-1β, MDC), its potential functionality dermatitis. alleviated AD-like phenotypes, such as redness, scaling/dryness, excoriation, DNCB. Histopathological revealed that decreased epidermal thickness mast infiltration dermis. administration reduced mouse scratching depression-related behaviors, with faster onset than classical treatment dexamethasone. quantitative real-time polymerase chain reaction (qRT-PCR) analysis, significant increase levels htrb2c, sert, tph-1, associated serotonin, LF216EV-treated group, along total serum serotonin levels. Gut microbiome group altered microbiota profile. Correlation genera Desulfovibrio differences intestinal metabolites, serotonin. Our findings demonstrate mitigates symptoms promoting synthesis modulation metabolome composition.

Language: Английский

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Extracellular Vesicles in Fungi: Past, Present, and Future Perspectives

Frontiers in Cellular and Infection Microbiology, Journal Year: 2020, Volume and Issue: 10

Published: July 15, 2020

Extracellular vesicles (EVs) have garnered much interest in the cell biology and biomedical research fields. Many studies reported existence of EVs all types living cells, including fifteen different fungal genera. play diverse biological roles, from regulation physiological events response to specific environmental conditions mediation highly complex interkingdom communications. This review will provide a historical perspective on produced by fungi an overview recent discoveries field. We also current knowledge about EV biogenesis cargo, their role cell-to-cell interactions, methods analysis. Finally, we discuss perspectives as vehicles for delivery biologically active molecules.

Language: Английский

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The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes

Journal of Lipid Research, Journal Year: 2019, Volume and Issue: 61(5), P. 676 - 686

