Summary Ras is mutated in up to 30% of cancers, including 90% of pancreatic ductal adenocarcinomas, causing it to be constitutively GTP-bound, and leading to activation of downstream effectors that promote a tumorigenic phenotype. As targeting Ras directly is difficult, there is a significant effort to understand the downstream biological processes that underlie its pro-tumorigenic activity. Here, we show that expression of oncogenic Ras or direct activation of the MAPK pathway leads to increased mitochondrial fragmentation and that blocking this phenotype, through knockdown of the mitochondrial fission-mediating GTPase Drp1, inhibits tumor growth. This fission is driven by Erk2-mediated phosphorylation of Drp1 on Serine 616 and both this phosphorylation and mitochondrial fragmentation are increased in human pancreatic cancer. Finally, this phosphorylation is required for Ras-associated mitochondrial fission and its inhibition is sufficient to block xenograft growth. Collectively, these data suggest mitochondrial fission may be a target for treating MAPK-driven malignancies.

Disease foci of the conifer root and butt decay pathogen Heterobasidion irregulare are typically initiated following germination of spores deposited on freshly cut stumps, followed by expansion by tree to tree spread through root contacts and grafts. Although most abundant in autumn, inoculum of H. irregulare is also available during some cold winter periods in northern portions of the eastern United States. In both laboratory and field experiments, fresh stem discs of red pine (Pinus resinosa) were inoculated with H. irregulare conidia to test the null hypothesis that the pathogen would not survive prolonged exposure to cold temperatures experienced during winters in those regions. After exposure to cold for various periods of time, discs were incubated and then observed for presence of the Spiniger state of the pathogen. In each of two laboratory trials, the fungus survived on red pine discs incubated at ≤−20°C for 90 days. The field experiment was conducted during each of two winters at two infested red pine plantations. Inoculated discs were deployed periodically beginning in early winter and retrieved after various periods of time until spring. The Spiniger state of the pathogen was frequently observed on discs after laboratory incubation, even after field exposure of up to 6 months, during which temperatures ≤−25°C were sometimes recorded. Whether viable due to growth from inoculum initially placed on the discs, or natural inoculum deposited on discs exposed in the infested plantations, winter temperatures did not eliminate survival of the pathogen on this natural substrate. The potential for survival on stump surfaces during sub‐freezing temperatures during which application of stump protectants in water is impractical should be considered in evaluating the potential risk from H. irregulare to economically and environmentally valuable conifer forests of northcentral and northeastern North America.

No abstract

No abstract

Summary The fungal pathogen Heterobasidion irregulare has caused substantial damage to pine species in much of the south‐eastern United States, but the potential for damage from Heterobasidion root disease to forest tree species of the Great Lakes Region has not been thoroughly investigated. In each of three trials in two infested stands, fresh stem discs of six native conifer species were exposed to natural inoculum and examined for the asexual Spiniger stage of H. irregulare after incubation in the laboratory. In the first trial, the fungus was infrequently observed on discs, and differences among species were not found. But in the other two trials, detection of the pathogen was much more frequent on discs of tamarack (Larix laricina), red pine (Pinus resinosa) and white spruce (Picea glauca) than those of northern white cedar (Thuja occidentalis), eastern hemlock (Tsuga canadensis) and balsam fir (Abies balsamea). In a second study, the ability of an isolate of H. irregulare to decay root sapwood of these same species was compared using a soil‐block decay test. After 16 weeks of incubation, weight loss due to decay was greatest for red pine (23.2%) and larch (19.1%) and least for balsam fir (1.3%). Differences in the ability of H. irregulare to infect and saprophytically utilize substrate of these important tree species should prompt additional investigation of the relative risk posed to forests of the Great Lakes Region.