| 1. |
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| 2. |
- Bar, N., et al.
(author)
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A reference map of potential determinants for the human serum metabolome
- 2020
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In: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Journal article (peer-reviewed)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 3. |
- Wilman, H. R., et al.
(author)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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In: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Journal article (peer-reviewed)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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| 4. |
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| 5. |
- Morabito, L., et al.
(author)
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Sub-arcsecond imaging with the International LOFAR Telescope: I. Foundational calibration strategy and pipeline
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
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Journal article (peer-reviewed)abstract
- The International LOFAR Telescope is an interferometer with stations spread across Europe. With baselines of up to ∼2000 km, LOFAR has the unique capability of achieving sub-arcsecond resolution at frequencies below 200 MHz. However, it is technically and logistically challenging to process LOFAR data at this resolution. To date only a handful of publications have exploited this capability. Here we present a calibration strategy that builds on previous high-resolution work with LOFAR. It is implemented in a pipeline using mostly dedicated LOFAR software tools and the same processing framework as the LOFAR Two-metre Sky Survey (LoTSS). We give an overview of the calibration strategy and discuss the special challenges inherent to enacting high-resolution imaging with LOFAR, and describe the pipeline, which is publicly available, in detail. We demonstrate the calibration strategy by using the pipeline on P205+55, a typical LoTSS pointing with an 8 h observation and 13 international stations. We perform in-field delay calibration, solution referencing to other calibrators in the field, self-calibration of these calibrators, and imaging of example directions of interest in the field. We find that for this specific field and these ionospheric conditions, dispersive delay solutions can be transferred between calibrators up to ∼1.5° away, while phase solution transferral works well over ∼1°. We also demonstrate a check of the astrometry and flux density scale with the in-field delay calibrator source. Imaging in 17 directions, we find the restoring beam is typically ∼0.3″ ×0.2″ although this varies slightly over the entire 5 deg2 field of view. We find we can achieve ∼80-300 μJy bm-1 image rms noise, which is dependent on the distance from the phase centre; typical values are ∼90 μJy bm-1 for the 8 h observation with 48 MHz of bandwidth. Seventy percent of processed sources are detected, and from this we estimate that we should be able to image roughly 900 sources per LoTSS pointing. This equates to ∼ 3 million sources in the northern sky, which LoTSS will entirely cover in the next several years. Future optimisation of the calibration strategy for efficient post-processing of LoTSS at high resolution makes this estimate a lower limit.
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| 6. |
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| 7. |
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| 8. |
- Groeneveld, Tom, et al.
(author)
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Interactions of the extracellular matrix proteoglycans decorin and biglycan with C1q and collectins
- 2005
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In: Journal of Immunology. - 1550-6606. ; 175:7, s. 4715-4723
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Journal article (peer-reviewed)abstract
- Decorin and biglycan are closely related abundant extracellular matrix proteoglycans that have been shown to bind to C1q. Given the overall structural similarities between C1q and mannose-binding lectin (MBL), the two key recognition molecules of the classical and the lectin complement pathways, respectively, we have examined functional consequences of the interaction of C1q and MBL with decorin and biglycan. Recombinant forms of human decorin and biglycan bound C1q via both collagen and globular domains and inhibited the classical pathway. Decorin also bound C1 without activating complement. Furthermore, decorin and biglycan bound efficiently to MBL, but only biglycan could inhibit activation of the lectin pathway. Other members of the collectin family, including human surfactant protein D, bovine collectin-43, and conglutinin also showed binding to decorin and biglycan. Decorin and biglycan strongly inhibited C1q binding to human endothelial cells and U937 cells, and biglycan suppressed C1q-induced MCP-1 and IL-8 production by human endothelial cells. In conclusion, decorin and biglycan act as inhibitors of activation of the complement cascade, cellular interactions, and proinflammatory cytokine production mediated by C1q. These two proteoglycans are likely to down-regulate proinflammatory effects mediated by C1q, and possibly also the collectins, at the tissue level.
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| 9. |
- Viborg Lindskrog, Sia, et al.