Published: Dec. 30, 2019

Cellular membranes are not homogenous mixtures of proteins; rather, they segregated into microdomains on the basis preferential association between specific lipids and proteins. These microdomains, called lipid rafts, well known for their role in receptor signaling plasma membrane (PM) essential to such cellular functions as signal transduction spatial organization PM. A number disease states, including atherosclerosis other cardiovascular disorders, may be caused by dysfunctional maintenance rafts. Lipid rafts do occur only PM but also have been found intracellular extracellular vesicles (EVs). Here, we focus discussing newly discovered membranes, protein trafficking from ER, Golgi bodies, endosomes PM, examine raft involvement production composition EVs. Because small transient, visualization remains challenging. Future work with advanced techniques will continue expand our knowledge about roles functioning. autophagy beclin 1 regulator ER-resident cholesterol transport caveolin-1 cardiolipin cholesteryl ester dynamin-like detergent-resistant vesicle free disialoganglioside three glycosyl groups LDL mitochondria-associated mitofusin nascent HDL Niemann-Pick type C phosphatidylcholine phosphatidylethanolamine phosphatidylserine scavenger BI triglyceride trans-Golgi network proteins, composed some which segregate enriched (FC) glycosphingolipids, like SM, resistant detergent extraction. In this review, domains FC SM designated "lipid rafts," while that characterized, particularly those mitochondria, referred microdomains. The segregation these structures regulates polarity vesicular traffic cell pathways affecting a plethora biological processes (1Sorci-Thomas M.G. Thomas M.J. Microdomains, inflammation, atherosclerosis.Circ. Res. 2016; 118: 679-691Crossref PubMed Scopus (102) Google Scholar). However, over two decades since functional model was first published Simons Ikonen (2Simons K. E. Functional membranes.Nature. 1997; 387: 569-572Crossref (7883) Scholar), many fundamental questions biogenesis structure still remain unanswered. Although less so today than past, experimental obstacles visualizing hampered progress understanding size, when where formed, how turned or removed cell. new developed provide clearer vision form function. Since previous review inflammatory great deal information has emerged providing insights affect states. current discuss contribution Two common types described: planar invaginated curve inward termed caveolae. Caveolae specialized very high numbers adipocytes, associate (CAV1) concave regions (3Ariotti, N., M. A., Fernandez-Rojo, Y., Zhou, M., Hill, T. L., Rodkey, Inder, L. B. Tanner, R. Wenk, J. F. Hancock, G. Parton. 2014. regulate nanoscale remotely control Ras signaling. Cell Biol., 204: 777–792.Google Formation is due phase separation within thermodynamically driven depends amounts both components Regions rich more ordered often liquid-ordered compared rest membrane, liquid-disordered phase. size estimated average around 500 nm2, lifetimes range seconds minutes (4Pralle A. Keller P. Florin E.L. Horber J.K. Sphingolipid-cholesterol diffuse entities mammalian cells.J. Biol. 2000; 148: 997-1008Crossref (831) mobile "float" an iceberg phase, can larger raft-domains, proteins facilitate oligomerization complexes. Studies rabbit erythrocytes Chinese hamster ovary cells suggest PMs accommodate having different packing sizes (5Sanchez S.A. Tricerri M.A. Gratton Laurdan generalized polarization fluctuations measures micro-heterogeneity vivo.Proc. Natl. Acad. Sci. USA. 2012; 109: 7314-7319Crossref (116) Scholar, 6Levental I. Grzybek Raft variable properties compositions vesicles.Proc. 2011; 108: 11411-11416Crossref (167) Changes composition, modulates content, mobility. For example, increasing concentration THP1 leads increased chemotactic response monocyte chemoattractant protein-1 (MCP-1) alterations C-C motif chemokine 2 (CCR2) levels Modulating human affected rolling E-selectin-coated surfaces changing E-selectin counterreceptor CD44 distribution suggesting mechanism through adhesion regulation mobility (7Saha A.K. Mousavi Dallo S.F. Evani S.J. Ramasubramanian Influence chemotaxis.Cell. Immunol. 2018; 324: 74-77Crossref (3) 8Saha Osmulski Gaczynska Huang T.H. Cholesterol distribution.Biophys. 2017; 112: 1481-1488Abstract Full Text PDF (12) All outer protective barrier made up phospholipid bilayer associates variety aiding integrity communication. highly organized displays asymmetry respect phospholipids inner leaflets distribution. (PC) predominates higher percentage PC leaflet, (PS) (PE) preferentially leaflet (9van Meer Voelker D.R. Feigenson G.W. Membrane lipids: behave.Nat. Rev. Mol. 2008; 9: 112-124Crossref (4079) 10Rivel Ramseyer C. Yesylevskyy S. content influence uptake cisplatin.Sci. Rep. 2019; 5627Crossref (50) Bilayers associated organelles somewhat ratios, reported asymmetrically distributed (11Liu, R., Sheng, H., Jung, Wang, E., Stec, J., O'Connor, Song, Bikkavilli, Winn, D. Lee, . 