When should we treat isolated high triglycerides?

No evidence exists that treating isolated high triglyceride levels in the absence of other risk factors prevents coronary events. Although elevated triglycerides in some studies correlates with coronary events, the association weakens when controlled for factors such as diabetes, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, body mass index, and other cardiac risk factors. Coincident lowering of triglycerides, while treating other dyslipidemias (such as high LDL and low HDL), can contribute to decreasing coronary events (strength of recommendation [SOR]: A, based randomized controlled trials). Treating triglyceride levels over 500 to 1000 mg/dL may reduce the risk of pancreatitis (SOR: C, expert opinion)

Fine-scale spatial ecology drives kin selection relatedness among cooperating amoebae

Cooperation among microbes is important for traits as diverse as antibiotic resistance, pathogen virulence, and sporulation. The evolutionary stability of cooperation against “cheater” mutants depends critically on the extent to which microbes interact with genetically similar individuals. The causes of this genetic social structure in natural microbial systems, however, are unknown. Here, we show that social structure among cooperative Dictyostelium amoebae is driven by the population ecology of colonization, growth, and dispersal acting at spatial scales as small as fruiting bodies themselves. Despite the fact that amoebae disperse while grazing, all it takes to create substantial genetic clonality within multicellular fruiting bodies is a few millimeters distance between the cells colonizing a feeding site. Even adjacent fruiting bodies can consist of different genotypes. Soil populations of amoebae are sparse and patchily distributed at millimeter scales. The fine-scale spatial structure of cells and genotypes can thus account for the otherwise unexplained high genetic uniformity of spores in fruiting bodies from natural substrates. These results show how a full understanding of microbial cooperation requires understanding ecology and social structure at the small spatial scales microbes themselves experience

Fruiting bodies of the social amoeba \u3ci\u3eDictyostelium discoideum\u3c/i\u3e increase spore transport by Drosophila

Background: Many microbial phenotypes are the product of cooperative interactions among cells, but their putative fitness benefits are often not well understood. In the cellular slime mold Dictyostelium discoideum , unicellular amoebae aggregate when starved and form multicellular fruiting bodies in which stress-resistant spores are held aloft by dead stalk cells. Fruiting bodies are thought to be adaptations for dispersing spores to new feeding sites, but this has not been directly tested. Here we experimentally test whether fruiting bodies increase the rate at which spores are acquired by passing invertebrates. Results: Drosophila melanogaster accumulate spores on their surfaces more quickly when exposed to intact fruiting bodies than when exposed to fruiting bodies physically disrupted to dislodge spore masses from stalks. Flies also ingest and excrete spores that still express a red fluorescent protein marker. Conclusions: Multicellular fruiting bodies created by D. discoideum increase the likelihood that invertebrates acquire spores that can then be transported to new feeding sites. These results thus support the long-hypothesized dispersal benefits of altruism in a model system for microbial cooperation

In the social amoeba, Dictyostelium discoideum , density, not farming status, determines predatory success on unpalatable Escherichia coli

Background The social amoeba Dictyostelium discoideum interacts with bacteria in a variety of ways. It is a predator of bacteria, can be infected or harmed by bacteria, and can form symbiotic associations with bacteria. Some clones of D. discoideum function as primitive farmers because they carry bacteria through the normally sterile D. discoideum social stage, then release them after dispersal so the bacteria can proliferate and be harvested. Some farmer-associated bacteria produce small molecules that promote host farmer growth but inhibit the growth of non-farmer competitors. To test whether the farmers’ tolerance is specific or extends to other growth inhibitory bacteria, we tested whether farmer and non-farmer amoebae are differentially affected by E. coli strains of varying pathogenicity. Because the numbers of each organism may influence the outcome of amoeba-bacteria interactions, we also examined the influence of amoeba and bacteria density on the ability of D. discoideum to grow and develop on distinct bacterial strains. Results A subset of E. coli strains did not support amoeba proliferation on rich medium, independent of whether the amoebae were farmers or non-farmers. However, amoebae could proliferate on these strains if amoebae numbers are high relative to bacteria numbers, but again there was no difference in this ability between farmer and non-farmer clones of D. discoideum. Conclusions Our results show that farmer and non-farmers did not differ in their abilities to consume novel strains of E. coli, suggesting that farmer resistance to their own carried bacteria does not extend to foreign bacteria. We see that increasing the numbers of bacteria or amoebae increases their respective likelihood of competitive victory over the other, thus showing Allee effects. We hypothesize that higher bacteria numbers may result in higher concentrations of a toxic product or in a reduction of resources critical for amoeba survival, producing an environment inhospitable to amoeba predators. Greater amoeba numbers may counter this growth inhibition, possibly through reducing bacterial numbers via increased predation rates, or by producing something that neutralizes a potentially toxic bacterial product

