Cell migration on material-driven fibronectin microenvironments

Cell migration is a fundamental process involved in a wide range of biological phenomena. However, how the underlying mechanisms that control migration are orchestrated is not fully understood. In this work, we explore the migratory characteristics of human fibroblasts using different organisations of fibronectin (FN) triggered by two chemically similar surfaces, poly(ethyl acrylate) (PEA) and poly(methyl acrylate) (PMA); cell migration is mediated via an intermediate layer of fibronectin (FN). FN is organised into nanonetworks upon simple adsorption on PEA whereas a globular conformation is observed on PMA. We studied cell speed over the course of 24 h and the morphology of focal adhesions in terms of area and length. Additionally, we analysed the amount of cell-secreted FN as well as FN remodelling. Velocity of human fibroblasts was found to exhibit a biphasic behaviour on PEA, whereas it remained fairly constant on PMA. FA analysis revealed more mature focal adhesions on PEA over time contrary to smaller FAs found on PMA. Finally, human fibroblasts seemed to remodel adsorbed FN more on PMA than on PEA. Overall, these results indicate that the cell–protein–material interface affects cell migratory behaviour. Analysis of FAs together with FN secretion and remodelling were associated with differences in cell velocity providing insights into the factors that can modulate cell motility

Semiclassical and quantum Liouville theory

We develop a functional integral approach to quantum Liouville field theory completely independent of the hamiltonian approach. To this end on the sphere topology we solve the Riemann-Hilbert problem for three singularities of finite strength and a fourth one infinitesimal, by determining perturbatively the Poincare' accessory parameters. This provides the semiclassical four point vertex function with three finite charges and a fourth infinitesimal. Some of the results are extended to the case of n finite charges and m infinitesimal. With the same technique we compute the exact Green function on the sphere on the background of three finite singularities. Turning to the full quantum problem we address the calculation of the quantum determinant on the background of three finite charges and of the further perturbative corrections. The zeta function regularization provides a theory which is not invariant under local conformal transformations. Instead by employing a regularization suggested in the case of the pseudosphere by Zamolodchikov and Zamolodchikov we obtain the correct quantum conformal dimensions from the one loop calculation and we show explicitly that the two loop corrections do not change such dimensions. We then apply the method to the case of the pseudosphere with one finite singularity and compute the exact value for the quantum determinant. Such results are compared to those of the conformal bootstrap approach finding complete agreement.Comment: 12 pages, 1 figure, Contributed to 5th Meeting on Constrained Dynamics and Quantum Gravity (QG05), Cala Gonone, Sardinia, Italy, 12-16 Sep 200

Graph clustering and portable X-Ray Fluorescence: An application for in situ, fast and preliminary classification of transport amphoras

In the last decade, numerous papers have been delivered on the potential of portable X-Ray Fluorescence (XRF) in archaeological ceramics. Additionally, new chemometric methods have been proposed to manage chemical dataset and facilitate the use of geochemical discrimination for provenance classification of ancient ceramics. In this contribute, the potential of portable Energy Dispersive X-Ray Fluorescence (ED-XRF) analysis and chemical data processing by Graph Clustering is evaluated for provenance classification of archaeological potteries, discussing possible merits and limits of the employed routine. A ceramic assemblage represented by seventy-three transport amphorae classified by typological analysis have been used as testing materials; spectra have been collected on samples simulating in situ analysis conditions (e.g. on fresh cut surfaces without any preparation) and Graph Clustering method has been applied in chemical data processing; comparison with classical Cluster Analysis (CA) and Principal Component Analysis (PCA) is also evaluated. The obtained results favor the use of Graph Clustering for a preliminary classification of ceramics, which can be chemically analyzed in easy, fast and non-destructive way. With a 75.35% of correct attribution, the study shows the suitability of portable ED-XRF in rapid screening of a large number of ceramic samples usually recovered in the framework of archaeological excavation. Misclassifications have been mostly verified for samples exhibiting a coarse-grained clay paste, suggesting that the method is particularly suitable for fine-grained ceramic materials

Duration of remission after halving of the etanercept dose in patients with ankylosing spondylitis: a randomized, prospective, long-term, follow-up study

Fabrizio Cantini, Laura Niccoli, Emanuele Cassarà, Olga Kaloudi, Carlotta NanniniDivision of Rheumatology, Misericordia e Dolce Hospital, Prato, ItalyBackground: The aim of this study was to evaluate the proportion of patients with ankylosing spondylitis maintaining clinical remission after reduction of their subcutaneous etanercept dose to 50 mg every other week compared with that in patients receiving etanercept 50 mg weekly.Methods: In the first phase of this randomized, prospective, follow-up study, all biologic-naïve patients identified between January 2005 and December 2009 as satisfying the modified New York clinical criteria for ankylosing spondylitis treated with etanercept 50 mg weekly were evaluated for disease remission in January 2010. In the second phase, patients meeting the criteria for remission were randomized to receive subcutaneous etanercept as either 50 mg weekly or 50 mg every other week. The randomization allocation was 1:1. Remission was defined as Bath Ankylosing Spondylitis Disease Activity Index < 4, no extra-axial manifestations of peripheral arthritis, dactylitis, tenosynovitis, or iridocyclitis, and normal acute-phase reactants. The patients were assessed at baseline, at weeks 4 and 12, and every 12 weeks thereafter. The last visit constituted the end of the follow-up.Results: During the first phase, 78 patients with ankylosing spondylitis (57 males and 21 females, median age 38 years, median disease duration 12 years) were recruited. In January 2010, after a mean follow-up of 25 ± 11 months, 43 (55.1%) patients achieving clinical remission were randomized to one of the two treatment arms. Twenty-two patients received etanercept 50 mg every other week (group 1) and 21 received etanercept 50 mg weekly (group 2). At the end of follow-up, 19 of 22 (86.3%) subjects in group 1 and 19 of 21 (90.4%) in group 2 were still in remission, with no significant difference between the two groups. The mean follow-up duration in group 1 and group 2 was 22 ± 1 months and 21 ± 1.6 months, respectively.Conclusion: Remission of ankylosing spondylitis is possible in at least 50% of patients treated with etanercept 50 mg weekly. After halving of the etanercept dose, remission is maintained in a high percentage of patients during long-term follow-up, with important economic implications.Keywords: ankylosing spondylitis, anti-tumor necrosis factor, etanercept, remission, dose reductio

Investigating the epi-miRNome: Identification of epi-miRNAs using transfection experiments

Aim: Growing evidence shows a strong interplay between post-transcriptional regulation, mediated by miRNAs (miRs) and epigenetic regulation. Nevertheless, the number of experimentally validated miRs (called epi-miRs) involved in these regulatory circuitries is still very small. Material & methods: We propose a pipeline to prioritize candidate epi-miRs and to identify potential epigenetic interactors of any given miR starting from miR transfection experiment datasets. Results & conclusion: We identified 34 candidate epi-miRs: 19 of them are known epi-miRs, while 15 are new. Moreover, using an in-house generated gene expression dataset, we experimentally proved that a component of the polycomb-repressive complex 2, the histone methyltransferase enhancer of zeste homolog 2 (EZH2), interacts with miR-214, a well-known prometastatic miR in melanoma and breast cancer, highlighting a miR-214-EZH2 regulatory axis potentially relevant in tumor progression

Functional approach to 2+1 dimensional gravity coupled to particles

The quantum gravity problem of N point particles interacting with the gravitational field in 2+1 dimensions is approached working out the phase-space functional integral. The maximally slicing gauge is adopted for a non compact open universe with the topology of the plane. The conjugate momenta to the gravitational field are related to a class of meromorphic quadratic differentials. The boundary term for the non compact space is worked out in detail. In the extraction of the physical degrees of freedom functional determinants related to the puncture formulation of string theory occur and cancel out in the final reduction. Finally the ordering problem in the definition of the functional integral is discussed.Comment: 29 pages LaTe

Polygon model from first order gravity

The gauge fixed polygon model of 2+1 gravity with zero cosmological constant and arbitrary number of spinless point particles is reconstructed from the first order formalism of the theory in terms of the triad and the spin connection. The induced symplectic structure is calculated and shown to agree with the canonical one in terms of the variables.Comment: 20 pages, presentation improved, typos correcte