Modulación de la interacción de péptidos derivados de factores de transcripción con secuencias específicas de ADN

En esta tesis doctoral se han estudiado diversas aproximaciones para lograr emular las propiedades de unión al ADN de los factores de transcripción naturales. el trabajo se divide en cuatro capítulos

Diplomado de profundización cisco ccnp solución de dos escenarios presentes en entornos

En el desarrollo del presente trabajo se simularon dos escenarios de redes, los cuales son ampliamente implementados en las redes cotidianas, en las cuales se busca alcanzar los objetivos de no solo configurar de manera correcta las redes, si no también aprender de los diferentes comandos de networking, y solucionar aquellos inconvenientes que se pudieran presentar, ya que en el día a día de un administrador de red, este se ve en la necesidad de superar diferentes desafíos para mantener la conectividad de una organización y que no se pare la producción de los usuarios finales, dicha simulación se hará mediante el uso de software que asemejan a los dispositivos reales que componen una red de datos. Para el primer escenario se documenta la configuración de una red que utiliza dispositivos routers, se configuran las diferentes interfaces de acuerdo a los protocolos de enrutamiento OSPF, EGIRP solicitados en el diseño, se crean las diferentes loopback, teniendo en cuenta el direccionamiento ip, se analiza las tablas de enrutamiento y finalmente se comprueba la conexión de los diferentes dispositivos a través del comando “show ip route”. En el segundo escenario se documenta la configuración de una red conmutada, la creación de interfaces virtuales VLANs, puertos troncales, Port-channels teniendo en cuenta protocolos PAgP / LACP sugeridos en el diseño de la red y se verifica las diferentes conexiones y tablas de enrutamiento mediante los comandos “show vlan”, “show interfaces trunk”, “Show interface port-channel” y “show spanning-tree”. Palabras Clave: CISCO, CCNP, CONMUTACIÓN, ENRUTAMIENTO, REDES, ELECTRÓNICA.In the development of this work, two network scenarios were simulated, which are widely implemented in everyday networks, in which it is sought to achieve the objectives of not only configuring the networks correctly, but also learning from the different commands of networking, and solve those problems that may arise, since in the day-to-day life of a network administrator, he sees the need to overcome different challenges to maintain the connectivity of an organization and that the production of the end users, said simulation will be done through the use of software that resembles the real devices that make up a data network. For the first scenario, the configuration of a network that uses router devices is documented, the different interfaces are configured according to the OSPF and EGIRP routing protocols requested in the design, the different loopbacks are created, taking into account the IP addressing, it analyzes the routing tables and finally the connection of the different devices is checked through the command "show ip route". In the second scenario, the configuration of a network that uses switch devices is documented, the creation of VLANs, trunk ports, Port-channels, taking into account PAgP / LACP protocols suggested in the network design, and the different connections and tables are verified. Routing using the “show vlan”, “show interfaces trunk”, “Show interface port-channel” and “show spanning-tree” commands

Selective DNA-Binding by Designed Bisbenzamidine-Homeodomain Chimeras

We report the construction of conjugates between three variants of the helix 3 region of a Q50K engrailed homeodomain and bisbenzamidine minor-groove DNA binders. The hybrid featuring the sequence of the native protein failed to bind to DNA; however, modifications that increased the α-helical folding propensity of the peptide allowed specific DNA binding by a bipartite (major/minor groove) interactionMinisterio de Economía y Competitividad. Grant Numbers: SAF2010-20822-C02, CTQ2012-31341 Consolider Ingenio. Grant Number: 2010 CSD2007-00006 Xunta de Galicia. Grant Number: GRC2013/14 European Regional Development Fund European Research Council. Grant Number: Na 340055 Ministerio de Ciencia e Innovación Fundación Gil DávilaS

Nickel-promoted recognition of long DNA sites by designed peptide derivatives

NOTICE: This is the peer reviewed version of the following article: Jessica Rodríguez, Jesús Mosquera, M. Eugenio Vázquez*, José L. Mascareñas* (2016), Nickel-promoted Recognition of long DNA sites by designed Peptide Derivatives. ChemEurJ., 22 (38), 13474-13477 [doi:10.1002/chem.201602783]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for selfarchivingWe describe the synthesis of designed peptidic modules that self-assemble in specific DNA sequences of 12 base pairs in the presence of NiII salts. The modules consist of modified fragments of transcription factors that have been appropriately engineered to include metal-chelating His and bipyridine ligandsWe are thankful for the support given by the Spanish grants SAF2013-41943-R, CTQ2015-70698-R, and CTQ2013-49317-EXP, the Xunta de Galicia GRC2013-041, the ERDF, and the European Research Council (Advanced Grant No. 340055). Support of COST Action CM1105, COST CM1306 and the orfeo-cinqa network are also kindly acknowledged. J.R. thanks the Xunta de Galicia for a PhD fellowshipS

