Novel isatin-derived molecules activate p53 via interference with Mdm2 to promote apoptosis

The p53 protein is a key tumor suppressor in mammals. In response to various forms of genotoxic stress p53 stimulates expression of genes whose products induce cell cycle arrest and/or apoptosis. An E3-ubiquitin ligase, Mdm2 (mouse-double-minute 2) and its human ortholog Hdm2, physically interact with the amino-terminus of p53 to mediate its ubiquitin-mediated degradation via the proteasome. Thus, pharmacological inhibition of the p53-Mdm2 interaction leads to overall stabilization of p53 and stimulation of its anti-tumorigenic activity. In this study we characterize the biological effects of a novel class of non-genotoxic isatin Schiff and Mannich base derivatives (ISMBDs) that stabilize p53 on the protein level. The likely mechanism behind their positive effect on p53 is mediated via the competitive interaction with Mdm2. Importantly, unlike Nutlin, these compounds selectively promoted p53-mediated cell death. These novel pharmacological activators of p53 can serve as valuable molecular tools for probing p53-positive tumors and set up the stage for development of new anti-cancer drugs.     

Biogeographic variation of food habits and body size of the America puma

Summary The puma (Felis concolor) has the most extensive range of any terrestrial mammal in the Western Hemisphere, covering over 100° latitude. Food habits of different puma subspecies vary with latitude. Subspecies from temperate habitats generally eat larger prey and specialize on a smaller number of prey taxa, whereas, in tropical habitats, they prey on smaller, more varied prey. In North America, ungulates (primarily deer) represented 68% of the puma's diet by frequency of occurrence. Mean weight of vertebrate prey (MWVP) was positively correlated (r=0.875) with puma body weight and inversely correlated (r=-0.836) with food niche breadth in all America. In general, MWVP was lower in areas closer to the Equator. Patterns of puma prey selection are probably influenced by prey availability and vulnerability, habitat characteristics, and potential competition from the jaguar (Panthera onca).     

Genetic assessment of paternity and relatedness in a managed population of cougars

Understanding the social dynamics of large carnivores is critical to effective conservation and management planning. We made the first attempt to delineate both paternity and relatedness for a population of cougar (Puma concolor) using microsatellite data. We analyzed a long-term genetic dataset collected from a hunted population in the Garnet Mountains of western Montana. We assigned paternity for 62.5% of litters sampled using both exclusion and likelihood analyses. Attempts at reconstructing unsampled paternal genotypes resulted in delineating possible sires for 8 more litters. Sires were on average younger than reported for males involved in pairings assessed via field data in other cougar populations. Although most mating pairs were unrelated, 5 of 17 pairings involved cougars with levels of relatedness corresponding to half-sibling and full-sibling or parent offspring relationship (r = 0.215–0.575). Relatedness among adult and subadult males was higher than relatedness levels among adult and subadult females. Relatedness among males in the Garnet population differed from patterns hypothesized to occur under male-biased dispersal theories for cougars. The long-term impact of the turnover of resident cougars in hunted populations is still unclear and warrants additional research. Our results highlight the utility of monitoring cougar demographic parameters using a combination of genetic and field data that in turn may assist managers with determining cougar harvest quotas or strategies, harvest seasons, sustainable harvest, and the appropriate management level of cougar populations. © 2011 The Wildlife Society.     

Long-Distance Dispersal of a Female Cougar in a Basin and Range Landscape

Abstract: We used Global Positioning System technology to document distance, movement path, vegetation, and elevations used by a dispersing subadult female cougar (Puma concolor) through the fragmented habitat of the Intermountain West, USA. Over the course of 1 year, female number 31 moved 357 linear km, but an actual distance of 1,341 km from the Oquirrh Mountains, Utah to the White River Plateau, Colorado, constituting the farthest dispersal yet documented for a female cougar. This cougar successfully negotiated 4 major rivers and one interstate highway while traversing portions of 3 states. Our data suggest that transient survival, and therefore total distance moved, may be enhanced when dispersal occurs during the snow-free season due to low hunting pressure and greater access to high elevation habitats. Long-distance movements by both sexes will be required for the recolonization of vacant habitats, and thus inter-state management may be warranted where state boundaries do not coincide with effective dispersal barriers.     