(author)
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An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer
- 2021
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.
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| 10. |
- Chagas, Vinicius S., et al.
(author)
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RTNduals an R/Bioconductor package for analysis of co-regulation and inference of dual regulons
- 2019
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In: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 35:24, s. 5357-5358
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Journal article (peer-reviewed)abstract
- MOTIVATION: Transcription factors (TFs) are key regulators of gene expression, and can activate or repress multiple target genes, forming regulatory units, or regulons. Understanding downstream effects of these regulators includes evaluating how TFs cooperate or compete within regulatory networks. Here we present RTNduals, an R/Bioconductor package that implements a general method for analyzing pairs of regulons. RESULTS: RTNduals identifies a dual regulon when the number of targets shared between a pair of regulators is statistically significant. The package extends the RTN (Reconstruction of Transcriptional Networks) package, and uses RTN transcriptional networks to identify significant co-regulatory associations between regulons. The Supplementary Information reports two case studies for TFs using the METABRIC and TCGA breast cancer cohorts. AVAILABILITY AND IMPLEMENTATION: RTNduals is written in the R language, and is available from the Bioconductor project at http://bioconductor.org/packages/RTNduals/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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| 11. |
- Clay, P. M., et al.
(author)
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Implementation of integrated ecosystem assessments in the International Council for the Exploration of the Sea-conceptualizations, practice, and progress
- 2023
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In: Ices Journal of Marine Science. - 1054-3139. ; 80:5, s. 1516-1528
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Journal article (peer-reviewed)abstract
- With increasing activities of multiple sectors in marine spaces, management of marine social-ecological systems requires more holistic approaches. Adopting such an approach, however, presents difficult institutional and disciplinary challenges. Here, we use the International Council for the Exploration of the Sea (ICES) as a case study on the implementation of ecosystem-based management (EBM) and integrated ecosystem assessments (IEAs). ICES includes EBM and IEAs in its Science Priorities and established IEA Working Groups (WGs) to carry out regional IEAs. But to what degree does this IEA WG work follow best practices? We examine policy documents, academic literature, and interview data from chairs of all IEA WGs. Results indicate mixed success. All groups acknowledge the holistic goals of IEA, and many use the IEA model as laid out by Levin et al. However, we found a significant variation in the degree to which the full model is applied. We identified two primary areas for improvement: (1) integration of social and economic issues and (2) involvement of stakeholders. We offer examples of how WGs have been making progress towards full IEAs, discuss how ICES can further support this transition, and suggest lessons with respect to the adoption of EBM and IEAs more broadly.
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| 12. |
- Flores, H., et al.
(author)
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Impact of climate change on Antarctic krill
- 2012
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In: Marine Ecology-Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 458, s. 1-19
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Journal article (peer-reviewed)abstract
- Antarctic krill Euphausia superba (hereafter 'krill') occur in regions undergoing rapid environmental change, particularly loss of winter sea ice. During recent years, harvesting of krill has in creased, possibly enhancing stress on krill and Antarctic ecosystems. Here we review the overall impact of climate change on krill and Antarctic ecosystems, discuss implications for an ecosystem-based fisheries management approach and identify critical knowledge gaps. Sea ice decline, ocean warming and other environmental stressors act in concert to modify the abundance, distribution and life cycle of krill. Although some of these changes can have positive effects on krill, their cumulative impact is most likely negative. Recruitment, driven largely by the winter survival of larval krill, is probably the population parameter most susceptible to climate change. Predicting changes to krill populations is urgent, because they will seriously impact Antarctic ecosystems. Such predictions, however, are complicated by an intense inter-annual variability in recruitment success and krill abundance. To improve the responsiveness of the ecosystem-based management approach adopted by the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR), critical knowledge gaps need to be filled. In addition to a better understanding of the factors influencing recruitment, management will require a better understanding of the resilience and the genetic plasticity of krill life stages, and a quantitative understanding of under-ice and benthic habitat use. Current precautionary management measures of CCAMLR should be maintained until a better understanding of these processes has been achieved. [GRAPHICS] .
