Deglacial Variability of Antarctic Intermediate Water Penetration into the North Atlantic from Authigenic Neodymium Isotope Ratios

Understanding intermediate water circulation across the last deglacial is critical in assessing the role of oceanic heat transport associated with Atlantic Meridional Overturning Circulation variability across abrupt climate events. However, the links between intermediate water circulation and abrupt climate events such as the Younger Dryas (YD) and Heinrich Event 1 (H1) are still poorly constrained. Here, we reconstruct changes in Antarctic Intermediate Water (AAIW) circulation in the subtropical North Atlantic over the past 25 kyr by measuring authigenic neodymium isotope ratios in sediments from two sites in the Florida Straits. Our authigenic Nd isotope records suggest that there was little to no penetration of AAIW into the subtropical North Atlantic during the YD and H1. Variations in the northward penetration of AAIW into the Florida Straits documented in our authigenic Nd isotope record are synchronous with multiple climatic archives, including the Greenland ice core δ18O record, the Cariaco Basin atmosphere Δ14C reconstruction, the Bermuda Rise sedimentary Pa/Th record, and nutrient and stable isotope data from the tropical North Atlantic. The synchroneity of our Nd records with multiple climatic archives suggests a tight connection between AAIW variability and high-latitude North Atlantic climate change

Isotopic evidence for complex biogeochemical cycling of Cd in the eastern tropical South Pacific

Over the past decades, observations have confirmed decreasing oxygen levels and shoaling of oxygen minimum zones (OMZs) in the tropical oceans. Such changes impact the biogeochemical cycling of micronutrients such as Cd, but the potential consequences are only poorly constrained. Here, we present seawater Cd concentrations and isotope compositions for 12 depth profiles at coastal, nearshore and offshore stations from 4◦S to 14◦S in the eastern tropical South Pacific, where one of the world’s strongest OMZs prevails. The depth profiles of Cd isotopes display high δ114/110Cd at the surface and decreasing δ114/110Cd with increasing water depth, consistent with preferential utilization of lighter Cd isotopes during biological uptake in the euphotic zone and subsequent remineralization of the sinking biomass. In the surface and subsurface ocean, seawater displays similar δ114/110Cd signatures of 0.47 ± 0.23‰ to 0.82 ± 0.05‰ across the entire eastern tropical South Pacific despite highly variable Cd concentrations between 0.01 and 0.84 nmol/kg. This observation, best explained by an open system steady-state fractionation model, contrasts with previous studies of the South Atlantic and South Pacific Oceans, where only Cd-deficient waters have a relatively constant Cd isotope signature. For the subsurface to about 500 m depth, the variability of seawater Cd isotope compositions can be modeled by mixing of remineralized Cd with subsurface water from the base of the mixed layer. In the intermediate and deep eastern tropical South Pacific (>500 m), seawater [Cd] and δ114/110Cd appear to follow the distribution and mixing of major water masses. We identified modified AAIW of the ETSP to be more enriched in [Cd] than AAIW from the source region, whilst both water masses have similar δ114/110Cd. A mass balance estimate thus constrains a δ114/110Cd of between 0.38‰ and 0.56‰ for the accumulated remineralized Cd in the ETSP. Nearly all samples show a tight coupling of Cd and PO4 concentrations, whereby surface and deeper waters define two distinct linear trends. However, seawater at a coastal station located within a pronounced plume of H2S, is depleted in [Cd] and features significantly higher δ114/110Cd. This signature is attributed to the formation of authigenic CdS with preferential incorporation of lighter Cd isotopes. The process follows a Rayleigh fractionation model with a fractionation factor of α114/110Cdseawater-CdS = 1.00029. Further deviations from the deep Cd–PO4 trend were observed for samples with O2 < 10 μmol/kg and are best explained by in situ CdS precipitation within the decaying organic matter even though dissolved H2S was not detectable in ambient seawater

Effects of 238U variability and physical transport on water column 234Th downward fluxes in the coastal upwelling system off Peru

