Endothelial cell impact on smooth muscle cell properties: role of hemodynamic forces

The vascular endothelium is a dynamic cell monolayer located at the interface of the vessel wall and bloodstream, where it regulates the physiological effects of humoral and hemodynamic stimuli on vessel tone and remodelling. Hemodynamic forces are of particular interest and include shear stress, the frictional force generated by blood as it drags against the endothelium, and cyclic strain, transmural pressure due to the pulsatile nature of blood flow. Both forces can profoundly modulate vascular endothelial metabolism and function and, within normal physiological ranges, typically impart an atheroprotective effect which disfavours pathological remodelling of the vessel wall. Changes to arterial wall architecture (i.e. remodelling) are a key feature of vascular diseases (e.g. atherosclerosis) and often stem from disruption of normal blood flow patterns, leading to vascular endothelial dysfunction and dysregulation of the underlying smooth muscle cell layer. The focus of the PhD project was to investigate hemodynamic challenge of vascular endothelial cells impacts smooth muscle cells. In order to assess the hemodynamic challenge of vascular endothelial cells, shear stress and cyclic strain were applied to BAECs. Both forces resulted in morphological realignment of cells along with a clear realignment for the actin cytoskeleton in the direction of flow. Furthermore, ZO-1 localisation also increased at the cell-border. We next investigated how hemodynamic challenge of vascular endothelial cells putatively impacts vascular smooth muscle cell growth properties. Four experimental models were employed namely; laminar shear stress, turbulent shear stress, pulsatile shear stress with co-culture and cyclic strain using in vitro hemodynamic modelling. Laminar shear stress, pulsatile shear stress with co-culture and cyclic strain of endothelial cells resulted in a decrease in BASMC proliferation with a parallel increase in apoptosis. Turbulent shear resulted in the opposite effect caused a slight increase in BASMC proliferation with no effect on apoptosis. This indicated that physiological forces impart an atheroprotective effect. In the hemodynamic models, BAECs and BASMCs were not in physical contact. This suggested that BAECs secreted factor(s) acting directly on the BASMC (or indirectly) on the BAECs were responsible for these effects. As the BAECs and BASMCs were not in physical contact this suggested that BAECs secreted factor(s) acting directly on the BASMC (or indirectly) on the BAECs were responsible for these effects. To investigate the endothelial signalling pathways and effectors putatively mediating these effects specific pharmacological inhibitors were employed. The results revealed that an integrin-Rac1 pathway possibly upstream of NO production may be mediating this endothelial regulatory response under LSS. We investigated the impact of LSS-derived BCM on the expression of cell cycle associated genes within the smooth muscle cells both single gene- and microarray-based RealTime PCR methodologies. Our results highlighted key CDK, cyclins and other cell cycle regulatory proteins. This study confirms the importance of hemodynamic challenge on the endothelium and the putative interactions between endothelial and smooth muscle cells in vascular remodelling

Ion neutral coupling in the high latitude thermosphere, part 1

Measurements of the neutral wind in the polar F region from Dynamics Explorer-2 (DE-2) were used to illustrate asymmetries in the neutral circulation that are dependent on the sign of the B sub y component of the interplanetary magnetic field (IMF). Individual DE-2 orbits and averaged data sets from different Universal times are presented. The data are categorized according to the sign of the hourly averaged IMF B sub y component measured by ISEE-3 for the hour preceding the DE-2 measurement. The major features observed are: (1) an asymmetry in the polar cap neutral flow velocity with the region of most rapid antisunward flow shifting from the dawn side to the dusk side of the polar cap as B sub y changes from positive to negative; (2) a shift in magnetic local time of the region of entry of neutral gas into the polar cap from a location on the dawn side of the noon-midnight meridian for B sub y positive to one more biased towards the dusk side for B sub y negative; (3) an enhancement in the velocities associated with the dawn, anti-clockwise neutral vortex B suby y negative relative to those observed for B sub y positive. The B sub y neutral wind asymmetries can be explained by similar asymmetries, previously observed, in the polar ion convection pattern. They imply a direct causal relationship between solar wind/magnetosphere coupling and neutral thermospheric dynamics

