Lithium in the Intermediate-Age Open Cluster, NGC 3680

High-dispersion spectra centered on the Li 6708 A line have been obtained for 70 potential members of the open cluster NGC 3680, with an emphasis on stars in the turnoff region. A measurable Li abundance has been derived for 53 stars, 39 of which have radial velocities and proper motions consistent with cluster membership. After being transferred to common temperature and abundance scales, previous Li estimates have been combined to generate a sample of 49 members, 40 of which bracket the cluster Li-dip. Spectroscopic elemental analysis of 8 giants and 5 turnoff stars produces [Fe/H] = -0.17 +/- 0.07 (sd) and -0.07 +/- 0.02 (sd), respectively. We also report measurements of Ca, Si and Ni which are consistent with scaled-solar ratios within the errors. Adopting [Fe/H] = -0.08 (Sect. 3.6), Y^2 isochrone comparisons lead to an age of 1.75 +/- 0.10 Gyr and an apparent modulus of (m-M) = 10.30 +/- 0.15 for the cluster, placing the center of the Li-dip at 1.35 +/- 0.03 solar masses. Among the giants, 5 of 9 cluster members are now known to have measurable Li with A(Li) near 1.0. A combined sample of dwarfs in the Hyades and Praesepe is used to delineate the Li-dip profile at 0.7 Gyr and [Fe/H] = +0.15, establishing its center at 1.42 +/- 0.02 solar masses and noting the possible existence of secondary dip on its red boundary. When evolved to the typical age of the clusters NGC 752, IC 4651 and NGC 3680, the Hyades/Praesepe Li-dip profile reproduces the observed morphology of the combined Li-dip within the CMD's of the intermediate-age clusters while implying a metallicity dependence for the central mass of the Li-dip given by Mass = (1.38 +/-0.04) + (0.4 +/- 0.2)[Fe/H]. The implications of the similarity of the Li-dichotomy among giants in NGC 752 and IC 4651 and the disagreement with the pattern among NGC 3680 giants are discussed.Comment: Latex ms. is 56 pages, including 10 figures and 4 tables. Accepted for the Astronomical Journa

Relationships between plasma lipids species, gender, risk factors and Alzheimer’s disease

Background: Lipid metabolism is altered in Alzheimer’s disease (AD); however, the relationship between AD risk factors (age, APOE ɛ4, and gender) and lipid metabolism is not well defined. Objective: We investigated whether altered lipid metabolism associated with increased age, gender, and APOE status may contribute to the development of AD by examining these risk factors in healthy controls and also clinically diagnosed AD individuals. Methods: We performed plasma lipidomic profiling (582 lipid species) of the Australian Imaging, Biomarkers and Lifestyle flagship study of aging cohort (AIBL) using liquid chromatography-mass spectrometry. Linear regression and interaction analysis were used to explore the relationship between risk factors and plasma lipid species. Results: We observed strong associations between plasma lipid species with gender and increasing age in cognitively normal individuals. However, APOE ɛ4 was relatively weakly associated with plasma lipid species. Interaction analysis identified differential associations of sphingolipids and polyunsaturated fatty acid esterified lipid species with AD based on age and gender, respectively. These data indicate that the risk associated with age, gender, and APOE ɛ4 may, in part, be mediated by changes in lipid metabolism. Conclusion: This study extends our existing knowledge of the relationship between the lipidome and AD and highlights the complexity of the relationships between lipid metabolism and AD at different ages and between men and women. This has important implications for how we assess AD risk and also for potential therapeutic strategies involving modulation of lipid metabolic pathways

Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease

© 2020, The Author(s). Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation. In this study we examined peripheral samples of two cohorts (AIBL, n = 1112 and ADNI, n = 800). We are able to identify concordant peripheral signatures associated with prevalent AD arising from lipid pathways including; ether lipids, sphingolipids (notably GM3 gangliosides) and lipid classes previously associated with cardiometabolic disease (phosphatidylethanolamine and triglycerides). We subsequently identified similar lipid signatures in both cohorts with future disease. Lastly, we developed multivariate lipid models that improved classification and prediction. Our results provide a holistic view between the lipidome and AD using a comprehensive approach, providing targets for further mechanistic investigation

APOE ε2 resilience for Alzheimer’s disease is mediated by plasma lipid species: Analysis of three independent cohort studies

