A Chemo-Mechanical Approach to Model Cell Contraction and Spreading on Elastic Substrates

Biological tissues are very particular types of materials that have the ability to change their structure, properties and chemistry in response to external cues. Contractile cells, i.e. fibroblasts, are key players of tissue adaptivity as they are capable of reorganizing their surrounding extra-cellular matrix (ECM) by contracting and generating mechanical forces. This contractile behavior is attributed to the development of a stress-fiber (SF) network within the cell's cytoskeleton, a process that is known to be highly dependent of the nature of the mechanical environment (such as ECM stiffness or the presence of stress and strain). To describe these processes in a consistent manner, the present thesis introduces a multiphasic formulation (fluid/solid/solute mixture) that accounts for four major elements of cell contraction: cytoskeleton, cytosol, SF and actin monomers, as well as their interactions. The model represents the cross-talks between mechanics and chemistry through various means: (a) a mechano-sensitive formation and dissociation of an anisotropic SF network described by mass exchange between actin monomer and polymers, (b) a bio-mechanical model for SF contraction that captures the well-known length-tension and velocity-tension relation for muscles cells and (c) a convection/diffusion description for the transport of fluid and monomers within the cell. Numerical investigations show that the multiphasic model is able to capture the dependency of cell contraction on the stiffness of the mechanical environment and accurately describes the development of an oriented SF network observed in contracting fibroblasts. From a numerical view-point, cell and substrate are discretized on a single, regular finite element mesh, while the potentially complex cell geometry is defined in terms of a level-set function that is independent of discretization. Field discontinuities across the cell membrane are then naturally enforced using enriched shape functions traditionally used in the XFEM formulation. The resulting method provides a flexible platform that can handle complex cell geometries, avoid expensive meshing techniques, and can potentially be extended to study cell growth and migration on an elastic substrate. In addition, the XFEM formalism facilitates the consideration of the cell's cortical elasticity, a feature that is known to be important during cell deformation. The proposed method is illustrated with a few biologically relevant examples of cell-substrate interactions. Generally, the method is able to capture some key phenomena observed in biological systems and displays numerical versatility and accuracy at a moderate computational cost. Recent research have shown that cell spreading is highly dependent on the contractile behavior of the cell and mechanical properties of the environment it is located in. The dynamics of such process is critical for the development of tissue engineering strategy but is also a key player in wound contraction, tissue maintenance and angiogenesis. To better understand the underlying physics of such phenomena, this presentation describes a mathematical formulation of cell spreading and contraction that couples the processes of stress fiber formation, protrusion growth through actin polymerization at the cell edge and dynamics of cross-membrane protein (integrins) enabling cell-substrate attachment. The model is based on mixture model which accurately capture the interactions and mass exchange between three constituents, namely, the cell's cytoskeleton, actin monomers and stress fibers. On the one hand, monomers are allowed to polymerize into stress fiber to generate contraction while on the other hand, they may polymerize into an actin meshwork at the cell's boundary to push the membrane forward. In addition, a mechano-sensitive model of the diffusion and attachment integrins to the substrate permit to quantify the physics of the above processes in terms of substrate mechanica

Data in support of comparative physiology and proteomic analysis of two wheat genotypes contrasting in drought tolerance

AbstractHere, we present the data from a comparative physiology and proteomics approach used to analyze the response of two wheat genotypes (SERI M 82 (SE) and SW89.5193/kAu2 (SW)) with contrasting responses to drought stress. Proteomic analysis resulted in identification of 49 unique proteins with significant change in abundance (2-fold) under water shortage in roots and leaves. Gene ontology analysis of drought-responsive proteins (DRPs) suggested an induction of proteins related to cell wall biogenesis, ATP synthesis, photosynthesis, and carbohydrate/energy metabolism in leaves under stress condition. A large fraction of root proteins were identified to be involved in defense and oxidative stress response. In addition, a significant change was detected in proteins related to protein synthesis, ATP synthesis, and germin-like proteins in response to drought stress. A detailed analysis of this data may be obtained from Ref. [1]

Rutin activates the MAPK pathway and BDNF gene expression onbeta-amyloid induced neurotoxicity in rats

Flavonoids are present in foods such as fruits and vegetables. A relationship between the consumption offlavonoid-rich foods and prevention of human disease including neurodegenerative disorders has beendemonstrated. We assessed the effect of rutin (3,3�,4�,5,7-pentahydroxyflavone-3-rhamnoglucoside) onthe mitogen-activated protein kinase (MAPK) pathway, memory retrieval and oxidative stress in ratsinjected with �-amyloid (A�), which is implicated to have an important role in Alzheimer’s disease (AD).A� was injected bilaterally in the deep frontal cortex of rat brain. Next, rutin and saline were injected(i.p.) for 3 weeks. In comparison to the control group, rutin significantly increased extracellular signal-regulated protein kinase 1 (ERK1), cAMP response element-binding protein (CREB) and brain-derivedneurotrophic factor (BDNF) gene expression in the hippocampus of rats. Rutin (100 mg/kg) significantlyincreased memory retrieval compared to the control group. Malondialdehyde (MDA) level in the hip-pocampus of the rutin group was significantly lower than those in the control group. The content ofsulfhydryl groups in the rutin group was higher than that in the control group. The findings show apossibility that rutin may have beneficial effects against neurotoxicity of A� on memory in rats

