Design of decorated self-assembling peptide hydrogels as architecture for mesenchymal stem cells

Hydrogels from self-assembling ionic complementary peptides have been receiving a lot of interest from the scientific community as mimetic of the extracellular matrix that can offer three-dimensional supports for cell growth or can become vehicles for the delivery of stem cells, drugs or bioactive proteins. In order to develop a 3D "architecture" for mesenchymal stem cells, we propose the introduction in the hydrogel of conjugates obtained by chemoselective ligation between a ionic-complementary self-assembling peptide (called EAK) and three different bioactive molecules: an adhesive sequence with 4 Glycine-Arginine-Glycine-Aspartic Acid-Serine-Proline (GRGDSP) motifs per chain, an adhesive peptide mapped on h-Vitronectin and the growth factor Insulin-like Growth Factor-1 (IGF-1). The mesenchymal stem cell adhesion assays showed a significant increase in adhesion and proliferation for the hydrogels decorated with each of the synthesized conjugates; moreover, such functionalized 3D hydrogels support cell spreading and elongation, validating the use of this class of self-assembly peptides-based material as very promising 3D model scaffolds for cell cultures, at variance of the less realistic 2D ones. Furthermore, small amplitude oscillatory shear tests showed that the presence of IGF-1-conjugate did not alter significantly the viscoelastic properties of the hydrogels even though differences were observed in the nanoscale structure of the scaffolds obtained by changing their composition, ranging from long, well-defined fibers for conjugates with adhesion sequences to the compact and dense film for the IGF-1-conjugate

Volcanogenic particulates and gases from Etna volcano (Italy)

Volcanic emissions represent one of the most relevant natural sources of trace elements to the troposphere. Due to their potential toxicity they may have important environmental impacts from the local to the global scale and they can severely affect the atmospheric and terrestrial environment also at timescales ranging from a few to million years. Etna volcano is known as one of the largest global contributors of magmatic gases (CO2, SO2, and halogens) and particulate matter, including some toxic trace elements. The aim of this study was to characterize the chemical composition and the mineralogical features of the volcanogenic aerosol passively emitted from Mt. Etna. Nine samples were collected by using the filtration technique at different sites on summer 2010 and 2011. Chemical and mineralogical analyses allowed to discriminate two main constituents: the first is mainly referable to the silicate component in the volcanic plume, like lithic and juvenile fragments, crystals (e.g., plagioclases, pyroxenes, oxides) and shards of volcanic glass; the second one is linked to the soluble components like sulfosalts or halide minerals (sulfates, chlorides and fluorides). These investigations are especially important in the study area because the summit of Mt. Etna is yearly visited by nearly one hundred thousand tourists that are exposed to potentially harmful compounds

Chiral Recognition of Flexible Melatonin Receptor Ligands Induced by Conformational Equilibria

N-anilinoethylamides are a class of melatoninergic agents with the aniline portion mimicking the indole ring of the natural ligand and the ethylamide chain reproducing that of melatonin. The simplest compound in this class, N-{2-[(3-methoxyphenyl)methylamino]ethyl}acetamide (UCM793), has nanomolar binding affinity for MT1 and MT2 membrane receptors. To explore the effect of chain conformation on receptor binding, a methyl group was inserted on the methylene alpha or beta to the amide nitrogen and conformational equilibria were investigated by NMR spectroscopy and molecular dynamics simulations. Receptor affinity was conserved only for the beta-methyl derivative, which also showed significant stereoselectivity, with the (S) enantiomer being the eutomer. Molecular dynamics simulations, validated by NMR spectroscopy, showed that the beta-methyl group affects the conformational preferences of the ethylamide chain. Docking into the receptor crystal structure provides a rationale for the observed chiral recognition, suggesting that the (S)-beta-methyl group favors the conformation that better fits the receptor binding site

Elastin-coated biodegradable photopolymer scaffolds for tissue engineering applications

One of the main open issues in modern vascular surgery is the nonbiodegradability of implants used for stent interventions, which can lead to small caliber-related thrombosis and neointimal hyperplasia. Some new, resorbable polymeric materials have been proposed to substitute traditional stainless-steel stents, but so far they were affected by poor mechanical properties and low biocompatibility. In this respect, a new material, polypropylene fumarate (PPF), may be considered as a promising candidate to implement the development of next generation stents, due to its complete biodegradability, and excellent mechanical properties and the ease to be precisely patterned. Besides all these benefits, PPF has not been tested yet for vascular prosthesis, mainly because it proved to be almost inert, while the ability to elicit a specific biological function would be of paramount importance in such critical surgery applications. Here, we propose a biomimetic functionalization process, aimed at obtaining specific bioactivation and thus improved cell-polymer interaction. Porous PPF-based scaffolds produced by deep-UV photocuring were coated by elastin and the functionalized scaffolds were extensively characterized, revealing a stable bound between the protein and the polymer surface. Both 3T3 and HUVEC cell lines were used for in vitro tests displaying an enhancement of cells adhesion and proliferation on the functionalized scaffolds