The eastern boundary region of the southeastern Pacific Ocean hosts one of the world's most dynamic and productive upwelling systems with an associated oxygen minimum zone (OMZ). The variability in downward export fluxes in this region, with strongly varying surface productivity, upwelling intensities and water column oxygen content, is however poorly understood. Thorium-234 (234Th) is a powerful tracer to study the dynamics of export fluxes of carbon and other elements, yet intense advection and diffusion in nearshore environments impact the assessment of depth-integrated 234Th fluxes when not properly evaluated. Here we use vessel-mounted acoustic Doppler current profiler (VmADCP) current velocities, satellite wind speed and in situ microstructure measurements to determine the magnitude of advective and diffusive fluxes over the entire 234Th flux budget at 25 stations from 11 to 16∘ S in the Peruvian OMZ. Contrary to findings along the GEOTRACES P16 eastern section, our results showed that weak surface wind speed during our cruises induced low upwelling rates and minimal upwelled 234Th fluxes, whereas vertical diffusive 234Th fluxes were important only at a few shallow shelf stations. Horizontal advective and diffusive 234Th fluxes were negligible because of small alongshore 234Th gradients. Our data indicated a poor correlation between seawater 238U activity and salinity. Assuming a linear relationship between the two would lead to significant underestimations of the total 234Th flux by up to 40 % in our study. Proper evaluation of both physical transport and variability in 238U activity is thus crucial in coastal 234Th flux studies. Finally, we showed large temporal variations on 234Th residence times across the Peruvian upwelling zone and cautioned future carbon export studies to take these temporal variabilities into consideration while evaluating carbon export efficiency

Sediment release in the Benguela Upwelling System dominates trace metal input to the shelf and eastern South Atlantic Ocean

Upwelling of subsurface waters injects macronutrients (fixed N, P and Si) and micronutrient trace metals (TMs) into surface waters supporting elevated primary production in Eastern Boundary Upwelling Regions (EBUR). The eastern South Atlantic features a highly productive shelf sea transitioning to a low productivity N-Fe (co)limited open ocean. Whilst a gradient in most TM concentrations is expected in any off-shelf transect, the factors controlling the magnitude of cross-shelf TM fluxes are poorly constrained. Here, we present dissolved TM concentrations of Fe, Co, Mn, Cd, Ni and Cu within the Benguela Upwelling System (BUS) from the coastal section of the GEOTRACES GA08 cruise. Elevated dissolved Fe, Co, Mn, Cd, Ni, Cu and macronutrient concentrations were observed near shelf sediments. Benthic sources supplied 2.22 ± 0.99 μmol Fe m-2 d-1, 0.05 ± 0.03 μmol Co m-2 d-1, 0.28 ± 0.11 μmol Mn m-2 d-1 and were found to be the dominant source to shallow shelf waters compared to atmospheric depositions. Similarly, off-shelf transfer was a more important source of TMs to the eastern South Atlantic Ocean compared to atmospheric deposition. Assessment of surface (shelf, upper 200 m) and subsurface (shelf edge, 200 - 500 m) fluxes of Fe and Co indicated TM fluxes from subsurface were 2 - 5 times larger than those from surface into the eastern South Atlantic Ocean. Under future conditions of increasing ocean deoxygenation, these fluxes may increase further, potentially contributing to a shift towards more extensive regional limitation of primary production by fixed N availability. Key Points Shelf sediments release redox-sensitive trace metals (TMs) to overlying oxygen-depleted waters in the Benguela Upwelling System (BUS) Sediment-derived TMs are upwelled and laterally transported constituting a major source to shelf waters and to the eastern South Atlantic Subsurface fluxes of dissolved Fe and Co from the shelf edge play an important role in supplying Fe and Co to the eastern South Atlanti

Clinical Significance of PTEN Deletion, Mutation, and Loss of PTEN Expression in De Novo Diffuse Large B-Cell Lymphoma

