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International audience; The reaction between P2-type honeycomb layered oxides Na2Ni2TeO6 and K2Ni2TeO6 enables the formation of NaKNi2TeO6. The compound is characterized by X-ray diffraction and 23Na solid-state nuclear magnetic resonance spectroscopy, and the structure is discussed through density functional theory calculations. In addition to the honeycomb Ni/Te cationic ordering, NaKNi2TeO6 exhibits a unique example of alternation of sodium and potassium layers instead of a random alkali-mixed occupancy. Stacking fault simulations underline the impact of the successive position of the Ni/Te honeycomb layers and validate the presence of multiple stacking sequences within the powder material, in proportions that evolve with the synthesis conditions. In a broader context, this work contributes to a better understanding of the alkali-mixed layered compounds.

Diagnosis of transmissible spongiform encephalopathies (TSEs), or prion diseases, is based on the detection of proteinase K (PK)-resistant PrPSc in post-mortem tissues as indication of infection and disease. Since PrPSc detection is not considered a reliable method for in vivo diagnosis in most TSEs, it is of crucial importance to identify an alternative source of biomarkers to provide useful alternatives for current diagnostic methodology. Ovine scrapie is the prototype of TSEs and has been known for a long time. Using this natural model of TSE, we investigated the presence of PrPSc in exosomes derived from plasma and cerebrospinal fluid (CSF) by protein misfolding cyclic amplification (PMCA) and the levels of candidate microRNAs (miRNAs) by quantitative PCR (qPCR). Significant scrapie-associated increase was found for miR-21-5p in plasma-derived but not in CSF-derived exosomes. However, miR-342-3p, miR-146a-5p, miR-128-3p and miR-21-5p displayed higher levels in total CSF from scrapie-infected sheep. The analysis of overexpressed miRNAs in this biofluid, together with plasma exosomal miR-21-5p, could help in scrapie diagnosis once the presence of the disease is suspected. In addition, we found the presence of PrPSc in most CSF-derived exosomes from clinically affected sheep, which may facilitate in vivo diagnosis of prion diseases, at least during the clinical stage.

Microemulsions, as thermodynamically stable mixtures of oil, water, and surfactant, are known and have been studied for more than 70 years. However, even today there are still quite a number of unclear aspects, and more recent research work has modified and extended our picture. This review gives a short overview of how the understanding of microemulsions has developed, the current view on their properties and structural features, and in particular, how they are related to applications. We also discuss more recent developments regarding nonclassical microemulsions such as surfactant-free (ultraflexible) microemulsions or ones containing uncommon solvents or amphiphiles (like antagonistic salts). These new findings challenge to some extent our previous understanding of microemulsions, which therefore has to be extended to look at the different types of microemulsions in a unified way. In particular, the flexibility of the amphiphilic film is the key property to classify different microemulsion types and their properties in this review. Such a classification of microemulsions requires a thorough determination of their structural properties, and therefore, the experimental methods to determine microemulsion structure and dynamics are reviewed briefly, with a particular emphasis on recent developments in the field of direct imaging by means of electron microscopy. Based on this classification of microemulsions, we then discuss their applications, where the application demands have to be met by the properties of the microemulsion, which in turn are controlled by the flexibility of their amphiphilic interface. Another frequently important aspect for applications is the control of the rheological properties. Normally, microemulsions are low viscous and therefore enhancing viscosity has to be achieved by either having high concentrations (often not wished for) or additives, which do not significantly interfere with the microemulsion. Accordingly, this review gives a comprehensive account of the properties of microemulsions, including most recent developments and bringing them together from a united viewpoint, with an emphasis on how this affects the way of formulating microemulsions for a given application with desired properties., T.Z. thanks the German Science Foundation (DFG) for providing a Mercator professorship within the International Research Training Group (IRTG) 1524 (SSNI) at the Technische Universität Berlin, as well as the Agence Nationale de la Recherche (ANR) for the LABEX “Chemisyst” grant ANR 2011-01-05 that made the long-term collaboration possible.

International audience; In a first instance, the effect of the microwave irradiation on the 1,3-Dioxa-[3,3]-sigmatropic rearrangement of aryl allylic carbamates was investigated. Under these new conditions, the reaction acceleration was clearly highlighted compared to conventional heating conditions. Depending on the electronic nature of substituents on the aromatic group, this type of rearrangement can be faster with similar or improved yields. Due to this experimental improvement, the diversity of aryl allylic carbamates able to undergo this rearrangement in a reasonable reaction time (30 min.) and with acceptable to high yields was greatly extended. Finally, an original synthetic way involving this microwave-assisted process to access new six-membered heterocyclic structures such as (E)-5-arylidene-1,3-oxazinane-2,4-diones was developed from Morita-Baylis-Hillman (MBH) adducts showing the interest of this molecular rearrangement approach. DFT and Fragment Distortion studies showed in general polar transition structures and connected high deformation and interaction energies with lower activation barriers.

International audience; Herein we present design, synthesis, chiral HPLC resolution, and kinetics of racemization of axially chiral Ni(II) complexes of glycine and di-(benzyl)glycine Schiff bases. We found that while the ortho-fluoro derivatives are configuration-ally unstable, the pure enantiomers of corresponding axially chiral ortho-chloro-containing complexes can be isolated by preparative HPLC and show exceptional configurational stability (t 1/2 from 4 to 216 centuries) at ambient conditions. Synthetic implications of this discovery for the development of new generation of axially chiral auxiliaries, useful for general asymmetric synthesis of α-amino acids, are discussed.

Chromatin accessibility to protein factors is critical for genome activities. Dynamic changes in nucleosomal DNA compaction and higher order chromatin structures are expected to allow specific sites to be accessible to regulatory factors and the transcriptional machinery. However, the dynamic properties of chromatin that regulate its accessibility are poorly understood. Here, we took advantage of the microenvironment sensitivity of the fluorescence lifetime of EGFP-H4 histone incorporated in chromatin to map in the nucleus of live cells the dynamics of chromatin condensation and its direct interaction with a tail acetylation recognition domain (the double bromodomain module of human TAFII250, dBD). We reveal chromatin condensation fluctuations supported by mechanisms fundamentally distinct from that of condensation. Fluctuations are spontaneous, yet their amplitudes are affected by their sub-nuclear localization and by distinct and competing mechanisms dependent on histone acetylation, ATP, and both. Moreover, we show that accessibility of acetylated histone H4 to dBD is not restricted by chromatin condensation nor predicted by acetylation, rather, it is predicted by chromatin condensation fluctuations.SignificanceIn higher eukaryotes, the structure and compaction of chromatin are considered as barriers to genome activities. Epigenetic marks such as post-translational modifications of histones can modify the structure and compaction of chromatin. The accessibility of protein factors to these epigenetic marks is therefore of paramount importance for genome activities. We reveal chromatin condensation fluctuations supported by mechanisms fundamentally distinct from that of condensation itself. We show that accessibility of acetylated histone H4 to double bromodomains is not restricted by chromatin condensation nor predicted by acetylation, rather, it is predicted by chromatin condensation fluctuations.ClassificationBiological Sciences, Cell Biology

International audience; Composites carbon foams based on sucrose-based char matrix and graphite filler were prepared and characterised with the aim of hosting sugar alcohols as phase-change materials (PCMs) in the context of thermal energy storage (TES). Seasonal solar TES demands an excellent undercooling of the molten PCM infiltrated in the foam, so that the heat can be stored as long as possible. The present paper demonstrates how the surface of such composite foams, i.e., comprising two carbon phases of different reactivities, can be modified for promoting undercooling. For that purpose, 8 different hydrophobisation treatments were applied, and the results were compared with those of the non-treated foam, in which heterogeneous nucleation could not be avoided. We show that one kind of functionalisation was successful, i.e., it fully preserved the melting point and the enthalpy of melting of the hosted phase-change material and completely avoided the heterogeneous nucleation of the PCM, while maintaining the thermal conductivity in the range required for this kind of application.

Cobalt nanoparticles (NPs) have been prepared by hydrogenation of the organometallic complex [Co(η 3 -C 8 H 13 )(η 4 -C 8 H 12 )] in 1-heptanol in the absence of any other stabilizer and then transformed into Co 3 O 4 NPs using mild oxidative reaction conditions. After deposition onto glassy carbon rotating disk electrodes, the electrocatalytic performance of the Co 3 O 4 NPs in water oxidation has been tested in 1M NaOH. The activity has been benchmarked with that of state-of-the-art Co 3 O 4 NPs through electrochemically-active surface area (ECSA) and specific current density measurements. Furthermore, the covalent grafting of photosensitive polypyridyl-based Ru II complexes onto the surface of Co 3 O 4 NPs afforded hybrid nanostructured materials able to photo-oxidize water into O 2 , while steady-state and time-resolved spectroscopic measurements gave some further insight into kinetics and pertinent reaction steps following excitation. These first-row transition metal oxide hybrid nanocatalysts display better catalytic performance than simple mixtures of non-grafted photosensitizers and Co 3 O 4 NPs, thus evidencing the advantage of the direct coupling between the two entities for the photo-induced water oxidation reaction.