Cellular uptake of nanoparticles versus small molecules : a matter of size

The primary function of the cell membrane is to protect cells from their surroundings. This entails a strict regulation on controlling the exchange of matter between the cell and its environment. A key factor when considering potential biological applications of a particular chemical structure has to do with its ability to internalize into cells. Molecules that can readily cross cell membranes are frequently needed in biological research and medicine, since most therapeutic entities are designed to modulate intracellular components. However, the design of molecules that do not penetrate cells is also relevant toward, for example, extracellular contrast agents, which are most widely used in clinical diagnosis.Small molecules have occupied the forefront of biomedical research until recently, but the past few decades have seen an increasing use of larger chemical structures, such as proteins or nanoparticles, leading to unprecedented and often unexpectedly novel research. Great achievements have been made toward understanding the rules that govern cellular uptake, which show that cell internalization of molecules is largely affected by their size. For example, macromolecules such as proteins and nucleic acids are usually unable to internalize cells. Intriguingly, in the case of nanoparticles, larger sizes seem to facilitate internalization via endocytic pathways, through which the particles remain trapped in lysosomes and endosomes.In this Account, we aimed at presenting our personal view of how different chemical structures behave in terms of cell internalization due to their size, ranging from small drugs to large nanoparticles. We first introduce the properties of cell membranes and the main mechanisms involved in cellular uptake. We then discuss the cellular internalization of molecules, distinguishing between those with molecular weights below 1 kDa and biological macromolecules such as proteins and nucleic acids. In the last section, we review the biological behavior of nanoparticles, with a special emphasis on plasmonic nanoparticles, which feature a high potential in the biomedical field. For each group of chemical structures, we discuss the parameters affecting their cellular internalization but also strategies that can be applied to achieve the desired intracellular delivery. Particular attention is paid to approaches that allow conditional regulation of the cell internalization process using external triggers, such as activable cell penetrating peptides, due to the impact that these systems may have in drug delivery and sensing applications. The Account ends with a "Conclusions and Outlook" section, where general lessons and future directions toward further advancements are briefly presented

Reversible supramolecular assembly at specific DNA sites: Ni-promoted, bivalent DNA binding with designed peptide and bipyridylbisbenzamidine components

At specific DNA sites, nickel(II) salts promote the assembly of designed components, namely a bis(histidine)-modified peptide that is derived from a bZIP transcription factor and a bis(benzamidine) unit that is equipped with a bipyridine. This programmed supramolecular system with emergent properties reproduces some key characteristics of naturally occurring DNA-binding proteins, such as bivalence, selectivity, responsiveness to external agents, and reversibility.We are thankful for support from Spanish grants (SAF2010-20822-C02 and CTQ2012-31341), Consolider Ingenio 2010 (CSD2007-00006), the Xunta de Galicia (GRC2013-041, INCITE09 209084PR, and PGIDIT08CSA-047209PR), the ERDF, and the European Research Council (Advanced Grant 340055). J.M. and M.I.S. thank the Spanish MCINN for their Ph.D. fellowships.S

Pots&Plants Aplicació de Realitat Augmentada

Curs 2013-2014Joc de Realitat Augmentada on l’usuari haurà de complir petits reptes interactuant amb els elements virtuals de l’escena. Aquests elements es presentaran fent us de marcadors. El projecte és un joc on l’usuari ha de cuidar unes plantes. Per a poder fer aquesta feina el jugador realitzarà 3 tipus de reptes. Aquests reptes són petits jocs, és a dir, que hi ha tres tipus de “mini-jocs” dintre de la Aplicació. Degut a que cada jugador té preferències diferents, aquesta divisió́ de jocs permet accedir a un major nombre d’usuaris. Pel seu desenvolupament s'ha fet un recull d’informació i evolució històrica de la Realitat Augmentada. S'han agafant referents de jocs similars en el mercat: PC, Apps i videoconsoles com a base d’inspiració per a la creació de la historia del joc. I finalment una recollida de requeriments tècnics per al desenvolupament tecnològic a nivell de programació i disseny. Amb tota aquesta informació i tenint com a medis de desenvolupament Blender, Unity + Vuforia s'ha complert la implementació del joc.Augmented Reality game where the user must solve small challenges interacting with virtual elements of the scene. These elements are presented using markers. The project is a game where the user must take care of some plants. To do it the player ought to performed three types of challenges . These challenges are mini games, in fact, there are three types of "mini-games" running inside the application. Because each player has different preferences, this division of the games allows to access to a greater number of users. To develop the game, the first we need is collect information about historical development of Augmented Reality. To have the inspiration for the creation of the history of the game is necessary to know similar games on the market: PCs, game consoles and Apps. And the last part of the benchmark is done to get requirements about the programming and the design techniques. With this information and having Blender and Unity + Vuforia as frameworks we can complete the implementation of the game.Director/a: Sergi Gra

Ruthenium bipyridyl complexes as photocleavable dimerizers: deactivation of DNA-binding peptides using visible light

We report a photolabile biselectrophilic Ru(II) complex that can be used for homo- or heterodimerization of cysteine-containing peptides. The resulting dimers can be efficiently disassembled by long-wavelength light. As proof-of-concept, we describe the preparation of homo- and heterodimeric bZIP peptides whose DNA-binding properties can be turned off using visible lightSpanish MINECO. Grant Numbers: SAF2010-20822-C02-01/02, CTQ2010-20714-C02-01/BQU, CSD2007-00006 ERDF Xunta de Galicia. Grant Numbers: GRC2010/12, GR2013-041, INCITE09 209084PR, EM2013/036 European Research Council. Grant Number: 340055 CAM. Grant Number: S2009/PPQ-1634, AVANCA