2017. Orthogonal sensors identify transbilayer cholesterol. Nat. Chem. 13: 268–274.Google 12Ogasawara Kano Murata Kimura Y. Kioka N. Ueda asymmetric streptolysin O pore formation.Sci. 4548Crossref (14) 13Steck T.L. Lange Transverse cholesterol: picking sides.Traffic. 19: 750-760Crossref (62) Recent studies long chain C24 sphingolipids modulate (14Courtney, C., W., Pezeshkian, Raghupathy, Zhang, Darbyson, Ipsen, Ford, H. Khandelia, Presley, X. Zha. 2018. govern lateral live-cell membranes. Reports., 24: 1037–1049.Google Despite years research, controversial. dynamic nature proportions non-raft difficult quantify image real time. most method study isolate (DRM) (15Raggi, Diociaiuti, G., Caracciolo, F., Fratini, Fantozzi, Piccaro, Fecchi, Pizzi, Marano, Ciaffoni, 2019. Caveolin-1 endows order cholesterol-rich Biomolecules., E287.Google DRMs contain subset lipid-anchored integral Intact membrane-associated visualized using fluorescently labeled antibodies recognize fluorescent ganglioside analogs (16Suzuki, Ando, Komura, Konishi, Imamura, Ishida, Kiso, Fujiwara, Kusumi. Revealing domain single-molecule imaging analogs. Methods Enzymol., 598: 267–282.Google Scholar) sequestered regions. Newer, non-detergent methods isolating bulk permitting analysis (17Macdonald J.L. Pike L.J. simplified preparation detergent-free rafts.J. 2005; 46: 1061-1067Abstract (280) 18Sorci-Thomas, S., Owen, B., Fulp, Bhat, X., Zhu, Parks, Shah, W. Jerome, Gerelus, Zabalawi, 2012. Nascent density lipoproteins formed ABCA1 resemble structurally ApoA-I monomers. Res., 53: 1890–1909.Google More detailed investigations recently employed Foster resonance energy transfer (FRET), atomic force microscopy, stimulated emission depletion microscopy (STED), super-resolution techniques. An overall consensus diameter 5 80 nm, relatively short lifetimes, rapidly responding needs. With refinement techniques, now poised discover factors leading elusive condense dissolve. derived endogenously de novo synthesis ER exogenously vesicles. Newly synthesized leaves mostly nonvesicular mechanisms bypassing ER-Golgi (19Baumann, P., Sullivan, Ohvo-Rekila, Simonot, Pottekat, Z., Klaassen, Beh, Menon. 2005. Transport sterol sterol-enriched occurs via equilibration. Biochemistry., 44: 5816–5826.Google 20Heino Lusa Somerharju Ehnholm Olkkonen V.M. Dissecting complex biosynthetic surface.Proc. 97: 8375-8380Crossref (206) maintaining low illustrated Fig. 1. produced transported thereby becoming available acceptors (21Lusa Heino Differential mobilization precursors 2003; 278: 19844-19851Abstract (34) it pools compartments, e.g., (22Cruz J.C. Chang T.Y. Fate C1 275: 41309-41316Abstract (79) Interestingly, membrane-FC-gradient exists lowest approaches excess cytotoxic cannot effectively catabolism, devote considerable effort sensing adjusting receptor-mediated lipoprotein efflux balance gradient maintain proper levels. When diet consumed, perturbs balance, thus impacting homeostasis (23Hermetet Buffiere Aznague Pais Barros J.P. Bastie J.N. Delva Quéré High-fat disturbs raft/TGF-beta signaling-mediated hematopoietic stem mouse bone marrow.Nat. Commun. 10: 523Crossref (26) Excess either stored (CE) actively exported pathways. peripheral tissues then back liver HDLs recycling, conversion bile acids, excretion feces, accounting 1.1 g per day (24Millar J.S. Cuchel metabolism humans: comparison results.Curr. Opin. Lipidol. 29: 1-9Crossref (11) mediated manner main nuclear systems, SREBPs LXRs. Activated SREBP undergoes assisted migration further cleaved releasing SREBP-nuclear element, migrates nucleus causing transcription gene products increase circulating (25Goldstein DeBose-Boyd R.A. Brown M.S. Protein sterols.Cell. 2006; 124: 35-46Abstract (1175) LXR activation oxysterols promotes (26Tontonoz Mangelsdorf D.J. Liver X disease.Mol. Endocrinol. 17: 985-993Crossref (512) Key pool take place at several subcellular localizations; therefore, sites important concentration. transferred [reviewed (27Maxfield F.R. Tabas Role disease.Nature. 