In this study, the potential of hexadecyl trimethyl ammonium bromide modified montmorillonite (HDTMA-Mt) to remove the synthetic dyes Alizarin Red S (ARS) and Bromocresol Green (BCG) from aqueous media was assessed. The effect of different factors including surfactant loading rate onto the clay, contact time, pH, adsorbent dosage and dye concentrations, on the removal of ARS and BCG in batch systems were investigated. The adsorbent was characterized by means of scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffractometry (XRD). The equilibrium time for ARS and BCG was reached at 40 and 20 min, respectively, under optimized conditions (i.e. pH = 3, adsorbent dosage=1 g/L, surfactant loading rate onto the clay 70% of the cation exchange capacity (CEC) for ARS and 120% of the CEC for BCG, ARS concentration 50 mg/L and BCG concentration 500 mg/L). The adsorption rate of both dyes fitted the pseudo-second-order kinetic model and the equilibrium data was described by the Freundlich isotherm equation. The maximum monolayer adsorption capacities were equal to 666.6 and 1250 mg/g for ARS and BCG, respectively. Therefore, the HDTMA-Mt can be considered as an effective adsorbent for the removal of ARS and BCG from aqueous solutions.

Inhibitor design incorporating features of the reaction coordinate and transition-state structure has emerged as a powerful approach for the development of enzyme inhibitors. Such inhibitors find use as mechanistic probes, chemical biology tools, and therapeutics. Endo-α-1,2-mannosidases and endo-α-1,2-mannanases, members of glycoside hydrolase family 99 (GH99), are interesting targets for inhibitor development as they play key roles in N-glycan maturation and microbiotal yeast mannan degradation, respectively. These enzymes are proposed to act via a 1,2-anhydrosugar “epoxide” mechanism that proceeds through an unusual conformational itinerary. Here, we explore how shape and charge contribute to binding of diverse inhibitors of these enzymes. We report the synthesis of neutral dideoxy, glucal and cyclohexenyl disaccharide inhibitors, their binding to GH99 endo-α-1,2-mannanases, and their structural analysis by X-ray crystallography. Quantum mechanical calculations of the free energy landscapes reveal how the neutral inhibitors provide shape but not charge mimicry of the proposed intermediate and transition state structures. Building upon the knowledge of shape and charge contributions to inhibition of family GH99 enzymes, we design and synthesize α-Man-1,3-noeuromycin, which is revealed to be the most potent inhibitor (KD 13 nM for Bacteroides xylanisolvens GH99 enzyme) of these enzymes yet reported. This work reveals how shape and charge mimicry of transition state features can enable the rational design of potent inhibitors.

Isolated supraoptic neurones generate spontaneous [Ca(2+)]i oscillations in isolated conditions. Here we report in depth analysis of the contribution of plasmalemmal ion channels (Ca(2+), Na(+)), Na(+)/Ca(2+) exchanger (NCX), intracellular Ca(2+) release channels (InsP3Rs and RyRs), Ca(2+) storage organelles, plasma membrane Ca(2+) pump and intracellular signal transduction cascades into spontaneous Ca(2+) activity. While removal of extracellular Ca(2+) or incubation with non-specific voltage-gated Ca(2+) channel (VGCC) blocker Cd(2+) suppressed the oscillations, neither Ni(2+) nor TTA-P2, the T-type VGCC blockers, had an effect. Inhibitors of VGCC nicardipine, ω-conotoxin GVIA, ω-conotoxin MVIIC, ω-agatoxin IVA (for L-, N-, P and P/Q-type channels, respectively) did not affect [Ca(2+)]i oscillations. In contrast, a specific R-type VGCC blocker SNX-482 attenuated [Ca(2+)]i oscillations. Incubation with TTX had no effect, whereas removal of the extracellular Na(+) or application of an inhibitor of the reverse operation mode of Na(+)/Ca(2+) exchanger KB-R7943 blocked the oscillations. The mitochondrial uncoupler CCCP irreversibly blocked spontaneous [Ca(2+)]i activity. Exposure of neurones to Ca(2+) mobilisers (thapsigargin, cyclopiazonic acid, caffeine and ryanodine); 4-aminopyridine (A-type K(+) current blocker); phospholipase C and adenylyl cyclase pathways blockers U-73122, Rp-cAMP, SQ-22536 and H-89 had no effect. Oscillations were blocked by GABA, but not by glutamate, apamin or dynorphin. In conclusion, spontaneous oscillations in magnocellular neurones are mediated by a concerted action of R-type Ca(2+) channels and the NCX fluctuating between forward and reverse modes.

International audience; Mixtures of enantiomerically pure (S)-N-formyl-1-phenylethyamine and various racemic N-formyl-1-arylethylamine derivatives, when submitted to achiral medium pressure liquid chromatography, afforded elution profiles in which the enantiomers of N-formyl-1-arylethylamines standout as separate peaks and can be isolated. In all of the investigated N-formyl-1-arylethylamine substrates, the virtually enantiomerically pure (S)-enantiomer eluted as a less polar fraction and subsequently, the (R)-enriched enantiomer mixtures were eluted in the more polar fractions.

International audience; Phosphatidyl-myo-inositol mannosyltransferase A (PimA) is an essential glycosyltransferase that initiates the biosynthetic pathway of phosphatidyl-myo-inositol mannoside, lipomannan, and lipoarabinomannan, which are key glycolipids/lipoglycans of the mycobacterial cell envelope. PimA belongs to a large family of membrane-associated glycosyltransferases for which the understanding of the molecular mechanism and conformational changes that govern substrate/membrane recognition and catalysis remains a major challenge. Here, we determined that PimA preferentially binds to negatively charged phosphatidyl-myo-inositol substrate and non-substrate membrane model systems (small unilamellar vesicle) through its N-terminal domain, inducing an important structural reorganization of anionic phospholipids. By using a combination of single-point mutagen-esis, circular dichroism, and a variety of fluorescence spectros-copy techniques, we determined that this interaction is mainly mediated by an amphipathic-helix (2), which undergoes a substantial conformational change and localizes in the vicinity of the negatively charged lipid headgroups and the very first carbon atoms of the acyl chains, at the PimA-phospholipid interface. Interestingly, a flexible region within the N-terminal domain, which undergoes-strand-to-helix and-helix-to-strand transitions during catalysis, interacts with anionic phospholipids; however, the effect is markedly less pronounced to that observed for the amphipathic 2, likely reflecting structural plasticity/variability. Altogether, we propose a model in which conformational transitions observed in PimA might reflect a molten globule state that confers to PimA, a higher affinity toward the dynamic and highly fluctuating lipid bilayer.

International audience; The variational stochastic self-consistent harmonic approximation is combined with the calculation of thirdorderanharmonic coefficients within density functional perturbation theory and the 2n + 1 theorem to calculateanharmonic properties of crystals. It is demonstrated that in the perturbative limit, the combination of thesetwo methods yields the perturbative phonon linewidth and frequency shift in a very efficient way, avoidingthe explicit calculation of fourth-order anharmonic coefficients. Moreover, it also allows calculating phononlifetimes and inelastic neutron-scattering spectra in solids where the harmonic approximation breaks down anda nonperturbative approach is required to deal with anharmonicity. To validate our approach, we calculate theanharmonic phonon linewidth in the strongly anharmonic palladium hydrides. We show that due to the largeanharmonicity of hydrogen optical modes, the inelastic neutron-scattering spectra are not characterized by aLorentzian line shape, but by a complex structure including satellite peaks

International audience; We present to our knowledge the first structural characterization of the proliferating-cell-nuclear-antigen-associated factor p15(PAF), showing that it is monomeric and intrinsically disordered in solution but has nonrandom conformational preferences at sites of protein-protein interactions. p15(PAF) is a 12 kDa nuclear protein that acts as a regulator of DNA repair during DNA replication. The p15(PAF) gene is overexpressed in several types of human cancer. The nearly complete NMR backbone assignment of p15(PAF) allowed us to measure 86 N-H(N) residual dipolar couplings. Our residual dipolar coupling analysis reveals nonrandom conformational preferences in distinct regions, including the proliferating-cell-nuclear-antigen-interacting protein motif (PIP-box) and the KEN-box (recognized by the ubiquitin ligase that targets p15(PAF) for degradation). In accordance with these findings, analysis of the (15)N R2 relaxation rates shows a relatively reduced mobility for the residues in these regions. The agreement between the experimental small angle x-ray scattering curve of p15(PAF) and that computed from a statistical coil ensemble corrected for the presence of local secondary structural elements further validates our structural model for p15(PAF). The coincidence of these transiently structured regions with protein-protein interaction and posttranslational modification sites suggests a possible role for these structures as molecular recognition elements for p15(PAF).

