TREX1 - Apex predator of cytosolic DNA metabolism.
Ontology highlight
ABSTRACT:
SUBMITTER: Simpson SR
PROVIDER: S-EPMC7985832 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
TREX1 - Apex predator of cytosolic DNA metabolism.
Simpson Sean R SR Hemphill Wayne O WO Hudson Teesha T Perrino Fred W FW
DNA repair 20200612
The cytosolic Three prime Repair EXonuclease 1 (TREX1) is a powerful DNA-degrading enzyme required for clearing cytosolic DNA to prevent aberrant inflammation and autoimmunity. In the absence of TREX1 activity, cytosolic DNA pattern recognition receptors of the innate immune system are constitutively activated by undegraded TREX1 substrates. This triggers a chronic inflammatory response in humans expressing mutant TREX1 alleles, eliciting a spectrum of rare autoimmune diseases dependent on the n ...[more]
Similar Datasets
Project description:Cyclic GMP-AMP synthase (cGAS) recognition of cytosolic DNA is critical for the immune response to cancer and pathogen infection. Here, we discover that cGAS-DNA phase separation is required to resist negative regulation and allow efficient sensing of immunostimulatory DNA. We map the molecular determinants of cGAS condensate formation and demonstrate that phase separation functions to limit activity of the cytosolic exonuclease TREX1. Mechanistically, phase separation forms a selective environment that suppresses TREX1 catalytic function and restricts DNA degradation to an outer shell at the droplet periphery. We identify a TREX1 mutation associated with the severe autoimmune disease Aicardi-Goutières syndrome that increases penetration of TREX1 into the repressive droplet interior and specifically impairs degradation of phase-separated DNA. Our results define a critical function of cGAS-DNA phase separation and reveal a molecular mechanism that balances cytosolic DNA degradation and innate immune activation.
| S-EPMC7899126 | biostudies-literature
Project description:Despite the importance of ontogenetic data on early diverging euarthropods to our understanding of the ecology and evolution of past life, the data are distinctly lacking, as reconstructing life histories of fossil animals is often challenging. Here we report the growth trajectory of frontal appendages of the apex predator Amplectobelua symbrachiata, one of the most common radiodont arthropods from the early Cambrian Chengjiang biota (c. 520 Ma) of China. Analysis of 432 specimens (9.1-137.1 mm length; 1.3-25.6 mm height) reveals that appendages grew isometrically, with an estimated maximum size of the whole animal of c. 90 cm. Individuals grew rapidly compared to extant arthropods, as assessed using the electronic length-frequency analysis (ELEFAN) approach. Therefore, we show that the Cambrian apex predator A. symbrachiata was an extremely fast-growing arthropod, with an unusual life history strategy that formed as part of the escalatory 'arms race' that shaped the Cambrian explosion over 500 Ma.
| S-EPMC10833464 | biostudies-literature
Project description:Wildlife can respond to urbanization positively (synanthropic) or negatively (misanthropic), and for some species, this is a nonlinear process, whereby low levels of urbanization elicit a positive response, but this response becomes negative at high levels of urbanization. We applied concepts from foraging theory to predict positive and negative behavioral responses of coyotes (Canis latrans) along an urbanization gradient in the Chicago metropolitan area, USA. We estimated home range size and complexity, and metrics of 3 movement behaviors (encamped, foraging, and traveling) using Hidden Markov movement models. We found coyotes exhibited negative behavioral responses to highly urbanized landscapes: coyotes viewed the landscape as lower quality, riskier, and more fragmented (home range size and complexity, and time spent encamped increased). Conversely, we found evidence of both positive and negative responses to suburban landscapes: coyotes not only viewed the landscape as higher quality than natural fragments and equally risky, but also viewed it as fragmented (home range size decreased, time spent encamped did not change, and home range complexity increased). Although the spatial and behavioral responses of coyotes to urbanization became increasingly negative as urbanization increased, coyotes were still able to occupy highly urbanized landscapes. Our study demonstrates how wildlife behavioral responses can be dependent on the degree of urbanization and represents one of the first descriptions of apex predator space use and movement in a highly urbanized landscape.
