Development of an intrabody capable of activating interferon regulatory factor-1 [IRF-1] and identification of IRF-1-binding peptide motifs

Interferon regulatory factor 1 (IRF-1) is a tumour suppressor protein and transcription factor. It has been shown to modulate target gene expression in response to stimuli, which include viral infection and DNA damage, and to be down- regulated in several forms o f cancer. This thesis details the development o f an intrabody, an intracellular antibody, that binds specifically to endogenous IRF-1. The binding o f the intrabody to ERF-1 enhanced transcription from ERF-1-responsive reporter gene constructs and endogenous promoters, thus it was shown to activate IRF-1. Intrabody binding also increased the rate at which IRF-1 was degraded, suggesting that the intrabody epitope may be regulating both IRF-1 activity and turnover. These results were supported point mutation within the intrabody epitope (P325 to A ) as the resultant mutant also displayed both a higher transcriptional activity and increased rate o f degradation.In an effort to understand the mechanisms which regulate IRF-1 activity a search for novel IRF-1-interacting proteins was carried out using phage peptide display. This invitro technique enables the identification o f peptides able to bind a specific target protein. The sequence o f these peptides can then be used to search protein databases for homologous, full-length proteins that could also bind the target protein. This led to the identification o f an IRF-1-binding peptide that held sequence similar to a region o f Zinc Finger 350 (ZNF350), a transcription factor involved in regulating the D N A damage response. Subsequently, endogenous ZNF350 and IRF-1 were co- immunoprecipitated from a human cancer cell line. The extreme C-terminus o f ERF-1 was shown to be sufficient for an interaction with ZNF350, although a second, more N-terminal site was also shown to be essential for a stable intracellular interaction.This data sheds new light on the role o f the extreme C-terminus o f IRF-1 in modulating the protein’s activity. This study also provides new and IRF-1-specific molecular tools, in the form o f intrabodies and IRF-1-binding peptides, which could be used in the future to further characterise the activity and regulation o f this tumour suppressor protein

Ámbitos temáticos. Creación de un sistema de clasificación alternativo a la CDU basada en las tendencias de los usuarios

[ES] mbitos temáticos: creación de un sistema de clasificación alternativo a la CDU basada en las tendencias de los usuarios fue presentado como proyecto final de grado en la Universidad Oberta de Catalunya (UOC) y resultó ganador del 3er Premio al Proyecto universitario más innovador en el ámbito de la Gestión de la Información y la Documentación, convocado por la Sociedad Española de Documentación en Información Científica (SEDIC) en colaboración con el Departamento de Biblioteconomía y Documentación de la Universidad Complutense de Madrid. Los ámbitos temáticos han sido implementados en la Biblioteca pública Can Pedrals del municipio de Granollers (Barcelona); sin embargo, es ésta una propuesta aplicable a cualquier tipo de biblioteca. Como dice la autora: “No hay una ruta exclusiva para llegar a ser más accesibles para el usuario”. ¿Lo comprobamos?

WAVELET ANALYSIS CONSIDERATIONS FOR EXPERIMENTAL NONSTATIONARY FLOW PHENOMENA

In this work, wavelet transforms are the analysis tools for studying transient and discontinuous phenomena associated to turbulent flows. The application in quest results from velocity measurements with hot wire anemometry in the transient wake considering a circular cylinder in an aerodynamic channel. Continuous and discrete wavelet transforms are applied and compared with the corresponding results given by the Fourier transform. For the continuous wavelet transform, the Morlet function was adopted as transform basis, and for the discrete case, the Daubechies orthonormal wavelet with 20 null moments. Results using the discrete wavelet packet transform are also presented and compared. A wake past a cylinder was analytically simulated and compared with the actual one, both in transient flow. The ability of the wavelet transforms in the analysis of unsteady phenomena and the potential of the wavelet approach as a complementary tool to the Fourier spectrum for the analysis of stationary phenomena is presented and discussed

Polymer nano-doplets forming liquid bridges in chemically structured slit pores: A computer simulation

Using a coarse-grained bead-spring model of flexible polymer chains, the structure of a polymeric nanodroplet adsorbed on a chemically decorated flat wall is investigated by means of Molecular Dynamics simulation. We consider sessile drops on a lyophilic (attractive for the monomers) region of circular shape with radius R_D while the remaining part of the substrate is lyophobic. The variation of the droplet shape, including its contact angle, with R_D is studied, and the density profiles across these droplets also are obtained. In addition, the interaction of droplets adsorbed on two walls forming a slit pore with two lyophilic circular regions just opposite of one another is investigated, paying attention to the formation of a liquid bridge between both walls. A central result of our study is the measurement of the force between the two substrate walls at varying wall separation as well as the kinetics of droplet merging. Our results are compared to various phenomenological theories developed for liquid droplets of mesoscopic rather than nanoscopic size.Comment: 8 pages, 9 figures, accepted in J. Chem. Phys. 200

Comments and illustrations of the WFUMB CEUS liver guidelines: Rare benign focal liver lesion, part II.

It is important to be familiar with the typical imaging features of the uncommon or even extremely rare focal liver lesions (FLL). Current guidelines of the World Federation for Ultrasound in Medicine and Biology (WFUMB) is aimed at assessing the usefulness of contrast enhanced ultrasound (CEUS) in the management of various FLL. In this review, we aim to summarize the ultrasound and CEUS characteristics with literature review of some extremely rare benign FLL, which might be helpful for improving diagnostic efficiency clinically