Mechanical regulation of cardiac development

Mechanical forces are essential contributors to and unavoidable components of cardiac formation, both inducing and orchestrating local and global molecular and cellular changes. Experimental animal studies have contributed substantially to understanding the mechanobiology of heart development. More recent integration of high-resolution imaging modalities with computational modeling has greatly improved our quantitative understanding of hemodynamic flow in heart development. Merging these latest experimental technologies with molecular and genetic signaling analysis will accelerate our understanding of the relationships integrating mechanical and biological signaling for proper cardiac formation. These advances will likely be essential for clinically translatable guidance for targeted interventions to rescue malforming hearts and/or reconfigure malformed circulations for optimal performance. This review summarizes our current understanding on the levels of mechanical signaling in the heart and their roles in orchestrating cardiac development

The healing effects of the topical mesenchymal stem cells application on colonic anastomosis subjected to ischemia reperfusion injury

Intestinal ischemia reperfusion injury (IRI) is a challenging problem and it adversely affects the healing of colonic anastomosis. Our experimental study aimed to investigate the role of mesenchymal stem cells (MSC) administration in the healing of colonic anastomosis. A total of 33 rats were grouped as Control, IRI and MSC treatment groups. Three rats were reserved for obtaining MSCs. Colonic resection and anastomosis procedure was performed in all groups. Anastomotic line was wrapped with MSCs impregnated spongostan after colonic anastomosis in the rats of the MSC treatment group. All rats were sacrificed and anastomotic line were sampled for examination on the post operative seventh day. Tissue hydroxyproline (HP) levels and anastomotic bursting pressures were statistically compared. Anastomotic bursting pressures were found to be significantly high in MSC treatment group rats. The lowest anastomotic bursting pressure was detected in IRI group rats. Hydroxyproline content of the anastomotic sites were also found to be significantly higher in the rats of the MSC treatment group when compared with the IRI group rats. Our study showed that the detrimental effects of IRI on the healing process of colonic anastomosis in an experimental model may be alleviated with the treatment of MSCs. © 2021, Veteriner Fakultesi Dergisi. All rights reserved

Karpal tünel sendromlu hastalarda elektrodiyagnostik tanı ile Washington Nöropatik Ağrı Ölçeği arasındaki ilişki

Objectives: We undertook this study to examine the relationships between clinical symptoms as evaluated by Washington Neuropathic Pain Scale (NPS) and electrodiagnostic classification in patients with carpal tunnel syndrome (CTS). Methods: Eighty patients with unilateral CTS were included in this study. After diagnosis of CTS by electromyography, all patients completed a 10-item questionnaire (NPS). Results: A statistically significant correlation between total NPS score and severity of CTS was found (p=0.013, r=0.276). Conclusion: The present study indicates that using NPS might be useful in evaluating the clinical outcome of patients with CTS

An integrated acoustic and dielectrophoretic particle manipulation in a microfluidic device for particle wash and separation fabricated by mechanical machining

In this study, acoustophoresis and dielectrophoresis are utilized in an integrated manner to combine the two different operations on a single polydimethylsiloxane (PDMS) chip in sequential manner, namely, particle wash (buffer exchange) and particle separation. In the washing step, particles are washed with buffer solution with low conductivity for dielectrophoretic based separation to avoid the adverse effects of Joule heating. Acoustic waves generated by piezoelectric material are utilized for washing, which creates standing waves along the whole width of the channel. Coupled electro-mechanical acoustic 3D multi-physics analysis showed that the position and orientation of the piezoelectric actuators are critical for successful operation. A unique mold is designed for the precise alignment of the piezoelectric materials and 3D side-wall electrodes for a highly reproducible fabrication. To achieve the throughput matching of acoustophoresis and dielectrophoresis in the integration, 3D side-wall electrodes are used. The integrated device is fabricated by PDMS molding. The mold of the integrated device is fabricated using high-precision mechanical machining. With a unique mold design, the placements of the two piezoelectric materials and the 3D sidewall electrodes are accomplished during the molding process. It is shown that the proposed device can handle the wash and dielectrophoretic separation successfully. © 2016 AIP Publishing LLC

The transition between stochastic and deterministic behavior in an excitable gene circuit

We explore the connection between a stochastic simulation model and an ordinary differential equations (ODEs) model of the dynamics of an excitable gene circuit that exhibits noise-induced oscillations. Near a bifurcation point in the ODE model, the stochastic simulation model yields behavior dramatically different from that predicted by the ODE model. We analyze how that behavior depends on the gene copy number and find very slow convergence to the large number limit near the bifurcation point. The implications for understanding the dynamics of gene circuits and other birth-death dynamical systems with small numbers of constituents are discussed.Comment: PLoS ONE: Research Article, published 11 Apr 201

Hydrology in the Sea of Marmara during the last 23 ka : implications for timing of Black Sea connections and sapropel deposition

Author Posting. © American Geophysical Union, 2010. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 25 (2010): PA1205, doi:10.1029/2009PA001735.Sediments deposited under lacustrine and marine conditions in the Sea of Marmara hold a Late Quaternary record for water exchange between the Black Sea and the Mediterranean Sea. Here we report a multiproxy data set based on oxygen and strontium isotope results obtained from carbonate shells, major and trace elements, and specific organic biomarker measurements, as well as a micropaleontological study from a 14C-dated sediment core retrieved from the Sea of Marmara. Pronounced changes occurred in δ18O and 87Sr/86Sr values at the fresh and marine water transition, providing additional information in relation to micropaleontological data. Organic biomarker concentrations documented the marine origin of the sapropelic layer while changes in n-alkane concentrations clearly indicated an enhanced contribution for organic matter of terrestrial origin before and after the event. When compared with the Black Sea record, the results suggest that the Black Sea was outflowing to the Sea of Marmara from the Last Glacial Maximum until the warmer Bølling-Allerød. The first marine incursion in the Sea of Marmara occurred at 14.7 cal ka B.P. However, salinification of the basin was gradual, indicating that Black Sea freshwaters were still contributing to the Marmara seawater budget. After the Younger Dryas (which is associated with a high input of organic matter of terrestrial origin) both basins were disconnected, resulting in a salinity increase in the Sea of Marmara. The deposition of organic-rich sapropel that followed was mainly related to enhanced primary productivity characterized by a reorganization of the phytoplankton population.We acknowledge support from INSU and the French Polar Institute IPEV

