2,802 research outputs found

    Positively Correlated miRNA-miRNA Regulatory Networks in Mouse Frontal Cortex During Early Stages of Alcohol Dependence

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    Although the study of gene regulation via the action of specific microRNAs (miRNAs) has experienced a boom in recent years, the analysis of genome-wide interaction networks among miRNAs and respective targeted mRNAs has lagged behind. MicroRNAs simultaneously target many transcripts and fine-tune the expression of genes through cooperative/combinatorial targeting. Therefore, they have a large regulatory potential that could widely impact development and progression of diseases, as well as contribute unpredicted collateral effects due to their natural, pathophysiological, or treatment-induced modulation. We support the viewpoint that whole mirnome-transcriptome interaction analysis is required to better understand the mechanisms and potential consequences of miRNA regulation and/or deregulation in relevant biological models. In this study, we tested the hypotheses that ethanol consumption induces changes in miRNA-mRNA interaction networks in the mouse frontal cortex and that some of the changes observed in the mouse are equivalent to changes in similar brain regions from human alcoholics. Results: miRNA-mRNA interaction networks responding to ethanol insult were identified by differential expression analysis and weighted gene coexpression network analysis (WGCNA). Important pathways (coexpressed modular networks detected by WGCNA) and hub genes central to the neuronal response to ethanol are highlighted, as well as key miRNAs that regulate these processes and therefore represent potential therapeutic targets for treating alcohol addiction. Importantly, we discovered a conserved signature of changing miRNAs between ethanol-treated mice and human alcoholics, which provides a valuable tool for future biomarker/diagnostic studies in humans. We report positively correlated miRNA-mRNA expression networks that suggest an adaptive, targeted miRNA response due to binge ethanol drinking. Conclusions: This study provides new evidence for the role of miRNA regulation in brain homeostasis and sheds new light on current understanding of the development of alcohol dependence. To our knowledge this is the first report that activated expression of miRNAs correlates with activated expression of mRNAs rather than with mRNA downregulation in an in vivo model. We speculate that early activation of miRNAs designed to limit the effects of alcohol-induced genes may be an essential adaptive response during disease progression.NIAAA 5R01AA012404, 5P20AA017838, 5U01AA013520, P01AA020683, 5T32AA007471-24/25Waggoner Center for Alcohol and Addiction Researc

    Bio-electrospraying 3-D Organotypic Human Skin Cultures

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    Organotypic 3D tissue models have greatly contributed to understand a wide range of molecular and cellular characteristics within a functional or diseased tissue. Human skin reconstructs which act as models are most useful for a wide range of investigations, ranging from tissue engineering and regenerative medicine, drug development, screening, and discovery to name a few. There are many approaches for reconstructing 3D skin tissue models, however, to date there have been very few that are able to generate organotypic 3D constructs with a single technology having minimal processing steps to finally scalability. The many manifestations of 3D bioprinting have contributed to this endeavor, having said that, the technology's limitations have tempered those reconstructed models, as they are known to contain low cell numbers/concentrations to those having damaged/dead molecules/cells within the reconstructed tissue, which are not desirable, for exploring as tissues models. Contrary to 3D bioprinting approaches, bio-electrosprays have been demonstrated to possess the ability to handle large concentrations of cells and molecules to whole fertilized embryos without damaging them from a molecular level upwards. Consequently, this article demonstrates, for the first time, bio-electrospray's capacity to reconstruct skin-like structures in vitro and its potential in reconstructing full-thickness 3D organotypic human skin tissues

    One dimensional Coulomb-like problem in deformed space with minimal length

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    Spectrum and eigenfunctions in the momentum representation for 1D Coulomb potential with deformed Heisenberg algebra leading to minimal length are found exactly. It is shown that correction due to the deformation is proportional to square root of the deformation parameter. We obtain the same spectrum using Bohr-Sommerfeld quantization condition.Comment: 11 pages, typos corrected, references adde

    Geometry of the extreme Kerr black holes

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    Geometrical properties of the extreme Kerr black holes in the topological sectors of nonextreme and extreme configurations are studied. We find that the Euler characteristic plays an essential role to distinguish these two kinds of extreme black holes. The relationship between the geometrical properties and the intrinsic thermodynamics are investigated.Comment: Latex version, 10 page

    Fungi in a Warmer World - Fungal diversity from the Peak Warming of the Miocene Climate Optimum as Recorded in the Latah Formation, Clarkia, Idaho, USA

