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3. The complete DNA sequence of yeast chromosome III

Author

Oliver, S.G., van der Aart, Q.J.M., Agostoni-Carbone, M.L., Aigle, M., Alberghina, L., Alexandraki, D., Antoine, G., Anwar, R., Ballesta, J.P.G., Benit, P., Berben, G., Bergantino, E., Biteau, N., Bolle, P.A., Bolotin-Fukuhara, M., Brown, A., Brown, A.J.P., Buhler, J.M., Carcano, C., Carignani, G., Cederberg, H., Chanet, R., Contreras, R., Crouzet, M., Daignan-Fornier, B., Defoor, E., Delgado, M., Demolder, J., Doira, C., Dubois, E., Dujon, B., Dusterhoft, A., Erdmann, D., Esteban, M., Fabre, F., Fairhead, C., Faye, G., Feldmann, H., Fiers, W., Francingues-Gaillard, M.C., Franco, L., Frontali, L., Fukuhara, H., Fuller, L.J., Galland, P., Gent, M.E., Gigot, D., Gilliquet, V., Glansdorff, N., Goffeau, A., Grenson, M., Grisanti, P., Grivell, L.A., de Haan, M., Haasemann, M., Hatat, D., Hoenicka, J., Hegemann, J., Herbert, C.J., Hilger, F., Hohmann, S., Hollenberg, C.P., Huse, K., Iborra, F., Indge, K.J., Isono, K., Jacq, C., Jacquet, M., James, C.M., Jauniaux, J.C., Jia, Y., Jimenez, A., Kelly, A., Kleinhans, U., Kreisl, P., Lanfranchi, G., Lewis, C., van der Linden, C.G., Lucchini, G., Lutzenkirchen, K., Maat, M.J., Mallet, L., Mannhaupt, G., Martegani, E., Mathieu, A., Maurer, C.T.C., McConnell, D., McKee, R.A., Messenguy, F., Mewes, H.W., Molemans, F., Montague, M.A., Muzi Falconi, M., Navas, L., Newlon, C.S., Noone, D., Pallier, C., Panzeri, L., Pearson, B.M., Perea, J., Philippsen, P., Pierard, A., Planta, R.J., Plevani, P., Poetsch, B., Pohl, F., Purnelle, B., Ramezani Rad, M., Rasmussen, S.W., Raynal, A., Remacha, M., Richterich, P., Roberts, A.B., Rodriguez, F., Sanz, E., Schaaff-Gerstenschlager, I., Scherens, B., Schweitzer, B., Shu, Y., Skala, J., Slonimski, P.P., Sor, F., Soustelle, C., Spiegelberg, R., Stateva, L.I., Steensma, H.Y., Steiner, S., Thierry, A., Thireos, G., Tzermia, M., Urrestarazu, L.A., Valle, G., Vetter, I., van Vliet-Reedijk, J.C., Voet, M., Volckaert, G., Vreken, P., Wang, H., Warmington, J.R., von Wettstein, D., Wicksteed, B.L., Wilson, C., Wurst, H., Xu, G., Yoshikawa, A., Zimmermann, F.K., and Sgouros, J.G.

Subjects
Saccharomyces -- Genetic aspects, Nucleotide sequence -- Research, Plant chromosomes -- Research, Genomes -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Published
1992

