The International Monetary Fund and its role as a guarantor of global financial stability

Artículo de revistaGiven the growing real and financial integration of economies worldwide, there is a need for the presence of supranational mechanisms to address crisis situations. The International Monetary Fund (IMF) is the multilateral institution at the core of the global financial safety net (GFSN). The swift development of other elements of this net since the last global financial crisis, such as the regional financing arrangements, has made the system sounder but also poses fresh challenges. The broad membership of the IMF, the volume of its resources and its accumulated global experience in crisis management make the organisation key to shoring up global monetary and financial stability. However, the IMF is subject to recurrent discussions about its governance and lending policies, including the size and composition of its resources, and the distribution of power within the organisation. The IMF is currently immersed in the Fifteenth General Review of Quotas. The backdrop to this negotiation is the risk that, in the absence of a satisfactory agreement on the size and distribution of its resources, the IMF’s financial sufficiency and its degree of representativeness among its members may be diminished in the coming years. This might significantly undermine the stabilising capacity of the GFS

Generadores de electricidad bioinorgánicos. Conversión de energía química renovable a través de materiales piezoeléctricos funcionalizados con enzimas

In this project we have developed a new generation of bio-inorganic generators aimed at the electri­city production from renewable fuels. These systems are presented as an alternative to electroche­mical fueled cells. In this context, we have fabricated a new hybrid system, which fuses a biological machinery able to transform chemical energy into mechanical energy (pressure and vibration), with a piezoelectric material who convert such mechanical energy into electricity (bio-inorganic generator). The mechanical stimuli, as pressure and vibration, are generated as an outcome of the produced gases coming from renewable fuels; this reaction is catalyzed by the biological machinery (enzymes) which are part of the generator. These devices are able to produce electricity at the microscopic scale starting from renewable fuels as sugars and alcohols coming from the biomass. This fact is very significant allowing the indirect production of electricity with zero emissions. Moreover, these bio-inorganic generators open a passionate spectrum of new applications in different fields like sensing, robotics and energetics.En este proyecto hemos desarrollado una nueva generación de generadores bioinorgánicos para producir electricidad a partir de combustibles renovables. Estos sistemas se presentan como alternativa a las pilas de combustible basadas en procesos electroquímicos. En este contexto, hemos fabricado un nuevo sistema híbrido que fusiona una maquinaria biológica, capaz de transformar un combustible en energía mecánica (presión y vibración), con un material piezoeléctrico que transforma esa energía mecánica en electricidad (generador bioinorgánico). Los estímulos mecánicos de presión y vibración son generados gracias a la producción de gases a partir de combustibles. Esta reacción está catalizada por la maquinaria biológica (enzimas) que forma parte del generador. Estos dispositivos son capaces de producir electricidad a escala microscópica a partir de combustibles procedentes de fuentes renovables como azúcares y alcoholes provenientes de la biomasa. Este hecho es muy significativo, puesto que indirectamente permite generar electricidad con cero emisiones. Además, estos generadores bioinorgánicos abren un abanico apasionante de nuevas aplicaciones en campos tan diversos como la sensórica, la robótica y la energía

Development of a hybrid bioinorganic nanobiocatalyst : Remarkable impact of the immobilization conditions on activity and stability of β-galactosidase

Hybrid bioinorganic biocatalysts have received much attention due to their simple syn-thesis, high efficiency, and structural features that favor enzyme activity and stability. The present work introduces a biomineralization strategy for the formation of hybrid nanocrystals from β-ga-lactosidase. The effects of the immobilization conditions were studied, identifying the important effect of metal ions and pH on the immobilization yield and the recovered activity. For a deeper understanding of the biomineralization process, an in silico study was carried out to identify the ion binding sites at the different conditions. The selected β-galactosidase nanocrystals showed high specific activity (35,000 IU/g biocatalyst) and remarkable thermal stability with a half-life 11 times higher than the soluble enzyme. The nanobiocatalyst was successfully tested for the synthesis of galacto-oligosaccharides, achieving an outstanding performance, showing no signs of diffusional limitations. Thus, a new, simple, biocompatible and inexpensive nanobiocatalyst was produced with high enzyme recovery (82%), exhibiting high specific activity and high stability, with promis-ing industrial applications

Self-sufficient flow-biocatalysis by coimmobilization of pyridoxal 5′-phosphate and ω-transaminases onto porous carriers

We expanded the application of self-sufficient heterogeneous biocatalysts containing coimmobilized w-transaminases and pyridoxal 5´-phosphate (PLP) to efficiently operate packed-bed reactors in continuous flow. Using a w-transaminase from Halomonas elongata co-immobilized with PLP onto porous methacrylate-based carriers coated with polyethyleneimine, we operated a packed-bed reactor continuously for up to 50 column volumes at 1.45 mL x min-1 in the enantioselective deamination of model amines (α-methylbenzyl amine), yielding > 90% conversion in all cycles without exogenous addition of cofactor. In this work, we expanded the concept of self-sufficient heterogeneous biocatalysts to other w-transaminases such as the ones from Chromobacterium violaceum and Pseudomonas fluorescens. We found that enzymes with lower affinities towards PLP present lower operational stabilities in flow, even when coimmobilizing PLP. Furthermore, w-transaminases co-immobilized with PLP were successfully implemented for the continuous synthesis of amines and the sustainable metrics were assessed. These results give some clues to exploit PLP-dependent w-transaminases under industrially relevant continuous operations in a more cost-effective and environmentally friendly process

Métodos de caracterización cinética de biocatalizadores heterogéneos a nivel de partícula simple

En este trabajo se ha desarrollado un método de análisis de imagen de microscopía de fluorescencia que permite caracterizar cinéticamente el biocatalizador heterogéneo a nivel de partícula simple. Para ello, monitorizando la fluorescencia del interior de las micropartículas se han obtenido los cursos de reacción a nivel de partícula simple de las enzimas inmovilizadas en su interior. Esto ha sido posible debido al tipo de muestras analizadas, con enzimas dependientes de cofactores de nicotamida autofluorescentes en su forma reducida (NADH/NADPH), permitiendo asociar la fluorescencia con la concentración de cofactor, y por tanto con la actividad enzimática. Posteriormente, estos cursos de reacción enzimáticos han sido ajustados con una función Lambert W para calcular sus parámetros cinéticos. A lo largo de este trabajo se explican las diferentes fases llevadas a cabo para, partiendo de las imágenes iniciales de fluorescencia, obtener los parámetros cinéticos finales en las partículas del biocatalizador. Para este trabajo han sido analizadas muestras de diferentes sistemas enzimáticos donde las enzimas, co-inmovilizadas con los cofactores en micropartículas porosas, catalizaron distintas reacciones monitorizadas en el microscopio de fluorescencia.<br /

Selective Immobilization of Fluorescent Proteins for the Fabrication of Photoactive Materials

The immobilization of fluorescent proteins is a key technology enabling to fabricate a new generation of photoactive materials with potential technological applications. Herein we have exploited superfolder green (sGFP) and red (RFP) fluorescent proteins expressed with different polypeptide tags. We fused these fluorescent proteins to His-tags to immobilize them on graphene 3D hydrogels, and Cys-tags to immobilize them on porous microparticles activated with either epoxy or disulfide groups and with Lys-tags to immobilize them on upconverting nanoparticles functionalized with carboxylic groups. Genetically programming sGFP and RFP with Cys-tag and His-tag, respectively, allowed tuning the protein spatial organization either across the porous structure of two microbeads with different functional groups (agarose-based materials activated with metal chelates and epoxy-methacrylate materials) or across the surface of a single microbead functionalized with both metal-chelates and disulfide groups. By using different polypeptide tags, we can control the attachment chemistry but also the localization of the fluorescent proteins across the material surfaces. The resulting photoactive material formed by His-RFP immobilized on graphene hydrogels has been tested as pH indicator to measure pH changes in the alkaline region, although the immobilized fluorescent protein exhibited a narrower dynamic range to measure pH than the soluble fluorescent protein. Likewise, the immobilization of Lys-sGFP on alginate-coated upconverting nanoparticles enabled the infrared excitation of the fluorescent protein to be used as a green light emitter. These novel photoactive biomaterials open new avenues for innovative technological developments towards the fabrication of biosensors and photonic devices

