Search

Nuptial and extranuptial nectaries are involved in interactions with different animal functional groups. Nectar traits involved in pollination mutualisms are well known. However, we know little about those traits involved in other mutualisms, such as ant–plant interactions, especially when both types of nectaries are in the same plant organ, the flower. Here we investigated if when two types of nectaries are exploited by distinct functional groups of floral visitors, even being within the same plant organ, the nectar secreted presents distinct features that fit animal requirements. We compared nectar secretion dynamics, floral visitors and nectar chemical composition of both nuptial and extranuptial nectaries in natural populations of the liana Amphilophium mansoanum (Bignoniaceae). For that we characterized nectar sugar, amino acid and specialized metabolite composition by high-performance liquid chromatography. Nuptial nectaries were visited by three medium- and large-sized bee species and extranuptial nectaries were visited mainly by ants, but also by cockroaches, wasps and flies. Nuptial and extranuptial nectar differed regarding volume, concentration, milligrams of sugars per flower and secretion dynamics. Nuptial nectar was sucrose-dominated, with high amounts of γ-aminobutyric acid and β-aminobutyric acid and with theophylline-like alkaloid, which were all exclusive of nuptial nectar. Whereas extranuptial nectar was hexose-rich, had a richer and less variable amino acid chemical profile, with high amounts of serine and alanine amino acids and with higher amounts of the specialized metabolite tyramine. The nectar traits from nuptial and extranuptial nectaries differ in energy amount and nutritional value, as well as in neuroactive specialized metabolites. These differences seem to match floral visitors’ requirements, since they exclusively consume one of the two nectar types and may be exerting selective pressures on the composition of the respective resources of interest.

Living organisms do not disregard the laws of thermodynamics and must therefore consume energy for their survival. In this way, cellular energy exchanges, which aim above all at the production of ATP, a fundamental molecule used by the cell for its metabolisms, favor the formation of waste products that, if not properly disposed of, can contribute to cellular aging and damage. Numerous genes have been linked to aging, with some favoring it (gerontogenes) and others blocking it (longevity pathways). Animal model studies have shown that calorie restriction (CR) may promote longevity pathways, but given the difficult application of CR in humans, research is investigating the use of CR-mimetic substances capable of producing the same effect. These include some phytonutrients such as oleuropein, hydroxytyrosol, epigallo-catechin-gallate, fisetin, quercetin, and curcumin and minerals such as magnesium and selenium. Some of them also have senolytic effects, which promote the apoptosis of defective cells that accumulate over the years (senescent cells) and disrupt normal metabolism. In this article, we review the properties of these natural elements that can promote a longer and healthier life.

3D cell cultures are in-vitro models representing a significant improvement with respect to traditional monolayers. Their diffusion and applicability, however, are hampered by the complexity of 3D systems, that add new physical variables for experimental analyses. In order to account for these additional features and improve the study of 3D cultures, we here present SALSA (ScAffoLd SimulAtor), a general purpose computational tool that can simulate the behavior of a population of cells cultured in a 3D scaffold. This software allows for the complete customization of both the polymeric template structure and the cell population behavior and characteristics. In the following the technical description of SALSA will be presented, together with its validation and an example of how it could be used to optimize the experimental analysis of two breast cancer cell lines cultured in collagen scaffolds. This work contributes to the growing field of integrated in-silico/in-vitro analysis of biological systems, which have great potential for the study of complex cell population behaviours and could lead to improve and facilitate the effectiveness and diffusion of 3D cell culture models.

L’évolution des loisirs nocturnes a été explorée dans sa relation avec les processus de déréglementation des activités commerciales et avec des évolutions des modes de vie. Cependant, le rôle joué par les transformations dans la production de la matérialité de la ville, et en particulier de l’espace public, reste relativement peu interrogé. À partir des cas de Montpellier et de Lisbonne, cet article montre que les conflictualités associées au développement des loisirs nocturnes relèvent de plusieurs impensés et ambiguïtés dans la prise en compte des usages et de leurs temporalités dans la production urbaine, notamment des espaces publics. Ce faisant, l’article montre comment la nuit peut être un espace-temps privilégié pour analyser certaines des ambi- guïtés et contradictions qui caractérisent les politiques de revitalisation des centres historiques des villes européennes.

L’appropriation de la nuit urbaine par des activités économiques, sociales et culturelles a connu au XXe siècle une accélération sans précédent. L’intérêt croissant des sciences sociales pour cet objet de recherche a permis de mieux connaître les dyna- miques caractérisant l’évolution de l’espace-temps nocturne dans les différentes parties du globe. Cette introduction souligne la nécessité de poursuivre l’exploration de cet espace-temps complexe. Ce numéro, en réunissant des contributions de différentes disciplines et sur des régions géographiques variées, propose de lier tendances globales et spécificités locales qui (re)configurent la nuit urbaine dans la ville contemporaine. Les apports de ces contributions sont présentés et articulés autour de quatre axes : lieux et usages différenciés des pratiques nocturnes, attractivité et conflits, inégalités nocturnes, méthodologies des enquêtes sur la nuit.