4. The Yeast Genome Directory

Author

Goffeau, A., Aert, R., Agostini-Carbone, M. L., Ahmed, A., Aigle, M., Alberghina, L., Albermann, K., Albers, M., Aldea, M., Alexandraki, D., Aljinovic, G., Allen, E., Alt-Mörbe, J., André, B., Andrews, S., Ansorge, W., Antoine, G., Anwar, R., Aparicio, A., Araujo, R., Arino, J., Arnold, F., Arroyo, J., Aviles, E., Backes, U., Baclet, M. C., Badcock, K., Bahr, A., Baladron, V., Ballesta, J. P. G., Bankier, A. T., Banrevi, A., Bargues, M., Baron, L., Barreiros, T., Barrell, B. G., Barthe, C., Barton, A. B., Baur, A., Bécam, A.-M., Becker, A., Becker, I., Beinhauer, J., Benes, V., Benit, P., Berben, G., Bergantino, E., Bergez, P., Berno, A., Bertani, I., Biteau, N., Bjourson, A. J., Blöcker, H., Blugeon, C., Bohn, C., Boles, E., Bolle, P. A., Bolotin-Fukuhara, M., Bordonné, R., Boskovic, J., Bossier, P., Botstein, D., Bou, G., Bowman, S., Boyer, J., Brandt, P., Brandt, T., Brendel, M., Brennan, T., Brinkman, R., Brown, A., Brown, A. J. P., Brown, D., Brückner, M., Bruschi, C. V., Buhler, J. M., Buitrago, M. J., Bussereau, F., Bussey, H., Camasses, A., Carcano, C., Carignani, G., Carpenter, J., Casamayor, A., Casas, C., Castagnoli, L., Cederberg, H., Cerdan, E., Chalwatzis, N., Chanet, R., Chen, E., Chéret, G., Cherry, J. M., Chillingworth, T., Christiansen, C., Chuat, J.-C., Chung, E., Churcher, C., Churcher, C. M., Clark, M. W., Clemente, M. L., Coblenz, A., Coglievina, M., Coissac, E., Colleaux, L., Connor, R., Contreras, R., Cooper, J., Copsey, T., Coster, F., Coster, R., Couch, J., Crouzet, M., Cziepluch, C., Daignan-Fornier, B., Dal Paro, F., Dang, D. V., D’Angelo, M., Davies, C. J., Davis, K., Davis, R. W., De Antoni, A., Dear, S., Dedman, K., Defoor, E., De Haan, M., Delaveau, Th., Del Bino, S., Delgado, M., Delius, H., Delneri, D., Del Rey, F., Demolder, J., Démolis, N., Devlin, K., de Wergifosse, P., Dietrich, F. S., Ding, H., Dion, C., Dipaolo, T., Doignon, F., Doira, C., Domdey, H., Dover, J., Du, Z., Dubois, E., Dujon, B., Duncan, M., Durand, P., Düsterhöft, A., Düsterhus, S., Eki, T., El Bakkoury, M., Eide, L. G., Entian, K.-D., Eraso, P., Erdmann, D., Erfle, H., Escribano, V., Esteban, M., Fabiani, L., Fabre, F., Fairhead, C., Fartmann, B., Favello, A., Faye, G., Feldmann, H., Fernandes, L., Feroli, F., Feuermann, M., Fiedler, T., Fiers, W., Fleig, U. N., Flöth, M., Fobo, G. M., Fortin, N., Foury, F., Francingues-Gaillard, M. C., Franco, L., Fraser, A., Friesen, J.D., Fritz, C., Frontali, L., Fukuhara, H., Fulton, L., Fuller, L. J., Gabel, C., Gaillardin, C., Gaillon, L., Galibert, F., Galisson, F., Galland, P., Gamo, F.-J., Gancedo, C., Garcia-Cantalejo, J. M., García-Gonzalez, M. I., Garcia-Ramirez, J. J., García-Saéz, M., Gassenhuber, H., Gatius, M., Gattung, S., Geisel, C., Gent, M. E., Gentles, S., Ghazvini, M., Gigot, D., Gilliquet, V., Glansdorff, N., Gómez-Peris, A., Gonzaléz, A., Goulding, S. E., Granotier, C., Greco, T., Grenson, M., Grisanti, P., Grivell, L. A., Grothues, D., Gueldener, U., Guerreiro, P., Guzman, E., Haasemann, M., Habbig, B., Hagiwara, H., Hall, J., Hallsworth, K., Hamlin, N., Hand, N. J., Hanemann, V., Hani, J., Hankeln, T., Hansen, M., Harris, D., Harris, D. E., Hartzell, G., Hatat, D., Hattenhorst, U., Hawkins, J., Hebling, U., Hegemann, J., Hein, C., Hennemann, A., Hennessy, K., Herbert, C. J., Hernandez, K., Hernando, Y., Herrero, E., Heumann, K., Heuss- Neitzel, D., Hewitt, N., Hiesel, R., Hilbert, H., Hilger, F., Hillier, L., Ho, C., Hoenicka, J., Hofmann, B., Hoheisel, J., Hohmann, S., Hollenberg, C. P., Holmstrøm, K., Horaitis, O., Horsnell, T. S., Huang, M.-E., Hughes, B., Hunicke-Smith, S., Hunt, S., Hunt, S. E., Huse, K., Hyman, R. W., Iborra, F., Indge, K. J., Iraqui Houssaini, I., Isono, K., Jacq, C., Jacquet, M., Jacquier, A., Jagels, K., Jäger, W., James, C. M., Jauniaux, J. C., Jia, Y., Jier, M., Jimenez, A., Johnson, D., Johnston, L., Johnston, M., Jones, M., Jonniaux, J.-L., Kaback, D. B., Kallesøe, T., Kalman, S., Kalogeropoulos, A., Karpfinger-Hartl, L., Kashkari, D., Katsoulou, C., Kayser, A., Kelly, A., Keng, T., Keuchel, H., Kiesau, P., Kirchrath, L., Kirsten, J., Kleine, K., Kleinhans, U., Klima, R., Komp, C., Kordes, E., Korol, S., Kötter, P., Krämer, C., Kramer, B., Kreisl, P., Kucaba, T., Kuester, H., Kurdi, O., Laamanen, P., Lafuente, M. J., Landt, O., Lanfranchi, G., Langston, Y., Lashkari, D., Latreille, P., Lauquin, G., Le, T., Legrain, P., Legros, Y., Lepingle, A., Lesveque, H., Leuther, H., Lew, H., Lewis, C., Li, Z. Y., Liebl, S., Lin, A., Lin, D., Logghe, M., Lohan, A. J. E., Louis, E. J., Lucchini, G., Lutzenkirchen, K., Lyck, R., Lye, G., Maarse, A. C., Maat, M. J., Macri, C., Madania, A., Maftahi, M., Maia e Silva, A., Maillier, E., Mallet, L., Mannhaupt, G., Manus, V., Marathe, R., Marck, C., Marconi, A., Mardis, E., Martegani, E., Martin, R., Mathieu, A., Maurer, C. T. C., Mazón, M. J., Mazzoni, C., McConnell, D., McDonald, S., McKee, R. A., McReynolds, A. D. K., Melchioretto, P., Menezes, S., Messenguy, F., Mewes, H. W., Michaux, G., Miller, N., Minenkova, O., Miosga, T., Mirtipati, S., Möller-Rieker, S., Möstl, D., Molemans, F., Monnet, A., Monnier, A-L., Montague, M. A., Moro, M., Mosedale, D., Möstl, D., Moule, S., Mouser, L., Murakami, Y., Müller-Auer, S., Mulligan, J., Murphy, L., Muzi Falconi, M., Naitou, M., Nakahara, K., Namath, A., Nasr, F., Navas, L., Nawrocki, A., Nelson, J., Nentwich, U., Netter, P., Neu, R., Newlon, C. S., Nhan, M., Nicaud, J.-M., Niedenthal, R. K., Nombela, C., Noone, D., Norgren, R., Nußbaumer, B., Obermaier, B., Odell, C., Öfner, P., Oh, C., Oliver, K., Oliver, S. G., Ouellette, B. F., Ozawa, M., Paces, V., Pallier, C., Pandolfo, D., Panzeri, L., Paoluzi, S., Parle-Mcdermott, A. G., Pascolo, S., Patricio, N., Pauley, A., Paulin, L., Pearson, B. M., Pearson, D., Peluso, D., Perea, J., Pérez-Alonso, M., Pérez-Ortin, J. E., Perrin, A., Petel, F. X., Pettersson, B., Pfeiffer, F., Philippsen, P., Piérard, A., Piravandi, E., Planta, R. J., Plevani, P., Poch, O., Poetsch, B., Pohl, F. M., Pohl, T. M., Pöhlmann, R., Poirey, R., Portetelle, D., Portillo, F., Potier, S., Proft, M., Prydz, H., Pujol, A., Purnelle, B., Puzos, V., Rajandream, M. A., Ramezani Rad, M., Rasmussen, S. W., Raynal, A., Rechmann, S., Remacha, M., Revuelta, J. L., Rice, P., Richard, G-F., Richterich, P., Rieger, M., Rifken, L., Riles, L., Rinaldi, T., Rinke, M., Roberts, A. B., Roberts, D., Rodriguez, F., Rodriguez-Belmonte, E., Rodriguez-Pousada, C., Rodriguez-Torres, A. M., Rose, M., Rossau, R., Rowley, N., Rupp, T., Ruzzi, M., Saeger, W., Saiz, J. E., Saliola, M., Salom, D., Saluz, H. P., Sánchez-Perez, M., Santos, M. A., Sanz, E., Sanz, J. E., Saren, A.-M., Sartorello, F., Sasanuma, M., Sasanuma, S-I., Scarcez, T., Schaaf-Gerstenschläger, I., Schäfer, B., Schäfer, M., Scharfe, M., Scherens, B., Schroff, N., Sen-Gupta, M., Shibata, T., Schmidheini, T., Schmidt, E. R., Schneider, C., Scholler, P., Schramm, S., Schreer, A., Schröder, M., Schwager, C., Schwarz, S., Schwarzlose, C., Schweitzer, B., Schweizer, M., Sdicu, A-M., Sehl, P., Sensen, C., Sgouros, J. G., Shogren, T., Shore, L., Shu, Y., Skala, J., Skelton, J., Slonimski, P. P., Smit, P. H. M., Smith, V., Soares, H., Soeda, E., Soler-Mira, A., Sor, F., Soriano, N., Souciet, J. L., Soustelle, C., Spiegelberg, R., Stateva, L. I., Steensma, H. Y., Stegemann, J., Steiner, S., Stellyes, L., Sterky, F., Storms, R. K., St. Peter, H., Stucka, R., Taich, A., Talla, E., Tarassov, I., Tashiro, H., Taylor, P., Teodoru, C., Tettelin, H., Thierry, A., Thireos, G., Tobiasch, E., Tovan, D., Trevaskis, E., Tsuchiya, Y., Tzermia, M., Uhlen, M., Underwood, A., Unseld, M., Urbanus, J. H. M., Urrestarazu, A., Ushinsky, S., Valens, M., Valle, G., Van Broekhoven, A., Vandenbol, M., Van Der Aart, Q. J. M., Van Der Linden, C. G., Van Dyck, L., Vanoni, M., Van Vliet-Reedijk, J. C., Vassarotti, A., Vaudin, M., Vaughan, K., Verhasselt, P., Vetter, I., Vierendeels, F., Vignati, D., Vilela, C., Vissers, S., Vleck, C., Vo, D. T., Vo, D. H., Voet, M., Volckaert, G., Von Wettstein, D., Voss, H., Vreken, P., Wagner, G., Walsh, S. V., Wambutt, R., Wang, H., Wang, Y., Warmington, J. R., Waterston, R., Watson, M. D., Weber, N., Wedler, E., Wedler, H., Wei, Y., Whitehead, S., Wicksteed, B. L., Wiemann, S., Wilcox, L., Wilson, C., Wilson, R., Winant, A., Winnett, E., Winsor, B., Wipfli, P., Wölfl, S., Wohldman, P., Wolf, K., Wolfe, K. H., Wright, L. F., Wurst, H., Xu, G., Yamasaki, M., Yelton, M. A., Yokohama, K., Yoshikawa, A., Yuping, S., Zaccaria, P., Zagulski, M., Zimmermann, F. K., Zimmermann, J., Zimmermann, M., Zhong, W-W., Zollner, A., and Zumstein, E.

Published
1997
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5. [In Process Citation]

Author

Atanasova, R., Tefit, M., Guitard, J., Fairhead, C., Mazier, D., Hennequin, C., Institut de génétique et microbiologie [Orsay] (IGM), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2013
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7. The complete genome of Blastobotrys (Arxula) adeninivorans LS3 - A yeast of biotechnological interest

Author

UCL - SST/ELI/ELIA - Agronomy, Kunze, G., Gaillardin, C., Czernicka, M., Durrens, P., Martin, T., Böer, E., Gabaldón, T., Cruz, J.A., Talla, E., Marck, C., Goffeau, A., Barbe, V., Baret, Philippe, Baronian, K., Beier, S., Bleykasten, C., Bode, R., Casaregola, S., Despons, L., Fairhead, C., Giersberg, M., Gierski, P.P., Hähnel, U., Hartmann, A., Jankowska, D., Jubin, C., Jung, P., Lafontaine, I., Leh-Louis, V., Lemaire, M., Marcet-Houben, M., Mascher, M., Morel, G., Richard, G.-F., Riechen, J., Sacerdot, C., Sarkar, A., Savel, G., Schacherer, J., Sherman, D.J., Stein, N., Straub, M.-L., Thierry, A., Trautwein-Schult, A., Vacherie, B., Westhof, E., Worch, S., Dujon, B., Souciet, J.-L., Wincker, P., Scholz, U., Neuvéglise, C., UCL - SST/ELI/ELIA - Agronomy, Kunze, G., Gaillardin, C., Czernicka, M., Durrens, P., Martin, T., Böer, E., Gabaldón, T., Cruz, J.A., Talla, E., Marck, C., Goffeau, A., Barbe, V., Baret, Philippe, Baronian, K., Beier, S., Bleykasten, C., Bode, R., Casaregola, S., Despons, L., Fairhead, C., Giersberg, M., Gierski, P.P., Hähnel, U., Hartmann, A., Jankowska, D., Jubin, C., Jung, P., Lafontaine, I., Leh-Louis, V., Lemaire, M., Marcet-Houben, M., Mascher, M., Morel, G., Richard, G.-F., Riechen, J., Sacerdot, C., Sarkar, A., Savel, G., Schacherer, J., Sherman, D.J., Stein, N., Straub, M.-L., Thierry, A., Trautwein-Schult, A., Vacherie, B., Westhof, E., Worch, S., Dujon, B., Souciet, J.-L., Wincker, P., Scholz, U., and Neuvéglise, C.

