High Haematocrit Blood Flow and Adsorption of Micro and Nanoparticles on an Atherosclerotic Plaque : An In-silico Study

Background: The continuing inflammatory response entailed by atherosclerosis is categorised by a pathological surface expression of certain proteins over the endothelium, namely, P-selectins. Thus, to boost the efficiency of drug carriers, these proteins can be used as binding targets. Method: An in-silico patient-specific model of a Left Anterior Descending (LAD) coronary artery considering the luminal unevenness was built and meshed using the finite element method. Objectives: Delivery of particles in a specific size range, from 200 to 3200 nm, covered by P-selectin aptamers (PSA), to an atherosclerotic plaque in a pathologically high haematocrit (Hct) blood flow was simulated. The surface of the plaque was assumed to possess a pathologically high expression of P-Selectins. Results: The distribution of deposited particles over the plaque in high Hct blood was significantly more homogenous compared to that of particles that travelled in normal blood Hct. Moreover, in the high Hct, the increase in the particle size, from 800 nm forwards, had a trivial effect on the upsurge in the surface density of adhered particles (SDAs) over the targeted endothelium. Yet, in normal blood Hct (45% in this research), the increase in the particle diameter from 800 nm forwards resulted in a significant increase in the SDAs over the targeted plaque. Interestingly, unlike the adsorption pattern of particles in normal Hct, a significant distribution of deposited particles in the post-constriction region of the atherosclerotic plaque was observed. Conclusion: Our findings provide insights into designing optimum carriers of anti-thrombotic/inflammatory drugs specifically for high blood Hct conditions.acceptedVersionPeer reviewe

Potential role of the regulatory miR1119-MYC2 module in wheat (Triticum aestivum L.) drought tolerance

MicroRNA (miRNA)-target gene modules are essential components of plants' abiotic stress signalling pathways Little is known about the drought-responsive miRNA-target modules in wheat, but systems biology approaches have enabled the prediction of these regulatory modules and systematic study of their roles in responses to abiotic stresses. Using such an approach, we sought miRNA-target module(s) that may be differentially expressed under drought and non-stressed conditions by mining Expressed Sequence Tag (EST) libraries of wheat roots and identified a strong candidate (miR1119-MYC2). We then assessed molecular and physiochemical differences between two wheat genotypes with contrasting drought tolerance in a controlled drought experiment and assessed possible relationships between their tolerance and evaluated traits. We found that the miR1119-MYC2 module significantly responds to drought stress in wheat roots. It is differentially expressed between the contrasting wheat genotypes and under drought versus non-stressed conditions. We also found significant associations between the module's expression profiles and ABA hormone content, water relations, photosynthetic activities, H2O2 levels, plasma membrane damage, and antioxidant enzyme activities in wheat. Collectively, our results suggest that a regulatory module consisting of miR1119 and MYC2 may play an important role in wheat's drought tolerance

The Effect of Fatigue on the Time to Stability in Jumping and Landing in Football Players Who Have Undergone Anterior Cruciate Ligament Reconstruction

Background: Jumping and landing are common activities in soccer that are often reported in connection with anterior cruciate ligament injury. As most injuries occur during fatigue, the present study aimed to investigate the effect of fatigue on the component of time to stability (TTS) during landing between healthy soccer players and soccer players who have undergone anterior cruciate ligament reconstruction.Methods: This quasi-experimental study included 24 professional soccer players who were divided into control and experimental groups. Twelve active professional soccer players (control group) and 12 soccer players with 6-24 months of anterior cruciate ligament reconstruction with hamstring graft (experimental group) participated in this study. Athletes jumped and landed on the obstacle to a height of 7.5 cm. After the fatigue protocol, these movements were repeated. TTS data was collected using force plate. MANOVA test at the significant level of p <0.05 was used to compare pre-test and post-test data between the groups.Results: According to the results of this study, fatigue did not affect the time to stability in any of the anterior-posterior (p=0.104), internal-external (p=0.668), or vertical components (p=0.894) between the two groups, and fatigue could not make a significant difference between the two groups. Moreover, before fatigue, no significant difference was observed between the two groups in any of the components.Conclusion: It seems that a plyometric fatigue training session will not be effective in differentiating between healthy soccer players and soccer players who have had anterior cruciate ligament reconstruction

Effect of Material and Population on the Delivery of Nanoparticles to an Atherosclerotic Plaque : A Patient-specific In Silico Study

acceptedVersionPeer reviewe

Potential role of the regulatory miR1119-MYC2 module in wheat (Triticum aestivum L.) drought tolerance

MicroRNA (miRNA)-target gene modules are essential components of plants’ abiotic stress signalling pathways Little is known about the drought-responsive miRNA-target modules in wheat, but systems biology approaches have enabled the prediction of these regulatory modules and systematic study of their roles in responses to abiotic stresses. Using such an approach, we sought miRNA-target module(s) that may be differentially expressed under drought and non-stressed conditions by mining Expressed Sequence Tag (EST) libraries of wheat roots and identified a strong candidate (miR1119-MYC2). We then assessed molecular and physiochemical differences between two wheat genotypes with contrasting drought tolerance in a controlled drought experiment and assessed possible relationships between their tolerance and evaluated traits. We found that the miR1119-MYC2 module significantly responds to drought stress in wheat roots. It is differentially expressed between the contrasting wheat genotypes and under drought versus non-stressed conditions. We also found significant associations between the module’s expression profiles and ABA hormone content, water relations, photosynthetic activities, H2O2 levels, plasma membrane damage, and antioxidant enzyme activities in wheat. Collectively, our results suggest that a regulatory module consisting of miR1119 and MYC2 may play an important role in wheat’s drought tolerance