Introduction The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late-onset Alzheimer\u27s disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood. Methods We performed lipidomic analysis on three independent cohorts (the Australian Imaging, Biomarkers and Lifestyle [AIBL] flagship study, n = 1087; the Alzheimer\u27s Disease Neuroimaging Initiative [ADNI] 1 study, n = 819; and the Busselton Health Study [BHS], n = 4384), and we defined associations between APOE ε2 and ε4 and 569 plasma/serum lipid species. Mediation analysis defined the proportion of the treatment effect of the APOE genotype mediated by plasma/serum lipid species. Results A total of 237 and 104 lipid species were associated with APOE ε2 and ε4, respectively. Of these 68 (ε2) and 24 (ε4) were associated with prevalent Alzheimer\u27s disease. Individual lipid species or lipidomic models of APOE genotypes mediated up to 30% and 10% of APOE ε2 and ε4 treatment effect, respectively. Discussion Plasma lipid species mediate the treatment effect of APOE genotypes on Alzheimer\u27s disease and as such represent a potential therapeutic target

Alzheimer\u27s Disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology

Introduction Cerebrospinal fluid (CSF) biomarkers, although of established utility in the diagnostic evaluation of Alzheimer’s disease (AD), are known to be sensitive to variation based on pre-analytical sample processing. We assessed whether gravity droplet collection versus syringe aspiration was another factor influencing CSF biomarker analyte concentrations and reproducibility. Methods Standardized lumbar puncture using small calibre atraumatic spinal needles and CSF collection using gravity fed collection followed by syringe aspirated extraction was performed in a sample of elderly individuals participating in a large long-term observational research trial. Analyte assay concentrations were compared. Results For the 44 total paired samples of gravity collection and aspiration, reproducibility was high for biomarker CSF analyte assay concentrations (concordance correlation [95%CI]: beta-amyloid1-42 (Aβ42) 0.83 [0.71 - 0.90]), t-tau 0.99 [0.98 - 0.99], and phosphorylated tau (p-tau) 0.82 [95 % CI 0.71 - 0.89]) and Bonferroni corrected paired sample t-tests showed no significant differences (group means (SD): Aβ42 366.5 (86.8) vs 354.3 (82.6), p = 0.10; t-tau 83.9 (46.6) vs 84.7 (47.4) p = 0.49; p-tau 43.5 (22.8) vs 40.0 (17.7), p = 0.05). The mean duration of collection was 10.9 minutes for gravity collection andaspiration. Conclusions Our results demonstrate that aspiration of CSF is comparable to gravity droplet collection for AD biomarker analyses but could considerably accelerate throughput and improve the procedural tolerability for assessment of CSF biomarkers. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼ 456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P \u3c 1 × 10−3), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases

Reconciliation of the carbon budget in the ocean’s twilight zone

Photosynthesis in the surface ocean produces approximately 100 gigatonnes of organic carbon per year, of which 5 to 15 per cent is exported to the deep ocean1, 2. The rate at which the sinking carbon is converted into carbon dioxide by heterotrophic organisms at depth is important in controlling oceanic carbon storage3. It remains uncertain, however, to what extent surface ocean carbon supply meets the demand of water-column biota; the discrepancy between known carbon sources and sinks is as much as two orders of magnitude4, 5, 6, 7, 8. Here we present field measurements, respiration rate estimates and a steady-state model that allow us to balance carbon sources and sinks to within observational uncertainties at the Porcupine Abyssal Plain site in the eastern North Atlantic Ocean. We find that prokaryotes are responsible for 70 to 92 per cent of the estimated remineralization in the twilight zone (depths of 50 to 1,000 metres) despite the fact that much of the organic carbon is exported in the form of large, fast-sinking particles accessible to larger zooplankton. We suggest that this occurs because zooplankton fragment and ingest half of the fast-sinking particles, of which more than 30 per cent may be released as suspended and slowly sinking matter, stimulating the deep-ocean microbial loop. The synergy between microbes and zooplankton in the twilight zone is important to our understanding of the processes controlling the oceanic carbon sink

Readout of a quantum processor with high dynamic range Josephson parametric amplifiers

We demonstrate a high dynamic range Josephson parametric amplifier (JPA) in which the active nonlinear element is implemented using an array of rf-SQUIDs. The device is matched to the 50 $\Omega$ environment with a Klopfenstein-taper impedance transformer and achieves a bandwidth of 250-300 MHz, with input saturation powers up to -95 dBm at 20 dB gain. A 54-qubit Sycamore processor was used to benchmark these devices, providing a calibration for readout power, an estimate of amplifier added noise, and a platform for comparison against standard impedance matched parametric amplifiers with a single dc-SQUID. We find that the high power rf-SQUID array design has no adverse effect on system noise, readout fidelity, or qubit dephasing, and we estimate an upper bound on amplifier added noise at 1.6 times the quantum limit. Lastly, amplifiers with this design show no degradation in readout fidelity due to gain compression, which can occur in multi-tone multiplexed readout with traditional JPAs.Comment: 9 pages, 8 figure