Abstract

Background: The industrially important yeast Blastobotrys (Arxula) adeninivorans is an asexual hemiascomycete phylogenetically very distant from Saccharomyces cerevisiae. Its unusual metabolic flexibility allows it to use a wide range of carbon and nitrogen sources, while being thermotolerant, xerotolerant and osmotolerant. Results: The sequencing of strain LS3 revealed that the nuclear genome of A. adeninivorans is 11.8 Mb long and consists of four chromosomes with regional centromeres. Its closest sequenced relative is Yarrowia lipolytica, although mean conservation of orthologs is low. With 914 introns within 6116 genes, A. adeninivorans is one of the most intron-rich hemiascomycetes sequenced to date. Several large species-specific families appear to result from multiple rounds of segmental duplications of tandem gene arrays, a novel mechanism not yet described in yeasts. An analysis of the genome and its transcriptome revealed enzymes with biotechnological potential, such as two extracellular tannases (Atan1p and Atan2p) of the tannic-acid catabolic route, and a new pathway for the assimilation of n-butanol via butyric aldehyde and butyric acid. Conclusions: The high-quality genome of this species that diverged early in Saccharomycotina will allow further fundamental studies on comparative genomics, evolution and phylogenetics. Protein components of different pathways for carbon and nitrogen source utilization were identified, which so far has remained unexplored in yeast, offering clues for further biotechnological developments. In the course of identifying alternative microorganisms for biotechnological interest, A. adeninivorans has already proved its strengthened competitiveness as a promising cell factory for many more applications. © 2014 Kunze et al.; licensee BioMed Central Ltd.

Published
2014

9. Androgen Receptor Copy Number Variation and Androgenetic Alopecia: A Case-Control Study

Author

Fairhead, C, Cobb, JE, White, SJ, Harrap, SB, Ellis, JA, Fairhead, C, Cobb, JE, White, SJ, Harrap, SB, and Ellis, JA

Abstract

BACKGROUND: The functional polymorphism that explains the established association of the androgen receptor (AR) with androgenetic alopecia (AGA) remains unidentified, but Copy Number Variation (CNV) might be relevant. CNV involves changes in copy number of large segments of DNA, leading to the altered dosage of gene regulators or genes themselves. Two recent reports indicate regions of CNV in and around AR, and these have not been studied in relation to AGA. The aim of this preliminary case-control study was to determine if AR CNV is associated with AGA, with the hypothesis that CNV is the functional AR variant contributing to this condition. METHODOLOGY/PRINCIPAL FINDINGS: Multiplex Ligation-dependent Probe Amplification was used to screen for CNV in five AR exons and a conserved, non-coding region upstream of AR in 85 men carefully selected as cases and controls for maximal phenotypic contrast. There was no evidence of CNV in AR in any of the cases or controls, and thus no evidence of significant association between AGA and AR CNV. CONCLUSIONS/SIGNIFICANCE: The results suggest this form of genomic variation at the AR locus is unlikely to predispose to AGA.

Published
2009

11. Cell cycle genes are the evolutionarily conserved targets of the E2F4 transcription factor.

Author

Fairhead, C, Conboy, CM, Spyrou, C, Thorne, NP, Wade, EJ, Barbosa-Morais, NL, Wilson, MD, Bhattacharjee, A, Young, RA, Tavaré, S, Lees, JA, Odom, DT, Fairhead, C, Conboy, CM, Spyrou, C, Thorne, NP, Wade, EJ, Barbosa-Morais, NL, Wilson, MD, Bhattacharjee, A, Young, RA, Tavaré, S, Lees, JA, and Odom, DT

Abstract

Maintaining quiescent cells in G0 phase is achieved in part through the multiprotein subunit complex known as DREAM, and in human cell lines the transcription factor E2F4 directs this complex to its cell cycle targets. We found that E2F4 binds a highly overlapping set of human genes among three diverse primary tissues and an asynchronous cell line, which suggests that tissue-specific binding partners and chromatin structure have minimal influence on E2F4 targeting. To investigate the conservation of these transcription factor binding events, we identified the mouse genes bound by E2f4 in seven primary mouse tissues and a cell line. E2f4 bound a set of mouse genes that was common among mouse tissues, but largely distinct from the genes bound in human. The evolutionarily conserved set of E2F4 bound genes is highly enriched for functionally relevant regulatory interactions important for maintaining cellular quiescence. In contrast, we found minimal mRNA expression perturbations in this core set of E2f4 bound genes in the liver, kidney, and testes of E2f4 null mice. Thus, the regulatory mechanisms maintaining quiescence are robust even to complete loss of conserved transcription factor binding events.

Published
2007

12. The nucleotide sequence of Saccharomyces cerevisiae chromosome XV

Author

Dujon B, Albermann K, Aldea M, Alexandraki D, Ansorge W, Arino J, Vladimir Benes, Bohn C, Bolotin-Fukuhara M, Bordonné R, Boyer J, Camasses A, Casamayor A, Casas C, Chéret G, Cziepluch C, Daignan-Fornier B, Dv, Dang, de Haan M, Delius H, Durand P, Fairhead C, Feldmann H, Gaillon L, and Kleine K

Subjects
Open Reading Frames, Base Sequence, Saccharomyces cerevisiae, Chromosomes, Fungal, DNA, Fungal
Abstract

Chromosome XV was one of the last two chromosomes of Saccharomyces cerevisiae to be discovered. It is the third-largest yeast chromosome after chromosomes XII and IV, and is very similar in size to chromosome VII. It alone represents 9% of the yeast genome (8% if ribosomal DNA is included). When systematic sequencing of chromosome XV was started, 93 genes or markers were identified, and most of them were mapped. However, very little else was known about chromosome XV which, in contrast to shorter chromosomes, had not been the object of comprehensive genetic or molecular analysis. It was therefore decided to start sequencing chromosome XV only in the third phase of the European Yeast Genome Sequencing Programme, after experience was gained on chromosomes III, XI and II. The sequence of chromosome XV has been determined from a set of partly overlapping cosmid clones derived from a unique yeast strain, and physically mapped at 3.3-kilobase resolution before sequencing. As well as numerous new open reading frames (ORFs) and genes encoding tRNA or small RNA molecules, the sequence of 1,091,283 base pairs confirms the high proportion of orphan genes and reveals a number of ancestral and successive duplications with other yeast chromosomes.

Published
1997

14. Multilocus Microsatellite Markers for Molecular Typing of Candida glabrata : Application to Analysis of Genetic Relationships between Bloodstream and Digestive System Isolates

Author

Enache-Angoulvant, A., primary, Bourget, M., additional, Brisse, S., additional, Stockman-Pannier, C., additional, Diancourt, L., additional, François, N., additional, Rimek, D., additional, Fairhead, C., additional, Poulain, Daniel, additional, and Hennequin, C., additional

Published
2010
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15. The complete sequence of the yeast chromosome III

Author

Oliver, S. G., van der Aart, Q. J. M., Agostoni Carbone, M. L., Aigle, M., Alberghina, L., Alexandraki, D., Antoine, G., Anwar, R., Ballesta, J. P. G., Benit, P., Berben, G., Bergantino, Elisabetta, Biteau, N., Bolle, P. A., Bolotin Fukuhara, M., Brown, A., Brown, A. J. P., Buhler, J. M., Carcano, C., Carignani, G., Cederberg, H., Chanet, R., Contreras, R., Crouzet, M., Daignan Fornier, B., Defoor, E., Delgado, M., Demolder, J., Doira, C., Dubois, E., Dujon, B., Dusterhoft, A., Erdmann, D., Esteban, M., Fabre, F., Fairhead, C., Faye, G., Feldmann, H., Fiers, W., Francingues Gaillard, M. C., Franco, L., Frontali, L., Fukuhara, H., Fuller, L. J., Galland, P., Gent, M. E., Gigot, D., Gilliquet, V., Glansdorff, N., Goffeau, A., Grenson, M., Grisanti, P., Grivell, L. A., de Haan, M., Haasemann, M., Hatat, D., Hoenicka, J., Hegemann, J., Herbert, C. J., Hilger, F., Hohmann, S., Hollenberg, C. P., Huse, K., Iborra, F., Indje, K. J., Isono, K., Jacq, C., Jacquet, M., James, C. M., Jauniaux, J. C., Jia, Y., Jimenez, A., Kelly, A., Kleinhans, U., Kreisl, P., Lanfranchi, Gerolamo, Lewis, C, Vanderlinden, C. G., Lucchini, G., Lutzenkirchen, K, Maat, M. J., Mallet, L., Mannhaupet, G., Martegani, E., Mathieu, A., Maurer, C. T. C., Mcconnell, D., Mckee, R. A., Messenguy, F., Mewes, H. W., Molemans, F., Montague, M. A., Muzi Falconi, M., Navas, L., Newlon, C. S., Noone, D., Pallier, C., Panzeri, L., Pearson, B. M., Perea, J., Philippsen, P., Pierard, A., Planta, R. J., Plevani, P., Poetsch, B., Pohl, F., Purnelle, B., Ramezani Rad, M., Rasmussen, S. W., Raynal, A., Remacha, M., Richterich, P., Roberts, A. B., Rodriguez, F., Sanz, E., Schaaff Gerstenschlager, I., Scherens, B., Schweitzer, B., Shu, Y., Skala, J., Slonimski, P. P., Sor, F., Soustelle, C., Spiegelberg, R., Stateva, L. I., Steensma, S., Steiner, H. Y., Thierry, A., Thireos, G., Tzermia, M., Urrestarazu, L. A., Valle, Giorgio, Vetter, I., van Vliet Reedijk, J. C., Voet, M., Volckaert, G., Vreken, P., Wang, H., Warmington, J. R., von Wettstein, D., Wicksteed, B. L., Wilson, C., Wurst, H., Xu, G., Yoshikawa, A., Zimmermann, F. K., and Sgouros, J. G.

