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Color Plates

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COLOR PLATE 1

Working model of the cell wall of This schematic depicts the components known to be present, shown in the key. However, several aspects of this model remain to be investigated. The distribution of individual components within the wall and the exact linkages between them are largely undetermined. Chitin is shown linked to p-1,3-glucan based upon data in , but this linkage has not been examined directly in . Also, the model illustrates chitosan as linked to chitin or p-1,6-glucan, but this remains to be determined biochemically. The distribution of chitin and chitosan is still under investigation. Chitosan in a wild-type cell is normally stained by Eosin Y but can be inaccessible to the dye in the absence of p-1,6-glucan, suggesting that it is normally localized to the outside of the wall. We show a-1,3-glucan in the outer wall since electron microscopy immunogold labeling suggests that it is largely found in the periphery, and it is known to be an essential component for capsule binding. The β-glucans are shown distributed throughout since there is little evidence to the contrary. GPI-CWPs are shown linked to P-1,6-glucan, but the mechanism of cell wall association of noncanonical cell wall proteins (those lacking a Ser/Thrrich region and a GPI anchor, depicted in purple) is unknown. We have depicted vesicles traversing the wall, or being deposited in the wall, based on recent findings. There may be vesicles of different sizes and cargos that are important for delivery of cell wall, capsule, and other secreted material, and the mechanism by which secreted vesicles traverse the cell wall matrix is yet to be determined. Concentric layers of melanin granules have been observed within the cryptococcal cell wall, but it is unclear whether the layers are present in the inner or outer wall or are present throughout.

Citation: Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A. 2011. Color Plates, In . ASM Press, Washington, DC.
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COLOR PLATE 2

locus structure of and closely related species. Homeodomain genes are highlighted in blue and pheromone and receptor genes are highlighted in red. Genes in black are present in the MAT locus of the pathogenic species, while genes in yellow are additional genes identified in the other closely related species. The size of each locus is indicated below.

Citation: Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A. 2011. Color Plates, In . ASM Press, Washington, DC.
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COLOR PLATE 3

A model of the evolution of the bipolar locus in the pathogenic species. We proposed that the locus descended from an ancestral tetrapolar system with two unlinked HD and P/R loci. These loci expanded via gene acquisition, forming two unlinked gene clusters, and additional genes were gradually incorporated into the -specific region at both the HD and P/R loci. Chromosomal translocation then occurred to fuse the two unlinked loci to one contiguous allele, resulting in the intermediate tripolar state. The tripolar system then further collapsed into a bipolar system via recombination between the two alleles. Lastly, ongoing gene rearrangements, gene inversions, and gene conversions have contributed to shape the gene order and gene content of the locus.

Citation: Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A. 2011. Color Plates, In . ASM Press, Washington, DC.
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COLOR PLATE 4

View of the active site cleft of Plb1/human cPLA showing conserved residues. The catalytic residues in both proteins are circled. Cap domain residues 415 to 424 for cPLA, which partially occlude the active site in the X-ray structure (PDB: 1CYJ), have been removed for clarity. Labeled residues are shown in stick form and colored: carbon yellow, nitrogen blue, and oxygen red. Other residues are depicted as a surface representation using a probe radius of 1.4 A. Residues 577 and 578 have been rendered as transparent surface to reveal the backbone carbonyl oxygen of F576. Hydrogen bonds between the side chain of R200 and the backbone carbonyl oxygen of F576 and F678, as well as the side chain of T680, are depicted as green lines. The backbone nitrogen atoms of G197 (labeled) and G198 (visible beneath T680) form a putative oxyanion hole, with S228 and D549 forming the catalytic dyad. R200 is thought to bind the phosphate moiety of the lipid head group and may also stabilize the geometry of the oxyanion hole. Published with permission from the American Chemical Society; license # 2171070482164.

Citation: Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A. 2011. Color Plates, In . ASM Press, Washington, DC.
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COLOR PLATE 5

Map of (A) reported cases, (B) environmental sampling, and (C) forecasted ecological niche of on Vancouver Island and the British Columbia mainland. (A) Human and animal cases (1999 to 2007) are mapped by place of residence at a geographic scale that does not identify individuals. Cases on the British Columbia mainland with travel to Vancouver Island or other endemic areas prior to onset of illness are excluded from the map. (B) Environmental sampling (2001 to 2007) for and the biogeoclimatic zones of British Columbia. The Coastal Douglas Fir and Coastal Western Hemlock (very dry) zones are of particular interest for epidemiology in British Columbia. (C) Forecasted ecological niche model for in British Columbia. Geographic areas with the optimal environmental conditions to support in British Columbia are illustrated in red and orange.

Citation: Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A. 2011. Color Plates, In . ASM Press, Washington, DC.
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COLOR PLATE 6

(A) Cat with cryptococcal rhinosinusitis with invasion of the tissues over the nasal bones. This case was erroneously given corticosteroids, which caused the disease to suddenly progress. Note the secondary lesion on the skin of the pinna (ear). (B) The cat responded very favorably to long-term monotherapy with fluconazole, although some scarring with depigmentation of the nasal bridge region is evident. Photographs courtesy of Phillip Druce.

Citation: Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A. 2011. Color Plates, In . ASM Press, Washington, DC.
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COLOR PLATE 7

Multifocal skin lesions on (A) the head and (B) the trunk of an FIV-positive cat with disseminated cutaneous cryptococcosis. The primary site of infection was the nasal cavity. Many of the skin lesions have ulcerated.

Citation: Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A. 2011. Color Plates, In . ASM Press, Washington, DC.
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COLOR PLATE 8

Invasive deforming cryptococcal rhinitis due to (VGIIb). There is deformity of the right-hand side of the nasal planum (arrow), and erosion of a blood vessel has resulted in severe epistaxis (bleeding from the nose). This koala subsequently responded to a long course of subcutaneous amphotericin B, plus consolidation therapy with fluconazole.

Citation: Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A. 2011. Color Plates, In . ASM Press, Washington, DC.
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COLOR PLATE 9

Invasive and proliferative cryptococcal rhinitis in a goat from southwestern Western Australia. We suspect this was a VGIIb infection. (A) Photograph of the animal’s head. (B) A cross-section through the nasal cavity of a similarly affected greyhound.

Citation: Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A. 2011. Color Plates, In . ASM Press, Washington, DC.
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