PTEN loss has been associated with poorer prognosis in many solid tumors. However, such investigation in lymphomas is limited. In this study, PTEN cytoplasmic and nuclear expression, PTEN gene deletion, and PTEN mutations were evaluated in two independent cohorts of diffuse large B-cell lymphoma (DLBCL). Cytoplasmic PTEN expression was found in approximately 67% of total 747 DLBCL cases, more frequently in the activated B-cell-like subtype. Nuclear PTEN expression was less frequent and at lower levels, which significantly correlated with higher PTEN mRNA expression. Remarkably, loss of PTEN protein expression was associated with poorer survival only in DLBCL with AKT hyperactivation. In contrast, high PTEN expression was associated with Myc expression and poorer survival in cases without abnormal AKT activation. Genetic and epigenetic mechanisms for loss of PTEN expression were investigated. PTEN deletions (mostly heterozygous) were detected in 11.3% of DLBCL, and showed opposite prognostic effects in patients with AKT hyperactivation and in MYC rearranged DLBCL patients. PTEN mutations, detected in 10.6% of patients, were associated with upregulation of genes involved in central nervous system function, metabolism, and AKT/mTOR signaling regulation. Loss of PTEN cytoplasmic expression was also associated with TP53 mutations, higher PTEN-targeting microRNA expression, and lower PD-L1 expression. Remarkably, low PTEN mRNA expression was associated with down-regulation of a group of genes involved in immune responses and B-cell development/differentiation, and poorer survival in DLBCL independent of AKT activation. Collectively, multi-levels of PTEN abnormalities and dysregulation may play important roles in PTEN expression and loss, and that loss of PTEN tumor-suppressor function contributes to the poor survival of DLBCL patients with AKT hyperactivation

Glacial-interglacial changes in central tropical Pacific surface seawater property gradients

Much uncertainty exists about the state of the oceanic and atmospheric circulation in the tropical Pacific over the last glacial cycle. Studies have been hampered by the fact that sediment cores suitable for study were concentrated in the western and eastern parts of the tropical Pacific, with little information from the central tropical Pacific. Here we present information from a suite of sediment cores collected from the Line Islands Ridge in the central tropical Pacific, which show sedimentation rates and stratigraphies suitable for paleoceanographic investigations. Based on the radiocarbon and oxygen isotope measurements on the planktonic foraminifera Globigerinoides ruber, we construct preliminary age models for selected cores and show that the gradient in the oxygen isotope ratio of G. ruber between the equator and 8°N is enhanced during glacial stages relative to interglacial stages. This stronger gradient could reflect enhanced equatorial cooling (perhaps reflecting a stronger Walker circulation) or an enhanced salinity gradient (perhaps reflecting increased rainfall in the central tropical Pacific).This is the publisher’s final pdf. The article is copyrighted by American Geophysical Union and published by John Wiley & Sons Ltd. It can be found at: http://agupubs.onlinelibrary.wiley.com/agu/journal/10.1002/%28ISSN%291944-9186/Keywords: tropical Pacific, oxygen isotopes, foraminifer

Organic matter fluxes and biogeochemical processes in the OMZ off Peru, Cruise No. M138, 01 June - 03 July 2017, Callao (Peru) - Bahia Las Minas (Panama)

The oxygen minimum zone (OMZ) in the eastern tropical South Pacific Ocean is tightly connected to the coastal upwelling system off Peru. The high biological productivity off Peru is therefore, driven by the complex interplay between the amount of nutrients recycled by remineralisation processes in the OMZ and the upwelling which brings these nutrients to the surface layer. However, surprisingly little is known about organic matter cycling and its effects on biogeochemical processes in the OMZ off Peru. To this end we conducted a first comprehensive study on the role of organic matter for the biogeochemical processes and the maintenance of the OMZ off Peru. M138 combined measurements of marine biogeochemistry, microbiology, physical oceanography and air chemistry with foci on (i) the efficiency of the biological pump, (ii) the nitrogen cycle processes in the OMZ, (iii) the ventilation of the OMZ as well as (iv) the air/sea gas exchange across the ocean/atmosphere interface and (v) aerosol deposition. The METEOR cruise M138 was performed as part of the third phase of the SFB754 'Climate-Biogeochemistry Interactions in the Tropical Ocean' (www.sfb754.de)

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets

Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6.

BACKGROUND: Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear. RESULTS: Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction. CONCLUSIONS: Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.BH

Discovery of novel heart rate-associated loci using the Exome Chip

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses. Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods. We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants. Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies