Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis

Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18) and one strain of Paracoccidioides lutzii (Pb01). These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic species of Onygenales to transfer from soil to animal hosts.     

Paternal obesity induces epigenetic aberrations and gene expression changes in placenta and fetus

Paternal epigenome regulates placental and fetal growth. However, the effect of paternal obesity on placenta and its subsequent effect on the fetus via sperm remains unknown. We previously discovered abnormal methylation of imprinted genes involved in placental and fetal development in the spermatozoa of obese rats. In the present study, elaborate epigenetic characterization of sperm, placenta, and fetus was performed. For 16 weeks, male rats were fed either control or a high-fat diet. Following mating studies, sperm, placenta, and fetal tissue were collected. Significant changes were observed in placental weights, morphology, and cell populations. Methylation status of imprinted genes—Igf2, Peg3, Cdkn1c, and Gnas in spermatozoa, correlated with their expression in the placenta and fetus. Placental DNA methylating enzymes and 5-methylCytosine levels increased. Furthermore, in spermatozoa, DNA methylation of a few genes involved in pathways associated with placental endocrine function—gonadotropin-releasing hormone, prolactin, estrogen, and vascular endothelial growth factor, correlated with their expression in placenta and fetus. Changes in histone-modifying enzymes were also observed in the placenta. Histone marks H3K4me3, H3K9me3, and H4ac were downregulated, while H3K27me3 and H3ac were upregulated in placentas derived from obese male rats. This study shows that obesity-related changes in sperm methylome translate into abnormal expression in the F1-placenta fathered by the obese male, presumably affecting placental and fetal development.     

Environmental and nutritional responses of a Pinus radiata plantation to biosolids application

Since the mid-1990s, a Pinus radiata (D. Don) plantation growing on a sandy, low fertility soil at Rabbit Island near Nelson, New Zealand received aerobically digested liquid biosolids. An experimental research trial was established on the site to investigate the effects of biosolids applications on tree growth, nutrition, soil and ground water quality. Biosolids were applied to the trial site in 1997 and 2000, at three application rates: 0 (control), 300 (standard) and 600 kg N ha⁻¹ (high). Biosolids application significantly increased tree growth. This was mainly attributed to improved N supply, demonstrated by the enhanced N concentration in the tree foliage. Soil analysis indicated that biosolids application have not caused significant changes in concentrations of most nutrients. However, biosolids treatments significantly increased the available P (Olsen P). Of the heavy metals only total Cu concentrations in the soil increased after biosolids application. Groundwater quality, which was monitored quarterly, has not been affected by biosolids application. The concentrations of nitrate and heavy metals in groundwater were well below the maximum acceptable values in drinking water standards. Biological treatment of sewage and digestion of sewage sludge resulted in the enrichment of ¹⁵N in the biosolids (δ¹⁵N values between 5.0 and 8.7‰). Such enrichment was used as a tracer to study the fate of biosolids derived N. The elevated δ¹⁵N in biosolids treated pine foliage indicated that a considerable amount N was sourced from biosolids. Analysis of δ¹⁵N in understorey plants showed that both non-legume and legume understorey plants took up N from the biosolids, and acted as a N sink, reducing N availability for leaching. Our study showed that application of biosolids to a plantation forest can significantly improve tree nutrition and site productivity without resulting in any measurable adverse effect on the receiving environment.     

Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis

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