18 research outputs found
Accurate Prediction of Peptide Binding Sites on Protein Surfaces
Many important proteinâprotein interactions are mediated by the binding of a short peptide stretch in one protein to a large globular segment in another. Recent efforts have provided hundreds of examples of new peptides binding to proteins for which a three-dimensional structure is available (either known experimentally or readily modeled) but where no structure of the proteinâpeptide complex is known. To address this gap, we present an approach that can accurately predict peptide binding sites on protein surfaces. For peptides known to bind a particular protein, the method predicts binding sites with great accuracy, and the specificity of the approach means that it can also be used to predict whether or not a putative or predicted peptide partner will bind. We used known proteinâpeptide complexes to derive preferences, in the form of spatial position specific scoring matrices, which describe the binding-site environment in globular proteins for each type of amino acid in bound peptides. We then scan the surface of a putative binding protein for sites for each of the amino acids present in a peptide partner and search for combinations of high-scoring amino acid sites that satisfy constraints deduced from the peptide sequence. The method performed well in a benchmark and largely agreed with experimental data mapping binding sites for several recently discovered interactions mediated by peptides, including RG-rich proteins with SMN domains, Epstein-Barr virus LMP1 with TRADD domains, DBC1 with Sir2, and the Ago hook with Argonaute PIWI domain. The method, and associated statistics, is an excellent tool for predicting and studying binding sites for newly discovered peptides mediating critical events in biology
Cooperative learning in a Engineering Teaching Framework: an introductory experience to Teamworking
Proyecto de InnovaciĂłn Educativa PIE13-021: Aprendizaje Cooperativo/Colaborativo en el ĂĄmbito de la IngenierĂa (ACAI)La enseñanza universitaria en el ĂĄmbito de la IngenierĂa ha estado tradicionalmente orientada al trabajo individual del alumno, lo cual dificulta la adquisiciĂłn de una de las aptitudes mĂĄs valoradas en el mercado laboral, como es la competencia de trabajo en grupo. Este trabajo tiene como objetivo fomentar una componente de esta competencia, como es la interacciĂłn entre los estudiantes. Para ello se han diseñado y puesto en prĂĄctica una serie de actividades docentes en la asignatura âMicrocontroladoresâ, asignatura de 2Âș curso comĂșn a los estudios de Grado en IngenierĂa de Sistemas ElectrĂłnicos, Sistemas de TelecomunicaciĂłn, TelemĂĄtica, TecnologĂas de TelecomunicaciĂłn, y Sonido e Imagen, en la Universidad de MĂĄlaga. Asimismo, se ha establecido un conjunto de indicadores que permiten evaluar el grado de consecuciĂłn de la meta planteada. Los resultados han puesto de manifiesto que la interacciĂłn entre los estudiantes se puede fomentar mediante el conjunto de acciones planificadas, aunque las mismas requieren un esfuerzo adicional por parte del profesorado. Finalmente, se han propuesto algunas mejoras en el diseño del procedimiento, para mejorar su eficacia. Este trabajo se enmarca en el proyecto ACAI, cuyo objetivo es implementar un diseño curricular para el desarrollo de la competencia de Trabajo en Grupo. AsĂ, se propone continuar la experiencia aquĂ presentada fomentando, para los mismos estudiantes, otras componentes de la competencia en asignaturas de 3Âș y 4Âș de los grados mencionados.Proyecto de InnovaciĂłn Educativa PIE13-021, concedido por el Vicerrectorado de Profesorado, FormaciĂłn, y CoordinaciĂłn de la Universidad de MĂĄlaga
CD2v interacts with Adaptor Protein AP-1 during African swine fever infection
African swine fever virus (ASFV) CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golgi network (TGN) protein complex AP-1, a key element in cellular traffic. This interaction was disrupted by brefeldin A even though the location of CD2v around the viral factory remained unchanged. CD2v-AP-1 binding was independent of CD2v glycosylation and occurred on the carboxy-terminal part of CD2v, where a canonical di-Leu motif previously reported to mediate AP-1 binding in eukaryotic cells, was identified. This motif was shown to be functionally interchangeable with the di-Leu motif present in HIV-Nef protein in an AP-1 binding assay. However, we demonstrated that it was not involved either in CD2v cellular distribution or in CD2v-AP-1 binding. Taken together, these findings shed light on CD2v function during ASFV infection by identifying AP-1 as a cellular factor targeted by CD2v and hence elucidate the cellular pathways used by the virus to enhance infectivity.This work was supported by Ministerio de Ciencia e InnovaciĂłn of Spain, BFU2010-17794 (YR); European Communityâs Seventh Framework Programme, KBBE.2012.1.3-02-ASFORCE (YR). Ricardo Madrid was funded by an Amarauto research program and by FIS-641 PS09/01386.Peer Reviewe
A new collaborative shared control strategy for continuous elder/robot assisted navigation
In nowadays aging society, many people require mobility assistance. Autonomous wheelchairs may provide some help, but they are not supposed to overtake all control
on human mobility, as this is reported to lead to loss of residual capabilities and frustration. Instead, persons and wheelchairs are expected to cooperate. Traditionally, shared control hands control from human to robot depending on a triggering event. In this paper, though, we propose a method to allow constant cooperation between humans and robots, so that both have some weight in the emergent navigating behavior. We have tested the proposed method on a robotized Meyra wheelchair at Santa Lucia Hospedale in
Rome with several volunteering in-patients presenting different disabilities. Results in indoor environments have been satisfactory both from a quantitative and qualitative point of view.Peer ReviewedPostprint (authorâs final draft
Update 1 of: Enantioselective enzymatic desymmetrizations in organic synthesis.