Metal substrate catalysis in the confined space for platinum drug delivery

[EN] Catalysis-based approaches for the activation of anticancer agents hold considerable promise. These principally rely on the use of metal catalysts capable of deprotecting inactive precursors of organic drugs or transforming key biomolecules available in the cellular environment. Nevertheless, the efficiency of most of the schemes described so far is rather low, limiting the benefits of catalytic amplification as strategy for controlling the therapeutic effects of anticancer compounds. In the work presented here, we show that flavin reactivity within a hydrogel matrix provides a viable solution for the efficient catalytic activation and delivery of cisplatin, a worldwide clinically-approved inorganic chemotherapy agent. This is achieved by ionically adsorbing a flavin catalyst and a Pt(iv) prodrug as substrate into porous amino-functionalized agarose beads. The hydrogel chassis supplies high local concentrations of electron donating groups/molecules in the surrounding of the catalyst, ultimately boosting substrate conversion rates (TOF >200 min(-1)) and enabling controlled liberation of the drug by light or chemical stimuli. Overall, this approach can afford platforms for the efficient delivery of platinum drugs as demonstrated herein by using a transdermal diffusion model simulating the human skin.We acknowledge financial support from the Spanish State Research Agency (grants CTQ2016-80844-R, PID2019-109111RBI00, RTI2018-094398-B-I00, BIO2014-61838-EXP) and the Basque Government (Eusko Jaurlaritza, grant PIBA_2021_1_0034). S. V. L. thanks the Mexican Council of Science and Technology (CONACyT) for the postdoctoral fellowship she received (ref. CVU-267390). C. S. C. thanks Gipuzkoa Foru Aldundia (Gipuzkoa Fellows program; grant number 2019-FELL-000018-01/62/2019) for.nancial support. L. S. thanks the Spanish MultiMetDrugs network (RED2018-102471-T) for fruitful discussion. FLG thanks the Spanish Biocatalysis network (RED2018-102403T) and the European Research Council (ERC-Co-2018 818089). This work was performed under the Maria de Maeztu and Severo Ochoa Centres of Excellence Programme run by the Spanish State Research Agency, Grant No. MDM-2017-0720 (CIC biomaGUNE) and CEX2018-000867-S (DIPC)

Engineering the substrate specificity of a thermophilic penicillin acylase from thermus thermophilus

A homologue of the Escherichia coli penicillin acylase is encoded in the genomes of several thermophiles, including in different Thermus thermophilus strains. Although the natural substrate of this enzyme is not known, this acylase shows a marked preference for penicillin K over penicillin G. Three-dimensional models were created in which the catalytic residues and the substrate binding pocket were identified. Through rational redesign, residues were replaced to mimic the aromatic binding site of the E. coli penicillin G acylase. A set of enzyme variants containing between one and four amino acid replacements was generated, with altered catalytic properties in the hydrolyses of penicillins K and G. The introduction of a single phenylalanine residue in position α188, α189, or β24 improved the Km for penicillin G between 9- and 12-fold, and the catalytic efficiency of these variants for penicillin G was improved up to 6.6-fold. Structural models, as well as docking analyses, can predict the positioning of penicillins G and K for catalysis and can demonstrate how binding in a productive pose is compromised when more than one bulky phenylalanine residue is introduced into the active site. © 2013, American Society for Microbiology.Spanish Ministry of Science (CIT no. 010000-2009-29, RyC2006-02441, and BIO2010-18875); Fundación Ramón ArecesPeer Reviewe

Mechanistic studies of a lipase unveil effect of pH on hydrolysis products of small PET modules