438: 612-621Crossref (921) Scholar)]. Figure illustrates movement surface. Modulation contribute certain conditions. metastatic ovarian tumor reportedly promote tumor-associated macrophages, depleting macrophage turn reduces interferon-γ expression increases interleukin-4-mediated reprogramming. This series events explains macrophages forced adopt tumor-promoting immunosuppressive rather intrinsic tumoricidal activity, would normally suppress development (28Goossens, Rodriguez-Vita, Etzerodt, Masse, O., Rastoin, V., Gouirand, Ulas, O. Papantonopoulou, Van Eck, Auphan-Anezin, drives reprogramming progression. Metab., 1376–1389.e4.Google alternative acquisition contained lipoproteins. apoB- apoE-containing particles, chylomicron remnants, VLDLs, LDLs, bind (LDLr) bound transmembrane domain, raft. After binding LDLr, LDL-LDLr endocytosed clathrin-coated sorting endosome (Fig. 1) LDLr dissociate lower pH. recycled surface, acidic lysosomal compartments CEs hydrolyzed FC. although multivesicular bodies harbor endocytic pathway (29Möbius, van Donselaar, Ohno-Iwashita, Shimada, Heijnen, Slot, Geuze. 2003. Recycling internal pathway. Traffic., 4: 222–231.Google poor (30Friedland Liou H.L. Lobel Stock A.M. Structure cholesterol-binding deficient C2 disease.Proc. 100: 2512-2517Crossref (251) Multivesicular late (NPC)1 NPC2, moving out endosomal system. Genetic phenotypic evidence mutant mice NPC participate steps same neither compensate (31Sleat, Wiseman, El-Banna, Price, Verot, Shen, Tint, Vanier, U. Walkley, Lobel. 2004. nonredundant cooperativity NPC1 NPC2 transport. Proc. USA., 101: 5886–5891.Google Deficiency accumulation LDL-derived (32Sturley S.L. Patterson M.C. Balch Liscum pathophysiology NP-C disease.Biochim. Biophys. Acta. 2004; 1685: 83-87Crossref (122) advances revealed architecture NPC1, luminal interaction (33Zhao Ren Harlos Stuart D.I. glycosylated reveals Ebola virus interactions.FEBS Lett. 590: 605-612Crossref (29) 34Li Saha Li Blobel Pfeffer S.R. Clues middle lumenal NPC2.Proc. 113: 10079-10084Crossref (99) membrane-embedded sterol-sensing (35Li Wang Coutavas Shi Hao Q. protein.Proc. 8212-8217Crossref C-terminal (36Li, Lu, Trinh, Schmiege, Seemann, Blobel. 3.3 Å function 114: 9116–9121.Google Current hypotheses binds lysosome hands off membrane-spanning lysosomal/endosomal membrane. Transfer cytoplasm under active investigation. suggested ABCA1-mediated flux (endo)lysosomal compartment toward (37Boadu Nelson R.C. Francis G.A. ABCA1-dependent requires protein.Biochim. 1821: 396-404Crossref (31) crossroads flow Golgi, lysosomes, compartments. Sorting (early) give rise recycling endosomes, constant exchange They source multi-vesicular mature (TGN) fuse release exosomes. endolysosomal system, delivered and, steroid hormone-producing cells, mitochondria. exceeds ∼30 mol% total lipid, accessible forms, moves moderate (38Das Anderson D.D. Goldstein Radhakrishnan Three relation homeostasis.eLife. 2014; 3 (: doi:10.7554/eLife.02882.)Crossref (182) 39Infante R.E. Continuous fraction endoplasmic reticulum cholesterol.eLife. 6 doi:10.7554/eLife.25466.)Crossref (83) Exactly membrane(s) serve initial acceptor yet determined; however, recent findings argue LDL-cholesterol SREBP-mediated takes lipoprotein-derived needs ER. post-NPC1 largely unknown 1), despite presence FC-binding ER-interacting (40Luo Jiang Yang Song B-L. Routes post-endosomal trafficking: story never ends.Traffic. 18: 209-217Crossref (54) Oxysterol-binding protein-related 1L (ORP1L) StAR-related (STARD3) vesicle-associated (VAP) bridging ORP1L STARD3 employing VAP partner (41Eden E.R. Sanchez-Heras Tsapara Sobota Levine T.P. Futter C.E. Annexin A1 tethers contact mediate transport.Dev. Cell. 37: 473-483Abstract (93) 42Wilhelm, Wendling, Védie, T., Kobayashi, M-P., Chenard, Tomasetto, Drin, Alpy. mediates reticulum-to-endosome sites. EMBO 36: 1412–1433.Google Scavenger (SR-BI) selective CE lipoproteins, receptor. HDL-cholesterol distinct pathway, does require clathrin-dependent whole particle degradation 1). SR-BI removes transports neutral hydrolase (43Connelly Kellner-Weibel Rothblat G.H. Williams D.L. SR-BI-directed HDL-cholesteryl hydrolysis.J. 331-341Abstract (46) identity carboxyesterase tissue (44Yuan Bie Ghosh S.S. Cooperation hepatic hydrolysis HDL-CE.J. 2013; 54: 3078-3084Abstract (16) Recently (Aster-A, -B, -C) were described its removal (45Sandhu, Li, Fairall, Pfisterer, Gurnett, Xiao, Weston, Vashi, Ferrari, Orozco, Aster cells. Cell., 175: 514–529.e20.Google Moreover, Aster-B shown move downstream way, enable sense link SREBP-2 above homeostatic levels, Asters bridges sterol-binding ASTER extracts down Efflux ATP-dependent process carried ABCA1, across apoA-I generating send reverse (46Wang Silver Costet Tall A.R. Specific ApoA-I, enhanced efflux, altered morphology expressing ABC1.J. 33053-33058Abstract (491) packages FC, (nHDL) particles (18Sorci-Thomas, FC-rich remodeled LCAT, PC-sterol acyltransferase, core CE. Alternatively, apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE (47Remaley, Stonik, Demosky, Neufeld, Bocharov, Vishnyakova, Eggerman, Patterson, Duverger, Santamarina-Fojo, 2001. Apolipoprotein specificity ABCAI transporter. Biochem. 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Language: Английский

