39 research outputs found

    Melting of the Na layers in solid Na0.8CoO2

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    Data of 23Na NMR spectra- and relaxation measurements are interpreted as suggesting that, upon increasing temperature the Na layers in Na0.8CoO2 adopt a 2D liquid state at T=291 K. The corresponding first order phase transition is preceded by a rapidly increasing mobility and diffusion of Na ions above 200K. Above 291 K the 23Na NMR response is similar to that previously observed in superionic conductors with planar Na layers.Comment: 4 pages, 4 figure

    Phenolic Substitution in Fidaxomicin: A Semisynthetic Approach to Antibiotic Activity Across Species

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    Fidaxomicin (Fdx) is a natural product antibiotic with potent activity against Clostridioides difficile and other Gram-positive bacteria such as Mycobacterium tuberculosis. Only a few Fdx derivatives have been synthesized and examined for their biological activity in the 50 years since its discovery. Fdx has a well-studied mechanism of action, namely inhibition of the bacterial RNA polymerase. Yet, the targeted organisms harbor different target protein sequences, which poses a challenge for the rational development of new semisynthetic Fdx derivatives. We introduced substituents on the two phenolic hydroxy groups of Fdx and evaluated the resulting trends in antibiotic activity against M. tuberculosis, C. difficile, and the Gram-negative model organism Caulobacter crescentus. As suggested by the target protein structures, we identified the preferable derivatisation site for each organism. The derivative ortho-methyl Fdx also exhibited activity against the Gram-negative C. crescentus wild type, a first for fidaxomicin antibiotics. These insights will guide the synthesis of next-generation fidaxomicin antibiotics

    Multi-Parametric Analysis and Modeling of Relationships between Mitochondrial Morphology and Apoptosis

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    Mitochondria exist as a network of interconnected organelles undergoing constant fission and fusion. Current approaches to study mitochondrial morphology are limited by low data sampling coupled with manual identification and classification of complex morphological phenotypes. Here we propose an integrated mechanistic and data-driven modeling approach to analyze heterogeneous, quantified datasets and infer relations between mitochondrial morphology and apoptotic events. We initially performed high-content, multi-parametric measurements of mitochondrial morphological, apoptotic, and energetic states by high-resolution imaging of human breast carcinoma MCF-7 cells. Subsequently, decision tree-based analysis was used to automatically classify networked, fragmented, and swollen mitochondrial subpopulations, at the single-cell level and within cell populations. Our results revealed subtle but significant differences in morphology class distributions in response to various apoptotic stimuli. Furthermore, key mitochondrial functional parameters including mitochondrial membrane potential and Bax activation, were measured under matched conditions. Data-driven fuzzy logic modeling was used to explore the non-linear relationships between mitochondrial morphology and apoptotic signaling, combining morphological and functional data as a single model. Modeling results are in accordance with previous studies, where Bax regulates mitochondrial fragmentation, and mitochondrial morphology influences mitochondrial membrane potential. In summary, we established and validated a platform for mitochondrial morphological and functional analysis that can be readily extended with additional datasets. We further discuss the benefits of a flexible systematic approach for elucidating specific and general relationships between mitochondrial morphology and apoptosis

    Recent advances in understanding the roles of whole genome duplications in evolution

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    Ancient whole-genome duplications (WGDs)—paleopolyploidy events—are key to solving Darwin’s ‘abominable mystery’ of how flowering plants evolved and radiated into a rich variety of species. The vertebrates also emerged from their invertebrate ancestors via two WGDs, and genomes of diverse gymnosperm trees, unicellular eukaryotes, invertebrates, fishes, amphibians and even a rodent carry evidence of lineage-specific WGDs. Modern polyploidy is common in eukaryotes, and it can be induced, enabling mechanisms and short-term cost-benefit assessments of polyploidy to be studied experimentally. However, the ancient WGDs can be reconstructed only by comparative genomics: these studies are difficult because the DNA duplicates have been through tens or hundreds of millions of years of gene losses, mutations, and chromosomal rearrangements that culminate in resolution of the polyploid genomes back into diploid ones (rediploidisation). Intriguing asymmetries in patterns of post-WGD gene loss and retention between duplicated sets of chromosomes have been discovered recently, and elaborations of signal transduction systems are lasting legacies from several WGDs. The data imply that simpler signalling pathways in the pre-WGD ancestors were converted via WGDs into multi-stranded parallelised networks. Genetic and biochemical studies in plants, yeasts and vertebrates suggest a paradigm in which different combinations of sister paralogues in the post-WGD regulatory networks are co-regulated under different conditions. In principle, such networks can respond to a wide array of environmental, sensory and hormonal stimuli and integrate them to generate phenotypic variety in cell types and behaviours. Patterns are also being discerned in how the post-WGD signalling networks are reconfigured in human cancers and neurological conditions. It is fascinating to unpick how ancient genomic events impact on complexity, variety and disease in modern life

    High-pressure phases of uranium monophosphide studied by synchrotron x-ray diffraction

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    X-ray diffraction studies have been performed on UP powder for pressures up to 51 GPa using synchrotron radiation and a diamond-anvil cell. At ambient pressure UP has the rocksalt structure. The bulk modulus has been determined to B0_0=102(4) GPa and its pressure derivative to B'0_0 =4.0(8). The cubic phase has been found to transform to a new phase, UP II, at about 10 GPa. UP II can be characterized by a rhombohedral Bravais lattice. UP II transforms to an orthorhombic phase, UP III, at 28 GPa. No volume change has been observed at the two transitions. The influence of the 5f electrons on the transformations is discussed

    Ce3\text{}_{3}Cu3\text{}_{3}Sb4\text{}^{4}: a Canted Antiferromagnetic Semimetal

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    It has been claimed by Patil et al., that Ce3\text{}_{3}Cu3\text{}_{3}Sb4\text{}_{4} is the first Ce-based semiconducting ferromagnet. In this paper it is shown, mainly with Hall effect and far infrared spectroscopy that no gap in the excitation spectrum exists, as well above as below the magnetic ordering temperature. A maximum in the resistivity near TC\text{}_{C} is due to trapped magnetic polarons. The resistivity is an effect of the mobility of the charge carriers. The structure of the magnetic unit cell has been determined with elastic neutron scattering

    NEUTRON DIFFRACTION AND MAGNETIZATION STUDY OF THE MAGNETIC PHASE DIAGRAM OF UAs0.75Se0.25 SINGLE CRYSTAL

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    The magnetic phase diagram (magnetic field versus temperature) of UAs0.75Se0.25 has been determined by neutron diffraction and magnetization of single crystals in magnetic fields up to 67.2 and 190 kOe, respectively, applied along the cubic [001] axis
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