High-frequency imagery to capture coral tissue (Montipora capricornis) response to environmental stress, a pilot study.

Environment stress is a major threat to the existence of coral reefs and has generated a lot of interest in the coral research community. Under the environmental stress, corals can experience tissue loss and/or the breakdown of symbiosis between the cnidarian host and its symbiotic algae causing the coral tissue to appear white as the skeleton can be seen by transparency. Image analysis is a common method used to assess tissue response under the environmental stress. However, the traditional approach is limited by the dynamic nature of the coral-algae symbiosis. Here, we observed coral tissue response in the scleractinian coral, Montipora capricornis, using high frequency image analysis throughout the experiment, as opposed to the typical start/end point assessment method. Color analysis reveals that the process can be divided into five stages with two critical stages according to coral tissue morphology and color ratio. We further explore changes to the morphology of individual polyps by means of the Pearson correlation coefficient and recurrence plots, where the quasi-periodic and nonstationary dynamics can be identified. The recurrence quantification analysis also allows the comparison between the different polyps. Our research provides a detailed visual and mathematical analysis of coral tissue response to environmental stress, which potentially shows universal applicability. Moreover, our approach provides a robust quantitative advancement for improving our insight into a suite of biotic responses in the perspective of coral health evaluation and fate prediction.

Applying model approaches in non-model systems: A review and case study on coral cell culture.

Model systems approaches search for commonality in patterns underlying biological diversity and complexity led by common evolutionary paths. The success of the approach does not rest on the species chosen but on the scalability of the model and methods used to develop the model and engage research. Fine-tuning approaches to improve coral cell cultures will provide a robust platform for studying symbiosis breakdown, the calcification mechanism and its disruption, protein interactions, micronutrient transport/exchange, and the toxicity of nanoparticles, among other key biological aspects, with the added advantage of minimizing the ethical conundrum of repeated testing on ecologically threatened organisms. The work presented here aimed to lay the foundation towards development of effective methods to sort and culture reef-building coral cells with the ultimate goal of obtaining immortal cell lines for the study of bleaching, disease and toxicity at the cellular and polyp levels. To achieve this objective, the team conducted a thorough review and tested the available methods (i.e. cell dissociation, isolation, sorting, attachment and proliferation). The most effective and reproducible techniques were combined to consolidate culture methods and generate uncontaminated coral cell cultures for ~7 days (10 days maximum). The tests were conducted on scleractinian corals Pocillopora acuta of the same genotype to harmonize results and reduce variation linked to genetic diversity. The development of cell separation and identification methods in conjunction with further investigations into coral cell-type specific metabolic requirements will allow us to tailor growth media for optimized monocultures as a tool for studying essential reef-building coral traits such as symbiosis, wound healing and calcification at multiple scales.

Analysis of Inter-Domain and Cross-Domain Drug Review Polarity Classification.

Individuals increasingly rely on social media to discuss health-related issues. One way to provide easier access to relevant in- formation is through sentiment analysis - classifying text into polarity classes such as positive and negative. In this paper, we generated freely available datasets of WebMD.com drug reviews and star ratings for Common, Cancer, Depression, Diabetes, and Hypertension drugs. We explored four supervised learning models: Naive Bayes, Random Forests, Support Vector Machines, and Convolutional Neural Networks for the purpose of determining the polarity of drug reviews. We conducted inter-domain and cross-domain evaluations. We found that SVM obtained the highest f-measure on average and that cross-domain training produced similar or higher results to models trained directly on their respective datasets.

Effectiveness of hand washing on the removal of iron oxide nanoparticles from human skin ex vivo.

In this study, the effectiveness of washing with soap and water in removing nanoparticles from exposed skin was investigated. Dry, nanoscale hematite (α-Fe2O3) or maghemite (γ-Fe2O3) powder, with primary particle diameters between 20-30 nm, were applied to two samples each of fresh and frozen ex vivo human skin in two independent experiments. The permeation of nanoparticles through skin, and the removal of nanoparticles after washing with soap and water were investigated. Bare iron oxide nanoparticles remained primarily on the surface of the skin, without penetrating beyond the stratum corneum. Skin exposed to iron oxide nanoparticles for 1 and 20 hr resulted in removal of 85% and 90%, respectively, of the original dose after washing. In the event of dermal exposure to chemicals, removal is essential to avoid potential local irritation or permeation across skin. Although manufactured at an industrial scale and used extensively in laboratory experiments, limited data are available on the removal of engineered nanoparticles after skin contact. Our finding raises questions about the potential consequences of nanoparticles remaining on the skin and whether alternative washing methods should be proposed. Further studies on skin decontamination beyond use of soap and water are needed to improve the understanding of the potential health consequences of dermal exposure to nanoparticles.

Air-Liquid Interface Cell Exposures to Nanoparticle Aerosols.

