2,200 research outputs found
Dynamics of Cell Shape and Forces on Micropatterned Substrates Predicted by a Cellular Potts Model
Micropatterned substrates are often used to standardize cell experiments and
to quantitatively study the relation between cell shape and function. Moreover,
they are increasingly used in combination with traction force microscopy on
soft elastic substrates. To predict the dynamics and steady states of cell
shape and forces without any a priori knowledge of how the cell will spread on
a given micropattern, here we extend earlier formulations of the
two-dimensional cellular Potts model. The third dimension is treated as an area
reservoir for spreading. To account for local contour reinforcement by
peripheral bundles, we augment the cellular Potts model by elements of the
tension-elasticity model. We first parameterize our model and show that it
accounts for momentum conservation. We then demonstrate that it is in good
agreement with experimental data for shape, spreading dynamics, and traction
force patterns of cells on micropatterned substrates. We finally predict shapes
and forces for micropatterns that have not yet been experimentally studied.Comment: Revtex, 32 pages, 11 PDF figures, to appear in Biophysical Journa
Dynamics of Cell Ensembles on Adhesive Micropatterns: Bridging the Gap between Single Cell Spreading and Collective Cell Migration
The collective dynamics of multicellular systems arise from the interplay of a few fundamental elements: growth, division and apoptosis of single cells; their mechanical and adhesive interactions with neighboring cells and the extracellular matrix; and the tendency of polarized cells to move. Micropatterned substrates are increasingly used to dissect the relative roles of these fundamental processes and to control the resulting dynamics. Here we show that a unifying computational framework based on the cellular Potts model can describe the experimentally observed cell dynamics over all relevant length scales. For single cells, the model correctly predicts the statistical distribution of the orientation of the cell division axis as well as the final organisation of the two daughters on a large range of micropatterns, including those situations in which a stable configuration is not achieved and rotation ensues. Large ensembles migrating in heterogeneous environments form non-adhesive regions of inward-curved arcs like in epithelial bridge formation. Collective migration leads to swirl formation with variations in cell area as observed experimentally. In each case, we also use our model to predict cell dynamics on patterns that have not been studied before
Influence of smoking on the prognostic value of cardiovascular computed tomography coronary angiography
Aims Computed tomography coronary angiography (CTA) is an important non-invasive imaging modality increasingly used for the diagnosis and prognosis of coronary artery disease (CAD). The purpose of the current study was to determine the influence of smoking status on the prognostic value of CTA in patients with suspected or known CAD. Methods and results In 1207 patients (57% male, age 57 ± 12 years) referred for CTA, the presence of significant CAD (≥50% stenosis) was determined. During follow-up (FU) the following events were recorded: all cause mortality, and non-fatal infarction. The prognostic value of CTA in smokers and non-smokers was compared using an interaction term in the Cox proportional hazard regression analysis. Significant CAD was observed in 327 patients (27%), and 273 patients (23%) were smokers. During a median FU time of 2.2 years, an event occurred in 50 patients. After correction for baseline characteristics including smoking in a multivariate model, significant CAD remained an independent predictor of events. Furthermore, a significant interaction (P < 0.05) was observed between significant CAD and smoking. The annualized event rate in smokers with significant CAD was 8.78% compared with 0.99% in smokers without significant CAD (P < 0.001). In non-smokers with significant CAD the annualized event rate was 2.07% compared with 1.01% in non-smokers without significant CAD (P= 0.058). Conclusion The prognostic value of CTA was significantly influenced by smoking status. The event rates in patients with significant CAD were approximately four-fold higher in smokers compared with non-smokers. These findings suggest that smoking cessation needs to be aggressively pursued, especially in smokers with significant CA
A mock circulation loop to test extracorporeal CO2 elimination setups
Background: Extracorporeal carbon dioxide removal (ECCO2R) is a promising yet
limited researched therapy for hypercapnic respiratory failure in acute respiratory
distress syndrome and exacerbated chronic obstructive pulmonary disease. Herein,
we describe a new mock circuit that enables experimental ECCO2R research without
animal models. In a second step, we use this model to investigate three experimental
scenarios of ECCO2R: (I) the influence of hemoglobin concentration on CO2 removal. (II)
a potentially portable ECCO2R that uses air instead of oxygen, (III) a low-flow ECCO2R
that achieves effective CO2 clearance by recirculation and acidification of the limited
blood volume of a small dual lumen cannula (such as a dialysis catheter).
Results: With the presented ECCO2R mock, CO2 removal rates comparable to previous
studies were obtained. The mock works with either fresh porcine blood or diluted
expired human packed red blood cells. However, fresh porcine blood was preferred
because of better handling and availability. In the second step of this work, hemoglobin
concentration was identified as an important factor for CO2 removal. In the second
scenario, an air-driven ECCO2R setup showed only a slightly lower CO2 wash-out than the
same setup with pure oxygen as sweep gas. In the last scenario, the low-flow ECCO2R,
the blood flow at the test membrane lung was successfully raised with a recirculation
channel without the need to increase cannula flow. Low recirculation ratios resulted in
increased efficiency, while high recirculation ratios caused slightly reduced CO2 removal
rates. Acidification of the CO2 depleted blood in the recirculation channel caused an
increase in CO2 removal rate.