Gas and seismicity within the Istanbul seismic gap

Understanding micro-seismicity is a critical question for earthquake hazard assessment. Since the devastating earthquakes of Izmit and Duzce in 1999, the seismicity along the submerged section of North Anatolian Fault within the Sea of Marmara (comprising the “Istanbul seismic gap”) has been extensively studied in order to infer its mechanical behaviour (creeping vs locked). So far, the seismicity has been interpreted only in terms of being tectonic-driven, although the Main Marmara Fault (MMF) is known to strike across multiple hydrocarbon gas sources. Here, we show that a large number of the aftershocks that followed the M 5.1 earthquake of July, 25th 2011 in the western Sea of Marmara, occurred within a zone of gas overpressuring in the 1.5–5 km depth range, from where pressurized gas is expected to migrate along the MMF, up to the surface sediment layers. Hence, gas-related processes should also be considered for a complete interpretation of the micro-seismicity (~M < 3) within the Istanbul offshore domain

Optimal Strategy for Competence Differentiation in Bacteria

A phylogenetically diverse subset of bacterial species are naturally competent for transformation by DNA. Transformation entails recombination of genes between different lineages, representing a form of bacterial sex that increases standing genetic variation. We first assess whether homologous recombination by transformation is favored by evolution. Using stochastic population genetic computer simulations in which beneficial and deleterious mutations occur at many loci throughout the whole genome, we find that transformation can increase both the rate of adaptive evolution and the equilibrium level of fitness. Secondly, motivated by experimental observations of Bacillus subtilis, we assume that competence additionally entails a weak persister phenotype, i.e., the rates of birth and death are reduced for these cells. Consequently, persisters evolve more slowly than non-persisters. We show via simulation that strains which stochastically switch into and out of the competent phenotype are evolutionarily favored over strains that express only a single phenotype. Our model's simplicity enables us to derive and numerically solve a system of finite- deterministic equations that describe the evolutionary dynamics. The observed tradeoff between the benefit of recombination and the cost of persistence may explain the previously mysterious observation that only a fractional subpopulation of B. subtilis cells express competence. More generally, this work demonstrates that population genetic forces can give rise to phenotypic diversity even in an unchanging and homogeneous environment

Mass flows, turbidity currents and other hydrodynamic consequences of small and moderate earthquakes in the Sea of Marmara

Earthquake-induced submarine slope destabilization is known to cause mass wasting and turbidity currents, but the hydrodynamic processes associated with these events remain poorly understood. Instrumental records are rare, and this notably limits our ability to interpret marine paleoseismological sedimentary records. An instrumented frame comprising a pressure recorder and a Doppler recording current meter deployed at the seafloor in the Sea of Marmara Central Basin recorded the consequences of a Mw 5.8 earthquake occurring on 26 September 2019 and of a Mw 4.7 foreshock 2 d before. The smaller event caused sediment resuspension and weak current (&lt;4 cm s−1) in the water column. The larger event triggered a complex response involving a debris flow and turbidity currents with variable velocities and orientations, which may have resulted from multiple slope failures. A long delay of 10 h is observed between the earthquake and the passing of the strongest turbidity current. The distance traveled by the sediment particles during the event is estimated to have extended over several kilometers, which could account for a local deposit on a sediment fan at the outlet of a canyon (where the instrument was located), but the sedimentation event did not likely cover the whole basin floor. We show that after a moderate earthquake, delayed turbidity current initiation may occur, possibly by ignition of a cloud of resuspended sediment.</p

Mapping the Environmental Fitness Landscape of a Synthetic Gene Circuit

Gene expression actualizes the organismal phenotypes encoded within the genome in an environment-dependent manner. Among all encoded phenotypes, cell population growth rate (fitness) is perhaps the most important, since it determines how well-adapted a genotype is in various environments. Traditional biological measurement techniques have revealed the connection between the environment and fitness based on the gene expression mean. Yet, recently it became clear that cells with identical genomes exposed to the same environment can differ dramatically from the population average in their gene expression and division rate (individual fitness). For cell populations with bimodal gene expression, this difference is particularly pronounced, and may involve stochastic transitions between two cellular states that form distinct sub-populations. Currently it remains unclear how a cell population's growth rate and its subpopulation fractions emerge from the molecular-level kinetics of gene networks and the division rates of single cells. To address this question we developed and quantitatively characterized an inducible, bistable synthetic gene circuit controlling the expression of a bifunctional antibiotic resistance gene in Saccharomyces cerevisiae. Following fitness and fluorescence measurements in two distinct environments (inducer alone and antibiotic alone), we applied a computational approach to predict cell population fitness and subpopulation fractions in the combination of these environments based on stochastic cellular movement in gene expression space and fitness space. We found that knowing the fitness and nongenetic (cellular) memory associated with specific gene expression states were necessary for predicting the overall fitness of cell populations in combined environments. We validated these predictions experimentally and identified environmental conditions that defined a “sweet spot” of drug resistance. These findings may provide a roadmap for connecting the molecular-level kinetics of gene networks to cell population fitness in well-defined environments, and may have important implications for phenotypic variability of drug resistance in natural settings