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| 13. |
- Gallagher, S. J., et al.
(author)
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The enigma of rare Quaternary oolites in the Indian and Pacific Oceans : A result of global oceanographic physicochemical conditions or a sampling bias?
- 2018
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In: Quaternary Science Reviews. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0277-3791 .- 1873-457X. ; 200, s. 114-122
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Journal article (peer-reviewed)abstract
- Marine ooids are iconic indicators of shallow seawater carbonate saturation state, and their formation has traditionally been ascribed to physicochemical processes. The Indo-Pacific stands out as a region devoid of oolites, particularly during the Quaternary: the "ooid enigma". Here we present results from recent coring by the International Ocean Discovery Program (IODP Expedition 356) off west Australia that shows that ooid horizons are common in Pleistocene strata up to 730,000 years old. Extensive "ooid factories" were created due to the presence of long-lived tidally influenced flat topped tropical platforms suitable for intermittent ooid accretion over hundreds to thousands of years during highstands and times of lower sea level. This work suggests marine ooids may actually be more common in Indo-Pacific than previously reported. Past global ocean alkalinity was elevated during Pleistocene glacial periods and continental climate was generally more arid in the Indo-Pacific region compared to interglacials and the Holocene. Therefore, increased aridity associated with higher alkalinity conditions during the glacials facilitated ooid precipitation on adjacent tropical carbonate platforms particularly offshore from arid Australia. This confluence of factors suggests that more "ooid factories" may be encountered by further coring Indo-Pacific regions with Pleistocene flat long-lived carbonate shelves. However, Indo-Pacific Quaternary ooid occurrences outside Australia are rare, suggesting that the Northwest Shelf may be a unique archive of this non-skeletal precipitate. Further investigations into the petrography and geochemistry of pre-Holocene ooid occurrences will provide insights into their origin and the relative role of biotic, physicochemical and other factors in their formation. (C) 2018 Elsevier Ltd. All rights reserved.
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| 14. |
- Golla, Sandeep S V, et al.
(author)
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Parametric Binding Images of the TSPO Ligand 18F-DPA-714.
- 2016
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 57:10, s. 1543-1547
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Journal article (peer-reviewed)abstract
- (18)F-labeled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide (DPA-714) is a radioligand for the 18-kDa translocator protein. The purpose of the present study was to identify the best method for generating quantitative parametric images of (18)F-DPA-714 binding.METHODS: Ninety-minute dynamic (18)F-DPA-714 PET scans with full arterial sampling from 6 healthy subjects and 9 Alzheimer disease (AD) patients were used. Plasma-input-based Logan graphical analysis and spectral analysis were used to generate parametric volume of distribution (VT) images. Five versions of Ichise, reference Logan, and 2 basis function implementations (receptor parametric mapping and simplified reference tissue model 2 [SRTM2]) of SRTM, all using gray matter cerebellum as the reference region, were applied to generate nondisplaceable binding potential (BPND) images.RESULTS: Plasma-input Logan analysis (r(2) = 0.99; slope, 0.88) and spectral analysis (r(2) = 0.99, slope, 0.93) generated estimates of VT that correlated well with values obtained using nonlinear regression. BPND values generated using SRTM2 (r(2) = 0.83; slope, 0.95) and reference Logan analysis (r(2) = 0.88; slope, 1.01) correlated well with nonlinear regression-based estimates.CONCLUSION: Both Logan analysis and spectral analysis can be used to obtain quantitatively accurate VT images of (18)F-DPA-714. In addition, SRTM2 and reference Logan analysis can provide accurate BPND images. These parametric images could be used for voxel-based comparisons.
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| 15. |
- Groeneveld, Jeroen, et al.
(author)
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Australian shelf sediments reveal shifts in Miocene Southern Hemisphere westerlies
- 2017
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 3:5
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Journal article (peer-reviewed)abstract
- Global climate underwent a major reorganization when the Antarctic ice sheet expanded ~14 million years ago (Ma) (1). This event affected global atmospheric circulation, including the strength and position of the westerlies and the Intertropical Convergence Zone (ITCZ), and, therefore, precipitation patterns (2–5). We present new shallow-marine sediment records from the continental shelf of Australia (International Ocean Discovery Program Sites U1459 and U1464) providing the first empirical evidence linking high-latitude cooling around Antarctica to climate change in the (sub)tropics during the Miocene. We show that Western Australia was arid during most of the Middle Miocene. Southwest Australia became wetter during the Late Miocene, creating a climate gradient with the arid interior, whereas northwest Australia remained arid throughout. Precipitation and river runoff in southwest Australia gradually increased from 12 to 8 Ma, which we relate to a northward migration or intensification of the westerlies possibly due to increased sea ice in the Southern Ocean (5). Abrupt aridification indicates that the westerlies shifted back to a position south of Australia after 8 Ma. Our midlatitude Southern Hemisphere data are consistent with the inference that expansion of sea ice around Antarctica resulted in a northward movement of the westerlies. In turn, this may have pushed tropical atmospheric circulation and the ITCZ northward, shifting the main precipitation belt over large parts of Southeast Asia (4).
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| 16. |
- Kamoun, Aurélie, et al.
(author)
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A Consensus Molecular Classification of Muscle-invasive Bladder Cancer
- 2020
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In: European Urology. - : Elsevier BV. - 0302-2838. ; 77:4, s. 420-433
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Journal article (peer-reviewed)abstract
- Background: Muscle-invasive bladder cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, but the diversity of their subtype sets impedes their clinical application. Objective: To achieve an international consensus on MIBC molecular subtypes that reconciles the published classification schemes. Design, setting, and participants: We used 1750 MIBC transcriptomic profiles from 16 published datasets and two additional cohorts. Outcome measurements and statistical analysis: We performed a network-based analysis of six independent MIBC classification systems to identify a consensus set of molecular classes. Association with survival was assessed using multivariable Cox models. Results and limitations: We report the results of an international effort to reach a consensus on MIBC molecular subtypes. We identified a consensus set of six molecular classes: luminal papillary (24%), luminal nonspecified (8%), luminal unstable (15%), stroma-rich (15%), basal/squamous (35%), and neuroendocrine-like (3%). These consensus classes differ regarding underlying oncogenic mechanisms, infiltration by immune and stromal cells, and histological and clinical characteristics, including outcomes. We provide a single-sample classifier that assigns a consensus class label to a tumor sample's transcriptome. Limitations of the work are retrospective clinical data collection and a lack of complete information regarding patient treatment. Conclusions: This consensus system offers a robust framework that will enable testing and validation of predictive biomarkers in future prospective clinical trials. Patient summary: Bladder cancers are heterogeneous at the molecular level, and scientists have proposed several classifications into sets of molecular classes. While these classifications may be useful to stratify patients for prognosis or response to treatment, a consensus classification would facilitate the clinical use of molecular classes. Conducted by multidisciplinary expert teams in the field, this study proposes such a consensus and provides a tool for applying the consensus classification in the clinical setting.
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| 17. |
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| 18. |
- Kotthoff, U., et al.
