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Dual imaging dramatically improves detection and early diagnosis of cancer. In this work we present an oil in water (O/W) nano-emulsion stabilized with lecithin and loaded with cobalt ferrite oxide (Co 0.5 Fe 2.5 O 4 ) nanocubes for photo-acoustic and magnetic resonance dual imaging. The nanocarrier is responsive in in vitro photo-acoustic and magnetic resonance imaging (MRI) tests. A clear and significant time-dependent accumulation in tumor tissue is shown in in vivo photo-acoustic studies on a murine melanoma xenograft model. The proposed O/W nano-emulsion exhibits also high values of r 2 /r 1 (ranging from 45 to 85, depending on the magnetic field) suggesting a possible use as T 2 weighted image contrast agents. In addition, viability and cellular uptake studies show no significant cytotoxicity on the fibroblast cell line. We also tested the O/W nano-emulsion loaded with curcumin against melanoma cancer cells demonstrating a significant cytotoxicity and thus showing possible therapeutic effects in addition to the in vivo imaging. [ABSTRACT FROM AUTHOR]

Microglia reactivity entails a large-scale remodeling of cellular geometry, but the behavior of the microtubule cytoskeleton during these changes remains unexplored. Here we show that activated microglia provide an example of microtubule reorganization from a non-centrosomal array of parallel and stable microtubules to a radial array of more dynamic microtubules. While in the homeostatic state, microglia nucleate microtubules at Golgi outposts, and activating signaling induces recruitment of nucleating material nearby the centrosome, a process inhibited by microtubule stabilization. Our results demonstrate that a hallmark of microglia reactivity is a striking remodeling of the microtubule cytoskeleton and suggest that while pericentrosomal microtubule nucleation may serve as a distinct marker of microglia activation, inhibition of microtubule dynamics may provide a different strategy to reduce microglia reactivity in inflammatory disease. [Display omitted] • Reactive microglia dramatically remodel their microtubule cytoskeleton • Golgi outposts nucleate acentrosomal microtubules in homeostatic microglia • Control of microtubule dynamics enables proper cytokine release in reactive microglia Rosito et al. find that in microglia cells, the transition between homeostatic and reactive states is characterized by a dramatic reorganization of the microtubule cytoskeleton from a Golgi-outpost-nucleated acentrosomal array to a pericentrosomal radial array to enable proper cytokine release. [ABSTRACT FROM AUTHOR]

Nanoscale echogenic bubbles (NBs), can be used as a theranostic platform for the localized delivery of encapsulated drugs. However, the generation of NBs is challenging, because they have lifetimes as short as milliseconds in solution. The aim of this work has been the optimization of a preparation method for the generation of stable NBs, characterized by measuring: a) acoustic efficiency, b) nano-size, to ensure passive tumour targeting, c) stability during storage and after injection and d) ability to entrap drugs. NBs are monodisperse and ultra-stable, their stability achieved by generation of an amphiphilic multilamellar shell able to efficiently retain the PFC gas. The NBs perform as good acoustic enhancers over a wide frequency range and out of resonant conditions, as tested in both in vitro and in vivo experiments, proving to be a potential platform for the production of versatile carriers to be used in ultrasound-assisted diagnostic, therapeutic and theranostic applications. Ultra-stable NBs generation has been achieved by the optimization of a novel preparation method. These systems have been deeply characterized to assess NBs existence, in terms of physical chemical and acoustic features. The selected NBs had been tested in both in vitro and in vivo experiments, checking their capability as a potential platform for the production of versatile carriers to be used in ultrasound-assisted diagnostic, therapeutic, and theranostic applications. [Display omitted] • Generation of stable gas-filled nanobubbles • Nanobubbles are long-lived thanks to their multi-layered lipid/surfactant shell. • Nanobubbles can carry lipophilic and hydrophilic drugs. • Nanobubbles perform as good acoustic enhancers in vitro. • Nanobubbles are useful contrast agents in in vivo pilot test in a mouse model. [ABSTRACT FROM AUTHOR]

The ultrastructure of mature spermatozoa from three leech species, Haemadipsa zeylanica ( Moquin-Tandon, 1826 ) (Haemadipsidae), Theromyzon tessulatum ( Müller, 1774 ) and Placobdella costata (Fr. Müller, 1846 ) (Glossiphoniidae), was investigated by means of transmission electron microscopy. While the three species showed the general features of hirudinid spermatozoa, considerable variation was found in nearly all characters examined: the anterior acrosome varied in length and in shape; the nuclei also varied in size and show a very complicated shape which is maintained for the whole length in the two glossiphonids, while in the haemadipsid, it showed two different morphological regions. The single mitochondrion, which is surrounded by an electron-dense sheath, is straight in H and T. tessulatum, but twisted in P. costata. The flagellum in the three studied species is of the prominent central sheath type. The basal body is absent in the three species and the central apparatus of the flagellum was observed penetrating to the mitochondrion. By comparing the present data with those from “oligochaeta”, Branchiobdellida and Acanthobdellida, we found that only the presence of an anterior acrosome characterizes the true leeches and at present should be regarded as an autapomorphic character of Euhirudinea. [ABSTRACT FROM AUTHOR]

Abstract: The ultrastructure of the cuticle and mature spermatozoa of the oligochaete Propappus volki Michaelsen, 1916 is described with the aim of providing additional data for clarifying the systematic position of the taxon. P. volki is a fresh-water species living in streams, and is easily recognized by its proboscis on the pre-segmental prostomium and, in mature specimens, by a clitellum covering the segments XII–XIV. The cuticle is composed of a proximal fibre zone and a distal layered epicuticle covered with membrane-bound epicuticular projections. The fibre zone consists of collagenous fibres in a matrix, arranged in either densely packed parallel layers with the fibres oriented in the same direction, or with more loosely distributed fibres, although with the same main orientation. The epicuticular projections are pyramidal with the base leaning on the outer surface of the epicuticle. The cuticle covering the proboscis differs in morphology from that of the rest of the worm; the fibre zone is composed of thin and short fibrils running in all directions, and the epicuticular projections are longer and more narrow than the projections in other regions of the worm. The spermatozoa are filiform cells formed, in sequence, by an acrosome, an elongated nucleus, a long midpiece, and a flagellum. The acrosomal tube is short and straight with a completely external acrosomal vesicle. Following the acrosome is a apically corkscrew-shaped and basally straight nucleus. The midpiece is twisted and formed by five mitochondria. The flagellum shows a prominent central sheath arrangement. A comparison with ultrastructurally described cuticles and spermatozoa from other clitellate species reveals most similarities with enchytraeids. [Copyright &y& Elsevier]