Proteomic Identification Reveals the Role of Ciliary Extracellular‐Like Vesicle in Cardiovascular Function

Primary cilia are shown to have membrane swelling, also known as ciliary bulbs. However, the role of these structures and their physiological relevance remains unknown. Here, it is reported that a ciliary bulb has extracellular vesicle (EV)‐like characteristics. The ciliary extracellular‐like vesicle (cELV) has a unique dynamic movement and can be released by mechanical fluid force. To better identify the cELV, differential multidimensional proteomic analyses are performed on the cELV. A database of 172 cELV proteins is generated, and all that examined are confirmed to be in the cELV. Repressing the expression of these proteins in vitro and in vivo inhibits cELV formation. In addition to the randomized heart looping, hydrocephalus, and cystic kidney in fish, compensated heart contractility is observed in both fish and mouse models. Specifically, low circulation of cELV results in hypotension with compensated heart function, left ventricular hypertrophy, cardiac fibrosis, and arrhythmogenic characteristics, which result in a high mortality rate in mice. Furthermore, the overall ejection fraction, stroke volume, and cardiac output are significantly decreased in mice lacking cELV. It is thus proposed that the cELV as a nanocompartment within a primary cilium plays an important role in cardiovascular functions

Microfluidics: reframing biological enquiry

The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools - in conjunction with advanced imaging, bioinformatics and molecular biology approaches - will transform biology into a precision science

Role of α and β Transmembrane Domains in Integrin Clustering

Integrins are transmembrane proteins playing a crucial role in the mechanical signal transduction from the outside to the inside of a cell, and vice versa. Nevertheless, this signal transduction could not be implemented by a single protein. Rather, in order for integrins to be able to participate in signal transduction, they need to be activated and produce clusters first. As integrins consist of α- and β-subunits that are separate in the active state, studying both subunits separately is of a great importance, for, in the active state, the distance between α- and β-subunits is long enough that they do not influence one another significantly. Thus, this study aims to investigate the tendency of transmembrane domains of integrins to form homodimers. We used both Steered and MARTINI Coarse-grained molecular dynamics method to perform our simulations, mainly because of a better resolution and computational feasibility that each of these methods could provide to us. Using the Steered molecular dynamics method for α- and β-subunits, we found that the localized lipid packing prevented them from clustering. Nonetheless, the lipid packing phenomenon was found to be an artifact after investigating this process using a coarse grained (CG) model. Exploiting the coarse-grained molecular dynamics simulations, we found that α- and β-subunits tend to form a stable homo-dimer

CFD study of droplet formation in a cross-Junction microfluidic device: investigating the impact of outflow channel design and viscosity ratio

This study employed computational fluid dynamics (CFD) to investigate various regimes of droplet formation in a square microfluidic cross-junction device. The first part of the study focused on investigating the impact of viscosity ratios ranging from 0.1 to 5 on droplet characteristics under different flow rate ratios. The transition regime between the dripping and jetting exhibited particularly interesting behavior, with droplet volume being proportional to viscosity ratio. However, when conditions were far from the transition regime, the volume of droplets did not vary significantly with respect to viscosity ratios greater than one. The results of the study indicate the feasibility of reducing droplet volume to the appropriate level while minimizing the impact on the continuous phase's flow rate and the risk of transitioning to jetting. Moreover, in the final part of the study, we investigated the potential of shifting the transition boundary between the squeezing and jetting regimes. Our findings indicate that modifying the outflow channel's design can increase the frequency of droplet generation without altering the operating conditions for both the continuous and dispersed phases

Design and Parameter Study of Integrated Microfluidic Platform for CTC Isolation and Enquiry; A Numerical Approach

Being the second cause of mortality across the globe, there is now a persistent effort to establish new cancer medication and therapies. Any accomplishment in treating cancers entails the existence of accurate identification systems empowering the early diagnosis. Recent studies indicate CTCs&rsquo; potential in cancer prognosis as well as therapy monitoring. The chief shortcoming with CTCs is that they are exceedingly rare cells in their clinically relevant concentration. Here, we simulated a microfluidic construct devised for immunomagnetic separation of the particles of interest from the background cells. This separation unit is integrated with a mixer subunit. The mixer is envisioned for mixing the CTC enriched stream with lysis buffer to extract the biological material of the cell. Some modification was proposed on mixing geometry improving the efficacy of the functional unit. A valuation of engaged forces was made and some forces were neglected due to their order of magnitude. The position of the magnet was also optimized by doing parametric study. For the mixer unit, the effect of applied voltage and frequency on mixing index was studied to find the optimal voltage and frequency which provides better mixing. Above-mentioned studies were done on isolated units and the effect of each functional unit on the other is not studied. As the final step, an integrated microfluidic platform composed of both functional subunits was simulated simultaneously. To ensure the independence of results from the grid, grid studies were also performed. The studies carried out on the construct reveal its potential for diagnostic application