Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis

National Institutes of Health grants GM-38765 and P50-DE016191 (C.N.S.), Welcome Trust Programme grant 086867/Z/08/Z (R.J.F. and M.P.) and Project grant 085903/Z/08 (R.J.F.) and Arthritis Research Campaign UK fellowships 18445 and 18103 (to L.V.N. and D.C., respectively). M.S. received a National Research Service Award from the NHLBI (HL087526)

Inflammatory Transcriptome Profiling of Human Monocytes Exposed Acutely to Cigarette Smoke

<div><h3>Background</h3><p>Cigarette smoking is responsible for 5 million deaths worldwide each year, and is a major risk factor for cardiovascular and lung diseases. Cigarette smoke contains a complex mixture of over 4000 chemicals containing 10¹⁵ free radicals. Studies show smoke is perceived by cells as an inflammatory and xenobiotic stimulus, which activates an immune response. The specific cellular mechanisms driving cigarette smoke-induced inflammation and disease are not fully understood, although the innate immune system is involved in the pathology of smoking related diseases.</p> <h3>Methodology/Principle findings</h3><p>To address the impact of smoke as an inflammagen on the innate immune system, THP-1 cells and Human PBMCs were stimulated with 3 and 10% (v/v) cigarette smoke extract (CSE) for 8 and 24 hours. Total RNA was extracted and the transcriptome analysed using Illumina BeadChip arrays. In THP-1 cells, 10% CSE resulted in 80 genes being upregulated and 37 downregulated by ≥1.5 fold after 8 hours. In PBMCs stimulated with 10% CSE for 8 hours, 199 genes were upregulated and 206 genes downregulated by ≥1.5 fold. After 24 hours, the number of genes activated and repressed by ≥1.5 fold had risen to 311 and 306 respectively. The major pathways that were altered are associated with cell survival, such as inducible antioxidants, protein chaperone and folding proteins, and the ubiquitin/proteosome pathway.</p> <h3>Conclusions</h3><p>Our results suggest that cigarette smoke causes inflammation and has detrimental effects on the metabolism and function of innate immune cells. In addition, THP-1 cells provide a genetically stable alternative to primary cells for the study of the effects of cigarette smoke on human monocytes.</p> </div

The boom and bust dynamics of California market squid (Doryteuthis opalescens)

Why do animal populations boom and bust? This is the central question of population biology. Market squid (Doryteuthis opalescens) are an excellent study species for this question as they are fast growing, semelparous, and short-lived. Their rapid population growth allows them to support the largest fishery in California. However the population exhibits dramatic swings in abundance, periodically resulting in the complete collapse of the fishery. Despite their importance, relatively little is known about the drivers of their abundance. Here, I combine laboratory experiments, field observations, and novel statistical techniques to better understand what causes market squid to boom and bust. In the first half of my thesis, I perform a simulation study and find that nonparametric time series methods are particularly useful for understanding the dynamics of short-lived species such as market squid. Indeed, for short-lived, highly productive species, I find that parameter estimates of traditional mechanistic models may be severely biased when calibrated using conventional statistical techniques. Further, I perform a meta-analysis of the Ransom A. Meyers global stock-recruitment database and find that simple time series methods are able to uncover broad patterns of determinism in fish recruitment, thus validating their usefulness for understanding ecological dynamics. In the second half of my thesis, I combine these time series methods with laboratory and field observations to uncover the drivers of market squid abundance. In a mesocosm experiment, I obtain the first empirical estimates of the mortality rate and egg-deposition rate of spawning market squid. I also obtain unique insights into the life-history and vulnerability of spawning market squid. I then combine these insights with a study of market squid paralarvae collected in the 60-year CalCOFI program which includes a time series analysis, a growth analysis, and a size- distribution analysis. The time series analysis shows that variables acting on the juvenile and adult stage (but not the paralarval stage) are critical for forecasting future squid abundance. In agreement with this, the growth analysis shows that paralarvae grow quite well in the "bad" years of El Nino. Finally, the size-distribution analysis shows that paralarvae mortality is actually elevated during the "good'' years of La Nina, again indicating that the paralarvae stage is not the population bottleneck. This suggests, in contrast to conventional expectations, that the juvenile and adult stage are in fact the critical stages for determining population abundance. I conclude with a discussion of the research approach implemented her

Supplement 1. MATLAB function for generating predictions using the SSR forecasting method.

<h2>File List</h2><div> <p><a href="SSR_Forecasting_Code_New.txt">SSR_Forecasting_Code_New.txt</a> (md5: 18bc5b10effa84ff271dbba316c68689) </p> </div><h2>Description</h2><div> SSR_Forecasting_Code_New.txt: This function generates predictions using the SSR forecasting method as described in the manuscript.</div

Appendix A. Tables and figures describing parameter values used for simulations, convergence diagnostics, and forecast performance of all methods.

Tables and figures describing parameter values used for simulations, convergence diagnostics, and forecast performance of all methods

Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor

Aspirin (ASA) and dexamethasone (DEX) are widely used anti-inflammatory agents yet their mechanism(s) for blocking polymorphonuclear neutrophil (PMN) accumulation at sites of inflammation remains unclear. Here, we report that inhibition of PMN infiltration by ASA and DEX is a property shared by aspirin-triggered lipoxins (ATL) and the glucocorticoid-induced annexin 1 (ANXA1)-derived peptides that are both generated in vivo and act at the lipoxin A4 receptor (ALXR/FPRL1) to halt PMN diapedesis. These structurally diverse ligands specifically interact directly with recombinant human ALXR demonstrated by specific radioligand binding and function as well as immunoprecipitation of PMN receptors. In addition, the combination of both ATL and ANXA1-derived peptides limited PMN infiltration and reduced production of inflammatory mediators (that is, prostaglandins and chemokines) in vivo. Together, these results indicate functional redundancies in endogenous lipid and peptide anti-inflammatory circuits that are spatially and temporally separate, where both ATL and specific ANXA1-derived peptides act in concert at ALXR to downregulate PMN recruitment to inflammatory loci

Temporal resolutions in species distribution models of highly mobile marine animals: recommendations for ecologists and managers

While ecologists have long recognized the influence of spatial resolution on species distribution models (SDMs), they have given relatively little attention to the influence of temporal resolution. Considering temporal resolutions is critical in distribution modelling of highly mobile marine animals, as they interact with dynamic oceanographic processes that vary at time-scales from seconds to decades. We guide ecologists in selecting temporal resolutions that best match ecological questions and ecosystems, and managers in applying these models. We group the temporal resolutions of environmental variables used in SDMs into three classes: instantaneous, contemporaneous and climatological. We posit that animal associations with fine-scale and ephemeral features are best modelled with instantaneous covariates. Associations with large scale and persistent oceanographic features are best modelled with climatological covariates. Associations with mesoscale features are best modelled with instantaneous or contemporaneous covariates if ephemeral processes are present or interannual variability occurs, and climatological covariates if seasonal processes dominate and interannual variability is weak