text:
Yu and Yao, Xuebiao},
  month = nov,
  year = {2008},
  pages = {639-644},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Online tools\\Ren et al_2008_CSS-Palm 2.pdf;C:\\Users\\charl\\Zotero\\storage\\JM4FAVW8\\1592142.html}
}

@article{maechler2019,
  title = {Cluster: {{Cluster Analysis Basics}} and {{Extensions}}. {{R}} Package Version 2.0.8},
  author = {Maechler, Martin and Rousseeuw, Peter and Struwf, Anja and Hubert, Mia and Hornik, Kurt},
  year = {2019}
}

@article{rida2006,
  title = {Yeast-to-{{Hyphal Transition Triggers Formin}}-Dependent {{Golgi Localization}} to the {{Growing Tip}} in {{Candida}} Albicans},
  volume = {17},
  issn = {1059-1524},
  abstract = {Rapid and long-distance secretion of membrane components is critical for hyphal formation in filamentous fungi, but the mechanisms responsible for polarized trafficking are not well understood. Here, we demonstrate that in Candida albicans, the majority of the Golgi complex is redistributed to the distal region during hyphal formation. Randomly distributed Golgi puncta in yeast cells cluster toward the growing tip during hyphal formation, remain associated with the distal portion of the filament during its extension, and are almost absent from the cell body. This restricted Golgi localization pattern is distinct from other organelles, including the endoplasmic reticulum, vacuole and mitochondria, which remain distributed throughout the cell body and hypha. Hyphal-induced positioning of the Golgi and the maintenance of its structural integrity requires actin cytoskeleton, but not microtubules. Absence of the formin Bni1 causes a hyphal-specific dispersal of the Golgi into a haze of finely dispersed vesicles with a sedimentation density no different from that of normal Golgi. These results demonstrate the existence of a hyphal-specific, Bni1-dependent cue for Golgi integrity and positioning at the distal portion of the hyphal tip, and suggest that filamentous fungi have evolved a novel strategy for polarized secretion, involving a redistribution of the Golgi to the growing tip.},
  number = {10},
  journal = {Molecular Biology of the Cell},
  doi = {10.1091/mbc.e06-02-0143},
  author = {Rida, Padmashree C.G. and Nishikawa, Akiko and Won, Gena Y. and Dean, Neta},
  month = jul,
  year = {2006},
  keywords = {ABP1},
  pages = {4364-4378},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\EV markers\\Candida 60\\Rida et al_2006_Yeast-to-Hyphal Transition Triggers Formin-dependent Golgi Localization to the.pdf;C:\\Users\\charl\\Zotero\\storage\\YWEYW4GC\\mbc.html}
}

@article{broxton2016,
  title = {An {{Adaptation}} to {{Low Copper}} in {{Candida}} Albicans {{Involving SOD Enzymes}} and the {{Alternative Oxidase}}},
  volume = {11},
  issn = {1932-6203},
  abstract = {In eukaryotes, the Cu/Zn superoxide dismutase (SOD1) is a major cytosolic cuproprotein with a small fraction residing in the mitochondrial intermembrane space (IMS) to protect against respiratory superoxide. Curiously, the opportunistic human fungal pathogen Candida albicans is predicted to express two cytosolic SODs including Cu/Zn containing SOD1 and manganese containing SOD3. As part of a copper starvation response, C. albicans represses SOD1 and induces the non-copper alternative SOD3. While both SOD1 and SOD3 are predicted to exist in the same cytosolic compartment, their potential role in mitochondrial oxidative stress had yet to be investigated. We show here that under copper replete conditions, a fraction of the Cu/Zn containing SOD1 localizes to the mitochondrial IMS to guard against mitochondrial superoxide. However in copper starved cells, localization of the manganese containing SOD3 is restricted to the cytosol leaving the mitochondrial IMS devoid of SOD. We observe that during copper starvation, an alternative oxidase (AOX) form of respiration is induced that is not coupled to ATP synthesis but maintains mitochondrial superoxide at low levels even in the absence of IMS SOD. Surprisingly, the copper-dependent cytochrome c oxidase (COX) form of respiration remains high with copper starvation. We provide evidence that repression of SOD1 during copper limitation serves to spare copper for COX and maintain COX respiration. Overall, the complex copper starvation response of C. albicans involving SOD1, SOD3 and AOX minimizes mitochondrial oxidative damage whilst maximizing COX respiration essential for fungal pathogenesis.},
  language = {en},
  number = {12},
  journal = {PLOS ONE},
  doi = {10.1371/journal.pone.0168400},
  author = {Broxton, Chynna N. and Culotta, Valeria C.},
  month = dec,
  year = {2016},
  keywords = {Mitochondria,Candida albicans,Cytosol,Manganese,Oxygen consumption,Respiration,SOD2,Superoxide dismutase,Superoxides},
  pages = {e0168400},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\EV markers\\Candida 60\\Broxton_Culotta_2016_An Adaptation to Low Copper in Candida albicans Involving SOD Enzymes and the.pdf;C:\\Users\\charl\\Zotero\\storage\\2UL6EKP7\\article.html}
}

@article{lopez2014,
  title = {Candida Albicans {{Uses}} the {{Surface Protein Gpm1}} to {{Attach}} to {{Human Endothelial Cells}} and to {{Keratinocytes}} via the {{Adhesive Protein Vitronectin}}},
  volume = {9},
  issn = {1932-6203},
  abstract = {Candida albicans is a major cause of invasive fungal infections worldwide. Upon infection and when in contact with human plasma as well as body fluids the fungus is challenged by the activated complement system a central part of the human innate immune response. C. albicans controls and evades host complement attack by binding several human complement regulators like Factor H, Factor H-like protein 1 and C4BP to the surface. Gpm1 (Phosphoglycerate mutase 1) is one fungal Factor H/FHL1 -binding protein. As Gpm1 is surface exposed, we asked whether Gpm1 also contributes to host cell attachment. Here, we show by flow cytometry and by laser scanning microscopy that candida Gpm1 binds to human umbilical vein endothelial cells (HUVEC) to keratinocytes (HaCaT), and also to monocytic U937 cells. Wild type candida did bind, but the candida gpm1{$\Delta$}/{$\Delta$} knock-out mutant did not bind to these human cells. In addition Gpm1when attached to latex beads also conferred attachment to human endothelial cells. When analyzing Gpm1-binding to a panel of extracellular matrix proteins, the human glycoprotein vitronectin was identified as a new Gpm1 ligand. Vitronectin is a component of the extracellular matrix and also a regulator of the terminal complement pathway. Vitronectin is present on the surface of HUVEC and keratinocytes and acts as a surface ligand for fungal Gpm1. Gpm1 and vitronectin colocalize on the surface of HUVEC and HaCaT as revealed by laser scanning microscopy. The Gpm1 vitronectin interaction is inhibited by heparin and the interaction is also ionic strength dependent. Taken together, Gpm1 the candida surface protein binds to vitronectin and mediates fungal adhesion to human endothelial cells. Thus fungal Gpm1 and human vitronectin represent a new set of proteins that are relevant for fungal attachment to human cells interaction. Blockade of the Gpm1 vitronectin interaction might provide a new target for therapy.},
  language = {en},
  number = {3},
  journal = {PLOS ONE},
  doi = {10.1371/journal.pone.0090796},
  author = {Lopez, Crisanto M. and Wallich, Reinhard and Riesbeck, Kristian and Skerka, Christine and Zipfel, Peter F.},
  month = mar,
  year = {2014},
  keywords = {Candida albicans,Extracellular matrix proteins,Endothelial cells,Candida,Keratinocytes,Fungal pathogens,Complement system,GPM1,Immune serum},
  pages = {e90796},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\EV markers\\Candida 60\\Lopez et al_2014_Candida albicans Uses the Surface Protein Gpm1 to Attach to Human Endothelial.pdf;C:\\Users\\charl\\Zotero\\storage\\HJ8ECYCL\\article.html}
}

@article{kim2010,
  title = {Roles of Dihydrolipoamide Dehydrogenase {{Lpd1}} in {{Candida}} Albicans Filamentation},
  volume = {47},
  issn = {1087-1845},
  abstract = {Acetyl coenzyme A, a key intermediate of the mitochondrial carbon metabolism, is formed by the mitochondrial pyruvate dehydrogenase complex (PDC). The dihydrolipoamide dehydrogenase Lpd1 is a catalytic component of PDC. Lpd1 has been recovered during 2D-PAGE screening for the hypha-specific proteins in Candida albicans. The Lpd1 protein, as visualized by a GFP-fusion, was localized in the mitochondria during the logarithmic yeast growth and the filamentous growth. The GFP signal was prevalent and relatively uniform toward the tip of the hyphae. The functions of the LPD1 gene were investigated by construction of lpd1/lpd1 mutant strain. This homozygous deletion mutant was unable to grow on non-fermentable carbon sources including glycerol, ethanol, acetate, and citrate. In addition, the lpd1/lpd1 strain exhibited a slow-growth phenotype on glucose-containing media and a marked sensitivity to 0.5mM of hydrogen peroxide. LPD1 was shown to be required for filamentous growth under a serum-containing hyphal-inducing condition. These results suggest a possible relationship between mitochondrial respiration and filamentous growth.},
  number = {9},
  journal = {Fungal Genetics and Biology},
  doi = {10.1016/j.fgb.2010.06.005},
  author = {Kim, Seung-Yeop and Kim, Jinmi},
  month = sep,
  year = {2010},
  keywords = {Dihydrolipoamide dehydrogenase,Filamentation,GFP-fusion,LPD1,Pyruvate dehydrogenase},
  pages = {782-788},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\GFP fusions\\Kim_Kim_2010_Roles of dihydrolipoamide dehydrogenase Lpd1 in Candida albicans filamentation.pdf;C:\\Users\\charl\\Zotero\\storage\\HQG5XV4W\\S1087184510001076.html}
}

@article{bauerova2012,
  title = {Nitrogen Source and Growth Stage of {{Candida}} Albicans Influence Expression Level of Vacuolar Aspartic Protease {{Aprlp}} and Carboxypeptidase {{Cpylp}}},
  volume = {58},
  issn = {0008-4166},
  language = {English},
  number = {5},
  journal = {Canadian Journal of Microbiology},
  author = {Bauerova, Vaclava and Pichova, Iva and {Hruskova-Heidingsfeldova}, Olga},
  month = may,
  year = {2012},
  keywords = {Candida albicans,APR1,Bacterial growth,Nitrogen (Nutrient),Proteases},
  pages = {678-681},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\EV markers\\Candida 60\\Bauerova et al_2012_Nitrogen source and growth stage of Candida albicans influence expression level.pdf},
  note = {678}
}

@article{zimmerman2016,
  title = {Crystal {{Structure}} of a {{Full}}-{{Length Human Tetraspanin Reveals}} a {{Cholesterol}}-{{Binding Pocket}}},
  volume = {167},
  issn = {0092-8674},
  abstract = {Summary
Tetraspanins comprise a diverse family of four-pass transmembrane proteins that play critical roles in the immune, reproductive, genitourinary, and auditory systems. Despite their pervasive roles in human physiology, little is known about the structure of tetraspanins or the molecular mechanisms underlying their various functions. Here, we report the crystal structure of human CD81, a full-length tetraspanin. The transmembrane segments of CD81 pack as two largely separated pairs of helices, capped by the large extracellular loop (EC2) at the outer membrane leaflet. The two pairs of helices converge at the inner leaflet to create an intramembrane pocket with additional electron density corresponding to a~bound cholesterol molecule within the cavity. Molecular dynamics simulations identify an additional conformation in which EC2 separates substantially from the transmembrane domain. Cholesterol binding appears to modulate CD81 activity in cells, suggesting a potential mechanism for regulation of tetraspanin function.},
  number = {4},
  journal = {Cell},
  doi = {10.1016/j.cell.2016.09.056},
  author = {Zimmerman, Brandon and Kelly, Brendan and McMillan, Brian J. and Seegar, Tom C. M. and Dror, Ron O. and Kruse, Andrew C. and Blacklow, Stephen C.},
  month = nov,
  year = {2016},
  keywords = {CD81,CD19,membrane protein,protein structure,protein trafficking,X-ray crystallography},
  pages = {1041-1051.e11},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Tetraspanins\\CD81\\Zimmerman et al_2016_Crystal Structure of a Full-Length Human Tetraspanin Reveals a.pdf;C:\\Users\\charl\\Zotero\\storage\\7GFKA642\\S0092867416313800.html}
}

@article{delandre2009,
  title = {Mutation of Juxtamembrane Cysteines in the Tetraspanin {{CD81}} Affects Palmitoylation and Alters Interaction with Other Proteins at the Cell Surface},
  volume = {315},
  issn = {0014-4827},
  abstract = {Palmitoylation of tetraspanins affects protein\textendash{}protein interactions, suggesting a key role in the assembly of the tetraspanin web. Since palmitoylation occurs on intracellular cysteine residues, we examined whether mutating these residues in the human tetraspanin CD81 would affect the association of CD81 with other surface membrane proteins. Mutation of at least six of the eight juxtamembrane cysteines was required to completely eliminate detectable CD81 palmitoylation, indicating that several sites can be palmitoylated. Interestingly, these mutated proteins exhibited reduced cell surface detection by antibody compared to wild-type CD81, but this was not due to differences in the level of protein expression, trafficking to the cell surface, protein stability, or anti-CD81 antibody binding affinity. Instead, the mutant CD81 proteins appeared to be partially hidden from detection by anti-CD81 antibody, presumably due to altered interactions with other proteins at the cell surface. Associations with the known CD81-interacting proteins CD9 and EWI-2 were also impaired with the mutant CD81 proteins. Taken together, these findings indicate that mutation of juxtamembrane cysteines alters the interaction of CD81 with other proteins, either because of reduced palmitoylation, structural alterations in the mutant proteins, or a combination of both factors, and this affects the CD81 microenvironment on the cell surface.},
  number = {11},
  journal = {Experimental Cell Research},
  doi = {10.1016/j.yexcr.2009.03.013},
  author = {Delandre, Caroline and Penabaz, Taryn R. and Passarelli, A. Lorena and Chapes, Stephen K. and Clem, Rollie J.},
  month = jul,
  year = {2009},
  keywords = {CD81,CD9,Tetraspanin,EWI-2,Palmitoylation,Proteolysis},
  pages = {1953-1963},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Tetraspanins\\CD81\\Delandre et al_2009_Mutation of juxtamembrane cysteines in the tetraspanin CD81 affects.pdf;C:\\Users\\charl\\Zotero\\storage\\BAL7BDHA\\S0014482709001311.html}
}

@article{tsirigos2015,
  title = {The {{TOPCONS}} Web Server for Consensus Prediction of Membrane Protein Topology and Signal Peptides},
  volume = {43},
  issn = {0305-1048},
  abstract = {Abstract.  TOPCONS (http://topcons.net/) is a widely used web server for consensus prediction of membrane protein topology. We hereby present a major update to},
  language = {en},
  number = {W1},
  journal = {Nucleic Acids Research},
  doi = {10.1093/nar/gkv485},
  author = {Tsirigos, Konstantinos D. and Peters, Christoph and Shu, Nanjiang and K{\"a}ll, Lukas and Elofsson, Arne},
  month = jul,
  year = {2015},
  pages = {W401-W407},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Online tools\\Tsirigos et al_2015_The TOPCONS web server for consensus prediction of membrane protein topology.pdf;C:\\Users\\charl\\Zotero\\storage\\PB9BBP63\\2467930.html}
}

@article{takahashi2013,
  title = {Visualization and in Vivo Tracking of the Exosomes of Murine Melanoma {{B16}}-{{BL6}} Cells in Mice after Intravenous Injection},
  volume = {165},
  issn = {0168-1656},
  abstract = {The development of exosomes as delivery vehicles requires understanding how and where exogenously administered exosomes are distributed in vivo. In the present study, we designed a fusion protein consisting of Gaussia luciferase and a truncated lactadherin, gLuc-lactadherin, and constructed a plasmid expressing the fusion protein. B16-BL6 murine melanoma cells were transfected with the plasmid, and exosomes released from the cells were collected by ultracentrifugation. Strong luciferase activity was detected in the fraction containing exosomes, indicating their efficient labeling with gLuc-lactadherin. Then, the labeled B16-BL6 exosomes were intravenously injected into mice, and their tissue distribution was evaluated. Pharmacokinetic analysis of the exosome blood concentration\textendash{}time profile revealed that B16-BL6 exosomes disappeared very quickly from the blood circulation with a half-life of approximately 2min. Little luciferase activity was detected in the serum at 4h after exosome injection, suggesting rapid clearance of B16-BL6 exosomes in vivo. Moreover, sequential in vivo imaging revealed that the B16-BL6 exosome-derived signals distributed first to the liver and then to the lungs. These results indicate that gLuc-lactadherin labeling is useful for tracing exosomes in vivo and that B16-BL6 exosomes are rapidly cleared from the blood circulation after systemic administration.},
  number = {2},
  journal = {Journal of Biotechnology},
  doi = {10.1016/j.jbiotec.2013.03.013},
  author = {Takahashi, Yuki and Nishikawa, Makiya and Shinotsuka, Haruka and Matsui, Yuriko and Ohara, Saori and Imai, Takafumi and Takakura, Yoshinobu},
  month = may,
  year = {2013},
  keywords = {Biodistribution,Exosome,Lactadherin,luciferase},
  pages = {77-84},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\EV markers\\Mammalian\\Takahashi et al_2013_Visualization and in vivo tracking of the exosomes of murine melanoma B16-BL6.pdf;C:\\Users\\charl\\Zotero\\storage\\J9U8T37X\\S0168165613001648.html}
}

@article{verweij2018,
  title = {Quantifying Exosome Secretion from Single Cells Reveals a Modulatory Role for {{GPCR}} Signaling},
  volume = {217},
  copyright = {\textcopyright{} 2018 Verweij et al.. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).},
  issn = {0021-9525, 1540-8140},
  abstract = {Exosomes are small endosome-derived extracellular vesicles implicated in cell\textendash{}cell communication and are secreted by living cells when multivesicular bodies (MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome physiology are based on isolation procedures after secretion, precluding direct and dynamic insight into the mechanics of exosome biogenesis and the regulation of their release. In this study, we propose real-time visualization of MVB\textendash{}PM fusion to overcome these limitations. We designed tetraspanin-based pH-sensitive optical reporters that detect MVB\textendash{}PM fusion using live total internal reflection fluorescence and dynamic correlative light\textendash{}electron microscopy. Quantitative analysis demonstrates that MVB\textendash{}PM fusion frequency is reduced by depleting the target membrane SNAREs SNAP23 and syntaxin-4 but also can be induced in single cells by stimulation of the histamine H1 receptor (H1HR). Interestingly, activation of H1R1 in HeLa cells increases Ser110 phosphorylation of SNAP23, promoting MVB\textendash{}PM fusion and the release of CD63-enriched exosomes. Using this single-cell resolution approach, we highlight the modulatory dynamics of MVB exocytosis that will help to increase our understanding of exosome physiology and identify druggable targets in exosome-associated pathologies.},
  language = {en},
  number = {3},
  journal = {Journal of Cell Biology},
  doi = {10.1083/jcb.201703206},
  author = {Verweij, Frederik Johannes and Bebelman, Maarten P. and Jimenez, Connie R. and {Garcia-Vallejo}, Juan J. and Janssen, Hans and Neefjes, Jacques and Knol, Jaco C. and Haas, Richard de Goeij-de and Piersma, Sander R. and Baglio, S. Rubina and Verhage, Matthijs and Middeldorp, Jaap M. and Zomer, Anoek and van Rheenen, Jacco and Coppolino, Marc G. and Hurbain, Ilse and Raposo, Gra{\c c}a and Smit, Martine J. and Toonen, Ruud F. G. and van Niel, Guillaume and Pegtel, D. Michiel},
  month = mar,
  year = {2018},
  pages = {1129-1142},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\EV biogenesis\\Research\\Verweij et al_2018_Quantifying exosome secretion from single cells reveals a modulatory role for.pdf;C:\\Users\\charl\\Zotero\\storage\\Z9A3FZXI\\1129.html},
  pmid = {29339438}
}

@article{oliveira2010b,
  title = {Extracellular {{Vesicles}} from {{Cryptococcus}} Neoformans {{Modulate Macrophage Functions}}},
  volume = {78},
  copyright = {American Society for Microbiology},
  issn = {0019-9567, 1098-5522},
  abstract = {Cryptococcus neoformans and distantly related fungal species release extracellular vesicles that traverse the cell wall and contain a varied assortment of components, some of which have been associated with virulence. Previous studies have suggested that these extracellular vesicles are produced in vitro and during animal infection, but the role of vesicular secretion during the interaction of fungi with host cells remains unknown. In this report, we demonstrate by fluorescence microscopy that mammalian macrophages can incorporate extracellular vesicles produced by C. neoformans. Incubation of cryptococcal vesicles with murine macrophages resulted in increased levels of extracellular tumor necrosis factor alpha (TNF-{$\alpha$}), interleukin-10 (IL-10), and transforming growth factor {$\beta$} (TGF-{$\beta$}). Vesicle preparations also resulted in a dose-dependent stimulation of nitric oxide production by phagocytes, suggesting that vesicle components stimulate macrophages to produce antimicrobial compounds. Treated macrophages were more effective at killing C. neoformans yeast. Our results indicate that the extracellular vesicles of C. neoformans can stimulate macrophage function, apparently activating these phagocytic cells to enhance their antimicrobial activity. These results establish that cryptococcal vesicles are biologically active.},
  language = {en},
  number = {4},
  journal = {Infection and Immunity},
  doi = {10.1128/IAI.01171-09},
  author = {Oliveira, D{\'e}bora L. and {Freire-de-Lima}, C{\'e}lio G. and Nosanchuk, Joshua D. and Casadevall, Arturo and Rodrigues, Marcio L. and Nimrichter, Leonardo},
  month = apr,
  year = {2010},
  pages = {1601-1609},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Fungal EVs\\Crypto EVs\\Oliveira et al_2010_Extracellular Vesicles from Cryptococcus neoformans Modulate Macrophage.pdf;C:\\Users\\charl\\Zotero\\storage\\WYCR26A6\\1601.html},
  pmid = {20145096}
}

@article{gomez2000,
  title = {Biochemical and {{Immunological Characterization}} of {{MP65}}, a {{Major Mannoprotein Antigen}} of the {{Opportunistic Human PathogenCandida}} Albicans},
  volume = {68},
  copyright = {Copyright \textcopyright{} 2000 American Society for Microbiology},
  issn = {0019-9567, 1098-5522},
  abstract = {In the search of the antigenic determinants of a 65-kDa mannoprotein (MP65) of Candida albicans, tryptic fragments of immunoaffinity-purified MP65 preparations were tested for their ability to induce lymphoproliferation of human peripheral blood mononuclear cells (PBMC). Five major peptides (T1 to T5) were shown to induce a vigorous proliferation of PBMC from the majority of the eight healthy human subjects tested. With the use of synthetic peptides, critical amino acid sequences of the two most immunoactive (T1 and T2) peptides were determined. Similar to what was found for the MP65 molecule, no PBMC multiplication was induced by the antigenic peptides in cultures of naive cord blood cells. The amino acid sequence analysis of tryptic and chymotryptic peptides of MP65 demonstrated a substantial homology with the deduced sequences of two cell wall proteins ofSaccharomyces cerevisiae, encoded by the genesYRM305C and YGR279C. However, the antigenic peptides were those showing the least similarity with the corresponding regions of the above proteins. In particular, the lymphoproliferation-inducing sequence of the T1 peptide scored only 20\% identity with the homologous regions of S. cerevisiaeproteins. Besides disclosing the amino acid sequence of MP65, this study provides an initial characterization of some of its antigenic determinants, as well as of synthetic peptides of potential use to detect specific immune responses against MP65, a major target of anticandidal cell-mediated immunity in humans.},
  language = {en},
  number = {2},
  journal = {Infection and Immunity},
  doi = {10.1128/IAI.68.2.694-701.2000},
  author = {Gomez, Maria J. and Maras, Bruno and Barca, Alessandra and Valle, Roberto La and Barra, Donatella and Cassone, Antonio},
  month = feb,
  year = {2000},
  pages = {694-701},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Fungal EVs\\Candida EVs\\Cargo\\M-R\\Gomez et al_2000_Biochemical and Immunological Characterization of MP65, a Major Mannoprotein.pdf;C:\\Users\\charl\\Zotero\\storage\\RQ9MS4FX\\694.html},
  pmid = {10639435}
}

@article{oliveira2009,
  title = {Cryptococcus Neoformans Cryoultramicrotomy and Vesicle Fractionation Reveals an Intimate Association between Membrane Lipids and Glucuronoxylomannan},
  volume = {46},
  issn = {1087-1845},
  abstract = {Cryptococcus neoformans is an encapsulated pathogenic fungus. The cryptococcal capsule is composed of polysaccharides and is necessary for virulence. It has been previously reported that glucuronoxylomannan (GXM), the major capsular component, is synthesized in cytoplasmic compartments and transported to the extracellular space in vesicles, but knowledge on the organelles involved in polysaccharide synthesis and traffic is extremely limited. In this paper we report the GXM distribution in C. neoformans cells sectioned by cryoultramicrotomy and visualized by transmission electron microscopy (TEM) and polysaccharide immunogold staining. Cryosections of fungal cells showed high preservation of intracellular organelles and cell wall structure. Incubation of cryosections with an antibody to GXM revealed that cytoplasmic structures associated to vesicular compartments and reticular membranes are in close proximity to the polysaccharide. GXM was generally found in association with the membrane of intracellular compartments and within different layers of the cell wall. Analysis of extracellular fractions from cryptococcal supernatants by transmission electron microscopy in combination with serologic, chromatographic and spectroscopic methods revealed fractions containing GXM and lipids. These results indicate an intimate association of GXM and lipids in both intracellular and extracellular spaces consistent with polysaccharide synthesis and transport in membrane-associated structures.},
  number = {12},
  journal = {Fungal Genetics and Biology},
  doi = {10.1016/j.fgb.2009.09.001},
  author = {Oliveira, D{\'e}bora L. and Nimrichter, Leonardo and Miranda, Kildare and Frases, Susana and Faull, Kym F. and Casadevall, Arturo and Rodrigues, Marcio L.},
  month = dec,
  year = {2009},
  keywords = {Cryoimmunoelectronmicroscopy,GXM transport,Secretory vesicles},
  pages = {956-963},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Fungal EVs\\Crypto EVs\\Oliveira et al_2009_Cryptococcus neoformans cryoultramicrotomy and vesicle fractionation reveals an.pdf;C:\\Users\\charl\\Zotero\\storage\\QYV4D86K\\S1087184509001613.html}
}

