We report here that overexpression of the tuberous sclerosis-1 (TSC1) gene product hamartin results in the inhibition of growth, as well as changes in cell morphology. Growth inhibition was associated with an increase in the endogenous level of the product of the tuberous sclerosis-2 (TSC2) gene, tuberin. As overexpression of tuberin inhibits cell growth, and hamartin is known to bind tuberin, these results suggested that hamartin stabilizes tuberin and this contributes to the inhibition of cell growth. Indeed, transient transfection of TSC1 increased the endogenous level of tuberin, and transient co-transfection of TSC1 with TSC2 resulted in higher tuberin levels. The stabilization was explained by the ®nding that tuberin is highly ubiquitinated in cells, while the fraction of tuberin that is bound to hamartin is not ubiquitinated. Co-expression of tuberin stabilized hamartin, which is weakly ubiquitinated, in transiently transfected cells. The amino-terminal two-thirds of tuberin was responsible for its ubiquitination and for stabilization of hamartin. A mutant of tuberin from a patient missense mutation of TSC2 was also highly ubiquitinated, and was unable to stabilize hamartin. We conclude that hamartin is a growth inhibitory protein whose biological e ect is likely dependent on its interaction with tuberin. Oncogene (2000) 19, 6306 ± 6316.

Efficient decision-making integrates previous experience with new information. Tactical use of misinformation can alter choice in humans. Whether misinformation affects decision-making in other free-living species, including problem species, is unknown. Here, we show that sensory misinformation tactics can reduce the impacts of predators on vulnerable bird populations as effectively as lethal control. We repeatedly exposed invasive mammalian predators to unprofitable bird odors for 5 weeks before native shorebirds arrived for nesting and for 8 weeks thereafter. Chick production increased 1.7-fold at odor-treated sites over 25 to 35 days, with doubled or tripled odds of successful hatching, resulting in a 127% increase in modeled population size in 25 years. We demonstrate that decision-making processes that respond to changes in information reliability are vulnerable to tactical manipulation by misinformation. Altering perceptions of prey availability offers an innovative, nonlethal approach to managing problem predators and improving conservation outcomes for threatened species.

Empathy, the understanding of the emotional state of others, can be examined across species using the Perception Action Model, where shared affect promotes an action by “Observers” to aid a distressed “Target”. The anterior insula (AI) has garnered interest in empathic behavior due to its role integrating sensory and emotional information of self and other. In the following studies, the AI was inhibited pharmacologically and chemogenetically during targeted helping. We demonstrate the insula is active during, and is necessary for the maintenance of, targeted helping. Analysis of ultrasonic vocalizations revealed distress calls from Targets increased when Observers’ helping was attenuated due to insula inhibition. Targets’ elevated distress was directly correlated to Observers’ diminished helping behavior, suggesting emotional transfer between Observer and Target is blunted following Observer AI inhibition. Finally, the AI may selectively blunt targeted helping, as social exploration did not change in a social reward place conditioning task. These studies help further establish the anterior insula as a critical node in the empathic brain during targeted helping, even in the absence of direct social contact.

Invasive mammalian predators can cause the decline and extinction of vulnerable native species. Many invasive mammalian predators are dietary generalists that hunt a variety of prey. These predators often rely upon olfaction when foraging, particularly at night. Little is understood about how prey odor cues are used to inform foraging decisions. Prey cues can vary spatially and temporally in their association with prey and can either reveal the location of prey or lead to unsuccessful foraging. Here we examine how two wild-caught invasive mammalian bird predator species (European hedgehogs Erinaceus europaeus and ferrets Mustela putorius furo) respond to unrewarded bird odors over successive exposures, first demonstrating that the odors are perceptually different using house mice (Mus musculus) as a biological olfactometer. We aim to test if introduced predators categorize odor cues of similar prey together, a tactic that could increase foraging efficiency. We exposed house mice to the odors using a standard habituation/dishabituation test in a laboratory setting, and wild-caught European hedgehogs and ferrets in an outdoor enclosure using a similar procedure. Mice discriminated among all bird odors presented, showing more interest in chicken odor than quail or gull odor. Both predator species showed a decline in interest toward unrewarded prey odor (i.e., habituation), but only ferrets generalized their response from one unrewarded bird odor to another bird odor. Hedgehog responses to unrewarded bird odors were highly variable between individuals. Taken together, our results reveal interspecific and intraspecific differences in response to prey odors, which we argue are a consequence of different diet breadth, life and evolutionary histories, and the conditions in each experiment. Generalization of prey odors may have enabled some species of invasive predators to efficiently hunt a range of intraguild prey species, for example, ground-nesting shorebirds. Olfactory manipulation of predators may be a useful conservation tool for threatened prey if it reduces the conspicuousness of vulnerable prey.

No abstract