3D printing has opened exciting new opportunities for the in vitro fabrication of biocompatible hybrid pseudo-tissues. Technologies based on additive manufacturing herald a near future when patients will receive therapies delivering functional tissue substitutes for the repair of their musculoskeletal tissue defects. In particular, bone tissue engineering (BTE) might extensively benefit from such an approach. However, designing an optimal 3D scaffold with adequate stiffness and biodegradability properties also guaranteeing the correct cell adhesion, proliferation, and differentiation, is still a challenge. The aim of this work was the rewiring of a commercial fuse deposition modeling (FDM) 3D printer into a 3D bioplotter, aiming at obtaining scaffold fiber thickness and porosity control during its manufacturing. Although it is well-established that FDM is a fast and low-price technology, the high temperatures required for printing lead to limitations in the biomaterials that can be used. In our hands, modifying the printing head of the FDM device with a custom-made holder has allowed to print hydrogels commonly used for embedding living cells. The results highlight a good resolution, reproducibility and repeatability of alginate/gelatin scaffolds obtained via our custom 3D bioplotter prototype, showing a viable strategy to equip a small-medium laboratory with an instrument for manufacturing good-quality 3D scaffolds for cell culture and tissue engineering applications.

Objective. 3D cell cultures are becoming a fundamental resource for in-vitro studies, as they mimic more closely in-vivo behavior. The analysis of these constructs, however, generally rely on destructive techniques, that prevent the monitoring over time of the same construct, thus increasing the results variability and the resources needed for each experiment. Approach. In this work, we focus on mineralization, a crucial process during maturation of artificial bone models, and propose electrical impedance tomography (EIT) as an alternative non-destructive approach. In particular, we discuss the development of an integrated hardware/software system capable of acquiring experimental data from 3D scaffolds and reconstructing the corresponding conductivity maps. We also show how the same software can test how the measurement is affected by biological features such as scaffold shrinking during the culture. Main results. An initial validation, comprising the acquisition of both a non- conductive phantom and alginate/gelatin scaffolds with known calcium content will be presented, together with the in-silico study of a cell-induced mineralization process. This analysis will allow for an initial verification of the systems functionality while limiting the effects of biological variability due to cell number and activity. Significance. Our results show the potential of EIT for the non-destructive quantification of matrix mineralization in 3D scaffolds, and open to the possible long term monitoring of this fundamental hallmark of osteogenic differentiation in hybrid tissue engineered constructs.

Publisher's version (útgefin grein), The availability of engineered biological tissues holds great potential for both clinical applications and basic research in a life science laboratory. A prototype standalone perfusion/compression bioreactor system was proposed to address the osteogenic commitment of stem cells seeded onboard of 3D chitosan-graphene (CHT/G) templates. Testing involved the coordinated administration of a 1 mL/min medium flow rate together with dynamic compression (1% strain at 1 Hz; applied twice daily for 30 min) for one week. When compared to traditional static culture conditions, the application of perfusion and compression stimuli to human bone marrow stem cells using the 3D CHT/G template scaffold induced a sizable effect. After using the dynamic culture protocol, there was evidence of a larger number of viable cells within the inner core of the scaffold and of enhanced extracellular matrix mineralization. These observations show that our novel device would be suitable for addressing and investigating the osteogenic phenotype commitment of stem cells, for both potential clinical applications and basic research., "Peer Reviewed"

Tissue engineering strategies can be relevant for cartilage repair and regeneration. A collagen matrix was functionalized with the addition of poly-lactic-co-glycolic acid microcarriers (PLGA-MCs) carrying a human Transforming Growth Factor β1 (hTFG-β1) payload, to provide a 3D biomimetic environment with the capacity to direct stem cell commitment towards a chondrogenic phenotype. PLGA-MCs (mean size 3 ± 0.9 μm) were prepared via supercritical emulsion extraction technology and tailored to sustain delivery of payload into the collagen hydrogel for 21 days. PLGA-MCs were coseeded with human Bone Marrow Mesenchymal Stem Cells (hBM-MSCs) in the collagen matrix. Chondrogenic induction was suggested when dynamic perfusion was applied as indicated by transcriptional upregulation of COL2A1 gene (5-fold, p &lt, 0.01) and downregulation of COL1A1 (0.07-fold, 0.05) and COL3A1 (0.11-fold, 0.05) genes, at day 16, as monitored by qRT-PCR. Histological and quantitative-immunofluorescence (qIF) analysis confirmed cell activity by remodeling the synthetic extracellular matrix when cultured in perfused conditions. Static constructs lacked evidence of chondrogenic specific gene overexpression, which was probably due to a reduced mass exchange, as determined by 3D system Finite Element Modelling (FEM) analysis. Proinflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokine gene expression by hBM-MSC was observed only in dynamic culture (TNF and IL-1β 10-fold, p &lt, 0.001, TGF-β1 4-fold, p &lt, 0.01 at Day 16) confirming the cells’ immunomodulatory activity mainly in relation to their commitment and not due to the synthetic environment. This study supports the use of 3D hydrogel scaffolds, equipped for growth factor controlled delivery, as tissue engineered models for the study of in vitro chondrogenic differentiation and opens clinical perspectives for injectable collagen-based advanced therapy systems.

