Improving the understanding of cytoneme-mediated morphogen gradients by in silico modeling

Morphogen gradients are crucial for the development of organisms. The biochemical properties of many morphogens prevent their extracellular free diffusion, indicating the need of an active mechanism for transport. The involvement of filopodial structures (cytonemes) has been proposed for morphogen signaling. Here, we describe an in silico model based on the main general features of cytoneme-meditated gradient formation and its implementation into Cytomorph, an open software tool. We have tested the spatial and temporal adaptability of our model quantifying Hedgehog (Hh) gradient formation in two Drosophila tissues. Cytomorph is able to reproduce the gradient and explain the different scaling between the two epithelia. After experimental validation, we studied the predicted impact of a range of features such as length, size, density, dynamics and contact behavior of cytonemes on Hh morphogen distribution. Our results illustrate Cytomorph as an adaptive tool to test different morphogens gradients and to generate hypotheses that are difficult to study experimentally.

Metal Nanoparticles as Sustainable Tools for C–N Bond Formation via C–H Activation

The design of highly active metal nanoparticles to be employed as efficient heterogeneous catalysts is a key tool for the construction of complex organic molecules and the minimization of their environmental costs. The formation of novel C–N bonds via C–H activation is an effective atom-economical strategy to access high value materials in pharmaceuticals, polymers, and natural product production. In this contribution, the literature of the last ten years on the use of metal nanoparticles in the processes involving direct C–N bond formation will be discussed. Where possible, a discussion on the role and influence of the support used for the immobilization and/or the metal chosen is reported. Particular attention was given to the description of the experiments performed to elucidate the active mechanism.

Exosomal microRNAs in hepatocellular carcinoma

Hepatocellular carcinoma is one of the most common malignant tumors worldwide and the fourth leading cause of cancer-related deaths. The prognosis of hepatocellular carcinoma patients is extremely poor due to the occult onset and high metastasis of hepatocellular carcinoma. Therefore, biomarkers with high specificity and sensitivity are of great importance in early screening, diagnosis prognosis, and treatment of hepatocellular carcinoma patients. Exosomes are tiny vesicles secreted by various types of cells, which can serve as mediators of intercellular communication to regulate the tumor microenvironment, and play a key role in the occurrence, development, prognosis, monitor and treatment of hepatocellular carcinoma. As microRNA deliverer, exosomes are involved in multiple life activities by regulating target genes of recipient cells such as proliferation, invasion, metastasis and apoptosis of cancer cells. In this review, we summarized the composition, active mechanism and function of exosomal microRNAs in hepatocellular carcinoma, and elaborated on their potential application value of early diagnosis and treatment in hepatocellular carcinoma.

Improving the understanding of cytoneme-mediated morphogen gradients by in silico modeling

Morphogen gradients are crucial for the development of organisms, but there is still no agreement on the mechanisms involved in their establishment. The biochemical properties of many morphogens prevent their extracellular free diffusion, indicating the need for an active mechanism for transport. The involvement of filopodial structures (cytonemes) has been proposed for morphogen signaling, although a detailed description of the mechanism is pending. Here, we describe the development of an in silico model based on the main general features of cytoneme-meditated gradient formation and its implementation into an open software tool we named Cytomorph. We have tested the spatial and temporal adaptability of our model experimentally quantifying Hedgehog (Hh) gradient formation in Drosophila and found that Cytomorph is able to reproduce the gradient and explain its scaling between different epithelia. After experimental validation, we studied the predicted impact of a range of features such as length, size, density, dynamics and contact behavior of cytonemes on morphogen distribution. Our results illustrate Cytomorph as an adaptive tool to test and generate hypotheses that are difficult to study experimentally.

Subcellular Organization of Viral Particles During Maturation of Nucleus-Forming Jumbo Phage

SummaryMany eukaryotic viruses assemble mature particles within distinct subcellular compartments, but bacteriophages were long assumed to assemble randomly throughout the host cell cytoplasm. Here we visualized the subcellular location of viral particles formed during replication of Pseudomonas nucleus-forming jumbo phages and discovered that they assemble a unique structure inside cells we term phage bouquets. We show that after capsids complete DNA packaging at the surface of the phage nucleus, tails assemble and attach to the capsids, and these particles accumulate to form bouquets at specific subcellular locations. In these bouquets, the viral particles are arranged in a spherical pattern with tails oriented inward and the heads outwards. Localized at fixed distances on either side of the phage nucleus, bouquets grow in size and number over time as new phage particles are added. In the presence of mutations that cause the phage nucleus to be mispositioned away from its typical position at the midcell, bouquets still localize at the same fixed distance from the nucleus, suggesting an active mechanism for their formation and positioning. These results mark the discovery of a pathway for organizing mature viral particles inside bacteria and demonstrate that nucleus-forming jumbo phage, like most eukaryotic viruses, are highly spatially organized during all stages of their lytic cycle.

