scholarly journals A composite computational model of liver glucose homeostasis. I. Building the composite model

2011 ◽  
Vol 9 (69) ◽  
pp. 689-700 ◽  
Author(s):  
J. Hetherington ◽  
T. Sumner ◽  
R. M. Seymour ◽  
L. Li ◽  
M. Varela Rey ◽  
...  
Keyword(s):  
Computational Model ◽  
Composite Model ◽  
Physiological Data ◽  
Small Scale ◽  
Model Parameters ◽  
High Scale ◽  
Composite Models ◽  
The Individual ◽  
Component Models

A computational model of the glucagon/insulin-driven liver glucohomeostasis function, focusing on the buffering of glucose into glycogen, has been developed. The model exemplifies an ‘engineering’ approach to modelling in systems biology, and was produced by linking together seven component models of separate aspects of the physiology. The component models use a variety of modelling paradigms and degrees of simplification. Model parameters were determined by an iterative hybrid of fitting to high-scale physiological data, and determination from small-scale in vitro experiments or molecular biological techniques. The component models were not originally designed for inclusion within such a composite model, but were integrated, with modification, using our published modelling software and computational frameworks. This approach facilitates the development of large and complex composite models, although, inevitably, some compromises must be made when composing the individual models. Composite models of this form have not previously been demonstrated.

scholarly journals Time Lapse Observation Based Modeling and Identification of Cell Behaviors in Angiogenic Sprout Development

2010 ◽  
Author(s):  
Levi B. Wood ◽  
Roger D. Kamm ◽  
H. Harry Asada
Keyword(s):  
Blood Vessel ◽  
Real Time ◽  
Time Lapse ◽  
Model Parameters ◽  
Cell Behaviors ◽  
The Matrix ◽  
The Individual ◽  
Sprout Formation ◽  
Cell Motion

This paper presents a method for deriving dynamic equations for Endothelial Cell (EC) motion and estimating parameters based on time lapse imagery of angiogenic sprout development. Angiogenesis is the process whereby a collection of endothelial cells sprout out from an existing blood vessel, degrade the surrounding scaffold and form a new blood vessel. Sprout formation requires that a collection of ECs all work together and coordinate their movements and behaviors. The process is initiated and guided by a collection of external growth factors. In addition, the individual cells communicate and respond to each other’s movements to behave in a coordinated fashion. The mechanics of cell coordination are extremely complex and include both chemical and mechanical communication between cells and between cells and the matrix. Despite the complexity of the physical system, with many variables that cannot be measured in real time, the ECs behave in a predictable manner based on just a few quantities that can be measured in real time. This work presents a methodology for constructing a set of simple stochastic equations for cell motion dependent only on quantities obtained from time lapse data observed from in vitro experiments. Model parameters are identified from time lapse data using a Maximum Likelihood Estimator.

scholarly journals A composite computational model of liver glucose homeostasis. II. Exploring system behaviour

2012 ◽  
Vol 9 (69) ◽  
pp. 701-706 ◽  
Author(s):  
T. Sumner ◽  
J. Hetherington ◽  
R. M. Seymour ◽  
L. Li ◽  
M. Varela Rey ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Computational Model ◽  
Glucose Homeostasis ◽  
Bifurcation Analysis ◽  
Stable Limit Cycle ◽  
Glucose Variability ◽  
Composite Model ◽  
Model Parameters ◽  
Stable Limit ◽  
Oscillatory Behaviour

Using a composite model of the glucose homeostasis system, consisting of seven interconnected submodels, we enumerate the possible behaviours of the model in response to variation of liver insulin sensitivity and dietary glucose variability. The model can reproduce published experimental manipulations of the glucose homeostasis system and clearly illustrates several important properties of glucose homeostasis—boundedness in model parameters of the region of efficient homeostasis, existence of an insulin sensitivity that allows effective homeostatic control and the importance of transient and oscillatory behaviour in characterizing homeostatic failure. Bifurcation analysis shows that the appearance of a stable limit cycle can be identified.

scholarly journals In VitroAnalyses of the Effects of Heparin and Parabens on Candida albicans Biofilms and Planktonic Cells

2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
High Dose ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Content Type ◽  
Heparin Sodium ◽  
The Individual

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

scholarly journals Improved Antioxidant Capacity of Black Tea Waste Utilizing PlantCrystals

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 592 ◽  
Author(s):  
Abraham M. Abraham ◽  
Reem M. Alnemari ◽  
Jana Brüßler ◽  
Cornelia M. Keck
Keyword(s):  
Antioxidant Capacity ◽  
Aqueous Media ◽  
Natural Antioxidants ◽  
Black Tea ◽  
Pharmaceutical Products ◽  
Small Scale ◽  
Alternative Source ◽  
Significant Difference ◽  
Plant Waste

