Cell shape determines gene expression in cardiomyocytes

The fundamental biological processes involve sensing biophysical stress, strain and forces along with conversion of these stimuli into chemical signals. These processes are linked to the atrophic and hypertrophic responses. Deficiencies in these biological processes are associated with different diseases, particularly in the circulation system. Although cardiomyocytes are exposed to significant hemodynamic stimuli that alter their shapes, it was not known until recently whether changes in cardiomyocyte shape impact gene expression. However, recent progress in single-cell RNA sequencing have enabled the profiling of transcriptomes of individual cardiomyocytes with engineered geometries, which are specific to normal or pathological conditions such as preload or afterload. Cardiomyocytes undergo considerable changes in cell morphology, either due to mutations, causing various cardiomyopathies such as hypertrophic cardiomyopathy or dilated cardiomyopathy or via changes in hemodynamic conditions. Moreover, because of various patterns of contraction-relaxation cycles, the membrane of cardiomyocytes is dynamically reshaped in each beating cycle. The overall aim of this thesis was to investigate the effects of cardiomyocyte geometry on gene expression and signaling. In study I, we engineered a novel platform to study cardiomyocyte morphology. In this article, we presented a single-cardiomyocyte trapping strategy, consisting of a method for growing neonatal rat cardiomyocytes with different aspect ratios. The study also proposes a protocol to sort patterned cardiomyocytes based on their acquired geometrical aspect ratios and pick up these adherent cells from their pattern. The described approach paved the way to profile the transcriptome of single cardiomyocytes with specific geometric aspect ratio. In study II, we employed single-cell RNA sequencing to investigate impacts of cardiomyocyte aspect ratio on its transcriptome, using the approach proposed in study I. We observed that distinct morphotypic cardiomyocytes had noticeably varied gene expression patterns, implying that the shape of a cardiomyocyte plays a role in gene expression. This was apparent from the separate cluster of cells, detected in unsupervised clustering analyses. In study III, we proposed a mathematical model of a sarcomere to examine whether and how signaling activity at the membrane of cardiomyocyte depends on its beating rate. Based on this model, a multiphysics program was designed to simulate the cardiomyocyte dynamic geometry throughout the contraction and relaxation phases. The main finding of this study was that an increase in the rate of cardiomyocyte contraction leads to an increase in the concentration of activated Src kinase, especially underneath the costameres. Since hypertrophy of cardiomyocyte modifies the ratio of surface to volume at the plane of membrane, the finding of this study suggests that hypertrophy might be considered as part of a feedback, equilibrating membrane-mediated signaling cascades. These studies identify the shape of the cardiomyocyte as a significant determinant of its gene expression and signaling. Our findings illustrate a novel and important observation, with potentially far-reaching impacts in medicine and biology

Effect of topical honey application along with intralesional injection of glucantime in the treatment of cutaneous leishmaniasis

<p>Abstract</p> <p>Background</p> <p>Leishmaniasis is an endemic disease in Iran. Although many treatments have been suggested for this disease, there hasn't been an effective and safe treatment yet. Regarding the healing effect of honey in the chronic ulcers and its reported therapeutic effect in cutaneous leishmaniasis, we performed a study to better evaluate the efficacy of honey in cutaneous leishmaniasis and its final scar.</p> <p>Methods</p> <p>In a prospective clinical trial, 100 patients with confirmed cutaneous leishmaniasis were selected and randomized into 2 groups. Group A were treated with topical honey twice daily along with intralesional injection of glucantime once weekly until complete healing of the ulcer or for maximum of 6 weeks. Group B were treated with intralesional injection of glucantime alone until complete healing of the ulcer or for a maximum of 6 weeks, too. The patients were followed for 4 months. The collected data were analyzed statistically using statistical tests including Chi-square, Mann Whitney and Kaplan – Mayer tests.</p> <p>Results</p> <p>In this study, 45 patients that had cutaneous leishmaniasis were treated with intralesional glucantime alone and 45 patients were treated with topical honey and glucantime . Ten patients left out the study. In the glucantime alone treated group, 32 patients (71.1%) had complete cure whereas in the group treated with both glucantime & topical honey, 23 patients (51.1%) achieved complete cure. This difference was significant statistically (p = 0.04).</p> <p>Conclusion</p> <p>Further studies to better clarify the efficacy of honey in cutaneous leishmaniasis is needed. We suggest that in another study, the efficacy of honey with standardized level of antibacterial activity is evaluated against cutaneous leishmaniasis.</p