The Comparison of Procalcitonin Guidance Administer Antibiotics with Empiric Antibiotic Therapy in Critically Ill Patients Admitted in Intensive Care Unit

The empiric antibiotic therapy can result in antibiotic overuse, development of bacterial resistance and increasing costs in critically ill patients. The aim of the present study was to evaluate the effect of procalcitonin (PCT) guide treatment on antibiotic use and clinical outcomes of patients admitted to intensive care unit (ICU) with systemic inflammatory response syndrome (SIRS).  A total of 60 patients were enrolled in this study and randomly divided into two groups, cases that underwent antibiotic treatment based on serum level of PCT as PCT group (n=30) and patients who undergoing antibiotic empiric therapy as control group (n=30). Our primary endpoint was the use of antibiotic treatment. Additional endpoints were changed in clinical status and early mortality. Antibiotics use was lower in PCT group compared to control group (P=0.03). Current data showed that difference in SOFA score from the first day to the second day after admitting patients in ICU did not significantly differ (P=0.88). Patients in PCT group had a significantly shorter median ICU stay, four days versus six days (P=0.01). However, hospital stay was not statistically significant different between two groups, 20 days versus 22 days (P=0.23).  Early mortality was similar between two groups. PCT guidance administers antibiotics reduce antibiotics exposure and length of ICU stay, and we found no differences in clinical outcomes and early mortality rates between the two studied groups

Comparative physiology and proteomic analysis of two wheat genotypes contrasting in drought tolerance

Comparative physiology and proteomic analyses were conducted to monitor the stress response of two wheat genotypes (SERI M 82 (SE) and SW89.5193/kAu2 (SW)) with contrasting responses to drought stress. Under stress condition, the tolerant genotype (SE) produced higher shoot and root biomasses, longer roots and accumulated higher level of ABA in leaves. Physiological measurements suggested that the SE genotype was more efficient in water absorption and could preserve more water presumably by controlling stomata closure. Proteomic analysis showed an increased abundance of proteins related to defense and oxidative stress responses such as GLPs, GST, and SOD, and those related to protein processing such as small HSPs in roots of both genotypes in response to drought stress. Interestingly, the abundance of proteins such as endo-1,3-beta-glucosidase, peroxidase, SAMS, and MDH significantly increased in roots or leaves of the SE genotype and decreased in that of the SW one. In addition, an increased abundance of APX was detected in leaves and roots of the SE genotype and a decreased abundance of 14-3-3 and ribosomal proteins were noted in the SW one in response to drought stress. Our findings led to a better understanding about the integrated physiology and proteome responses of wheat genotypes with nearly contrasting responses to drought stress. Biological significance: We applied a comparative physiology and proteomic analysis to decipher the differential responses of two contrasting wheat genotypes to drought stress. Based on physiological measurements the tolerant genotype (SE) showed better drought response by developing deep root system, higher root and shoot biomasses, and higher level of ABA in leaves. Proteomic analysis showed an increased abundance of proteins related to defense and oxidative stress responses such as GLPs, GST, and SOD, and those related to protein processing such as small HSPs in roots of both genotypes in response to drought stress. In addition, the abundance of proteins such as glucan endo-1,3-beta-glucosidase, peroxidases, SAMS, and MDH increased in roots or leaves of the tolerant genotype (SE) and decreased in that of the sensitive genotype (SW). Overall, proteins related to oxidative stress, protein processing and photosynthesis showed decreased abundance to a greater extent in the sensitive genotype (SW).15 page(s

Prophylactic Administration of Fibrinogen Concentrate in Perioperative Period of Total Hip Arthroplasty: a Randomized Clinical Trial Study

According to limitations in blood product resources and to prevent unnecessary transfusions and afterwards complications in perioperative period of total hip arthroplasty, authors administered fibrinogen concentrate in a pilot randomized clinical trial to evaluate bleeding and need to blood transfusion in preoperative period. Thirty patients (3-75 years old) with ASA physical status class I or II and candidate for total hip arthroplasty consequently enrolled in this study and randomly assigned into two groups: taking fibrinogen concentrate and control. Two groups were similar in serum concentration of fibrinogen, hemoglobin, and platelet preoperatively. After induction of general anesthesia 30 mg/kg fibrinogen concentrate was administered in the fibrinogen group. Blood loss, need to blood transfusion and probable complications were compared between two groups. The mean operation time was 3.3 ± 0.8 hours in the fibrinogen group and 2.8 ± 0.6 hours in the placebo group, and this difference was statistically significant (P=0.04). There was a significant correlation between operation time and blood loss during surgery (P=0.002). The mean transfused blood products in the fibrinogen and control group was 0.8 ± 1.01 units and 1.06 ± 1.2 units respectively (P=0.53). The mean of perioperative blood loss was 976 ± 553 ml in the fibrinogen group and 1100 ± 350 ml in the control group, but this difference was not significant between two groups. By adjusting time factor for two groups, we identified that the patients in fibrinogen group had lower perioperative bleeding after adjusting time factor for two groups (P=0.046). None of the patients had complications related to fibrinogen concentrate administration. The prophylactic administration of fibrinogen concentrate was safe and effective in reducing bleeding in the perioperative period of total hip arthroplasty