During the recent past years, tremendous efforts have been made to establish enantioselective routes for the preparation of enantiomerically pure compounds due to their importance in the pharmaceutical, agricultural, and food industries. This is reflected in the fact that the sales of single-enantiomer small-molecule drugs has reached c. US $10 billion in 2002.1 Moreover, the FDA has become increasingly reluctant to permit the introduction of additional racemic drugs, as these therapies are by definition saddled with 50% of chemical ballast.2 Enzymes are nowadays widely recognized among the most active and selective catalysts for the preparation of optically active compounds.3 Some of the factors that account for this popularity are (1) They are chemo-, regio-, and stereoselective, and environmentally friendly. (2) Because of the mild conditions under which they operate, enzymatic reactions are affected to a lesser extent by side reactions (viz. isomerization, racemization, epimerization, and rearrangement of molecules) as compared to nonenzymatic processes. Nevertheless, organic chemists have been traditionally reluctant to employ biocatalysts in their syntheses. This is mainly because, in their natural form, most of the enzymes are very sensitive catalysts that exert their activity mainly in aqueous solution. Moreover, their handling requires some biochemistry knowledge. However, some recent advances carried out in the biocatalysis field have âapproachedâ enzymes to organic synthesis:â (a) They can operate in nonaqueous media accepting a broad range of substrates;4 (b) immobilization techniques increase their stability and simplify their handling.5 Thus, many enzymes can now be acquired and used as any other chemical.Stereoselective biotransformations can be grouped into two main different classes:â asymmetric synthesis and kinetic resolution of racemic mixtures (KR). Conceptually, they differ from each other in the fact that while asymmetric synthesis implies the formation of one or more chirality elements in a substrate, a KR is based on a transformation, which, subsequently, makes easier the separation of the two enantiomers of the racemic substrate. This fact involves a practical difference:â in a kinetic resolution only half of the starting material is used. When only one enantiomer of a substrate is required this fact constitutes a disadvantage of KRs and different approaches have been developed to overcome this limitation.6 The one on which more attention has been recently paid is the dynamic KR7 and consists of carrying out an in situ continuous racemization of the substrate, so that, theoretically, all of the racemic starting material can be used for transformation into one enantiomer. Nevertheless, many substrates employed in enzyme-catalyzed kinetic resolutions are not liable to undergo racemization.The desymmetrization of symmetric compounds consists of a modification that eliminates one or more elements of symmetry of the substrate. If the symmetry elements that preclude chirality are eliminated, enantioselectivity can be achieved.8 Enantioselective enzymatic desymmetrizations (EEDs) belong to the field of asymmetric synthesis and, accordingly, a maximum yield of 100% can be attained.9 For this reason, they constitute a very interesting alternative to KRs for the preparation of optically active compounds, which is reflected in the increasing number of enzymatic desymmetrizations applied to synthesis published in the literature during the recent past years. This review deals with the developments made in the use of biocatalysts for the desymmetrization of meso and prochiral compounds, especially from 1999 on. It is structured according to a synthetic rather than a biocatalytic point of view and, as a rule of thumb, only those examples useful from a synthetic point of view are included, i.e., EEDs that constitute or can constitute a key step in a synthetic route, or aid to rationalize either the substrate specificity of an enzyme or the desymmetrization of a certain class of compounds. Accordingly, important parameters to which attention has been paid are enantioselectivity and the yield of the EED, which should be higher than 50% so that the desymmetrization implies a clear advantage over KRs. Nevertheless, exceptions can be made on the basis of novelty and difficulty of obtaining a compound by other means.Peer reviewe
Factors affecting inflation in Latvia
Bakalaura darba tÄma âInflÄciju ietekmÄjoĆĄie faktori LatvijÄâ ir aktuÄla patreizÄjÄ ekonomiskajÄ situÄcijÄ. StraujÄ ekonomiskÄ izaugsme LatvijÄ ir nesusi lÄ«dzi vispÄrÄju cenu lÄ«meĆa paaugstinÄĆĄanos, kas liecina par nesabalansÄtu ekonomikas attÄ«stÄ«bu un izjauktu ekonomisko lÄ«dzsvaru. Augstais inflÄcijas lÄ«menis kavÄ sasniegt Latvijas valdÄ«bas nospraustos makroekonomiskos mÄrÄ·us un apdraud Latvijas tÄlÄko ekonomisko attÄ«stÄ«bu.
Lai inflÄciju pakÄŒautu kontrolei, vispirms nepiecieĆĄams noskaidrot cÄloĆus, kas to izsauc. Ć im mÄrÄ·im veltÄ«tas darba visas 7 nodaÄŒas. DarbÄ aplĆ«koti inflÄcijas teorÄtiskie pamati, inflÄcijas struktĆ«ra un dinamika LatvijÄ no 2004. lÄ«dz 2007.gadam, analizÄta pieprasÄ«juma un izmaksu inflÄcija, kÄ arÄ« atseviĆĄÄ·as nodaÄŒas veltÄ«tas, pÄc autores domÄm, nozÄ«mÄ«gÄkajiem inflÄciju ietekmÄjoĆĄajiem faktoriem: inflÄcijas gaidÄm, darba produktivitÄtei, monetÄrajai un fiskÄlajai politikai.
Darba izstrÄdes gaitÄ autore ir nonÄkusi pie secinÄjumiem, ka inflÄcijas gaidas inflÄciju nozÄ«mÄ«gi ir ietekmÄjuĆĄas tikai Ä«si pirms Latvijas pievienoĆĄanÄ Eiropas savienÄ«bai, zemÄ darba produktivitÄte un straujais darba samaksas kÄpums veicina gan pieprasÄ«juma, gan izmaksu inflÄciju, pÄtÄmajÄ periodÄ nav vÄrojama nepamatota papÄ«rnaudas emisija, valdÄ«ba realizÄjusi ekspansÄ«vu fiskÄlo politiku, kas veicinÄjusi gan ekonomisko attÄ«stÄ«bu, gan strauju inflÄcijas kÄpumu.The theme of bachelor work âFactors affecting inflation in Latviaâ is actual in instant economical situation. Impetuous economical development in Latvia has brought overall promotion of price level that indicates unbalanced economical development and disarranged economical balance. High-ranking level of inflation prevents to attain the stated macroeconomical goals of Latvian government and exposes to danger Latviaâs further economical development.
To control inflation, first of all is necessary to clarify the whys and wherefores of inflation. To this aim is devoted all 7 chapters of this work. There is examined a theory of inflation, structure and dynamics of inflation in Latvia in 2004.-2007.year, influence of demand and producing expenses. Separate chapters are devoted to main factors affecting inflation, according to the author: expectation of inflation, labor productivity, monetary and fiscal politics.
As the result of work, author has made conclusions, that expectation of inflation had considerable impact on inflation only in one period- shortly before Latvia has joined European Union; low level of labor productivity and rapid grow affect both demand and producing expenses; in investigated period is not observed unreasoned issue of money; expansive fiscal politics realized by Latvian government has contributed as economical growth as hay level of inflation
CD2v Interacts with Adaptor Protein AP-1 during African Swine Fever Infection
African swine fever virus (ASFV) CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golgi network (TGN) protein complex AP-1, a key element in cellular traffic. This interaction was disrupted by brefeldin A even though the location of CD2v around the viral factory remained unchanged. CD2v-AP-1 binding was independent of CD2v glycosylation and occurred on the carboxy-terminal part of CD2v, where a canonical di-Leu motif previously reported to mediate AP-1 binding in eukaryotic cells, was identified. This motif was shown to be functionally interchangeable with the di-Leu motif present in HIV-Nef protein in an AP-1 binding assay. However, we demonstrated that it was not involved either in CD2v cellular distribution or in CD2v-AP-1 binding. Taken together, these findings shed light on CD2v function during ASFV infection by identifying AP-1 as a cellular factor targeted by CD2v and hence elucidate the cellular pathways used by the virus to enhance infectivity.Depto. de GenĂ©tica, FisiologĂa y MicrobiologĂaFac. de Ciencias BiolĂłgicasTRUEpu
A new collaborative shared control strategy for continuous elder/robot assisted navigation
In nowadays aging society, many people require mobility assistance. Autonomous wheelchairs may provide some help, but they are not supposed to overtake all control
on human mobility, as this is reported to lead to loss of residual capabilities and frustration. Instead, persons and wheelchairs are expected to cooperate. Traditionally, shared control hands control from human to robot depending on a triggering event. In this paper, though, we propose a method to allow constant cooperation between humans and robots, so that both have some weight in the emergent navigating behavior. We have tested the proposed method on a robotized Meyra wheelchair at Santa Lucia Hospedale in
Rome with several volunteering in-patients presenting different disabilities. Results in indoor environments have been satisfactory both from a quantitative and qualitative point of view.Peer Reviewe
Analytical and electrochemical investigations of reinforcement corrosion
SIGLEAvailable from British Library Document Supply Centre- DSC:3425.926(TRRL-CR--30) / BLDSC - British Library Document Supply CentreGBUnited Kingdo
CD2v colocalized with AP-1 in both infected and transfected cells.
<p>A: COS cells were MOCK-infected or infected with ASFV-E70 and immune-stained 16 hpi with α-γ-adaptin (AP-1) and α-CD2v. B: COS cells were MOCK-infected or infected with ASFV-E70 for 6h, and then treated with BFA for 3 h. At 9 hpi, cells were immune-stained as in A.</p