Response of the North Atlantic surface and intermediate ocean structure to climate warming of MIS 11

Investigating past interglacial climates not only help to understand how the climate system operates in general, it also forms a vital basis for climate predictions. We reconstructed vertical stratification changes in temperature and salinity in the North Atlantic for a period some 400 ka ago (MIS11), an interglacial time analogue of a future climate. As inferred from a unique set of biogeochemical, geochemical, and faunal data, the internal upper ocean stratification across MIS 11 shows distinct depth-dependent dynamical changes related to vertical as well as lateral shifts in the upper Atlantic meridional circulation system. Importantly, transient cold events are recognized near the end of the long phase of postglacial warming at surface, subsurface, mid, and deeper water layers. These data demonstrate that MIS 11 coolings over the North Atlantic were initially triggered by freshwater input at the surface and expansion of cold polar waters into the Subpolar Gyre. The cooling signal was then transmitted downwards into mid-water depths. Since the cold events occurred after the main deglacial phase we suggest that their cause might be related to continuous melting of the Greenland ice sheet, a mechanism that might also be relevant for the present and upcoming climate

Asynchronous responses of aquatic ecosystems to hydroclimatic forcing on the Tibetan Plateau

High-altitude ecosystems react sensitively to hydroclimatic triggers. Here we evaluated the ecological and hydrological changes in a glacier-influenced lake (Hala Hu, China) since the last glacial. Rapid fluctuations of aquatic biomarker concentrations, ratios, and hydrogen isotope values, from 15 to 14,000 and 8 to 5000 years before present, provided evidence for aquatic regime shifts and changes in lake hydrology. In contrast, most negative hydrogen isotope values of terrestrial biomarkers were observed between 9 and 7,000 years before present. This shows that shifts of vapour sources and increased precipitation amounts were not relevant drivers behind ecosystem changes in the studied lake. Instead, receding glaciers and increased meltwater discharge, driven by higher temperatures, caused the pronounced ecological responses. The shifts within phytoplankton communities in the Late Glacial and mid Holocene illustrate the vulnerability of comparable ecosystems to climatic and hydrological changes. This is relevant to assess future ecological responses to global warming

Hydrogen isotopic ratios of long-chain diols reflect salinity

Long-chain diols (LCDs) are ubiquitous lipids produced by freshwater and marine algae. A combination of semi-preparative high performance liquid chromatography and gas chromatography isotope ratio monitoring mass spectrometry, allowed the measurement of δ2H of individual LCDs from cultures, which indicated a correlation with the hydrogen isotope composition of the growth water and a species-specific effect. Results from environmental samples along a salinity gradient indicated the potential of δ2H ratios of LCDs to trace the hydrogen isotopic composition of water and sea surface salinity.ISSN:0146-638

Carbon isotopic ratios of modern C3 and C4 vegetation on the Indian peninsula and changes along the plant–soil–river continuum – implications for vegetation reconstructions

The large difference in the fractionation of stable carbon isotopes between C3 and C4 plants is widely used in vegetation reconstructions, where the predominance of C3 plants suggests wetter and that of C4 plants drier conditions. The stable carbon isotopic composition of organic carbon (OC) preserved in soils or sediments may be a valuable (paleo-)environmental indicator, based on the assumption that plant-derived material retains the stable carbon isotopic value of its photosynthetic pathway during transfer from plant to sediment. In this study, we investigated the bulk carbon isotopic values of C3 and C4 plants (δ13C) and of organic carbon (δ13Corg) in soils, river suspended particulate matter (SPM) and riverbed sediments to gain insight into the control of precipitation on C3 and C4 plant δ13C values and to assess changes in δ13Corg values along the plant–soil–river continuum. This information allows us to elucidate the implications of different δ13C end-members on C3 / C4 vegetation reconstructions. Our analysis was performed in the Godavari River basin, located in the core monsoon zone in peninsular India, a region that integrates the hydroclimatic and vegetation changes caused by variation in monsoonal strength. The basin has distinct wet and dry seasons and is characterised by natural gradients in soil type (from clay-rich to sandy), precipitation (∼ 500 to 1500 mm yr−1) and vegetation type (from mixed C3 / C4 to primarily C3) from the upper to the lower basin. The δ13C values of Godavari C3 plants were strongly controlled by mean annual precipitation (MAP), showing an isotopic enrichment of ∼ 2.2 ‰ from ∼ 1500 to 500 mm yr−1. Tracing δ13Corg values from plant to soils and rivers revealed that soils and riverbed sediments reflected the transition from mixed C3 and C4 vegetation in the dry upper basin to more C3 vegetation in the humid lower basin. Soil degradation and stabilisation processes and hydrodynamic sorting within the river altered the plant-derived δ13C signal. Phytoplankton dominated the δ13Corg signal carried by SPM in the dry season and year-round in the upper basin. Application of a linear mixing model showed that the %C4 plants in the different subbasins was ∼ 7 %–15 % higher using plant end-members based on measurement of the Godavari vegetation and tailored to local moisture availability than using those derived from data compilations of global vegetation. Including a correction for the 13C enrichment in Godavari C3 plants due to drought resulted in maximally 6 % lower estimated C4 plant cover. Our results from the Godavari basin underline the importance of making informed choices about the plant δ13C end-members for vegetation reconstructions, considering characteristics of the regional vegetation and environmental factors such as MAP in monsoonal regions

A cold and fresh ocean surface in the Nordic Seas during MIS 11: Significance for the future ocean

