Shear induced autoregulation is the natural ability of organs to maintain the local hemodynamic stresses in a stable condition in spite of altering perfusion rate. Endothelium cells are shear sensitive mechanoreceptors that are responsible for regulating the arterial wall architecture and mechanical properties in order to maintain homeostasis. This occurs by means of vasoactive mediators, which cause vasodilation or vasoconstriction. In this paper we presented a multiscale model of local flow regulation. First, a lumped parameter model of the whole cardiovascular system was implemented. Then a 3D numerical model of human common carotid artery was constructed considering fluid-structure interaction. The CCA inflow waveform obtained from the extended 0D model was applied to the 3D model as the boundary condition. After applying the Head-Up Tilt test, the local hemodynamics were disturbed. By considering the wall shear stress as the regulation criterion, then altering the arterial mechanical properties and the following vasodilation, shear forces exerted on the inner lining of the vessel were regulated and returned to the normal range. The resulting 0D/3D model can be considered as a plat-form for a more complete model containing local and systemic cardiovascular control mechanisms and patient-specific geometries which can be used for clinical purposes.

The Suppressor of forked protein is the Drosophila homolog of the 77K subunit of human cleavage stimulation factor, a complex required for the first step of the mRNA 3′-end-processing reaction. We have shown previously that wild-type su(f) function is required for the accumulation of a truncated su(f) transcript polyadenylated in intron 4 of the gene. This led us to propose a model in which the Su(f) protein would negatively regulate its own accumulation by stimulating 3′-end formation of this truncated su(f) RNA. In this article, we demonstrate this model and show that su(f) autoregulation is tissue specific. The Su(f) protein accumulates at a high level in dividing tissues, but not in nondividing tissues. We show that this distribution of the Su(f) protein results from stimulation by Su(f) of the tissue-specific utilization of the su(f) intronic poly(A) site, leading to the accumulation of the truncated su(f) transcript in nondividing tissues. Utilization of this intronic poly(A) site is affected in a su(f) mutant and restored in the mutant with a transgene encoding wild-type Su(f) protein. These data provide an in vivo example of cell-type-specific regulation of a protein level by poly(A) site choice, and confirm the role of Su(f) in regulation of poly(A) site utilization.

A small decrease in cerebral blood flow (approximately 10%) in response to 100% oxygen (O2) administration is well recognized. This observation was based on human volunteer studies, which employed a nitrous oxide washout method for the measurement of cerebral blood flow. Because this method is now appreciated to be subject to potential errors we have examined the cerebral blood flow response to 100% oxygen using a magnetic resonance imaging technique to quantify changes in carotid and basilar artery flow. The study, was performed in 12 normal male subjects aged 23–42 years. We report decreases in cerebral blood flow ranging from 9 to 31% with a mean value of over 20%. The decrease in cerebral blood flow was greater in seven young subjects (aged 23–26 years) with decreases in cerebral blood flow of 19.3–31.4% (mean 26.8%). In five older subjects (aged 32–42 years), decreases in CBF were smaller (mean 16.2%). The administration of 100% O2 was accompanied by a small decrease in end-tidal CO2 (3.7–7.1%), insufficient to explain the changes in cerebral blood flow. We conclude that the decrease in cerebral blood flow in response to O2 administration is greater than previously described and appears to be greater in young adults.