Cougars’ key to survival through the Late Pleistocene extinction: insights from dental microwear texture analysis

Cougars (Puma concolor) are one of only two large cats in North America to have survived the Late Pleistocene extinction (LPE), yet the specific key(s) to their relative success remains unknown. Here, we compare the dental microwear textures of Pleistocene cougars with sympatric felids from the La Brea Tar Pits in southern California that went extinct at the LPE (Panthera atrox and Smilodon fatalis), to clarify potential dietary factors that led to the cougar''s persistence through the LPE. We further assess whether the physical properties of food consumed have changed over time when compared with modern cougars in southern California. Using dental microwear texture analysis (DMTA), which quantifies surface features in three dimensions, we find that modern and Pleistocene cougars are not significantly different from modern African lions in any DMTA attributes, suggesting moderate durophagy (i.e. bone processing). Pleistocene cougars from La Brea have significantly greater complexity and textural fill volume than Panthera atrox (inferred to have primarily consumed flesh from fresh kills) and significantly greater variance in complexity values than S. fatalis. Ultimately, these results suggest that cougars already used or adopted a more generalized dietary strategy during the Pleistocene that may have been key to their subsequent success.     

Detection of Bim and Puma in mouse hair follicles using immunofluorescence and TUNEL assay double staining

Apoptosis in hair follicles often is studied under pathological conditions; little is known about apoptotic mechanisms during normal hair follicle formation and maintenance. We investigated proteins of intrinsic apoptotic pathway, Bim and Puma, during hair follicle development and the first catagen stage using immunofluorescence to describe their expression patterns and to correlate them with apoptosis as determined by TUNEL assay. Both proteins were found in developing follicles. Bim and Puma overlapped apoptosis only partially during physiological apoptotic stage and they were present in non-apoptotic parts of the follicles. Our findings suggest that these primary apoptotic molecules participate in postnatal development and maintenance of hair follicles.     

Scavenging Makes Cougars Susceptible to Snaring at Wolf Bait Stations

Abstract: In western Canada it is illegal to trap or snare cougars (Puma concolor), but cougars are sometimes caught accidentally in snares placed near carrion baits, a technique commonly used by trappers to harvest wolves (Canis lupus). We studied cougar foraging ecology and survival in west-central Alberta to estimate the propensity for cougars to scavenge, their susceptibility to snaring at trapper bait stations, and the implications these have for managing cougar populations. During 2005–2008, we used data from visits to 3,407 Global Positioning System (GPS) location clusters and >400 km of snow tracking of 44 cougars to locate foraging events and calculate scavenging rates. We identified 83 instances of scavenging, and 64% of monitored cougars scavenged at least once. Scavenging rates were higher in winter (0.12 events/week) than in summer (0.04 events/week), reflecting seasonal variation in carrion availability. Individual cougars scavenged at different rates, and winter feeding on carrion occupied up to 50% of total carcass handling time for some cougars. Based on these results we conclude that cougars are facultative scavengers. A propensity to scavenge made cougars susceptible to snaring causing high annual mortality in radiocollared cougars (0.11, 95% CI = 0.03–0.21). Provincial cougar mortality data demonstrate that snaring has increased dramatically as a mortality source in Alberta over the last 2 decades. Mortalities of radiocollared cougars during our study were 100% human caused and the addition of snaring mortality to already high hunting mortality resulted in low annual survival (0.67, 95% CI = 0.53–0.81). Our study is one of the first to identify population-level consequences for nontarget animals killed unintentionally by indiscriminate harvest techniques in a terrestrial ecosystem. Maintaining sustainable cougar harvest where snaring at carrion baits is permitted may require flexible hunting quotas capable of accommodating high cougar snaring mortalities in some years.     

Have natural disasters created opportunities to initiate Big Cat Tourism in South America?

Livestock is the predominant biomass in terrestrial systems around the world, and conflict with livestock inventories continues to threaten large carnivore persistence in increasingly fragmented habitats. Nevertheless, social tolerance for large carnivores is increasing, as is interest in predator tourism, which can facilitate wildlife–livestock coexistence strategies. We report two case studies in which natural disasters led to a reduction in local livestock inventories, and subsequent economic hardships that in turn created opportunities for initiating predator tourism: jaguar tourism in the Pantanal of Brazil and puma tourism in the Patagonia steppe grasslands of southern Chile. Any time livestock numbers are reduced, whether through management decisions or natural disasters, may be considered opportunities to reduce dependency upon livestock and to weigh diversifying revenue streams via alternative activities, such as tourism. Livestock reductions in combination with a surge in the global demand for wildlife tourism have made jaguar and puma tourism an increasingly important economic activity for both regions. Well-managed predator tourism can be effective carnivore conservation, and if integrated among other strategies, can augment conservation agendas.