Selected plasma fatty acid levels in subsistence fed sled dogs along the Yukon River: a pilot study for biomonitoring

The introduction of the ‘western diet' marked a decline in omega-3 fatty acids rich foods and a concurrent increase in saturated and omega-6 fatty acids that persists today. Historically, circumpolar people have had a low incidence of obesity, diabetes and cardiovascular disease and this has been largely attributed to polyphenolic compounds and omega-3 fatty acids offered from subsistence foods. In this report, we studied sled dogs as an Arctic sentinel species for monitoring the effect of a changing diet on lipid profiles along the Yukon River. Subsistence fed village sled dogs along the Yukon River, maintained largely on salmon were compared with a control kennel maintained on commercial food. Profiles showed higher levels for long chain omega-3 fatty acids in village subsistence fed dogs compared to control dogs and an opposite trend for omega-6 fatty acids, establishing baseline levels for follow up studies. A comparison with data for previously published mercury levels from the same cohort of dogs revealed a positive correlation with alpha-linolenic fatty acid and a negative correlation with linoleic fatty acid. Food and nutritional security is a concern in the Arctic as the impacts of climate change and transport of contaminants become obvious. This study supports not only the nutritional value of a subsistence diet but also the utility of sled dogs as a sentinel for human dietary chang

Southwest Atlantic water mass evolution during the last deglaciation

The rise in atmospheric CO2 during Heinrich Stadial 1 (HS1; 14.5–17.5 kyr B.P.) may have been driven by the release of carbon from the abyssal ocean. Model simulations suggest that wind‐driven upwelling in the Southern Ocean can liberate 13C‐depleted carbon from the abyss, causing atmospheric CO2 to increase and the δ13C of CO2 to decrease. One prediction of the Southern Ocean hypothesis is that water mass tracers in the deep South Atlantic should register a circulation response early in the deglaciation. Here we test this idea using a depth transect of 12 cores from the Brazil Margin. We show that records below 2300 m remained 13C‐depleted until 15 kyr B.P. or later, indicating that the abyssal South Atlantic was an unlikely source of light carbon to the atmosphere during HS1. Benthic δ18O results are consistent with abyssal South Atlantic isolation until 15 kyr B.P., in contrast to shallower sites. The depth dependent timing of the δ18O signal suggests that correcting δ18O for ice volume is problematic on glacial terminations. New data from 2700 to 3000 m show that the deep SW Atlantic was isotopically distinct from the abyss during HS1. As a result, we find that mid‐depth δ13C minima were most likely driven by an abrupt drop in δ13C of northern component water. Low δ13C at the Brazil Margin also coincided with an ~80‰ decrease in Δ14C. Our results are consistent with a weakening of the Atlantic meridional overturning circulation and point toward a northern hemisphere trigger for the initial rise in atmospheric CO2 during HS1.Key PointsDeep SW Atlantic was unlikely source of light carbon to atmosphere during HS1Mid‐depth isotopic anomalies due to change in northern component waterNorthern component water had robust influence in South Atlantic during HS1Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111970/1/palo20190.pd

Impact of sympathetic nervous system activity on post-exercise flow-mediated dilatation in humans

Transient reduction in vascular function following systemic large muscle group exercise has previously been reported in humans. The mechanisms responsible are currently unknown. We hypothesised that sympathetic nervous system activation, induced by cycle ergometer exercise, would contribute to post-exercise reductions in flow-mediated dilatation (FMD). Ten healthy male subjects (28 ± 5 years) undertook two 30 min sessions of cycle exercise at 75% HRmax. Prior to exercise, individuals ingested either a placebo or an α1-adrenoreceptor blocker (prazosin; 0.05 mg kg−1). Central haemodynamics, brachial artery shear rate (SR) and blood flow profiles were assessed throughout each exercise bout and in response to brachial artery FMD, measured prior to, immediately after and 60 min after exercise. Cycle exercise increased both mean and antegrade SR (P < 0.001) with retrograde SR also elevated under both conditions (P < 0.001). Pre-exercise FMD was similar on both occasions, and was significantly reduced (27%) immediately following exercise in the placebo condition (t-test, P = 0.03). In contrast, FMD increased (37%) immediately following exercise in the prazosin condition (t-test, P = 0.004, interaction effect P = 0.01). Post-exercise FMD remained different between conditions after correction for baseline diameters preceding cuff deflation and also post-deflation SR. No differences in FMD or other variables were evident 60 min following recovery. Our results indicate that sympathetic vasoconstriction competes with endothelium-dependent dilator activity to determine post-exercise arterial function. These findings have implications for understanding the chronic impacts of interventions, such as exercise training, which affect both sympathetic activity and arterial shear stress

