Dissipative quantum disordered models

This article reviews recent studies of mean-field and one dimensional quantum disordered spin systems coupled to different types of dissipative environments. The main issues discussed are: (i) The real-time dynamics in the glassy phase and how they compare to the behaviour of the same models in their classical limit. (ii) The phase transition separating the ordered -- glassy -- phase from the disordered phase that, for some long-range interactions, is of second order at high temperatures and of first order close to the quantum critical point (similarly to what has been observed in random dipolar magnets). (iii) The static properties of the Griffiths phase in random Ising chains. (iv) The dependence of all these properties on the environment. The analytic and numeric techniques used to derive these results are briefly mentioned.Comment: Contribution to the 12th International Conference on Recent Progress in Many-Body Theories, Santa Fe, New Mexico, USA, August 2004; 10 pages no fig

A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome

Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration and considered as an endoplasmic reticulum (ER) disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome and the identification of two causative genes, Wolfram syndrome 1 (WFS1) and Wolfram syndrome 2 (WFS2), a molecular mechanism linking the ER to death of neurons and β cells has not been elucidated. Here we implicate calpain 2 in the mechanism of cell death in Wolfram syndrome. Calpain 2 is negatively regulated by WFS2, and elevated activation of calpain 2 by WFS2-knockdown correlates with cell death. Calpain activation is also induced by high cytosolic calcium mediated by the loss of function of WFS1. Calpain hyperactivation is observed in the WFS1 knockout mouse as well as in neural progenitor cells derived from induced pluripotent stem (iPS) cells of Wolfram syndrome patients. A small-scale small-molecule screen targeting ER calcium homeostasis reveals that dantrolene can prevent cell death in neural progenitor cells derived from Wolfram syndrome iPS cells. Our results demonstrate that calpain and the pathway leading its activation provides potential therapeutic targets for Wolfram syndrome and other ER diseases

Targeting cellular calcium homeostasis to prevent cytokine-mediated beta cell death

AbstractPro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca2+-ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.</jats:p

Planck Scale Physics and the Testability of SU(5) Supergravity GUT

GUT scale threshold corrections in minimal SU(5) supergravity grand unification are discussed. It is shown that predictions may be made despite uncertainties associated with the high energy scale. A bound relating the strong coupling constant to the mass scales associated with proton decay and supersymmetry is derived, and a sensitive probe of the underlying theory is outlined. In particular, low energy measurements can in principle determine the presence of Planck scale ($1 / {{\rm M}_{\rm Pl}}$) terms.Comment: 12 pages, REVTeX, 2 figures included in an uuencoded Z-compressed PostScript file. Ready to print PostScript version (with figures) may be picked up at ftp://phys.tamu.edu/urano/planck/paper_prep.p

Hubbard chains network on corner-sharing tetrahedra: origin of the heavy fermion state in LiV_2O_4

We investigate the Hubbard chains network model defined on corner-sharing tetrahedra (the pyrochlore lattice) which is a possible microscopic model for the heavy fermion state of LiV_2O_4. Based upon this model, we can explain transport, magnetic, and thermodynamic properties of LiV_2O_4. We calculate the spin susceptibility, and the specific heat coefficient, exploiting the Bethe ansatz exact solution of the 1D Hubbard model and bosonization method. The results are quite consistent with experimental observations. We obtain the large specific heat coefficient $\gamma\sim 222 {\rm mJ/mol K^2}$.Comment: 5 pages, 2 figures, a postscript file of Figure 1 is not included, to appear in Physical Review

A strategy for the rapid identification of fungal metabolites and the discovery of the antiviral activity of pyrenocine a and harzianopyridon

The isolation and identification of bioactive metabolites from complex extracts obtained from microbial growth media is a time consuming, costly, and labor-intensive task. A strategy to rapidly identify secondary metabolites isolated from extracts obtained from the culture media of marine-derived and endophytic fungal strains is described. Identification was achieved by HPLC-UV-MS and 1H NMR analyses in combination with data obtained from the Dictionary of Natural Products. Among the compounds identified, (-)-naphthoquinoneimine, citreorosein, emodin, pyrenocine A and harzianopyridone displayed moderate to potent antiviral activity. (-)-Naphthoquinoneimine was isolated as the enantiomer of its previously reported dextrorotatory congener, while 6,7-dihydroxy-2,2-dimethyl-4-chromanone is herein reported for the first time as a natural product396720731CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPBEX 4498-14-32010/50190-2; 2013/50228-8; 2011/08064-2; 2008/00331-9; 2013/23153-

The Role of IRE1α in the Degradation of Insulin mRNA in Pancreatic β-Cells

The endoplasmic reticulum (ER) is a cellular compartment for the biosynthesis and folding of newly synthesized secretory proteins such as insulin. Perturbations to ER homeostasis cause ER stress and subsequently activate cell signaling pathways, collectively known as the Unfolded Protein Response (UPR). IRE1α is a central component of the UPR. In pancreatic β-cells, IRE1α also functions in the regulation of insulin biosynthesis.Here we report that hyperactivation of IRE1α caused by chronic high glucose treatment or IRE1α overexpression leads to insulin mRNA degradation in pancreatic β-cells. Inhibition of IRE1α signaling using its dominant negative form prevents insulin mRNA degradation. Islets from mice heterozygous for IRE1α retain expression of more insulin mRNA after chronic high glucose treatment than do their wild-type littermates.These results reveal a role of IRE1α in insulin mRNA expression under ER stress conditions caused by chronic high glucose. The rapid degradation of insulin mRNA could provide immediate relief for the ER and free up the translocation machinery. Thus, this mechanism would preserve ER homeostasis and help ensure that the insulin already inside the ER can be properly folded and secreted. This adaptation may be crucial for the maintenance of β-cell homeostasis and may explain why the β-cells of type 2 diabetic patients with chronic hyperglycemia stop producing insulin in the absence of apoptosis. This mechanism may also be involved in suppression of the autoimmune type 1 diabetes by reducing the amount of misfolded insulin, which could be a source of “neo-autoantigens.