Honoring the Mother of All People; Contemporary Indigenous Leadership in Revitalizing Environmental and Cultural Sustainability

This series of events brings Indigenous perspectives from 22 Indigenous speakers across the U.S. and Arctic regions to discussions of sustainable futures within the New Hampshire community. There is growing movement in the academic community to understand how Indigenous knowledge and cultural heritage can deepen our thinking about sustainable futures. While most researchers recognize that anthropogenic climate change and other sustainability challenges require humanistic as well as scientific approaches, many have yet to thoroughly understand the colonial legacies that initiated many of these sustainability problems and continue to impede our study and solutions. The 2020-2021 Sidore Series was designed to increase awareness about Indigenous perspectives on climate change and cultural resilience; showcase examples of how Indigenous groups are engaged in regional, national, and international dialogues on climate and sustainability; explore how the University of New Hampshire can bring these ideas into teaching, research, and scholarship; and initiate relationships with Indigenous communities to pursue collaborative capacity-building for the co-production of knowledge

Autoantibodies Against dsDNA Modulate Contraction of Blood Clots

© 2017, Springer Science+Business Media, LLC. The degree and rate of clot contraction (retraction) in systemic lupus erythematosus (SLE) patients, especially in those with a high level of anti-double stranded DNA (dsDNA) antibodies in the blood, was significantly reduced compared to healthy donors. We hypothesized that this effect was caused by the anti-dsDNA antibodies. To test this assumption, we investigated the kinetics of blood clot contraction in vitro in the absence and presence of anti-dsDNA antibodies purified from the blood serum of SLE patients. The degree of clot contraction was increased immediately after addition of the anti-DNA antibodies in a concentration-dependent manner. This stimulating effect was abrogated by a monoclonal antibody against the platelet Fc-receptor. On the contrary, after prolonged incubation (for hours) of the blood samples with the anti-DNA antibodies, the extent of clot contraction was significantly reduced. These results suggest that anti-dsDNA antibodies in SLE induce Fc-receptor-mediated chronic platelet hyperactivation, resulting in platelet exhaustion and dysfunction, including reduced contractility. The impaired contraction of blood clots and thrombi caused by autoantibodies may be an important pathogenic mechanism that affects the course and outcomes of thrombotic complications in SLE

Activated Monocytes Enhance Platelet-Driven Contraction of Blood Clots via Tissue Factor Expression

© 2017 The Author(s). Platelet-driven reduction in blood clot volume (clot contraction or retraction) has been implicated to play a role in hemostasis and thrombosis. Although these processes are often linked with inflammation, the role of inflammatory cells in contraction of blood clots and thrombi has not been investigated. The aim of this work was to study the influence of activated monocytes on clot contraction. The effects of monocytes were evaluated using a quantitative optical tracking methodology to follow volume changes in a blood clot formed in vitro. When a physiologically relevant number of isolated human monocytes pre-activated with phorbol-12-myristate-13-acetate (PMA) were added back into whole blood, the extent and rate of clot contraction were increased compared to addition of non-activated cells. Inhibition of tissue factor expression or its inactivation on the surface of PMA-treated monocytes reduced the extent and rate of clot contraction back to control levels with non-activated monocytes. On the contrary, addition of tissue factor enhanced clot contraction, mimicking the effects of tissue factor expressed on the activated monocytes. These data suggest that the inflammatory cells through their expression of tissue factor can directly affect hemostasis and thrombosis by modulating the size and density of intra- and extravascular clots and thrombi

Shape changes of erythrocytes during blood clot contraction and the structure of polyhedrocytes

