191 research outputs found

    Diversity of regulatory mechanisms in the C/N metabolism of the marine cyanobacteria Prochlorococcus and synechococcus

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    Marine picocyanobacteria are the most abundant photosynthetic organisms on Earth, with only two genera, Prochlorococcus (Johnson et al., 2006, Olson et al., 1990, Partensky et al., 1999) and Synechococcus (Scanlan, 2003, Scanlan & West, 2002) numerically dominating most oceanic waters. During this research project our main goal was to study the diversity of the regulatory mechanisms in the C/N metabolism of these cyanobacteria. Recent advances in the knowledge of nitrogen metabolism of Prochlorococcus have shown that it has fine regulatory systems to optimize nitrogen assimilation (Rocap et al., 2003, García-Fernández et al., 2004, Lindell et al., 2002). Thus, we have studied the role of 2-oxoglutarate in the control of the C/N balance in order to check whether there exist differences with respect to other model cyanobacteria and among strains of Prochlorococcus. The comparative study performed show that 2-oxoglutarate is the molecule responsible in Prochlorococcus to control the balance between carbon and nitrogen metabolism and there are differences among strains in sensing this metabolite. These results could be an explanation for its adaptation to different ecological niches in the ocean. Besides, we wanted to know how Synechococcus is able to successfully coexist with Prochlorococcus. For that, the hypothesis was that Synechococcus could be more efficient at the utilization of low concentration of nitrate. The results showed that when concentrations of nitrate in the range of nanomolar are present, the genes related with the assimilation of that source are up-regulated in Synechococcus WH7803. Therefore, these facts suggest that the machinery is working at transcriptional level in order to uptake the nitrate. This could be an evolutionary advantage against Prochlorococcus in the real field.Las picocianobacterias marinas son los organismos fotosintéticos más abundantes en la Tierra, con sólo dos géneros, Prochlorococcus (Johnson et al., 2006, Olson et al., 1990, Partensky et al., 1999) y Synechococcus (Scanlan, 2003, Scanlan & West, 2002) dominando la mayor parte de los océanos. El principal objetivo durante este proyecto de investigación ha sido estudiar la diversidad de mecanismos regulatorios del metabolismo del C/N en estas cianobacterias. Recientes avances en la regulación del metabolismo del nitrógeno en Prochlorococcus muestran que tienen una fina regulación para optimizar la asimilación del nitrógeno (Rocap et al., 2003, García-Fernández & Diez, 2004, Lindell et al., 2002). Por lo tanto, hemos estudiado el papel del 2-oxoglutarato en el control del balance C/N con el fin de comprobar si existen diferencias con respecto a otras cianobacterias modelos, e incluso si estas diferencias se encuentran entre estirpes. Lo resultados obtenidos del estudio comparativo mostraron que el 2-oxoglutarato es la molécula responsable del control del balance C/N en Prochlorococcus y que existen diferencias entre estirpes en la detección de este metabolito. Esto pueden ser una explicación de la adaptación a diferentes nichos ecológicos en el océano. Además, nosotros queríamos responder a la pregunta de cómo Synechococcus es capaz de coexistir con éxito con Prochlorococcus. Para ello, la hipótesis era que Synechococcus puede ser más eficaz en la utilización de concentraciones bajas de nitrato. Los resultados mostraron que cuando hay concentraciones de nitrato en el rango de nanomolar, se sobreexpresan los genes relacionados con la asimilación de esta fuente en Synechococcus WH7803. Estos hechos sugieren que hay una regulación a nivel transcripcional con el objetivo de absorber el nitrato a concentraciones bajas. Esto podría ser una ventaja evolutiva respecto a Prochlorococcus en los ecosistemas donde conviven

    Molecular basis for the distinct divalent cation requirement in the uridylylation of the signal transduction proteins GlnJ and GlnB from Rhodospirillum rubrum

