RGS10 shapes the hemostatic response to injury through its differential effects on intracellular signaling by platelet agonists.

Platelets express ≥2 members of the regulators of G protein signaling (RGS) family. Here, we have focused on the most abundant, RGS10, examining its impact on the hemostatic response in vivo and the mechanisms involved. We have previously shown that the hemostatic thrombi formed in response to penetrating injuries consist of a core of fully activated densely packed platelets overlaid by a shell of less-activated platelets responding to adenosine 5\u27-diphosphate (ADP) and thromboxane A2 (TxA2). Hemostatic thrombi formed in RGS10-/- mice were larger than in controls, with the increase due to expansion of the shell but not the core. Clot retraction was slower, and average packing density was reduced. Deleting RGS10 had agonist-specific effects on signaling. There was a leftward shift in the dose/response curve for the thrombin receptor (PAR4) agonist peptide AYPGKF but no increase in the maximum response. This contrasted with ADP and TxA2, both of which evoked considerably greater maximum responses in RGS10-/- platelets with enhanced Gq- and Gi-mediated signaling. Shape change, which is G13-mediated, was unaffected. Finally, we found that free RGS10 levels in platelets are actively regulated. In resting platelets, RGS10 was bound to 2 scaffold proteins: spinophilin and 14-3-3γ. Platelet activation caused an increase in free RGS10, as did the endothelium-derived platelet antagonist prostacyclin. Collectively, these observations show that RGS10 serves as an actively regulated node on the platelet signaling network, helping to produce smaller and more densely packed hemostatic thrombi with a greater proportion of fully activated platelets

Mixed-Reality Simulations to Build Capacity for Advocating for Diversity, Equity, and Inclusion in Geosciences

We report on data collected at 3 time points during a 1-year intervention designed to teach a purposive sample of geoscience faculty members (n = 29) from 27 universities throughout the United States how to identify and address issues related to diversity, equity, and inclusion in their departments. For the intervention we used mixed-reality simulations to help participants practice specific skills to address common situations in geoscience departments. The intervention also included an intensive 3-day workshop and 3 journal clubs. Using a Bayesian analytical approach we explored: (a) general trends in participants’ self- and collective efficacy for identifying and addressing diversity, equity, and inclusion over a 1-year period; (b) relationships between self-efficacy and collective efficacy; and (c) demographic factors that explain variation in self- and collective efficacy. Results showed that self- and collective efficacy rose sharply from preintervention to 5 months after beginning. Although both self- and collective efficacy retreated toward baseline at the 1-year mark, only 1-year self-efficacy was still credibly higher than preintervention. Also, preintervention self-efficacy predicted 5-month collective efficacy. Efficacy beliefs varied as a function of race/ethnicity. Only collective efficacy varied as a function of academic rank. We discuss these findings in relation to social– cognitive theory and the literature regarding the use of digital learning environments to address diversity, equity, and inclusion

Kinetics and mechanics of clot contraction are governed by the molecular and cellular composition of the blood

© 2016 by The American Society of Hematology. Platelet-driven blood clot contraction (retraction) is thought to promote wound closure and secure hemostasis while preventing vascular occlusion. Notwithstanding its importance, clot contraction remains a poorly understood process, partially because of the lack of methodology to quantify its dynamics and requirements. We used a novel automated optical analyzer to continuously track in vitro changes in the size of contracting clots in whole blood and in variously reconstituted samples. Kinetics of contraction was complemented with dynamic rheometry to characterize the viscoelasticity of contracting clots. This combined approach enabled investigation of the coordinated mechanistic impact of platelets, including nonmuscle my osin II, red blood cells (RBCs), fibrin(ogen), factor XIIIa (FXIIIa), and thrombin on the kinetics and mechanics of the contraction process. Clot contraction is composed of 3 sequential phases, each characterized by a distinct rate constant. Thrombin, Ca2+, the integrin αIIbβ3, myosin IIa, FXIIIa cross-linking, and platelet count all promote 1 or more phases of the clot contraction process. In contrast, RBCs impair contraction and reduce elasticity, while increasing the overall contractile stress generated by the platelet fibrin meshwork. A better understanding of the mechanisms by which blood cells, fibrin(ogen), and platelet-fibrin interactions modulate clot contraction may generate novel approaches to reveal and to manage thrombosis and hemostatic disorders