Genome-wide identification and analysis of prognostic features in human cancers

Clinical decisions in cancer rely on precisely assessing patient risk. To improve our ability to identify the most aggressive malignancies, we constructed genome-wide survival models using gene expression, copy number, methylation, and mutation data from 10,884 patients. We identified more than 100,000 significant prognostic biomarkers and demonstrate that these genomic features can predict patient outcomes in clinically ambiguous situations. While adverse biomarkers are commonly believed to represent cancer driver genes and promising therapeutic targets, we show that cancer features associated with shorter survival times are not enriched for either oncogenes or for successful drug targets. Instead, the strongest adverse biomarkers represent widely expressed cell-cycle and housekeeping genes, and, correspondingly, nearly all therapies directed against these features have failed in clinical trials. In total, our analysis establishes a rich resource for prognostic biomarker analysis and clarifies the use of patient survival data in preclinical cancer research and therapeutic development

NCER Assistance Agreement Annual Progress Report for Grant #83582401 - Assessment of Stormwater Harvesting via Manage Aquifer Recharge (MAR) to Develop New Water Supplies in the Arid West: The Salt Lake Valley Example

The aims of the original proposed project remain the same, that is, to test the hypothesis that Managed Aquifer Recharge (MAR) for stormwater harvesting is a technically feasible, socially and environmentally acceptable, economically viable, and permittable option for developing new water supplies for arid Western urban ecosystems experiencing increasing population, and climate change pressures on existing water resources. The project is being carried out via three distinct but integrated components that include: 1) Monitoring of existing distributed Managed Aquifer Recharge (MAR) harvesting schemes involving a growing number of demonstration Green Infrastructure (GI) test sites; 2) Integrated stormwater/vadose zone/groundwater/ ecosystem services modeling; and 3) Social Science research assessing Stakeholder attitudes, and solicitation of their collaboration on feasible distributed MAR scenario development and subsequent analysis of scenario outcomes. Each of these components are discussed separately in the material presented below

Self-Regulatory Responses to Unattainable Goals: The Role of Goal Motives

Does motivation for goal pursuit predict how individuals will respond when confronted with unattainable goals? Two studies examined the role of autonomous and controlled motives when pursuing an unattainable goal without (Study 1) or with (Study 2) the opportunity to reengage in alternative goal pursuit. Autonomous motives positively predicted the cognitive ease of reengagement with an alternative goal when the current goal was perceived as unattainable, especially whenparticipants realized goal unattainability relatively early during goal striving. Autonomous motives, however, were negative predictors of cognitive ease of disengagement from an unattainable goal. When faced with failure, autonomously motivated individuals are better off realizing early the goal unattainability. Otherwise, they will find it difficult to disengage cognitively from the pursued goal(despite reengaging cognitively in an alternative goal), possibly due to interfering rumination

Btk Regulated Macrophage Polarization in Response to Lipopolysaccharide

Bacterial Lipopolysaccharide (LPS) is a strong inducer of inflammation and does so by inducing polarization of macrophages to the classic inflammatory M1 population. Given the role of Btk as a critical signal transducer downstream of TLR4, we investigated its role in M1/M2 induction. In Btk deficient (Btk−\−) mice we observed markedly reduced recruitment of M1 macrophages following intraperitoneal administration of LPS. Ex vivo analysis demonstrated an impaired ability of Btk−/− macrophages to polarize into M1 macrophages, instead showing enhanced induction of immunosuppressive M2-associated markers in response to M1 polarizing stimuli, a finding accompanied by reduced phosphorylation of STAT1 and enhanced STAT6 phosphorylation. In addition to STAT activation, M1 and M2 polarizing signals modulate the expression of inflammatory genes via differential activation of transcription factors and regulatory proteins, including NF-κB and SHIP1. In keeping with a critical role for Btk in macrophage polarization, we observed reduced levels of NF-κB p65 and Akt phosphorylation, as well as reduced induction of the M1 associated marker iNOS in Btk−/− macrophages in response to M1 polarizing stimuli. Additionally enhanced expression of SHIP1, a key negative regulator of macrophage polarisation, was observed in Btk−/− macrophages in response to M2 polarizing stimuli. Employing classic models of allergic M2 inflammation, treatment of Btk−/− mice with either Schistosoma mansoni eggs or chitin resulted in increased recruitment of M2 macrophages and induction of M2-associated genes. This demonstrates an enhanced M2 skew in the absence of Btk, thus promoting the development of allergic inflammation