30,920 research outputs found

    Mouse models of diabetes, obesity and related kidney disease

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    © 2016 Glastras et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Multiple rodent models have been used to study diabetic kidney disease (DKD). The purpose of the present study was to compare models of diabetes and obesity-induced metabolic syndrome and determine differences in renal outcomes. C57BL/6 male mice were fed either normal chow or high fat diet (HFD). At postnatal week 8, chow-fed mice were randomly assigned to low-dose streptozotocin (STZ, 55 mg/kg/day, five consecutive days) or vehicle control, whereas HFD-fed mice were given either one high-dose of STZ (100 mg/kg) or vehicle control. Intraperitoneal glucose tolerance tests were performed at Week 14, 20 and 30. Urinary albumin to creatinine ratio (ACR) and serum creatinine were measured, and renal structure was assessed using Periodic Acid Schiff (PAS) staining at Week 32. Results showed that chow-fed mice exposed to five doses of STZ resembled type 1 diabetes mellitus with a lean phenotype, hyperglycaemia, microalbuminuria and increased serum creatinine levels. Their kidneys demonstrated moderate tubular injury with evidence of tubular dilatation and glycogenated nuclear inclusion bodies. HFD-fed mice resembled metabolic syndrome as they were obese with dyslipidaemia, insulin resistance, and significantly impaired glucose tolerance. One dose STZ, in addition to HFD, did not worsen metabolic features (including fasting glucose, non esterified fatty acid, and triglyceride levels). There were significant increases in urinary ACR and serum creatinine levels, and renal structural changes were predominantly related to interstitial vacuolation and tubular dilatation in HFD-fed mice

    FXR expression is associated with dysregulated glucose and lipid levels in the offspring kidney induced by maternal obesity

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    © 2015 Glastras et al. Background: Maternal obesity is associated with dysregulation of glucose and lipid metabolism with consequent exposure of the fetus to an abnormal metabolic milieu. It is recognized that maternal obesity predisposes offspring to chronic kidney disease (CKD). We aimed to determine whether the nuclear Farnesoid X receptor (FXR), known to play a role in maintaining homeostasis of glucose and lipid metabolism, is involved in renal injury in offspring of obese mothers. Methods: Maternal obesity was established in a rat model by feeding dams with high-fat diet prior to and during pregnancy and lactation. The offspring's kidneys were examined at postnatal Day 1and Day 20. Human kidney 2 (HK2) cells were exposed to high glucose with or without the FXR agonist GW4064 or when FXR mRNA was silenced. Results: Glucose intolerance in the offspring of obese mothers was evident at weaning, with associated downregulation of renal FXR expression and upregulation of monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-β1 (TGF-β1). HK2 cells exposed to high glucose had reduced FXR expression and increased MCP-1, TGF-β1, fibronectin and collagen IV expression, which was reversed in the presence of GW4064. FXR-silenced HK2 cells had amplified pro-inflammatory and pro-fibrotic markers under high glucose conditions. Conclusions: Maternal obesity influences renal expression of pro-inflammatory and fibrotic factors that predispose the offspring to CKD. This was associated with the downregulation of the renal FXR expression suggesting a potential protective role for FXR

    Balanced electric-magnetic dihole in Kaluza-Klein theory

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    We present a four-dimensional double-black-hole (or dihole) solution in Kaluza-Klein theory, describing a superposition of an electrically charged and a magnetically charged black hole. This system can be balanced for appropriately chosen parameters, and the resulting space-time is completely regular on and outside the event horizons. This solution was constructed using the inverse-scattering method in five-dimensional vacuum gravity, in which it describes a rotating black ring surrounding a static black hole on a Taub-NUT background space. Various properties of this solution are studied, from both a four- and five-dimensional perspective.Comment: 33 pages, 6 figures; v2: expanded discussion of phase space, published versio

    Collective decision-making on triadic graphs

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    Many real-world networks exhibit community structures and non-trivial clustering associated with the occurrence of a considerable number of triangular subgraphs known as triadic motifs. Triads are a set of distinct triangles that do not share an edge with any other triangle in the network. Network motifs are subgraphs that occur significantly more often compared to random topologies. Two prominent examples, the feedforward loop and the feedback loop, occur in various real-world networks such as gene-regulatory networks, food webs or neuronal networks. However, as triangular connections are also prevalent in communication topologies of complex collective systems, it is worthwhile investigating the influence of triadic motifs on the collective decision-making dynamics. To this end, we generate networks called Triadic Graphs (TGs) exclusively from distinct triadic motifs. We then apply TGs as underlying topologies of systems with collective dynamics inspired from locust marching bands. We demonstrate that the motif type constituting the networks can have a paramount influence on group decision-making that cannot be explained solely in terms of the degree distribution. We find that, in contrast to the feedback loop, when the feedforward loop is the dominant subgraph, the resulting network is hierarchical and inhibits coherent behavior

    Low-dose hydralazine reduces albuminuria and glomerulosclerosis in a mouse model of obesity-related chronic kidney disease.