Biochemical energy is the fundamental element that maintains both the adequate turnover of the biomolecular structures and the functional metabolic viability of unicellular organisms. The levels of ATP, ADP and AMP reflect roughly the energetic status of the cell, and a precise ratio relating them was proposed by Atkinson as the adenylate energy charge (AEC). Under growth-phase conditions, cells maintain the AEC within narrow physiological values, despite extremely large fluctuations in the adenine nucleotides concentration. Intensive experimental studies have shown that these AEC values are preserved in a wide variety of organisms, both eukaryotes and prokaryotes. Here, to understand some of the functional elements involved in the cellular energy status, we present a computational model conformed by some key essential parts of the adenylate energy system. Specifically, we have considered (I) the main synthesis process of ATP from ADP, (II) the main catalyzed phosphotransfer reaction for interconversion of ATP, ADP and AMP, (III) the enzymatic hydrolysis of ATP yielding ADP, and (IV) the enzymatic hydrolysis of ATP providing AMP. This leads to a dynamic metabolic model (with the form of a delayed differential system) in which the enzymatic rate equations and all the physiological kinetic parameters have been explicitly considered and experimentally tested in vitro. Our central hypothesis is that cells are characterized by changing energy dynamics (homeorhesis). The results show that the AEC presents stable transitions between steady states and periodic oscillations and, in agreement with experimental data these oscillations range within the narrow AEC window. Furthermore, the model shows sustained oscillations in the Gibbs free energy and in the total nucleotide pool. The present study provides a step forward towards the understanding of the fundamental principles and quantitative laws governing the adenylate energy system, which is a fundamental element for unveiling the dynamics of cellular life.

Palladium hydrides display the largest isotope effect anomaly known in literature. Replacement of hydrogen with the heavier isotopes leads to higher superconducting temperatures, a behavior inconsistent with harmonic theory. Solving the self-consistent harmonic approximation by a stochastic approach, we obtain the anharmonic free energy, the thermal expansion and the superconducting properties fully ab initio. We find that the phonon spectra are strongly renormalized by anharmonicity far beyond the perturbative regime. Superconductivity is phonon mediated, but the harmonic approximation largely overestimates the superconducting critical temperatures. We explain the inverse isotope effect, obtaining a -0.38 value for the isotope coefficient in good agreement with experiments, hydrogen anharmonicity being the main responsible for the isotope anomaly., 5 pages, 3 figures

The biosynthesis of membrane lipids is an essential pathway for virtually all bacteria. Despite its potential importance for the development of novel antibiotics, little is known about the underlying signaling mechanisms that allow bacteria to control their membrane lipid composition within narrow limits. Recent studies disclosed an elaborate feed-forward system that senses the levels of malonyl-CoA and modulates the transcription of genes that mediate fatty acid and phospholipid synthesis in many Gram-positive bacteria including several human pathogens. A key component of this network is FapR, a transcriptional regulator that binds malonyl-CoA, but whose mode of action remains enigmatic. We report here the crystal structures of FapR from Staphylococcus aureus (SaFapR) in three relevant states of its regulation cycle. The repressor-DNA complex reveals that the operator binds two SaFapR homodimers with different affinities, involving sequence-specific contacts from the helix-turn-helix motifs to the major and minor grooves of DNA. In contrast with the elongated conformation observed for the DNA-bound FapR homodimer, binding of malonyl-CoA stabilizes a different, more compact, quaternary arrangement of the repressor, in which the two DNA-binding domains are attached to either side of the central thioesterase-like domain, resulting in a non-productive overall conformation that precludes DNA binding. The structural transition between the DNA-bound and malonyl-CoA-bound states of SaFapR involves substantial changes and large (>30 Å) inter-domain movements; however, both conformational states can be populated by the ligand-free repressor species, as confirmed by the structure of SaFapR in two distinct crystal forms. Disruption of the ability of SaFapR to monitor malonyl-CoA compromises cell growth, revealing the essentiality of membrane lipid homeostasis for S. aureus survival and uncovering novel opportunities for the development of antibiotics against this major human pathogen., Author Summary An opportunistic Gram-positive pathogen, Staphylococcus aureus is a major threat to humans and animals, being responsible for a variety of infections ranging from mild superficial to severe infections such as infective endocarditis, septic arthritis, osteomyelitis and sepsis. The increasing resistance of S. aureus against most current antibiotics emphasizes the need to develop new approaches to control this important pathogen. The lipid biosynthetic pathway is one appealing target actively pursued to develop anti-Staphylococcal agents. Despite its potential biomedical importance, however, little is known about the signaling mechanisms that allow S. aureus to control its phospholipid content. In order to shed light on this fundamental mechanism, we studied S. aureus FapR (SaFapR) a transcription factor that senses the levels of malonyl-CoA, a key intermediate in fatty acid biosynthesis, and modulates the expression of genes involved in fatty acid and phospholipid biosynthesis. Our studies of SaFapR uncovered the mechanistic basis of a complex biological switch that controls membrane lipid homeostasis in S. aureus. We also discovered that disruption of the ability of SaFapR to recognize malonyl-CoA, the ligand that controls SaFapR binding to DNA, compromises S. aureus viability, thus revealing new opportunities for the development of antibiotics against this major human pathogen.

This work is licensed under a Creative Commons Attribution 3.0 Unported license., Boron nitride is a promising material for nanotechnology applications due to its two-dimensional graphene-like, insulating, and highly-resistant structure. Recently it has received a lot of attention as a substrate to grow and isolate graphene as well as for its intrinsic UV lasing response. Similar to carbon, one-dimensional boron nitride nanotubes (BNNTs) have been theoretically predicted and later synthesised. Here we use first principles simulations to unambiguously demonstrate that i) BN nanotubes inherit the highly efficient UV luminescence of hexagonal BN; ii) the application of an external perpendicular field closes the electronic gap keeping the UV lasing with lower yield; iii) defects in BNNTS are responsible for tunable light emission from the UV to the visible controlled by a transverse electric field (TEF). Our present findings pave the road towards optoelectronic applications of BN-nanotube-based devices that are simple to implement because they do not require any special doping or complex growth., We acknowledge financial support also from the European Research Council Advanced Grant DYNamo (ERC-2010-AdG-267374), Spanish Grant (FIS2010-21282-C02-01), Grupos Consolidados UPV/EHU del Gobierno Vasco (IT578-13), Ikerbasque and the European Commission project CRONOS (Grant number 280879-2). Computational time was granted by i2basque and BSC Red Espanola de Supercomputacion and GENCI-IDRIS (Nos. 100063 and No. 091827). A. M. acknowledges funding by MIUR FIRB Grant No. RBFR12SW0J.

International audience; A specific methodology was developed to collate the interlayer configurations resulting from Grand-Canonical Monte Carlo (GCMC) simulations with experimental X-ray and neutron diffraction data for two synthetic Na-saturated saponites having contrasting layer charge. Numerical simulations were performed assuming different existing sets of atomic partial charge and Lennard-Jones parameters for clay and water. For each parameter set and for the two samples in both the mono- and bihydrated states, the water contents resulting from GCMC simulations were first compared to water vapor desorption gravimetry data. The density distributions of interlayer species were then used to generate 00l intensities that were compared to X-ray and neutron diffraction data, the latter being recorded on both hydrogenated and deuterated specimens. The CLAYFF model [Cygan et al. J. Phys. Chem. B2004, 108, 1255] is shown to better account for water content and organization compared to the model developed by Skipper et al. (Clays Clay Miner.1995, 43, 285) and modified by Smith (Langmuir1998, 14, 5959). However, diffraction patterns calculated for bihydrated samples from CLAYFF simulations did not match satisfactorily the diffraction data. Lennard-Jones parameters were thus modified for oxygen atoms from the clay layer. When combined with the SPC/E water model, this modified version of CLAYFF allows matching experimental water contents and fitting the complete set of diffraction data. Relevant information may thus be derived on the influence of layer charge on the orientational properties of interlayer water molecules which differs for the different clay models. Finally, the approach used in the present study proved powerful for assessing atomic interaction parameters considered for computational simulations.

Transaminases are a class of enzymes with promising applications for the preparation and resolution of a vast diversity of valued amines. Their poor operational stability has fueled many investigations on its stabilization due to their biotechnological relevance. In this work, we screened the stabilization of the tetrameric ω-transaminase from Pseudomonas fluorescens (PfωTA) through both carrier-bound and carrier-free immobilization techniques. The best heterogeneous biocatalyst was the PfωTA immobilized as cross-linked enzyme aggregates (PfωTA-CLEA) which resulted after studying different parameters as the precipitant, additives and glutaraldehyde concentrations. The best conditions for maximum recovered activity (29 %) and maximum thermostability at 60 ºC and 70 ºC (100 % and 71 % residual activity after 1 h, respectively) were achieved by enzyme precipitation with 90% acetone or ethanol, in presence of BSA (100 mg/mL) and employing glutaraldehyde (100 mM) as cross-linker. Studies on different conditions for PfωTA-CLEA preparation yielded a biocatalyst that exhibited 31 and 4.6 times enhanced thermal stability at 60 °C and 70 °C, respectively, compared to its soluble counterpart. The PfωTA-CLEA was successfully used in the bioamination of 4-hydroxybenzaldehyde to 4-hydroxybenzylamine. To the best of our knowledge, this is the first report describing a transaminase cross-linked enzyme aggregates as immobilization strategy to generate a biocatalyst with outstanding thermostability., S. Velasco grateful CONACyT for the granted postdoctoral fellowship. L. Betancor, E. Jackson and M. Ripoll acknowledge PEDECIBA, National Research and Innovation Agency of Uruguay (ANII) FSE_1_2016_1_132115 and POS_NAC_2019_1_158182) and Universidad ORT Uruguay. Fernando López acknowledges the funding of IKERBASQUE and Spanish Government (BIO2015-69887-R).