Antioxidants are recommended to prevent and treat oxidative stress diseases. Plants are a balanced source of natural antioxidants, but the poor solubility of plant active molecules in aqueous media can be a problem for the formulation of pharmaceutical products. The potential of PlantCrystal technology is known to improve the extraction efficacy and antioxidant capacity (AOC) of different plants. However, it is not yet proved for plant waste. Black tea (BT) infusion is consumed worldwide and thus a huge amount of waste occurs as a result. Therefore, BT waste was recycled into PlantCrystals using small-scale bead milling. Their characteristics were compared with the bulk-materials and tea infusion, including particle size and antioxidant capacity (AOC) in-vitro. Waste PlantCrystals possessed a size of about 280 nm. Their AOC increased with decreasing size according to the DPPH (1,1-diphenyl-2-picrylhydrazyl) and ORAC (oxygen radical absorbance capacity) assays. The AOC of the waste increased about nine-fold upon nanonization, leading to a significantly higher AOC than the bulk-waste and showed no significant difference to the infusion and the used standard according to DPPH assay. Based on the results, it is confirmed that the PlantCrystal technology represents a natural, cost-effective plant-waste recycling method and presents an alternative source of antioxidant phenolic compounds.

scholarly journals A Model-Based Tool for Assessing the Impact of Land Use Change Scenarios on Flood Risk in Small-Scale River Systems—Part 1: Pre-Processing of Scenario Based Flood Characteristics for the Current State of Land Use

Hydrology ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 102
Author(s):  
Frauke Kachholz ◽  
Jens Tränckner
Keyword(s):  
Land Use ◽  
River Flow ◽  
Land Use Changes ◽  
Small Rivers ◽  
Small Scale ◽  
Model Parameters ◽  
Ungauged Catchments ◽  
Model Based ◽  
Current State ◽  
The Impact

Land use changes influence the water balance and often increase surface runoff. The resulting impacts on river flow, water level, and flood should be identified beforehand in the phase of spatial planning. In two consecutive papers, we develop a model-based decision support system for quantifying the hydrological and stream hydraulic impacts of land use changes. Part 1 presents the semi-automatic set-up of physically based hydrological and hydraulic models on the basis of geodata analysis for the current state. Appropriate hydrological model parameters for ungauged catchments are derived by a transfer from a calibrated model. In the regarded lowland river basins, parameters of surface and groundwater inflow turned out to be particularly important. While the calibration delivers very good to good model results for flow (Evol =2.4%, R = 0.84, NSE = 0.84), the model performance is good to satisfactory (Evol = −9.6%, R = 0.88, NSE = 0.59) in a different river system parametrized with the transfer procedure. After transferring the concept to a larger area with various small rivers, the current state is analyzed by running simulations based on statistical rainfall scenarios. Results include watercourse section-specific capacities and excess volumes in case of flooding. The developed approach can relatively quickly generate physically reliable and spatially high-resolution results. Part 2 builds on the data generated in part 1 and presents the subsequent approach to assess hydrologic/hydrodynamic impacts of potential land use changes.

scholarly journals PenA, a penicillin-binding protein-type thioesterase specialized for small peptide cyclization

2021 ◽  
Author(s):  
Kenichi Matsuda ◽  
Kei Fujita ◽  
Toshiyuki Wakimoto
Keyword(s):  
Enzymatic Activity ◽  
Computational Model ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Small Peptide ◽  
Peptide Cyclization ◽  
Chain Lengths ◽  
Non Ribosomal Peptides

Abstract Penicillin binding protein-type thioesterases (PBP-type TEs) are a recently identified group of peptide cyclases that catalyze head-to-tail macrolactamization of non-ribosomal peptides. PenA, a new member of this group, is involved in the biosyntheses of cyclic pentapeptides. In this study, we demonstrated the enzymatic activity of PenA in vitro, and analyzed its substrate scope with a series of synthetic substrates. A comparison of the reaction profiles between PenA and SurE, a representative PBP-type TE, showed that PenA is more specialized for small peptide cyclization. A computational model provided a possible structural rationale for the altered specificity for substrate chain lengths.

scholarly journals Combined Luteolin and Indole-3-Carbinol Synergistically Constrains ERα-Positive Breast Cancer by Dual Inhibiting Estrogen Receptor Alpha and Cyclin-Dependent Kinase 4/6 Pathway in Cultured Cells and Xenograft Mice

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2116
Author(s):  
Xiaoyong Wang ◽  
Lijuan Zhang ◽  
Qi Dai ◽  
Hongzong Si ◽  
Longyun Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cultured Cells ◽  
Inhibitory Effect ◽  
Cyclin Dependent Kinase ◽  
Xenograft Mice ◽  
The Individual