The field of nanomedicine is steadily growing and several nanomedicines are currently approved for clinical use with even more in the pipeline. Yet, while the use of nanotechnology to improve targeted drug delivery to the lungs has received some attention, the use of nanoparticles for inhalation drug delivery has not yet resulted in successful translation to market as compared to intravenous drug delivery. The reasons behind the lack of inhaled nanomedicines approved for clinical use or under preclinical development are unclear, but challenges related to safety are likely to contribute. Although inhalation toxicology studies often begin using animal models, there has been an increase in the development and use of in vitro air-liquid interface (ALI) exposure systems for toxicity testing of engineered nanoparticle aerosols, which will be useful for rapid testing of candidate substances and formulations. This chapter describes an ALI cell exposure assay for measuring toxicological effects, specifically cell viability and oxidative stress, resulting from exposure to aerosols containing nanoparticles.

T cells enhance gold nanoparticle delivery to tumors in vivo.

Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

Size-controlled synthesis of monodispersed gold nanoparticles via carbon monoxide gas reduction.

An in depth analysis of gold nanoparticle (AuNP) synthesis and size tuning, utilizing carbon monoxide (CO) gas as a reducing agent, is presented for the first time. The sizes of the AuNPs are tunable from ~4 to 100 nm by altering the concentration of HAuCl4 and inlet CO gas-injection flow rate. It is also found that speciation of aqueous HAuCl4, prior to reduction, influences the size, morphology, and properties of AuNPs when reduced with CO gas. Ensemble extinction spectra and TEM images provide clear evidence that CO reduction offers a high level of monodispersity with standard deviations as low as 3%. Upon synthesis, no excess reducing agent remains in solution eliminating the need for purification. The time necessary to synthesize AuNPs, using CO, is less than 2 min.

A new era for cancer treatment: gold-nanoparticle-mediated thermal therapies.

Nanotechnology-based cancer treatment approaches potentially provide localized, targeted therapies that aim to enhance efficacy, reduce side effects, and improve patient quality of life. Gold-nanoparticle-mediated hyperthermia shows particular promise in animal studies, and early clinical testing is currently underway. In this article, the rapidly evolving field of gold nanoparticle thermal therapy is reviewed, highlighting recent literature and describing current challenges to clinical translation of the technology.

Nanoshell-mediated photothermal therapy improves survival in a murine glioma model.

We are developing a novel treatment for high-grade gliomas using near infrared-absorbing silica-gold nanoshells that are thermally activated upon exposure to a near infrared laser, thereby irreversibly damaging cancerous cells. The goal of this work was to determine the efficacy of nanoshell-mediated photothermal therapy in vivo in murine xenograft models. Tumors were induced in male IcrTac:ICR-Prkdc(SCID) mice by subcutaneous implantation of Firefly Luciferase-labeled U373 human glioma cells and biodistribution and survival studies were performed. To evaluate nanoparticle biodistribution, nanoshells were delivered intravenously to tumor-bearing mice and after 6, 24, or 48 h the tumor, liver, spleen, brain, muscle, and blood were assessed for gold content by inductively coupled plasma-mass spectrometry (ICP-MS) and histology. Nanoshell concentrations in the tumor increased for the first 24 h and stabilized thereafter. Treatment efficacy was evaluated by delivering saline or nanoshells intravenously and externally irradiating tumors with a near infrared laser 24 h post-injection. Success of treatment was assessed by monitoring tumor size, tumor luminescence, and survival time of the mice following laser irradiation. There was a significant improvement in survival for the nanoshell treatment group versus the control (P < 0.02) and 57% of the mice in the nanoshell treatment group remained tumor free at the end of the 90-day study period. By comparison, none of the mice in the control group survived beyond 24 days and mean survival was only 13.3 days. The results of these studies suggest that nanoshell-mediated photothermal therapy represents a promising novel treatment strategy for malignant glioma.

Optically tunable nanoparticle contrast agents for early cancer detection: model-based analysis of gold nanoshells.

Many optical diagnostic approaches rely on changes in scattering and absorption properties to generate optical contrast between normal and diseased tissue. Recently, there has been increasing interest in using exogenous agents to enhance this intrinsic contrast with particular emphasis on the development for targeting specific molecular features of disease. Gold nanoshells are a class of core-shell nanoparticles with an extremely tunable peak optical resonance ranging from the near-UV to the mid-IR wavelengths. Using current chemistries, nanoshells of a wide variety of core and shell sizes can easily be fabricated to scatter and/or absorb light with optical cross sections often several times larger than the geometric cross section. Using gold nanoshells of different size and optical parameters, we employ Monte Carlo models to predict the effect of varying concentrations of nanoshells on tissue reflectance. The models demonstrate the importance of absorption from the nanoshells on remitted signals even when the optical extinction is dominated by scattering. Furthermore, because of the strong optical response of nanoshells, a considerable change in reflectance is observed with only a very small concentration of nanoshells. Characterizing the optical behavior of gold nanoshells in tissue will aid in developing nanoshells as contrast agents for optical diagnostics.