Comparative chemical analysis of six ancient italian sweet cherry (Prunus avium L.) varieties showing antiangiogenic activity.

In this study, cherry fruits and petioles from six ancient Italian Prunus avium L. varieties (Ferrovia, Capellina, Morellina, Ciambellana, Napoletana, and Bianca), were compared by chemical and bioinformatic analyses and evaluated for their antiangiogenic activity. The highest levels of total phenols and flavonoids were found in Napoletana petioles, and Morellina and Capellina fruits. HPLC-PDA-MS analyses showed similar phenolic profiles for all fruit extracts, with cyanidin-3-O-rutinoside, flavonols glycosides, and quinic acid derivatives as major components. Flavonoid glycosides were found in all petiole extracts, while proanthocyanidins B type were predominant in Capellina, Napoletana and Bianca. Accordingly to their higher polyphenolic content, petiole extracts exhibited stronger radical scavenging activity compared to the fruits. The best antiangiogenic response was exhibited by Morellina, Ferrovia, and Ciambellana petiole extracts, and by Ferrovia, Morellina, and Capellina fruit extracts; by bioinformatic studies rutin and cyanidin 3-O-rutinoside were recognised as the best candidate bioactive compounds. In conclusion, sweet cherry varietes were confirmed as valuable sources of phenols, showing also potential angiomodulator properties.

Urban stormwater and crude oil injury pathways converge on the developing heart of a shore-spawning marine forage fish.

Understanding how aquatic organisms respond to complex chemical mixtures remains one of the foremost challenges in modern ecotoxicology. Although oil spills are typically high-profile disasters that release hundreds or thousands of chemicals into the environment, there is growing evidence for a common adverse outcome pathway (AOP) for the vulnerable embryos and larvae of fish species that spawn in oiled habitats. Molecular initiating events involve the disruption of excitation-contraction coupling in individual cardiomyocytes, which then dysregulate the form and function of the embryonic heart. Phenanthrenes and other three-ring (tricyclic) polycyclic aromatic hydrocarbons (PAHs) are key drivers for this developmental cardiotoxicity and are also relatively enriched in land-based urban runoff. Similar to oil spills, stormwater discharged from roadways and other high-traffic impervious surfaces contains myriad contaminants, many of which are uncharacterized in terms of their chemical identity and toxicity to aquatic organisms. Nevertheless, given the exceptional sensitivity of the developing heart to tricyclic PAHs and the ubiquitous presence of these compounds in road runoff, cardiotoxicity may also be a dominant aspect of the stormwater-induced injury phenotype in fish early life stages. Here we assessed the effects of traffic-related runoff on the embryos and early larvae of Pacific herring (Clupea pallasii), a marine forage fish that spawns along the coastline of western North America. We used the well-characterized central features of the oil toxicity AOP for herring embryos as benchmarks for a detailed analysis of embryolarval cardiotoxicity across a dilution gradient ranging from 12 to 50% stormwater diluted in clean seawater. These injury indicators included measures of circulatory function, ventricular area, heart chamber looping, and the contractility of both the atrium and the ventricle. We also determined tissue concentrations of phenanthrenes and other PAHs in herring embryos. We find that tricyclic PAHs are readily bioavailable during cardiogenesis, and that stormwater-induced toxicity is in many respects indistinguishable from canonical crude oil toxicity. Given the chemical complexity of urban runoff, non-tricyclic PAH-mediated mechanisms of developmental toxicity in fish remain likely. However, from the standpoint of managing wild herring populations, our results suggest that stormwater-driven threats to individual survival (both near-term and delayed mortality) can be understood from decades of past research on crude oil toxicity. Moreover, Pacific herring embryos are promising sentinels for water quality monitoring in nearshore marine habitats, as in situand sensitive indicators of both toxic runoff and the effectiveness of pollution reduction efforts such as green stormwater infrastructure.

Functional Bio-inorganic Hybrids from Silicon Quantum Dots and Biological Molecules.

Quantum dots (QDs) are semiconductor nanoparticles that exhibit photoluminescent properties useful for applications in the field of diagnostics and medicine. Successful implementation of these QDs for bio-imaging and bio/chemical sensing typically involves conjugation to biologically active molecules for recognition and signal generation. Unfortunately, traditional and widely studied QDs are based upon heavy metals and other toxic elements (e.g., Cd- and Pb-based QDs), which precludes their safe use in actual biological systems. Silicon quantum dots (SiQDs) offer the same advantages as these heavy-metal-based QDs with the added benefits of nontoxicity and abundance. The preparation of functional bio-inorganic hybrids from SiQDs and biomolecules has lagged significantly compared to their traditional toxic counterparts because of the challenges associated with the synthesis of water-soluble SiQDs and their relative instability in aqueous environments. Advances in SiQD synthesis and surface functionalization, however, have made possible the preparation of functional bio-inorganic hybrids from SiQDs and biological molecules through different bioconjugation reactions. In this contribution, we review the various bioconjugate reactions by which SiQDs have been linked to biomolecules and implemented as platforms for bio-imaging and bio/chemical sensing. We also highlight the challenges that need to be addressed and overcome for these materials to reach their full potential. Lastly, we give prospective applications where this unique class of nontoxic and biocompatible materials can be of great utility in the future.

