Comparative Genome Analysis of Trichophyton rubrum and Related Dermatophytes Reveals Candidate Genes Involved in Infection

The major cause of athlete's foot is Trichophyton rubrum, a dermatophyte or fungal pathogen of human skin. To facilitate molecular analyses of the dermatophytes, we sequenced T. rubrum and four related species, Trichophyton tonsurans, Trichophyton equinum, Microsporum canis, and Microsporum gypseum. These species differ in host range, mating, and disease progression. The dermatophyte genomes are highly colinear yet contain gene family expansions not found in other human-associated fungi. Dermatophyte genomes are enriched for gene families containing the LysM domain, which binds chitin and potentially related carbohydrates. These LysM domains differ in sequence from those in other species in regions of the peptide that could affect substrate binding. The dermatophytes also encode novel sets of fungus-specific kinases with unknown specificity, including nonfunctional pseudokinases, which may inhibit phosphorylation by competing for kinase sites within substrates, acting as allosteric effectors, or acting as scaffolds for signaling. The dermatophytes are also enriched for a large number of enzymes that synthesize secondary metabolites, including dermatophyte-specific genes that could synthesize novel compounds. Finally, dermatophytes are enriched in several classes of proteases that are necessary for fungal growth and nutrient acquisition on keratinized tissues. Despite differences in mating ability, genes involved in mating and meiosis are conserved across species, suggesting the possibility of cryptic mating in species where it has not been previously detected. These genome analyses identify gene families that are important to our understanding of how dermatophytes cause chronic infections, how they interact with epithelial cells, and how they respond to the host immune response. IMPORTANCE Athlete's foot, jock itch, ringworm, and nail infections are common fungal infections, all caused by fungi known as dermatophytes (fungi that infect skin). This report presents the genome sequences of Trichophyton rubrum, the most frequent cause of athlete's foot, as well as four other common dermatophytes. Dermatophyte genomes are enriched for four gene classes that may contribute to the ability of these fungi to cause disease. These include (i) proteases secreted to degrade skin; (ii) kinases, including pseudokinases, that are involved in signaling necessary for adapting to skin; (iii) secondary metabolites, compounds that act as toxins or signals in the interactions between fungus and host; and (iv) a class of proteins (LysM) that appear to bind and mask cell wall components and carbohydrates, thus avoiding the host's immune response to the fungi. These genome sequences provide a strong foundation for future work in understanding how dermatophytes cause disease.

Depositional age, provenance and metamorphic age of metasedimentary rocks from southern Madagascar

Southern Madagascar is the core of a >1 million km(2) Gondwanan metasedimentary belt that forms much of the southern East African Orogen of eastern Africa, Madagascar, southern India and Sri Lanka. Here the Vohibory Series yielded U-Pb isotopic data from detrital zircon cores that indicate that it was deposited in the latest Tonian to late Cryogenian (between -900 and 640 Ma). The deposition of the Graphite and Androyen Series protoliths is poorly constrained to between the late Palaeoproterozoic and the Cambrian (similar to 1830-530 Ma). The Vohibory Series protoliths were sourced from very restricted-aged sources with a maximum age range between 910 and 760 Ma. The Androyen and Graphite Series protoliths were sourced from Palaeoproterozoic rocks ranging in age between 2300 and 1800 Ma. The best evidence of the timing of metamorphism in the Vohibory Series is a weighted mean Pb-206/U-238 age of 642 +/- 8 Ma from 3 analyses of zircon from sample M03-01. A considerably younger Pb-206/U-238 metamorphic age of 531 +/- 7 Ma is produced from 10 analyses of zircon from sample M03-28 in the Androyen Series. This similar to 110 Ma difference in age is correlated with the early East African Orogeny affecting the west of Madagascar along with its type area in East Africa, whereas the Cambrian Malagasy Orogeny affected the east of Madagascar and southern India during the final suturing of the Mozambique Ocean. (C) 2011 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

Beyond "Cirrhosis" A Proposal From the International Liver Pathology Study Group

Cirrhosis is a moiphologic term that has been used for almost 200 years to denote the end stage of a variety of chronic liver diseases. The term implies a condition with adverse prognosis due to the well-known complications of portal hypertension, hepatocellular carcinoma, and liver failure. However, recent advances in the diagnosis and treatment of chronic liver diseases have changed the natural history of cirrhosis significantly. This consensus document by the International Liver Pathology Study Group challenges the usefulness of the word cirrhosis in modern medicine and suggests that this is an appropriate time to consider discontinuing the use of this term. The role of pathologists should evolve to the diagnosis of advanced stage of chronic liver disease, with emphasis on etiology, grade of activity, features suggestive of progression or regression, presence of other diseases, and risk factors for malignancy, within the perspective of an integrated clinicopathologic assessment.