@article{wolf2015,
  title = {Lipid {{Biosynthetic Genes Affect Candida}} Albicans {{Extracellular Vesicle Morphology}}, {{Cargo}}, and {{Immunostimulatory Properties}}},
  volume = {14},
  copyright = {Copyright \textcopyright{} 2015, American Society for Microbiology. All Rights Reserved.},
  issn = {1535-9778, 1535-9786},
  abstract = {Microbial secretion is integral for regulating cell homeostasis as well as releasing virulence factors during infection. The genes encoding phosphatidylserine synthase (CHO1) and phosphatidylserine decarboxylase (PSD1 and PSD2) are Candida albicans genes involved in phospholipid biosynthesis, and mutations in these genes affect mitochondrial function, cell wall thickness, and virulence in mice. We tested the roles of these genes in several agar-based secretion assays and observed that the cho1{$\Delta$}/{$\Delta$} and psd1{$\Delta$}/{$\Delta$} psd2{$\Delta$}/{$\Delta$} strains manifested less protease and phospholipase activity. Since extracellular vesicles (EVs) are surrounded by a lipid membrane, we investigated the effects of these mutations on EV structure, composition, and biological activity. The cho1{$\Delta$}/{$\Delta$} mutant releases EVs comparable in size to wild-type EVs, but EVs from the psd1{$\Delta$}/{$\Delta$} psd2{$\Delta$}/{$\Delta$} strain are much larger than those from the wild type, including a population of {$>$}100-nm EVs not observed in the EVs from the wild type. Proteomic analysis revealed that EVs from both mutants had a significantly different protein cargo than that of EVs from the wild type. EVs were tested for their ability to activate NF-{$\kappa$}B in bone marrow-derived macrophage cells. While wild-type and psd1{$\Delta$}/{$\Delta$} psd2{$\Delta$}/{$\Delta$} mutant-derived EVs activated NF-{$\kappa$}B, the cho1{$\Delta$}/{$\Delta$} mutant-derived EV did not. These studies indicate that the presence and absence of these C. albicans genes have qualitative and quantitative effects on EV size, composition, and immunostimulatory phenotypes that highlight a complex interplay between lipid metabolism and vesicle production.},
  language = {en},
  number = {8},
  journal = {Eukaryotic Cell},
  doi = {10.1128/EC.00054-15},
  author = {Wolf, Julie M. and Espadas, Javier and {Luque-Garcia}, Jose and Reynolds, Todd and Casadevall, Arturo},
  month = aug,
  year = {2015},
  pages = {745-754},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Fungal EVs\\Candida EVs\\Research\\Wolf et al_2015_Lipid Biosynthetic Genes Affect Candida albicans Extracellular Vesicle.pdf;C:\\Users\\charl\\Zotero\\storage\\6JRCXGQ6\\745.html},
  pmid = {26024904}
}

@article{vallejo2011,
  title = {The {{Pathogenic Fungus Paracoccidioides}} Brasiliensis {{Exports Extracellular Vesicles Containing Highly Immunogenic}} {$\alpha$}-{{Galactosyl Epitopes}}},
  volume = {10},
  copyright = {Copyright \textcopyright{} 2011, American Society for Microbiology.},
  issn = {1535-9778, 1535-9786},
  abstract = {Exosome-like vesicles containing virulence factors, enzymes, and antigens have recently been characterized in fungal pathogens, such as Cryptococcus neoformans and Histoplasma capsulatum. Here, we describe extracellular vesicles carrying highly immunogenic {$\alpha$}-linked galactopyranosyl ({$\alpha$}-Gal) epitopes in Paracoccidioides brasiliensis. P. brasiliensis is a dimorphic fungus that causes human paracoccidioidomycosis (PCM). For vesicle preparations, cell-free supernatant fluids from yeast cells cultivated in Ham's defined medium-glucose were concentrated in an Amicon ultrafiltration system and ultracentrifuged at 100,000 \texttimes{} g. P. brasiliensis antigens were present in preparations from phylogenetically distinct isolates Pb18 and Pb3, as observed in immunoblots revealed with sera from PCM patients. In an enzyme-linked immunosorbent assay (ELISA), vesicle components containing {$\alpha$}-Gal epitopes reacted strongly with anti-{$\alpha$}-Gal antibodies isolated from both Chagas' disease and PCM patients, with Marasmius oreades agglutinin (MOA) (a lectin that recognizes terminal {$\alpha$}-Gal), but only faintly with natural anti-{$\alpha$}-Gal. Reactivity was inhibited after treatment with {$\alpha$}-galactosidase. Vesicle preparations analyzed by electron microscopy showed vesicular structures of 20 to 200 nm that were labeled both on the surface and in the lumen with MOA. In P. brasiliensis cells, components carrying {$\alpha$}-Gal epitopes were found distributed on the cell wall, following a punctuated confocal pattern, and inside large intracellular vacuoles. Lipid-free vesicle fractions reacted with anti-{$\alpha$}-Gal in ELISA only when not digested with {$\alpha$}-galactosidase, while reactivity with glycoproteins was reduced after {$\beta$}-elimination, which is indicative of partial O-linked chain localization. Our findings open new areas to explore in terms of host-parasite relationships in PCM and the role played in vivo by vesicle components and {$\alpha$}-galactosyl epitopes.},
  language = {en},
  number = {3},
  journal = {Eukaryotic Cell},
  doi = {10.1128/EC.00227-10},
  author = {Vallejo, Milene C. and Matsuo, Alisson L. and Ganiko, Luciane and Medeiros, Lia C. Soares and Miranda, Kildare and Silva, Luiz S. and {Freym{\"u}ller-Haapalainen}, Edna and {Sinigaglia-Coimbra}, Rita and Almeida, Igor C. and Puccia, Rosana},
  month = mar,
  year = {2011},
  pages = {343-351},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Fungal EVs\\Para EVs\\Vallejo et al_2011_The Pathogenic Fungus Paracoccidioides brasiliensis Exports Extracellular.pdf;C:\\Users\\charl\\Zotero\\storage\\QE7J2P4D\\343.html},
  pmid = {21216942}
}

@article{rodrigues2007,
  title = {Vesicular {{Polysaccharide Export}} in {{Cryptococcus}} Neoformans {{Is}} a {{Eukaryotic Solution}} to the {{Problem}} of {{Fungal Trans}}-{{Cell Wall Transport}}},
  volume = {6},
  copyright = {American Society for Microbiology},
  issn = {1535-9778, 1535-9786},
  abstract = {The mechanisms by which macromolecules are transported through the cell wall of fungi are not known. A central question in the biology of Cryptococcus neoformans, the causative agent of cryptococcosis, is the mechanism by which capsular polysaccharide synthesized inside the cell is exported to the extracellular environment for capsule assembly and release. We demonstrate that C. neoformans produces extracellular vesicles during in vitro growth and animal infection. Vesicular compartments, which are transferred to the extracellular space by cell wall passage, contain glucuronoxylomannan (GXM), a component of the cryptococcal capsule, and key lipids, such as glucosylceramide and sterols. A correlation between GXM-containing vesicles and capsule expression was observed. The results imply a novel mechanism for the release of the major virulence factor of C. neoformans whereby polysaccharide packaged in lipid vesicles crosses the cell wall and the capsule network to reach the extracellular environment.},
  language = {en},
  number = {1},
  journal = {Eukaryotic Cell},
  doi = {10.1128/EC.00318-06},
  author = {Rodrigues, Marcio L. and Nimrichter, Leonardo and Oliveira, D{\'e}bora L. and Frases, Susana and Miranda, Kildare and Zaragoza, Oscar and Alvarez, Mauricio and Nakouzi, Antonio and Feldmesser, Marta and Casadevall, Arturo},
  month = jan,
  year = {2007},
  pages = {48-59},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Fungal EVs\\Crypto EVs\\Rodrigues et al_2007_Vesicular Polysaccharide Export in Cryptococcus neoformans Is a Eukaryotic.pdf;C:\\Users\\charl\\Zotero\\storage\\R74WFBEZ\\48.html},
  pmid = {17114598}
}

@article{rodrigues2008,
  title = {Extracellular {{Vesicles Produced}} by {{Cryptococcus}} Neoformans {{Contain Protein Components Associated}} with {{Virulence}}},
  volume = {7},
  copyright = {American Society for Microbiology},
  issn = {1535-9778, 1535-9786},
  abstract = {Cryptococcus neoformans produces vesicles containing its major virulence factor, the capsular polysaccharide glucuronoxylomannan (GXM). These vesicles cross the cell wall to reach the extracellular space, where the polysaccharide is supposedly used for capsule growth or delivered into host tissues. In the present study, we characterized vesicle morphology and protein composition by a combination of techniques including electron microscopy, proteomics, enzymatic activity, and serological reactivity. Secretory vesicles in C. neoformans appear to be correlated with exosome-like compartments derived from multivesicular bodies. Extracellular vesicles manifested various sizes and morphologies, including electron-lucid membrane bodies and electron-dense vesicles. Seventy-six proteins were identified by proteomic analysis, including several related to virulence and protection against oxidative stress. Biochemical tests indicated laccase and urease activities in vesicles. In addition, different vesicle proteins were recognized by sera from patients with cryptococcosis. These results reveal an efficient and general mechanism of secretion of pathogenesis-related molecules in C. neoformans, suggesting that extracellular vesicles function as ``virulence bags'' that deliver a concentrated payload of fungal products to host effector cells and tissues.},
  language = {en},
  number = {1},
  journal = {Eukaryotic Cell},
  doi = {10.1128/EC.00370-07},
  author = {Rodrigues, Marcio L. and Nakayasu, Ernesto S. and Oliveira, Debora L. and Nimrichter, Leonardo and Nosanchuk, Joshua D. and Almeida, Igor C. and Casadevall, Arturo},
  month = jan,
  year = {2008},
  pages = {58-67},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Fungal EVs\\Crypto EVs\\Rodrigues et al_2008_Extracellular Vesicles Produced by Cryptococcus neoformans Contain Protein.pdf;C:\\Users\\charl\\Zotero\\storage\\CJW8CAM7\\58.html},
  pmid = {18039940}
}

@article{dunkler2007,
  title = {Candida Albicans {{Rho}}-{{Type GTPase}}-{{Encoding Genes Required}} for {{Polarized Cell Growth}} and {{Cell Separation}}},
  volume = {6},
  copyright = {American Society for Microbiology},
  issn = {1535-9778, 1535-9786},
  abstract = {Rho proteins are essential regulators of morphogenesis in eukaryotic cells. In this report, we investigate the role of two previously uncharacterized Rho proteins, encoded by the Candida albicans RHO3 (CaRHO3) and CaCRL1/CaRHO4 genes. The CaRHO3 gene was found to contain one intron. Promoter shutdown experiments using a MET3 promoter-controlled RHO3 revealed a strong cell polarity defect and a partially depolarized actin cytoskeleton. Hyphal growth after promoter shutdown was abolished in rho3 mutants even in the presence of a constitutively active ras1(G13V) allele, and existing germ tubes became swollen. Deletion of C. albicans RHO4 indicated that it is a nonessential gene and that rho4 mutants were phenotypically different from rho3. Two distinct phenotypes of rho4 cells were elongated cell morphology and an unexpected cell separation defect generating chains of cells. Colony morphology of crl1/rho4 resulted in a growth-dependent smooth (long cell cycle length) or wrinkled (short cell cycle length) phenotype. This phenotype was additionally dependent on the rho4 cell separation defect and was also found in a Cacht3 chitinase mutant that shows a strong cytokinesis defect. The overexpression of the endoglucanase encoding the ENG1 gene, but not CHT3, suppressed the cell separation defect of crl1/rho4 but could not suppress the cell elongation phenotype. C. albicans Crl1/Rho4 and Bnr1 both localize to septal sites in yeast and hyphal cells but not to the hyphal tip. Deletion of RHO4 and BNR1 produced similar morphological phenotypes. Based on the localization of Rho4 and on the rho4 mutant phenotype, we propose a model in which Rho4p may function as a regulator of cell polarity, breaking the initial axis of polarity found during early bud growth to promote the construction of a septum.},
  language = {en},
  number = {5},
  journal = {Eukaryotic Cell},
  doi = {10.1128/EC.00201-06},
  author = {D{\"u}nkler, Alexander and Wendland, J{\"u}rgen},
  month = may,
  year = {2007},
  pages = {844-854},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\GFP fusions\\Dünkler_Wendland_2007_Candida albicans Rho-Type GTPase-Encoding Genes Required for Polarized Cell.pdf;C:\\Users\\charl\\Zotero\\storage\\4JYIKDE5\\844.html},
  pmid = {17351079}
}

@article{bassilana2006,
  title = {Rac1 and {{Cdc42 Have Different Roles}} in {{Candida}} Albicans {{Development}}},
  volume = {5},
  copyright = {American Society for Microbiology},
  issn = {1535-9778, 1535-9786},
  abstract = {We investigated the role of the highly conserved G protein Rac1 in the opportunistic pathogen Candida albicans. We identified and disrupted RAC1 and show here that, in contrast to CDC42, it is not necessary for viability or serum-induced hyphal growth but is essential for filamentous growth when cells are embedded in a matrix. Rac1 is localized to the plasma membrane, yet its distribution is more homogenous than that of Cdc42, with no enrichment at the tips of either buds or hyphae. In addition, fluorescence recovery after photobleaching results indicate that Rac1 and Cdc42 have different dynamics at the membrane. Furthermore, overexpression of Rac1 does not complement Cdc42 function, and conversely, overexpression of Cdc42 does not complement Rac1 function. Thus, Rac1 and Cdc42, although highly similar to one another, have different roles in C. albicans development.},
  language = {en},
  number = {2},
  journal = {Eukaryotic Cell},
  doi = {10.1128/EC.5.2.321-329.2006},
  author = {Bassilana, Martine and Arkowitz, Robert A.},
  month = feb,
  year = {2006},
  pages = {321-329},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\GFP fusions\\Bassilana_Arkowitz_2006_Rac1 and Cdc42 Have Different Roles in Candida albicans Development.pdf;C:\\Users\\charl\\Zotero\\storage\\WENV4Q5P\\321.html},
  pmid = {16467473}
}

