Trichothecenes are a family of terpenoid toxins produced by multiple genera of fungi, including plant and insect pathogens. Some trichothecenes produced by the fungus Fusarium are among the mycotoxins of greatest concern to food and feed safety because of their toxicity and frequent occurrence in cereal crops, and trichothecene production contributes to pathogenesis of some Fusarium species on plants. Collectively, fungi produce over 150 trichothecene analogs: i.e., molecules that share the same core structure but differ in patterns of substituents attached to the core structure. Here, we carried out genomic, phylogenetic, gene-function, and analytical chemistry studies of strains from nine fungal genera to identify genetic variation responsible for trichothecene structural diversity and to gain insight into evolutionary processes that have contributed to the variation. The results indicate that structural diversity has resulted from gain, loss, and functional changes of trichothecene biosynthetic (TRI) genes. The results also indicate that the presence of some substituents has arisen independently in different fungi by gain of different genes with the same function. Variation in TRI gene duplication and number of TRI loci was also observed among the fungi examined, but there was no evidence that such genetic differences have contributed to trichothecene structural variation. We also inferred ancestral states of the TRI cluster and trichothecene biosynthetic pathway, and proposed scenarios for changes in trichothecene structures during divergence of TRI cluster homologs. Together, our findings provide insight into evolutionary processes responsible for structural diversification of toxins produced by pathogenic fungi.

Maternal obesity is associated with pregnancy complications and increases the risk for the infant to develop obesity, diabetes and cardiovascular disease later in life. However, the mechanisms linking the maternal obesogenic environment to adverse short- and long-term outcomes remain poorly understood. As compared with pregnant women with normal BMI, women entering pregnancy obese have more pronounced insulin resistance, higher circulating plasma insulin, leptin, IGF-1, lipids and possibly proinflammatory cytokines and lower plasma adiponectin. Importantly, the changes in maternal levels of nutrients, growth factors and hormones in maternal obesity modulate placental function. For example, high insulin, leptin, IGF-1 and low adiponectin in obese pregnant women activate mTOR signaling in the placenta, promoting protein synthesis, mitochondrial function and nutrient transport. These changes are believed to increase fetal nutrient supply and contribute to fetal overgrowth and/or adiposity in offspring, which increases the risk to develop disease later in life. However, the majority of obese women give birth to normal weight infants and these pregnancies are also associated with activation of inflammatory signaling pathways, oxidative stress, decreased oxidative phosphorylation and lipid accumulation in the placenta. Recent bioinformatics approaches have expanded our understanding of how maternal obesity affects the placenta; however, the link between changes in placental function and adverse outcomes in obese women giving birth to normal sized infants is unclear. Interventions that specifically target placental function, such as activation of placental adiponectin receptors, may prevent the transmission of metabolic disease from obese women to the next generation.

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Even deadly prions may be widespread in nature if they spread by infection faster than they kill off their hosts. The yeast prions [PSI+] and [URE3] (amyloids of Sup35p and Ure2p) were not found in 70 wild strains, while [PIN+] (amyloid of Rnq1p) was found in ∼16% of the same population. Yeast prion infection occurs only by mating, balancing the detrimental effects of carrying the prion. We estimated the frequency of outcross mating as about 1% of mitotic doublings from the known detriment of carrying the 2-μm DNA plasmid (∼1%) and its frequency in wild populations (38/70). We also estimated the fraction of total matings that are outcross matings (∼23-46%) from the fraction of heterozygosity at the highly polymorphic RNQ1 locus (∼46% [PIN+] of S. cerevisiae are parallel in-register β-sheet amyloids of Sup35p, Ure2p, and Rnq1p, respectively (7-10); the [Het-s] prion of P. anserina is a β-helical amyloid of the HET-s protein (11). Sup35p is a subunit of the translation termination factor (12, 13), Ure2p is a regulator of nitrogen catabolism (14), and Rnq1p has no known function (15).The mammalian prions are uniformly lethal but nonetheless are found in wild animals. For example, chronic wasting disease of deer and elk is found in ∼10% of wild deer in parts of Wyoming, Colorado, Illinois, and Wisconsin (16). Evidently, infectious spread outpaces the lethal effects on the animals. The [Het-s] prion of P. anserina is involved in heterokaryon incompatibility, a normal function of that species, and, as a result, ∼80% of wild strains with the appropriate chromosomal genotype carry the [Het-s] (20), a result confirmed by others (21) and which we interpreted as meaning that they are substantially detrimental. Nonetheless, others argue that these prions are beneficial, promoting survival by allowing cells to resist stress (22, 23), although the reported effects were not reproducible with the same strains (24). It is reported further that certain stress conditions increase the frequency of[PSI+] when assayed using a synthetic Sup35p with an elevated prion-forming tendency (25). Here we test these conditions for an effect on prion formation by the wild-type Sup35p.Our argument, that the rare occurrence of an infectious agent in nature implies pathologic effects on the host, relies on outcross mating being a fairly frequent event. Yeast prions spread only by mating (there is no extracellular prion species in the replication cycle), and if outcross mating is extremely rare, then yeast prions could be rare even if their effects on the host were neutral. Yeast spores germinate with mating type either a or α, and a and α spores from the same tetrad may mate (intratetrad or brothersister). The mating-type switching system (homothallism) results in the clone from a single germinated spore becoming a mixture of a and α cells which can mate with each other. These two kinds of "selfing" are unlikely to spread any virus, plasmid, or prion, because probably both mating partners will lack the element, or both will have it. Alternat...