Susceptibilidad in vitro de dermatofitos, candida y otros hongos frente a Natamicina

Se investigó la actividad cuantitativa in vitro de Natamicina, un polieno de amplio espectro, frente a 98 cepas de Dermatofitos, Candida y otros hongos, aislados de muestras clínicas en Valdivia, Chile.Los resultados obtenidos muestran que el 100% de las cepas de Microsporum canis fue susceptible a 2S microgramos o menos y el 93,7% a 12,5 microgramos de Natamicina por ml. de agar.Trichophyton mentagrophytes fue inhibido en un 84,1% a 25 microgramos de Natamicina y Trichophyton rubrum, el 100% a 25 microgramos por ml. de agar.Candida albicans fue inhibida en un 85 y 100% respectivamente a C.I.M. de 6,25 y 12,5 microgramos de Natamicina por ml. de agar

L’intégration des citoyens vénézuéliens en Colombie: discours des dirigeants d’immigration à Bogotá et Cúcuta

Producto de la crisis que enfrenta Venezuela, miles de ciudadanos venezolanos han ingresado a Colombia; movimiento migratorio que supone una serie de desafíos tanto para el gobierno como para la sociedad civil. El presente artículo analiza la configuración del imaginario social de la integración de los inmigrantes venezolanos, a partir de entrevistas realizadas a ocho líderes inmigrantes radicados en las ciudades de Bogotá y Cúcuta. El imaginario se analiza desde los conceptos axiales de la obra de M. A. Baeza y la integración como proceso en tres niveles desde el abordaje de F. Aliaga Saéz. Se realizó análisis hermenéutico de los discursos y en el corpus se han identificado los campos semánticos que los líderes describen como aspectos clave para impulsar el proceso de integración: necesidad de orientación e información, atender la precariedad e informalidad laboral, el lazo entre Colombia y Venezuela, caracterizar la población inmigrante, sensibilización frente al fenómeno y evitar situaciones de conflictos.Como resultado da crise que a Venezuela enfrenta, milhares de cidadãos venezuelanos entraram na Colômbia; um movimento migratório que coloca uma série de desafios tanto para o governo como para a sociedade civil. Este artigo analisa a configuração do imaginário social da integração dos imigrantes venezuelanos, com base em entrevistas a oito líderes imigrantes baseados nas cidades de Bogotá e Cúcuta. O imaginário é analisado a partir dos conceitos axiais do trabalho de M. A. Baeza e a integração como um processo em três níveis a partir da abordagem de F. Aliaga Saéz. Foi realizada uma análise hermenêutica dos discursos e no corpus foram identificados os campos semânticos que os líderes descrevem como aspectos chave para promover o processo de integração: necessidade de orientação e informação, para atender à precariedade e informalidade laboral, a ligação entre Colômbia e Venezuela, para caracterizar a população imigrante, sensibilização perante o fenómeno e evitar situações de conflito.As a result of the crisis facing Venezuela, thousands of Venezuelan citizens have entered Colombia; migratory movement that supposes a series of challenges so much for the government as for the civil society. This article analyses the configuration of the social imaginary of the integration of Venezuelan immigrants, based on interviews with eight immigrant leaders living in the cities of Bogotá and Cúcuta. The imaginary is analysed from the axial concepts of the work of M. A. Baeza and the integration as a process in three levels from the approach of F. Aliaga Saéz. Hermeneutical analysis was done of the discourse and semantic fields have been identified in the corpus that the leaders describe as key aspects to impulse the integration process: need for guidance and information, attend job insecurity and informality, the link between Colombia and Venezuela, characterize the immigrant population, awareness of the phenomenon and avoid conflict situations.La crise que traverse le Venezuela a poussé des milliers de Vénézuéliens vers la Colombie, créant un mouvement migratoire qui soulève une série de défis pour le gouvernement comme pour la société civile. Cet article analyse la configuration de l’imaginaire social de l’intégration des immigrants vénézuéliens, à partir d’entretiens avec huit leaders immigrants installés à Bogotá et à Cúcuta. L’imaginaire est analysé à partir des concepts centraux du travail de M. A. Baeza et l’intégration comme un processus à trois niveaux, à partir de l’approche de F. Aliaga Saéz. Une analyse herméneutique des discours a permis d’identifier les champs sémantiques que les leaders décrivent comme des éléments-clés pour promouvoir le processus d’intégration : le besoin d’orientation et d’information, pour faire face à la précarité et à l’informalité du travail, la relation entre la Colombie et le Vénézuéla, pour caractériser la population immigrante, la sensibilisation face au phénomène pour éviter les situations de conflit

