A migrating epithelial monolayer flows like a Maxwell viscoelastic liquid

We perform a bidimensional Stokes experiment in an active cellular material: an autonomously migrating monolayer of Madin-Darby Canine Kidney (MDCK) epithelial cells flows around a circular obstacle within a long and narrow channel, involving an interplay between cell shape changes and neighbour rearrangements. Based on image analysis of tissue flow and coarse-grained cell anisotropy, we determine the tissue strain rate, cell deformation and rearrangement rate fields, which are spatially heterogeneous. We find that the cell deformation and rearrangement rate fields correlate strongly, which is compatible with a Maxwell viscoelastic liquid behaviour (and not with a Kelvin-Voigt viscoelastic solid behaviour). The value of the associated relaxation time is measured as $\tau = 70 \pm 15$~min, is observed to be independent of obstacle size and division rate, and is increased by inhibiting myosin activity. In this experiment, the monolayer behaves as a flowing material with a Weissenberg number close to one which shows that both elastic and viscous effects can have comparable contributions in the process of collective cell migration.Comment: 17 pages, 15 figure

Fast determination of coarse grained cell anisotropy and size in epithelial tissue images using Fourier transform

Mechanical strain and stress play a major role in biological processes such as wound healing or morphogenesis. To assess this role quantitatively, fixed or live images of tissues are acquired at a cellular precision in large fields of views. To exploit these data, large numbers of cells have to be analyzed to extract cell shape anisotropy and cell size. Most frequently, this is performed through detailed individual cell contour determination, using so-called segmentation computer programs, complemented if necessary by manual detection and error corrections. However, a coarse grained and faster technique can be recommended in at least three situations. First, when detailed information on individual cell contours is not required, for instance in studies which require only coarse-grained average information on cell anisotropy. Second, as an exploratory step to determine whether full segmentation can be potentially useful. Third, when segmentation is too difficult, for instance due to poor image quality or too large a cell number. We developed a user-friendly, Fourier transform-based image analysis pipeline. It is fast (typically $10^4$ cells per minute with a current laptop computer) and suitable for time, space or ensemble averages. We validate it on one set of artificial images and on two sets of fully segmented images, one from a Drosophila pupa and the other from a chicken embryo; the pipeline results are robust. Perspectives include \textit{in vitro} tissues, non-biological cellular patterns such as foams, and $xyz$ stacks.Comment: 13 pages; 9 figure

Sterol composition of caper (Capparis spinosa) seeds

Caper is a perennial shrub of the Mediterranean Basin. The most important economical species is Capparis spinosa. Sterols of C. spinosa seed oil isolated from seven Tunisian stands were identified andquantified. C. spinosa contained  high levels of phytosterols (2240.4 mg/kg of total extracted lipids), of which -sitosterol, with 1390 mg/kg, was the most abundant (57.53%). Campesterol and stigmasterol accounted for 382 and 265 mg/kg, respectively (17.05 and 11.85% of the total sterols, respectively). C. spinosa seed oil also contained a high level of 5-avenasterol (6%). We detect also brassicasterol (3.39 mg/kg). Cholesterol and campestanol are detected in much lower levels. These results bring attention to the richness of C.spinosa seed oil with sterols which are the most important class of the minor components

miR-27a-3p regulates expression of intercellular junctions at the brain endothelium and controls the endothelial barrier permeability

Background The brain endothelial barrier permeability is governed by tight and adherens junction protein complexes that restrict paracellular permeability at the blood-brain barrier (BBB). Dysfunction of the inter-endothelial junctions has been implicated in neurological disorders such as multiple sclerosis, stroke and Alzheimer’s disease. The molecular mechanisms underlying junctional dysfunction during BBB impairment remain elusive. MicroRNAs (miRNAs) have emerged as versatile regulators of the BBB function under physiological and pathological conditions, and altered levels of BBB-associated microRNAs were demonstrated in a number of brain pathologies including neurodegeneration and neuroinflammatory diseases. Among the altered micro-RNAs, miR-27a-3p was found to be downregulated in a number of neurological diseases characterized by loss of inter-endothelial junctions and disruption of the barrier integrity. However, the relationship between miR-27a-3p and tight and adherens junctions at the brain endothelium remains unexplored. Whether miR-27a-3p is involved in regulation of the junctions at the brain endothelium remains to be determined. Methods Using a gain-and-loss of function approach, we modulated levels of miR-27a-3p in an in-vitro model of the brain endothelium, key component of the BBB, and examined the resultant effect on the barrier paracellular permeability and on the expression of essential tight and adherens junctions. The mechanisms governing the regulation of junctional proteins by miR-27a-3p were also explored. Results Our results showed that miR-27a-3p inhibitor increases the barrier permeability and causes reduction of claudin-5 and occludin, two proteins highly enriched at the tight junction, while miR-27a-3p mimic reduced the paracellular leakage and increased claudin-5 and occludin protein levels. Interestingly, we found that miR-27-3p induces expression of claudin-5 and occludin by downregulating Glycogen Synthase Kinase 3 beta (GSK3ß) and activating Wnt/ ß-catenin signaling, a key pathway required for the BBB maintenance. Conclusion For the first time, we showed that miR-27a-3p is a positive regulator of key tight junction proteins, claudin-5 and occludin, at the brain endothelium through targeting GSK3ß gene and activating Wnt/ß-catenin signaling. Thus, miR-27a-3p may constitute a novel therapeutic target that could be exploited to prevent BBB dysfunction and preserves its integrity in neurological disorders characterized by impairment of the barrier’s function

Case study of MHD blood flow in a porous medium with CNTs and thermal analysis

This articles deals with unsteady MHD free convection flow of blood with carbon nanotubes. The flow is over an oscillating vertical plate embedded in a porous medium. Both single-wall carbon nanotubes (SWCNTs) and multiple-wall carbon nanotubes (MWCNTs) are used with human blood as base fluid. The problem is modelled and then solved for exact solution using the Laplace transform technique. Expressions for velocity and temperature are determined and expressed in terms of complementary error functions. Results are plotted and discussed for embedded parameters. It is observed that velocity decreases with increasing CNTs volume fraction and an increase in CNTs volume fraction increases the blood temperature, which leads to an increase in the heat transfer rates. A validation of the present work is shown by comparing the current results with existing literature

Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish

The notochord defines the axial structure of all vertebrates during development. Notogenesis is a result of major cell reorganization in the mesoderm, the convergence and the extension of the axial cells. However, it is currently not fully understood how these processes act together in a coordinated way during notochord formation. The prechordal plate is an actively migrating cell population in the central mesoderm anterior to the trailing notochordal plate cells. We show that prechordal plate cells express Protocadherin 18a (Pcdh18a), a member of the cadherin superfamily. We find that Pcdh18a-mediated recycling of E-cadherin adhesion complexes transforms prechordal plate cells into a cohesive and fast migrating cell group. In turn, the prechordal plate cells subsequently instruct the trailing mesoderm. We simulated cell migration during early mesoderm formation using a lattice-based mathematical framework and predicted that the requirement for an anterior, local motile cell cluster could guide the intercalation and extension of the posterior, axial cells. Indeed, a grafting experiment validated the prediction and local Pcdh18a expression induced an ectopic prechordal plate-like cell group migrating towards the animal pole. Our findings indicate that the Pcdh18a is important for prechordal plate formation, which influences the trailing mesodermal cell sheet by orchestrating the morphogenesis of the notochord

A cost effectiveness analysis of salt reduction policies to reduce coronary heart disease in four Eastern Mediterranean countries.

BACKGROUND: Coronary Heart Disease (CHD) is rising in middle income countries. Population based strategies to reduce specific CHD risk factors have an important role to play in reducing overall CHD mortality. Reducing dietary salt consumption is a potentially cost-effective way to reduce CHD events. This paper presents an economic evaluation of population based salt reduction policies in Tunisia, Syria, Palestine and Turkey. METHODS AND FINDINGS: Three policies to reduce dietary salt intake were evaluated: a health promotion campaign, labelling of food packaging and mandatory reformulation of salt content in processed food. These were evaluated separately and in combination. Estimates of the effectiveness of salt reduction on blood pressure were based on a literature review. The reduction in mortality was estimated using the IMPACT CHD model specific to that country. Cumulative population health effects were quantified as life years gained (LYG) over a 10 year time frame. The costs of each policy were estimated using evidence from comparable policies and expert opinion including public sector costs and costs to the food industry. Health care costs associated with CHDs were estimated using standardized unit costs. The total cost of implementing each policy was compared against the current baseline (no policy). All costs were calculated using 2010 PPP exchange rates. In all four countries most policies were cost saving compared with the baseline. The combination of all three policies (reducing salt consumption by 30%) resulted in estimated cost savings of $235,000,000 and 6455 LYG in Tunisia;$39,000,000 and 31674 LYG in Syria; $6,000,000 and 2682 LYG in Palestine and$1,3000,000,000 and 378439 LYG in Turkey. CONCLUSION: Decreasing dietary salt intake will reduce coronary heart disease deaths in the four countries. A comprehensive strategy of health education and food industry actions to label and reduce salt content would save both money and lives

Combined anti-AGEs and antioxidant activities of different solvent extracts of Solanum elaeagnifolium Cav. (Solanaceae) fruits during ripening and related to their phytochemical compositions

Oxidative stress and advanced glycation end products (AGEs) are known as key factors for the development of diabetic complications such as retinopathy, cataract as well as atherosclerosis and neurodegenerative diseases, including Alzheimer’s diseases. In this context, natural products have been previously identified as promising sources for antioxidant and anti-glycation compounds. The current study focuses on the evaluation of antioxidant and glycation inhibitory activities of different solvent extracts of Solanum elaeagnifolium Cav (Solanaceae) fruits at different ripening stages. The results showed that antioxidant and anti-AGEs activities were significantly influenced by solvents polarities and ripening stages of S. elaeagnifolium Cav. With one exception, methanolic extract of overripe S. elaeagnifolium Cav fruit showed important protective effects against cellular oxidative stress. The aqueous extract showed the highest ABTS+ scavenging ability. Principal component analysis showed that total phenolic and flavonoid contents correlated well with observed antioxidants and anti-glycation activities. These results bring attention to the possible use of S. elaeagnifolium Cav as a valuable source of bioactive compounds exhibiting antioxidant effects and potentially alleviating diabetic complications

Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish

This is the final version. Available on open access from Springer via the DOI in this recordThe notochord defines the axial structure of all vertebrates during development. Notogenesis is a result of major cell reorganization in the mesoderm, the convergence and the extension of the axial cells. However, it is currently not fully understood how these processes act together in a coordinated way during notochord formation. The prechordal plate is an actively migrating cell population in the central mesoderm anterior to the trailing notochordal plate cells. We show that prechordal plate cells express Protocadherin 18a (Pcdh18a), a member of the cadherin superfamily. We find that Pcdh18a-mediated recycling of E-cadherin adhesion complexes transforms prechordal plate cells into a cohesive and fast migrating cell group. In turn, the prechordal plate cells subsequently instruct the trailing mesoderm. We simulated cell migration during early mesoderm formation using a lattice-based mathematical framework and predicted that the requirement for an anterior, local motile cell cluster could guide the intercalation and extension of the posterior, axial cells. Indeed, a grafting experiment validated the prediction and local Pcdh18a expression induced an ectopic prechordal plate-like cell group migrating towards the animal pole. Our findings indicate that the Pcdh18a is important for prechordal plate formation, which influences the trailing mesodermal cell sheet by orchestrating the morphogenesis of the notochord