Shear stress activation of nitric oxide synthase and increased NO levels in human red blood cells

Since the discovery of nitric oxide (NO) as a vasoactive molecule, red blood cells (RBC) have been considered to participate in NO-mediated control of the circulation. The classical role attributed to RBC was scavenging of NO, thereby impacting the local bioavailability of this important regulator of vascular tone^1^. RBC have been shown to be a source of NO, primarily via its transport bound to haemoglobin^2, 3^. Under specific conditions, haemoglobin plays an active role in converting NO derivatives (e.g., nitrite) to NO^4, 5^, with this NO originating from RBC being an effective modulator of vascular smooth muscle tone^6^. Interestingly, RBC contain a NO synthase (NOS) protein^7^, can actively synthesize NO using L-arginine as a substrate^8^, and can export NO under appropriate conditions^8, 9^. It has been previously hypothesized that RBC NOS may be activated by shear forces acting on the cell^10^, and we have recently shown that RBC NOS phosphorylation can be enhanced by subjecting RBC in suspension to shearing forces^9^: NO concentration in the suspending medium was increased subsequent to flow of RBC suspensions through five [mu]m pores^11^. We have now directly demonstrated increased RBC NOS activity and intracellular NO levels in immobilized RBC exposed to well-defined fluid shear stress. Immunostaining for serine 1177 phosphorylation and the NO-sensitive fluorescent probe diaminofluorescein were employed. Our results suggest that RBC deformation in constricted vessels may increase NO levels and favor vasodilation, thereby providing an important role for RBC in regulating the circulation

Some potential blood flow experiments for space

Blood is a colloidal suspension of cells, predominantly erythrocytes, (red cells) in an aqueous solution called plasma. Because the red cells are more dense than the plasma, and because they tend to aggregate, erythrocyte sedimentation can be significant when the shear stresses in flowing blood are small. This behavior, coupled with equipment restrictions, has prevented certain definitive fluid mechanical studies from being performed with blood in ground-based experiments. Among such experiments, which could be satisfactorily performed in a microgravity environment, are the following: (1) studies of blood flow in small tubes, to obtain pressure-flow rate relationships, to determine if increased red cell aggregation can be an aid to blood circulation, and to determine vessel entrance lengths, and (2) studies of blood flow through vessel junctions (bifurcations), to obtain information on cell distribution in downstream vessels of (arterial) bifurcations, and to test flow models of stratified convergent blood flows downstream from (venous) bifurcations

The Impact of Corequisite Math on Community College Student Outcomes: Evidence from Texas

Developmental education (dev-ed) aims to help students acquire knowledge and skills necessary to succeed in college-level coursework, but the traditional prerequisite approach to dev-ed—where students take courses that do not count toward a credential—appears to stymie progress toward a degree. Corequisite remediation is a structural reform that places students directly into a college-level course in the same term they receive dev-ed support. Using state administrative data from Texas community colleges and a regression discontinuity design, we examine whether taking corequisite math improves student success compared with traditional prerequisite dev-ed. We find that corequisite math quickly improves student completion of math requirements without any obvious drawbacks. Although additional follow-up may be necessary to understand long-term effects (given generally low degree attainment in the current follow-up window), we find that students in corequisite math were not substantially closer to degree completion than their peers in traditional dev-ed within 3 years.National Science Foundation grant #1856720 (EHR/IUSE); Eunice Kennedy Shriver National Institute of Child Health and Human Development grant #P2CHD042849 (Population Research Center)Economic