204 research outputs found

    Sirtuin1 protects endothelial Caveolin-1 expression and preserves endothelial function via suppressing miR-204 and endoplasmic reticulum stress.

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    Sirtuin1 (Sirt1) is a class III histone deacetylase that regulates a variety of physiological processes, including endothelial function. Caveolin1 (Cav1) is also an important determinant of endothelial function. We asked if Sirt1 governs endothelial Cav1 and endothelial function by regulating miR-204 expression and endoplasmic reticulum (ER) stress. Knockdown of Sirt1 in endothelial cells, and in vivo deletion of endothelial Sirt1, induced endothelial ER stress and miR-204 expression, reduced Cav1, and impaired endothelium-dependent vasorelaxation. All of these effects were reversed by a miR-204 inhibitor (miR-204 I) or with overexpression of Cav1. A miR-204 mimic (miR-204 M) decreased Cav1 in endothelial cells. In addition, high-fat diet (HFD) feeding induced vascular miR-204 and reduced endothelial Cav1. MiR-204-I protected against HFD-induced downregulation of endothelial Cav1. Moreover, pharmacologic induction of ER stress with tunicamycin downregulated endothelial Cav1 and impaired endothelium-dependent vasorelaxation that was rescued by overexpressing Cav1. In conclusion, Sirt1 preserves Cav1-dependent endothelial function by mitigating miR-204-mediated vascular ER stress

    Chronic inhibition of endoplasmic reticulum stress and inflammation prevents ischaemia-induced vascular pathology in type II diabetic mice

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    Endoplasmic reticulum (ER) stress and inflammation are important mechanisms that underlie many of the serious consequences of type II diabetes. However, the role of ER stress and inflammation in impaired ischaemia-induced neovascularization in type II diabetes is unknown. We studied ischaemia-induced neovascularization in the hind-limb of 4-week-old db - /db- mice and their controls treated with or without the ER stress inhibitor (tauroursodeoxycholic acid, TUDCA, 150 mg/kg per day) and interleukin-1 receptor antagonist (anakinra, 0.5 microg/mouse per day) for 4 weeks. Blood pressure was similar in all groups of mice. Blood glucose, insulin levels, and body weight were reduced in db - /db- mice treated with TUDCA. Increased cholesterol and reduced adiponectin in db - /db- mice were restored by TUDCA and anakinra treatment. ER stress and inflammation in the ischaemic hind-limb in db - /db- mice were attenuated by TUDCA and anakinra treatment. Ischaemia-induced neovascularization and blood flow recovery were significantly reduced in db - /db- mice compared to control. Interestingly, neovascularization and blood flow recovery were restored in db - /db- mice treated with TUDCA or anakinra compared to non-treated db - /db- mice. TUDCA and anakinra enhanced eNOS-cGMP, VEGFR2, and reduced ERK1/2 MAP-kinase signalling, while endothelial progenitor cell number was similar in all groups of mice. Our findings demonstrate that the inhibition of ER stress and inflammation prevents impaired ischaemia-induced neovascularization in type II diabetic mice. Thus, ER stress and inflammation could be potential targets for a novel therapeutic approach to prevent impaired ischaemia-induced vascular pathology in type II diabetes

    Ordering and frustrations in generalized Ising chain

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    The Ising model on a one-dimensional monoatomic equidistant lattice with different nearest-neighbour and second-neighbour exchange interactions is researched. Generalized Kramers-Wannier transfer-matrix with translation on two periods of a lattice is introduced. A property similar to supercooling and superheating is detected. At the triple points phases are not individualized, but completely frustrated which corresponds to the phenomenon of critical opalescence. Exact analytical expressions for free energy, heat capacity and entropy including zero-temperature entropy are obtained. Various new special cases were analyzed and compared with all known results. All frustration fields for magnetization, frustration values for the zero-temperature entropy and magnetization are found. © Published under licence by IOP Publishing Ltd.Ural Branch, Russian Academy of Sciences, UB RAS: 18-2-2-11The research was carried out within the state assignment of Minobrnauki of Russia (theme ”Quantum” No. AAAA-A18-118020190095-4), supported in part by Ural Branch of the Russian Academy of Sciences (project No. 18-2-2-11)

    The Ferromagnetic Potts model under an external magnetic field: an exact renormalization group approach

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    The q-state ferromagnetic Potts model under a non-zero magnetic field coupled with the 0^th Potts state was investigated by an exact real-space renormalization group approach. The model was defined on a family of diamond hierarchical lattices of several fractal dimensions d_F. On these lattices, the renormalization group transformations became exact for such a model when a correlation coupling that singles out the 0^th Potts state was included in the Hamiltonian. The rich criticality presented by the model with q=3 and d_F=2 was fully analyzed. Apart from the Potts criticality for the zero field, an Ising-like phase transition was found whenever the system was submitted to a strong reverse magnetic field. Unusual characteristics such as cusps and dimensional reduction were observed on the critical surface.Comment: 8 pages, 6 figures. Accepted to be published in Phys. Rev B (2006

    GENERALIZED ISING MODEL IN A MAGNETIC FIELD

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    The Ising model is generalized to an arbitrary number translations of a linear chain in an external magnetic field taking into account various interactions between spins. The values of frustrating entropies and magnetizations can be expressed through the limit ratio of certain number sequences.Работа выполнена в рамках государственного задания Министерства науки и высшего образования РФ (тема «Квант», No АААА-А18-118020190095-4) и «Сплавы», No AAAA-A19-119070890020-3 и при частичной поддержке Уральского отделения Российской академии наук (проект No 18-2-2-11)

    Positioning of Weight Bias: Moving towards Social Justice

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    Weight bias is a form of stigma with detrimental effects on the health and wellness of individuals with large bodies. Researchers from various disciplines have recognized weight bias as an important topic for public health and for professional practice. To date, researchers from various areas have approached weight bias from independent perspectives and from differing theoretical orientations. In this paper, we examined the similarities and differences between three perspectives (i.e., weight-centric, nonweight-centric (health-centric), and health at every size) used to understand weight bias and approach weight bias research with regard to (a) language about people with large bodies, (b) theoretical position, (c) identified consequences of weight bias, and (d) identified influences on weight-based social inequity. We suggest that, despite differences, each perspective acknowledges the negative influences that position weight as being within individual control and the negative consequences of weight bias. We call for recognition and discussion of weight bias as a social justice issue in order to change the discourse and professional practices extended towards individuals with large bodies. We advocate for an emphasis on social justice as a uniting framework for interdisciplinary research on weight bias

    Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics

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    The human rights implications of virginity testing in South Africa

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    This article examines the historical context of virginity testing in Southern Africa with a focus on South Africa. It then examines the arguments often adduced in justifying the introduction of this practice. The two major arguments to support the reintroduction of virginity testing, namely, that it helps in reducing the spread of HIV and in preserving societal moral values are critically examined. Thereafter, the article discusses how the ever contentious debate between universalists and relativists applies to virginity testing. The last part of the article then considers the human rights implications of virginity testing

    Enhancement strategies for transdermal drug delivery systems: current trends and applications

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