Published
1992

17. Mass-murdering: deletion of twenty-three ORFs from Saccharomyces cerevisiae chromosome XI reveals five genes essential for growth and three genes conferring detectable mutant phenotype.

Author

UCL - AGRO/CABI - Département de chimie appliquée et des bio-industries, Wysocki, R, Van Dyck, E, Fairhead, C, Foury, Françoise, UCL - AGRO/CABI - Département de chimie appliquée et des bio-industries, Wysocki, R, Van Dyck, E, Fairhead, C, and Foury, Françoise

Abstract

In the frame of the European Network for Functional Analysis (EUROFAN), two regions from chromosome XI covering 54kb have been subjected to 'mass-murder'. Ten deletions covering 23 novel open reading frames (ORFs) were constructed in haploid and diploid strains. Six deletions were lethal in haploid strains. One deletion caused slow germination of spores and slow cellular growth, and another one was associated with both cellular growth thermosensitivity and poor growth on glycerol. These two defects were assigned to two different genes. All mutant phenotypes were complemented by a single gene, enabling us to identify five genes essential for vegetative growth, three genes with detectable phenotype and 15 dispensable genes under standard physiological conditions.

Published
1999

18. The nucleotide sequence of Saccharomyces cerevisiae chromosome XV

Author

Dujon, B, Albermann, K, Aldea, M, Alexandraki, D, Ansorge, W, Arino, J, Benes, V, Bohn, C, BolotinFukuhara, M, Bordonne, R, Boyer, J, Camasses, A, Casamayor, A, Casas, C, Cheret, G, Cziepluch, C, DaignanFornier, B, Dang, V, deHaan, M, Delius, H, Durand, P, Fairhead, C, Feldmann, H, Gaillon, L, Galisson, F, Gamo, J, Gancedo, C, Goffeau, A, Goulding, E, Grivell, A, Habbig, B, Hand, J, Hani, J, Hattenhorst, U, Hebling, U, Hernando, Y, Herrero, E, Heumann, K, Hiesel, R, Hilger, F, Hofmann, B, Hollenberg, P, Hughes, B, Jauniaux, C, Kalogeropoulos, A, Katsoulou, C, Kordes, E, Lafuente, J, Landt, O, Louis, J, Maarse, C, Madania, A, Mannhaupt, G, Marck, C, Martin, P, Mewes, W, Michaux, G, Paces, V, ParleMcDermott, G, Pearson, M, Perrin, A, Pettersson, B, Poch, O, Pohl, M, Poirey, R, Portetelle, D, Pujol, A, Purnelle, B, Rad, R, Rechmann, S, Schwager, C, Schweizer, M, Sor, F, Sterky, Fredrik, Tarassov, A, Teodoru, C, Tettelin, H, Thierry, A, Tobiasch, E, Tzermia, M, Uhlen, Mathias, Unseld, M, Valens, M, Vandenbol, M, Vetter, I, Vicek, C, Voet, M, Volckaert, G, Voss, H, Wambutt, R, Wedler, H, Wiemann, S, Winsor, B, Wolfe, H, Zollner, A, Zumstein, E, Kleine, K, Dujon, B, Albermann, K, Aldea, M, Alexandraki, D, Ansorge, W, Arino, J, Benes, V, Bohn, C, BolotinFukuhara, M, Bordonne, R, Boyer, J, Camasses, A, Casamayor, A, Casas, C, Cheret, G, Cziepluch, C, DaignanFornier, B, Dang, V, deHaan, M, Delius, H, Durand, P, Fairhead, C, Feldmann, H, Gaillon, L, Galisson, F, Gamo, J, Gancedo, C, Goffeau, A, Goulding, E, Grivell, A, Habbig, B, Hand, J, Hani, J, Hattenhorst, U, Hebling, U, Hernando, Y, Herrero, E, Heumann, K, Hiesel, R, Hilger, F, Hofmann, B, Hollenberg, P, Hughes, B, Jauniaux, C, Kalogeropoulos, A, Katsoulou, C, Kordes, E, Lafuente, J, Landt, O, Louis, J, Maarse, C, Madania, A, Mannhaupt, G, Marck, C, Martin, P, Mewes, W, Michaux, G, Paces, V, ParleMcDermott, G, Pearson, M, Perrin, A, Pettersson, B, Poch, O, Pohl, M, Poirey, R, Portetelle, D, Pujol, A, Purnelle, B, Rad, R, Rechmann, S, Schwager, C, Schweizer, M, Sor, F, Sterky, Fredrik, Tarassov, A, Teodoru, C, Tettelin, H, Thierry, A, Tobiasch, E, Tzermia, M, Uhlen, Mathias, Unseld, M, Valens, M, Vandenbol, M, Vetter, I, Vicek, C, Voet, M, Volckaert, G, Voss, H, Wambutt, R, Wedler, H, Wiemann, S, Winsor, B, Wolfe, H, Zollner, A, Zumstein, E, and Kleine, K

Abstract

Chromosome XV was one of the last two chromosomes of Saccharomyces cerevisiae to be discovered(1). It is the third-largest yeast chromosome after chromosomes XII and IV, and is very similar in size to chromosome VII. It alone represents 9% of the yeast genome (8% if ribosomal DNA is included). When systematic sequencing of chromosome XV was started, 93 genes or markers were identified, and most of them were mapped(2). However, very little else was known about chromosome XV which, in contrast to shorter chromosomes, had not been the object of comprehensive genetic or molecular analysis. It was therefore decided to start sequencing chromosome XV only in the third phase of the European Yeast Genome Sequencing Programme, after experience was gained on chromosomes III, XI and II (refs 3-5). The sequence of chromosome XV has been determined from a set of partly overlapping cosmid clones derived from a unique yeast strain, and physically mapped at 3.3-kilobase resolution before sequencing. As well as numerous new open reading frames (ORFs) and genes encoding tRNA or small RNA molecules, the sequence of 1,091,283 base pairs confirms the high proportion of orphan genes and reveals a number of ancestral and successive duplications with other yeast chromosomes., QC 20100812

Published
1997
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20. Reasons for participating in formal employer-led carpool schemes as perceived by their users.

Author

Canning, P. E., Hughes, S. J., Hellawell, E. E., Gatersleben, B. C. M., and Fairhead, C. J.

Subjects
CARPOOLS, CAR sharing, AUTOMOBILE parking, TRAFFIC surveys, WEB-based user interfaces, AUTOMOTIVE transportation
Abstract

Carpooling, the process by which individuals share a private vehicle for a particular journey or journeys, has been undertaken both formally and informally for a great number of years. A variety of computational methods for undertaking the 'ride-matching' element for the formation of carpools have been developed and subsequently made into integrated tools to allow the formation of multiple carpools. Such tools are commonly used by both Local Authorities and employers who are looking to establish and operate their own formal carpool scheme, increasingly using a web-based interface. The aim of this paper is to understand how users enrolled with employer-led carpool schemes perceive the importance of several different factors in their decision to participate. It is a further aim to determine the importance they attach to employer provided priority parking spaces. A survey-based approach investigates the perceptions of users from six different employer operated carpool schemes in the UK. The paper suggests that saving money was perceived as the most important reason for an individual's decision to use a formal employer-led carpool scheme - even amongst carpool schemes where the employer provides significant incentives to participate. No regular access to their own vehicle and 'more sociable travel' were generally perceived as less important reasons to participate. For employers who offer priority parking to carpoolers, this was generally valued as important by participants, even when the employment location did not have significant parking pressures. [ABSTRACT FROM AUTHOR]

Published
2010
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21. Rapid Discrimination between Candida glabrata, Candida nivariensis, and Candida bracarensisby Use of a Singleplex PCR

Author

Enache-Angoulvant, A., Guitard, J., Grenouillet, F., Martin, T., Durrens, P., Fairhead, C., and Hennequin, C.

Abstract

ABSTRACTWe report here a PCR-based assay using a single primer pair targeting the RPL31gene that allows discrimination between Candida glabrata, Candida bracarensis, and Candida nivariensisaccording to the size of the generated amplicon.

Published
2011
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25. Complete transcriptional map of yeast chromosome XI in different life conditions11Edited by M. Yaniv

Author

Richard, G.-F., Fairhead, C., and Dujon, B.

Abstract

Systematic sequencing of the genome of Saccharomyces cerevisiaehas demonstrated the existence of many novel genes, whose functions need to be studied. Entire chromosome sequences also offer the possibility to examine functional properties of the genome at a higher hierarchical level than the genes themselves. We used ordered DNA fragments of chromosome XI to systematically probe yeast DNA and total RNA extracted from MATa, MATα and diploid cells grown under three different conditions. Taking into account transcript sizes and uniqueness of probes, we attributed 94 transcripts to sequence-predicted open reading frames (ORFs) or tRNA genes; another 83 being tentatively assigned. The remaining 187 ORFs on chromosome XI do not correspond to transcripts detected under our conditions. More than 80% of transcripts are constitutively expressed, others are regulated by medium composition or cell type, the most frequent regulations being determined by carbon source (glycerol/glucose) or rich versussynthetic medium. Moreover, we show that transcript levels and regulation patterns are not statistically different between ORFs of unknown function, which constitute ca. 40% of the total, and previously identified genes (ca. 30%) or their structural homologues.