Stoichiometric and irreversible cysteine-selective protein modification using carbonylacrylic reagents

Maleimides remain the reagents of choice for the preparation of therapeutic and imaging protein conjugates despite the known instability of the resulting products that undergo thiol-exchange reactions $\textit{in vivo}$. Here we present the rational design of carbonylacrylic reagents for chemoselective cysteine bioconjugation. These reagents undergo rapid thiol Michael-addition under biocompatible conditions in stoichiometric amounts. When using carbonylacrylic reagents equipped with PEG or fluorophore moieties, this method enables access to protein and antibody conjugates precisely modified at pre-determined sites. Importantly, the conjugates formed are resistant to degradation in plasma and are biologically functional, as demonstrated by the selective imaging and detection of apoptotic and HER2+ cells, respectively. The straightforward preparation, stoichiometric use and exquisite cysteine selectivity of the carbonylacrylic reagents combined with the stability of the products and the availability of biologically relevant cysteine-tagged proteins make this method suitable for the routine preparation of chemically defined conjugates for $\textit{in vivo}$ applications.FAPESP (Grant IDs: 2012/22274-2; BEPE 2015/07509-1, 2013/25504-1), Xunta de Galicia, FCT Portugal (FCT Investigator, SFRH/BPD/103172/2014 Postdoctoral fellowship, SFRH/BD/111556/2015 PhD Studentship), European Union (Marie-Sklodowska Curie ITN Protein Conjugates), Engineering and Physical Sciences Research Council, MECD (‘Salvador Madariaga’ mobility grant PRX15/00638), MINECO (CTQ2015-70524-R, RYC-2013-14706 ), Royal Society, European Research Council Starting Grant (TagIt

First record of the alien pest Rhaponticum repens (Compositae) in the Iberian Peninsula

First record of the alien pest Rhaponticum repens (Compositae) in the Iberian Peninsula.- Rhaponticum repens is reported for the first time for the flora of the Iberian Peninsula. The species is native from Central Asia and has become invasive in Argentina, Canada, Europe and the USA. It was detected for the first time in abandoned fields from Vilablareix, near the city of Girona (Catalonia, Spain) and in the valley of the Vinalopó in Alicante (Valencia, Spain), where it was collected as early as in 1959 but misdentified. Molecular data, based on nrDNA region ITS, suggest that the reported populations may be closely related to plants from the United States. Due to the extremely noxious character of the species and the possible relationship of Spanish plants with the invasive American populations, some kind of monitoring is recommended.Rhaponticum repens (Compositae), una nueva planta alóctona para la Península Ibérica.- Se cita por primera vez la especie Rhaponticum repens para la flora de la Península Ibérica. Rhaponticum repens es una especie nativa de Asia central que actúa como invasora en diversos países como Argentina, Canadá o los Estados Unidos. Se ha encontrado por primera vez en campos de cultivo abandonados en el pueblo de Vilablareix, cerca de la ciudad de Girona (Cataluña, España) y en el valle del Vinalopó (Valencia, España), donde fue recolectada y mal identificada en 1959. Los datos moleculares, obtenidos a partir de la región ITS del nrDNA, sugieren que estas poblaciones podrían estar relacionadas con plantas invasoras de Estados Unidos. Debido al carácter extremadamente invasor de la especie, y a su posible origen secundario a partir de las poblaciones norteamericanas, se recomienda el seguimiento de estas poblacione

Enhanced Permeability and Binding Activity of Isobutylene-Grafted Peptides.

We present a new peptide-macrocyclization strategy with an isobutylene graft. The reaction is mild and proceeds rapidly and efficiently both for linear and cyclic peptides. The resulting isobutylene-grafted peptides possess improved passive membrane permeability due to the shielding of the polar backbone of the amides, as demonstrated by NMR spectroscopy and molecular dynamics simulations. The isobutylene-stapled structures are fully stable in human plasma and in the presence of glutathione. This strategy can be applied to bioactive cyclic peptides such as somatostatin. Importantly, we found that structural preorganization forced by the isobutylene graft leads to a significant improvement in binding. The combined advantages of directness, selectivity, and smallness could allow application to peptide macrocyclization based on this attachment of the isobutylene graft

The use of fluoroproline in MUC1 antigen enables efficient detection of antibodies in patients with prostate cancer

A structure-based design of a new gene22ration tumor-associated glycopeptides with improved affinity against two anti-MUC1 antibodies is described. These unique antigens feature a fluorinated proline residue, such as a (4S)-4-fluoro-L-proline or 4,4-difluoroproline, at the most immunogenic domain. Binding assays using bio-layer interferometry reveal 3-fold to 10-fold affinity improvement with respect to the natural (glyco)peptides. According to X-ray crystallography and MD simulations, the fluorinated residues stabilize the antigen-antibody complex by enhancing key CH/ interactions. Interestingly, a notable improvement in detection of cancer-associated anti-MUC1 antibodies from serum of patients with prostate cancer is achieved with the non-natural antigens, which proves that these derivatives can be considered better diagnostic tools than the natural antigen for this type of cancer.We thank the Ministerio de Economía y Competitividad (projects CTQ2015-67727-R, UNLR13-4E-1931, CTQ2013-44367-C2-2-P, CTQ2015-64597-C2-1P, and BFU2016-75633-P). I. A. B. thanks the Asociación Española Contra el Cancer en La Rioja for a grant. I. S. A. and G. J. L. B. thank FCT Portugal (PhD studentship and FCT Investigator, respectively) and the EPSRC for funding. G. J. L. B. holds a Royal Society URF and an ERC StG (TagIt). F.C. and G. J. L. B thank the EU (Marie-Sklodowska Curie ITN, Protein Conjugates). R.H-G. thanks Agencia Aragonesa para la Investigación y Desarrollo (ARAID) and the Diputación General de Aragón (DGA, B89) for financial support. The research leading to these results has also received funding from the FP7 (2007-2013) under BioStruct-X (grant agreement N°283570 and BIOSTRUCTX_5186). We thank synchrotron radiation source DIAMOND (Oxford) and beamline I04 (number of experiment mx10121-19). Hokkaido University group acknowledges to JSPS KAKENHI Grant Number 25220206 and JSPS Wakate B KAKENHI Grant Number 24710242. We also thank CESGA (Santiago de Compostela) for computer support

Chameleonic Generalized Brans--Dicke model and late-time acceleration

In this paper we consider Chameleonic Generalized Brans--Dicke Cosmology in the framework of FRW universes. The bouncing solution and phantom crossing is investigated for the model. Two independent cosmological tests: Cosmological Redshift Drift (CRD) and distance modulus are applied to test the model with the observation.Comment: 20 pages, 15 figures, to be published in Astrophys. Space Sci. (2011

Stretch-induced activation of pannexin 1 channels can be prevented by pka-dependent phosphorylation

Indexación ScopusPannexin 1 channels located in the cell membrane are permeable to ions, metabolites, and signaling molecules. While the activity of these channels is known to be modulated by phosphorylation on T198, T308, and S206, the possible involvement of other putative phosphorylation sites remains unknown. Here, we describe that the activity of Panx1 channels induced by mechanical stretch is reduced by adenosine via a PKA-dependent pathway. The mechanical stretch-induced activity—measured by changes in DAPI uptake—of Panx1 channels expressed in HeLa cell transfectants was inhibited by adenosine or cAMP analogs that permeate the cell membrane. Moreover, inhibition of PKA but not PKC, p38 MAPK, Akt, or PKG prevented the effects of cAMP analogs, suggesting the involvement of Panx1 phosphorylation by PKA. Accordingly, alanine substitution of T302 or S328, two putative PKA phosphorylation sites, prevented the inhibitory effect of cAMP analogs. Moreover, phosphomimetic mutation of either T302 or S328 to aspartate prevented the mechanical stretch-induced activation of Panx1 channels. A molecular dynamics simulation revealed that T302 and S328 are located in the water–lipid interphase near the lateral tunnel of the intracellular region, suggesting that their phosphorylation could promote conformational changes in lateral tunnels. Thus, Panx1 phosphorylation via PKA could be modulated by G protein-coupled receptors associated with the Gs subunit. © 2020, MDPI AG. All rights reserved.https://www.mdpi.com/1422-0067/21/23/918

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria