Dynamical maximum entropy approach to flocking

Peer reviewedPublisher PD

Multiple outcome meta-analysis of gene-expression data in inflammatory bowel disease

We performed a multivariate meta-analysis of microarray data in Crohn's disease (CD) and Ulcerative colitis (UC), which are the main forms of inflammatory bowel disease (IBD). They share similar symptoms but differ in the location and extent of inflammation and in complications. We identified 249 differentially expressed genes (DEGs) in CD and 38 in UC at a false discovery rate of 1%. 20 of the DEGs were common to both diseases. A multivariate test identified 260 DEGs associated with IBD, 53 of which were not found in any of the disorders. We identified important molecular pathways implicated in the pathogenesis of IBD, such as the JAK/STAT and interferon-gamma signaling pathways, genes involved in cell adhesion, apoptosis and carcinogenesis. Among others, BCAT1 and GZMB are interesting novel DEGs that deserve further investigation in experimental models. The method could also be useful to other cases of meta-analysis of gene expression data

Generation of induced Pluripotent Stem Cells (UNIBSi008-A, UNIBSi008-B, UNIBSi008-C) from an Ataxia-Telangiectasia (AT) patient carrying a novel homozygous deletion in ATM gene.

Abstract Using a Sendai Virus based vector delivering Yamanaka Factors, we generated induced Pluripotent Stem Cells (iPSCs) from peripheral blood mononuclear cells of a patient affected by Ataxia Telangiectasia (AT), caused by a novel homozygous deletion in ATM, spanning exons 5 to 7. Three clones were fully characterized for pluripotency and capability to differentiate. These clones preserved the causative mutation of parental cells and genomic stability over time (>100 passages). Furthermore, in AT derived iPSCs we confirmed the impaired DNA damage response after ionizing radiation. All these data underline potential usefulness of our clones as in vitro AT disease model

Measuring Accessibility Using Gravity and Radiation Models

Since the presentation of the radiation model, much work has been done to compare its findings with those obtained from gravitational models. These comparisons always aim at measuring the accuracy with which the models reproduce the mobility described by origin–destination matrices. This has been done at different spatial scales using different datasets, and several versions of the models have been proposed to adjust to various spatial systems. However, the models, to our knowledge, have never been compared with respect to policy testing scenarios. For this reason, here we use the models to analyse the impact of the introduction of a new transportation network, a bus rapid transport system, in the city of Teresina in Brazil. We do this by measuring the estimated variation in the trip distribution, and formulate an accessibility to employment indicator for the different zones of the city. By comparing the results obtained with the two approaches, we are able to not only better assess the goodness of fit and the impact of this intervention, but also understand reasons for the systematic similarities and differences in their predictions

Tangent map intermittency as an approximate analysis of intermittency in a high dimensional fully stochastic dynamical system: The Tangled Nature model

It is well known that low-dimensional nonlinear deterministic maps close to a tangent bifurcation exhibit intermittency and this circumstance has been exploited, e.g. by Procaccia and Schuster [Phys. Rev. A 28, 1210 (1983)], to develop a general theory of 1/f spectra. This suggests it is interesting to study the extent to which the behavior of a high-dimensional stochastic system can be described by such tangent maps. The Tangled Nature (TaNa) Model of evolutionary ecology is an ideal candidate for such a study, a significant model as it is capable of reproducing a broad range of the phenomenology of macroevolution and ecosystems. The TaNa model exhibits strong intermittency reminiscent of Punctuated Equilibrium and, like the fossil record of mass extinction, the intermittency in the model is found to be non-stationary, a feature typical of many complex systems. We derive a mean-field version for the evolution of the likelihood function controlling the reproduction of species and find a local map close to tangency. This mean-field map, by our own local approximation, is able to describe qualitatively only one episode of the intermittent dynamics of the full TaNa model. To complement this result we construct a complete nonlinear dynamical system model consisting of successive tangent bifurcations that generates time evolution patterns resembling those of the full TaNa model in macroscopic scales. The switch from one tangent bifurcation to the next in the sequences produced in this model is stochastic in nature, based on criteria obtained from the local mean-field approximation, and capable of imitating the changing set of types of species and total population in the TaNa model. The model combines full deterministic dynamics with instantaneous parameter random jumps at stochastically drawn times. In spite of the limitations of our approach, that entails a drastic collapse of degrees of freedom, the description of a high-dimensional model system in terms of a low-dimensional one appears to be illuminating

Generation of three iPSC lines from fibroblasts of a patient with Aicardi Goutières Syndrome mutated in TREX1

Fibroblasts from a patient with Aicardi Gouti\ue8res Syndrome (AGS) carrying a compound heterozygous mutation in TREX1, were reprogrammed into induced pluripotent stem cells (iPSCs) to establish isogenic clonal stem cell lines: UNIBSi006-A, UNIBSi006-B, and UNIBSi006-C. Cells were transduced using the episomal Sendai viral vectors, containing human OCT4, SOX2, c-MYC and KLF4 transcription factors. The transgene-free iPSC lines showed normal karyotype, expressed pluripotent markers and displayed in vitro differentiation potential toward cells of the three embryonic germ layers

Gemcitabine-releasing mesenchymal stromal cells inhibit in vitro proliferation of human pancreatic carcinoma cells

BACKGROUND AIMS: Pancreatic cancer (pCa) is a tumor characterized by a fibrotic state and associated with a poor prognosis. The observation that mesenchymal stromal cells (MSCs) migrate toward inflammatory micro-environments and engraft into tumor stroma after systemic administration suggested new therapeutic approaches with the use of engineered MSCs to deliver and produce anti-cancer molecules directly within the tumor. Previously, we demonstrated that without any genetic modifications, MSCs are able to deliver anti-cancer drugs. MSCs loaded with paclitaxel by exposure to high concentrations release the drug both in vitro and in vivo, inhibiting tumor proliferation. On the basis of these observations, we evaluated the ability of MSCs (from bone marrow and pancreas) to uptake and release gemcitabine (GCB), a drug widely used in pCa treatment. METHODS: MSCs were primed by 24-h exposure to 2000 ng/mL of GCB. The anti-tumor potential of primed MSCs was then investigated by in vitro anti-proliferation assays with the use of CFPAC-1, a pancreatic tumor cell line sensitive to GCB. The uptake/release ability was confirmed by means of high-performance liquid chromatography analysis. A cell-cycle study and secretome evaluation were also conducted to better understand the characteristics of primed MSCs. RESULTS: GCB-releasing MSCs inhibit the growth of a human pCa cell line in vitro. CONCLUSIONS: The use of MSCs as a "trojan horse" can open the way to a new pCa therapeutic approach; GCB-loaded MSCs that integrate into the tumor mass could deliver much higher concentrations of the drug in situ than can be achieved by intravenous injection