This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (NanoMOFdeli), ERC-2016-COG 726380, Innovate UK (104384) and EPSRC IAA (IAA/RG85685). N.R. acknowledges the support of the Cambridge International Scholarship and the TrinityHenry Barlow Scholarship (Honorary). O.K.F. and R.Q.S. acknowledge funding from the U.S. Department of Energy (DE-FG02-08ER15967). R.S.F. and D.B. acknowledge funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (SCoTMOF), ERC-2015-StG 677289. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-NA-0003525. The authors gratefully acknowledge funding from the U.S. Department of Energy, Office of Energy Efficiency and Renewable Energy, Hydrogen and Fuel Cell Technologies Office, through the Hydrogen Storage Materials Advanced Research Consortium (HyMARC). This paper describes objective technical results and analysis. Any subjective views or opinions that might be expressed in the paper do not necessarily represent the views of the U.S. Department of Energy or the United States Government. J.D.E. acknowledges the support of the Alexander von Humboldt Foundation and the Center for Information Services and High Performance Computing (ZIH) at TU Dresden. S.K.G. and S.M. acknowledge SERB (Project No. CRG/2019/000906), India for financial support. K.K. and R.K. acknowledge Active Co. Research Grant for funding. S.K. acknowledges funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (COSMOS), ERC-2017-StG 756489. N.L. and J.G.M acknowledge funding from the European Commission through the H2020-MSCA-RISE-2019 program (ZEOBIOCHEM -872102) and the Spanish MICINN and AEI/FEDER (RTI2018-099504-B-C21). N.L. thanks the University of Alicante for funding (UATALENTO17-05). ICN2 is supported by the Severo Ochoa program from the Spanish MINECO (Grant No. SEV-2017-0706) S.M.J.R. and A.L. wish to thank the Fund for Scientific Research Flanders (FWO), under grant nos. 12T3519N and 11D2220N. L.S. was supported by the EPSRC Cambridge NanoDTC EP/L015978/1. C.T.Y. and T.S.N. acknowledges funds from the National Research Foundation of Korea, NRF-2017M3A7B4042140 and NRF-2017M3A7B4042235. P.F. and H. Y. acknowledge US Department of Energy, Office of Basic Energy Sciences, Materials Sciences and Engineering Division under Award No. DE-SC0010596 (P.F.). R.O. would like to acknowledge funding support during his Ph.D. study from Indonesian Endowment Fund for Education-LPDP with the contract No. 202002220216006. Daniel Siderius: Official contribution of the National Institute of Standards and Technology (NIST), not subject to copyright in the United States of America. Daniel Siderius: Certain commercially available items may be identified in this paper. This identification does not imply recommendation by NIST, nor does it imply that it is the best available for the purposes described. B.V.L, S.T.E and A.M.P acknowledge funding from the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Program (Grant agreement no. 639233, COFLeaf)., Porosity and surface area analysis play a prominent role in modern materials science. At the heart of this sits the Brunauer–Emmett–Teller (BET) theory, which has been a remarkably successful contribution to the field of materials science. The BET method was developed in the 1930s for open surfaces but is now the most widely used metric for the estimation of surface areas of microand mesoporous materials. Despite its widespread use, the calculation of BET surface areas causes a spread in reported areas, resulting in reproducibility problems in both academia and industry. To prove this, for this analysis, 18 already-measured raw adsorption isotherms were provided to sixty-one labs, who were asked to calculate the corresponding BET areas. This roundrobin exercise resulted in a wide range of values. Here, the reproducibility of BET area determination from identical isotherms is demonstrated to be a largely ignored issue, raising critical concerns over the reliability of reported BET areas. To solve this major issue, a new computational approach to accurately and systematically determine the BET area of nanoporous materials is developed. The software, called “BET surface identification” (BETSI), expands on the well-known Rouquerol criteria and makes an unambiguous BET area assignment possible., European Research Council (ERC) ERC-2016-COG 726380 ERC-2015-StG 677289 ERC-2017-StG 756489 639233, UK Research & Innovation (UKRI) Innovate UK 104384 UK Research & Innovation (UKRI), Engineering & Physical Sciences Research Council (EPSRC) IAA/RG85685, Cambridge International Scholarship TrinityHenry Barlow Scholarship, United States Department of Energy (DOE) DE-FG02-08ER15967, National Nuclear Security Administration DE-NA-0003525, United States Department of Energy (DOE), Alexander von Humboldt Foundation, Center for Information Services and High Performance Computing (ZIH) at TU Dresden, Department of Science & Technology (India), Science Engineering Research Board (SERB), India CRG/2019/000906, Active Co. Research Grant, European Commission through the H2020-MSCA-RISE-2019 program ZEOBIOCHEM -872102, Spanish MICINN and AEI/FEDER RTI2018-099504-B-C21, University of Alicante UATALENTO17-05, Spanish Government SEV-2017-0706 FWO 12T3519N 11D2220N, UK Research & Innovation (UKRI), Engineering & Physical Sciences Research Council (EPSRC) EP/L015978/1, National Research Foundation of Korea NRF-2017M3A7B4042140 NRF-2017M3A7B4042235, United States Department of Energy (DOE) DE-SC0010596, Indonesian Endowment Fund for Education-LPDP 202002220216006

International audience; Even though reversible interactions within ionic hydrogels are well-studied, underlying mechanisms responsible for the high-value added performance of ionic nanocomposites remain almost unexplored. We herein propose a fundamental understanding aiming at elucidating the mechanism behind the reversible breaking and reformation of ionic bonding in the case of organic–inorganic hybrids made of a combination of imidazolium-functionalized poly(ethylene glycol)-based polyurethane (im-PU) and surface-modified sulfonate silica nanoparticles (SiO2–SO3H). Such ionic hybrids already demonstrated unique features related to the presence of electrostatic interactions, but the underlying mechanisms governing the overall material performance have never been discussed. To dissociate the reinforcement role of nanoparticles and ionic interactions, either standard nonionic SiO2 or ionic SiO2–SO3H nanoparticles were introduced into im-PU. Mechanical performances, thermal transitions, relaxation processes, and the morphology of the hybrids were deeply investigated to better comprehend the mechanisms at the origin of the ionic material reinforcement. In addition, a mechanistic investigation is proposed to quantify the dissipation energy ability of the as-proposed ionic hybrids, and an approach is presented to identify a characteristic time for restoration of reversible ionic bonds under different loading scenarios.

The theoretical prediction of drug-decorated nanoparticles (DDNPs) has become a very important task in medical applications. For the current paper, Perturbation Theory Machine Learning (PTML) models were built to predict the probability of different pairs of drugs and nanoparticles creating DDNP complexes with anti-glioblastoma activity. PTML models use the perturbations of molecular descriptors of drugs and nanoparticles as inputs in experimental conditions. The raw dataset was obtained by mixing the nanoparticle experimental data with drug assays from the ChEMBL database. Ten types of machine learning methods have been tested. Only 41 features have been selected for 855,129 drug-nanoparticle complexes. The best model was obtained with the Bagging classifier, an ensemble meta-estimator based on 20 decision trees, with an area under the receiver operating characteristic curve (AUROC) of 0.96, and an accuracy of 87% (test subset). This model could be useful for the virtual screening of nanoparticle-drug complexes in glioblastoma. All the calculations can be reproduced with the datasets and python scripts, which are freely available as a GitHub repository from authors., The APC was funded by IKERDATA, S.L. under grant 3/12/DP/2021/00102, This work is supported by the “Collaborative Project in Genomic Data Integration (CICLOGEN)” PI17/01826 funded by the Carlos III Health Institute, from the Spanish National Plan for Scientific and Technical Research and Innovation 2013–2016 and the European Regional Development Funds (FEDER)—“A way to build Europe”. This project was also supported by the General Directorate of Culture, Education and University Management of Xunta de Galicia (Ref. ED431G/01, ED431D 2017/16), the “Galician Network for Colorectal Cancer Research” (Ref. ED431D 2017/23), Competitive Reference Groups (Ref. ED431C 2018/49), and the Spanish Ministry of Economy and Competitiveness via funding of the unique installation BIOCAI (UNLC08-1E-002, UNLC13-13-3503) and the European Regional Development Funds (FEDER). Lastly, the authors also acknowledge research grants from the Ministry of Economy and Competitiveness, MINECO, Spain (FEDER CTQ2016-74881-P), the Basque government (IT1045-16), and the kind support of Ikerbasque, Basque Foundation for Science and Zitek.