| S-EPMC6562302 | biostudies-literature
Project description:Tiger sharks (Galeocerdo cuvier) are apex predators occurring in most tropical and warm temperate marine ecosystems, but we know relatively little of their patterns of residency and movement over large spatial and temporal scales. We deployed satellite tags on eleven tiger sharks off the north-western coast of Western Australia and used the Brownian Bridge kernel method to calculate home ranges and analyse movement behaviour. One individual recorded one of the largest geographical ranges of movement ever reported for the species, travelling over 4000 km during 517 days of monitoring. Tags on the remainder of the sharks reported for shorter periods (7-191 days). Most of these sharks had restricted movements and long-term (30-188 days) residency in coastal waters in the vicinity of the area where they were tagged. Core home range areas of sharks varied greatly from 1166.9 to 634,944 km2. Tiger sharks spent most of their time in water temperatures between 23°-26°C but experienced temperatures ranging from 6°C to 33°C. One shark displayed seasonal movements among three distinct home range cores spread along most of the coast of Western Australia and generalized linear models showed that this individual had different patterns of temperature and depth occupancy in each region of the coast, with the highest probability of residency occurring in the shallowest areas of the coast with water temperatures above 23°C. These results suggest that tiger sharks can migrate over very large distances and across latitudes ranging from tropical to the cool temperate waters. Such extensive long-term movements may be a key element influencing the connectivity of populations within and among ocean basins.
| S-EPMC4324986 | biostudies-literature
Project description:Habitat loss, overexploitation, and numerous other stressors have caused global declines in apex predators. This "trophic downgrading" has generated widespread concern because of the fundamental role that apex predators can play in ecosystem functioning, disease regulation, and biodiversity maintenance. In attempts to combat declines, managers have conducted reintroductions, imposed stricter harvest regulations, and implemented protected areas. We suggest that full recovery of viable apex predator populations is currently the exception rather than the rule. We argue that, in addition to well-known considerations, such as continued exploitation and slow life histories, there are several underappreciated factors that complicate predator recoveries. These factors include three challenges. First, a priori identification of the suite of trophic interactions, such as resource limitation and competition that will influence recovery can be difficult. Second, defining and accomplishing predator recovery in the context of a dynamic ecosystem requires an appreciation of the timing of recovery, which can determine the relative density of apex predators and other predators and therefore affect competitive outcomes. Third, successful recovery programs require designing adaptive sequences of management strategies that embrace key environmental and species interactions as they emerge. Consideration of recent research on food web modules, alternative stable states, and community assembly offer important insights for predator recovery efforts and restoration ecology more generally. Foremost among these is the importance of a social-ecological perspective in facilitating a long-lasting predator restoration while avoiding unintended consequences.
| S-EPMC4928970 | biostudies-literature
Project description:Constitutive low level DNA damage is linked to innate immune activation. Hierarchical clustering of over 9000 transcripts revealed remarkably similar profiles in a patient with lupus erythematosus and a patient with AGS with up-regulation of genes involved in DNA damage signaling, p53-inducible genes, senescence-associated genes as well as up-regulation of interferon-stimulated genes. Transcriptional profiling of fibroblasts exposed to oxidative stress showed a marked up-regulation of genes involved in DNA replication/repair and replication licensing in TREX1-deficient cells compared to wild type cells suggesting massive replication stress. Comparison of transcriptional profiles of unstressed patient fibroblasts with wild type cells as well as fibroblasts exposed to oxidative stress
2016-05-30 | E-GEOD-59233 | biostudies-arrayexpress
Project description:Large "hypercarnivorous" felids are recognized for their role as apex predators and hence as key elements in food webs and ecosystem functioning through competition and depredation. Here we show that cougars (Puma concolor), one of the largest and the most widely ranging apex felid predators with a strictly carnivorous diet, could also be effective secondary long distance seed dispersers, potentially establishing direct and non-herbivore mediated interactions with plant species at the bottom of the food web. Cougars accidently ingest and disseminate large amounts of seeds (31,678 seeds in 123 scats) of plant species initially consumed by their main prey, the Eared Dove Zenaida auriculata. The germination potential of seeds for the three plant species most abundantly found in cougar scats (19,570 seeds) was not significantly different from that observed in seeds obtained from dove gizzards, indicating that seed passage through cougar guts did not affect seed germination. Considering the estimated cougar density in our study area, dispersal of seeds by cougars could allow a mean, annual seed spread of ~5,000 seeds per km(2). Our results demonstrate that strictly carnivorous, felid predators could have broad and overlooked ecological functions related to ecosystem structuring and functioning.