Published
1997
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26. The complete DNA sequence of yeast chromosome III

Author

Oliver, S. G., Aart, Q. J. M., Agostoni-Carbone, M. L., Aigle, M., Alberghina, L., Alexandraki, D., Antoine, G., Anwar, R., Ballesta, J. P. G., Benit, P., Berben, G., Bergantino, E., Biteau, N., Bolle, P. A., Bolotin-Fukuhara, M., Brown, A., Brown, A. J. P., Buhler, J. M., Carcano, C., Carignani, G., Cederberg, H., Chanet, R., Contreras, R., Crouzet, M., Daignan-Fornier, B., Defoor, E., Delgado, M., Demolder, J., Doira, C., Dubois, E., Dujon, B., Dusterhoft, A., Erdmann, D., Esteban, M., Fabre, F., Fairhead, C., Faye, G., Feldmann, H., Fiers, W., Francingues-Gaillard, M. C., Franco, L., Frontali, L., Fukuhara, H., Fuller, L. J., Galland, P., Gent, M. E., Gigot, D., Gilliquet, V., Glansdorff, N., Goffeau, A., Grenson, M., Grisanti, P., Grivell, L. A., Haan, M., Haasemann, M., Hatat, D., Hoenicka, J., Hegemann, J., Herbert, C. J., Hilger, F., Hohmann, S., Hollenberg, C. P., Huse, K., Iborra, F., Indge, K. J., Isono, K., Jacq, C., Jacquet, M., James, C. M., Jauniaux, J. C., Jia, Y., Jimenez, A., Kelly, A., Kleinhans, U., Kreisl, P., Lanfranchi, G., Lewis, C., Linden, C. G., Lucchini, G., Lutzenkirchen, K., Maat, M. J., Mallet, L., Mannhaupt, G., Martegani, E., Mathieu, A., Maurer, C. T. C., Mcconnell, D., Mckee, R. A., Messenguy, F., Mewes, H. W., Molemans, F., Montague, M. A., Falconi, M. M., Navas, L., Newlon, C. S., Noone, D., Pallier, C., Panzeri, L., and Pearson, B. M.

27. Large-scale exploration of growth inhibition caused by overexpression of genomic fragments in Saccharomyces cerevisiae

Author

Boyer, J., Badis, G., Fairhead, C., Talla, E., Hantraye, F., Fabre, E., Gilles Fischer, Hennequin, C., Koszul, R., Lafontaine, I., Ozier-Kalogeropoulos, O., Ricchetti, M., Richard, G. F., Thierry, A., Dujon, B., Génétique Moléculaire des Levures, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Génétique des Interactions Macromoléculaires, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie bactérienne (LCB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique et Biochimie du Développement, This work was supported in part by the EUROFAN2 project (Bio4-CT97-2294) from the European Commission (DGXII). E.T. was supported by the European contract CYGD (QLRI-CT 1999-01333), R.K. is a recipient of a CNRS-BDI fellowship. B.D. is a member of the Institut Universitaire de France., Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie - Mycologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
Reading Frames, [SDV]Life Sciences [q-bio], Genes, Fungal, Method, MESH: Transgenes, Saccharomyces cerevisiae, Transfection, MESH: Phenotype, Open Reading Frames, Gene Expression Regulation, Fungal, MESH: Cloning, Molecular, Transgenes, Cloning, Molecular, DNA, Fungal, Genes, Suppressor, MESH: Reading Frames, MESH: Transfection, MESH: Open Reading Frames, MESH: Saccharomyces cerevisiae, MESH: DNA, Fungal, Phenotype, MESH: Genes, Suppressor, MESH: Genome, Fungal, Genes, Lethal, MESH: Genes, Lethal, Genome, Fungal, MESH: Genes, Fungal, MESH: Gene Expression Regulation, Fungal
Abstract

A screen of the Saccharomyces cerevisiae genome for fragments conferring a growth-impairment phenotype identified 714 fragments in about 84,000 clones tested., We have screened the genome of Saccharomyces cerevisiae for fragments that confer a growth-retardation phenotype when overexpressed in a multicopy plasmid with a tetracycline-regulatable (Tet-off) promoter. We selected 714 such fragments with a mean size of 700 base-pairs out of around 84,000 clones tested. These include 493 in-frame open reading frame fragments corresponding to 454 distinct genes (of which 91 are of unknown function), and 162 out-of-frame, antisense and intergenic genomic fragments, representing the largest collection of toxic inserts published so far in yeast.

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28. A new role in managing depression.

Author

Fairhead C

Subjects
*PRIMARY care, *PSYCHIATRIC nurses, *THERAPEUTICS, *MENTAL depression
Abstract

Two years ago a Northampton health centre introduced the new role of the primary care mental health nurse (PCMHN). Christina Fairhead shares some of her experiences. [ABSTRACT FROM AUTHOR]

Published
2003
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29. Insertion site preference of Mu, Tn5, and Tn7 transposons

Author

Green Brian, Bouchier Christiane, Fairhead Cécile, Craig Nancy L, and Cormack Brendan P

Subjects
Tn7, Mu, Tn5, Mutagenesis, Insertion site, DNA transposon, Mobile element, Genetics, QH426-470
Abstract

Abstract Background Transposons, segments of DNA that can mobilize to other locations in a genome, are often used for insertion mutagenesis or to generate priming sites for sequencing of large DNA molecules. For both of these uses, a transposon with minimal insertion bias is desired to allow complete coverage with minimal oversampling. Findings Three transposons, Mu, Tn5, and Tn7, were used to generate insertions in the same set of fosmids containing Candida glabrata genomic DNA. Tn7 demonstrates markedly less insertion bias than either Mu or Tn5, with both Mu and Tn5 biased toward sequences containing guanosine (G) and cytidine (C). This preference of Mu and Tn5 yields less uniform spacing of insertions than for Tn7, in the adenosine (A) and thymidine (T) rich genome of C. glabrata (39% GC). Conclusions In light of its more uniform distribution of insertions, Tn7 should be considered for applications in which insertion bias is deleterious.

Published
2012
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31. Lenacapavir to prevent HIV infection: current prices versus estimated costs of production.

Author

Hill A, Levi J, Fairhead C, Pilkington V, Wang J, Johnson M, Layne J, Roberts D, and Fortunak J

Subjects
Commerce economics, Drug Industry economics, Chemistry, Pharmaceutical economics, Anti-HIV Agents economics, Drug Costs, HIV Infections prevention & control
Abstract

Background: Despite improvements in treatment and oral pre-exposure prophylaxis (PrEP) access, 1.3 million people acquired HIV in 2022. Six-monthly lenacapavir PrEP could benefit tens of millions of people at high risk of infection. However, prices are currently up to $44 819 per person per year (pppy)., Objectives: We projected minimum lenacapavir pricing based on generic mass production and a Cost-Plus (Cost+) model., Methods: Current active pharmaceutical ingredient (API) and key starting materials (KSMs) costs were obtained from export databases. The routes of synthesis (ROS) were analysed to project a cost of goods (COGs). Formulation, vials and profit margin costs were included using standardized algorithms and Cost+ pricing. We estimated prices with scale-up to supply 1 million then 10 million treatment-years, comparing this with national list prices., Results: The lenacapavir API is currently exported from India for $64 480/kg on 1 kg scale. Based on the ROS and KSMs, API COGs of $25 000/kg and $10 000/kg are achievable for a committed demand of 1 million (2 million tonnes/annum of API) and 10 million treatment-years, respectively. Including formulation steps, injectable lenacapavir could be mass produced for approximately $94 pppy for 1 million and $41 for 10 million treatment-years, if voluntary licences are in place and competition between generic suppliers substantially improves. Greater scale-up with improvements in manufacturers' ROS could reduce prices further. Currently lenacapavir costs $25 395-44 819 pppy., Conclusions: Lenacapavir could be mass produced for <$100 pppy at launch. Voluntary licensing and multiple suppliers are required to achieve these low prices. This mechanism is already in place for other antiretrovirals. To date, Gilead has not agreed lenacapavir voluntary licences with the Medicines Patent Pool., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
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33. Low CD4 counts predict excessive weight gains during first-line treatment for HIV.

Author

Hill A, Tovar Sanchez T, Delaporte E, Sokhela S, Simmons B, Kouanfack C, Mccann K, Levi J, Fairhead C, and Venter F

Subjects
Humans, Female, Male, CD4 Lymphocyte Count, Adult, Middle Aged, Oxazines therapeutic use, Oxazines adverse effects, Body Mass Index, Obesity, HIV Infections drug therapy, Weight Gain drug effects, Anti-HIV Agents therapeutic use, Anti-HIV Agents adverse effects, Benzoxazines therapeutic use, Benzoxazines adverse effects, Alkynes therapeutic use, Tenofovir therapeutic use, Tenofovir adverse effects, Cyclopropanes therapeutic use
Abstract

Background: Weight gain is common after antiretroviral initiation, especially among females, those of black race and lower baseline CD4, although this may potentially be due to lower baseline weight. Use of tenofovir disoproxil fumarate or efavirenz can suppress weight gain., Methods: Data were pooled from the ADVANCE (n = 1053), NAMSAL (n = 613) and WHRI001 (n = 536) trials investigating first-line regimen. Week 96 weight and body mass index (BMI) was stratified by baseline CD4. Multivariable models of weight change and incident obesity (BMI ≥30 kg/m2) were adjusted for baseline CD4, age, sex, tenofovir disoproxil fumarate, efavirenz, baseline BMI and trial., Results: Participants across all treatment arms experienced weight gain from baseline to week 96, with baseline CD4 count, baseline HIV RNA, tenofovir alafenamide and dolutegravir use, and female sex significant predictors. Mean unadjusted weight change was highest with CD4 < 100 (+8.6 kg; SD = 8.2) and lowest with CD4 ≥ 350 (+3.0 kg; SD = 6.5). This weight gain in CD4 < 100 was highest for participants on tenofovir alafenamide-inclusive treatment, such that absolute weight at week 96 was highest in the CD4 < 100 group. Although not statistically significant, obesity rate (BMI ≥ 30 kg/m2) in those taking TAF/FTC + DTG with CD4 < 100 overtook that seen in CD4 ≥ 350, despite lower baseline obesity prevalence. The unadjusted findings were corroborated in multivariable longitudinal models., Conclusions: Participants with low CD4 may demonstrate significant 'overshoot' weight gain, in addition to 'return to health', with a trend towards increased risk of obesity when initiated on TAF/FTC + DTG. Use of tenofovir disoproxil fumarate and efavirenz were associated with smaller weight gains. Effective weight management strategies are needed, especially for individuals with low baseline CD4., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
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34. In vivo CRISPR-Cas9 expression in Candida glabrata, Candida bracarensis, and Candida nivariensis: A versatile tool to study chromosomal break repair.