The high concentrations of individual phytochemicals in vitro studies cannot be physiologically achieved in humans. Our solution for this concentration gap between in vitro and human studies is to combine two or more phytochemicals. We screened 12 phytochemicals by pairwise combining two compounds at a low level to select combinations exerting the synergistic inhibitory effect of breast cancer cell proliferation. A novel combination of luteolin at 30 μM (LUT30) and indole-3-carbinol 40 μM (I3C40) identified that this combination (L30I40) synergistically constrains ERα+ breast cancer cell (MCF7 and T47D) proliferation only, but not triple-negative breast cancer cells. At the same time, the individual LUT30 and I3C40 do not have this anti-proliferative effect in ERα+ breast cancer cells. Moreover, this combination L30I40 does not have toxicity on endothelial cells compared to the current commercial drugs. Similarly, the combination of LUT and I3C (LUT10 mg + I3C10 mg/kg/day) (IP injection) synergistically suppresses tumor growth in MCF7 cells-derived xenograft mice, but the individual LUT (10 mg/kg/day) and I3C (20 mg/kg/day) do not show an inhibitory effect. This combination synergistically downregulates two major therapeutic targets ERα and cyclin dependent kinase (CDK) 4/6/retinoblastoma (Rb) pathway, both in cultured cells and xenograft tumors. These results provide a solid foundation that a combination of LUT and I3C may be a practical approach to treat ERα+ breast cancer cells after clinical trials.

scholarly journals Antiviral Activity of the PropylamylatinTM Formula against the Novel Coronavirus SARS-CoV-2 In Vitro Using Direct Injection and Gas Assays in Virus Suspensions

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 415
Author(s):  
Ashley N. Brown ◽  
Gary Strobel ◽  
Kaley C. Hanrahan ◽  
Joe Sears
Keyword(s):  
Propionic Acid ◽  
Infectious Virus ◽  
Direct Injection ◽  
Plaque Assay ◽  
Antiviral Effect ◽  
Dependent Manner ◽  
Global Public Health ◽  
Novel Coronavirus ◽  
The Individual

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of novel coronavirus disease 2019 (COVID-19), has become a severe threat to global public health. There are currently no antiviral therapies approved for the treatment or prevention of mild to moderate COVID-19 as remdesivir is only approved for severe COVID-19 cases. Here, we evaluated the antiviral potential of a Propylamylatin formula, which is a mixture of propionic acid and isoamyl hexanoates. The Propylamylatin formula was investigated in gaseous and liquid phases against 1 mL viral suspensions containing 105 PFU of SARS-CoV-2. Viral suspensions were sampled at various times post-exposure and infectious virus was quantified by plaque assay on Vero E6 cells. Propylamylatin formula vapors were effective at inactivating infectious SARS-CoV-2 to undetectable levels at room temperature and body temperature, but the decline in virus was substantially faster at the higher temperature (15 min versus 24 h). The direct injection of liquid Propylamylatin formula into viral suspensions also completely inactivated SARS-CoV-2 and the rapidity of inactivation occurred in an exposure dependent manner. The overall volume that resulted in 90% viral inactivation over the course of the direct injection experiment (EC90) was 4.28 µls. Further investigation revealed that the majority of the antiviral effect was attributed to the propionic acid which yielded an overall EC90 value of 11.50 µls whereas the isoamyl hexanoates provided at most a 10-fold reduction in infectious virus. The combination of propionic acid and isoamyl hexanoates was much more potent than the individual components alone, suggesting synergy between these components. These findings illustrate the therapeutic promise of the Propylamylatin formula as a potential treatment strategy for COVID-19 and future studies are warranted.

scholarly journals Preclinical Testing of Radiopharmaceuticals for the Detection and Characterization of Osteomyelitis: Experiences from a Porcine Model

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4221
Author(s):  
Aage Kristian Olsen Alstrup ◽  
Svend Borup Jensen ◽  
Ole Lerberg Nielsen ◽  
Lars Jødal ◽  
Pia Afzelius
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Porcine Model ◽  
Animal Experiments ◽  
Radioactive Tracers ◽  
The Individual ◽  
Selection Of

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.

scholarly journals Proteome Profiling of PMJ2-R and Primary Peritoneal Macrophages

2021 ◽  
Vol 22 (12) ◽  
pp. 6323
Author(s):  
Alexander L. Rusanov ◽  
Peter M. Kozhin ◽  
Olga V. Tikhonova ◽  
Victor G. Zgoda ◽  
Dmitry S. Loginov ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Living Organism ◽  
Peritoneal Macrophages ◽  
In Vitro Models ◽  
Individual Characteristics ◽  
Essential Proteins ◽  
Comparative Proteomic Analysis ◽  
Immortalized Cell ◽  
The Individual

In vitro models are often used for studying macrophage functions, including the process of phagocytosis. The application of primary macrophages has limitations associated with the individual characteristics of animals, which can lead to insufficient standardization and higher variability of the obtained results. Immortalized cell lines do not have these disadvantages, but their responses to various signals can differ from those of the living organism. In the present study, a comparative proteomic analysis of immortalized PMJ2-R cell line and primary peritoneal macrophages isolated from C57BL/6 mice was performed. A total of 4005 proteins were identified, of which 797 were quantified. Obtained results indicate significant differences in the abundances of many proteins, including essential proteins associated with the process of phagocytosis, such as Elmo1, Gsn, Hspa8, Itgb1, Ncf2, Rac2, Rack1, Sirpa, Sod1, C3, and Msr1. These findings indicate that outcomes of studies utilizing PMJ2-R cells as a model of peritoneal macrophages should be carefully validated. All MS data are deposited in ProteomeXchange with the identifier PXD022133.

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