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    Background: PII proteins have a fundamental role in the control of nitrogen metabolism in bacteria, through interactions with different PII targets, controlled by metabolite binding and post-translational modification, uridylylation in most organisms. In the photosynthetic bacterium Rhodospirillum rubrum, the PII proteins GlnB and GlnJ were shown, in spite of their high degree of similarity, to have different requirements for post-translational uridylylation, with respect to the divalent cations, Mg2+ and Mn2+. Results: Given the importance of uridylylation in the functional interactions of PII proteins, we have hypothesized that the difference in the divalent cation requirement for the uridylylation is related to efficient binding of Mg/Mn-ATP to the PII proteins. We concluded that the amino acids at positions 42 and 85 in GlnJ and GlnB (in the vicinity of the ATP binding site) influence the divalent cation requirement for uridylylation catalyzed by GlnD. Conclusions: Efficient binding of Mg/Mn-ATP to the PII proteins is required for uridylylation by GlnD. Our results show that by simply exchanging two amino acid residues, we could modulate the divalent cation requirement in the uridylylation of GlnJ and GlnB. Considering that post-translational uridylylation of PII proteins modulates their signaling properties, a different requirement for divalent cations in the modification of GlnB and GlnJ adds an extra regulatory layer to the already intricate control of PII functio

    Lentes de contacto para vehiculizar principios activos: una prometedora herramienta terapéutica

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    The ocular administration of drugs using traditional pharmaceutical forms, including eye drops or ointments, results in low bioavailability, as well as requiring multiple administrations per day, with the consequent danger of therapeutic non-compliance. Although, through the use of pharmaceutical technology, attempts have been made to use various solutions in order to increase bioavailability in the most common pharmaceutical forms, it has not been entirely satisfactory. In this context, contact lenses are presented as drug delivery systems that largely remedy these two major problems and offer other additional advantages. Therefore, the use of contact lenses as drug carrying systems has been increasingly investigated in recent years, as they can increase the bioavailability of these drugs, leading to an increase in therapeutic efficacy and compliance. The main techniques used to achieve this goal are included in this review, including immersion in drug solutions, use of vitamin E barriers, molecular printing, colloidal systems, etc. The most interesting results, depending on the different eye pathologies, are presented. Although the use of contact lenses as a vehicle for the release of active ingredients is a relatively novel strategy, there are already many studies and trials that support it. In any case, further research needs to be carried out to finally reach an effective, safe, and stable product that can be marketed.nLa administración ocular de fármacos utilizando formas farmacéuticas tradicionales, comolas gotas oftálmicas o pomadas entre otras, proporciona una baja biodisponibilidad delos fármacos así como múltiples administraciones al día con el consiguiente peligro deincumplimiento terapéutico. Aunque la Tecnología Farmacéutica ha intentado proponer diversas soluciones para aumentar la biodisponibilidad en las formas farmacéuticas más comunes, no ha sido del todo satisfactorio. En este contexto, las lentes de contacto se pre- sentan como sistemas de liberación de fármacos que subsanan en gran medida estos dos grandes problemas y ofrecen otras ventajas adicionales. Por ello, en los últimos an˜ os, se ha investigado con más empen˜ o el uso de lentes de contacto como sistemas portadores de fármacos, ya que pueden aumentar la biodisponibilidad de los mismos, proporcionando un aumento de la eficacia y cumplimiento terapéuticos. En la presente revisión se han referenciado las principales técnicas utilizadas para alcanzar dicho fin: inmersión en soluciones de fármaco, uso de barreras de vitamina E, impresión molecular, sistemas coloidales, etc. A continuación se recogen los resultados más intere- santes encontrados en función de las distintas patologías oculares. El uso de lentes de contacto para la vehiculización y liberación de principios activos es una estrategia relativamente novedosa aunque ya tiene muchos estudios y ensayos que lo sustentan. De todas formas se deben seguir investigando para alcanzar finalmente un producto eficaz, seguro y estable, y que pueda llegar a ser comercializado

    UPCBLAS: a library for parallel matrix computations in Unified Parallel C

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    This is the peer reviewed version of the following article: González‐Domínguez, J. , Martín, M. J., Taboada, G. L., Touriño, J. , Doallo, R. , Mallón, D. A. and Wibecan, B. (2012), UPCBLAS: a library for parallel matrix computations in Unified Parallel C. Concurrency Computat.: Pract. Exper., 24: 1645-1667. doi:10.1002/cpe.1914, which has been published in final form at https://doi.org/10.1002/cpe.1914. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.[Abstract] The popularity of Partitioned Global Address Space (PGAS) languages has increased during the last years thanks to their high programmability and performance through an efficient exploitation of data locality, especially on hierarchical architectures such as multicore clusters. This paper describes UPCBLAS, a parallel numerical library for dense matrix computations using the PGAS Unified Parallel C language. The routines developed in UPCBLAS are built on top of sequential basic linear algebra subprograms functions and exploit the particularities of the PGAS paradigm, taking into account data locality in order to achieve a good performance. Furthermore, the routines implement other optimization techniques, several of them by automatically taking into account the hardware characteristics of the underlying systems on which they are executed. The library has been experimentally evaluated on a multicore supercomputer and compared with a message‐passing‐based parallel numerical library, demonstrating good scalability and efficiency.Ministerio de Ciencia e Innovación; TIN2010-16735Ministerio de Educación; AP2008-0157