Author

Métivier K, Zhou-Li Y, and Fairhead C

Subjects
Plasmids genetics, DNA End-Joining Repair, DNA Repair, CRISPR-Cas Systems, Candida genetics, Candida glabrata genetics, Gene Editing methods, DNA Breaks, Double-Stranded
Abstract

The CRISPR-Cas9 system is extremely useful for genome editing in many species, including the model yeast Saccharomyces cerevisiae, and other yeast species. We have previously reported the use of an inducible CRISPR-Cas9 system in Candida glabrata, which allows genome editing but also the study of double-strand break (DSB) repair. We report, in this study, a comparable system for C. glabrata, relying on a new plasmid, which is more stable than the previous one. We also report the use of this plasmid to induce DSBs in two additional human pathogens, Candida bracarensis and Candida nivariensis. We examine lethality induced by an in vivo DSB in the three species and describe the different types of nonhomologous end-joining (NHEJ) events detected in these three pathogens., (© 2024 John Wiley & Sons Ltd.)

Published
2024
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35. Challenges for novel antiretroviral development in an era of widespread TLD availability.

Author

Fairhead C, Levi J, and Hill A

Abstract

Over 80% of people living with HIV in low-and-middle-income countries (LMICs) take first-line TDF/XTC/DTG (TLD). Due to hard-fought activism, in >100 LMICs TLD now costs under $45pppy under Voluntary License. With final DTG patents expiring by 2029, generic TLD will soon be available globally. We identify seven critical benchmarks underpinning TLDs success which novel ART should now meet, and an eighth for which novel ART should aim. These are superior efficacy; a high genetic barrier to resistance; safety in hepatitis B coinfection; favourable drug-drug interaction profiles including with antimycobacterials; efficacy in HIV-2; safety in pregnancy, long-acting formulation availability and affordable pricing from the outset. We illustrate when generic TLD will become available worldwide and compare this with trial programmes and approval timelines for two case-study novel ART combinations: islatravir/doravirine and cabotegravir/rilpivirine. We demonstrate that currently these regimens and trial programmes will not meet key benchmarks required to compete with TLD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
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36. Intersections between HIV and obesity in emerging economies.

Author

Levi J, Fairhead C, and Hill A

Subjects
Humans, Obesity epidemiology, HIV Infections drug therapy, Acquired Immunodeficiency Syndrome
Abstract

Purpose of Review: HIV epidemics are increasing in many emerging economy countries, whilst the very process of 'economic emergence' is obesogenic. Annual deaths related to obesity and overweight are now four times more than for HIV globally. We describe the intersections between HIV and obesity in emerging economies, and highlight potential mitigation options, including antiobesity medications (AOMs), which are safe and effective, but inaccessibly priced., Recent Findings: We summarize what is known about weight-change in HIV and review strategies including public health policies and clinical interventions for emerging economy countries to fight obesity. We also illustrate the landscape from a selection of 'emerging economy' countries with available data from UNAIDS, World Bank and World Obesity Federation to visualize the developing challenges faced. AOM course prices are high in many countries, but could be manufactured and sold profitably for much less. We present lessons from the early HIV/AIDS movements on how to improve access and pricing for AOMs for people with HIV with obesity in emerging economy countries., Summary: We illustrate the complex intersectional issues that 'emerging economy countries' may experience, with a 'double burden' of increasing HIV and obesity epidemics, and explore potential mitigation options, focussing on AOM access and pricing., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2024
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38. Neutralizing antibody activity in convalescent sera from infection in humans with SARS-CoV-2 and variants of concern.

Author

Dupont L, Snell LB, Graham C, Seow J, Merrick B, Lechmere T, Maguire TJA, Hallett SR, Pickering S, Charalampous T, Alcolea-Medina A, Huettner I, Jimenez-Guardeño JM, Acors S, Almeida N, Cox D, Dickenson RE, Galao RP, Kouphou N, Lista MJ, Ortega-Prieto AM, Wilson H, Winstone H, Fairhead C, Su JZ, Nebbia G, Batra R, Neil S, Shankar-Hari M, Edgeworth JD, Malim MH, and Doores KJ

Subjects
Adult, Aged, Aged, 80 and over, Antibodies, Viral immunology, COVID-19 therapy, COVID-19 virology, COVID-19 Vaccines, Female, Humans, Immunization, Passive, Immunoglobulin G, Immunoglobulin M, Male, Middle Aged, Mutation, Neutralization Tests, SARS-CoV-2 genetics, Spike Glycoprotein, Coronavirus genetics, Vaccination, Young Adult, COVID-19 Serotherapy, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Antibodies, Viral blood, COVID-19 immunology, SARS-CoV-2 immunology
Abstract

COVID-19 vaccine design and vaccination rollout need to take into account a detailed understanding of antibody durability and cross-neutralizing potential against SARS-CoV-2 and emerging variants of concern (VOCs). Analyses of convalescent sera provide unique insights into antibody longevity and cross-neutralizing activity induced by variant spike proteins, which are putative vaccine candidates. Using sera from 38 individuals infected in wave 1, we show that cross-neutralizing activity can be detected up to 305 days pos onset of symptoms, although sera were less potent against B.1.1.7 (Alpha) and B1.351 (Beta). Over time, despite a reduction in overall neutralization activity, differences in sera neutralization potency against SARS-CoV-2 and the Alpha and Beta variants decreased, which suggests that continued antibody maturation improves tolerance to spike mutations. We also compared the cross-neutralizing activity of wave 1 sera with sera from individuals infected with the Alpha, the Beta or the B.1.617.2 (Delta) variants up to 79 days post onset of symptoms. While these sera neutralize the infecting VOC and parental virus to similar levels, cross-neutralization of different SARS-CoV-2 VOC lineages is reduced. These findings will inform the optimization of vaccines to protect against SARS-CoV-2 variants., (© 2021. The Author(s).)

Published
2021
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39. Lessons from the Nakaseomyces: mating-type switching, DSB repair and evolution of Ho.

Author

Maroc L and Fairhead C

Subjects
Clustered Regularly Interspaced Short Palindromic Repeats, Candida glabrata genetics, DNA Breaks, Double-Stranded, DNA Repair, DNA, Fungal, Genes, Mating Type, Fungal
Abstract

This short paper aims to review what our recent studies in the Nakaseomyces yeasts, principally Candida glabrata, reveal about the evolution of the mating-type switching system and its components, as well as about the repair of chromosomal double-strand breaks in this clade. In the model yeast Saccharomyces cerevisiae, the study of mating-type switching has, over the years, led to major discoveries in how cells process chromosomal breaks. Indeed, in this species, switching, which allows every haploid cell to produce cells of opposite mating types that can mate together, is initiated by the Ho endonuclease, linking sexual reproduction to a programmed chromosomal cut. More recently, the availability of other yeasts' genomes from type strains and from populations, and the ability to manipulate and edit the genomes of most yeasts in the laboratory, has enabled scientists to explore mating-type switching in new species, thus enriching our evolutionary perspective on this phenomenon. In this review, we will show how the study of mating-type switching in C. glabrata and Nakaseomyces delphensis has allowed us to reveal possible additional roles for Ho, and also to discover major differences in DSB repair at central and subtelomeric sexual loci. In addition, we report how the study of repair of chromosomal breaks induced by CRISPR-Cas9 reveals that efficient and faithful NHEJ is a major repair pathway in C. glabrata., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2021
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41. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial.