© 2018, The Author(s). Polyhedral erythrocytes, named polyhedrocytes, are formed in contracted blood clots and thrombi, as a result of compression by activated contractile platelets pulling on fibrin. This deformation was shown to be mechanical in nature and polyhedrocytes were characterized using light and electron microscopy. Through three-dimensional reconstruction, we quantified the geometry of biconcave, intermediate, and polyhedral erythrocytes within contracting blood clots. During compression, erythrocytes became less oblate and more prolate than the biconcave cells and largely corresponded to convex, irregular polyhedra with a total number of faces ranging from 10 to 16. Faces were polygons with 3 to 6 sides. The majority of the faces were quadrilaterals, though not all sides were straight and not all faces were flat. There were no changes in the surface area or volume. These results describe the gradual natural deformation of erythrocytes as a part of compaction into a tightly packed array that is an important but understudied component of mature blood clots and thrombi

Autoantibodies Against dsDNA Modulate Contraction of Blood Clots

© 2017, Springer Science+Business Media, LLC. The degree and rate of clot contraction (retraction) in systemic lupus erythematosus (SLE) patients, especially in those with a high level of anti-double stranded DNA (dsDNA) antibodies in the blood, was significantly reduced compared to healthy donors. We hypothesized that this effect was caused by the anti-dsDNA antibodies. To test this assumption, we investigated the kinetics of blood clot contraction in vitro in the absence and presence of anti-dsDNA antibodies purified from the blood serum of SLE patients. The degree of clot contraction was increased immediately after addition of the anti-DNA antibodies in a concentration-dependent manner. This stimulating effect was abrogated by a monoclonal antibody against the platelet Fc-receptor. On the contrary, after prolonged incubation (for hours) of the blood samples with the anti-DNA antibodies, the extent of clot contraction was significantly reduced. These results suggest that anti-dsDNA antibodies in SLE induce Fc-receptor-mediated chronic platelet hyperactivation, resulting in platelet exhaustion and dysfunction, including reduced contractility. The impaired contraction of blood clots and thrombi caused by autoantibodies may be an important pathogenic mechanism that affects the course and outcomes of thrombotic complications in SLE

Differential Sensitivity of Various Markers of Platelet Activation with Adenosine Diphosphate

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. A number of techniques have been available to assess platelet activation, but their relative sensitivity is unknown and their usage is variable and not based on any rational criteria. Here, we compared the ability of several techniques based on morphological and biochemical markers to detect the first signs of ADP-induced platelet activation. Scanning electron microscopy of platelets was performed in parallel with flow cytometry to quantify the surface expression of P-selectin (marked by labeled anti-CD62P antibodies), active αIIbβ3-intergrin (assessed by the binding of labeled fibrinogen), and phosphatidylserine (assessed by the binding of labeled Annexin V). When expressed as a fraction of activated platelets, shape changes were the most sensitive to a low ADP concentration compared to the biochemical markers in the following order of sensitivity: morphological changes>fibrinogen binding capacity>P-selectin expression> phosphatidylserine exposure. These results suggest the greater sensitivity of platelet microscopy and the importance of its combination with flow cytometry used to detect surface expression of the molecular markers of platelet activation

Differential Sensitivity of Various Markers of Platelet Activation with Adenosine Diphosphate

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. A number of techniques have been available to assess platelet activation, but their relative sensitivity is unknown and their usage is variable and not based on any rational criteria. Here, we compared the ability of several techniques based on morphological and biochemical markers to detect the first signs of ADP-induced platelet activation. Scanning electron microscopy of platelets was performed in parallel with flow cytometry to quantify the surface expression of P-selectin (marked by labeled anti-CD62P antibodies), active αIIbβ3-intergrin (assessed by the binding of labeled fibrinogen), and phosphatidylserine (assessed by the binding of labeled Annexin V). When expressed as a fraction of activated platelets, shape changes were the most sensitive to a low ADP concentration compared to the biochemical markers in the following order of sensitivity: morphological changes>fibrinogen binding capacity>P-selectin expression> phosphatidylserine exposure. These results suggest the greater sensitivity of platelet microscopy and the importance of its combination with flow cytometry used to detect surface expression of the molecular markers of platelet activation

Activated Monocytes Enhance Platelet-Driven Contraction of Blood Clots via Tissue Factor Expression