Conventional 2D cell culture, a traditional tool in pre-clinical studies, can hardly be regarded as a representation of a natural cell microenvironment. In this respect, it might result in altered cellular behaviors. To overcome such a limitation, different approaches have been tested to conduct more representative in vitro studies. In particular, the use of 3D cell culture introduces variables, such as cell-cell and cell-extracellular matrix interactions; cell features such as survival, proliferation and migration are consequently influenced. For an example, an enhanced drug resistance and increased invasiveness are shown by cancer cells when cultured in 3D versus 2D conventional culture models. In this setting however, non-uniform cell distribution and biological behaviors appear throughout the scaffold, due to reduced diffusion of oxygen and nutrients. Perfusion in bioreactor systems can be used to improve medium transport. In this line of reasoning, this study proposes a breast cancer cell culture model sustained by an integrated approach that couples a 3D environment and a fluid perfusion. This model improves viability and uniformness of cell distribution, while inducing morphological, functional and molecular cancer cell remodeling.

The present work described a bio-functionalized 3D fibrous construct, as an interactive teno-inductive graft model to study tenogenic potential events of human mesenchymal stem cells collected from Wharton’s Jelly (hWJ-MSCs). The 3D-biomimetic and bioresorbable scaffold was functionalized with nanocarriers for the local controlled delivery of a teno-inductive factor, i.e., the human Growth Differentiation factor 5 (hGDF-5). Significant results in terms of gene expression were obtained. Namely, the up-regulation of Scleraxis (350-fold, p ≤ 0.05), type I Collagen (8-fold), Decorin (2.5-fold), and Tenascin-C (1.3-fold) was detected at day 14, on the other hand, when hGDF-5 was supplemented in the external medium only (in absence of nanocarriers), a limited effect on gene expression was evident. Teno-inductive environment also induced pro-inflammatory, (IL-6 (1.6-fold), TNF (45-fold, p ≤ 0.001), and IL-12A (1.4-fold)), and anti-inflammatory (IL-10 (120-fold) and TGF-β1 (1.8-fold)) cytokine expression upregulation at day 14. The presented 3D construct opens perspectives for the study of drug controlled delivery devices to promote teno-regenerative events.

Purpose The aim of this study was to evaluate the effects exerted over chondrogenic commitment of human adipose-derived mesenchymal stem cells (ADSCs) by a very low oxygen tension ( Materials/methods Cell morphology, mRNA levels of chondrocyte-specific marker genes and the involvement of p38 MAPK signalling were monitored in human ADSCs under a very low oxygen tension. Results Cell morphology was significantly changed after two days of hypoxic preconditioning when they featured as elongated spindle-shaped cells. SRY-box containing gene 9, aggrecan and collagen type II mRNA levels were enhanced under severe hypoxic culture conditions. Moreover, the inhibition of p38 MAPK resulted in a substantial reduction in transcription of the above-mentioned specific genes, proving the pivotal role of this pathway in the transcriptional regulation of chondrogenesis. Conclusions Here, we propose a protocol showing the early commitment of stem cells towards the chondrogenic phenotype in only 2 days of culture via a very low hypoxic environment, in the absence of growth factors added in the culture medium.

A series of hybrid compounds was designed to target histone deacetylases and ds-/G-quadruplex DNAs by merging structural features deriving from Scriptaid and compound 1. Compound 6 binds different DNA arrangements, inhibits HDACs both in vitro and in cells, and is able to induce a reduction of cell proliferation. Moreover, compound 6 displays cell phenotype-reprogramming properties since it prevents the epithelial to mesenchymal transition in cancer cells, inducing a less aggressive and migratory phenotype, which is one of the goals of present innovative strategies in cancer therapies.

International audience; This paper explores the relations between nocturnal practices, their negative impacts and the regulation, design and planning of public spaces. Focusing on the case of Montpellier and Bologna, two cities that have experienced the rise of several nightlife-related problems, it analyzes the variety of measures and regulations adopted by local administrations and their impacts. It suggests that the “disciplinary” approach adopted by these cities, that consider nightlife-related conflicts a problem of public order connected to excessive behaviors, often associated to alcohol consumption in the public space, has limited or even counterproductive results. A more structural action that takes into account the urban night in both urban policies and planning is needed to effectively tackle the night-time economy’s negative impacts. This implies to fully consider how the physical, social and cultural dimensions of public spaces influence night-time practices.; Cet article explore les relations qui existent entre les pratiques nocturnes, leurs impacts négatifs et la régulation, la planification et l’aménagement des espaces publics. En se concentrant sur les cas de Montpellier et de Bologne, deux villes qui ont connu une augmentation des problèmes liés à la vie nocturne, il analyse les mesures et réglementations adoptées par les administrations locales et leurs impacts. Il suggère que l'approche «disciplinaire» adoptée par ces villes, qui considèrent les conflits produits par la vie nocturne comme un problème d'ordre public lié à des comportements excessifs, souvent associés à la consommation d'alcool dans l'espace public, a des résultats limités, voire contre-productifs. Une action plus structurelle prenant en compte la nuit urbaine dans les politiques urbaines et la planification est nécessaire pour réduire efficacement les impacts négatifs de l'économie nocturne. Cela implique de prendre pleinement en compte l'influence des dimensions physiques, sociales et culturelles des espaces publics sur les pratiques nocturnes.

Epithelial to mesenchymal transition (EMT) is a complex biological process that plays a key role in cancer progression and metastasis formation. Its activation results in epithelial cells losing adhesion and polarity and becoming capable of migrating from their site of origin. At this step the disease is generally considered incurable. As EMT execution involves several individual molecular components, connected by nontrivial relations, in vitro techniques are often inadequate to capture its complexity. Computational models can be used to complement experiments and provide additional knowledge difficult to build up in a wetlab. Indeed in silico analysis gives the user total control on the system, allowing to identify the contribution of each independent element. In the following, two kinds of approaches to the computational study of EMT will be presented. The first relies on signal transduction networks description and details how changes in gene expression could influence this process, both focusing on specific aspects of the EMT and providing a general frame for this phenomenon easily comparable with experimental data. The second integrates single cell and population level descriptions in a multiscale model that can be considered a more accurate representation of the EMT. The advantages and disadvantages of each approach will be highlighted, together with the importance of coupling computational and experimental results. Finally, the main challenges that need to be addressed to improve our knowledge of the role of EMT in the neoplastic disease and the scientific and translational value of computational models in this respect will be presented. This article is categorized under: Analytical and Computational Methods > Computational Methods.

In this study, we explore the behaviour of intracellular magnesium during bone phenotype modulation in a 3D cell model built to mimic osteogenesis. In addition, we measured the amount of magnesium in the mineral depositions generated during osteogenic induction. A two-fold increase of intracellular magnesium content was found, both at three and seven days from the induction of differentiation. By X-ray microscopy, we characterized the morphology and chemical composition of the mineral depositions secreted by 3D cultured differentiated cells finding a marked co-localization of Mg with P at seven days of differentiation. This is the first experimental evidence on the presence of Mg in the mineral depositions generated during biomineralization, suggesting that Mg incorporation occurs during the bone forming process. In conclusion, this study on the one hand attests to an evident involvement of Mg in the process of cell differentiation, and, on the other hand, indicates that its multifaceted role needs further investigation.

Cisplatin-pemetrexed is a frequently adopted first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) ineligible for biological therapy, notwithstanding its limited efficacy. In the present study, the RAL cell line, an epidermal growth factor receptor (EGFR)-wild-type, p53- and KRAS-mutated model of NSCLC, was used to investigate novel biomarkers of resistance to this treatment. Cells were analyzed 96 h (96 h-post wo) and 21 days (21 days-post wo) after the combined treatment washout. Following an initial moderate sensitivity to the treatment, the cell growth proliferative capability had fully recovered. Gene expression analysis of the resistant surviving cells revealed a significant upregulation of CDKN1A expression in the cells at 96-h post-wo and, although to a lesser extent, in the cells at 21 days-post wo, accompanied by an enrichment of acetylated histone H3 in its promoter region. CDKN1A was also upregulated at the protein level, being mainly detected in the cytoplasm of the cells at 96 h-post wo. A marked increase in the number of apoptotic cells, together with a significant G1 phase block, were observed at 96-h post wo in the cells in which CDKN1A was knocked down, suggesting its involvement in the modulation of the response of RAL cells to the drug combination. On the whole, these data suggest that CDKN1A plays a role in the response to the cisplatin-pemetrexed combination in advanced KRAS-mutated NSCLC, thus suggesting that it may be used as a promising predictive marker.

