701 research outputs found

    IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

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    Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD

    Fitness consequences of Anopheles gambiae population hybridization

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    BACKGROUND: The use of transgenic mosquitoes with parasite inhibiting genes has been proposed as an integral strategy to control malaria transmission. However, release of exotic transgenic mosquitoes will bring in novel alleles along with parasite-inhibiting genes that may have unknown effects on native populations. Thus it is necessary to study the effects and dynamics of fitness traits in native mosquito populations in response to the introduction of novel genes. This study was designed to evaluate the dynamics of fitness traits in a simulation of introduction of novel alleles under laboratory conditions using two strains of Anopheles gambiae: Mbita strain from western Kenya and Ifakara strain from Tanzania. METHODS: The dynamics of fitness traits were evaluated under laboratory conditions using the two An. gambiae strains. These two geographically different strains were cross-bred and monitored for 20 generations to score fecundity, body size, blood-meal size, larval survival, and adult longevity, all of which are important determinants of the vector's potential in malaria transmission. Traits were analysed using pair-wise analysis of variance (ANOVA) for fecundity, body size, and blood-meal size while survival analysis was performed for larval survival and adult longevity. RESULTS: Fecundity and body size were significantly higher in the progeny up to the 20(th )generation compared to founder strains. Adult longevity had a significantly higher mean up to the 10(th )generation and average blood-meal size was significantly larger up to the 5(th )generation, indicating that hybrids fitness is enhanced over that of the founder strains. CONCLUSION: Hybridization of the two mosquito populations used in this study led to increased performance in the fitness traits studied. Given that the studied traits are important determinants of the vector's potential to transmit malaria, these results suggest the need to release genetically modified mosquitoes that have the same or very similar backgrounds to the native populations

    Poly A- Transcripts Expressed in HeLa Cells

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    BACKGROUND: Transcripts expressed in eukaryotes are classified as poly A+ transcripts or poly A- transcripts based on the presence or absence of the 3' poly A tail. Most transcripts identified so far are poly A+ transcripts, whereas the poly A- transcripts remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We developed the TRD (Total RNA Detection) system for transcript identification. The system detects the transcripts through the following steps: 1) depleting the abundant ribosomal and small-size transcripts; 2) synthesizing cDNA without regard to the status of the 3' poly A tail; 3) applying the 454 sequencing technology for massive 3' EST collection from the cDNA; and 4) determining the genome origins of the detected transcripts by mapping the sequences to the human genome reference sequences. Using this system, we characterized the cytoplasmic transcripts from HeLa cells. Of the 13,467 distinct 3' ESTs analyzed, 24% are poly A-, 36% are poly A+, and 40% are bimorphic with poly A+ features but without the 3' poly A tail. Most of the poly A- 3' ESTs do not match known transcript sequences; they have a similar distribution pattern in the genome as the poly A+ and bimorphic 3' ESTs, and their mapped intergenic regions are evolutionarily conserved. Experiments confirmed the authenticity of the detected poly A- transcripts. CONCLUSION/SIGNIFICANCE: Our study provides the first large-scale sequence evidence for the presence of poly A- transcripts in eukaryotes. The abundance of the poly A- transcripts highlights the need for comprehensive identification of these transcripts for decoding the transcriptome, annotating the genome and studying biological relevance of the poly A- transcripts

    Co3O4 Nanocrystals on Graphene as a Synergistic Catalyst for Oxygen Reduction Reaction

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    Catalysts for oxygen reduction and evolution reactions are at the heart of key renewable energy technologies including fuel cells and water splitting. Despite tremendous efforts, developing oxygen electrode catalysts with high activity at low costs remains a grand challenge. Here, we report a hybrid material of Co3O4 nanocrystals grown on reduced graphene oxide (GO) as a high-performance bi-functional catalyst for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). While Co3O4 or graphene oxide alone has little catalytic activity, their hybrid exhibits an unexpected, surprisingly high ORR activity that is further enhanced by nitrogen-doping of graphene. The Co3O4/N-doped graphene hybrid exhibits similar catalytic activity but superior stability to Pt in alkaline solutions. The same hybrid is also highly active for OER, making it a high performance non-precious metal based bi-catalyst for both ORR and OER. The unusual catalytic activity arises from synergetic chemical coupling effects between Co3O4 and graphene.Comment: published in Nature Material

    Cooling in strongly correlated optical lattices: prospects and challenges

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    Optical lattices have emerged as ideal simulators for Hubbard models of strongly correlated materials, such as the high-temperature superconducting cuprates. In optical lattice experiments, microscopic parameters such as the interaction strength between particles are well known and easily tunable. Unfortunately, this benefit of using optical lattices to study Hubbard models come with one clear disadvantage: the energy scales in atomic systems are typically nanoKelvin compared with Kelvin in solids, with a correspondingly miniscule temperature scale required to observe exotic phases such as d-wave superconductivity. The ultra-low temperatures necessary to reach the regime in which optical lattice simulation can have an impact-the domain in which our theoretical understanding fails-have been a barrier to progress in this field. To move forward, a concerted effort to develop new techniques for cooling and, by extension, techniques to measure even lower temperatures. This article will be devoted to discussing the concepts of cooling and thermometry, fundamental sources of heat in optical lattice experiments, and a review of proposed and implemented thermometry and cooling techniques.Comment: in review with Reports on Progress in Physic

    Carrier localization and electronic phase separation in a doped spin-orbit driven Mott phase in Sr3(Ir1-xRux)2O7

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    Interest in many strongly spin-orbit coupled 5d-transition metal oxide insulators stems from mapping their electronic structures to a J=1/2 Mott phase. One of the hopes is to establish their Mott parent states and explore these systems' potential of realizing novel electronic states upon carrier doping. However, once doped, little is understood regarding the role of their reduced Coulomb interaction U relative to their strongly correlated 3d-electron cousins. Here we show that, upon hole-doping a candidate J=1/2 Mott insulator, carriers remain localized within a nanoscale phase separated ground state. A percolative metal-insulator transition occurs with interplay between localized and itinerant regions, stabilizing an antiferromagnetic metallic phase beyond the critical region. Our results demonstrate a surprising parallel between doped 5d- and 3d-electron Mott systems and suggest either through the near degeneracy of nearby electronic phases or direct carrier localization that U is essential to the carrier response of this doped spin-orbit Mott insulator.Comment: 25 pages, 4 figures in main text, 4 figures in supplemental tex

    Surface-plasmon-polariton wave propagation supported by anisotropic materials: multiple modes and mixed exponential and linear localization characteristics

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    The canonical boundary-value problem for surface-plasmon-polariton (SPP) waves guided by the planar interface of a dielectric material and a plasmonic material was solved for cases wherein either partnering material could be a uniaxial material with optic axis lying in the interface plane.Numerical studies revealed that two different SPP waves, with different phase speeds, propagation lengths, and penetration depths, can propagate in a given direction in the interface plane; in contrast, the planar interface of isotropic partnering materials supports only one SPP wave for each propagation direction. Also, for a unique propagation direction in each quadrant of the interface plane, it was demonstrated that a new type of SPP wave--called a surface-plasmon-polariton-Voigt (SPP-V) wave--can exist. The fields of these SPP-V waves decay as the product of a linear and an exponential function of the distance from the interface in the anisotropic partnering material; in contrast, the fields of conventional SPP waves decay only exponentially with distance from the interface. Explicit analytic solutions of the dispersion relation for SPP-V waves exist and help establish constraints on the constitutive-parameter regimes for the partnering materials that support SPP-V-wave propagation
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