Mid-Miocene cooling and the extinction of tundra in continental Antarctica

A major obstacle in understanding the evolution of Cenozoic climate has been the lack of well dated terrestrial evidence from high-latitude, glaciated regions. Here, we report the discovery of exceptionally well preserved fossils of lacustrine and terrestrial organisms from the McMurdo Dry Valleys sector of the Transantarctic Mountains for which we have established a precise radiometric chronology. The fossils, which include diatoms, palynomorphs, mosses, ostracodes, and insects, represent the last vestige of a tundra community that inhabited the mountains before stepped cooling that first brought a full polar climate to Antarctica. Paleoecological analyses, 40Ar/39Ar analyses of associated ash fall, and climate inferences from glaciological modeling together suggest that mean summer temperatures in the region cooled by at least 8°C between 14.07 ± 0.05 Ma and 13.85 ± 0.03 Ma. These results provide novel constraints for the timing and amplitude of middle-Miocene cooling in Antarctica and reveal the ecological legacy of this global climate transition

Procoagulant Activity in Hemostasis and Thrombosis: Virchowʼs Triad Revisited

Virchow’s triad is traditionally invoked to explain pathophysiologic mechanisms leading to thrombosis, alleging concerted roles for abnormalities in blood composition, vessel wall components, and blood flow in the development of arterial and venous thrombosis. Given the tissue-specific bleeding observed in hemophilia patients, it may be instructive to consider the principles of Virchow’s triad when investigating mechanisms operant in hemostatic disorders as well. Blood composition (the function of circulating blood cells and plasma proteins) is the most well-studied component of the triad. For example, increased levels of plasma procoagulant proteins such as prothrombin and fibrinogen are established risk factors for thrombosis, whereas deficiencies in plasma factors VIII and IX result in bleeding (hemophilia A and B, respectively). Vessel wall (cellular) components contribute adhesion molecules that recruit circulating leukocytes and platelets to sites of vascular damage, tissue factor, which provides a procoagulant signal of vascular breach, and a surface upon which coagulation complexes are assembled. Blood flow is often characterized by two key variables: shear rate and shear stress. Shear rate affects several aspects of coagulation, including transport rates of platelets and plasma proteins to and from the injury site, platelet activation, and the kinetics of fibrin monomer formation and polymerization. Shear stress modulates adhesion rates of platelets and expression of adhesion molecules and procoagulant activity on endothelial cells lining the blood vessels. That no one abnormality in any component of Virchow’s triad fully predicts coagulopathy a priori suggests coagulopathies are complex, multifactorial and interactive. In this review, we focus on contributions of blood composition, vascular cells, and blood flow to hemostasis and thrombosis, and suggests cross-talk among the three components of Virchow’s triad is necessary for hemostasis and determines propensity for thrombosis or bleeding. Investigative models that permit interplay among these components are necessary to understand the operant pathophysiology, and effectively treat and prevent thrombotic and bleeding disorders

Elevated Prothrombin Promotes Venous, but Not Arterial, Thrombosis in Mice

Individuals with elevated prothrombin, including those with the prothrombin G20210A mutation, have increased risk of venous thrombosis. Although these individuals do not have increased circulating prothrombotic biomarkers, their plasma demonstrates increased tissue factor-dependent thrombin generation in vitro. The objectives of this study were to determine the pathologic role of elevated prothrombin in venous and arterial thrombosis in vivo, and distinguish thrombogenic mechanisms in these vessels

Sighting acute myocardial infarction through platelet gene expression

© 2019, The Author(s). Acute myocardial infarction is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression profiling at the time of an acute myocardial infarction provides information concerning the platelet gene expression preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet gene expression identified five differentially expressed genes: FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression model used to combine the gene expression in a STEMI vs healthy donors score showed an AUC of 0.95. The same five differentially expressed genes were externally validated using platelet gene expression data from patients with coronary atherosclerosis but without thrombosis. Platelet gene expression profile highlights five genes able to identify STEMI patients and to discriminate them in the background of atherosclerosis. Consequently, early signals of an imminent acute myocardial infarction are likely to be found by platelet gene expression profiling before the infarction occurs

Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition

Strontium isotopic, chemical, and sedimentological evidence for the evolution of Lake Lisan and the Dead Sea

Precise strontium isotope ratios, combined with chemical analyses and sedimentological information, are used to monitor the water sources and the evolution of the Dead Sea and its late Pleistocene precursor, Lake Lisan (70-18 kyr B.P.). The materials analyzed include bulk aragonite, water-leached soluble salts, and residual aragonite and gypsum from the Lisan Formation in the Perazim Valley (near the SW shore of the Dead Sea). The residual aragonite and the associated soluble salts display systematic fluctuations in 17Sr86Sr ratios between 0.70803 and 0.70806 and from 0.70805 to 0.70807, respectively. In individual soluble salt-residual aragonite pairs, the soluble salt displays a higher 87Sr86Sr ratio. Gypsum samples yield 17Sr86Sr ratios similar to the soluble salts from adjacent layers in the section. This shows that, in individual samples, the source of Sr in aragonite was distinct from that in soluble salts and the gypsum. The sterility of the Lisan sediments, their strictly nonbioturbated fine lamination, and their high content of chloride salts indicate that Lake Lisan was a saline, or even hypersaline water body. In the absence of alternative sources of HCO3− and S042− the abundance of primary aragonite and gypsum in the Lisan column reflects an import of very large volumes of freshwater into the otherwise saline lake, resulting in a density stratification of this water body. The history of the upper water layer and that of the lower brine is reflected in the chemical and strontium isotope composition of the aragonite and in that of the associated soluble salts and in the gypsum samples, respectively. Whereas the bicarbonate and much of the Ca2+ required for aragonite crystallization were supplied by the freshwater, the complementary Ca2+ (and Sr 2+) were added by the lower brine. The upper water layer of Lake Lisan acted as a SO42− capacitor during the lake's rise periods. It was removed therefrom, as prominent gypsum beds, upon climatic-induced (drier period) mixing or even complete overturn of the lake. The evolution of Lake Lisan took place between two distinct modes. The first was characterized by an extensive supply of freshwater and resulted in a rise of the lake's level, a (density) layered structure, and precipitation of aragonite. The second mode was marked by a diminishing freshwater input, resulting in mixing or complete overturn of its water, and precipitation of gypsum. These two modes reflect the climatic evolution of the region in the late Pleistocene which fluctuated between drier and wetter periods. The transition to the Holocene is accompanied by the dry up of Lake Lisan and its contraction to the present Dead Sea

Glauconitization episodes before the onset of Antarctic glaciation

9th SCAR Open Science Conference and XXXVI SCAR Meetings Hobart, Tasmania, Australia 31 July - 11 August 202

In vitro megakaryocyte culture from human bone marrow aspirates as a research and diagnostic tool

Megakaryocytes (MKs) are relatively rare in bone marrow, comprising <0.05% of the nucleated cells, which makes direct isolation from human bone marrow impractical. As such, in vitro expansion of primary MKs from patient samples offers exciting fundamental and clinical opportunities. As most of the developed ex vivo methods require a substantial volume of biomaterial, they are not widely performed on young patients. Here we propose a simple, robust, and adapted method of primary human MK culture from 1 mL of bone marrow aspirate. Our technique uses a small volume of bone marrow per culture, uses straightforward isolation methods, and generates approximately 6 × 105 mature MKs per culture. The relative high cell purity and yield achieved by this technique, combined with efficient use of low volumes of bone marrow, make this approach suitable for diagnostic and basic research of human megakaryopoiesis