Paleoceanographical studies of Marine Isotope Stage (MIS) 11 have revealed higher-than-present sea surface temperatures (SSTs) in the North Atlantic and in parts of the Arctic but lower-than-present SSTs in the Nordic Seas, the main throughflow area of warm water into the Arctic Ocean. We resolve this contradiction by complementing SST data based on planktic foraminiferal abundances with surface salinity changes using hydrogen isotopic compositions of alkenones in a core from the central Nordic Seas. The data indicate the prevalence of a relatively cold, low-salinity, surface water layer in the Nordic Seas during most of MIS 11. In spite of the low-density surface layer, which was kept buoyant by continuous melting of surrounding glaciers, warmer Atlantic water was still propagating northward at the subsurface thus maintaining meridional overturning circulation. This study can help to better constrain the impact of continuous melting of Greenland and Arctic ice on high-latitude ocean circulation and climate

Expression and regulation of HIF-1alpha in macrophages under inflammatory conditions; significant reduction of VEGF by CaMKII inhibitor

<p>Abstract</p> <p>Background</p> <p>Macrophages expressing the pro-angiogenic transcription factor hypoxia-inducible factor (HIF)-1alpha have been demonstrated in rheumatoid arthritis (RA) in the synovial tissue. Aim of the present study was to investigate intracellular signal transduction regulation of pro-inflammatory HIF-1 alpha expression in macrophages to identify possible new intervention strategies. We investigated the effects of CaMKII-inhibitors amongst other kinase inhibitors, on HIF-1 alpha expression and downstream production of pro-angiogenic factors in macrophages.</p> <p>Methods</p> <p>Differentiated THP-1 cells and synovial fluid (SF) macrophages were stimulated with 1 μg/ml LPS with or without pretreatment with specific inhibitors of the ERK pathway (PD98059), the PI3K pathway (LY294002), and the CaMKII pathway (KN93 and SMP-114). mRNA and protein expression of HIF-1 alpha, VEGF, MMP-9, and IL-8 was measured in cell lysates and cell supernatants.</p> <p>Results</p> <p>HIF-1 alpha protein expression in LPS-stimulated THP-1 macrophages could be blocked by ERK- and PI3K-inhibitors, but also by the CaMKII inhibitor KN93. THP-1 and SF macrophages produced high levels of VEGF, IL-8, and MMP-9, and VEGF protein production was significantly inhibited by PI3K-inhibitor, and by both CaMKII inhibitors. LPS stimulation in an hypoxic environment did not change VEGF levels, suggesting that LPS induced VEGF production in macrophages is more important than the hypoxic induction.</p> <p>Conclusions</p> <p>Expression of HIF-1 alpha and downstream effects in macrophages are regulated by ERK-, PI3K, but also by CaMKII pathways. Inhibition of HIF-1α protein expression and significant inhibition of VEGF production in macrophages was found using CaMKII inhibitors. This is an unknown but very interesting effect of the CaMKII inhibitor SMP-114, which has been in clinical trial as DMARD for the treatment of RA. This effect may contribute to the anti-arthritic effects of SMP-114.</p

Dysregulated innate and adaptive immune responses discriminate disease severity in COVID-19

The clinical spectrum of COVID-19 varies and the differences in host response characterizing this variation have not been fully elucidated. COVID-19 disease severity correlates with an excessive pro-inflammatory immune response and profound lymphopenia. Inflammatory responses according to disease severity were explored by plasma cytokine measurements and proteomics analysis in 147 COVID-19 patients. Furthermore, peripheral blood mononuclear cell cytokine production assays and whole blood flow cytometry were performed. Results confirm a hyperinflammatory innate immune state, while highlighting hepatocyte growth factor and stem cell factor as potential biomarkers for disease severity. Clustering analysis reveals no specific inflammatory endotypes in COVID-19 patients. Functional assays reveal abrogated adaptive cytokine production (interferon-gamma, interleukin-17 and interleukin-22) and prominent T cell exhaustion in critically ill patients, whereas innate immune responses were intact or hyperresponsive. Collectively, this extensive analysis provides a comprehensive insight into the pathobiology of severe to critical COVID-19 and highlight potential biomarkers of disease severity

Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer:A Randomized Clinical Trial

PURPOSE:Resectable non-small-cell lung cancer (NSCLC) with a high probability of mediastinal nodal involvement requires mediastinal staging by endosonography and, in the absence of nodal metastases, confirmatory mediastinoscopy according to current guidelines. However, randomized data regarding immediate lung tumor resection after systematic endosonography versus additional confirmatory mediastinoscopy before resection are lacking.METHODS:Patients with (suspected) resectable NSCLC and an indication for mediastinal staging after negative systematic endosonography were randomly assigned to immediate lung tumor resection or confirmatory mediastinoscopy followed by tumor resection. The primary outcome in this noninferiority trial (noninferiority margin of 8% that previously showed to not compromise survival, Pnoninferior &lt;.0250) was the presence of unforeseen N2 disease after tumor resection with lymph node dissection. Secondary outcomes were 30-day major morbidity and mortality.RESULTS:Between July 17, 2017, and October 5, 2020, 360 patients were randomly assigned, 178 to immediate lung tumor resection (seven dropouts) and 182 to confirmatory mediastinoscopy first (seven dropouts before and six after mediastinoscopy). Mediastinoscopy detected metastases in 8.0% (14/175; 95% CI, 4.8 to 13.0) of patients. Unforeseen N2 rate after immediate resection (8.8%) was noninferior compared with mediastinoscopy first (7.7%) in both intention-to-treat (Δ, 1.03%; UL 95% CIΔ, 7.2%; Pnoninferior =.0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; Pnoninferior =.0157). Major morbidity and 30-day mortality was 12.9% after immediate resection versus 15.4% after mediastinoscopy first (P =.4940).CONCLUSION:On the basis of our chosen noninferiority margin in the rate of unforeseen N2, confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.</p

T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation

CD4(+) T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4(+) memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4(+) memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4(+) memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4(+) memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation