A new perspective of the Alboran Upwelling System reconstruction during the Marine Isotope Stage 11: A high-resolution coccolithophore record

A high-resolution study of the MIS 12/MIS 11 transition and the MIS 11 (430–376 kyr) coccolithophore assemblages at Ocean Drilling Program Site 977 was conducted to reconstruct the palaeoceanographic and climatic changes in the Alboran Sea from the variability in surface water conditions. The nannofossil record was integrated with the planktonic oxygen and carbon stable isotopes, as well as the Uk'37 Sea Surface Temperature (SST) at the studied site during the investigated interval. The coccolithophore primary productivity, reconstructed from the PPP (primary productivity proxy = absolute values of Gephyrocapsa caribbeanica + small Gephyrocapsa group) revealed pronounced fluctuations, that were strongly associated with variations in the intensity of the regional Alboran Upwelling System. The comparison of the nannoplankton record with opal phytolith content for the studied site and the already available pollen record at the nearby Integrated Ocean Drilling Program Site U1385, suggests an association of the upwelling dynamics with the variability of the North Atlantic Oscillation-like (NAO-like) phase. High PPP during positive (+) NAO-like phases is the result of intensified upwelling, owing to the complete development of the surface hydrological structures at the Alboran Sea. This scenario was identified during the MIS 12/MIS 11 transition (428-422 kyr), the late MIS 11c (405-397 kyr), and MIS11 b to MIS 11a (397-376 kyr). Two short-term minima in the PPP and SST were observed during MIS 11 b and were coeval with the North Atlantic Heinrich-type (Ht) events Ht3 (∼390 kyr) and Ht2 (∼384 kyr). Increased abundance of the subpolar Coccolithus pelagicus subsp. pelagicus and Gephyrocapsa muellerae was consistent with the inflow of cold surface waters into the Mediterranean Sea during the Ht events. Lowered PPP during negative (−) NAO-like phases is the result of moderate upwelling by the incomplete development of surface hydrological structures at the Alboran Sea. This scenario is expressed during the early MIS 11c (422-405 kyr). Overall, the results of our study provide evidence of the important role of atmospheric circulation patterns in the North Atlantic region for controlling phytoplankton primary production and oceanographic circulation dynamics in the Western Mediterranean during MIS 11

Meltwater flux from northern ice-sheets to the Mediterranean during MIS 12

Planktonic foraminifer oxygen isotopes through MIS 12 were analysed from Ocean Drilling Program Site 977 in the Alboran Sea. After the correction of the sea surface temperature (SST) effect on the d18O composition of foraminiferal calcite, the resulting seawater d18O (d18Ow) was used to reconstruct variations in the d18Ow of the Atlantic inflow into the Mediterranean. A synchronous record from the KC01B core, in the Ionian Sea, was used to evaluate changes in the oxygen isotope gradient within the Mediterranean due to hydrological variations during MIS 12. Instead of the glacial d18Ow enrichment expected for the Mediterranean, lower values than today have been observed both in the Alboran and the Ionian seas, especially between 455 ka and the end of MIS 12 (424 ka). These negative oxygen isotope anomalies must have been caused by a flux of freshwater to the Mediterranean during MIS 12. Although the largest fraction of the freshwater anomalies entered the Mediterranean through the Atlantic inflow, especially during Heinrich stadials, the Mediterranean d18Ow gradient allowed us to identify other sources of freshwater to the eastern basin. One of these sources was probably the meltwater generated at the southern margin of the Fennoscandian ice-sheet that entered via the Caspian and Black seas. However, the proximity of core KC01B to the Adriatic Sea points to meltwater delivered from the Alpine ice-sheet and transported through the Po river into the Mediterranean as the main cause of the Ionian Sea 18O depletion

Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study

Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients