A logical model provides insights into T cell receptor signaling

Cellular decisions are determined by complex molecular interaction networks. Large-scale signaling networks are currently being reconstructed, but the kinetic parameters and quantitative data that would allow for dynamic modeling are still scarce. Therefore, computational studies based upon the structure of these networks are of great interest. Here, a methodology relying on a logical formalism is applied to the functional analysis of the complex signaling network governing the activation of T cells via the T cell receptor, the CD4/CD8 co-receptors, and the accessory signaling receptor CD28. Our large-scale Boolean model, which comprises 94 nodes and 123 interactions and is based upon well-established qualitative knowledge from primary T cells, reveals important structural features (e.g., feedback loops and network-wide dependencies) and recapitulates the global behavior of this network for an array of published data on T cell activation in wild-type and knock-out conditions. More importantly, the model predicted unexpected signaling events after antibody-mediated perturbation of CD28 and after genetic knockout of the kinase Fyn that were subsequently experimentally validated. Finally, we show that the logical model reveals key elements and potential failure modes in network functioning and provides candidates for missing links. In summary, our large-scale logical model for T cell activation proved to be a promising in silico tool, and it inspires immunologists to ask new questions. We think that it holds valuable potential in foreseeing the effects of drugs and network modifications.     

Small-molecule pheromones that control dauer development in Caenorhabditis elegans

In response to high population density or low food supply, the nematode Caenorhabditis elegans enters an alternative larval stage, known as the dauer, that can withstand adverse conditions for prolonged periods. C. elegans senses its population density through a small-molecule signal, traditionally called the dauer pheromone, that it secretes into its surroundings. Here we show that the dauer pheromone consists of several structurally related ascarosides-derivatives of the dideoxysugar ascarylose-and that two of these ascarosides (1 and 2) are roughly two orders of magnitude more potent at inducing dauer formation than a previously reported dauer pheromone component (3) and constitute a physiologically relevant signal. The identification of dauer pheromone components 1 and 2 will facilitate the identification of target receptors and downstream signaling proteins.     

Blooms of Pseudo-nitzschia and domoic acid in the San Pedro Channel and Los Angeles harbor areas of the Southern California Bight, 2003–2004

Abundances of Pseudo-nitzschia spp. and concentrations of particulate domoic acid (DA) were determined in the Southern California Bight (SCB) along the coasts of Los Angeles and Orange Counties during spring and summer of 2003 and 2004. At least 1500 km² were affected by a toxic event in May/June of 2003 when some of the highest particulate DA concentrations reported for US coastal waters were measured inside the Los Angeles harbor (12.7 μg DA L⁻¹). Particulate DA levels were an order of magnitude lower in spring of 2004 (February and March), but DA concentrations per cell at several sampling stations during 2004 exceeded previously reported maxima for natural populations of Pseudo-nitzschia (mean = 24 pg DA cell⁻¹, range = 0–117 pg DA cell⁻¹). Pseudo-nitzschia australis dominated the Pseudo-nitzschia assemblage in spring 2004. Overall, DA-poisoning was implicated in >1400 mammal stranding incidents within the SCB during 2003 and 2004. Ancillary physical and chemical data obtained during our regional surveys in 2004 revealed that Pseudo-nitzschia abundances, particulate DA and cellular DA concentrations were inversely correlated with concentrations of silicic acid, nitrogen and phosphate, and to specific nutrient ratios. Particulate DA was detected in sediment traps deployed at 550 and 800 m depth during spring of 2004 (0.29–7.6 μg DA (g sediment dry weight)⁻¹). The highest DA concentration in the traps was measured within 1 week of dramatic decreases in the abundances of Pseudo-nitzschia in surface waters. To our knowledge these are the deepest sediment trap collections from which DA has been detected. Sinking of the spring Pseudo-nitzschia bloom may constitute a potentially important link between DA production in surface waters and benthic communities in the coastal ocean near Los Angeles. Our study indicates that toxic blooms of Pseudo-nitzschia are a recurring phenomenon along one of the most densely populated coastal stretches of the SCB and that the severity and magnitude of these events can be comparable to or greater than these events in other geographical regions affected by domoic acid.     

Turbidity Structures the Controls of Ecosystem Metabolism and Associated Metabolic Process Domains Along a 75-km Segment of a Semiarid Stream

Ecosystems - Stream ecosystem metabolism contributes to global carbon cycling, yet predicting metabolism across ecosystems remains elusive. Even within stream segments, spatial variation in...     

Research Participation Influences Willingness to Reduce Zoonotic Exposure in Uganda

EcoHealth - The majority of emerging and re-emerging infectious diseases in people are zoonotic. Despite substantial research in communities adjacent to protected areas with high levels of...     

Spatial distribution and landscape associations of large-antlered deer

For more than a century, the Boone and Crockett Club has kept records of harvest locations for 38 categories of North American big game, which includes measurement details and sizes of enduring characteristics (e.g., antlers, skulls, horns). All white-tailed deer (Odocoileus virginianus) entered in the Club records (i.e., record deer) have large antlers because the measurements must meet or exceed a minimum size to qualify for entry. We used the records from the Club to test the hypothesis that the spatial distribution in the harvest of record deer was related to the number of antlered deer harvested, variations in land productivity, soil mineral content, and attributes of land cover for 9 states in the midwestern United States. We used a Bayesian theoretical framework to develop a spatial model that examined the influence of explanatory variables on the number of record deer harvested in each county. In our study area, 3,658 record deer were harvested in 692 of the 856 counties (80.8%). More record deer were harvested in counties that had more high-contrast edges, less contiguous land cover, and greater variation in soil productivity. These results provide information for managers and hunters to better understand the spatial distribution of record deer and factors that are correlated with their distribution. © 2019 The Wildlife Society.     

Can environmental flows moderate riparian invasions? The influence of seedling morphology and density on scour losses in experimental floods

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