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    BACKGROUND: Obesity is a major risk factor for the development and progression of chronic kidney disease (CKD). DNA methylation has been implicated in the progression of CKD to end stage kidney disease. Drugs modifying DNA methylation, such as low-dose hydralazine, may reduce CKD progression. Using a mouse model of obesity, we aimed to determine whether low-dose hydralazine prevents obesity-related CKD. METHODS: From 8 weeks of age, male C57BL/6 mice received high fat diet (HFD) or chow, with or without low-dose hydralazine (25 mg/L) in drinking water for 24 weeks. Biometric and metabolic parameters, renal functional and structural changes, renal global DNA methylation, DNA methylation profile and markers of renal fibrosis, injury, inflammation and oxidative stress were assessed. RESULTS: HFD-fed mice developed obesity, with glucose intolerance, hyperinsulinaemia and dyslipidaemia. Obesity increased albuminuria and glomerulosclerosis, which were significantly ameliorated by low-dose hydralazine in the absence of a blood pressure-lowering effect. Obesity increased renal global DNA methylation and this was attenuated by low-dose hydralazine. HFD-induced changes in methylation of individual loci were also significantly reversed by low-dose hydralazine. Obese mice demonstrated increased markers of kidney fibrosis, inflammation and oxidative stress, but these markers were not significantly improved by hydralazine. CONCLUSION: Low-dose hydralazine ameliorated HFD-induced albuminuria and glomerulosclerosis, independent of alterations in biometric and metabolic parameters or blood pressure regulation. Although the precise mechanism of renoprotection in obesity is unclear, an epigenetic basis may be implicated. These data support repurposing hydralazine as a novel therapy to prevent CKD progression in obese patients. This article is protected by copyright. All rights reserved

    Experimental magic state distillation for fault-tolerant quantum computing

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    Any physical quantum device for quantum information processing is subject to errors in implementation. In order to be reliable and efficient, quantum computers will need error correcting or error avoiding methods. Fault-tolerance achieved through quantum error correction will be an integral part of quantum computers. Of the many methods that have been discovered to implement it, a highly successful approach has been to use transversal gates and specific initial states. A critical element for its implementation is the availability of high-fidelity initial states such as |0> and the Magic State. Here we report an experiment, performed in a nuclear magnetic resonance (NMR) quantum processor, showing sufficient quantum control to improve the fidelity of imperfect initial magic states by distilling five of them into one with higher fidelity

    Observation of pseudogap behavior in a strongly interacting Fermi gas

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    Ultracold atomic Fermi gases present an opportunity to study strongly interacting Fermi systems in a controlled and uncomplicated setting. The ability to tune attractive interactions has led to the discovery of superfluidity in these systems with an extremely high transition temperature, near T/T_F = 0.2. This superfluidity is the electrically neutral analog of superconductivity; however, superfluidity in atomic Fermi gases occurs in the limit of strong interactions and defies a conventional BCS description. For these strong interactions, it is predicted that the onset of pairing and superfluidity can occur at different temperatures. This gives rise to a pseudogap region where, for a range of temperatures, the system retains some of the characteristics of the superfluid phase, such as a BCS-like dispersion and a partially gapped density of states, but does not exhibit superfluidity. By making two independent measurements: the direct observation of pair condensation in momentum space and a measurement of the single-particle spectral function using an analog to photoemission spectroscopy, we directly probe the pseudogap phase. Our measurements reveal a BCS-like dispersion with back-bending near the Fermi wave vector k_F that persists well above the transition temperature for pair condensation

    Bound states of holes in an antiferromagnet

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    The formation of bound states of holes in an antiferromagnetic spin-1/2 background is studied using numerical techniques applied to the tJ{\rm t-J} Hamiltonian on clusters with up to 26 sites. An analysis of the binding energy as a function of cluster size suggests that a two hole bound state is formed for couplings larger than a ``critical'' value J/t]c{\rm J/t]_c}. The symmetry of the bound state is \dx2y2. We also observed that its ``quasiparticle'' weight Z2h{\rm Z_{2h}} (defined in the text), is finite for all values of the coupling J/t{\rm J/t}. Thus, in the region J/tJ/t]c{\rm J/t \geq J/t]_c} the bound state of two holes behaves like a quasiparticle with charge Q=2eQ=2e, spin S=0S=0, and \dx2y2 internal symmetry. The relation with recent ideas that have suggested the possibility of d-wave pairing in the high temperature cuprate superconductors is briefly discussed.Comment: 12 pages and 3 figures (3 postscript files included), Report LPQTH-93/0
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