Dynamic Modeling of Cell Migration and Spreading Behaviors on Fibronectin Coated Planar Substrates and Micropatterned Geometries

An integrative cell migration model incorporating focal adhesion (FA) dynamics, cytoskeleton and nucleus remodeling, actin motor activity, and lamellipodia protrusion is developed for predicting cell spreading and migration behaviors. This work is motivated by two experimental works: (1) cell migration on 2-D substrates under various fibronectin concentrations and (2) cell spreading on 2-D micropatterned geometries. These works suggest (1) cell migration speed takes a maximum at a particular ligand density (~1140 molecules/µm2) and (2) that strong traction forces at the corners of the patterns may exist due to combined effects exerted by actin stress fibers (SFs). The integrative model of this paper successfully reproduced these experimental results and indicates the mechanism of cell migration and spreading. In this paper, the mechanical structure of the cell is modeled as having two elastic membranes: an outer cell membrane and an inner nuclear membrane. The two elastic membranes are connected by SFs, which are extended from focal adhesions on the cortical surface to the nuclear membrane. In addition, the model also includes ventral SFs bridging two focal adhesions on the cell surface. The cell deforms and gains traction as transmembrane integrins distributed over the outer cell membrane bond to ligands on the ECM surface, activate SFs, and form focal adhesions. The relationship between the cell migration speed and fibronectin concentration agrees with existing experimental data for Chinese hamster ovary (CHO) cell migrations on fibronectin coated surfaces. In addition, the integrated model is validated by showing persistent high stress concentrations at sharp geometrically patterned edges. This model will be used as a predictive model to assist in design and data processing of upcoming microfluidic cell migration assays

Classifying chimpanzee (Pan troglodytes) landscapes across large scale environmental gradients in Africa

Primates are sometimes categorized in terms of their habitat. Although such categorization can be over-simplistic, there are scientific benefits from the clarity and consistency that habitat categorization can bring. Chimpanzees (Pan troglodytes) inhabit various environments, but researchers often refer to ‘forest’ or ‘savanna’ chimpanzees. Despite the wide use of this forest-savanna distinction, clear definitions of these landscapes for chimpanzees, based on environmental variables at study sites or determined in relation to existing bioclimatic classifications, are lacking. The robustness of the forest-savanna distinction thus remains to be assessed. We review 43 chimpanzee study sites to assess how the landscape classifications of researchers fit with the environmental characteristics of study sites and with three bioclimatic classifications. We use scatterplots and Principal Components 15 Analysis to assess the distribution of chimpanzee field sites along gradients of environmental 16 variables (temperature, rainfall, precipitation seasonality, forest cover and satellite-derived 17 Hansen tree cover). This revealed an environmental continuum of chimpanzee study sites 18 from savanna to dense forest, with a rarely acknowledged forest mosaic category in between, 19 but with no natural separation into these three classes and inconsistencies with the bioclimatic 20 classifications assessed. The current forest–savanna dichotomy therefore masks a progression 21 of environmental adaptation for chimpanzees, and we propose that recognizing an additional, 22 intermediate ‘forest mosaic’ category is more meaningful than focusing on the ends of this 23 environmental gradient only. Future studies should acknowledge this habitat continuum, place their study sites on the forest–savanna gradient, and include detailed environmental data to support further attempts at quantification