Conclusions: We demonstrate a simple and cost effective, yet powerful, “in-vitro”
ECCO2R model that can be used as an alternative to animal experiments for many
research scenarios. Moreover, in our approach parameters such as hemoglobin level can
be modified more easily than in animal models
Comparison of Serial and Parallel Connections of Membrane Lungs against Refractory Hypoxemia in a Mock Circuit
Extracorporeal membrane oxygenation (ECMO) is an important rescue therapy method
for the treatment of severe hypoxic lung injury. In some cases, oxygen saturation and oxygen partial
pressure in the arterial blood are low despite ECMO therapy. There are case reports in which patients
with such instances of refractory hypoxemia received a second membrane lung, either in series or in
parallel, to overcome the hypoxemia. It remains unclear whether the parallel or serial connection
is more effective. Therefore, we used an improved version of our full-flow ECMO mock circuit to
test this. The measurements were performed under conditions in which the membrane lungs were
unable to completely oxygenate the blood. As a result, only the photometric pre- and post-oxygenator
saturations, blood flow and hemoglobin concentration were required for the calculation of oxygen
transfer rates. The results showed that for a pre-oxygenator saturation of 45% and a total blood flow of
10 L/min, the serial connection of two identical 5 L rated oxygenators is 17% more effective in terms
of oxygen transfer than the parallel connection. Although the idea of using a second membrane lung
if refractory hypoxia occurs is intriguing from a physiological point of view, due to the invasiveness
of the solution, further investigations are needed before this should be used in a wider clinical setting
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Unveiling the sensory and interneuronal pathways of the neuroendocrine connectome in <i>Drosophila</i>.
Neuroendocrine systems in animals maintain organismal homeostasis and regulate stress response. Although a great deal of work has been done on the neuropeptides and hormones that are released and act on target organs in the periphery, the synaptic inputs onto these neuroendocrine outputs in the brain are less well understood. Here, we use the transmission electron microscopy reconstruction of a whole central nervous system in the Drosophila larva to elucidate the sensory pathways and the interneurons that provide synaptic input to the neurosecretory cells projecting to the endocrine organs. Predicted by network modeling, we also identify a new carbon dioxide-responsive network that acts on a specific set of neurosecretory cells and that includes those expressing corazonin (Crz) and diuretic hormone 44 (Dh44) neuropeptides. Our analysis reveals a neuronal network architecture for combinatorial action based on sensory and interneuronal pathways that converge onto distinct combinations of neuroendocrine outputs
Comparison of Circular and Parallel-Plated Membrane Lungs for Extracorporeal Carbon Dioxide Elimination
Extracorporeal carbon dioxide removal (ECCO2R) is an important technique to treat critical lung diseases such as exacerbated chronic obstructive pulmonary disease (COPD) and mild or
moderate acute respiratory distress syndrome (ARDS). This study applies our previously presented
ECCO2R mock circuit to compare the CO2 removal capacity of circular versus parallel-plated membrane lungs at different sweep gas flow rates (0.5, 2, 4, 6 L/min) and blood flow rates (0.3 L/min,
0.9 L/min). For both designs, two low-flow polypropylene membrane lungs (Medos Hilte 1000,
Quadrox-i Neonatal) and two mid-flow polymethylpentene membrane lungs (Novalung Minilung,
Quadrox-iD Pediatric) were compared. While the parallel-plated Quadrox-iD Pediatric achieved the
overall highest CO2 removal rates under medium and high sweep gas flow rates, the two circular
membrane lungs performed relatively better at the lowest gas flow rate of 0.5 L/min. The low-flow
Hilite 1000, although overall better than the Quadrox i-Neonatal, had the most significant advantage
at a gas flow of 0.5 L/min. Moreover, the circular Minilung, despite being significantly less efficient
than the Quadrox-iD Pediatric at medium and high sweep gas flow rates, did not show a significantly
worse CO2 removal rate at a gas flow of 0.5 L/min but rather a slight advantage. We suggest that
circular membrane lungs have an advantage at low sweep gas flow rates due to reduced shunting as
a result of their fiber orientation. Efficiency for such low gas flow scenarios might be relevant for
possible future portable ECCO2R devices
Unveiling the sensory and interneuronal pathways of the neuroendocrine connectome in Drosophila.
Neuroendocrine systems in animals maintain organismal homeostasis and regulate stress response. Although a great deal of work has been done on the neuropeptides and hormones that are released and act on target organs in the periphery, the synaptic inputs onto these neuroendocrine outputs in the brain are less well understood. Here, we use the transmission electron microscopy reconstruction of a whole central nervous system in the Drosophila larva to elucidate the sensory pathways and the interneurons that provide synaptic input to the neurosecretory cells projecting to the endocrine organs. Predicted by network modeling, we also identify a new carbon dioxide-responsive network that acts on a specific set of neurosecretory cells and that includes those expressing corazonin (Crz) and diuretic hormone 44 (Dh44) neuropeptides. Our analysis reveals a neuronal network architecture for combinatorial action based on sensory and interneuronal pathways that converge onto distinct combinations of neuroendocrine outputs
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