Novel triblock co-polymer nanofibre system as an alternative support for embryonic stem cells growth and pluripotency

Conventionally, embryonic stem cells (ESCs) are cultured on gelatin or over a mitotically inactivated monolayer of mouse embryonic fibroblasts (MEFsi). Considering the lack of versatile, non-animal-derived and inexpensive materials for that purpose, we aimed to find a biomaterial able to support ESC growth in a pluripotent state that avoids the need for laborious and time-consuming MEFsi culture in parallel with mouse ESC (mESC) culture. Undifferentiated mESCs were cultured in a new nanofibre material designed for ESC culture, which is based on the self-assembly of a triblock co-polymer, poly(ethyleneglycol-β-trimethylsilyl methacrylate-β-methacrylic acid), conjugated with the peptide glycine-arginine-glycine-aspartate-serine, to evaluate its potential application in ESC research. The morphology, proliferation, viability, pluripotency and differentiation potential of mESCs were assessed. Compared to conventional stem cell culture methodologies, the nanofibres promoted a higher increase in mESCs number, enhanced pluripotency and were able to support differentiation after long-term culture. This newly developed synthetic system allows the elimination of animal-derived matrices and provides an economic method of ESC culture, made of a complex network of nanofibres in a scale similar to native extracellular matrices, where the functional properties of the cells can be observed and manipulated

Transcriptional Regulation of Glucose Metabolism: The Emerging Role of the HMGA1 Chromatin Factor

HMGA1 (high mobility group A1) is a nonhistone architectural chromosomal protein that functions mainly as a dynamic regulator of chromatin structure and gene transcription. As such, HMGA1 is involved in a variety of fundamental cellular processes, including gene expression, epigenetic regulation, cell differentiation and proliferation, as well as DNA repair. In the last years, many reports have demonstrated a role of HMGA1 in the transcriptional regulation of several genes implicated in glucose homeostasis. Initially, it was proved that HMGA1 is essential for normal expression of the insulin receptor (INSR), a critical link in insulin action and glucose homeostasis. Later, it was demonstrated that HMGA1 is also a downstream nuclear target of the INSR signaling pathway, representing a novel mediator of insulin action and function at this level. Moreover, other observations have indicated the role of HMGA1 as a positive modulator of the Forkhead box protein O1 (FoxO1), a master regulatory factor for gluconeogenesis and glycogenolysis, as well as a positive regulator of the expression of insulin and of a series of circulating proteins that are involved in glucose counterregulation, such as the insulin growth factor binding protein 1 (IGFBP1), and the retinol binding protein 4 (RBP4). Thus, several lines of evidence underscore the importance of HMGA1 in the regulation of glucose production and disposal. Consistently, lack of HMGA1 causes insulin resistance and diabetes in humans and mice, while variations in the HMGA1 gene are associated with the risk of type 2 diabetes and metabolic syndrome, two highly prevalent diseases that share insulin resistance as a common pathogenetic mechanism. This review intends to give an overview about our current knowledge on the role of HMGA1 in glucose metabolism. Although research in this field is ongoing, many aspects still remain elusive. Future directions to improve our insights into the pathophysiology of glucose homeostasis may include epigenetic studies and the use of "omics" strategies. We believe that a more comprehensive understanding of HMGA1 and its networks may reveal interesting molecular links between glucose metabolism and other biological processes, such as cell proliferation and differentiation

HMGA1 is a novel downstream nuclear target of the insulin receptor signaling pathway

High-mobility group AT-hook 1 (HMGA1) protein is an important nuclear factor that activates gene transcription by binding to AT-rich sequences in the promoter region of DNA. We previously demonstrated that HMGA1 is a key regulator of the insulin receptor (INSR) gene and individuals with defects in HMGA1 have decreased INSR expression and increased susceptibility to type 2 diabetes mellitus. In addition, there is evidence that intracellular regulatory molecules that are employed by the INSR signaling system are involved in post-translational modifications of HMGA1, including protein phosphorylation. It is known that phosphorylation of HMGA1 reduces DNA-binding affinity and transcriptional activation. In the present study, we investigated whether activation of the INSR by insulin affected HMGA1 protein phosphorylation and its regulation of gene transcription. Collectively, our findings indicate that HMGA1 is a novel downstream target of the INSR signaling pathway, thus representing a new critical nuclear mediator of insulin action and function

Study of the a_0(980) meson via the radiative decay phi->eta pi^0 gamma with the KLOE detector

We have studied the phi->a_0(980) gamma process with the KLOE detector at the Frascati phi-factory DAPhNE by detecting the phi->eta pi^0 gamma decays in the final states with eta->gamma gamma and eta->pi^+ pi^- pi^0. We have measured the branching ratios for both final states: Br(phi->eta pi^0 gamma)=(7.01 +/- 0.10 +/- 0.20)x10^-5 and (7.12 +/- 0.13 +/- 0.22)x10^-5 respectively. We have also extracted the a_0(980) mass and its couplings to eta pi^0, K^+ K^-, and to the phi meson from the fit of the eta pi^0 invariant mass distributions using different phenomenological models.Comment: 17 pages, 6 figures, submitted to Physics Letters B. Corrected typos in eq.

Charged kaon lifetime at KLOE

Preliminary result on the charged kaon lifetime, obtained by the KLOE experiment operating at DA$\Phi$NE, the Frascati $\phi$-factory, is presentedComment: 3 pages, 3 figures, to appear in the proceedings of 42nd Rencontres de Moriond on Electroweak Interactions and Unified Theories, La Thuile, Aosta Valley, Italy, 10-17 Mar 200

Measurement of hadronic cross section and preliminary results on the pion form factor using the radiative return at DAPHNE

In the fixed energy environment of the $e^{+}e^{-}$ collider DA$\Phi$NE, KLOE can measure the cross section of the process $e^{+}e^{-} \to$ hadrons as a function of the hadronic system energy using the radiative return. At energies below 1 GeV, $e^{+}e^{-} \to \rho \to \pi^{+}\pi^{-}$ is the dominating hadronic process. We report here on the status of the analysis for the e^{+}e^{-} \to \ppg channel, which allows to obtain a preliminary measurement of the pion form factor using an integrated luminosity of $\sim73 pb^{-1}$.Comment: Invited talk at the Seventh International Workshop on Tau Lepton Physics (TAU02-WE07), Santa Cruz, Ca, USA, Sept 2002, 9 pages, LaTeX, 9 eps figure

Measurements of the Absolute Branching Ratios for the Dominant KL Decays, the KL Lifetime, and Vus with the KLOE Detector

From a sample of about 10^9 Phi mesons produced at DAFNE, we have selected KL mesons tagged by observing KS->pi+pi- decays. We present results on the major KL branching ratios, including those of the semileptonic decays needed for the determination of Vus. These branching ratio measurements are fully inclusive with respect to final-state radiation. The KL lifetime has also been measured.Comment: Submitted to Phys. Lett.

Measuring the hadronic cross section via radiative return

Recently it has been demonstrated that particle factories, such as DAPHNE and PEP-II, operating at fixed center-of-mass energies, are able to measure hadronic cross sections as a function of the hadronic system energy using the raditive return. This paper is an experimental overview of the progress in this aera. Preliminary results from KLOE for the process e+e- -> \rho \gamma -> \pi+\pi-\gamma and a fit to the pion form factor are presented. Some first results from the BABAR collaboration are also shown.Comment: Invited talk presented at RADCOR/Loops and Legs 2002, Kloster Banz/Germany, September 8-13 2002, 6 pages, 2 Figures; v1: references added, typos correcte