At present, injuries or rupture of tendons are treated by surgical repair or conservative approaches with unpredictable clinical outcome. Alternative strategies to repair tendon defects without the undesirable side effects associated with the current options are needed. With this in mind, a tissue engineering approach has gained considerable attention as a promising strategy. Here we investigated a synthetic three-dimensional (3D) microenvironment able to interact with stem cells and inducing, via coupled biochemical and physical signals, their early commitment toward the tenogenic lineage. This multiphase 3D construct consisted of a braided hyaluronate elastic band merged with human bone marrow mesenchymal stem cells (hBMSCs) and poly-lactic-co-glycolic acid microcarriers loaded with human growth differentiation factor 5 (hGDF-5) by means of fibrin hydrogel. The multiphase structure allowed hBMSC culture under cyclic strain within a microenvironment where a controlled amount of hGDF-5 was regularly delivered. The cooperative biochemical and physical stimuli induced significantly increased expression of tenogenic markers, such as collagen type I and III, decorin, scleraxis, and tenascin-C, within only 3 days of dynamic hBMSC culture. This approach opens exciting perspectives for future development of engineered tendon tissue substitutes.

The article questions the construction and perceptions related to the lighting project « Ruta de los Rios de Luz » developed in the Spanish city of Valladolid. Adopting a performative approach to the visual experience, the article searches beyond the traditional vision of a relationship between visual experience and nightscape lighting mainly designed for a quality of seduction. Instead, superposition of different research methodologies helps to reveal a more complex visual experience of this lightscape, varied and multifaceted. This approach provides new perspectives on the performative and relational qualities of everyday engagement with urban aesthetics.

Cell-based in vitro biological models traditionally use monolayer cell cultures grown over plastic surfaces bathing in static media. Higher fidelity to a natural biological tissue is expected to result from growing the cells in a three-dimensional (3D) matrix. However, due to the decreased rate of diffusion inherent to increased distances within a tridimensional space, proper fluidic conditions are needed in this setting to better approximate a physiological environment. To this aim, we here propose a prototypal dynamic cell culture platform for the automatic medium replacement, via periodic perfusion flow, in a human umbilical vein endothelial cell (HUVECs) culture seeded in a Geltrex (TM) matrix. A state-of-the-art angiogenesis assay performed in these dynamic conditions showed sizable effects with respect to conventional static control cultures, with significantly enhanced pro-(dual antiplatelet therapy [DAPT]) and anti-(EDTA) angiogenic compound activity. In particular, dynamic culture conditions (a) enhance the 3D-organization of HUVECs into microtubule structure; (b) accelerate and improve endothelial tube formation by HUVECs in the presence of DAPT; (c) are able to completely revert the blocking effects of EDTA. These evidence emphasize the need of setting proper fluidic conditions for a better approximation of a physiological environment as an appropriate evolution of current cell culture paradigms.

Mesenchymal stem cells (MSC) have piqued worldwide interest for their extensive potential to treat a large array of clinical indications, their unique and controversial immunogenic and immune modulatory properties allowing ample discussions and debates for their possible applications. Emerging data demonstrating that the interaction of biomaterials and physical cues with MSC can guide their differentiation into specific cell lineages also provide new interesting insights for further MSC manipulation in different clinical applications. Moreover, recent discoveries of some regulatory molecules and signaling pathways in MSC niche that may regulate cell fate to distinct lineage herald breakthroughs in regenerative medicine. Although the advancement and success in the MSC field had led to an enormous increase in the amount of ongoing clinical trials, we still lack defined clinical therapeutic protocols. This review will explore the exciting opportunities offered by human and animal MSC, describing relevant biological properties of these cells in the light of the novel emerging evidence mentioned above while addressing the limitations and challenges MSC are still facing.

To engineer functional tissue substitutes, it is required a multi-component, multi-scale approach that combines both physical, chemical and biological cues. Fiber-based techniques have been explored in the field of tissue engineering to produce structures recapitulating tissue architecture and mechanical properties. In this work, we engineered biofunctional composite living fibers (CLF) as multi-compartment fibers with a mechanically competent core and a hydrogel layer. For this purpose, commercial silk suture threads were coated with a platelet lysate (PL) hydrogel by first embedding the threads in a thrombin solution and then incubating in PL. The fabrication set-up was optimized and the biological performance was studied by encapsulating human adipose-derived stem cells (hASCs). The developed coating process rendered CLF with a homogenous PL hydrogel layer covering suture threads. Encapsulated hASCs were viable up to 14 days in culture and were able to align at the surface of the core fiber and deposit collagen types I and III. In summary, the study shows that PL-hASCs hydrogel coated suture threads represent a simple multi-compartment and multifunctional system, with PL hydrogel offering biofunctionality to guide the biological activities of encapsulated cells in addition to the replication of tissue-level mechanical support provided by the suture threads., Work developed under the framework of the Cooperation Agreement established with the Serviço de Imuno-Hemoterapia do Centro Hospitalar de S. João, EPE. The authors would like to thank to the Plastic Surgery Department of Hospital da Prelada (Porto, Portugal) for providing lipoaspirate tissue samples. Authors acknowledge the financial support from the ERC Grant CoG MagTendon nr 772817; and the Project NORTE-01-0145-FEDER-000021 (RCA pos-doc grant): “Accelerating tissue engineering and personalized medicine discoveries by the integration of key enabling nanotechnologies, marine-derived biomaterials and stem cells”, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); FCT–Fundação para a Ciência e a Tecnologia for the PhD grant of IC (PD/BD/128088/2016) and pos-doc grant of RMAD (SFRH/BPD/112459/2015); and HORIZON 2020 under the TEAMING Grant agreement No 739572 - The Discoveries CTR. R.A. was the recipient of a scholarship from the School of Engineering of the University of Bologna (Italy).

Computational models constitute a fundamental asset for cancer research and drug R & D , as they provide controlled environments for testing of hypotheses and are characterized by the total knowledge of the system. These features are particularly useful for 3D cell culture models where a complex interaction among cells and their environments ensues. In this work, we present a programmable simulator capable of reproducing the behavior of cells cultured in 3D scaffolds and their response to pharmacological treatment. This system will be shown to be able to accurately describe the temporal evolution of the density of a population of MDA-MB-231 cells following their treatment with different concentrations of doxorubicin, together with a newly described drug-resistance mechanism and potential re-sensitization strategy. An extensive technical description of this model will be coupled to its experimental validation and to an analysis aimed at identifying which variables and behaviors account for differences in the response to treatment. Comprehensively, this work contributes to the growing field of integrated in-silico/in-vitro analysis of biological processes which has great potential for both the increase of our scientific knowledge and the development of novel, more effective treatments.

We developed a (three-dimensional) 3D scaffold, we named HY-FIB, incorporating a force-transmission band of braided hyaluronate embedded in a cell localizing fibrin hydrogel and poly-lactic-co-glycolic acid (PLGA) nanocarriers as transient components for growth factor controlled delivery. The tenogenic supporting capacity of HY-FIB on human-Bone Marrow Mesenchymal Stem Cells (hBM-MSCs) was explored under static conditions and under bioreactor-induced cyclic strain conditions. HY-FIB elasticity enabled to deliver a mean shear stress of 0.09 Pa for 4 h/day. Tendon and cytokine marker expression by hBM-MSCs were studied. Results: hBM-MSCs embedded in HY-FIB and subjected to mechanical stimulation, resulted in a typical tenogenic phenotype, as indicated by type 1 Collagen fiber immunofluorescence. RT-qPCR showed an increase of type 1 Collagen, scleraxis, and decorin gene expression (3-fold, 1600-fold, and 3-fold, respectively, at day 11) in dynamic conditions. Cells also showed pro-inflammatory (IL-6, TNF, IL-12A, IL-1&beta, ) and anti-inflammatory (IL-10, TGF-&beta, 1) cytokine gene expressions, with a significant increase of anti-inflammatory cytokines in dynamic conditions (IL-10 and TGF-&beta, 1 300-fold and 4-fold, respectively, at day 11). Mechanical signaling, conveyed by HY-FIB to hBM-MSCs, promoted tenogenic gene markers expression and a pro-repair cytokine balance. The results provide strong evidence in support of the HY-FIB system and its interaction with cells and its potential for use as a predictive in vitro model.

Poly-lactic-co-glycolic acid (PLGA) microcarriers (0.8 ± 0.2 μm) have been fabricated with a load of 20 μg/gPLGA by an emulsion-based-proprietary technology to sustained deliver human bone morphogenetic protein 2 (hBMP2), a growth factor largely used for osteogenic induction. hBMP2 release profile, measured in vitro, showed a moderate "burst" release of 20% of the load in first 3 days, followed by a sustained release of 3% of the load along the following 21 days. PLGA microbeads loaded with fluorescent marker (8 mg/gPLGA ) and hydroxyapatite (30 mg/gPLGA ) were also fabricated and successfully dispersed within three-dimensional (3D) alginate scaffold (Ca-alginate 2% wt/wt) in a range between 50 and 200 mg/cm3 ; the presence of microcarriers within the scaffold induced a variation of its stiffness between 0.03 and 0.06 MPa; whereas the scaffold surface area was monitored always in the range of 190-200 m2 /g. Uniform microcarriers dispersion was obtained up to 200 mg/cm3 ; higher loading values in the 3D scaffold produced large aggregates. The release data and the surface area were, then, used to simulate by finite element modeling the hBMP2 mass transfer within the 3D hydrogel bioengineered with stem cells, in dynamic and static cultivations. The simulation was developed with COMSOL Multiphysics® giving a good representation of hBMP2 mass balances along microbeads (bulk eroded) and on cell surface (cell binding). hBMP2 degradation rate was also taken into account in the simulations. hBMP2 concentration of 20 ng/cm3 was set as a target because it has been described as the minimum effective value for stem cells stimulation versus the osteogenic phenotype. The sensitivity analysis suggested the best microbeads/cells ratio in the 3D microenvironment, along 21 days of cultivations in both static and dynamic cultivation (perfusion) conditions. The simulated formulation was so assembled experimentally using human mesenchymal stem cells and an improved scaffold stiffness up to 0.09 MPa (n = 3; p ≤ 0.01) was monitored after 21 days of cultivation; moreover a uniform extracellular matrix deposition within the 3D system was detected by Von Kossa staining, especially in dynamic conditions. The results indicated that the described tool can be useful for the design of 3D bioengineered microarchitecture by quantitative understanding.

A series of random poly(butylene succinate)-based copolymers, (poly(butylene/triethylene succinate) (P(BSmTESn)), containing ether-oxygen atoms were successfully synthesized by melt polycondensation of succinic acid and 1,4-butanediol in the presence of triethylene glycol (TEG) (TEG content up to 40 mol %). The copolymers were characterized from the molecular, thermal, structural and mechanical point of view. Hydrolytic degradation studies were performed under physiological conditions. The biocompatibility of the samples under investigation through indirect and direct biocompatibility studies was investigated by using embryonic rat cardiac H9c2 cells. To evaluate the potential of these polymers also for controlled drug delivery systems, the diffusion profile of Dexamethasone, an anti-inflammatory drug, through nanoparticles prepared by oil-in-water miniemulsion process was investigated. Results showed that solid-state properties could be tailored nicely by simply varying copolymer composition. Crystallinity degree and hydrophobicity significantly decreased with the increase of triethylene succinate co-unit (TES) mol%. Moreover, hydrolytic degradation of PBS, depending on polymer crystallinity degree and hydrophilicity, was remarkably improved: the copolymer containing 40 mol% of triethylene succinate co-unit after 200 days lost over 22% of its initial weight. The newly developed biomaterials showed lack of cell cytotoxicity. Among them, PBS and the copolymers containing up to 20 mol% of TES co-units sustained a better cell adhesion and proliferation. In addition, such copolymers induced muscle phenotype commitment in H9c2 cells cultured onboard. Lastly, the release profile of Dexamethasone obeyed to a first order kinetic law, the copolymer richest in TES co-unit content showing the highest encapsulation capability and the fastest drug release kinetics. Anyway, PBS and the copolymers containing up to 20 mol% of TES co-unis sustained a better cell adhesion and proliferation, with the copolymers characterized by a myosin heavy chain expression, which appeared to be up to twofold increased on respect to the one of PBS homopolymer. (C) 2018 Elsevier Ltd. All rights reserved.