Integrated Approach Reveals Role of Mitochondrial Germ-Line Mutation F18L in Respiratory Chain, Oxidative Alterations, Drug Sensitivity, and Patient Prognosis in Glioblastoma

Glioblastoma is the most common and malignant primary brain tumour in adults, with a dismal prognosis. This is partly due to considerable inter- and intra-tumour heterogeneity. Changes in the cellular energy-producing mitochondrial respiratory chain complex (MRC) activities are a hallmark of glioblastoma relative to the normal brain, and associate with differential survival outcomes. Targeting MRC complexes with drugs can also facilitate anti-glioblastoma activity. Whether mutations in the mitochondrial DNA (mtDNA) that encode several components of the MRC contribute to these phenomena remains underexplored. We identified a germ-line mtDNA mutation (m. 14798T &gt; C), enriched in glioblastoma relative to healthy controls, that causes an amino acid substitution F18L within the core mtDNA-encoded cytochrome b subunit of MRC complex III. F18L is predicted to alter corresponding complex III activity, and sensitivity to complex III-targeting drugs. This could in turn alter reactive oxygen species (ROS) production, cell behaviour and, consequently, patient outcomes. Here we show that, despite a heterogeneous mitochondrial background in adult glioblastoma patient biopsy-derived cell cultures, the F18L substitution associates with alterations in individual MRC complex activities, in particular a 75% increase in MRC complex II_III activity, and a 34% reduction in CoQ10, the natural substrate for MRC complex III, levels. Downstream characterisation of an F18L-carrier revealed an 87% increase in intra-cellular ROS, an altered cellular distribution of mitochondrial-specific ROS, and a 64% increased sensitivity to clomipramine, a repurposed MRC complex III-targeting drug. In patients, F18L-carriers that received the current standard of care treatment had a poorer prognosis than non-carriers (373 days vs. 415 days, respectively). Single germ-line mitochondrial mutations could predispose individuals to differential prognoses, and sensitivity to mitochondrial targeted drugs. Thus, F18L, which is present in blood could serve as a useful non-invasive biomarker for the stratification of patients into prognostically relevant groups, one of which requires a lower dose of clomipramine to achieve clinical effect, thus minimising side-effects

Data Descriptor: A global multiproxy database for temperature reconstructions of the Common Era

Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high-and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python.(TABLE)Since the pioneering work of D'Arrigo and Jacoby1-3, as well as Mann et al. 4,5, temperature reconstructions of the Common Era have become a key component of climate assessments6-9. Such reconstructions depend strongly on the composition of the underlying network of climate proxies10, and it is therefore critical for the climate community to have access to a community-vetted, quality-controlled database of temperature-sensitive records stored in a self-describing format. The Past Global Changes (PAGES) 2k consortium, a self-organized, international group of experts, recently assembled such a database, and used it to reconstruct surface temperature over continental-scale regions11 (hereafter, ` PAGES2k-2013').This data descriptor presents version 2.0.0 of the PAGES2k proxy temperature database (Data Citation 1). It augments the PAGES2k-2013 collection of terrestrial records with marine records assembled by the Ocean2k working group at centennial12 and annual13 time scales. In addition to these previously published data compilations, this version includes substantially more records, extensive new metadata, and validation. Furthermore, the selection criteria for records included in this version are applied more uniformly and transparently across regions, resulting in a more cohesive data product.This data descriptor describes the contents of the database, the criteria for inclusion, and quantifies the relation of each record with instrumental temperature. In addition, the paleotemperature time series are summarized as composites to highlight the most salient decadal-to centennial-scale behaviour of the dataset and check mutual consistency between paleoclimate archives. We provide extensive Matlab code to probe the database-processing, filtering and aggregating it in various ways to investigate temperature variability over the Common Era. The unique approach to data stewardship and code-sharing employed here is designed to enable an unprecedented scale of investigation of the temperature history of the Common Era, by the scientific community and citizen-scientists alike