Because of its surface characteristics, once in the aquatic environment, graphene could act as a carrier of pollutants, such as polycyclic aromatic hydrocarbons (PAHs), to aquatic organisms. In this study we aimed to (1) assess the capacity of graphene oxide (GO) to sorb PAHs and (2) to evaluate the toxicity of GO alone and in combination with PAHs on zebrafish embryos and adults. GO showed a high sorption capacity for benzo(a)pyrene (B(a)P) (98% of B(a)P sorbed from a nominal concentration of 100 mu g/L) and for other PAHs of the water accommodated fraction (WAF) of a naphthenic North Sea crude oil, depending on their log Kow (95.7% of phenanthrene, 84.4% of fluorene and 51.5% of acenaphthene). In embryos exposed to different GO nanomaterials alone and with PAHs, no significant mortality was recorded for any treatment. Nevertheless, malformation rate increased significantly in embryos exposed to the highest concentrations (5 or 10 mg/L) of GO and reduced GO (rGO) alone and with sorbed B(a)P (GO-B(a)P). On the other hand, adults were exposed for 21 days to 2 mg/L of GO, GO-B(a)P and GO co-exposed with WAF (GO + WAF) and to 100 mu g/L B(a)P. Fish exposed to GO presented GO in the intestine lumen and liver vacuolisation. Transcription level of genes related to cell cycle regulation and oxidative stress was not altered, but the slight up-regulation of cyp1a measured in fish exposed to B(a)P for 3 days resulted in a significantly increased EROD activity. Fish exposed to GO-B(a)P and to B(a)P for 3 days and to GO + WAF for 21 days showed significantly higher catalase activity in the gills than control fish. Significantly lower acetylcholinesterase activity, indicating neurotoxic effects, was also observed in all fish treated for 21 days. Results demonstrated the capacity of GO to carry PAHs and to exert sublethal effects in zebrafish. This work has been funded by University of the Basque Country (predoctoral grant to IMA PIFBUR15/15), Basque Government (consolidated research group IT810-13 and IT1302-19), Spanish Ministry of Economy and Competitiveness project NACE (CTM2016-81130-R), French National Research Agency (No.-10-IDEX-03-02) and Cluster of Excellence Continental To coastal Ecosystems-COTE (ANR-10-LABX 45). Thanks to staff at Driftslaboratoriet Mongstad, Equinor (former Statoil) for supplying the sample of crude oil used in the experiments. The authors thank for technical and human support provided by SGIker (UPV/EHU/ERDF, EU).

A calorimetry method based on infrared thermography is showing promise for material screening, allowing the simultaneous detection of phase transitions of multiple samples at a time, hence enabling the establishment of phase diagrams in a record time. The working principle of this method is similar to the one of Differential Thermal Analysis. Therefore, this work aims at identifying if the melting enthalpy of materials could be estimated on the same basis using infrared thermography. In this work, the melting of six eutectic mixtures of fatty acids is estimated under three considerations. The results are compared to Differential Scanning Calorimetry measurements and literature data. The accuracy of the method is discussed and improvements are proposed.

Dye-sensitized solar cells (DSSCs) are an efficient photovoltaic technology for powering electronic applications such as wireless sensors with indoor light. Their low cost and abundant materials, as well as their capability to be manufactured as thin and light-weight flexible solar modules highlight their potential for economic indoor photovoltaics. However, their fabrication methods must be scaled to industrial manufacturing with high photovoltaic efficiency and performance stability under typical indoor conditions. This paper reviews the recent progress in DSSC research towards this goal through the development of new device structures, alternative redox shuttles, solid-state hole conductors, TiO2 photoelectrodes, catalyst materials, and sealing techniques. We discuss how each functional component of a DSSC has been improved with these new materials and fabrication techniques. In addition, we propose a scalable cell fabrication process that integrates these developments to a new monolithic cell design based on several features including inkjet and screen printing of the dye, a solid state hole conductor, PEDOT contact, compact TiO2, mesoporous TiO2, carbon nanotubes counter electrode, epoxy encapsulation layers and silver conductors. Finally, we discuss the need to design new stability testing protocols to assess the probable deployment of DSSCs in portable electronics and internet-of-things devices., Dye-sensitized solar cells (DSSCs) are an efficient photovoltaic technology for powering electronic applications such as wireless sensors with indoor light.

During glutamine sufficiency, both Notch‐positive and Notch‐negative T‐ALL cells promote glutamine catabolism, leading to mammalian target of rapamycin complex 1 (mTORC1) activation and cell growth and proliferation. However, during glutamine scarcity, only Notch‐negative T‐ALL cells can perform a metabolic adaptation by promoting glutamine synthesis. By contrast, Notch‐positive T‐ALL cells maintain glutamine catabolism during glutamine restriction, leading to glutamine addiction and mTORC1 dependency., The cellular receptor Notch1 is a central regulator of T‐cell development, and as a consequence, Notch1 pathway appears upregulated in > 65% of the cases of T‐cell acute lymphoblastic leukemia (T‐ALL). However, strategies targeting Notch1 signaling render only modest results in the clinic due to treatment resistance and severe side effects. While many investigations reported the different aspects of tumor cell growth and leukemia progression controlled by Notch1, less is known regarding the modifications of cellular metabolism induced by Notch1 upregulation in T‐ALL. Previously, glutaminolysis inhibition has been proposed to synergize with anti‐Notch therapies in T‐ALL models. In this work, we report that Notch1 upregulation in T‐ALL induced a change in the metabolism of the important amino acid glutamine, preventing glutamine synthesis through the downregulation of glutamine synthetase (GS). Downregulation of GS was responsible for glutamine addiction in Notch1‐driven T‐ALL both in vitro and in vivo. Our results also confirmed an increase in glutaminolysis mediated by Notch1. Increased glutaminolysis resulted in the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway, a central controller of cell growth. However, glutaminolysis did not play any role in Notch1‐induced glutamine addiction. Finally, the combined treatment targeting mTORC1 and limiting glutamine availability had a synergistic effect to induce apoptosis and to prevent Notch1‐driven leukemia progression. Our results placed glutamine limitation and mTORC1 inhibition as a potential therapy against Notch1‐driven leukemia.

The functionalization of the internal surface of macroporous carriers with glyoxyl groups has proven to highly stabilize a large variety of enzymes through multipoint covalent immobilization. In this work, we have translated the surface chemistry developed for the fabrication of glyoxyl-agarose carriers to macroporous cellulose (CEL). To that aim, CEL-based microbeads were functionalized with glyoxyl groups through a stepwise alkoxylation (or alkylation)/oxidation synthetic scheme. This functionalization sequence was analyzed by solid-state NMR, while the scanning electron miscroscopy of CEL microbeads reveals that the mild oxidation conditions negligibly affect the morphological properties of the material. Through the optimal functionalization protocol using rac-glycidol, we introduce up to 200 μmols of aldehyde groups per gram of wet CEL, a similar density to the one obtained for the benchmarked agarose-glyoxyl carrier. This novel CEL-based carrier succeeds to immobilize and stabilize industrially relevant enzymes such as d-amino acid oxidase from Trigonopsis variabilis and xylanases from Trichoderma reseei. Remarkably, the xylanases immobilized on the optimal CEL-based materials present a half-life time of 51 h at 60 °C and convert up to 90% of the xylan after four operation cycles for the synthesis of xylooligosaccharides., The authors acknowledge funding from the National Council for Scientific and Technological Development (CNPq) for financial support for the PhD scholarships of S.M.O (Process CsF 201683/2014–2008). J.M.G thanks the funding from the EU FP7 project Lignofood (Ingredients for Food and Beverage Industry from a Lignocellulosic Source, grant agreement no 606073). F.L-G acknowledges the funding of IKERBASQUE. This work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency—grant no. MDM-2017-0720. J.M.F., thanks to the funding from the Spanish Ministerio de Ciencia e Innovación (grant RTI2018-093431-BI00).