A Grid-based solution for management and analysis of microarrays in distributed experiments

Several systems have been presented in the last years in order to manage the complexity of large microarray experiments. Although good results have been achieved, most systems tend to lack in one or more fields. A Grid based approach may provide a shared, standardized and reliable solution for storage and analysis of biological data, in order to maximize the results of experimental efforts. A Grid framework has been therefore adopted due to the necessity of remotely accessing large amounts of distributed data as well as to scale computational performances for terabyte datasets. Two different biological studies have been planned in order to highlight the benefits that can emerge from our Grid based platform. The described environment relies on storage services and computational services provided by the gLite Grid middleware. The Grid environment is also able to exploit the added value of metadata in order to let users better classify and search experiments. A state-of-art Grid portal has been implemented in order to hide the complexity of framework from end users and to make them able to easily access available services and data. The functional architecture of the portal is described. As a first test of the system performances, a gene expression analysis has been performed on a dataset of Affymetrix GeneChip® Rat Expression Array RAE230A, from the ArrayExpress database. The sequence of analysis includes three steps: (i) group opening and image set uploading, (ii) normalization, and (iii) model based gene expression (based on PM/MM difference model). Two different Linux versions (sequential and parallel) of the dChip software have been developed to implement the analysis and have been tested on a cluster. From results, it emerges that the parallelization of the analysis process and the execution of parallel jobs on distributed computational resources actually improve the performances. Moreover, the Grid environment have been tested both against the possibility of uploading and accessing distributed datasets through the Grid middleware and against its ability in managing the execution of jobs on distributed computational resources. Results from the Grid test will be discussed in a further paper

A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model

The success of immunotherapeutic approaches strictly depends on the immune cells interaction with cancer cells. While conventional in vitro cell cultures under-represent the complexity and dynamic crosstalk of the tumor microenvironment, animal models do not allow deciphering the anti-tumor activity of the human immune system. Therefore, the development of reliable and predictive preclinical models has become crucial for the screening of immune-therapeutic approaches. We here present an organ-on-chip organ on chips (OOC)-based approach for recapitulating the immune cell Natural Killer (NK) migration under physiological fluid flow, infiltration within a 3D tumor matrix, and activation against neuroblastoma cancer cells in a humanized, fluid-dynamic environment. Circulating NK cells actively initiate a spontaneous "extravasation " process toward the physically separated tumor niche, retaining their ability to interact with matrix-embedded tumor cells, and to display a cytotoxic effect (tumor cell apoptosis). Since NK cells infiltration and phenotype is correlated with prognosis and response to immunotherapy, their phenotype is also investigated: most importantly, a clear decrease in CD16-positive NK cells within the migrated and infiltrated population is observed. The proposed immune-tumor OOC-based model represents a promising approach for faithfully recapitulating the human pathology and efficiently employing the immunotherapies testing, eventually in a personalized perspective. An immune-organ on chip to recapitulate the tumor-mediated infiltration of circulating immune cells within 3D tumor model

Passive degassing at Nyiragongo (D.R. Congo) and Etna (Italy) volcanoes

Volcanoes are well known as an impressive large natural source of trace elements into the troposphere. Etna (Italy) and Nyiragongo (D.R. Congo) are two stratovolcanoes located in different geological settings, both characterized by persistent passive degassing from their summit craters. Here, we present some re-sults on trace element composition in volcanic plume emissions, atmospheric bulk deposition (rainwater) and their uptake by the surrounding vegetation, with the aim to compare and identify differences and sim-ilarities between these two volcanoes. Volcanic emissions were sampled by using active filter-pack for acid gases (sulfur and halogens) and specific teflon filters for particulates (major and trace elements). The im-pact of the volcanogenic deposition in the surrounding of the crater rims was investigated by using differ-ent sampling techniques: bulk rain collectors gauges were used to collect atmospheric bulk deposition, and biomonitoring technique was carried out to collect gases and particulates by using endemic plant species. The estimates of the trace element fluxes confirm that Etna and Nyiragongo are large sources of metals in-to the atmosphere, especially considering their persistent state of passive degassing. The large amount of emitted trace elements has a strong impact on the close surrounding of both volcanoes. This is clearly re-flected by in the chemical composition of rainwater collected at the summit areas both for Etna and Nyira-gongo. Moreover, the biomonitoring results highlight that bioaccumulation of trace elements is extremely high in the proximity of the crater rim and decreases with the distance from the active craters