An economic model of long-term use of celecoxib in patients with osteoarthritis

<p>Abstract</p> <p>Background</p> <p>Previous evaluations of the cost-effectiveness of the cyclooxygenase-2 selective inhibitor celecoxib (Celebrex, Pfizer Inc, USA) have produced conflicting results. The recent controversy over the cardiovascular (CV) risks of rofecoxib and other coxibs has renewed interest in the economic profile of celecoxib, the only coxib now available in the United States. The objective of our study was to evaluate the long-term cost-effectiveness of celecoxib compared with nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in a population of 60-year-old osteoarthritis (OA) patients with average risks of upper gastrointestinal (UGI) complications who require chronic daily NSAID therapy.</p> <p>Methods</p> <p>We used decision analysis based on data from the literature to evaluate cost-effectiveness from a modified societal perspective over patients' lifetimes, with outcomes expressed as incremental costs per quality-adjusted life-year (QALY) gained. Sensitivity tests were performed to evaluate the impacts of advancing age, CV thromboembolic event risk, different analytic horizons and alternate treatment strategies after UGI adverse events.</p> <p>Results</p> <p>Our main findings were: 1) the base model incremental cost-effectiveness ratio (ICER) for celecoxib versus nsNSAIDs was $31,097 per QALY; 2) the ICER per QALY was$19,309 for a model in which UGI ulcer and ulcer complication event risks increased with advancing age; 3) the ICER per QALY was $17,120 in sensitivity analyses combining serious CV thromboembolic event (myocardial infarction, stroke, CV death) risks with base model assumptions.</p> <p>Conclusion</p> <p>Our model suggests that chronic celecoxib is cost-effective versus nsNSAIDs in a population of 60-year-old OA patients with average risks of UGI events.</p

A survey of the incidence of the Bromus species as weeds of winter cereals in England, Wales and parts of Scotland

In June 1989, a survey was made of 733 fields of winter cereals, 627 in England and Wales and 106 in Fife and the Lothian regions of Scotland. The occurrence of Bromus species was noted in three areas of each field: the uncropped field margin, the cropped headland and the field centre. Three arbitrarily defined infestation levels were recorded: severe,light and intermediate. The most common species recorded was Bromus sterilis L., which accounted for almost 87% of all sightings. Most of the other occurrences were almost equally distributed between B. hordeaceus L., and B. commutatus Schrad. Two other species were found, on one field each: B. diandrus Roth and B. x pseudothominii Hard. Surveyors were briefed to recognize B. secalinus L, but none was reported. The brome grasses were widespread throughout the surveyed regions. They were most common in the Lothians (81% of surveyed fields) and in the South East (60%) and the South West (52%) of England and least common in the Eng lish West Midlands, Fife and Wales (17%, 15% and 4% of surveyed fields). Distribution was biased towards the uncropped margins and field headlands. In England and Wales, there were 146 fields where Bromus species occurred in the field margins only, 179 in margins and headlands only and 63 with infestations in all three areas. In contrast, there were only 26 fields where they were restricted to the cropped areas. A similar pattern occurred in Scotland. The correlations between incidence of the Bromus species and management practices were much weaker than had been anticipated. The standard advice for control is to plough rather than use non-inversion tillage systems, to delay sowing and to avoid long runs of winter cereals. The conclusion of this survey is that, although these practices may be reducing or preventing increase of these weeds, they are not effective at eliminating infestations

Biomechanical characterization of the urethral musculature

Rigorous study of the associations between urethral structural anatomy and biomechanical function is necessary to advance the understanding of the development, progression, and treatment of urethral pathologies. An ex vivo model was utilized to define the relative biomechanical contributions of the active (muscle) elements of the female urethra relative to its passive (noncontractile) elements. Whole urethras from female, adult rats were tested under a range of applied intraluminal pressures (0 to 20 mmHg) as a laser micrometer simultaneously measured midurethral outer diameter. Active tissue characterization was performed during induced contraction of either smooth muscle alone (Nω-nitro-L-arginine, phenylephrine), striated muscle alone (sodium nitroprusside, atropine, hexamethonium, acetylcholine), or during collective activation of both muscles (Nω-nitro-L- arginine, phenylephrine, acetylcholine). The subsequent collection of paired passive biomechanical responses permitted the determination of parameters related to intrinsic muscle contractile function. Activation of each muscle layer significantly influenced the biomechanical responses of the tissue. Measures of muscle responsiveness over a wide range of sustained opposing pressures indicated that an activated striated muscle component was approximately one-third as effective as activated smooth muscle in resisting tissue deformation. The maximum circumferential stress generated by the striated muscle component under these conditions was also determined to be approximately one-third of that generated by the smooth muscle (748 ± 379 vs. 2,229 ± 409 N/m2). The experiments quantitatively reveal the relative influence of the intrinsic urethral smooth and striated muscle layers with regard to their effect on the mechanical properties and maximum functional responses of the urethra to applied intralumenal stresses in the complete absence of extrinsic influences. Copyright © 2006 the American Physiological Society