Integration of actomyosin contractility with cell-cell adhesion during dorsal closure.

In this work, we combine genetic perturbation, time-lapse imaging and quantitative image analysis to investigate how pulsatile actomyosin contractility drives cell oscillations, apical cell contraction and tissue closure during morphogenesis of the amnioserosa, the main force-generating tissue during the dorsal closure in Drosophila We show that Myosin activity determines the oscillatory and contractile behaviour of amnioserosa cells. Reducing Myosin activity prevents cell shape oscillations and reduces cell contractility. By contrast, increasing Myosin activity increases the amplitude of cell shape oscillations and the time cells spend in the contracted phase relative to the expanded phase during an oscillatory cycle, promoting cell contractility and tissue closure. Furthermore, we show that in AS cells, Rok controls Myosin foci formation and Mbs regulates not only Myosin phosphorylation but also adhesion dynamics through control of Moesin phosphorylation, showing that Mbs coordinates actomyosin contractility with cell-cell adhesion during amnioserosa morphogenesis.

Quinoxaline-Based Polymer Dots with Ultrabright Red to Near-Infrared Fluorescence for In Vivo Biological Imaging.

This article describes the design and synthesis of quinoxaline-based semiconducting polymer dots (Pdots) that exhibit near-infrared fluorescence, ultrahigh brightness, large Stokes shifts, and excellent cellular targeting capability. We also introduced fluorine atoms and long alkyl chains into polymer backbones and systematically investigated their effect on the fluorescence quantum yields of Pdots. These new series of quinoxaline-based Pdots have a fluorescence quantum yield as high as 47% with a Stokes shift larger than 150 nm. Single-particle analysis reveals that the average per-particle brightness of the Pdots is at least 6 times higher than that of the commercially available quantum dots. We further demonstrated the use of this new class of quinoxaline-based Pdots for effective and specific cellular and subcellular labeling without any noticeable nonspecific binding. Moreover, the cytotoxicity of Pdots were evaluated on HeLa cells and zebrafish embryos to demonstrate their great biocompatibility. By taking advantage of their extreme brightness and minimal cytotoxicity, we performed, for the first time, in vivo microangiography imaging on living zebrafish embryos using Pdots. These quinoxaline-based NIR-fluorescent Pdots are anticipated to find broad use in a variety of in vitro and in vivo biological research.

Design of a radiation facility for very small specimens used in radiobiology studies.

A design of a radiation facility for very small specimens used in radiobiology is presented. This micro-irradiator has been primarily designed to irradiate partial bodies in zebrafish embryos 3-4 mm in length. A miniature x-ray, 50 kV photon beam, is used as a radiation source. The source is inserted in a cylindrical brass collimator that has a pinhole of 1.0 mm in diameter along the central axis to produce a pencil photon beam. The collimator with the source is attached underneath a computer-controlled movable table which holds the specimens. Using a 45 degrees tilted mirror, a digital camera, connected to the computer, takes pictures of the specimen and the pinhole collimator. From the image provided by the camera, the relative distance from the specimen to the pinhole axis is calculated and coordinates are sent to the movable table to properly position the samples in the beam path. Due to its monitoring system, characteristic of the radiation beam, accuracy and precision of specimen positioning, and automatic image-based specimen recognition, this radiation facility is a suitable tool to irradiate partial bodies in zebrafish embryos, cell cultures or any other small specimen used in radiobiology research.

Characterization of a novel micro-irradiator using Monte Carlo radiation transport simulations.

Small animals are highly valuable resources for radiobiology research. While rodents have been widely used for decades, zebrafish embryos have recently become a very popular research model. However, unlike rodents, zebrafish embryos lack appropriate irradiation tools and methodologies. Therefore, the main purpose of this work is to use Monte Carlo radiation transport simulations to characterize dosimetric parameters, determine dosimetric sensitivity and help with the design of a new micro-irradiator capable of delivering irradiation fields as small as 1.0 mm in diameter. The system is based on a miniature x-ray source enclosed in a brass collimator with 3 cm diameter and 3 cm length. A pinhole of 1.0 mm diameter along the central axis of the collimator is used to produce a narrow photon beam. The MCNP5, Monte Carlo code, is used to study the beam energy spectrum, percentage depth dose curves, penumbra and effective field size, dose rate and radiation levels at 50 cm from the source. The results obtained from Monte Carlo simulations show that a beam produced by the miniature x-ray and the collimator system is adequate to totally or partially irradiate zebrafish embryos, cell cultures and other small specimens used in radiobiology research.