(author)
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Reconstructing Holocene temperature and salinity variations in the western Baltic Sea region: a multi-proxy comparison from the Little Belt (IODP Expedition 347, Site M0059)
- 2017
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In: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 14, s. 5607-5632
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Journal article (peer-reviewed)abstract
- Sediment records recovered from the Baltic Sea during Integrated Ocean Drilling Program Expedition 347 provide a unique opportunity to study paleoenvironmental and climate change in central and northern Europe. Such studies contribute to a better understanding of how environmental parameters change in continental shelf seas and enclosed basins. Here we present a multi-proxy-based reconstruction of paleotemperature (both marine and terrestrial), paleosalinity, and paleoecosystem changes from the Little Belt (Site M0059) over the past ∼ 8000 years and evaluate the applicability of inorganic- and organic-based proxies in this particular setting. All salinity proxies (diatoms, aquatic palynomorphs, ostracods, diol index) show that lacustrine conditions occurred in the Little Belt until ∼ 7400 cal yr BP. A connection to the Kattegat at this time can thus be excluded, but a direct connection to the Baltic Proper may have existed. The transition to the brackish–marine conditions of the Littorina Sea stage (more saline and warmer) occurred within ∼ 200 years when the connection to the Kattegat became established after ∼ 7400 cal yr BP. The different salinity proxies used here generally show similar trends in relative changes in salinity, but often do not allow quantitative estimates of salinity. The reconstruction of water temperatures is associated with particularly large uncertainties and variations in absolute values by up to 8 °C for bottom waters and up to 16 °C for surface waters. Concerning the reconstruction of temperature using foraminiferal Mg / Ca ratios, contamination by authigenic coatings in the deeper intervals may have led to an overestimation of temperatures. Differences in results based on the lipid paleothermometers (long chain diol index and TEXL86) can partly be explained by the application of modern-day proxy calibrations to intervals that experienced significant changes in depositional settings: in the case of our study, the change from freshwater to marine conditions. Our study shows that particular caution has to be taken when applying and interpreting proxies in coastal environments and marginal seas, where water mass conditions can experience more rapid and larger changes than in open ocean settings. Approaches using a multitude of independent proxies may thus allow a more robust paleoenvironmental assessment.
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| 19. |
- Müller, Birgit, et al.
(author)
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Standardised and transparent model descriptions for agent-based models : Current status and prospects
- 2014
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In: Environmental Modelling & Software. - : Elsevier BV. - 1364-8152 .- 1873-6726. ; 55, s. 156-163
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Journal article (peer-reviewed)abstract
- Agent-based models are helpful to investigate complex dynamics in coupled human natural systems. However, model assessment, model comparison and replication are hampered to a large extent by a lack of transparency and comprehensibility in model descriptions. In this article we address the question of whether an ideal standard for describing models exists. We first suggest a classification for structuring types of model descriptions. Secondly, we differentiate purposes for which model descriptions are important. Thirdly, we review the types of model descriptions and evaluate each on their utility for the purposes. Our evaluation finds that the choice of the appropriate model description type is purpose-dependent and that no single description type alone can fulfil all requirements simultaneously. However, we suggest a minimum standard of model description for good modelling practice, namely the provision of source code and an accessible natural language description, and argue for the development of a common standard.
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| 20. |
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| 21. |
- Steinke, Stephan, et al.
(author)
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Reconstructing the southern South China Sea upper water column structure since the Last Glacial Maximum : Implications for the East Asian winter monsoon development
- 2010
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In: Paleoceanography. - 0883-8305 .- 1944-9186. ; 25, s. PA2219-
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Journal article (peer-reviewed)abstract
- Upper water column dynamics in the southern South China Sea were reconstructed in order to track changes in the activity of the East Asian winter monsoon (EAWM) since the Last Glacial Maximum. We used the difference in the stable oxygen isotopes (Δδ18O) and Mg/Ca-based temperatures (ΔT) of surface-dwelling (G. ruber) and thermocline-dwelling (P. obliquiloculata) planktonic foraminifera and the temperature difference between alkenone- and P. obliquiloculata Mg/Ca-based temperatures to estimate the upper ocean thermal gradient at International Marine Past Global Change Study (IMAGES) core MD01-2390. Estimates of the upper ocean thermal gradient were used to reconstruct mixed layer dynamics. We find that our Δδ18O estimates are biased by changes in salinity and, thus, do not display a true upper ocean thermal gradient. The ΔT of G. ruber and P. obliquiloculata as well as the alkenone and P. obliquiloculata suggest increased surface water mixing during the late glacial, likely due to enhanced EAWM winds. Surface water mixing was weaker during the late Holocene, indicating a weaker influence of winter monsoon winds. The weakest winter monsoon activity occurred between 6.5 ka and 2.5 ka. Inferred EAWM changes since the Last Glacial Maximum coincide with EAWM changes as recorded in Chinese loess sediments. We find that the intensity of the EAWM and the East Asian summer monsoon show an inverse behavior during the last glacial and deglaciation but covaried during the middle to late Holocene.
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