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    Microfungi are a vital part of ecosystems as they help with key processes, such as carbon and nutrient cycling, especially through the actions of mycorrhizal and saprotrophic members (Nuñez Otaño et al., 2015, 2021; Willis et al., 2018). Microfungi can also be good indicators of plant biodiversity in an area because many fungal taxa are host-specific (Rutten et al., 2021; Francioli et al., 2021; Hu et al., 2021; Wijayawardene et al., 2022 ). Despite being crucial components in ecosystems, they are often overlooked. In the fossil record, microfungi have a high preservaon rate and they are often preserved close to the original substrate they were deposited in. This makes them an important proxy for understanding local past ecological and climatological conditions (Romero et al., 2021, O’Keefe et al., 2017). The Fungi in a Warmer World project seeks to use fossil fungal assemblages to study changes in biodiversity during the Miocene Climate Opmum (MCO), a period of peak warming that closely mirrors current and projected warming trends (Steinthorsdotter et al., 2021). The current atmospheric CO2 concentraon is around 420 ppm but is rapidly approaching the MCO average of 450-550 ppm (Steinthorsdotter et al., 2021).https://scholarworks.moreheadstate.edu/celebration_posters_2022/1045/thumbnail.jp

    Relativistic quantum mechanics of a Dirac oscillator

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    The Dirac oscillator is an exactly soluble model recently introduced in the context of many particle models in relativistic quantum mechanics. The model has been also considered as an interaction term for modelling quark confinement in quantum chromodynamics. These considerations should be enough for demonstrating that the Dirac oscillator can be an excellent example in relativistic quantum mechanics. In this paper we offer a solution to the problem and discuss some of its properties. We also discuss a physical picture for the Dirac oscillator's non-standard interaction, showing how it arises on describing the behaviour of a neutral particle carrying an anomalous magnetic moment and moving inside an uniformly charged sphere.Comment: 19 pages, 1 figur

    M-Theory solutions with AdS factors

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    Solutions of D=7 maximal gauged supergravity are constructed with metrics that are a product of a n-dimensional anti-de Sitter (AdS) space, with n=2,3,4,5, and certain Einstein manifolds. The gauge fields have the same form as in the recently constructed solutions describing the near-horizon limits of M5-branes wrapping supersymmetric cycles. The new solutions do not preserve any supersymmetry and can be uplifted to obtain new solutions of D=11 supergravity, which are warped and twisted products of the D=7 metric with a squashed four-sphere. Some aspects of the stability of the solutions are discussed.Comment: 30 pages. References adde

    Wrapped fivebranes and N=2 super Yang-Mills theory

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    We construct D=10 supergravity solutions corresponding to type IIB fivebranes wrapping a two-sphere in a Calabi-Yau two-fold. These are related in the IR to the large N limit of pure N=2 SU(N) super Yang-Mills theory. We show that the singularities in the IR correspond to the wrapped branes being distributed on a ring. We analyse the dynamics of a probe fivebrane and show that it incorporates the full perturbative structure of the gauge theory. For a class of solutions the two-dimensional moduli space is non-singular and we match the result for the corresponding slice of the Coulomb branch of the gauge theory.Comment: 24 Latex pages, two figures;v2 typos corrected, references adde

    Superconformal Gauge Theories and Non-Critical Superstrings

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    We consider effective actions for six-dimensional non-critical superstrings. We show that the addition of NN units of R-R flux and of NfN_f space-time filling D5-branes produces AdS5×S1AdS_5 \times S^1 solutions with curvature comparable to the string scale. These solutions have the right structure to be dual to N=1{\cal N}=1 supersymmetric SU(N) gauge theories with NfN_f flavors. We further suggest bounds on the mass-squared of tachyonic fields in this background that should restrict the theory to the conformal window.Comment: 16 pages, 1 figure v4: Minor change

    Band-structure trend in hole-doped cuprates and correlation with Tcmax

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    By calculation and analysis of the bare conduction bands in a large number of hole-doped high-temperature superconductors, we have identified the energy of the so-called axial-orbital as the essential, material-dependent parameter. It is uniquely related to the range of the intra-layer hopping. It controls the Cu 4s-character, influences the perpendicular hopping, and correlates with the observed Tc at optimal doping. We explain its dependence on chemical composition and structure, and present a generic tight-binding model.Comment: 5 pages, Latex, 5 eps figure
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