| S-EPMC4726145 | biostudies-other
Project description:Within optimality theory, an animal's home range can be considered a fitness-driven attempt to obtain resources for survival and reproduction while minimizing costs. We assessed whether brown bears (Ursus arctos) in two island populations maximized resource patches within home ranges (Resource Dispersion Hypothesis [RDH]) or occupied only areas necessary to meet their biological requirements (Temporal Resource Variability Hypothesis [TRVH]) at annual and seasonal scales. We further examined how intrinsic factors (age, reproductive status) affected optimal choices. We found dynamic patterns of space use between populations, with support for RDH and TRVH at both scales. The RDH was likely supported seasonally as a result of bears maximizing space use to obtain a mix of nutritional resources for weight gain. Annually, support for RDH likely reflected changing abundances and distributions of foods within different timber stand classes. TRVH was supported at both scales, with bears minimizing space use when food resources were temporally concentrated. Range sizes and optimal strategies varied among sex and reproductive classes, with males occupying larger ranges, supporting mate seeking behavior and increased metabolic demands of larger body sizes. This work emphasizes the importance of scale when examining animal movement ecology, as optimal behavioral decisions are scale dependent.
| S-EPMC8548348 | biostudies-literature
Project description:Apex predator reintroductions have proliferated across southern Africa, yet their ecological effects and proposed umbrella benefits of associated management lack empirical evaluations. Despite a rich theory on top-down ecosystem regulation via mesopredator suppression, a knowledge gap exists relating to the influence of lions (Panthera leo) over Africa's diverse mesocarnivore (less than 20 kg) communities. We investigate how geographical variation in mesocarnivore community richness and occupancy across South African reserves is associated with the presence of lions. An interesting duality emerged: lion reserves held more mesocarnivore-rich communities, yet mesocarnivore occupancy rates and evenness-weighted diversity were lower in the presence of lions. Human population density in the reserve surroundings had a similarly ubiquitous negative effect on mesocarnivore occupancy. The positive association between species richness and lion presence corroborated the umbrella species concept but translated into small differences in community size. Distributional contractions of mesocarnivore species within lion reserves, and potentially corresponding numerical reductions, suggest within-community mesopredator suppression by lions, probably as a result of lethal encounters and responses to a landscape of fear. Our findings offer empirical support for the theoretical understanding of processes underpinning carnivore community assembly and are of conservation relevance under current large-predator orientated management and conservation paradigms.
| S-EPMC7944110 | biostudies-literature
Project description:Climate change has broad ecological implications for species that rely on sensitive habitats. For some top predators, loss of habitat is expected to lead to cascading behavioral, nutritional, and reproductive changes that ultimately accelerate population declines. In the case of the polar bear (Ursus maritimus), declining Arctic sea ice reduces access to prey and lengthens seasonal fasting periods. We used a novel combination of physical capture, biopsy darting, and visual aerial observation data to project reproductive performance for polar bears by linking sea ice loss to changes in habitat use, body condition (i.e., fatness), and cub production. Satellite telemetry data from 43 (1991-1997) and 38 (2009-2015) adult female polar bears in the Baffin Bay subpopulation showed that bears now spend an additional 30 d on land (90 d in total) in the 2000s compared to the 1990s, a change closely correlated with changes in spring sea ice breakup and fall sea ice formation. Body condition declined for all sex, age, and reproductive classes and was positively correlated with sea ice availability in the current and previous year. Furthermore, cub litter size was positively correlated with maternal condition and spring breakup date (i.e., later breakup leading to larger litters), and negatively correlated with the duration of the ice-free period (i.e., longer ice-free periods leading to smaller litters). Based on these relationships, we projected reproductive performance three polar bear generations into the future (approximately 35 yr). Results indicate that two-cub litters, previously the norm, could largely disappear from Baffin Bay as sea ice loss continues. Our findings demonstrate how concurrent analysis of multiple data types collected over long periods from polar bears can provide a mechanistic understanding of the ecological implications of climate change. This information is needed for long-term conservation planning, which includes quantitative harvest risk assessments that incorporate estimated or assumed trends in future environmental carrying capacity.
| S-EPMC7317597 | biostudies-literature