114 research outputs found

    α-Synuclein Aggregation Inhibitory Prunolides and a Dibrominated β-Carboline Sulfamate from the Ascidian Synoicum prunum

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    Seven new polyaromatic bis-spiroketal-containing butenolides, the prunolides D–I (4–9) and cis-prunolide C (10), a new dibrominated β-carboline sulfamate named pityriacitrin C (11), alongside the known prunolides A–C (1–3) were isolated from the Australian colonial ascidian Synoicum prunum. The prunolides D–G (4–7) represent the first asymmetrically brominated prunolides, while cis-prunolide C (10) is the first reported with a cis-configuration about the prunolide’s bis-spiroketal core. The prunolides displayed binding activities with the Parkinson’s disease-implicated amyloid protein α-synuclein in a mass spectrometry binding assay, while the prunolides (1–5 and 10) were found to significantly inhibit the aggregation (>89.0%) of α-synuclein in a ThT amyloid dye assay. The prunolides A–C (1–3) were also tested for inhibition of pSyn aggregate formation in a primary embryonic mouse midbrain dopamine neuron model with prunolide B (2) displaying statistically significant inhibitory activity at 0.5 μM. The antiplasmodial and antibacterial activities of the isolates were also examined with prunolide C (3) displaying only weak activity against the 3D7 parasite strain of Plasmodium falciparum. Our findings reported herein suggest that the prunolides could provide a novel scaffold for the exploration of future therapeutics aimed at inhibiting amyloid protein aggregation and the treatment of numerous neurodegenerative diseases.Peer reviewe

    Non-fullerene acceptor photostability and its impact on organic solar cell lifetime

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    The development of non-fullerene acceptors (NFAs) has facilitated the realization of efficient organic solar cells (OSCs) with minimal burn-in losses and excellent long-term stability. However, the role of NFA molecular structures on device stability remains unclear, limiting commercialization of NFA-based OSCs. Herein, the photostability of 10 OSC devices, fabricated with various NFAs (O-IDTBR, EH-IDTBR, ITIC, and ITIC-M) blended with donor polymers (PTB7-Th, PffBT4T-2OD, and PBDB-T), is investigated. O-IDTBR and EH-IDTBR form highly stable devices with all three polymers, whereas ITIC and ITIC-M devices suffer from burn-in losses and long-term degradation. Conformational instability is found to be responsible for the poor photostability of ITIC and ITIC-M, resulting in poor device stability. Twisting and potential breakage of the chemical bond that links the end group to the main backbone of ITIC and ITIC-M molecules causes undesirable conformational changes. Potential strategies to overcome such detrimental photo-induced conformational changes in NFAs are proposed

    The complete genome sequence of Staphylothermus marinus reveals differences in sulfur metabolism among heterotrophic Crenarchaeota

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    <p>Abstract</p> <p>Background</p> <p><it>Staphylothermus marinus </it>is an anaerobic, sulfur-reducing peptide fermenter of the archaeal phylum Crenarchaeota. It is the third heterotrophic, obligate sulfur reducing crenarchaeote to be sequenced and provides an opportunity for comparative analysis of the three genomes.</p> <p>Results</p> <p>The 1.57 Mbp genome of the hyperthermophilic crenarchaeote <it>Staphylothermus marinus </it>has been completely sequenced. The main energy generating pathways likely involve 2-oxoacid:ferredoxin oxidoreductases and ADP-forming acetyl-CoA synthases. <it>S. marinus </it>possesses several enzymes not present in other crenarchaeotes including a sodium ion-translocating decarboxylase likely to be involved in amino acid degradation. <it>S. marinus </it>lacks sulfur-reducing enzymes present in the other two sulfur-reducing crenarchaeotes that have been sequenced – <it>Thermofilum pendens </it>and <it>Hyperthermus butylicus</it>. Instead it has three operons similar to the <it>mbh </it>and <it>mbx </it>operons of <it>Pyrococcus furiosus</it>, which may play a role in sulfur reduction and/or hydrogen production. The two marine organisms, <it>S. marinus </it>and <it>H. butylicus</it>, possess more sodium-dependent transporters than <it>T. pendens </it>and use symporters for potassium uptake while <it>T. pendens </it>uses an ATP-dependent potassium transporter. <it>T. pendens </it>has adapted to a nutrient-rich environment while <it>H. butylicus </it>is adapted to a nutrient-poor environment, and <it>S. marinus </it>lies between these two extremes.</p> <p>Conclusion</p> <p>The three heterotrophic sulfur-reducing crenarchaeotes have adapted to their habitats, terrestrial vs. marine, via their transporter content, and they have also adapted to environments with differing levels of nutrients. Despite the fact that they all use sulfur as an electron acceptor, they are likely to have different pathways for sulfur reduction.</p

    Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle

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    Polyclonal antibodies, derived from humans or hyperimmunized animals, have been used prophylactically or therapeutically as countermeasures for a variety of infectious diseases. SAB Biotherapeutics has successfully developed a transchromosomic (Tc) bovine platform technology that can produce fully human immunoglobulins rapidly, and in substantial quantities, against a variety of disease targets. In this study, two Tc bovines expressing high levels of fully human IgG were hyperimmunized with a recombinant glycoprotein (GP) vaccine consisting of the 2014 Ebola virus (EBOV) Makona isolate. Serum collected from these hyperimmunized Tc bovines contained high titers of human IgG against EBOV GP as determined by GP specific ELISA, surface plasmon resonance (SPR), and virus neutralization assays. Fully human polyclonal antibodies against EBOV were purified and evaluated in a mouse challenge model using mouse adapted Ebola virus (maEBOV). Intraperitoneal administration of the purified anti-EBOV IgG (100 mg/kg) to BALB/c mice one day after lethal challenge with maEBOV resulted in 90% protection; whereas 100% of the control animals succumbed. The results show that hyperimmunization of Tc bovines with EBOV GP can elicit protective and potent neutralizing fully human IgG antibodies rapidly and in commercially viable quantities

    Holographic quark gluon plasma with flavor

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    In this work I explore theoretical and phenomenological implications of chemical potentials and charge densities inside a strongly coupled thermal plasma, using the gauge/gravity correspondence. Strong coupling effects discovered in this model theory are interpreted geometrically and may be taken as qualitative predictions for heavy ion collisions at RHIC and LHC. In particular I examine the thermodynamics, spectral functions, transport coefficients and the phase diagram of the strongly coupled plasma. For example stable mesons, which are the analogs of the QCD Rho-mesons, are found to survive beyond the deconfinement transition. This paper is based on partly unpublished work performed in the context of my PhD thesis. New results and ideas extending significantly beyond those published until now are stressed.Comment: 45 figures, 166 page

    Genomic Characterization of Methanomicrobiales Reveals Three Classes of Methanogens

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    BACKGROUND:Methanomicrobiales is the least studied order of methanogens. While these organisms appear to be more closely related to the Methanosarcinales in ribosomal-based phylogenetic analyses, they are metabolically more similar to Class I methanogens. METHODOLOGY/PRINCIPAL FINDINGS:In order to improve our understanding of this lineage, we have completely sequenced the genomes of two members of this order, Methanocorpusculum labreanum Z and Methanoculleus marisnigri JR1, and compared them with the genome of a third, Methanospirillum hungatei JF-1. Similar to Class I methanogens, Methanomicrobiales use a partial reductive citric acid cycle for 2-oxoglutarate biosynthesis, and they have the Eha energy-converting hydrogenase. In common with Methanosarcinales, Methanomicrobiales possess the Ech hydrogenase and at least some of them may couple formylmethanofuran formation and heterodisulfide reduction to transmembrane ion gradients. Uniquely, M. labreanum and M. hungatei contain hydrogenases similar to the Pyrococcus furiosus Mbh hydrogenase, and all three Methanomicrobiales have anti-sigma factor and anti-anti-sigma factor regulatory proteins not found in other methanogens. Phylogenetic analysis based on seven core proteins of methanogenesis and cofactor biosynthesis places the Methanomicrobiales equidistant from Class I methanogens and Methanosarcinales. CONCLUSIONS/SIGNIFICANCE:Our results indicate that Methanomicrobiales, rather than being similar to Class I methanogens or Methanomicrobiales, share some features of both and have some unique properties. We find that there are three distinct classes of methanogens: the Class I methanogens, the Methanomicrobiales (Class II), and the Methanosarcinales (Class III)

    Evaluation of Spin-Triplet Superconductivity in Sr2RuO4

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    This review presents a summary and evaluations of the superconducting properties of the layered ruthenate Sr2RuO4 as they are known in the autumn of 2011. This paper appends the main progress that has been made since the preceding review by Mackenzie and Maeno was published in 2003. Here, special focus is placed on the critical evaluation of the spin-triplet, odd-parity pairing scenario applied to Sr2RuO4. After an introduction to superconductors with possible odd-parity pairing, accumulated evidence for the pairing symmetry of Sr2RuO4 is examined. Then, significant recent progress on the theoretical approaches to the superconducting pairing by Coulomb repulsion is reviewed. A section is devoted to some experimental properties of Sr2RuO4 that seem to defy simple explanations in terms of currently available spin-triplet scenario. The next section deals with some new developments using eutectic boundaries and micro-crystals, which reveals novel superconducting phenomena related to chiral edge states, odd-frequency pairing states, and half-fluxoid states. Some of these properties are intimately connected with the properties as a topological superconductor. The article concludes with a summary of knowledge emerged from the study of Sr2RuO4 that are now more widely applied to understand the physics of other unconventional superconductors, as well as with a brief discussion of relatively unexplored but promising areas of ongoing and future studies of Sr2RuO4.Comment: 31 pages, 35 figures, published in J. Phys. Soc. Jpn. as a review article of Special Topic
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