Biocatalysis is a key technology enabling plastic recycling. However, despite advances done in the development of plastic-degrading enzymes, the molecular mechanisms that govern their catalytic performance are poorly understood, hampering the engineering of more efficient enzyme-based technologies. In this work, we study the hydrolysis of PET-derived diesters and PET trimers catalyzed by the highly promiscuous lipase B from Candida antarctica (CALB) through QM/MM molecular dynamics simulations supported by experimental Michaelis–Menten kinetics. The computational studies reveal the role of the pH on the CALB regioselectivity toward the hydrolysis of bis-(hydroxyethyl) terephthalate (BHET). We exploit this insight to perform a pH-controlled biotransformation that selectively hydrolyzes BHET to either its corresponding diacid or monoesters using both soluble and immobilized CALB. The discoveries presented here can be exploited for the valorization of BHET resulting from the organocatalytic depolymerization of PET.This work was supported by the Spanish Agency of Research (AEI) (ref. PID2021–123332OB-C21, PID2021–124811OB-I00 and PID2019–107098RJ-I00), the Generalitat Valenciana (PROMETEO, with ref. CIPROM/2021/079, and SEJI/2020/007), Universitat Jaume I (UJI-A2019-04 and UJI-B2020-03). K.Ś. thanks Ministerio de Ciencia e Innovación and Fondo Social Europeo for a Ramon y Cajal contract (Ref. RYC2020-030596-I) and a European Cooperation in Science & Technology COST Action (ref. CA21101). This work was partially performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency Grant MDM-2017-0720. The authors acknowledge the computational resources founded by the Spanish Ministry of Science–European Regional Development Fund (REF: EQC2019-006018-P) installed at Universitat Jaume I. We thank Dr. Grajales for his assistance in the analysis of UPLC-MS samples

Dispositivo de fijación, cierre y acoplamiento para catéter de perfusión intravenosa

Introducción: los medios de fijación a la piel de un catéter venoso periférico, de un catéter venoso central o de un catéter arterial central presentan los siguientes graves inconvenientes: ser la sede de infecciones a nivel del lugar de la punción, provocar una saturación de la zona anatómica, la cual resulta muy difícil de soportar e incómodo para el paciente portador, y suponer un riesgo para el personal de enfermería cuando se usan hilos de sutura para fijar el soporte del catéter. Objetivo: por lo anteriormente expuesto, se ha detectado la necesidad de diseñar un dispositivo que reduzca la complejidad y aparatosidad de los sistemas conocidos y empleados en la actualidad, favoreciendo la asepsia y la movilidad del paciente. Método: el desarrollo presentado en este artículo se refiere a un sistema mecánico de fijación, cierre y acoplamiento para catéter de perfusión intravenosa. El sistema dispone de una pieza circular de pequeño espesor con al menos dos orificios para su fijación subcutánea, centralmente de uno o más conductos para acoplar lúmenes, y de una parte cilíndrica hueca que sobresale a uno de los lados, exteriormente roscada e interiormente lisa con un tetón de posición. Para uso domiciliario se dispone de un tapón de estanqueidad con uno o más tubos de pequeño diámetro que se acoplan en los orificios para lúmenes, una ranura de posición, un tirador y un tapón roscado ciego para el cierre hermético con la parte roscada. Para uso hospitalario se dispone de un tapón intermedio con una o más entradas para lúmenes, así como de un tapón roscado hueco que permite su acoplamiento hermético con la parte roscada. Resultados: el desarrollo descrito en este artículo va a ser utilizado en dos ambientes: ambiente domiciliario y ambiente hospitalario. Además, reduce el riesgo de infección y saturación de la zona anatómica de los pacientes en los que se realiza la punción cutánea en la que se fijan catéteres venosos periféricos, catéteres venosos centrales o catéteres arteriales centralesIntroduction: skin fixing devices in peripheral, central or arterial catheters have several important drawbacks: site infection, stacking of material in the anatomical area which is very annoying for the patient and medical staff risk when fixating stitches are used. Objective: to develop a fixing device that simplifies presently used systems, favoring asepsis and motility. Methods: the device herein described is composed by a mechanical fixation, a closing system and coupling for intravenous catheters. The system has a thin circular piece with at least two holes for subcutaneous fixation, one or several conducts for lumina and a hollow cylindrical part in one side, screwed exteriorly and flat inside, with an oriented protuberance. A watertight plug with one or several thin tubes that adapt to the lumina, a positional slot, a handle and a solid screwed tap for perfect closure are available for at home use. An intermediate plug with one or several lumina and a screwed hollow plug are provided for in hospital use. Results: the above described device is intended to be used in two settings: in hospital and at home. It is supposed to reduce the risk of infection and stacking of the anatomical site where cutaneo us puncture with fixation of peripheral, central or arterial catheters is performe