@article{barelle2006,
  title = {Candida Albicans {{VAC8 Is Required}} for {{Vacuolar Inheritance}} and {{Normal Hyphal Branching}}},
  volume = {5},
  copyright = {American Society for Microbiology},
  issn = {1535-9778, 1535-9786},
  abstract = {Hyphal growth is prevalent during most Candida albicans infections. Current cell division models, which are based on cytological analyses of C. albicans, predict that hyphal branching is intimately linked with vacuolar inheritance in this fungus. Here we report the molecular validation of this model, showing that a specific mutation that disrupts vacuolar inheritance also affects hyphal division. The armadillo repeat-containing protein Vac8p plays an important role in vacuolar inheritance in Saccharomyces cerevisiae. The VAC8 gene was identified in the C. albicans genome sequence and was resequenced. Homozygous C. albicans vac8{$\Delta$} deletion mutants were generated, and their phenotypes were examined. Mutant vac8{$\Delta$} cells contained fragmented vacuoles, and minimal vacuolar material was inherited by daughter cells in hyphal or budding forms. Normal rates of growth and hyphal extension were observed for the mutant hyphae on solid serum-containing medium. However, branching frequencies were significantly increased in the mutant hyphae. These observations are consistent with a causal relationship between vacuolar inheritance and the cell division cycle in the subapical compartments of C. albicans hyphae. The data support the hypothesis that cytoplasmic volume, rather than cell size, is critical for progression through G1.},
  language = {en},
  number = {2},
  journal = {Eukaryotic Cell},
  doi = {10.1128/EC.5.2.359-367.2006},
  author = {Barelle, Caroline J. and Richard, Mathias L. and Gaillardin, Claude and Gow, Neil A. R. and Brown, Alistair J. P.},
  month = feb,
  year = {2006},
  pages = {359-367},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Candida antibodies\\Barelle et al_2006_Candida albicans VAC8 Is Required for Vacuolar Inheritance and Normal Hyphal.pdf;C:\\Users\\charl\\Zotero\\storage\\6DAVIFZD\\359.html},
  pmid = {16467476}
}

@article{guinea2014,
  title = {Global Trends in the Distribution of {{Candida}} Species Causing Candidemia},
  volume = {20},
  issn = {1198-743X},
  abstract = {Only five species account for 92\% of cases of candidemia (Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, and C. krusei); however, their distribution varies in population-based studies conducted in different geographical areas. C. albicans is the most frequent species, but considerable differences are found between the number of cases caused by C. glabrata and C. parapsilosis. Studies from Northern Europe and the USA reported a high number of cases caused by C. glabrata, whereas studies from Spain and Brazil demonstrated a lower number of cases caused by C. glabrata and a higher number of cases attributed to C. parapsilosis. Globally, the frequency of C. albicans is decreasing, while that of C. glabrata and C. krusei is stable, and C. parapsilosis and C. tropicalis are increasing. Patient characteristics and prior antifungal therapy also have a considerable influence on the distribution and frequency of Candida spp., regardless of the geographical area. C. albicans is more frequent in patients aged up to 18 years, the frequency of C. parapsilosis decreases with age, and C. glabrata is more common in the elderly. Finally, the presence of horizontal transmission of Candida spp. isolates (reported mainly in patients from the adult medical and post-surgical ICU, patients from oncology\textendash{}haematology units, and neonates) can affect species distribution.},
  number = {Suppl. 6},
  journal = {Clinical Microbiology and Infection},
  doi = {10.1111/1469-0691.12539},
  author = {Guinea, J.},
  month = jun,
  year = {2014},
  keywords = {C. albicans,C. glabrata,C. parapsilosis,candidemia,invasive candidiasis,outbreaks,population-based,species distribution},
  pages = {5-10},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Candida pathogenesis\\Epidemiology\\Guinea_2014_Global trends in the distribution of Candida species causing candidemia.pdf;C:\\Users\\charl\\Zotero\\storage\\SPVCDXTW\\S1198743X14603268.html}
}

@article{vargas2015,
  title = {Compositional and Immunobiological Analyses of Extracellular Vesicles Released by {{Candida}} Albicans},
  volume = {17},
  copyright = {\textcopyright{} 2014 John Wiley \& Sons Ltd},
  issn = {1462-5822},
  abstract = {The release of extracellular vesicles (EV) by fungal organisms is considered an alternative transport mechanism to trans-cell wall passage of macromolecules. Previous studies have revealed the presence of EV in culture supernatants from fungal pathogens, such as Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii, Malassezia sympodialis and Candida albicans. Here we investigated the size, composition, kinetics of internalization by bone marrow-derived murine macrophages (MO) and dendritic cells (DC), and the immunomodulatory activity of C. albicans EV. We also evaluated the impact of EV on fungal virulence using the Galleria mellonella larvae model. By transmission electron microscopy and dynamic light scattering, we identified two populations ranging from 50 to 100 nm and 350 to 850 nm. Two predominant seroreactive proteins (27 kDa and 37 kDa) and a group of polydispersed mannoproteins were observed in EV by immunoblotting analysis. Proteomic analysis of C. albicans EV revealed proteins related to pathogenesis, cell organization, carbohydrate and lipid metabolism, response to stress, and several other functions. The major lipids detected by thin-layer chromatography were ergosterol, lanosterol and glucosylceramide. Short exposure of MO to EV resulted in internalization of these vesicles and production of nitric oxide, interleukin (IL)-12, transforming growth factor-beta (TGF-{$\beta$}) and IL-10. Similarly, EV-treated DC produced IL-12p40, IL-10 and tumour necrosis factor-alpha. In addition, EV treatment induced the up-regulation of CD86 and major histocompatibility complex class-II (MHC-II). Inoculation of G. mellonella larvae with EV followed by challenge with C. albicans reduced the number of recovered viable yeasts in comparison with infected larvae control. Taken together, our results demonstrate that C. albicans EV were immunologically active and could potentially interfere with the host responses in the setting of invasive candidiasis.},
  language = {en},
  number = {3},
  journal = {Cellular Microbiology},
  doi = {10.1111/cmi.12374},
  author = {Vargas, Gabriele and Rocha, Juliana D. B. and Oliveira, Debora Leite and Albuquerque, Priscila Costa and Frases, Susana and Santos, Suelen S. and Nosanchuk, Joshua Daniel and Gomes, Andre Marco Oliveira and Medeiros, Lia C. A. S. and Miranda, Kildare and Sobreira, Tiago J. P. and Nakayasu, Ernesto S. and Arigi, Emma A. and Casadevall, Arturo and Guimaraes, Allan J. and Rodrigues, Marcio L. and Freire-de-Lima, Celio Geraldo and Almeida, Igor C. and Nimrichter, Leonardo},
  month = mar,
  year = {2015},
  pages = {389-407},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Fungal EVs\\Candida EVs\\Research\\Vargas et al_2015_Compositional and immunobiological analyses of extracellular vesicles released.pdf;C:\\Users\\charl\\Zotero\\storage\\NARYFJT4\\cmi.html}
}

@article{ramage2002,
  title = {Inhibition of {{Candida}} Albicans {{Biofilm Formation}} by {{Farnesol}}, a {{Quorum}}-{{Sensing Molecule}}},
  volume = {68},
  copyright = {American Society for Microbiology},
  issn = {0099-2240, 1098-5336},
  abstract = {Farnesol is a quorum-sensing molecule that inhibits filamentation in Candida albicans. Both filamentation and quorum sensing are deemed to be important factors in C. albicans biofilm development. Here we examined the effect of farnesol on C. albicans biofilm formation. C. albicans adherent cell populations (after 0, 1, 2, and 4 h of adherence) and preformed biofilms (24 h) were treated with various concentrations of farnesol (0, 3, 30, and 300 {$\mu$}M) and incubated at 37\textdegree{}C for 24 h. The extent and characteristics of biofilm formation were then assessed microscopically and with a semiquantitative colorimetric technique based on the use of 2,3-bis(2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide. The results indicated that the effect of farnesol was dependent on the concentration of this compound and the initial adherence time, and preincubation with 300 {$\mu$}M farnesol completely inhibited biofilm formation. Supernatant media recovered from mature biofilms inhibited the ability of planktonic C. albicans to form filaments, indicating that a morphogenetic autoregulatory compound is produced in situ in biofilms. Northern blot analysis of RNA extracted from cells in biofilms indicated that the levels of expression of HWP1, encoding a hypha-specific wall protein, were decreased in farnesol-treated biofilms compared to the levels in controls. Our results indicate that farnesol acts as a naturally occurring quorum-sensing molecule which inhibits biofilm formation, and we discuss its potential for further development and use as a novel therapeutic agent.},
  language = {en},
  number = {11},
  journal = {Applied and Environmental Microbiology},
  doi = {10.1128/AEM.68.11.5459-5463.2002},
  author = {Ramage, Gordon and Saville, Stephen P. and Wickes, Brian L. and {L{\'o}pez-Ribot}, Jos{\'e} L.},
  month = nov,
  year = {2002},
  pages = {5459-5463},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Candida biofilm\\Research\\Ramage et al_2002_Inhibition of Candida albicans Biofilm Formation by Farnesol, a Quorum-Sensing.pdf;C:\\Users\\charl\\Zotero\\storage\\A4J8296H\\5459.html},
  pmid = {12406738}
}

@article{holmes2008,
  title = {{{ABC Transporter Cdr1p Contributes More}} than {{Cdr2p Does}} to {{Fluconazole Efflux}} in {{Fluconazole}}-{{Resistant Candida}} Albicans {{Clinical Isolates}}},
  volume = {52},
  copyright = {American Society for Microbiology},
  issn = {0066-4804, 1098-6596},
  abstract = {Fluconazole (FLC) remains the antifungal drug of choice for non-life-threatening Candida infections, but drug-resistant strains have been isolated during long-term therapy with azoles. Drug efflux, mediated by plasma membrane transporters, is a major resistance mechanism, and clinically significant resistance in Candida albicans is accompanied by increased transcription of the genes CDR1 and CDR2, encoding plasma membrane ABC-type transporters Cdr1p and Cdr2p. The relative importance of each transporter protein for efflux-mediated resistance in C. albicans, however, is unknown; neither the relative amounts of each polypeptide in resistant isolates nor their contributions to efflux function have been determined. We have exploited the pump-specific properties of two antibody preparations, and specific pump inhibitors, to determine the relative expression and functions of Cdr1p and Cdr2p in 18 clinical C. albicans isolates. The antibodies and inhibitors were standardized using recombinant Saccharomyces cerevisiae strains that hyper-express either protein in a host strain with a reduced endogenous pump background. In all 18 C. albicans strains, including 13 strains with reduced FLC susceptibilities, Cdr1p was present in greater amounts (2- to 20-fold) than Cdr2p. Compounds that inhibited Cdr1p-mediated function, but had no effect on Cdr2p efflux activity, significantly decreased the resistance to FLC of seven representative C. albicans isolates, whereas three other compounds that inhibited both pumps did not cause increased chemosensitization of these strains to FLC. We conclude that Cdr1p expression makes a greater functional contribution than does Cdr2p to FLC resistance in C. albicans.},
  language = {en},
  number = {11},
  journal = {Antimicrobial Agents and Chemotherapy},
  doi = {10.1128/AAC.00463-08},
  author = {Holmes, Ann R. and Lin, Ya-Hsun and Niimi, Kyoko and Lamping, Erwin and Keniya, Mikhail and Niimi, Masakazu and Tanabe, Koichi and Monk, Brian C. and Cannon, Richard D.},
  month = nov,
  year = {2008},
  pages = {3851-3862},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Candida antifungals\\Azoles\\Holmes et al_2008_ABC Transporter Cdr1p Contributes More than Cdr2p Does to Fluconazole Efflux in.pdf;C:\\Users\\charl\\Zotero\\storage\\QJSJKKAQ\\3851.html},
  pmid = {18710914}
}

@article{schorey2015,
  title = {Exosomes and Other Extracellular Vesicles in Host-Pathogen Interactions},
  volume = {16},
  copyright = {\textcopyright{} 2014 The Authors},
  issn = {1469-221X, 1469-3178},
  abstract = {An effective immune response requires the engagement of host receptors by pathogen-derived molecules and the stimulation of an appropriate cellular response. Therefore, a crucial factor in our ability to control an infection is the accessibility of our immune cells to the foreign material. Exosomes\textemdash{}which are extracellular vesicles that function in intercellular communication\textemdash{}may play a key role in the dissemination of pathogen- as well as host-derived molecules during infection. In this review, we highlight the composition and function of exosomes and other extracellular vesicles produced during viral, parasitic, fungal and bacterial infections and describe how these vesicles could function to either promote or inhibit host immunity.},
  language = {en},
  number = {1},
  journal = {EMBO reports},
  doi = {10.15252/embr.201439363},
  author = {Schorey, Jeffrey S. and Cheng, Yong and Singh, Prachi P. and Smith, Victoria L.},
  month = jan,
  year = {2015},
  keywords = {exosomes,extracellular vesicles,immunity,pathogens},
  pages = {24-43},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Review Fungal EV\\Schorey et al_2015_Exosomes and other extracellular vesicles in host–pathogen interactions.pdf;C:\\Users\\charl\\Zotero\\storage\\76FGG8R5\\24.html},
  pmid = {25488940}
}

@article{pfaller2007,
  title = {Epidemiology of {{Invasive Candidiasis}}: A {{Persistent Public Health Problem}}},
  volume = {20},
  copyright = {American Society for Microbiology},
  issn = {0893-8512, 1098-6618},
  shorttitle = {Epidemiology of {{Invasive Candidiasis}}},
  abstract = {Invasive candidiasis (IC) is a leading cause of mycosis-associated mortality in the United States. We examined data from the National Center for Health Statistics and reviewed recent literature in order to update the epidemiology of IC. IC-associated mortality has remained stable, at approximately 0.4 deaths per 100,000 population, since 1997, while mortality associated with invasive aspergillosis has continued to decline. Candida albicans remains the predominant cause of IC, accounting for over half of all cases, but Candida glabrata has emerged as the second most common cause of IC in the United States, and several less common Candida species may be emerging, some of which can exhibit resistance to triazoles and/or amphotericin B. Crude and attributable rates of mortality due to IC remain unacceptably high and unchanged for the past 2 decades. Nonpharmacologic preventive strategies should be emphasized, including hand hygiene; appropriate use, placement, and care of central venous catheters; and prudent use of antimicrobial therapy. Given that delays in appropriate antifungal therapy are associated with increased mortality, improved use of early empirical, preemptive, and prophylactic therapies should also help reduce IC-associated mortality. Several studies have now identified important variables that can be used to predict risk of IC and to help guide preventive strategies such as antifungal prophylaxis and early empirical therapy. However, improved non-culture-based diagnostics are needed to expand the potential for preemptive (or early directed) therapy. Further research to improve diagnostic, preventive, and therapeutic strategies is necessary to reduce the considerable morbidity and mortality associated with IC.},
  language = {en},
  number = {1},
  journal = {Clinical Microbiology Reviews},
  doi = {10.1128/CMR.00029-06},
  author = {Pfaller, M. A. and Diekema, D. J.},
  month = jan,
  year = {2007},
  pages = {133-163},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Candida pathogenesis\\Epidemiology\\Pfaller_Diekema_2007_Epidemiology of Invasive Candidiasis.pdf;C:\\Users\\charl\\Zotero\\storage\\HLEW2UU9\\133.html},
  pmid = {17223626}
}

@article{sandini2011,
  title = {The {{MP65}} Gene Is Required for Cell Wall Integrity, Adherence to Epithelial Cells and Biofilm Formation in {{Candida}} Albicans},
  volume = {11},
  issn = {1471-2180},
  abstract = {The MP65 gene of Candida albicans (orf19.1779) encodes a putative {$\beta$}-glucanase mannoprotein of 65 kDa, which plays a main role in a host-fungus relationship, morphogenesis and pathogenicity. In this study, we performed an extensive analysis of a mp65{$\Delta$} mutant to assess the role of this protein in cell wall integrity, adherence to epithelial cells and biofilm formation.},
  number = {1},
  journal = {BMC Microbiology},
  doi = {10.1186/1471-2180-11-106},
  author = {Sandini, Silvia and Stringaro, Annarita and Arancia, Silvia and Colone, Marisa and Mondello, Francesca and Murtas, Susanna and Girolamo, Antonietta and Mastrangelo, Nicolina and De Bernardis, Flavia},
  month = may,
  year = {2011},
  pages = {106},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Fungal EVs\\Candida EVs\\Cargo\\M-R\\Sandini et al_2011_The MP65 gene is required for cell wall integrity, adherence to epithelial.pdf;C:\\Users\\charl\\Zotero\\storage\\65EWFMQ5\\1471-2180-11-106.html}
}

@article{bishop2010,
  title = {Hyphal Growth in {{Candida}} Albicans Requires the Phosphorylation of {{Sec2}} by the {{Cdc28}}-{{Ccn1}}/{{Hgc1}} Kinase},
  volume = {29},
  copyright = {Copyright \textcopyright{} 2010 European Molecular Biology Organization},
  issn = {0261-4189, 1460-2075},
  abstract = {Polarized growth is a fundamental property of cell growth and development. It requires the delivery of post-Golgi secretory vesicles to the site of polarized growth. This process is mediated by Rab GTPases activated by their guanine exchange factors (GEFs). The human fungal pathogen, Candida albicans, can grow in a budded yeast form or in a highly polarized hyphal form, and thus provides a model to study this phenomenon. During hyphal, but not yeast growth, secretory vesicles accumulate in an apical body called a Spitzenk{\"o}rper, which acts to focus delivery of the vesicles to the tip. Post-Golgi transport of secretory vesicles is mediated by the Rab GTPase Sec4, activated by its GEF Sec2. Using a combination of deletion mapping, in vitro mutagenesis, an analogue-sensitive allele of Cdc28 and an in vitro kinase assay, we show that localization of Sec2 to the Spitzenk{\"o}rper and normal hyphal development requires phosphorylation of Serine 584 by the cyclin-dependent kinase Cdc28. Thus, as well as controlling passage through the cell cycle, Cdc28 has an important function in controlling polarized secretion.},
  language = {en},
  number = {17},
  journal = {The EMBO Journal},
  doi = {10.1038/emboj.2010.158},
  author = {Bishop, Amy and Lane, Rachel and Beniston, Richard and Chapa-y-Lazo, Bernardo and Smythe, Carl and Sudbery, Peter},
  month = sep,
  year = {2010},
  keywords = {cyclin‐dependent kinase,polarized exocytosis,polarized growth,Spitzenkörper},
  pages = {2930-2942},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\EV markers\\Candida 43\\Bishop et al_2010_Hyphal growth in Candida albicans requires the phosphorylation of Sec2 by the.pdf;C:\\Users\\charl\\Zotero\\storage\\HHVFZVAK\\2930.html},
  pmid = {20639857}
}

@article{alvarez2008,
  title = {The {{Sur7 Protein Regulates Plasma Membrane Organization}} and {{Prevents Intracellular Cell Wall Growth}} in {{Candida}} Albicans},
  volume = {19},
  issn = {1059-1524},
  abstract = {The Candida albicans plasma membrane plays important roles in cell growth and as a target for antifungal drugs. Analysis of Ca-Sur7 showed that this four transmembrane domain protein localized to stable punctate patches, similar to the plasma membrane subdomains known as eisosomes or MCC that were discovered in S. cerevisiae. The localization of Ca-Sur7 depended on sphingolipid synthesis. In contrast to S. cerevisiae, a C. albicans sur7{$\Delta$} mutant displayed defects in endocytosis and morphogenesis. Septins and actin were mislocalized, and cell wall synthesis was very abnormal, including long projections of cell wall into the cytoplasm. Several phenotypes of the sur7{$\Delta$} mutant are similar to the effects of inhibiting {$\beta$}-glucan synthase, suggesting that the abnormal cell wall synthesis is related to activation of chitin synthase activity seen under stress conditions. These results expand the roles of eisosomes by demonstrating that Sur7 is needed for proper plasma membrane organization and cell wall synthesis. A conserved Cys motif in the first extracellular loop of fungal Sur7 proteins is similar to a characteristic motif of the claudin proteins that form tight junctions in animal cells, suggesting a common role for these tetraspanning membrane proteins in forming specialized plasma membrane domains.},
  number = {12},
  journal = {Molecular Biology of the Cell},
  doi = {10.1091/mbc.e08-05-0479},
  author = {Alvarez, Francisco J. and Douglas, Lois M. and Rosebrock, Adam and Konopka, James B. and Lew, Daniel J.},
  month = sep,
  year = {2008},
  keywords = {SUR7},
  pages = {5214-5225},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Tetraspanins\\Sur7\\Alvarez et al_2008_The Sur7 Protein Regulates Plasma Membrane Organization and Prevents.pdf;C:\\Users\\charl\\Zotero\\storage\\IYD6IZA8\\mbc.html}
}

@article{palige2013,
  title = {Global {{Transcriptome Sequencing Identifies Chlamydospore Specific Markers}} in {{Candida}} Albicans and {{Candida}} Dubliniensis},
  volume = {8},
  issn = {1932-6203},
  abstract = {Candida albicans and Candida dubliniensis are pathogenic fungi that are highly related but differ in virulence and in some phenotypic traits. During in vitro growth on certain nutrient-poor media, C. albicans and C. dubliniensis are the only yeast species which are able to produce chlamydospores, large thick-walled cells of unknown function. Interestingly, only C. dubliniensis forms pseudohyphae with abundant chlamydospores when grown on Staib medium, while C. albicans grows exclusively as a budding yeast. In order to further our understanding of chlamydospore development and assembly, we compared the global transcriptional profile of both species during growth in liquid Staib medium by RNA sequencing. We also included a C. albicans mutant in our study which lacks the morphogenetic transcriptional repressor Nrg1. This strain, which is characterized by its constitutive pseudohyphal growth, specifically produces masses of chlamydospores in Staib medium, similar to C. dubliniensis. This comparative approach identified a set of putatively chlamydospore-related genes. Two of the homologous C. albicans and C. dubliniensis genes (CSP1 and CSP2) which were most strongly upregulated during chlamydospore development were analysed in more detail. By use of the green fluorescent protein as a reporter, the encoded putative cell wall related proteins were found to exclusively localize to C. albicans and C. dubliniensis chlamydospores. Our findings uncover the first chlamydospore specific markers in Candida species and provide novel insights in the complex morphogenetic development of these important fungal pathogens.},
  language = {en},
  number = {4},
  journal = {PLOS ONE},
  doi = {10.1371/journal.pone.0061940},
  author = {Palige, Katja and Linde, J{\"o}rg and Martin, Ronny and B{\"o}ttcher, Bettina and Citiulo, Francesco and Sullivan, Derek J. and Weber, Johann and Staib, Claudia and Rupp, Steffen and Hube, Bernhard and Morschh{\"a}user, Joachim and Staib, Peter},
  month = apr,
  year = {2013},
  keywords = {Candida,Candida albicans,Cell walls,Fluorescence microscopy,Fungal pathogens,Gene expression,Green fluorescent protein,orf19.6741,RNA sequencing},
  pages = {e61940},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\EV markers\\Candida 43\\Palige et al_2013_Global Transcriptome Sequencing Identifies Chlamydospore Specific Markers in.pdf;C:\\Users\\charl\\Zotero\\storage\\F3UZZMB7\\article.html}
}

@article{kenno2019,
  title = {Candida Albicans {{Factor H Binding Molecule Hgt1p}} \textendash{} {{A Low Glucose}}-{{Induced Transmembrane Protein Is Trafficked}} to the {{Cell Wall}} and {{Impairs Phagocytosis}} and {{Killing}} by {{Human Neutrophils}}},
  volume = {9},
  issn = {1664-302X},
  abstract = {ABSTRACT Complement is a tightly controlled arm of the innate immune system, facilitating phagocytosis and killing of invading pathogens. Factor H (FH) is the main fluid-phase inhibitor of the alternative pathway. Many pathogens can hijack FH from the host and protect themselves from complement-dependent killing. Candida albicans is a clinically important opportunistic yeast, expressing different FH binding molecules on its cell surface, which allow complement evasion. One such FH binding molecule is the transmembrane protein ``High affinity glucose transporter 1'' (Hgt1p), involved in glucose metabolism. This study demonstrated that Hgt1p transcription and expression is induced and highest at the low, but physiological glucose concentration of 0.1\%, why this concentration was used throughout the study. We also demonstrated the transport of Hgt1p to the fungal cell wall surface by vesicle trafficking and its release by exosomes containing Hgt1p integrated in the vesicular membrane. We corroborated Hgt1p as FH binding molecule. A polyclonal anti-Hgt1p antibody was created which interfered with the binding of FH, present in normal human serum to the fungal cell wall . A chimeric molecule consisting of FH domains 6 and 7 fused to human IgG1 Fc (FH6.7/Fc) even more comprehensively blocked FH binding, likely because FH6.7/Fc diverted FH away from fungal FH ligands other than Hgt1p. Reduced FH binding to the yeast was associated with a concomitant increase in C3b/iC3b deposition, resulted in significantly increased in vitro phagocytosis and killing by human neutrophils.In conclusion, Hgt1p also exhibits non-canonical functions such as binding FH after its export to the cell wall. Blocking Hgt1p-FH interactions may represent a tool to enhance complement activation on the fungal surface to promote phagocytosis and killing of C. albicans.},
  language = {English},
  journal = {Frontiers in Microbiology},
  doi = {10.3389/fmicb.2018.03319},
  author = {Kenno, Samyr and Speth, Cornelia and Rambach, G{\"u}nter and Binder, Ulrike and Chatterjee, Sneha and Caramalho, Rita and Haas, Hubertus and {Lass-Fl{\"o}rl}, Cornelia and Shaughnessy, Jutamas and Ram, Sanjay and Gow, Neil A. R. and {Orth-H{\"o}ller}, Dorothea and W{\"u}rzner, Reinhard},
  year = {2019},
  keywords = {Candida albicans,complement system,Factor H (FH),Fungal Infection,HGT1,Immune Evasion},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\EV markers\\Candida 43\\Kenno et al_2019_Candida albicans Factor H Binding Molecule Hgt1p – A Low Glucose-Induced.pdf}
}

@article{worst2017,
  title = {Database-Augmented {{Mass Spectrometry Analysis}} of {{Exosomes Identifies Claudin}} 3 as a {{Putative Prostate Cancer Biomarker}}},
  volume = {16},
  copyright = {\textcopyright{} 2017 by The American Society for Biochemistry and Molecular Biology, Inc.},
  issn = {1535-9476, 1535-9484},
  abstract = {In prostate cancer and other malignancies sensitive and robust biomarkers are lacking or have relevant limitations. Prostate specific antigen (PSA), the only biomarker widely used in prostate cancer, is suffering from low specificity. Exosomes offer new perspectives in the discovery of blood-based biomarkers. Here we present a proof-of principle study for a proteomics-based identification pipeline, implementing existing data sources, to exemplarily identify exosome-based biomarker candidates in prostate cancer.
Exosomes from malignant PC3 and benign PNT1A cells and from FBS-containing medium were isolated using sequential ultracentrifugation. Exosome and control samples were analyzed on an LTQ-Orbitrap XL mass spectrometer. Proteomic data is available via ProteomeXchange with identifier PXD003651. We developed a scoring scheme to rank 64 proteins exclusively found in PC3 exosomes, integrating data from four public databases and published mass spectrometry data sets. Among the top candidates, we focused on the tight junction protein claudin 3. Retests under serum-free conditions using immunoblotting and immunogold labeling confirmed the presence of claudin 3 on PC3 exosomes. Claudin 3 levels were determined in the blood plasma of patients with localized (n = 58; 42 with Gleason score 6\textendash{}7, 16 with Gleason score {$\geq$}8) and metastatic prostate cancer (n = 11) compared with patients with benign prostatic hyperplasia (n = 15) and healthy individuals (n = 15) using ELISA, without prior laborious exosome isolation. ANOVA showed different CLDN3 plasma levels in these groups (p = 0.004). CLDN3 levels were higher in patients with Gleason {$\geq$}8 tumors compared with patients with benign prostatic hyperplasia (p = 0.012) and Gleason 6\textendash{}7 tumors (p = 0.029). In patients with localized tumors CLDN3 levels predicted a Gleason score {$\geq$} 8 (AUC = 0.705; p = 0.016) and did not correlate with serum PSA.
By using the described workflow claudin 3 was identified and validated as a potential blood-based biomarker in prostate cancer. Furthermore this workflow could serve as a template to be used in other cancer entities.},
  language = {en},
  number = {6},
  journal = {Molecular \& Cellular Proteomics},
  doi = {10.1074/mcp.M117.068577},
  author = {Worst, Thomas Stefan and von Hardenberg, Jost and Gross, Julia Christina and Erben, Philipp and Schn{\"o}lzer, Martina and Hausser, Ingrid and Bugert, Peter and Michel, Maurice Stephan and Boutros, Michael},
  month = jun,
  year = {2017},
  pages = {998-1008},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Model papers\\EV\\Worst et al_2017_Database-augmented Mass Spectrometry Analysis of Exosomes Identifies Claudin 3.pdf;C:\\Users\\charl\\Zotero\\storage\\VNU54MML\\998.html},
  pmid = {28396511}
}