    Fluorescence enhancement of fungicide thiabendazole by van der Waals interaction with transition metal dichalcogenide nanosheets for highly specific sensors

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    Many molecules quench their fluorescence upon adsorption on surfaces. Herein we show that the interaction of thiabendazole, a widespread used fungicide of the benzimidazole family, with nanosheets of transition metal dichalcogenides, particularly of WS2, leads to a significant increase, more than a factor of 5, of the fluorescence yield. This surprising effect is rationalized by DFT calculations and found to be related to the inhibition of the intramolecular rotation between the benzimidazole and thiazole groups due to a bonding rigidization upon interaction with the MoS2 surface. This non-covalent adsorption leads to a redistribution of the molecular LUMO that blocks the non-radiative energy dissipation channel. This unusual behaviour does not operate either for other molecules of the same benzimidazole family or for other 2D materials (graphene or graphene oxide). Moreover, we found that a linear dependence of the emission with the concentration of thiabendazole in solution, which combined with the specificity of the process, allows the development of a highly sensitive and selective method towards thiabendazole determination that can be applied to real river water samples. An excellent detection limit of 2.7 nM, comparable to the best performing reported methods, is obtained with very good accuracy (Er ≤ 6.1%) and reproducibility (RSD ≤ 4.1%) in the concentration range assayedThe authors acknowledge financial support from the Spanish MINECO (MAT2017-85089-C2-1-R, MAT2017-85089-C2-2-R) and the EU via the ERC-Synergy Program (grant ERC-2013-SYG-610256 NANOCOSMOS) and Horizon 2020 Research and Innovation Program (Graphene Flagship-core2 – 785219) and the Comunidad Autónoma de Madrid (P2018/NMT-4349, TRANSNANOAVANSENS-CM and P2018/NMT-4367 FOTOART). J. I. M. acknowledges the support by the “Ramón y Cajal” Program of MINECO (grant RYC-2015-17730

    A 2D algorithm with asymmetric workload for the UPC conjugate gradient method

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    This is a post-peer-review, pre-copyedit version of an article published in Journal of Supercomputing. The final authenticated version is available online at: https://doi.org/10.1007/s11227-014-1300-0[Abstract] This paper examines four different strategies, each one with its own data distribution, for implementing the parallel conjugate gradient (CG) method and how they impact communication and overall performance. Firstly, typical 1D and 2D distributions of the matrix involved in CG computations are considered. Then, a new 2D version of the CG method with asymmetric workload, based on leaving some threads idle during part of the computation to reduce communication, is proposed. The four strategies are independent of sparse storage schemes and are implemented using Unified Parallel C (UPC), a Partitioned Global Address Space (PGAS) language. The strategies are evaluated on two different platforms through a set of matrices that exhibit distinct sparse patterns, demonstrating that our asymmetric proposal outperforms the others except for one matrix on one platform.Ministerio de Economía y Competitividad; TIN2013-42148-PXunta de Galicia; GRC2013/055United States. Department of Energy; DEAC03-76SF0009

    Physiological Regulation of Isocitrate Dehydrogenase and the Role of 2-Oxoglutarate in Prochlorococcus sp. Strain PCC 9511

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    The enzyme isocitrate dehydrogenase (ICDH; EC 1.1.1.42) catalyzes the oxidative decarboxylation of isocitrate, to produce 2- oxoglutarate. The incompleteness of the tricarboxylic acids cycle in marine cyanobacteria confers a special importance to isocitrate dehydrogenase in the C/N balance, since 2-oxoglutarate can only be metabolized through the glutamine synthetase/glutamate synthase pathway. The physiological regulation of isocitrate dehydrogenase was studied in cultures of Prochlorococcus sp. strain PCC 9511, by measuring enzyme activity and concentration using the NADPH production assay and Western blotting, respectively. The enzyme activity showed little changes under nitrogen or phosphorus starvation, or upon addition of the inhibitors DCMU, DBMIB and MSX. Azaserine, an inhibitor of glutamate synthase, induced clear increases in the isocitrate dehydrogenase activity and icd gene expression after 24 h, and also in the 2-oxoglutarate concentration. Iron starvation had the most significant effect, inducing a complete loss of isocitrate dehydrogenase activity, possibly mediated by a process of oxidative inactivation, while its concentration was unaffected. Our results suggest that isocitrate dehydrogenase responds to changes in the intracellular concentration of 2-oxoglutarate and to the redox status of the cells in Prochlorococcus

    Unveiling the collaborative effect at the cucurbit[8]urilMoS2 hybrid interface for electrochemical melatonin determination

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    Host-guest interactions are of paramount importance in supramolecular chemistry and in a wide range of applications. Particularly well known is the ability of cucurbit[n]urils (CB[n]) to selectively host small molecules. We show that the charge transfer and complexation capabilities of CB[n] are retained on the surface of 2D transition metal dichalcogenides (TMDs), allowing the development of efficient electrochemical sensing platforms. We unveil the mechanisms of host-guest recognition between the MoS2- CB[8] hybrid interface and melatonin (MLT), an important molecular regulator of vital constants in vertebrates. We find that CB[8] on MoS2 organizes the receptor portals perpendicularly to the surface, facilitating MLT complexation. This advantageous adsorption geometry is specific to TMDs and favours MLT electro-oxidation, as opposed to other 2D platforms like graphene, where one receptor portal is closed. This study rationalises the cooperative interaction in 2D hybrid systems to improve the efficiency and selectivity of electrochemical sensing platform

    Metodología para la determinación de disponibilidad y déficit de agua superficial en cuencas hidrológicas: aplicación al caso de la normativa mexicana

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    La existencia de disponibilidad media anual de agu superficial, conforme a la Leyde Aguas Nacionales mexicana, es condicionante para la autorización de nuevasconcesiones o asignaciones en una cuenca. La norma oficial mexicana NOM-011-CNA-2000 establece el procedimiento base para su determinación. Aunque elconcepto de déficit es opuesto al de disponibilidad, en la actualidad el primeroestá implícito en el segundo en la norma mexicana. En este trabajo se analizanambos conceptos, y se presenta un planteamiento matemático general y consistente,que permite determinar ambos de manera independiente; incluso se contempladescomponer el déficit total en interno y externo. Se demuestra la funcionalidadconceptual y numérica de la metodología que se propone a través de su aplicaciónal caso de la cuenca del río Bravo, que se presenta como ejemplo demostrativo. Elprocedimiento desarrollado es aplicable a cualquier cuenca, sin importar en qué paísse localice, y facilita la interpretación de los estudios de disponibilidad por parte dela sociedad, así como su uso para fines de planificación hídrica. De incorporarse losresultados de este trabajo en la NOM-011-CNA-2000, se contribuiría a enriquecereste importante instrumento normativo en México

    Evaluation of the immunogenicity and efficacy of BCG and MTBVAC vaccines using a natural transmission model of tuberculosis

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    International audienceAbstractEffective vaccines against tuberculosis (TB) are needed in order to prevent TB transmission in human and animal populations. Evaluation of TB vaccines may be facilitated by using reliable animal models that mimic host pathophysiology and natural transmission of the disease as closely as possible. In this study, we evaluated the immunogenicity and efficacy of two attenuated vaccines, BCG and MTBVAC, after each was given to 17 goats (2 months old) and then exposed for 9 months to goats infected with M. caprae. In general, MTBVAC-vaccinated goats showed higher interferon-gamma release than BCG vaccinated goats in response to bovine protein purified derivative and ESAT-6/CFP-10 antigens and the response was significantly higher than that observed in the control group until challenge. All animals showed lesions consistent with TB at the end of the study. Goats that received either vaccine showed significantly lower scores for pulmonary lymph nodes and total lesions than unvaccinated controls. Both MTBVAC and BCG vaccines proved to be immunogenic and effective in reducing severity of TB pathology caused by M. caprae. Our model system of natural TB transmission may be useful for evaluating and optimizing vaccines
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