This work describes the synthesis and pharmacological evaluation of 2-furoyl-based Melanostatin (MIF-1) peptidomimetics as dopamine D2 modulating agents. Eight novel peptidomimetics were tested for their ability to enhance the maximal effect of tritiated N-propylapomorphine ([3H]-NPA) at D2 receptors (D2R). In this series, 2-furoyl-l-leucylglycinamide (6a) produced a statistically significant increase in the maximal [3H]-NPA response at 10 pM (11 ± 1%), comparable to the effect of MIF-1 (18 ± 9%) at the same concentration. This result supports previous evidence that the replacement of proline residue by heteroaromatic scaffolds are tolerated at the allosteric binding site of MIF-1. Biological assays performed for peptidomimetic 6a using cortex neurons from 19-day-old Wistar-Kyoto rat embryos suggest that 6a displays no neurotoxicity up to 100 μM. Overall, the pharmacological and toxicological profile and the structural simplicity of 6a makes this peptidomimetic a potential lead compound for further development and optimization, paving the way for the development of novel modulating agents of D2R suitable for the treatment of CNS-related diseases. Additionally, the pharmacological and biological data herein reported, along with >20â000 outcomes of preclinical assays, was used to seek a general model to predict the allosteric modulatory potential of molecular candidates for a myriad of target receptors, organisms, cell lines, and biological activity parameters based on perturbation theory (PT) ideas and machine learning (ML) techniques, abbreviated as ALLOPTML. By doing so, ALLOPTML shows high specificity Sp = 89.2/89.4%, sensitivity Sn = 71.3/72.2%, and accuracy Ac = 86.1%/86.4% in training/validation series, respectively. To the best of our knowledge, ALLOPTML is the first general-purpose chemoinformatic tool using a PTML-based model for the multioutput and multicondition prediction of allosteric compounds, which is expected to save both time and resources during the early drug discovery of allosteric modulators., This research was funded by Fundação para a Ciência e Tecnologia (FCT, Portugal), through grants UIDB/50006/2020 (to LAQV-REQUIMTE Research Unit) and for project grants PTDC/BIA-MIB/29059/2017 and PEst-OE/QUI/UI0674/2013. This work was also supported by the Collaborative Project of Genomic Data Integration (CICLOGEN)., The support of Ikerbasque, Basque Foundation for Science and the research grants from Ministry of Economy and Competitiveness, MINECO, Spain (FEDER CTQ2016–74881-P), and Basque government (IT1045–16) are also acknowledged. The financial support (ED431G 2019/02) from the Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2019–2022) and the European Union (European Regional Development Fund—ERDF) is gratefully acknowledged. I.E.S.-D. thanks FCT for the doctoral grant SFRH/BD/93632/2013. X.G.-M. thanks Xunta de Galicia for financial support (GPC2014/003).

[Background] Non-alcoholic fatty liver disease (NAFLD) is affecting more people globally. Indeed, NAFLD is a spectrum of metabolic dysfunctions that can progress to hepatocellular carcinoma (NAFLD-HCC). This development can occur in a non-cirrhotic liver and thus, often lack clinical surveillance. The aim of this study was to develop non-invasive surveillance method for NAFLD-HCC., [Methods] Using comprehensive ultra-high-performance liquid chromatography mass-spectrometry, we investigated 1,295 metabolites in serum from 249 patients. Area under the receiver operating characteristic curve was calculated for all detected metabolites and used to establish their diagnostic potential. Logistic regression analysis was used to establish the diagnostic score., [Findings] We show that NAFLD-HCC is characterised by a complete rearrangement of the serum lipidome, which distinguishes NAFLD-HCC from non-cancerous individuals and other HCC patients. We used machine learning to build a diagnostic model for NAFLD-HCC. We quantified predictive metabolites and developed the NAFLD-HCC Diagnostic Score (NHDS), presenting superior diagnostic potential compared to alpha-fetoprotein (AFP). Patients’ metabolic landscapes show a progressive depletion in unsaturated fatty acids and acylcarnitines during transformation. Upregulation of fatty acid transporters in NAFLD-HCC tumours contribute to fatty acid depletion in the serum., [Interpretation] NAFLD-HCC patients can be efficiently distinguished by serum metabolic alterations from the healthy population and from HCC patients related to other aetiologies (alcohol and viral hepatitis). Our model can be used for non-invasive surveillance of individuals with metabolic syndrome(s), allowing for early detection of NAFLD-HCC. Therefore, serum metabolomics may provide valuable insight to monitor patients at risk, including morbidly obese, diabetics, and NAFLD patients., We thank all funding sources: The laboratory of JBA is supported by the Novo Nordisk Foundation (14040, 0058419), Danish Cancer Society (R98-A6446, R167-A10784, R278-A16638), and the Danish Medical Research Council (4183-00118A, 1030-00070B). Data used for validation in this study provided by JMB was funded by the Spanish Ministry of Economy and Competitiveness and ’Instituto de Salud Carlos III’ grants (PI18/01075, Miguel Servet Programme CON14/00129 and CPII19/00008) co-financed by ’Fondo Europeo de Desarrollo Regional’ (FEDER); CIBERehd, Spain; IKERBASQUE, Basque foundation for Science, Spain; BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD); Department of Health of the Basque Country (2017111010), Euskadi RIS3 (2019222054, 2020333010); Department of Industry of the Basque Country (Elkartek: KK-2020/00008), AECC Scientific Foundation and European Commission Horizon 2020 program (ESCALON project no.: 825510). Similarly, MAJ was funded by grants from the Fondo Nacional De Ciencia y Tecnología de Chile (FONDECYT #1191145 to M.A.) and the Comisión Nacional de Investigación, Ciencia y Tecnología (CONICYT, AFB170005, CARE Chile UC).

Biocatalytic cascades afford the development of economically sustainable and green processes. Herein we examined the unprecedented coupling of co-immobilised Gluconobacter oxydans and an isolated transaminase to synthesise serinol from glycerol. Through this approach, we manufactured up to 36 mM serinol, the highest titer ever reported for a non-fermentative biosynthesis. More importantly, similar productivities are obtained starting from the industrial by-product crude glycerol, demonstrating the possibilities of this hybrid heterogenenous biocatalyst for valorising bio-based raw materials., S. Velasco acknowledges CONACyT for the granted postdoctoral fellowship. L. Betancor, E. Jackson and M. Ripoll acknowledge PEDECIBA, National Research and Innovation Agency of Uruguay (ANII) (POS_NAC_2019_1_158182) and Universidad ORT Uruguay. Fernando López acknowledges the funding of IKERBASQUE and Spanish Government (BIO2015-69887-R). This work was performed under the Maria de Maeztu Units of Excellence Programme – Grant No. MDM-2017-0720 Ministry of Science, Innovation and Universities.

Two-dimensional materials (2DMs) have attracted tremendous research interest over the last two decades. Their unique optical, electronic, thermal, and mechanical properties make 2DMs key building blocks for the fabrication of novel complementary metal-oxide-semiconductor (CMOS) and beyond-CMOS devices. Major advances in device functionality and performance have been made by the covalent or noncovalent functionalization of 2DMs with molecules: while the molecular coating of metal electrodes and dielectrics allows for more efficient charge injection and transport through the 2DMs, the combination of dynamic molecular systems, capable to respond to external stimuli, with 2DMs makes it possible to generate hybrid systems possessing new properties by realizing stimuli-responsive functional devices and thereby enabling functional diversification in More-than-Moore technologies. In this review, we first introduce emerging 2DMs, various classes of (macro)molecules, and molecular switches and discuss their relevant properties. We then turn to 2DM/molecule hybrid systems and the various physical and chemical strategies used to synthesize them. Next, we discuss the use of molecules and assemblies thereof to boost the performance of 2D transistors for CMOS applications and to impart diverse functionalities in beyond-CMOS devices. Finally, we present the challenges, opportunities, and long-term perspectives in this technologically promising field., The activity in Strasbourg was supported by the EC through the ERC project SUPRA2DMAT (GA-833707) and the Graphene Flagship Core 3 project (GA-881603) as well as the Labex projects CSC (ANR-10LABX-0026 CSC) and NIE (ANR-11-LABX-0058 NIE) within the Investissement d’Avenir program ANR-10-IDEX-0002-02 the International Center for Frontier Research in Chemistry and the Institut Universitaire de France (IUF). The activity in San Sebastian was supported by the Spanish MICINN under the Maria de Maeztu Units of Excellence Programme (MDM-2016-0618) and under the Project Nos. RTI2018-094861-B-100 and PID2019-108153GA-I00. M.G. acknowledges support from la Caixa Foundation (ID 100010434) for a Junior Leader fellowship (Grant No. LCF/BQ/PI19/11690017). Y.Z. acknowledged the support from the National Natural Science Foundation of China (62090034, 62104214).

Understanding how the immobilization of enzymes on solid carriers affects their performance is paramount for the design of highly efficient heterogeneous biocatalysts. An efficient supply of substrates onto the solid phase is one of the main challenges to maximize the activity of the immobilized enzymes. Herein, we apply advanced single-particle analysis to decipher the optimal design of an immobilized NADH oxidase (NOX) whose activity depends both on O2 and NADH concentrations. Carrier physicochemical properties and its functionality along with the enzyme distribution across the carrier were implemented as design variables to study the effects of the intraparticle concentration of substrates (O2 and NADH) on the activity. Intraparticle O2-sensing analysis revealed the superior performance of the enzyme immobilized at the outer surface in terms of effective supply of O2. Furthermore, the co-immobilization of NADH and NOX within the tuned surface of porous microbeads increases the effective concentration of NADH in the surroundings of the enzyme. As a result, the optimal spatial organization of NOX and its confinement with NADH allow a 100% recovery of the activity of the soluble enzyme upon the immobilization process. By engineering these variables, we increase the NADH oxidation activity of the heterogeneous biocatalyst by up to 650% compared to NOX immobilized under suboptimal conditions. In conclusion, this work highlights the rational design and engineering of the enzyme–carrier interface to maximize the efficiency of heterogeneous biocatalysts., A.I.B.-M and F.L.G. are grateful to MINECO (RTI2018-094398-B-I00). ERC-Co (METACELL-878089)) and ERA-CoBioTech (Project ID: 61 HOMBIOCAT/ PCI2018-092984) projects are acknowledged for funding F.L.G. F.L.G. also thanks the IKERBASQUE Foundation. C.H. acknowledges ERASMUS+ for the student exchange grant from the University of Graz to the University of Zaragoza. J.M.B. acknowledges funding from the Government of Community of Madrid (2018-T1/BIO-10200).

Nitrate (NO3−) and ammonium (NH4+) are the main inorganic nitrogen sources available to plants. However, exclusive ammonium nutrition may lead to stress characterized by growth inhibition, generally associated with a profound metabolic reprogramming. In this work, we investigated how metabolism adapts according to leaf position in the vertical axis of tomato (Solanum lycopersicum cv. M82) plants grown with NH4+, NO3−, or NH4NO3 supply. We dissected leaf biomass composition and metabolism through an integrative analysis of metabolites, ions, and enzyme activities. Under ammonium nutrition, carbon and nitrogen metabolism were more perturbed in mature leaves than in young ones, overall suggesting a trade-off between NH4+ accumulation and assimilation to preserve young leaves from ammonium stress. Moreover, NH4+-fed plants exhibited changes in carbon partitioning, accumulating sugars and starch at the expense of organic acids, compared with plants supplied with NO3−. We explain such reallocation by the action of the biochemical pH-stat as a mechanism to compensate the differential proton production that depends on the nitrogen source provided. This work also underlines that the regulation of leaf primary metabolism is dependent on both leaf phenological stage and the nitrogen source provided.

Made available in DSpace on 2020-12-12T01:31:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-10-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) European Research Council Agencia Estatal de Investigación As a natural response to a stressful situation, the human body produces cortisol. For this reason, cortisol is also called “the stress hormone” and is considered to be the principal stress biomarker. Although cortisol response to stress is essential for survival, abnormal levels in biological fluids may represent serious health risks. In this work, we present a cortisol biosensor which relies on a highly sensitive technique (surface-enhanced Raman spectroscopy, SERS) and a specific recognition (immunoassay). Gold nanostars were used as SERS nanotags, since they provided a better response than nanorods or nanospheres. Using the same concept, two different immunoassay modalities were evaluated, using either magnetic beads or gold-coated glass slides decorated with cortisol antibodies as the capture substrates. The magnetically-assisted SERS immunoassay presented a better performance and was therefore selected to quantify cortisol content in biological fluids (urine and serum). Significant advantages of this assay were found over standard methods such as Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) and Enzyme-Linked Immunosorbent Assay (ELISA), including higher sensitivity and repeatability, minimum sample preparation, simplicity, and portability. Therefore, the proposed SERS immunoassay might be implemented as a highly efficient tool for in situ monitoring of human stress levels and cortisol-related disorders (e.g. Cushing's syndrome and Addison's disease). CIC biomaGUNE Basque Research and Technology Alliance (BRTA), Paseo de Miramón 182 Centro de Investigación Biomédica en Red Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Paseo de Miramón 182 Ikerbasque Basque Foundation for Science Instituto de Química and INCT-DATREM Universidade Estadual Paulista (UNESP), Araraquara Instituto de Química and INCT-DATREM Universidade Estadual Paulista (UNESP), Araraquara FAPESP: 2014/50945-4 FAPESP: 2018/24202-5 European Research Council: 787510 Agencia Estatal de Investigación: BIO2017-88030-R European Research Council: ERC-AdG 4D-bioSERS Agencia Estatal de Investigación: MAT2017-86659-R Agencia Estatal de Investigación: MDM-2017-0720

International audience; Herein, we report a general method for quantitative measurement of the con-figurational stability of the stereogenic nitrogen coordinated to M (II) in the corresponding square planar complexes. This stereochemical approach is quite sensitive to steric and electronic effects of the substituents and shown to work well for Ni(II), Pd(II), and Cu(II) complexes. Structural simplicity of the compounds used, coupled with high sensitivity and reliability of experimental procedures, bodes well for application of this approach in evaluation of chemical stability and stereochemical properties of newly designed chiral ligands for general asymmetric synthesis of tailor-made amino acids. KEYWORDS amino acids, chiral HPLC, kinetic of racemization, metal(II) complexes, Schiff bases, stereogenic nitrogen 1 | INTRODUCTION Tailor-made amino acids (AAs), 1 are essential structural features of numerous modern pharmaceuticals. 2 Application of AA residues in drug design allows for fairly accurate 3-D positioning of pharmacophoric moieties and mimicking the targeted biogenic peptide−receptor interactions. 3 Thus, over the past decade, about 20% of newly introduced drugs contained at least one tailor-made AA residue. 2 Consequently, the development of synthetic methodology for preparation of tailor-made AAs is currently in very high demand. 4 Following our long-standing interest in synthesis of sterically constrained 5 and fluorine-containing AAs, 6 we were actively contributing to the general asymmetric synthesis of α-AAs via Ni(II) complexes of AA Schiff bases (Scheme 1). 7

A new family of chiral C2 symmetric tetraazamacrocycles, coined ISAC for IminoSugar Aza-Crown, incorporating two iminosugars adopting a 4C1 conformation is disclosed. Multinuclear NMR experiments on the corresponding Cd2+ complex show that the ISAC is a strong chelator in water and its tetramine cavity adopts a conformation similar to that of the parent Cd−cyclam complex. Similar behavior is observed with Cu2+ in solution, with enhanced stability compared to the Cu−cyclam complex.

The rapid demand for protein-based molecules has stimulated much research on cell-free protein synthesis (CFPS); however, there are still many challenges in terms of cost-efficiency, process intensification, and sustainability. Herein, we describe the microcompartmentalization of CFPS of superfolded green fluorescent protein (sGFP) in alginate hydrogels, which were casted into a μ-channel device. CFPS was optimized for the microcompartmentalized environment and characterized in terms of synthesis yield. To extend the scope of this technology, the use of other biocompatible materials (collagen, laponite, and agarose) was explored. In addition, the diffusion of sGFP from the hydrogel microenvironment to the bulk was demonstrated, opening a promising opportunity for concurrent synthesis and delivery of proteins. Finally, we provide an application for this system: the CFPS of enzymes. The present design of the hydrogel μ-channel device may enhance the potential application of microcompartmentalized CFPS in biosensing, bioprototyping, and therapeutic development., A.I.B.-M., N.C., N.Z., and F.L.-G. are grateful to Spanish Ministry MINECO (BIO2014-61838-EXP and BIO2015-69887-R) for funding their research. A.I.B.-M. is grateful to the SELF Postdoctoral Fellowship she received from the University of Bern. F.L.-G. acknowledges IKERBASQUE and ARAID foundations for funding him. L.M-R. thanks the AECC foundation for the internship grant. T.R. acknowledges the Instituto de Salud Carlos III for the i-PFIS fellowship.

Hydrogen atom makes graphene magnetic Graphene has many extraordinary mechanical and electronic properties, but it's not magnetic. To make it so, the simplest strategy is to modify its electronic structure to create unpaired electrons. Researchers can do that by, for example, removing individual carbon atoms or adsorbing hydrogen onto graphene. This has to be done in a very controlled way because of a peculiarity of the graphene's crystal lattice, which consists of two sublattices. Gonzales-Herrero et al. deposited a single hydrogen atom on top of graphene and used scanning tunneling microscopy to detect magnetism on the sublattice lacking the deposited atom (see the Perspective by Hollen and Gupta). Science , this issue p. 437 ; see also p. 415

International audience; Recent advances in neuroscience have positioned brain circuits as key units in controlling behavior, implying that their positive or negative modulation necessarily leads to specific behavioral outcomes. However, emerging evidence suggests that the activation or inhibition of specific brain circuits can actually produce multimodal behavioral outcomes. This study shows that activation of a receptor at different subcellular locations in the same neuronal circuit can determine distinct behaviors. Pharmacological activation of type 1 cannabinoid (CB1) receptors in the striatonigral circuit elicits both antinociception and catalepsy in mice. The decrease in nociception depends on the activation of plasma membrane-residing CB1 receptors (pmCB1), leading to the inhibition of cytosolic PKA activity and substance P release. By contrast, mitochondrial-associated CB1 receptors (mtCB1) located at the same terminals mediate cannabinoid-induced catalepsy through the decrease in intra-mitochondrial PKA-dependent cellular respiration and synaptic transmission. Thus, subcellular-specific CB1 receptor signaling within striatonigral circuits determines multimodal control of behavior.

