WOOD JAMS OR BEAVER DAMS? PLIOCENE LIFE, SEDIMENT AND LANDSCAPE INTERACTIONS IN THE CANADIAN HIGH ARCTIC

ABSTRACT During the mid-Pliocene (Zanclean, ca. ∼ 3.9 Ma), parts of the Canadian High Arctic experienced mean annual temperatures that were 14–22°C warmer than today and supported diverse boreal-type forests. The landscapes of this vegetated polar region left behind a fragmented sedimentary record that crops out across several islands in the Canadian Arctic Archipelago as the Beaufort Formation and correlative strata. Paleoecological information from these strata provides a high-fidelity window onto Pliocene environments, and prominent fossil sites yield unparalleled insights into Cenozoic mammal evolution. Significantly, many of the strata reveal evidence for life-sediment interactions in a warm-climate Arctic, most notably in the form of extensive woody debris and phytoclast deposits. This paper presents original field data that refines the sedimentological context of plant debris accumulations from the anactualistic High Arctic forests, most notably at the ‘Fyles Leaf Beds' and ‘Beaver Pond' fossil-bearing sites in the ‘high terrace deposits' of central Ellesmere Island. The former is a remarkably well-preserved, leaf-rich deposit that is part of a complex of facies associations representing lacustrine, fluvio-deltaic and mire deposition above a paleotopographic unconformity. The latter yields tooth-marked woody debris within a peat layer that also contains a rich assemblage of vertebrate and plant fossils including abundant remains from the extinct beaver-group Dipoides. Here we present sedimentological data that provide circumstantial evidence that the woody debris deposit at Beaver Pond could record dam-building in the genus, by comparing the facies motif with new data from known Holocene beaver dam facies in England. Across the Pliocene of the High Arctic region, woody debris accumulations are shown to represent an array of biosedimentary deposits and landforms including mires, driftcretions, woody bedforms, and possible beaver dams, which help to contextualize mammal fossil sites, provide facies models for high-latitude forests, and reveal interactions between life and sedimentation in a vanished world that may be an analogue to that of the near-future.</jats:p

Dynamics and Regulation of RecA Polymerization and De-Polymerization on Double-Stranded DNA

10.1371/journal.pone.0066712PLoS ONE86

DAF-21/Hsp90 is required for C. elegans longevity by ensuring DAF-16/FOXO isoform A function

The FOXO transcription factor family is a conserved regulator of longevity and the downstream target of insulin/insulin-like signaling. In Caenorhabditis elegans, the FOXO ortholog DAF-16A and D/F isoforms extend lifespan in daf-2 insulin-like receptor mutants. Here we identify the DAF-21/Hsp90 chaperone as a longevity regulator. We find that reducing DAF-21 capacity by daf-21(RNAi) initiated either at the beginning or at the end of larval development shortens wild-type lifespan. daf-21 knockdown employed from the beginning of larval development also decreases longevity of daf-2 mutant and daf-2 silenced nematodes. daf-16 loss-of-function mitigates the lifespan shortening effect of daf-21 silencing. We demonstrate that DAF-21 specifically promotes daf-2 and heat-shock induced nuclear translocation of DAF-16A as well as the induction of DAF-16A-specific mRNAs, without affecting DAF-16D/F localization and transcriptional function. DAF-21 is dispensable for the stability and nuclear import of DAF-16A, excluding a chaperone-client interaction and suggesting that DAF-21 regulates DAF-16A activation upstream of its cellular traffic. Finally, we show a selective requirement for DAF-21 to extend lifespan of DAF-16A, but not DAF-16D/F, transgenic daf-2 mutant strains. Our findings indicate a spatiotemporal determination of multiple DAF-21 roles in fertility, development and longevity and reveal an isoform-specific regulation of DAF-16 activity. © 2018, The Author(s)

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)