Hyaluronic acid as an active agent to accelerate bone regeneration aftertooth extraction: a literature review

Tooth extraction is a dental treatment that is performed frequently in dentistry. This procedure will stimulate a sophisticated healing process involving a variety of biological factors although it takes a long time to complete. Three phases occur in this process i.e. the inflammatory phase, the proliferation phase, and the remodeling phase which aim to restore the tissue function. Several interventions can be used to accelerate bone formation after tooth extraction. Recently, hyaluronic acid (HA) has been commonly used in dentistry due to their essential physiological effects for the periodontal connective tissue, gingiva, and alveolar bone. Hyaluronic acidis a natural non-sulfate glycosaminoglycans compound that has high molecular weight consisting of D-glucuronic acid and N-acetylglucosamine. Hyaluronic acidis also a component of the extracellular matrix that plays an important role in morphogenesis and tissue healing. The mechanism of action of HA works in two ways, that is passive and active mechanism. The passive mechanism is depend on physical and chemical properties of HA that can change the molecular weight and concentration properties. The active mechanism of HA works by stimulating signal transduction pathway initiated by ligand binding with its receptors through autocrine or paracrine processes. The administration of HA can accelerate bone formation due to it can enhance bone morphogenetic protein (BMP) which belongs to the TGF- β superfamily that has high osteogenic capacity. The HA works through a passive mechanism that depends on its molecular weight and an active mechanism by increasing BMP activity.

Modeling of a Complete Morphing Mechanism Covered by a Paneled Morphing Skin

Presented in this paper is a method for modeling and simulation of a complete morphing mechanism. The said mechanism has a rigid panel morphing skin that morphs along with a driving mechanism. The said skin is made of segmented panels, inspired by fish scales. Since the gaps between these panels are undesirable, a gapless design is introduced in this paper by using shape-memory polymer (SMP) joints. This paper aims to solve two fundamental problems for the entire system: 1) motion control and 2) force control. The motion control is addressed through the kinematic modeling of two equations including A) the passive rigid panels and B) the passive rigid panels to the active mechanism. Force control is achieved through force modeling. This is to develop a relation of the SMP deformations to the required actuator forces. Experiment is carried out to determine the SMP forces versus deformation, and simulations are conducted to investigate how a complete morphing mechanism behaves. It also reveals that the workspace and singularity of the original mechanism will change after covered by a morphing skin. The developed method sheds lights on the design of a complete morphing mechanism.

A Strategic Move for Long-Term Bridge Performance within a Game Theory Framework by a Data-Driven Co-Active Mechanism

The Federal Highway Administration (FHWA) requires that states have less than 10% of the total deck area that is structurally deficient. It is a minimum risk benchmark for sustaining the National Highway System bridges. Yet, a decision-making framework is needed for obtaining the highest possible long-term return from investments on bridge maintenance, rehabilitation, and replacement (MRR). This study employs a data-driven coactive mechanism within a proposed game theory framework, which accounts for a strategic interaction between two players, the FHWA and a state Department of Transportation (DOT). The payoffs for the two players are quantified in terms of a change in service life. The proposed framework is used to investigate the element-level bridge inspection data from four US states (Georgia, Virginia, Pennsylvania, and New York). By reallocating 0.5% (from 10% to 10.5%) of the deck resources to expansion joints and joint seals, both federal and state transportation agencies (e.g., FHWA and state DOTs in the U.S.) will be able to improve the overall bridge performance. This strategic move in turn improves the deck condition by means of a co-active mechanism and yields a higher payoff for both players. It is concluded that the proposed game theory framework with a strategic move, which leverages element interactions for MRR, is most effective in New York where the average bridge service life is extended by 15 years. It is also concluded that the strategic move can lead to vastly different outcomes. Pennsylvania’s concrete bridge management strategy currently appears to leverage a co-active mechanism in its bridge MRR strategies. This is noteworthy because its bridges are exposed to similar environmental conditions to what is obtainable in Virginia and New York and are subjected to more aggressive weather conditions than those in Georgia. This study illustrates how a strategic move affects the payoffs of different players by numerically quantifying changes in service life from bridge time-dependent bridge performance relationships.