Author

Frater J, Ewer KJ, Ogbe A, Pace M, Adele S, Adland E, Alagaratnam J, Aley PK, Ali M, Ansari MA, Bara A, Bittaye M, Broadhead S, Brown A, Brown H, Cappuccini F, Cooney E, Dejnirattisai W, Dold C, Fairhead C, Fok H, Folegatti PM, Fowler J, Gibbs C, Goodman AL, Jenkin D, Jones M, Makinson R, Marchevsky NG, Mujadidi YF, Nguyen H, Parolini L, Petersen C, Plested E, Pollock KM, Ramasamy MN, Rhead S, Robinson H, Robinson N, Rongkard P, Ryan F, Serrano S, Tipoe T, Voysey M, Waters A, Zacharopoulou P, Barnes E, Dunachie S, Goulder P, Klenerman P, Screaton GR, Winston A, Hill AVS, Gilbert SC, Pollard AJ, Fidler S, Fox J, and Lambe T

Subjects
Adult, CD4 Lymphocyte Count, COVID-19 Vaccines adverse effects, ChAdOx1 nCoV-19, HIV Infections drug therapy, Humans, Male, Middle Aged, Vaccination, Antibodies, Viral blood, COVID-19 prevention & control, COVID-19 Vaccines immunology, HIV Infections immunology, SARS-CoV-2 immunology
Abstract

Background: Data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV., Methods: In this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18-55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (<50 copies per mL), and CD4 counts of more than 350 cells per μL. A prime-boost regimen of ChAdOx1 nCoV-19, with two doses was given 4-6 weeks apart. The primary outcomes for this substudy were safety and reactogenicity of the vaccine, as determined by serious adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated live virus neutralisation. Cell-mediated immune responses were measured by ex-vivo IFN-γ enzyme-linked immunospot assay (ELISpot) and T-cell proliferation. All outcomes were compared with an HIV-uninfected group from the main COV002 study within the same age group and dosing strategy and are reported until day 56 after prime vaccination. Outcomes were analysed in all participants who received both doses and with available samples. The COV002 study is registered with ClinicalTrials.gov, NCT04400838, and is ongoing., Findings: Between Nov 5 and Nov 24, 2020, 54 participants with HIV (all male, median age 42·5 years [IQR 37·2-49·8]) were enrolled and received two doses of ChAdOx1 nCoV-19. Median CD4 count at enrolment was 694·0 cells per μL (IQR 573·5-859·5). No serious adverse events occurred. Local and systemic reactions occurring during the first 7 days after prime vaccination included pain at the injection site (26 [49%] of 53 participants with available data), fatigue (25 [47%]), headache (25 [47%]), malaise (18 [34%]), chills (12 [23%]), muscle ache (19 [36%]), joint pain (five [9%]), and nausea (four [8%]), the frequencies of which were similar to the HIV-negative participants. Anti-spike IgG responses by ELISA peaked at day 42 (median 1440 ELISA units [EUs; IQR 704-2728]; n=50) and were sustained until day 56 (median 941 EUs [531-1445]; n=49). We found no correlation between the magnitude of the anti-spike IgG response at day 56 and CD4 cell count (p=0·93) or age (p=0·48). ELISpot and T-cell proliferative responses peaked at day 14 and 28 after prime dose and were sustained to day 56. Compared with participants without HIV, we found no difference in magnitude or persistence of SARS-CoV-2 spike-specific humoral or cellular responses (p>0·05 for all analyses)., Interpretation: In this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART., Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca., Competing Interests: Declaration of interests Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19 (AZD1222). SCG is cofounder of Vaccitech (a collaborator in the early development of this vaccine candidate) and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and a patent application covering this SARS-CoV-2 vaccine. TL is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was consultant to Vaccitech. PMF is a consultant to Vaccitech and has received research funding from the Brazilian Government. AJP is Chair of the UK Department of Health and Social Care's Joint Committee on Vaccination and Immunisation, but does not participate in policy advice on SARS-CoV-2 vaccines, and is a member of the WHO Strategic Advisory Group of Experts. AVSH is a cofounder of and consultant to Vaccitech and is named as an inventor on a patent covering design and use of ChAdOx1-vectored vaccines (PCT/GB2012/000467). SF is a consultant to Immunocore. GRS has received funding from Schmidt Futures and Wellcome Trust, consulting fees from GSK Vaccines Strategic Advisory Board, has patents on SARS-CoV-2 monoclonal antibodies, has leadership roles on Oxford University Council and Oxford University Hospitals NHS Foundation Trust, and holds stock in GSK. KP reports grants from the UK Medical Research Council UK Research and Innovation and National Institute of Health Research (NIHR) Vaccine Taskforce for RNA vaccine trial, COVAC1, and honoraria for Sanofi strategic advisory boards. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Published
2021
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42. The diagnostic performance of chest radiographs for lung malignancy in symptomatic primary-care populations: A systematic review and meta-analysis.

Author

Dwyer-Hemmings L and Fairhead C

Abstract

Objectives: To synthesise existing evidence for the diagnostic accuracy of chest radiographs to detect lung malignancy in symptomatic patients presenting to primary care., Methods: A systematic review was performed and reported in accordance with the PRISMA framework, using a protocol prospectively registered with the PROSPERO database (CRD42020212450). Nine databases were searched for relevant studies. Data were extracted and chest radiograph sensitivity and specificity calculated where possible. Risk of bias was assessed using a validated tool. Random effects meta-analysis was performed., Results: Ten studies were included. Sensitivity meta-analysis was performed in five studies which were not the high risk of bias, with summary sensitivity of 81% (95% CI: 74-87%). Specificity could be calculated in five studies, with summary specificity of 68% (95% CI: 49-87%)., Conclusions: The sensitivity of chest radiographs for detecting lung malignancy in primary care is relatively low. Physicians and policymakers must consider strategies to attenuate the possibility of false reassurance with a negative chest radiograph for this significant pathology. Options include widening access to cross-sectional imaging in primary care; however, any intervention would need to take into account the medical and financial costs of possible over-investigation. Prospective trials with long-term follow-up are required to further evaluate the risks and benefits of this strategy., Advances in Knowledge: The chest radiograph has a sensitivity of 81% and specificity of 68% for lung malignancy in a symptomatic primary-care population. A negative chest radiograph does not exclude lung cancer, and physicians should maintain a low threshold to consider specialist referral or cross-sectional imaging., (© 2021 The Authors. Published by the British Institute of Radiology.)

Published
2021
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43. Antibody longevity and cross-neutralizing activity following SARS-CoV-2 wave 1 and B.1.1.7 infections.

Author

Dupont L, Snell LB, Graham C, Seow J, Merrick B, Lechmere T, Hallett SR, Charalampous T, Alcolea-Medina A, Huettner I, Maguire TJA, Acors S, Almeida N, Cox D, Dickenson RE, Galao RP, Jimenez-Guardeño JM, Kouphou N, Lista MJ, Pickering S, Ortega-Prieto AM, Wilson H, Winstone H, Fairhead C, Su J, Nebbia G, Batra R, Neil S, Shankar-Hari M, Edgeworth JD, Malim MH, and Doores KJ

Abstract

As SARS-CoV-2 variants continue to emerge globally, a major challenge for COVID-19 vaccination is the generation of a durable antibody response with cross-neutralizing activity against both current and newly emerging viral variants. Cross-neutralizing activity against major variants of concern (B.1.1.7, P.1 and B.1.351) has been observed following vaccination, albeit at a reduced potency, but whether vaccines based on the Spike glycoprotein of these viral variants will produce a superior cross-neutralizing antibody response has not been fully investigated. Here, we used sera from individuals infected in wave 1 in the UK to study the long-term cross-neutralization up to 10 months post onset of symptoms (POS), as well as sera from individuals infected with the B.1.1.7 variant to compare cross-neutralizing activity profiles. We show that neutralizing antibodies with cross-neutralizing activity can be detected from wave 1 up to 10 months POS. Although neutralization of B.1.1.7 and B.1.351 is lower, the difference in neutralization potency decreases at later timepoints suggesting continued antibody maturation and improved tolerance to Spike mutations. Interestingly, we found that B.1.1.7 infection also generates a cross-neutralizing antibody response, which, although still less potent against B.1.351, can neutralize parental wave 1 virus to a similar degree as B.1.1.7. These findings have implications for the optimization of vaccines that protect against newly emerging viral variants.

Published
2021
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44. Genome editing in the yeast Nakaseomyces delphensis and description of its complete sexual cycle.

Author

Zhou Li Y, Boisnard S, Enache-Angoulvant A, and Fairhead C

Subjects
CRISPR-Cas Systems, Phylogeny, Reproduction genetics, DNA, Fungal genetics, Gene Editing, Genes, Mating Type, Fungal, Genome, Fungal, Meiosis, Saccharomycetales genetics, Saccharomycetales physiology
Abstract

The environmental yeast Nakaseomyces delphensis is, phylogenetically, the closest known species to Candida glabrata, a major fungal pathogen of humans. C. glabrata is haploid and described as asexual, while N. delphensis is also haploid, but has been described as competent for mating and meiosis. Both genomes contain homologues of all the genes necessary for sexual reproduction and also the genes for Ho-dependent mating-type switching, like Saccharomyces cerevisiae. We first report the construction of genetically engineered strains of N. delphensis, including by CRISPR-Cas 9 gene editing. We also report the description of the sexual cycle of N. delphensis. We show that it undergoes Ho-dependent mating-type switching in culture and that deletion of the HO gene prevents such switching and allows maintenance of stable, separate, MATa and MATalpha haploid strains. Rare, genetically selected diploids can be obtained through mating of haploid strains, mutated or not for the HO gene. In contrast to HO/HO diploids, which behave as expected, Δho/Δho diploids exhibit unusual profiles in flow cytometry. Both types of diploids can produce recombined haploid cells, which grow like the original haploid-type strain. Our experiments thus allow the genetic manipulation of N. delphensis and the reconstruction, in the laboratory, of its entire life cycle., (© 2020 John Wiley & Sons, Ltd.)