International audience; 1. INTRODUZIONE.-Negli ultimi decenni l'organizzazione e la visione della notte urbana nel mondo occidentale sono cambiate radicalmente. Tradizionalmente tempo rappresentato come morto e vuoto, oggi la notte, almeno nella sua prima parte, è animata da un numero crescente di pratiche economiche, sociali e culturali, tanto da far parlare alcuni autori di una "diurnificazione" della temporalità notturna (Gwiazdzinski, 2002) o di una "notturnalizzazione" della società. In realtà la tradizionale immagine della notte come temporalità caratterizzata da un'attività umana molto ridotta non è storicamente esatta avendo questo pro-cesso origini antiche. Diversi storici ne hanno fatto risalire le origini alla fine del XVII secolo a seguito della comparsa delle prime forme organizzate di illumina-zione pubblica (Schivelbusch, 1993; Cabantous, 2009; Delattre, 2004). Tuttavia è indubbio che negli ultimi decenni questo fenomeno abbia conosciuto un'accelera-zione senza precedenti (Gwiazdzinski, 2007). La notte è divenuta progressivamente parte dell'esperienza quotidiana della maggior parte della popolazione. In Francia, secondo un'inchiesta realizzata nel 2004, una persona su quattro esce la notte al-meno una volta alla settimana e solamente il 20% non lo fa mai, contro il 67% del 1973. Anche i ritmi circadiani della popolazione subiscono progressivamente delle variazioni. Secondo i dati dell'ISTAT, oggigiorno gli italiani vanno in media a letto mezz'ora più tardi che nel 1988 (Boffi et al., 2015). Questi cambiamenti hanno pro-fondamente rivoluzionato la maniera in cui la notte urbana è vissuta, consumata, governata e pensata tanto che la stessa definizione dei limiti temporali della notte è oggetto di discussione (Gwiazdzinski, 2007; Bromley et al., 2003; Rowe e Bavinton, 2011). Queste trasformazioni hanno attirato l'attenzione di ricercatori di diverse discipline. Un nuovo campo di ricerca, quello dei night studies, è progressivamente emerso, riunendo, tra gli altri, storici, geografi, urbanisti, sociologi, biologi, eco-nomisti, filosofi e antropologi (Boffi et al., 2015; Roberts e Eldridge, 2009; Talbot, 2007). In questo contesto le prospettive geografiche e spaziali hanno giocato un ruolo fondamentale. La notte urbana è divenuta un tema emergente nella letteratura geografica in lingua inglese (Roberts e Eldridge, 2009; van Liempt et al., 2015), francese (Gwiazdzinski, 2005, 2007; Espinasse et al., 2005), spagnola (Nofre, 2008) e tedesca (Schwegmann, 2016), e l'insieme di questi studi ha permesso di analiz-zare in diversi contesti spazio-temporali le dinamiche e gli effetti prodotti dalla crescente importanza assunta dalla temporalità notturna. Seppur con un certo ri

Graphene-based materials are the focus of intense research efforts to devise novel theranostic strategies for targeting the central nervous system. In this work, we have investigated the consequences of long-term exposure of primary rat astrocytes to pristine graphene (GR) and graphene oxide (GO) flakes. We demonstrate that GR/GO interfere with a variety of intracellular processes as a result of their internalization through the endo-lysosomal pathway. Graphene-exposed astrocytes acquire a more differentiated morphological phenotype associated with extensive cytoskeletal rearrangements. Profound functional alterations are induced by GO internalization, including the upregulation of inward-rectifying K+ channels and of Na+-dependent glutamate uptake, which are linked to the astrocyte capacity to control the extracellular homeostasis. Interestingly, GO-pretreated astrocytes promote the functional maturation of co-cultured primary neurons by inducing an increase in intrinsic excitability and in the density of GABAergic synapses. The results indicate that graphene nanomaterials profoundly affect astrocyte physiology in vitro, with consequences for neuronal network activity. This work supports the view that GO-based materials could be of great interest to address pathologies of the central nervous system associated to astrocyte dysfunctions., Comment: This document is the unedited Author's version of a Submitted Work that was subsequently accepted for publication in Nano Letters. To access the final edited and published work see https://pubs.acs.org/articlesonrequest/AOR-wvjrggcBp7kC8NwEImXr

International audience; In Barceloneta, one of the beachfront quarters of the city of Barcelona, the rapid expansion of illegal short-term rental apartments for tourists and noise problems related to both alcohol-fuelled nightlife consumption, are challenging community liveability and peaceful urban coexistence between different social groups. Similarly to other worldwide cases, the rapid expansion of touristification on the urban and socio-economic fabric of the city has increasingly become a source of dispute and residents' contestation. By taking a diachronical critical review, the first part of the text examines the role of urban planning developed in Barceloneta during the period 1950-2016 in transforming the quarter into a leisure-oriented, tourist-oriented quarter. The second part of the paper is based on a a 2-year ethnographic fieldwork that was conducted to capture the range of different voices, stories and discourses produced and reproduced by different actors affected and/or involved in the recent touristification of Barceloneta. Findings obtained confirm that current urban policy and planning are clearly insufficient to tackle and address negative community-based impacts aforementioned. Hence the final section highligts the urgent need for the development and implementation of a new community-based urban planning with the aim of ensuring community liveability and peaceful urban coexistence between different social groups in Barceloneta.

International audience; Practices of outdoor illumination have dramatically changed in the last decades as functional lighting has progressively given way to a more qualitative vision of light. Its traditional role for security purposes has been progressively matched by the use of illumination for city beautification. This is now a major consideration for new lighting strategies. As a result, a growing number of European cities explicitly include the development of nocturnal tourism among the objectives of their lighting policies. However, little attention has been paid by academic research to this growing trend. Focusing on the internationally renowned lighting project " Ruta de los Rios de Luz " this research paper explores the use of lighting design for tourism purposes. Through interviews with individuals who played an important role in the project, the discussion below scrutinizes the lighting design decisions and the economic, environmental and political objectives that inspire the growing utilization of spectacular forms of illumination for tourism purposes.