Abstract Herein, we have developed pH-responsive shape-persistent polymersomes made of well-defined amphiphilic poly(ethylene oxide)- block -poly(diisopropylaminoethyl methacrylate- co -furfuryl methacrylate)s PEO- b -P(DPA- co -FMA) by exploiting Diels-Alder chemistry as a robust and simple crosslinking method. Using Photo-induced Copper Mediated Reversible Deactivation Radical Polymerization, we synthesized PEO- b -P(DPA- co -FMA) with optimal block ratios that favor the formation of polymersomes in aqueous media having pH-responsive P(DPA-co-FMA) membranes. Owing to the existence of furfuryl pendant groups within the polymersome membranes, the crosslinking of pH-responsive P(DPA- co -FMA) chains can be achieved via Diels-Alder chemistry. Interestingly, the resulting crosslinked polymersomes swell when the pH in the solution is decreased so that it lies in a biologically relevant range, as was demonstrated by cryogenic transmission electron microscopy. Here, the polymersomes' ability to swell can be controlled by adjusting the amount of crosslinker. A minimum threshold of crosslinking density is needed for the polymersomes to swell while an excess amount of crosslinker quenched their ability to swell. Furthermore, crosslinked polymersomes are capable of encapsulating hydrophilic model drug, such as Rhodamine B. At pH 7.20, due to the compact and hydrophobic membrane, the diffusion of the dye from the interior of the polymersomes to the media is minimized, while the pronation of PDPA at an acidic pH of 4.00, enables a permeable membrane, allowing the loaded cargo to leak much more quickly. The shape-persistent polymersomes that we developed herein, are a promising nano-platform for use in drug delivery applications. Graphical abstract Image 1 Highlights • PDPA-based polymer is synthesized by photo-induced living radical polymerization. • PEO- b -PDPA self-assembles in water to form either micelles or polymersomes. • The membranes of pH-responsive polymersomes are crosslinked by Diels-Alder Chemistry. • Crosslinked polymersomes reversibly swell upon the switching the pH of the media. • Crosslinked polymersomes show the pH-triggered release of pre-loaded hydrophilic dye. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Drosophila PINK1B9 mutant is a model for Parkinson's disease. • The adult crop organ is an important and essential part of the gut. • PINK1B9 flies show morphological and functional impairment in the crop muscle. • PINK1B9 flies show an impairment in the 5-HT circuitry. • Mucuna pruriens extract rescues the crop impairment. Abstract Despite its great potentiality, little attention has been paid to modelling gastrointestinal symptoms of Parkinson's disease (PD) in Drosophila melanogaster (Dm). Our previous studies on standardized Mucuna pruriens extract (Mpe) have shown usefulness in the Drosophila model of PD. In this communication, we provide new information on the effect of Mpe on basal and serotonin treated contractions in the crop (i.e., an important and essential part of the gut) in Drosophila PD mutant for PTEN-induced putative kinase 1 (PINK1B9) gene. The effect of Mpe on PINK1B9 supplied with standard diet to larvae and/or adults, were assayed on 10–15 days old flies. Conversely from what we observed in the wild type flies, recordings demonstrated that exogenous applications of serotonin on crop muscles of untreated PINK1B9 affect neither the frequency nor the amplitude of the crop contraction, while the same muscle parameters are enhanced following brain injections of serotonin, thus suggesting that PINK1B9 mutants may likely have an impairment in the serotonergic pathways. Also, the mitochondrial morphology in the crop muscles is strongly compromised, as demonstrated by the transmission electron microscopy analysis. The Mpe treatment rescued the crop muscle parameters and also the mitochondrial morphology when supplied to both larvae and adults. Overall, this study strengthens the relevance of using PINK1B9 Dm as a translational model to study the gastrointestinal symptoms in PD and also confirms the useful employment of M. pruriens for PD treatment. [ABSTRACT FROM AUTHOR]

Summary The fatty acid ethanolamides (FAEs) are lipid mediators present in all organisms and involved in highly conserved biological functions, such as innate immunity, energy balance, and stress control. They are produced from membrane N -acylphosphatidylethanolamines (NAPEs) and include agonists for G protein-coupled receptors (e.g., cannabinoid receptors) and nuclear receptors (e.g., PPAR-α). Here, we report the crystal structure of human NAPE-hydrolyzing phospholipase D (NAPE-PLD) at 2.65 Å resolution, a membrane enzyme that catalyzes FAE formation in mammals. NAPE-PLD forms homodimers partly separated by an internal ∼9-Å-wide channel and uniquely adapted to associate with phospholipids. A hydrophobic cavity provides an entryway for NAPE into the active site, where a binuclear Zn 2+ center orchestrates its hydrolysis. Bile acids bind with high affinity to selective pockets in this cavity, enhancing dimer assembly and enabling catalysis. These elements offer multiple targets for the design of small-molecule NAPE-PLD modulators with potential applications in inflammation and metabolic disorders. [ABSTRACT FROM AUTHOR]