© 2017 The Author(s). Platelet-driven reduction in blood clot volume (clot contraction or retraction) has been implicated to play a role in hemostasis and thrombosis. Although these processes are often linked with inflammation, the role of inflammatory cells in contraction of blood clots and thrombi has not been investigated. The aim of this work was to study the influence of activated monocytes on clot contraction. The effects of monocytes were evaluated using a quantitative optical tracking methodology to follow volume changes in a blood clot formed in vitro. When a physiologically relevant number of isolated human monocytes pre-activated with phorbol-12-myristate-13-acetate (PMA) were added back into whole blood, the extent and rate of clot contraction were increased compared to addition of non-activated cells. Inhibition of tissue factor expression or its inactivation on the surface of PMA-treated monocytes reduced the extent and rate of clot contraction back to control levels with non-activated monocytes. On the contrary, addition of tissue factor enhanced clot contraction, mimicking the effects of tissue factor expressed on the activated monocytes. These data suggest that the inflammatory cells through their expression of tissue factor can directly affect hemostasis and thrombosis by modulating the size and density of intra- and extravascular clots and thrombi

Blood clot contraction differentially modulates internal and external fibrinolysis

© 2018 International Society on Thrombosis and Haemostasis Essentials Clot contraction influences the rate of fibrinolysis in vitro. Internal fibrinolysis is enhanced ∼2-fold in contracted vs. uncontracted blood clots. External fibrinolysis is ∼4-fold slower in contracted vs. uncontracted blood clots. Contraction can modulate lytic resistance and potentially the clinical outcome of thrombosis. Summary: Background Fibrinolysis involves dissolution of polymeric fibrin networks that is required to restore blood flow through vessels obstructed by thrombi. The efficiency of lysis depends in part on the susceptibility of fibrin to enzymatic digestion, which is governed by the structure and spatial organization of fibrin fibers. How platelet-driven clot contraction affects the efficacy of fibrinolysis has received relatively little study. Objective Here, we examined the effects of clot contraction on the rate of internal fibrinolysis emanating from within the clot to simulate (patho)physiological conditions and external fibrinolysis initiated from the clot exterior to simulate therapeutic thrombolysis. Methods Clot contraction was prevented by inhibiting platelet myosin IIa activity, actin polymerization or platelet-fibrin(ogen) binding. Internal fibrinolysis was measured by optical tracking of clot size. External fibrinolysis was determined by the release of radioactive fibrin degradation products. Results and Conclusions Clot contraction enhanced the rate of internal fibrinolysis ∼2-fold. In contrast, external fibrinolysis was ~4-fold slower in contracted clots. This dichotomy in the susceptibility of contracted and uncontracted clots to internal vs. external lysis suggests that the rate of lysis is dependent upon the interplay between accessibility of fibrin fibers to fibrinolytic agents, including clot permeability, and the spatial proximity of the fibrin fibers that modulate the effects of the fibrinolytic enzymes. Understanding how compaction of blood clots influences clot lysis might have important implications for prevention and treatment of thrombotic disorders

Shape changes of erythrocytes during blood clot contraction and the structure of polyhedrocytes

© 2018, The Author(s). Polyhedral erythrocytes, named polyhedrocytes, are formed in contracted blood clots and thrombi, as a result of compression by activated contractile platelets pulling on fibrin. This deformation was shown to be mechanical in nature and polyhedrocytes were characterized using light and electron microscopy. Through three-dimensional reconstruction, we quantified the geometry of biconcave, intermediate, and polyhedral erythrocytes within contracting blood clots. During compression, erythrocytes became less oblate and more prolate than the biconcave cells and largely corresponded to convex, irregular polyhedra with a total number of faces ranging from 10 to 16. Faces were polygons with 3 to 6 sides. The majority of the faces were quadrilaterals, though not all sides were straight and not all faces were flat. There were no changes in the surface area or volume. These results describe the gradual natural deformation of erythrocytes as a part of compaction into a tightly packed array that is an important but understudied component of mature blood clots and thrombi