@article{zhang2018,
  title = {Proteome-Wide Identification of Ubiquitin Interactions Using {{UbIA}}-{{MS}}},
  volume = {13},
  copyright = {2018 Nature Publishing Group},
  issn = {1750-2799},
  abstract = {Ubiquitin-binding proteins play an important role in eukaryotes by translating differently linked polyubiquitin chains into proper cellular responses. Current knowledge about ubiquitin-binding proteins and ubiquitin linkage-selective interactions is mostly based on case-by-case studies. We have recently reported a method called ubiquitin interactor affinity enrichment\textendash{}mass spectrometry (UbIA-MS), which enables comprehensive identification of ubiquitin interactors for all ubiquitin linkages from crude cell lysates. One major strength of UbIA-MS is the fact that ubiquitin interactors are enriched from crude cell lysates, in which proteins are present at endogenous levels, contain biologically relevant post-translational modifications (PTMs) and are assembled in native protein complexes. In addition, UbIA-MS uses chemically synthesized nonhydrolyzable diubiquitin, which mimics native diubiquitin and is inert to cleavage by endogenous deubiquitinases (DUBs). Here, we present a detailed protocol for UbIA-MS that proceeds in five stages: (i) chemical synthesis of ubiquitin precursors and click chemistry for the generation of biotinylated nonhydrolyzable diubiquitin baits, (ii) in vitro affinity purification of ubiquitin interactors, (iii) on-bead interactor digestion, (iv) liquid chromatography (LC)\textendash{}MS/MS analysis and (v) data analysis to identify differentially enriched proteins. The computational analysis tools are freely available as an open-source R software package, including a graphical interface. Typically, UbIA-MS allows the identification of dozens to hundreds of ubiquitin interactors from any type of cell lysate, and can be used to study cell type or stimulus-dependent ubiquitin interactions. The nonhydrolyzable diubiquitin synthesis can be completed in 3 weeks, followed by ubiquitin interactor enrichment and identification, which can be completed within another 2 weeks.},
  language = {en},
  number = {3},
  journal = {Nature Protocols},
  doi = {10.1038/nprot.2017.147},
  author = {Zhang, Xiaofei and Smits, Arne H. and {van Tilburg}, Gabrielle BA and Ovaa, Huib and Huber, Wolfgang and Vermeulen, Michiel},
  month = mar,
  year = {2018},
  pages = {530-550},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Methods\\R packages\\Zhang et al_2018_Proteome-wide identification of ubiquitin interactions using UbIA-MS.pdf;C:\\Users\\charl\\Zotero\\storage\\7X48K6FQ\\nprot.2017.html}
}

@article{tricarico2017,
  title = {Biology and Biogenesis of Shed Microvesicles},
  volume = {8},
  issn = {2154-1248},
  abstract = {The ability of cells to transmit bioactive molecules to recipient cells and the extracellular environment is a fundamental requirement for both normal physiology and disease pathogenesis. It has traditionally been thought that soluble factors released from cells were responsible for this cellular signaling but recent research has revealed a fundamental role for microvesicles in this process. Microvesicles are heterogeneous membrane-bound sacs that are shed from the surface of cells into the extracellular environment in a highly regulated process. They are shed following the selective incorporation of a host of molecular cargo including multiple types of proteins and nucleic acids. In addition to providing new insight into the etiology of complex human diseases, microvesicles also show great promise as a tool for advanced diagnosis and therapy as we move forward into a new age of personalized medicine. Here we review current status of the rapidly evolving field of microvesicle biology, highlighting critical regulatory roles for several small GTPases in the biology and biogenesis of shed microvesicles.},
  number = {4},
  journal = {Small GTPases},
  doi = {10.1080/21541248.2016.1215283},
  author = {Tricarico, Christopher and Clancy, James and {D'Souza-Schorey}, Crislyn},
  month = oct,
  year = {2017},
  keywords = {intercellular communication,microvesicles,small GTPases},
  pages = {220-232},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Review MV\\Tricarico et al_2017_Biology and biogenesis of shed microvesicles.pdf;C:\\Users\\charl\\Zotero\\storage\\5Y86SVRJ\\21541248.2016.html},
  pmid = {27494381}
}

@article{sedgwick2015,
  title = {Extracellular Microvesicles and Invadopodia Mediate Non-Overlapping Modes of Tumor Cell Invasion},
  volume = {5},
  copyright = {2015 Nature Publishing Group},
  issn = {2045-2322},
  abstract = {Tumor cell invasion requires the molecular and physical adaptation of both the cell and its microenvironment. Here we show that tumor cells are able to switch between the use of microvesicles and invadopodia to facilitate invasion through the extracellular matrix. Invadopodia formation accompanies the mesenchymal mode of migration on firm matrices and is facilitated by Rac1 activation. On the other hand, during invasion through compliant and deformable environments, tumor cells adopt an amoeboid phenotype and release microvesicles. Notably, firm matrices do not support microvesicle release, whereas compliant matrices are not conducive to invadopodia biogenesis. Furthermore, Rac1 activation is required for invadopodia function, while its inactivation promotes RhoA activation and actomyosin contractility required for microvesicle shedding. Suppression of RhoA signaling blocks microvesicle formation but enhances the formation of invadopodia. Finally, we describe Rho-mediated pathways involved in microvesicle biogenesis through the regulation of myosin light chain phosphatase. Our findings suggest that the ability of tumor cells to switch between the aforementioned qualitatively distinct modes of invasion may allow for dissemination across different microenvironments.},
  language = {en},
  journal = {Scientific Reports},
  doi = {10.1038/srep14748},
  author = {Sedgwick, Alanna E. and Clancy, James W. and Olivia Balmert, M. and {D'Souza-Schorey}, Crislyn},
  month = oct,
  year = {2015},
  pages = {14748},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\EV biogenesis\\Research\\Sedgwick et al_2015_Extracellular microvesicles and invadopodia mediate non-overlapping modes of.pdf;C:\\Users\\charl\\Zotero\\storage\\VQPSWEX7\\srep14748.html}
}

@article{brown2012,
  title = {Hidden {{Killers}}: {{Human Fungal Infections}}},
  volume = {4},
  issn = {1946-6234, 1946-6242},
  shorttitle = {Hidden {{Killers}}},
  language = {en},
  number = {165},
  journal = {Science Translational Medicine},
  doi = {10.1126/scitranslmed.3004404},
  author = {Brown, G. D. and Denning, D. W. and Gow, N. A. R. and Levitz, S. M. and Netea, M. G. and White, T. C.},
  month = dec,
  year = {2012},
  pages = {165rv13},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Honours\\Candida pathogenesis\\Epidemiology\\Brown et al_2012_Hidden Killers.pdf}
}

@article{saint-pol2017,
  title = {New Insights into the Tetraspanin {{Tspan5}} Using Novel Monoclonal Antibodies},
  volume = {292},
  issn = {0021-9258, 1083-351X},
  abstract = {Tspan5 is a member of a subgroup of tetraspanins referred to as TspanC8. These tetraspanins directly interact with the metalloprotease ADAM10, regulate its exit from the endoplasmic reticulum and subsequent trafficking, and differentially regulate its ability to cleave various substrates and activate Notch signaling. The study of Tspan5 has been limited by the lack of good antibodies. This study provides new insights into Tspan5 using new monoclonal antibodies (mAbs), including two mAbs recognizing both Tspan5 and the highly similar tetraspanin Tspan17. Using these mAbs, we show that endogenous Tspan5 associates with ADAM10 in human cell lines and in mouse tissues where it is the most abundant, such as the brain, the lung, the kidney, or the intestine. We also uncover two TspanC8-specific motifs in the large extracellular domain of Tspan5 that are important for ADAM10 interaction and exit from the endoplasmic reticulum. One of the anti-Tspan5 mAbs does not recognize Tspan5 associated with ADAM10, providing a convenient way to measure the fraction of Tspan5 not associated with ADAM10. This fraction is minor in the cell lines tested, and it increases upon transfection of cells with TspanC8 tetraspanins such as Tspan15 or Tspan33 that inhibit Notch signaling. Finally, two antibodies inhibit ligand-induced Notch signaling, and this effect is stronger in cells depleted of the TspanC8 tetraspanin Tspan14, further indicating that Tspan5 and Tspan14 can compensate for each other in Notch signaling.},
  language = {en},
  number = {23},
  journal = {Journal of Biological Chemistry},
  doi = {10.1074/jbc.M116.765669},
  author = {{Saint-Pol}, Julien and Billard, Martine and Dornier, Emmanuel and Eschenbrenner, Etienne and Danglot, Lydia and Boucheix, Claude and Charrin, St{\'e}phanie and Rubinstein, Eric},
  month = sep,
  year = {2017},
  pages = {9551-9566},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Saint-Pol et al_2017_New insights into the tetraspanin.pdf},
  pmid = {28428248}
}

@article{grove2017,
  title = {A New Panel of Epitope Mapped Monoclonal Antibodies Recognising the Prototypical Tetraspanin {{CD81}}},
  volume = {2},
  issn = {2398-502X},
  language = {en},
  journal = {Wellcome Open Research},
  doi = {10.12688/wellcomeopenres.12058.1},
  author = {Grove, Joe and Hu, Ke and Farquhar, Michelle J. and Goodall, Margaret and Walker, Lucas and Jamshad, Mohammed and Drummer, Heidi E. and Bill, Roslyn M. and Balfe, Peter and McKeating, Jane A.},
  month = sep,
  year = {2017},
  pages = {82},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Grove et al_2017_A new panel of epitope mapped.pdf}
}

@article{cook2002,
  title = {Identification of {{CD9}} Extracellular Domains Important in Regulation of {{CHO}} Cell Adhesion to Fibronectin and Fibronectin Pericellular Matrix Assembly},
  volume = {100},
  copyright = {Copyright \textcopyright{} 2002 The American Society of Hematology},
  issn = {0006-4971, 1528-0020},
  abstract = {CD9, a 24-kDa member of the tetraspanin family, influences cellular growth and development, activation, adhesion, and motility. Our investigation focuses on the hypothesis that the CD9 second extracellular loop (EC2) is important in modulating cell adhesive events. Using a Chinese hamster ovary (CHO) cell expression system, we previously reported that CD9 expression inhibited cell adhesion to fibronectin and fibronectin matrix assembly. For the first time, a functional epitope on CD9 EC2 that regulates these processes is described. Binding of mAb7, an EC2-specific anti-CD9 monoclonal antibody, reversed the CD9 inhibitory activity on CHO cell adhesion and fibronectin matrix assembly. This reversal of cell phenotype also was observed in CHO cells expressing CD9 EC2 truncations. Furthermore, our data showed that the EC2 sequence173LETFTVKSCPDAIKEVFDNK192 was largely responsible for the CD9-mediated CHO cell phenotype. Two peptides, 135K-V172 (peptide 5b) and168P-I185 (peptide 6a), selectively blocked mAb7 binding to soluble CD9 and to CD9 on intact cells. These active peptides reversed the influence of CD9 expression on CHO cell adhesion to fibronectin. In addition, confocal microscopy revealed that CD9 colocalized with the integrin {$\alpha$}5{$\beta$}1 and cytoskeletal F-actin in punctate clusters on the cell surface, particularly at the cell margins. Immunoprecipitation studies confirmed CD9 association with {$\beta$}1 integrin. The cellular distribution and colocalization of focal adhesion kinase and {$\alpha$}-actinin with cytoskeletal actin was also influenced by CD9 expression. Thus, CD9 may exhibit its effect by modulating the composition of adhesive complexes important in facilitating cell adhesion and matrix assembly.},
  language = {en},
  number = {13},
  journal = {Blood},
  doi = {10.1182/blood.V100.13.4502},
  author = {Cook, George A. and Longhurst, Celia M. and Grgurevich, Svetozar and Cholera, Shila and Crossno, Joseph T. and Jennings, Lisa K.},
  month = dec,
  year = {2002},
  pages = {4502-4511},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Cook et al_2002_Identification of CD9 extracellular.pdf},
  pmid = {12453879}
}

@article{kim2015,
  title = {Generation of a Human Antibody That Inhibits {{TSPAN8}}-Mediated Invasion of Metastatic Colorectal Cancer Cells},
  volume = {468},
  issn = {0006-291X},
  abstract = {Tetraspanin 8 (TSPAN8) is a tumor-associated antigen implicated in tumor progression and metastasis. However, the validation of TSPAN8 as a potential therapeutic target in metastatic colorectal cancer (mCRC) has not yet been studied. In this study, through several in~vitro methodologies, we identified a large extracellular loop of TSPAN8 (TSPAN8-LEL) as a key domain for regulating mCRC invasion. Using phage display technology, we developed a novel anti-TSPAN8-LEL human antibody with subnanomolar affinity that specifically recognizes amino acids 140\textendash{}205 of TSPAN8-LEL in a conformation-dependent manner. Finally, we demonstrated that the antibody specifically reduces invasion in the HCT116 and LoVo mCRC cell lines more potently than in the HCT-8 and SW480 non-mCRC cell lines. Our data suggest that TSPAN8-LEL may play an important role in mCRC cell invasion, and that the antibody we have developed could be a useful tool for inhibiting the invasion of TSPAN8-expressing mCRCs.},
  number = {4},
  journal = {Biochemical and Biophysical Research Communications},
  doi = {10.1016/j.bbrc.2015.11.031},
  author = {Kim, Taek-Keun and Park, Chang Sik and Jeoung, Mee Hyun and Lee, Woo Ran and Go, Nam Kyung and Choi, Jong Rip and Lee, Tae Sup and Shim, Hyunbo and Lee, Sukmook},
  month = dec,
  year = {2015},
  pages = {774-780},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Kim et al_2015_Generation of a human antibody that.pdf}
}

@article{gola2003,
  title = {New Modules for {{PCR}}-Based Gene Targeting in {{Candida}} Albicans: Rapid and Efficient Gene Targeting Using 100 Bp of Flanking Homology Region},
  volume = {20},
  copyright = {Copyright \textcopyright{} 2003 John Wiley \& Sons, Ltd.},
  issn = {1097-0061},
  shorttitle = {New Modules for {{PCR}}-Based Gene Targeting in {{Candida}} Albicans},
  abstract = {The use of PCR-based techniques for directed gene alterations has become a standard tool in Saccharomyces cerevisiae. In our efforts to increase the speed of functional analysis of Candida albicans genes, we constructed a modular system of plasmid vectors and successfully applied PCR-amplified functional analysis (FA)-cassettes in the transformation of C. albicans. These cassettes facilitate: (a) gene disruptions; (b) tagging of 3{${'}$}-ends of genes with green fluorescent protein (GFP); and (c) replacements of endogenous promoters to achieve regulated expression. The modules consists of a core of three selectable marker genes, CaURA3, CaHIS1 and CaARG4. Modules for C-terminal GFP-tagging were generated by adding GFP-sequences flanked at the 5{${'}$}-end by a (Gly-Ala)3-linker and at the 3{${'}$}-end by the S. cerevisiae URA3-terminator to these selection markers. Promoter exchange modules consist of the respective marker genes followed by the regulatable CaMAL2 or CaMET3 promoters at their 3{${'}$}-ends. In order to ensure a reliably high rate of homologous gene targeting, the flanking homology regions required a size of 100 bp of gene-specific sequences, which were provided with the oligonucleotide primers. The use of shorter flanking homology regions produced unsatisfactory results with C. albicans strain BWP17. With these new modules only a minimal set of primers is required to achieve the functional analysis of C. albicans genes and, therefore, provides a basic tool to increase the number of functionally characterized C. albicans genes of this human pathogen in the near future. Copyright \textcopyright{} 2003 John Wiley \& Sons, Ltd.},
  language = {en},
  number = {16},
  journal = {Yeast},
  doi = {10.1002/yea.1044},
  author = {Gola, Susanne and Martin, Ronny and Walther, Andrea and D{\"u}nkler, Alexander and Wendland, J{\"u}rgen},
  year = {2003},
  pages = {1339-1347},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Gola et al_2003_New modules for PCR-based gene.pdf}
}

@article{bernardo2014,
  title = {Secretion and Filamentation Are Mediated by the {{Candida}} Albicans T-{{SNAREs Sso2p}} and {{Sec9p}}},
  volume = {14},
  issn = {1567-1356},
  abstract = {The C. albicans t-SNARE proteins Sso2p and Sec9p are required for fundamental cellular processes and contribute to virulence-related attributes of C. albicans p},
  language = {en},
  number = {5},
  journal = {FEMS Yeast Research},
  doi = {10.1111/1567-1364.12165},
  author = {Bernardo, Stella M. and Rane, Hallie S. and {Chavez-Dozal}, Alba and Lee, Samuel A.},
  month = aug,
  year = {2014},
  pages = {762-775},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Bernardo et al_2014_Secretion and filamentation are.pdf}
}

@article{zhaoinpress,
  title = {Novel Cell Wall Remodelling Functions of Extracellular Vesicles Secreted by {{Saccharomyces}} Cerevisiae},
  journal = {Communications Biology},
  author = {Zhao, Kening and Bleackley, Mark and Chisanga, David and Gangoda, Lahiru and Liem, Michael and Kalra, Hina and Al Saffar, Haidar and Keerthikumar, Shivakumar and Ang, Ching-Seng and Adda, Christopher G. and Jiang, Lanzhou and Yap, Kuok and Poon, Ivan K. and Lock, Peter and Bulone, Vincent and Anderson, Marilyn and Mathivanan, Suresh},
  year = {in press}
}

@article{linnemannstons2018,
  title = {Ykt6 Membrane-to-Cytosol Cycling Regulates Exosomal {{Wnt}} Secretion},
  copyright = {\textcopyright{} 2018, Posted by Cold Spring Harbor Laboratory. The copyright holder for this pre-print is the author. All rights reserved. The material may not be redistributed, re-used or adapted without the author's permission.},
  abstract = {{$<$}h3{$>$}Abstract{$<$}/h3{$>$} {$<$}p{$>$}Protein trafficking in the secretory pathway, for example the secretion of Wnt proteins, requires tight regulation. These ligands activate Wnt signaling pathways and are crucially involved in development and disease. Wnt is transported to the plasma membrane by its cargo receptor Evi, where Wnt/Evi complexes are endocytosed and sorted onto exosomes for long-range secretion. However, the trafficking steps within the endosomal compartment are not fully understood. The promiscuous SNARE Ykt6 folds into an auto-inhibiting conformation in the cytosol, but a portion associates with membranes by its farnesylated and palmitoylated C-terminus. Here, we demonstrate that membrane detachment of Ykt6 is essential for exosomal Wnt secretion. We identified conserved phosphorylation sites within the SNARE domain of Ykt6, which block Ykt6 cycling from the membrane to the cytosol. In \emph{Drosophila}, Ykt6 RNAi-mediated block of Wg secretion is rescued by wildtype but not phosphomimicking Ykt6. We show that phosphomimicking Ykt6 accumulates at membranes, while wildtype Ykt6 regulates Wnt trafficking between the plasma membrane and multivesicular bodies in a dose-dependent manner. Taken together, we show that exosomal sorting of Wnts is fine-tuned by a regulatory switch in Ykt6 shifting it from a membrane-bound to cytosolic state at the level of endosomal maturation.{$<$}/p{$>$}},
  language = {en},
  journal = {bioRxiv},
  doi = {10.1101/485565},
  author = {Linnemannst{\"o}ns, Karen and Karuna, Pradhipa and Witte, Leonie and Kittel, Jeanette and Danieli, Adi and M{\"u}ller, Denise and Nitsch, Lena and {Honemann-Capito}, Mona and Grawe, Ferdinand and Wodarz, Andreas and Gross, Julia Christina},
  month = dec,
  year = {2018},
  pages = {485565},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Linnemannstons et al_2018_Ykt6 membrane-to-cytosol cycling.pdf}
}

@article{jedd1997,
  title = {Two {{New Ypt GTPases Are Required}} for {{Exit}} from the {{Yeast}} Trans-{{Golgi Compartment}}},
  volume = {137},
  copyright = {\textcopyright{} 1997 Rockefeller University Press},
  issn = {0021-9525, 1540-8140},
  abstract = {Small GTPases of the Ypt/rab family are involved in the regulation of vesicular transport. These GTPases apparently function during the targeting of vesicles to the acceptor compartment. Two members of the Ypt/rab family, Ypt1p and Sec4p, have been shown to regulate early and late steps of the yeast exocytic pathway, respectively. Here we tested the role of two newly identified GTPases, Ypt31p and Ypt32p. These two proteins share 81\% identity and 90\% similarity, and belong to the same protein subfamily as Ypt1p and Sec4p. Yeast cells can tolerate deletion of either the YPT31 or the YPT32 gene, but not both. These observations suggest that Ypt31p and Ypt32p perform identical or overlapping functions. Cells deleted for the YPT31 gene and carrying a conditional ypt32 mutation exhibit protein transport defects in the late exocytic pathway, but not in vacuolar protein sorting. The ypt31/ 32 mutant secretory defect is clearly downstream from that displayed by a ypt1 mutant and is similar to that of sec4 mutant cells. However, electron microscopy revealed that while sec4 mutant cells accumulate secretory vesicles, ypt31/32 mutant cells accumulate aberrant Golgi structures. The ypt31/32 phenotype is epistatic to that of a sec1 mutant, which accumulates secretory vesicles. Together, these results indicate that the Ypt31/32p GTPases are required for a step that occurs in the transGolgi compartment, between the reactions regulated by Ypt1p and Sec4p. This step might involve budding of vesicles from the trans-Golgi. Alternatively, Ypt31/ 32p might promote secretion indirectly, by allowing fusion of recycling vesicles with the trans-Golgi compartment.},
  language = {en},
  number = {3},
  journal = {The Journal of Cell Biology},
  doi = {10.1083/jcb.137.3.563},
  author = {Jedd, Gregory and Mulholland, Jon and Segev, Nava},
  month = may,
  year = {1997},
  pages = {563-580},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Jedd et al_1997_Two New Ypt GTPases Are Required for.pdf},
  pmid = {9151665}
}

@article{lupashin1997,
  title = {Characterization of a {{Novel Yeast SNARE Protein Implicated}} in {{Golgi Retrograde Traffic}}},
  volume = {8},
  issn = {1059-1524},
  abstract = {The protein trafficking machinery of eukaryotic cells is employed for protein secretion and for the localization of resident proteins of the exocytic and endocytic pathways. Protein transit between organelles is mediated by transport vesicles that bear integral membrane proteins (v-SNAREs) which selectively interact with similar proteins on the target membrane (t-SNAREs), resulting in a docked vesicle. A novelSaccharomyces cerevisiae SNARE protein, which has been termed Vti1p, was identified by its sequence similarity to known SNAREs. Vti1p is a predominantly Golgi-localized 25-kDa type II integral membrane protein that is essential for yeast viability. Vti1p can bind Sec17p (yeast SNAP) and enter into a Sec18p (NSF)-sensitive complex with the cis-Golgi t-SNARE Sed5p. This Sed5p/Vti1p complex is distinct from the previously described Sed5p/Sec22p anterograde vesicle docking complex. Depletion of Vti1p in vivo causes a defect in the transport of the vacuolar protein carboxypeptidase Y through the Golgi. Temperature-sensitive mutants of Vti1p show a similar carboxypeptidase Y trafficking defect, but the secretion of invertase and gp400/hsp150 is not significantly affected. The temperature-sensitive vti1 growth defect can be rescued by the overexpression of the v-SNARE, Ykt6p, which physically interacts with Vti1p. We propose that Vti1p, along with Ykt6p and perhaps Sft1p, acts as a retrograde v-SNARE capable of interacting with the cis-Golgi t-SNARE Sed5p.},
  number = {12},
  journal = {Molecular Biology of the Cell},
  doi = {10.1091/mbc.8.12.2659},
  author = {Lupashin, Vladimir V. and Pokrovskaya, Irina D. and McNew, James A. and Waters, M. Gerard},
  month = dec,
  year = {1997},
  pages = {2659-2676},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Lupashin et al_1997_Characterization of a Novel Yeast SNARE.pdf}
}

@article{mcnew1997,
  title = {Ykt6p, a {{Prenylated SNARE Essential}} for {{Endoplasmic Reticulum}}-{{Golgi Transport}}},
  volume = {272},
  issn = {0021-9258, 1083-351X},
  abstract = {Vesicular transport between secretory compartments requires specific recognition molecules called SNAREs. Here we report the identification of three putative SNAREs, p14 (Sft1p), p28 (Gos1p), and a detailed characterization of p26 (Ykt6p). All three were originally isolated as interacting partners of the cis Golgi target membrane-associated SNARE Sed5p, when Sec18p (yeast NSF) was inactivated. YKT6 is an essential gene that codes for a novel vesicle-associated SNARE functioning at the endoplasmic reticulum-Golgi transport step in the yeast secretory pathway. Depletion of Ykt6p results in the accumulation of the p1 precursor (endoplasmic reticulum form) of the vacuolar enzyme carboxypeptidase Y and morphological abnormalities consistent with a defect in secretion. Membrane localization of Ykt6p is essential for protein function and is normally mediated by isoprenylation. However, replacement of the isoprenylation motif with a bona fide transmembrane anchor results in a functional protein confirming that membrane localization, but not isoprenylation per se, is required for function. Ykt6p and its homologues are highly conserved from yeast to human as demonstrated by the functional complementation of the loss of Ykt6p by its human counterpart. This is the first example of a human SNARE protein functionally replacing a yeast SNARE. This observation implies that the specific details of the vesicle targeting code, like the genetic code, are conserved in evolution.},
  language = {en},
  number = {28},
  journal = {Journal of Biological Chemistry},
  doi = {10.1074/jbc.272.28.17776},
  author = {McNew, James A. and S{\o}gaard, Morten and Lampen, Nina M. and Machida, Sachiko and Ye, R. Ruby and Lacomis, Lynne and Tempst, Paul and Rothman, James E. and S{\"o}llner, Thomas H.},
  month = nov,
  year = {1997},
  pages = {17776-17783},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\McNew et al_1997_Ykt6p, a Prenylated SNARE Essential for.pdf},
  pmid = {9211930}
}

@article{kweon2003,
  title = {Ykt6p {{Is}} a {{Multifunctional Yeast R}}-{{SNARE That Is Required}} for {{Multiple Membrane Transport Pathways}} to the {{Vacuole}}},
  volume = {14},
  issn = {1059-1524},
  abstract = {Intracellular membrane fusion requires that membrane-bound soluble  N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)  proteins on both vesicle and target membranes form a highly specific complex  necessary to bring the membranes close in space. Ykt6p is a yeast R-SNARE  protein that has been implicated in retrograde transport to the  cis-Golgi compartment. Ykt6p has been also been found to fractionate  with vacuole membranes and participate in a vacuolar SNARE complex in  homotypic vacuole fusion. To investigate the role of Ykt6p in membrane traffic  to the vacuole we generated temperature-sensitive mutations in YKT6.  One mutation produces an early Golgi block to secretion, and overexpression of  the SNARE protein Sft1p suppresses the growth and secretion defects of this  mutation. These results are consistent with Ykt6p and Sft1p participating in a  SNARE complex associated with retrograde transport to the cis-Golgi.  A second set of mutations in YKT6 specifically affects post-Golgi  membrane traffic to the vacuole, and the effects of these mutations are not  suppressed by Sft1p overexpression. Defects are seen in carboxypeptidase Y  sorting, alkaline phosphatase transport, and aminopeptidase I delivery, and in  one mutant, overexpression of the SNARE protein Nyv1p suppresses the alkaline  phosphatase transport defect. By mutationally separating early and late  requirements for Ykt6p, our findings have revealed that Ykt6p is a R-SNARE  protein that functions directly in the three biosynthetic pathways to the  vacuole.},
  number = {5},
  journal = {Molecular Biology of the Cell},
  doi = {10.1091/mbc.e02-10-0687},
  author = {Kweon, Youngseok and Rothe, Anca and Conibear, Elizabeth and Stevens, Tom H.},
  month = jan,
  year = {2003},
  pages = {1868-1881},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Kweon et al_2003_Ykt6p Is a Multifunctional Yeast.pdf}
}