Seismic imaging of salt-influenced extensional forced folding

Master's thesis in Petroleum geosciences engineeringExtensional forced folds are formed by the presence of a ductile salt layer, decoupling the overlying folded strata from the underlying faulted strata. Hydrocarbons are generally trapped within secondary structures of forced folds. The objective of this thesis is to analyze the impact of salt-influenced extensional forced folding and seismic parameters on the resultant seismic image. Fine-tuning the seismic parameters of illumination direction and wave frequency can help to better understand and potentially improve seismic imaging of salt-influenced extensional forced folding and secondary faults. To achieve this objective, a synthetic workflow is carried out in 2D, consisting of: i. mechanical modeling of salt-influenced extensional forced folding; ii. computation of finite strain in the mechanical model; iii. modification of the initial acoustic properties of the model based on finite strain; iv. seismic imaging using pre-stack depth migration (PSDM). This workflow is applied to three models; model 1 includes siliciclastic sediments, model 2 includes a salt layer below the siliciclastic sediments, and model 3 includes salt, siliciclastic sediments and growth strata. All the simulations produce realistic but different geometries and strain fields, with model 1 resembling a graben, localized above the major fault zone, model 2 displaying a forced fold with a wide distribution of associated secondary faulting, and model 3 displaying a steeper forced fold, and a wider distribution of secondary faulting. Seismic images of these models include different illumination directions (specular, left side and right side) and wave frequencies (10, 20, 30 and 40 Hz). Specular illumination highlights the flat reflectors outside the fault zone, also highlighting fault related diffractions. Offside illuminations target the dipping reflectors, where the left side illumination highlights the antithetic faults and right side illumination highlights the forelimb of the forced fold and synthetic faults. At a high frequency (30 Hz), the seismic images are more defined, creating better characterization of forced folding and secondary faulting. The evaluation of the combination of seismic parameters (i.e. illumination direction and wave frequency) is to generate a better seismic characterization salt-influenced extensional forced folds and faults

The rearrangement of diamidosilyl ether ligands to amido-amino-siloxo ligands and their chromium complexes

The synthesis and characterization of three new symmetrical diamidosilyl ether ligands {[RNHSiMe2]2O} (H2[RNON]; R = Propyl, 3,5-Me2Ph, Ferrocenyl) are described. A retro-Brook-type silyl migration from oxygen to nitrogen of the dilithiated ligands {[RNLiSiMe2]2O} (R = Propyl, 3,5-Me2Ph, 2,4,6-Me3Ph, 2,6-iPr2Ph, 3,5-(CF3)2Ph) in THF resulted in new non-symmetrical mixed-donor amido-amino-siloxo ligands of the form {RNLiSiMe2N(R)SiMe2OLi}, termed Li2[RNN’O], in one step and quantitative yield; most were structurally characterized and exhibited a range of aggregate structures including triple-stacked cubes, ladders and rings. Reaction kinetics were determined by VT 1H NMR and show that the rate of rearrangement increases with decreasing steric hindrance, and with increasing electron-donating ability of the R substituents. Several paramagnetic chromium complexes including {Cr[Me3PhNN’O]•THF}2, {Cr[iPr2PhNN’O]}2, {Cr[Me3PhNN’O]2Li2•THF}, {(Cr2[Me3PhNN’O]2)2CrCl2}, and {Cr[PrNON]2} were synthesized. Amido- or siloxo-bridged binding motifs, a very strong ?2-(N,Cipso) arylamido interaction, and a Cr(II) ate complex are featured, along with their magnetic properties and activity towards ethylene polymerization

Two-dimensional chemo-elasticity under chemical equilibrium

a b s t r a c t The coupling between solid state diffusion and mechanical stress arises in a number of important technological applications. The theory that describes such coupling is termed chemo-elasticity. In this paper, a solution approach is developed for two-dimensional chemo-elasticity problems. First, a coupled system of nonlinear partial differential equations is derived in terms of an Airy stress function and the solute concentration. Then, this coupled system of nonlinear equations is solved asymptotically using a perturbation technique. Finally, based on this approach, asymptotic solutions are obtained for three fundamental problems in two-dimensional chemo-elasticity, namely, a circular hole in an infinite plate under uniaxial tension, a straight edge dislocation and a disclination

Pregnancy and Multiple Births rate after Transferring 2 or 3 Embryos

Background: In vitro fertilization (IVF) is a progressing common reproduction method and if the number of transferred embryo increases, the pregnancy rate and multiple pregnancies will increase which may lead to higher medical costs and human suffering. We compared pregnancy and multiple pregnancies rate after two or three transferred embryo via IVF.&#13; Methods: From April 2003 to June 2004, 301 referred infertile women to Isfahan infertility center underwent IVF with transferring two or three good quality embryos.&#13; Results: From 298 patients, 2 and 3 embryos were transferred in 155 patients and in 143 patients, respectively. Pregnancy rate was 19.4% versus 24.5% in 2 and 3 embryos transferred patients, respectively. Twin gestations were found in 5(3.2%) of 2 embryos transferred patients and in 11(7.7%) of 3 embryos transferred patients.&#13; Discussion: Transferring two or three embryos with good quality increase the rate of twin gestations in young women, without significant improve in the chance of singleton conception.&#13; Key words: In Vitro Fertilization, Multiple gestations, Embryo transfe

The Effect of Phase Separation on Diffusion Induced Stresses in Spherical and Cylindrical Electrode Particles

Experiments have frequently shown that phase separation in lithium-battery electrodes could lead to mechanical failure, poor cycling performance, and reduced capacity. Here, a phase-field model is utilized to investigate how phase separation affects the evolution of the concentration and stress profiles within the spherical/cylindrical electrode particles, during both insertion and extraction half-cycles. To this end, the governing equations are derived and then discretized using the central finite difference method. The resulting algebraic equations are solved numerically with the aid of the Newton-Raphson method to determine both the concentration and stress fields in the electrode particles. For further verification, the results are compared against predictions of an analytical core-shell model. The results suggest that, within the range of parameters considered here, phase separation could lead to a more than five-fold increase in the maximum tensile stress at the particles surface