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Understanding the Mechanisms of Positive Microbial Interactions That Benefit Lactic Acid Bacteria Co-cultures

Frontiers in Microbiology, Journal Year: 2020, Volume and Issue: 11

Published: Sept. 4, 2020

Microorganisms grow in concert, both natural communities and artificial or synthetic co-cultures. Positive interactions between associated microbes are paramount to achieve improved substrate conversion process performance biotransformation fermented food production. The mechanisms underlying such positive have been the focus of numerous studies recent decades now starting be well characterized. Lactic acid bacteria (LAB) contribute final organoleptic, nutritional, health properties products. However, LAB co-cultures little studied, apart from well-characterized co-culture used for yogurt manufacture. however multifunctional microorganisms that display considerable potential create them. This review describes why interest, particularly foods, how their extensive nutritional requirements can favor interactions. In respect, our highlights benefits different areas application, details aims show based on exploited efficient

Language: Английский

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Bacteriophage-mediated manipulation of the gut microbiome – promises and presents limitations

FEMS Microbiology Reviews, Journal Year: 2020, Volume and Issue: 44(4), P. 507 - 521

Published: June 3, 2020

ABSTRACT Gut microbiome (GM) composition and function are linked to human health disease, routes for manipulating the GM have become an area of intense research. Due its high treatment efficacy, use fecal microbiota transplantation (FMT) is generally accepted as a promising experimental patients suffering from imbalances (dysbiosis), e.g. caused by recurrent Clostridioides difficile infections (rCDI). Mounting evidence suggests that bacteriophages (phages) play key role in successful FMT restoring dysbiotic bacterial GM. As refinement FMT, removing component donor feces sterile filtration, also referred virome (FVT), decreases risk invasive bacteria. However, eukaryotic viruses prophage-encoded virulence factors remain safety issue. Recent vivo studies show how cascading effects initiated when phage communities transferred gut FVT, which leads changes composition, host metabolome, improve such alleviating symptoms obesity type-2-diabetes (T2D). In this review, we discuss promises limitations FVT along with perspectives using treat various diseases associated dysbiosis.

Language: Английский

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Outer Membrane Vesicles (OMVs) Produced by Gram-Negative Bacteria: Structure, Functions, Biogenesis, and Vaccine Application

BioMed Research International, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 16

Published: March 24, 2021

Gram-negative bacteria produce outer membrane vesicles (OMVs) with 10 to 300 nm of diameter. The contribution OMVs bacterial pathogenesis is a topic great interest, and their capacity be combined antigens impact in the future development vaccines.

Language: Английский

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Vesiduction: the fourth way of HGT

Environmental Microbiology, Journal Year: 2020, Volume and Issue: 22(7), P. 2457 - 2460

Published: May 4, 2020

Summary Besides the canonical gene transfer mechanisms transformation, transduction and conjugation, DNA involving extracellular vesicles is still under appreciated. However, this widespread phenomenon has been observed in three domains of life. Here, we propose term ‘Vesiduction’ as a fourth mode intercellular transfer.

Language: Английский

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Communication is key: extracellular vesicles as mediators of infection and defence during host–microbe interactions in animals and plants

FEMS Microbiology Reviews, Journal Year: 2021, Volume and Issue: 46(1)

Published: Aug. 27, 2021

ABSTRACT Extracellular vesicles (EVs) are now understood to be ubiquitous mediators of cellular communication. In this review, we suggest that EVs have evolved into a highly regulated system communication with complex functions including export wastes, toxins and nutrients, targeted delivery immune effectors vectors RNA silencing. Eukaryotic come in different shapes sizes been classified according their biogenesis size distributions. Small (or exosomes) released through fusion endosome-derived multivesicular bodies the plasma membrane. Medium microvesicles) bud off membrane as form exocytosis. Finally, large apoptotic bodies) produced result process. This review considers EV secretion uptake four eukaryotic kingdoms, three which produce cell walls. The impacts walls on plants fungi discussed, roles fungal virulence. Contributions plant development innate immunity presented. Compelling cases sporophytic self-incompatibility invasion by haustorium-forming filamentous pathogens. involvement all these processes is reconciled considering evolutionary history.

Language: Английский

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