Ion-neutral coupling in the high latitude thermosphere, part 2

On the 24th November, 1982, The North-South (Bz) component of the Interplanetary Magnetic Field (IMF) became positive for a period of about 11 hours reaching a relatively large and steady value of approximately 25 nT. During this rare occurrence, the Dynamics Explorer-2 (DE-2) spacecraft was in a configuration that enabled the dynamics of both ionic and neutral species of the high latitude F region to be measured simultaneously along the track of the polar orbiting satellite. Results from two Northern (winter) polar passes of DE-2, extracted from a larger data set, are shown to illustrate the response of the neutral F region to ion drag forcing arising from a configuration of ion convection characteristics of strongly northward IMF. The measured neutral winds differ appreciably from those more commonly observed for periods of southward IMF. The multi-cellular ion drift pattern associated with positive Bz is observed to drive a similar but less structured and weaker neutral wind configuration in the winter polar cap. Major features of the ion drift pattern are mimicked by the neutral circulation but smaller scale and more irregular sturctures of ion flow are not. This is ascribed to the relatively long time constant (few hours) for momentum exchange between the ion and neutral gases. The results demonstrate that sunward flow of neutral gas can be established and maintained by ion drag in the central polar cap for positive Bz

Seasonal dependence of mesospheric gravity waves ( <100 Km) at Peach Mountain Observatory, Michigan

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95502/1/grl9514.pd

Annual and semi‐annual temperature oscillations in the upper mesosphere

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94874/1/grl8615.pd

Vorticity and divergence in the high‐latitude upper thermosphere

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95126/1/grl5327.pd

Modeling growing confluent tissues using a lattice Boltzmann method: interface stability and fluctuations

Tissue growth underpins a wide array of biological and developmental processes, and numerical modeling of growing systems has been shown to be a useful tool for understanding these processes. However, the phenomena that can be captured are often limited by the size of systems that can be modeled. Here, we address this limitation by introducing a lattice Boltzmann method (LBM) for a growing system that is able to efficiently model hydrodynamic length scales. The model incorporates a bounce-back approach to describing the growing front of a tissue, which we use to investigate the dynamics of the interface of growing model tissues. We find that the interface grows with scaling in agreement with the Kardar-Parisi-Zhang (KPZ) universality class when growth in the system is bulk driven. Interestingly, we also find the emergence of a previously unreported hydrodynamic instability when proliferation is restricted to the tissue edge. We then develop an analytical theory to show that the instability arises due to a coupling between the number of cells actively proliferating and the position of the interface

Dynamics Explorer 2: Continued FPI and NACS instrument data analysis and associated scientific activity at the University of Michigan

The grant entitled 'Dynamics Explorer 2 - continued FPI and NACS instrument data analysis and associated scientific activity at the University of Michigan' is a continuation of a grant that began with instrument development for the Dynamics Explorer 2 (DE 2) satellite. Over the years, many publications and presentations at scientific meetings have occurred under the aegis of this grant. This present report details the progress that has been made in the final three years of the grant. In these last 4 years of the grant 26 papers have been published or are in press and about 10 more are in preparation or have been submitted. A large number of presentations have been made in the same time span: 36 are listed in Appendix 2. Evidence of the high educational utility of this research is indicated by the list of Ph. D. and M. S. theses that have been completed in the last 3 years that have involved work connected with NAG5-465. The structure of this report is as follows: a brief synopsis of the aims of the grant NAG5-465 is given in the next section; then there is a summary of the scientific accomplishments that have occurred over the grant period; last, we make some brief concluding remarks. Reprints of articles that have recently appeared in refereed journals are appended to the end of this document

Protein-DNA computation by stochastic assembly cascade

The assembly of RecA on single-stranded DNA is measured and interpreted as a stochastic finite-state machine that is able to discriminate fine differences between sequences, a basic computational operation. RecA filaments efficiently scan DNA sequence through a cascade of random nucleation and disassembly events that is mechanistically similar to the dynamic instability of microtubules. This iterative cascade is a multistage kinetic proofreading process that amplifies minute differences, even a single base change. Our measurements suggest that this stochastic Turing-like machine can compute certain integral transforms.Comment: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC129313/ http://www.pnas.org/content/99/18/11589.abstrac