9 pags., 8 figs., The optical properties of poly(3-hexylthiophene-2,5-diyl) (P3HT) can be controlled by processing the polymer in the form of nanoparticles dispersed in aqueous mediums. Colloids of P3HT were prepared by two different methods: flash –or reprecipitation- and miniemulsion precipitation technique, which result in the latter case in a polymer-water system whose stability is mediated by an ionic surfactant. Both systems yield different color dispersions, thus different absorption spectra, that is explained to be caused by the influence of the surfactant on the structure of P3HT. Differential scanning calorimetry and synchrotron radiation X-ray diffraction experiments reveal the origin of these optical differences, showing evidences of the formation of a blended structure formed due to the interaction between P3HT and the ionic surfactant. This work evidences the potential use of techniques for preparing nanoparticles in water dispersions as a tool to manipulate the structure and thus, the optical properties of these materials., This work has been supported by the Spanish Ministry of Science and Innovation under the projects PID2019-107514 GB-I00/AEI/10.13039/ 501100011033 and PID2019-106125 GB- I00/AEI/10.13039/ 501100011033, and Garantía Juvenil/Fondo Europeo. We thank E. Solano for assistance and support during beamtime in ALBA. J.M. thanks MCIU for the Ramon y Cajal contract and the grant Ref. PGC2018- 094620-A-I00 and Ikerbasque Foundation for the Fellow program

International audience; One of the most important effects of water on earth is that surfaces in air adsorb small amounts ofwater, usually in the form of a thin film. Real surfaces, especially the rather soft biomolecular surfaces, are covered by highly curved micro- and nanostructures, which induce more complex wetting geometries, such as films, droplets, and filaments. This effect, though ubiquitous, has not yet been investigated on the nanoscale. We have approached the situation by combining a soft proteinous surface, made up from very resilient tubular plant viruses, with ionic liquids. Their low vapor pressure allowed us to observe nanoscale wetting patterns at very high spatial resolution with AFM (atomic force microscopy), SEM (scanning electron microscopy) and STEM (scanning transmission electronmicroscopy).We found droplets, filaments and layers,withmeniscus diameters down to below10 nm. All geometries are comparablewith results obtained on the microscale, and with standard macroscale wetting models.

International audience; Herein, we disclose the design of a model Ni(II) complex of glycine Schiff base possessing single-nitrogen stereogenic center, which was successfully used for high-performance liquid chromatography (HPLC)-assisted assessment of its con-figurational stability. The major finding is that the configurational stability of the Ni(II)-coordinated nitrogen is profoundly dependent on the reaction conditions used, in particular the solvent, and can range from inconsequential (t ½ less than 5 min) to virtually completely stable (t ½ 90 y). The discovery reported in this study most likely to be of certain theoretical and synthetic value.

This article belongs to the Special Issue Advances in the Design and Characterization of Heterogeneous Biocatalysts., Understanding the functionality of immobilized enzymes with spatiotemporal resolution and under operando conditions is an unmet need in applied biocatalysis, as well as priceless information to guide the optimization of heterogeneous biocatalysts for industrial purposes. Unfortunately, enzyme immobilization still relies on trial-and-error approximations that prevail over rational designs. Hence, a modern fabrication process to achieve efficient and robust heterogeneous biocatalysts demands comprehensive characterization techniques to track and understand the immobilization process at the protein–material interface. Recently, our group has developed a new generation of self-sufficient heterogeneous biocatalysts based on alcohol dehydrogenases co-immobilized with nicotinamide cofactors on agarose porous microbeads. Harnessing the autofluorescence of NAD+(P)H and using time-lapse fluorescence microscopy, enzyme activity toward the redox cofactors can be monitored inside the beads. To analyze these data, herein we present an image analytical tool to quantify the apparent Michaelis–Menten parameters of alcohol dehydrogenases co-immobilized with NAD(P)+/H at the single-particle level. Using this tool, we found a strong negative correlation between the apparent catalytic performance of the immobilized enzymes and the bead radius when using exogenous bulky substrates in reduction reactions. Therefore, applying image analytics routines to microscopy studies, we can directly unravel the functional heterogeneity of different heterogeneous biocatalyst samples tested under different reaction conditions., A.I.B.-M. and F.L.-G. are grateful to MINECO (BIO2015-69887-R, BIO2014-61838-EXP and PCI2018-092984) and HOMBIOCAT ERA-CoBioTech project for funding their research. We also thank ARAID and IKERBASQUE foundations for funding F.L.-G. and P.R.-C., and S.V.-L. thanks the Mexican Council of Science and Technology (CONACyT) for the postdoctoral fellowship she received.

International audience; Synapses compute and transmit information to connect neural circuits and are at the basis of brain operations. Alterations in their function contribute to a vast range of neuropsychiatric and neurodegenerative disorders and synapse-based therapeutic intervention, such as selective inhibition of synaptic transmission, may significantly help against serious pathologies. Graphene is a two-dimensional nanomaterial largely exploited in multiple domains of science and technology, including biomedical applications. In hippocampal neurons in culture, small graphene oxide nanosheets (s-GO) selectively depress glutamatergic activity without altering cell viability. Glutamate is the main excitatory neurotransmitter in the central nervous system and growing evidence suggests its involvement in neuropsychiatric disorders. Here we demonstrate that s-GO directly targets the release of presynaptic vesicle. We propose that s-GO flakes reduce the availability of transmitter, via promoting its fast release and subsequent depletion, leading to a decline ofglutamatergic neurotransmission. We injected s-GO in the hippocampus in vivo, and 48 h after surgery ex vivo patch-clamp recordings from brain slices show a significant reduction in glutamatergic synaptic activity in respect to saline injections.

The combination of three different enzymes immobilized rationally on the same heterofunctional carrier allowed the selective oxidation of glycerol to 1,3‐dihydroxyacetone (DHA) coupled to in situ redox‐cofactor recycling and H2O2 elimination. In this cascade, engineered glycerol dehydrogenase with reduced product inhibition oxidized glycerol selectively to DHA with the concomitant reduction of NAD+ to NADH. NADH oxidase regenerated the NAD+ pool by oxidizing NADH to NAD+ to form H2O2 as the byproduct. Finally, catalase eliminated H2O2 to yield water and O2 as innocuous products, which avoided the spontaneous DHA oxidation triggered by H2O2. The co‐immobilization of the three enzymes on the same porous carrier allowed the in situ recycling and disproportionation of the redox cofactor and H2O2, respectively, to produce up to 9.5 mM DHA, which is 18‐ and 6‐fold higher than glycerol dehydrogenase itself and a soluble multienzyme system, respectively., This work has been supported by the Spanish Ministry of Economy and Innovation (project CTQ2009‐07568). We acknowledge COST action CM103‐System biocatalysis. We would like to thank IKERBASQUE, Basque foundation for Science for the PhD funding for F.L.‐G. We also thank the Comunidad de Madrid government for funding the PhD fellowship for J.R.‐M.

International audience; This paper is focused on the genesis of microstructures in friction stir welding (FSW) of the Ti-6Al-4V alloy. Several titanium joints, initially prepared with four different preheat treatments, were processed by FSW. Detailed microstructural analyses were performed in order to investigate change in the microstructure during the process. In this work, the FSW processing allows a controlled and stable microstructure to be produced in the stirring zone, regardless of the initial heat treatment or the welding conditions. The welded material undergoes a severe thermomechanical treatment which can be divided into two steps. First, the friction in the shoulder and the plastic strain give rise to the necessary conditions to allow a continuous dynamic recrystallization of the β phase. This operation produces a fine and equiaxed β grain structure. Second, once the pin has moved away, the temperature decreases, and the material undergoes a heat treatment equivalent to air quenching. The material thus exhibits a β → β + α transformation with germination of a fine intergranular Widmanstätten phase within the ex-fully-recrystallized-β grains.

This article belongs to the Special Issue Functional Nanomaterials for Biosensing and Bioimaging., Medical imaging is an active field of research that fosters the necessity for novel multimodal imaging probes. In this line, nanoparticle-based contrast agents are of special interest, since those can host functional entities either within their interior, reducing potential toxic effects of the imaging tracers, or on their surface, providing high payloads of probes, due to their large surface-to-volume ratio. The long-term stability of the particles in solution is an aspect usually under-tackled during probe design in research laboratories, since their performance is generally tested briefly after synthesis. This may jeopardize a later translation into practical medical devices, due to stability reasons. To dig into the effects of nanoparticle aging in solution, with respect to their behavior in vivo, iron oxide stealth nanoparticles were used at two stages (3 weeks vs. 9 months in solution), analyzing their biodistribution in mice. Both sets of nanoprobes showed similar sizes, zeta potentials, and morphology, as observed by dynamic light scattering (DLS) and transmission electronic microscopy (TEM), but fresh nanoparticles accumulated in the kidneys after systemic administration, while aged ones accumulated in liver and spleen, confirming an enormous effect of particle aging on their in vivo behavior, despite barely noticeable changes perceived on a simple inspection of their structural integrity., This research was funded by Ministerio de Ciencia, Innovación y Universidades (MEIC) (grant number SAF2017-87670-R and SAF2017-84494-C2-R), Programa Red Guipuzcoana de Ciencia, Tecnología e Información (Grant number 2018-CIEN-000058-01), and The EU (FET-OPEN NanoTBTech grant Number 801305). J.R.-C. and P.R.-C. are funded by Ikerbasque, The Basque foundation for science.