Immunological cross-reaction of bovine growth hormone (NIH-GH-B8) with the antiserum to the bovine diabetogenic protein

1. 1. The immunological cross-reaction of bovine growth hormone (BGH, NIH-GH-D8) with the antiserum to the bovine diabetogenic protein (BDP) has been determined to be the result of contamination of the BGH preparation with a highly anionic protein.2. 2. This highly anionic protein is probably BDP.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22095/1/0000519.pd

Influence of bovine diabetogenic peptide, growth hormone, and prolactin on tissue glycogen, liver fat, and liver water of fasting rats

1. 1. Bovine diabetogenic peptide, growth hormone, and prolactin were compared with respect to their effects on tissue glycogen, liver fat, and liver water in fasting rats.2. 2. Bovine diabetogenic peptide increases liver size, liver glycogen, liver water, and total liver lipids.3. 3. Bovine diabetogenic peptide, in contrast to growth hormone and prolactin, does not increase muscle glycogen levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33638/1/0000147.pd

Effect of a diabetogeic factor from bovine adenohypophysis on dog serum nefa levels

1. 1. Fasted dog serum non-esterified fatty acid (NEFA) levels were elevated 10 and 34 hours after administration of a diabetogenic protein (BDF) isolated from bovine adenohypophysis.2. 2. The fasting serum NEFA were elevated in spite of the presence of normal or high glucose and insulin levels.3. 3. After oral glucose administration to BDF-treated animals, a fall of serum NEFA paralleled inversely the increasing levels of blood glucose and serum insulin.4. 4. These data are discussed with respect to the insulin-antagonistic action of BDF. Even though the plasma NEFA fell in response to glucose in BDF-treated animals, the NEFA during the entire 3-hour glucose-tolerance test were always significantly higher than the levels observed in the control tests.5. 5. Since BDF is similar to the diabetogenic protein isolated from the urine of patients with lipoatrophic diabetes, its lipid-mobilizing action might help to explain the lipoatrophy, hyperlipaemia, diabetes mellitus, and insulin resistance seen in lipoatrophic diabetic patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34028/1/0000305.pd

Immunological characterization of a diabetogenic protein from bovine adenohypophysis

1. 1. A diabetogenic protein isolated from bovine adenohypophysis which had previously been demonstrated to cause fasting hyperglycemia and decreased glucose tolerance in dogs and man is highly antigenic when injected into rabbits.2. 2. Immunoelectrophoresis and gel double diffusion studies did not provide evidence of multiple antibodies or antigens in the bovine diabetogenic protein: anti-bovine diabetogenic system.3. 3. Results of agar diffusion studies in which anti-bovine diabetogenic protein serum did not visibly react with homologous bovine serum proteins, serum albumin, ACTH or prolactin lend supporting evidence for the homogeneity of the reaction between bovine diabetogenic protein and its antiserum.4. 4. A comparative immunological study of diabetogenic proteins from various species was performed using agar double diffusion studies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22094/1/0000518.pd

Glycostatic effect of a diabetogenic non-growth-promoting pituitary polypeptide

1. 1. Treatment with a mg. of a non-growth-promoting bovine diabetogenic peptide or growth hormone in two divided doses, one at the beginning and one 7-9 hours later, to hypophysectomized rats during a 24-hour fast maintained their muscle glycogen at a normal level.2. 2. Administration of bovine serum albumin or saline was accompanied by a sharp decrease of muscle glycogen.3. 3. The minimum dose of highly purified bovine diabetogenic peptide which is capable of maintaining muscle glycogen at normal levels was found to be 0.2-0.3 mg. in 135-150-g. rats.4. 4. Diabetogenic peptide maintains muscle glycogen in fasted hypophysectomizedadrenalectomized rats.5. 5. Diabetogenic peptide does not promote growth as measured by the tibia test.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33637/1/0000146.pd

Envelope from F. H. Mohns, Birmingham, Alabama to Mrs. T. C. McCorvey, University, Alabama, October 29, 1941

Written on front: Lease of A-3 Ala. Apt--Oct 1941 to Oct 1942