@article{perez-hernandez2013,
  title = {The {{Intracellular Interactome}} of {{Tetraspanin}}-Enriched {{Microdomains Reveals Their Function}} as {{Sorting Machineries}} toward {{Exosomes}}},
  volume = {288},
  issn = {0021-9258, 1083-351X},
  abstract = {Extracellular vesicles are emerging as a potent mechanism of intercellular communication because they can systemically exchange genetic and protein material between cells. Tetraspanin molecules are commonly used as protein markers of extracellular vesicles, although their role in the unexplored mechanisms of cargo selection into exosomes has not been addressed. For that purpose, we have characterized the intracellular tetraspanin-enriched microdomain (TEM) interactome by high throughput mass spectrometry, in both human lymphoblasts and their derived exosomes, revealing a clear pattern of interaction networks. Proteins interacting with TEM receptors cytoplasmic regions presented a considerable degree of overlap, although some highly specific CD81 tetraspanin ligands, such as Rac GTPase, were detected. Quantitative proteomics showed that TEM ligands account for a great proportion of the exosome proteome and that a selective repertoire of CD81-associated molecules, including Rac, is not correctly routed to exosomes in cells from CD81-deficient animals. Our data provide evidence that insertion into TEM may be necessary for protein inclusion into the exosome structure.},
  language = {en},
  number = {17},
  journal = {Journal of Biological Chemistry},
  doi = {10.1074/jbc.M112.445304},
  author = {{Perez-Hernandez}, Daniel and {Guti{\'e}rrez-V{\'a}zquez}, Cristina and Jorge, Inmaculada and {L{\'o}pez-Mart{\'i}n}, Soraya and Ursa, Angeles and {S{\'a}nchez-Madrid}, Francisco and V{\'a}zquez, Jes{\'u}s and {Y{\'a}{\~n}ez-M{\'o}}, Mar{\'i}a},
  month = apr,
  year = {2013},
  pages = {11649-11661},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Perez-Hernandez et al_2013_The Intracellular Interactome of.pdf},
  pmid = {23463506}
}

@article{fang2017,
  title = {Clinical Application of a Microfluidic Chip for Immunocapture and Quantification of Circulating Exosomes to Assist Breast Cancer Diagnosis and Molecular Classification},
  volume = {12},
  issn = {1932-6203},
  abstract = {Increasing attention has been attracted by exosomes in blood-based diagnosis because cancer cells release more exosomes in serum than normal cells and these exosomes overexpress a certain number of cancer-related biomarkers. However, capture and biomarker analysis of exosomes for clinical application are technically challenging. In this study, we developed a microfluidic chip for immunocapture and quantification of circulating exosomes from small sample volume and applied this device in clinical study. Circulating EpCAM-positive exosomes were measured in 6 cases breast cancer patients and 3 healthy controls to assist diagnosis. A significant increase in the EpCAM-positive exosome level in these patients was detected, compared to healthy controls. Furthermore, we quantified circulating HER2-positive exosomes in 19 cases of breast cancer patients for molecular classification. We demonstrated that the exosomal HER2 expression levels were almost consistent with that in tumor tissues assessed by immunohistochemical staining. The microfluidic chip might provide a new platform to assist breast cancer diagnosis and molecular classification.},
  language = {en},
  number = {4},
  journal = {PLOS ONE},
  doi = {10.1371/journal.pone.0175050},
  author = {Fang, Shimeng and Tian, Hongzhu and Li, Xiancheng and Jin, Dong and Li, Xiaojie and Kong, Jing and Yang, Chun and Yang, Xuesong and Lu, Yao and Luo, Yong and Lin, Bingcheng and Niu, Weidong and Liu, Tingjiao},
  month = apr,
  year = {2017},
  pages = {e0175050},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Fang et al_2017_Clinical application of a microfluidic.pdf}
}

@article{sina2016,
  title = {Real Time and Label Free Profiling of Clinically Relevant Exosomes},
  volume = {6},
  copyright = {2016 Nature Publishing Group},
  issn = {2045-2322},
  abstract = {Tumor-derived exosomes possess significant clinical relevance due to their unique composition of genetic and protein material that is representative of the parent tumor. Specific isolation as well as identification of proportions of these clinically relevant exosomes (CREs) from biological samples could help to better understand their clinical significance as cancer biomarkers. Herein, we present a simple approach for quantification of the proportion of CREs within the bulk exosome population isolated from patient serum. This proportion of CREs can potentially inform on the disease stage and enable non-invasive monitoring of inter-individual variations in tumor-receptor expression levels. Our approach utilises a Surface Plasmon Resonance (SPR) platform to quantify the proportion of CREs in a two-step strategy that involves (i) initial isolation of bulk exosome population using tetraspanin biomarkers (i.e., CD9, CD63), and (ii) subsequent detection of CREs within the captured bulk exosomes using tumor-specific markers (e.g., human epidermal growth factor receptor 2 (HER2)). We demonstrate the isolation of bulk exosome population and detection of as low as 10\% HER2(+) exosomes from samples containing designated proportions of HER2(+) BT474 and HER2(-) MDA-MB-231 cell derived exosomes. We also demonstrate the successful isolation of exosomes from a small cohort of breast cancer patient samples and identified that approximately 14\textendash{}35\% of their bulk population express HER2.},
  language = {en},
  journal = {Scientific Reports},
  doi = {10.1038/srep30460},
  author = {Sina, Abu Ali Ibn and Vaidyanathan, Ramanathan and Dey, Shuvashis and Carrascosa, Laura G. and Shiddiky, Muhammad J. A. and Trau, Matt},
  month = jul,
  year = {2016},
  pages = {30460},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Sina et al_2016_Real time and label free profiling of.pdf}
}

@article{hildonen2016,
  title = {Isolation and Mass Spectrometry Analysis of Urinary Extraexosomal Proteins},
  volume = {6},
  copyright = {2016 Nature Publishing Group},
  issn = {2045-2322},
  abstract = {The aim of the present study was to develop a LC-MS/MS-based proteomic analysis method of urinary exosomal proteins that has the potential to discover disease biomarkers. In short, urinary exosomes from healthy subjects were isolated by immunocapture on magnetic beads, detected by immunofluorescence and TEM, trypsin digested directly on the beads for an accelerated time with no addition of detergents before performing an LC-MS analysis of the trypsinate. To our knowledge, this is the first proteomic analysis of proteins displayed on the outer surface of exosomes. The outer exosome proteome may contain proteins that are of higher biomarker value compared to soluble cargo protein as the proteins projecting into the extracellular milieu might be more directly involved in physiological functions of exosomes. The proteomic analysis identified 49 proteins that were considered significant; the majority is involved in carbohydrate and lipid metabolism or in immune responses. Thirty of the proteins are linked to diseases. The developed proteomic method exploiting urinary exosomes might be of great value in search for diagnostic or prognostic biomarkers of especially metabolic and immune-related diseases.},
  language = {en},
  journal = {Scientific Reports},
  doi = {10.1038/srep36331},
  author = {Hildonen, Siri and Skarpen, Ellen and Halvorsen, Trine Gr{\o}nhaug and Reubsaet, L{\'e}on},
  month = nov,
  year = {2016},
  pages = {36331},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Hildonen et al_2016_Isolation and mass spectrometry.pdf}
}

@article{yu2015,
  title = {Candida Albicans Autophagy, No Longer a Bystander: {{Its}} Role in Tolerance to {{ER}} Stress-Related Antifungal Drugs},
  volume = {81},
  issn = {1087-1845},
  shorttitle = {Candida Albicans Autophagy, No Longer a Bystander},
  abstract = {Autophagy is a degradation process involved in pathogenicity of many pathogenic fungi. However, its roles in Candida albicans, the leading fungal pathogen in human beings, remain to be detailed. Most recently, we found that endoplasmic reticulum (ER) stress-inducing conditions led to transcriptional up-regulation of C. albicans autophagy-related (ATG) genes, implying a possible link between autophagy and ER stress response in this pathogen. Using a series of C. albicans ATG mutants and autophagy reporting systems, we found that both treatment of ER stress-related drugs and loss of the ER calcium pump Spf1 promoted autophagic flux of Atg8 and Lap41 (a homologue of Saccharomyces cerevisiae Ape1), indicating that these conditions induce autophagy. Moreover, deletion of ATG genes in the spf1{$\Delta$}/{$\Delta$} mutant rendered cells hypersensitive to these drugs and caused activation of UPR, revealing a role of autophagy in alleviating ER stress. In addition, only treatment of tunicamycin and loss of Spf1 in combination increased autophagic flux of the ER component Sec63, suggesting that most of the ER stress-related conditions cause non-selective autophagy rather than selective ER phagy. This study uncovers the important role of C. albicans autophagy in ER stress response and tolerance to antifungal drugs.},
  journal = {Fungal Genetics and Biology},
  doi = {10.1016/j.fgb.2015.02.008},
  author = {Yu, Qilin and Jia, Chang and Dong, Yijie and Zhang, Bing and Xiao, Chenpeng and Chen, Yulu and Wang, Yuzhou and Li, Xiaoling and Wang, Lei and Zhang, Biao and Li, Mingchun},
  month = aug,
  year = {2015},
  pages = {238-249},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Yu et al_2015_Candida albicans autophagy, no longer a.pdf}
}

@article{saporito-irwin1995,
  title = {{{PHR1}}, a {{pH}}-Regulated Gene of {{Candida}} Albicans, Is Required for Morphogenesis.},
  volume = {15},
  issn = {0270-7306, 1098-5549},
  abstract = {Candida albicans, like many fungi, exhibits morphological plasticity, a property which may be related to its biological capacity as an opportunistic pathogen of humans. Morphogenesis and alterations in cell shape require integration of many cellular functions and occur in response to environmental signals, most notably pH and temperature in the case of C. albicans. In the course of our studies of differential gene expression associated with dimorphism of C. albicans, we have isolated a gene, designated PHR1, which is regulated in response to the pH of the culture medium. PHR1 expression was repressed at pH values below 5.5 and induced at more alkaline pH. The predicted amino acid sequence of the PHR1 protein was 56\% identical to that of the Saccharomyces cerevisiae Ggp1/Gas1 protein, a highly glycosylated cell surface protein attached to the membrane via glycosylphosphatidylinositol. A homozygous null mutant of PHR1 was constructed and found to exhibit a pH-conditional morphological defect. At alkaline pH, the mutant, unlike the parental type, was unable to conduct apical growth of either yeast or hyphal growth forms. This morphological aberration was not associated with defective cytoskeletal polarization or secretion. The results suggest that PHR1 defines a novel function required for apical cell growth and morphogenesis.},
  language = {en},
  number = {2},
  journal = {Molecular and Cellular Biology},
  doi = {10.1128/MCB.15.2.601},
  author = {{Saporito-Irwin}, S. M. and Birse, C. E. and Sypherd, P. S. and Fonzi, W. A.},
  month = feb,
  year = {1995},
  pages = {601-613},
  file = {C:\\Users\\charl\\OneDrive\\zotero\\Saporito-Irwin et al_1995_PHR1, a pH-regulated gene of Candida.pdf},
  pmid = {7823929}
}

@article{obrien2013,
  title = {Exosomes from Triple-Negative Breast Cancer Cells Can Transfer Phenotypic Traits Representing Their Cells of Origin to Secondary Cells},
  volume = {49},
  issn = {0959-8049},
  abstract = {Background
Triple-negative breast cancer (TNBC) accounts for 15\textendash{}20\% of breast cancers but is responsible for a disproportionate number of deaths. We investigated the relevance, in TNBC, of nano-sized exosomes expelled from cells. Specifically, we compared effects of exosomes derived from the claudin-low TNBC cell line Hs578T and its more invasive Hs578Ts(i)8 variant, as well as exosomes from TNBC patient sera compared to normal sera.
Methods
Exosomes were isolated from conditioned media (CM) of Hs578T and Hs578Ts(i)8 cells and from sera by filtration and ultracentrifugation. Successful isolation was confirmed by transmission electron microscopy and immunoblotting. Subsequent analysis, of secondary/recipient cells in response to exosomes, included proliferation; motility/migration; invasion; anoikis assays and endothelial tubule formation assays.
Results
Hs578Ts(i)8-exosomes versus Hs578T-exosomes significantly increased the proliferation, migration and invasion capacity of all three recipient cell lines evaluated i.e. SKBR3, MDA-MB-231 and HCC1954. Exosomes from Hs578Ts(i)8 cells also conferred increased invasiveness to parent Hs578T cells. Hs578Ts(i)8-exosomes increased sensitivity of SKBR3, MDA-MB-231 and HCC1954 to anoikis when compared to the effects of Hs578T-exosomes reflecting the fact that Hs578Ts(i)8 cells are themselves innately more sensitive to anoikis. In relation to vasculogenesis and subsequent angiogenesis, Hs578Ts(i)8-exosomes versus Hs578T-exosomes stimulated significantly more endothelial tubules formation. Finally, our pilot translational study showed that exosomes from TNBC patients' sera significantly increased recipient cells' invasion when compared to those derived from age- and gender-matched healthy control sera.
Conclusion
This study supports the hypothesis that TNBC exosomes may be involved in cancer cell-to-cell communication, conferring phenotypic traits to secondary cells that reflect those of their cells of origin.},
  number = {8},
  journal = {European Journal of Cancer},
  doi = {10.1016/j.ejca.

license: MIT

license_type: permissive

branch_name: refs/heads/master

extension: bib