Published
2021
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45. A single Ho-induced double-strand break at the MAT locus is lethal in Candida glabrata.

Author

Maroc L, Zhou-Li Y, Boisnard S, and Fairhead C

Subjects
CRISPR-Cas Systems genetics, Cell Death genetics, Chromosomes, Fungal genetics, DNA Breaks, Double-Stranded, Gene Expression Regulation, Fungal genetics, Homologous Recombination genetics, Rad51 Recombinase genetics, Candida glabrata genetics, Deoxyribonucleases, Type II Site-Specific genetics, Endonucleases genetics, Genes, Mating Type, Fungal genetics, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins genetics
Abstract

Mating-type switching is a complex mechanism that promotes sexual reproduction in Saccharomycotina. In the model species Saccharomyces cerevisiae, mating-type switching is initiated by the Ho endonuclease that performs a site-specific double-strand break (DSB) at MAT, repaired by homologous recombination (HR) using one of the two silent mating-type loci, HMLalpha and HMRa. The reasons why all the elements of the mating-type switching system have been conserved in some Saccharomycotina, that do not show a sexual cycle nor mating-type switching, remain unknown. To gain insight on this phenomenon, we used the yeast Candida glabrata, phylogenetically close to S. cerevisiae, and for which no spontaneous and efficient mating-type switching has been observed. We have previously shown that expression of S. cerevisiae's Ho (ScHo) gene triggers mating-type switching in C. glabrata, but this leads to massive cell death. In addition, we unexpectedly found, that not only MAT but also HML was cut in this species, suggesting the formation of multiple chromosomal DSBs upon HO induction. We now report that HMR is also cut by ScHo in wild-type strains of C. glabrata. To understand the link between mating-type switching and cell death in C. glabrata, we constructed strains mutated precisely at the Ho recognition sites. We find that even when HML and HMR are protected from the Ho-cut, introducing a DSB at MAT is sufficient to induce cell death, whereas one DSB at HML or HMR is not. We demonstrate that mating-type switching in C. glabrata can be triggered using CRISPR-Cas9, without high lethality. We also show that switching is Rad51-dependent, as in S. cerevisiae, but that donor preference is not conserved in C. glabrata. Altogether, these results suggest that a DSB at MAT can be repaired by HR in C. glabrata, but that repair is prevented by ScHo., Competing Interests: The authors have declared that no competing interests exist.

Published
2020
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46. Functional networks of co-expressed genes to explore iron homeostasis processes in the pathogenic yeast Candida glabrata .

Author

Denecker T, Zhou Li Y, Fairhead C, Budin K, Camadro JM, Bolotin-Fukuhara M, Angoulvant A, and Lelandais G

Abstract

Candida glabrata is a cause of life-threatening invasive infections especially in elderly and immunocompromised patients. Part of human digestive and urogenital microbiota, C. glabrata faces varying iron availability, low during infection or high in digestive and urogenital tracts. To maintain its homeostasis, C. glabrata must get enough iron for essential cellular processes and resist toxic iron excess. The response of this pathogen to both depletion and lethal excess of iron at 30°C have been described in the literature using different strains and iron sources. However, adaptation to iron variations at 37°C, the human body temperature and to gentle overload, is poorly known. In this study, we performed transcriptomic experiments at 30°C and 37°C with low and high but sub-lethal ferrous concentrations. We identified iron responsive genes and clarified the potential effect of temperature on iron homeostasis. Our exploration of the datasets was facilitated by the inference of functional networks of co-expressed genes, which can be accessed through a web interface. Relying on stringent selection and independently of existing knowledge, we characterized a list of 214 genes as key elements of C. glabrata iron homeostasis and interesting candidates for medical applications., (© The Author(s) 2019. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

Published
2020
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47. A new inducible CRISPR-Cas9 system useful for genome editing and study of double-strand break repair in Candida glabrata.

Author

Maroc L and Fairhead C

Subjects
CRISPR-Associated Protein 9 metabolism, DNA Breaks, Double-Stranded, DNA End-Joining Repair, DNA Repair, Gene Editing, Gene Targeting, Homologous Recombination, Microbial Viability, Plasmids, Promoter Regions, Genetic, RNA, Guide, CRISPR-Cas Systems genetics, CRISPR-Associated Protein 9 genetics, CRISPR-Cas Systems genetics, Candida glabrata genetics, Genome, Fungal genetics, Transcriptional Activation
Abstract

In recent years, the CRISPR-Cas9 system has proven extremely useful for genome editing in many species, including the model yeast Saccharomyces cerevisiae and other yeast species such as Candida glabrata. Inducible CRISPR-Cas9 systems have the additional advantage of allowing to separate the transformation step of the organism by the CRISPR-Cas9 system, from the cutting and repair steps. This has indeed been developed in S. cerevisiae, where most inducible expression systems rely on the GAL promoters. Unfortunately, C. glabrata is gal - and lacks the GAL genes, like many other yeast species. We report here the use of a vector expressing cas9 under the control of the MET3 promoter, with the guide RNA cloned into the same plasmid. We show that it can be used efficiently in C. glabrata, for both described outcomes of CRISPR-Cas9-induced chromosome breaks; nonhomologous end joining in the absence of a homologous repair template; and homologous recombination in the presence of such a template. This system therefore allows easy editing of the genome of C. glabrata, and its inducibility may allow identification of essential genes in this asexual yeast, where spore lethality cannot be observed, as well as the study of double-strand break repair., (© 2019 John Wiley & Sons, Ltd.)

Published
2019
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48. André Goffeau's imprinting on second generation yeast "genomologists".

Author

Fairhead C, Fischer G, Liti G, Neuvéglise C, and Schacherer J

Subjects
Fermentation, Genetic Variation, Saccharomyces cerevisiae metabolism, Genome, Fungal, Genomics trends, Saccharomyces cerevisiae genetics
Abstract

All authors of the present paper have worked in labs that participated to the sequencing effort of the Saccharomyces cerevisiae reference genome, and we owe to this the fact that we have all chosen to work on genomics of yeasts. S. cerevisiae has been a popular model species for genetics since the 20th century as well as being a model for general eukaryotic cellular processes. Although it has also been used empirically in fermentation for millennia, there was until recently, a lack of knowledge about the natural and evolutionary history of this yeast. The achievement of the international effort to sequence its genome was the foundation for understanding many eukaryotic biological processes but also represented the first step towards the study of the genome and ecological diversity of yeast populations worldwide. We will describe recent advances in yeast comparative and population genomics that find their origins in the S. cerevisiae genome project initiated and pursued by André Goffeau., (© 2019 John Wiley & Sons, Ltd.)

Published
2019
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49. Genome Comparisons of Candida glabrata Serial Clinical Isolates Reveal Patterns of Genetic Variation in Infecting Clonal Populations.

Author

Carreté L, Ksiezopolska E, Gómez-Molero E, Angoulvant A, Bader O, Fairhead C, and Gabaldón T

Abstract

Candida glabrata is an opportunistic fungal pathogen that currently ranks as the second most common cause of candidiasis. Although the mechanisms underlying virulence and drug resistance in C. glabrata are now starting to be elucidated, we still lack a good understanding of how this yeast adapts during the course of an infection. Outstanding questions are whether the observed genomic plasticity of C. glabrata plays a role during infection, or what levels of genetic variation exist within an infecting clonal population. To shed light onto the genomic variation within infecting C. glabrata populations, we compared the genomes of 11 pairs and one trio of serial clinical isolates, each obtained from a single patient. Our results provide a catalog of genetic variations existing within clonal infecting isolates, and reveal an enrichment of non-synonymous changes in genes encoding cell-wall proteins. Genetic variation and the presence of non-synonymous mutations and copy number variations accumulated within the host, suggest that clonal populations entail a non-negligible level of genetic variation that may reflect selection processes that occur within the human body. As we show here, these genomic changes can underlie phenotypic differences in traits that are relevant for infection.

Published
2019
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50. Genomes shed light on the secret life of Candida glabrata: not so asexual, not so commensal.

Author

Gabaldón T and Fairhead C

Subjects
Candida glabrata classification, Candida glabrata physiology, Candidiasis microbiology, Host-Pathogen Interactions, Humans, Phylogeny, Reproduction genetics, Symbiosis, Candida glabrata genetics, Genes, Mating Type, Fungal genetics, Genome, Fungal genetics, Genomics methods
Abstract

Candida glabrata is an opportunistic yeast pathogen, whose incidence has increased over the last decades. Despite its genus name, this species is actually more closely related to the budding yeast Saccharomyces cerevisiae than to other Candida pathogens, such as Candida albicans. Hence, C. glabrata and C. albicans must have acquired the ability to infect humans independently, which is reflected in the use of different mechanism for virulence, and survival in the host. Yet, research on C. glabrata suffers from assumptions carried over from the more studied C. albicans. Regarding the adaptation of C. glabrata to the human host, the prejudice was that, just as C. albicans, C. glabrata is a natural human commensal that turns deadly when immune defenses weaken. It was also considered asexual, as no one has observed mating, diploids, or spores, despite great efforts. However, the recent analysis of whole genomes from globally distributed C. glabrata isolates have shaken these assumptions. C. glabrata seems to be only secondarily associated to humans, as indicated by a lack of co-evolution with its host, and genomic footprints of recombination shows compelling evidence that this yeast is able to have sex. Here, we discuss the implications of this and other recent findings and highlight the new questions opened by this change in paradigm.

Published
2019
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