A Pleiotropic Role for the Orphan Nuclear Receptor Small Heterodimer Partner in Lipid Homeostasis and Metabolic Pathways

Nuclear receptors (NRs) comprise one of the most abundant classes of transcriptional regulators of metabolic diseases and have emerged as promising pharmaceutical targets. Small heterodimer partner (SHP; NR0B2) is a unique orphan NR lacking a DNA-binding domain but contains a putative ligand-binding domain. SHP is a transcriptional regulator affecting multiple key biological functions and metabolic processes including cholesterol, bile acid, and fatty acid metabolism, as well as reproductive biology and glucose-energy homeostasis. About half of all mammalian NRs and several transcriptional coregulators can interact with SHP. The SHP-mediated repression of target transcription factors includes at least three mechanisms including direct interference with the C-terminal activation function 2 (AF2) coactivator domains of NRs, recruitment of corepressors, or direct interaction with the surface of NR/transcription factors. Future research must focus on synthetic ligands acting on SHP as a potential therapeutic target in a series of metabolic abnormalities. Current understanding about the pleiotropic role of SHP is examined in this paper, and principal metabolic aspects connected with SHP function will be also discussed

Ezetimibe: Its Novel Effects on the Prevention and the Treatment of Cholesterol Gallstones and Nonalcoholic Fatty Liver Disease

The cholesterol absorption inhibitor ezetimibe can significantly reduce plasma cholesterol concentrations by inhibiting the Niemann-Pick C1-like 1 protein (NPC1L1), an intestinal sterol influx transporter that can actively facilitate the uptake of cholesterol for intestinal absorption. Unexpectedly, ezetimibe treatment also induces a complete resistance to cholesterol gallstone formation and nonalcoholic fatty liver disease (NAFLD) in addition to preventing hypercholesterolemia in mice on a Western diet. Because chylomicrons are the vehicles with which the enterocytes transport cholesterol and fatty acids into the body, ezetimibe could prevent these two most prevalent hepatobiliary diseases possibly through the regulation of chylomicron-derived cholesterol and fatty acid metabolism in the liver. It is highly likely that there is an intestinal and hepatic cross-talk through the chylomicron pathway. Therefore, understanding the molecular mechanisms whereby cholesterol and fatty acids are absorbed from the intestine could offer an efficacious novel approach to the prevention and the treatment of cholesterol gallstones and NAFLD

The Role Of Diet In The Pathogenesis Of Cholesterol Gallstones

Cholesterol gallstone disease is a major health problem in Westernized countries and depends on a complex interplay between genetic factors, lifestyle and diet, acting on specific pathogenic mechanisms. Overweigh, obesity, dyslipidemia, insulin resistance and altered cholesterol homeostasis have been linked to increased gallstone occurrence, and several studies point to a number of specific nutrients as risk- or protective factors with respect to gallstone formation in humans, motivating a rising interest in the identification of common and modifiable dietetic factors that put the patients at risk of gallstones or that are able to prevent gallstone formation and growth. In particular, dietary models characterized by increased energy intake with highly refined sugars and sweet foods, high fructose intake, low fiber contents, high fat, consumption of fast food and low vitamin C intake increase the risk of gallstone formation. On the other hand, high intake of monounsaturated fats and fiber, olive oil and fish (ω-3 fatty acids) consumption, vegetable protein intake, fruit, coffee, moderate alcohol consumption and vitamin C supplementation exert a protective role. The effect of some confounding factors (e.g., physical activity) cannot be ruled out, but general recommendations about the multiple beneficial effects of diet on cholesterol gallstones must be kept in mind, in particular in groups at high risk of gallstone formation

Charge-order transition in the extended Hubbard model on a two-leg ladder

We investigate the charge-order transition at zero temperature in a two-leg Hubbard ladder with additional nearest-neighbor Coulomb repulsion V using the Density Matrix Renormalization Group technique. We consider electron densities between quarter and half filling. For quarter filling and U=8t, we find evidence for a continuous phase transition between a homogeneous state at small V and a broken-symmetry state with "checkerboard" [wavevector Q=(pi,pi)] charge order at large V. This transition to a checkerboard charge-ordered state remains present at all larger fillings, but becomes discontinuous at sufficiently large filling. We discuss the influence of U/t on the transition and estimate the position of the tricritical points.Comment: 4 pages, 5 figs, minor changes, accepted for publication in PRB R

Update on neutrino mixing in the early Universe

From the current cosmological observations of CMB and nuclear abundances we show, with an analytic procedure, that the total effective number of extra neutrino species $\Delta N_{\nu}^{\rm tot}< 0.3$. We also describe the possible signatures of non standard effects that could be revealed in future CMB observations. This cosmological information is then applied to neutrino mixing models. Taking into account the recent results from the SNO and SuperKamiokande experiments, disfavouring pure active to sterile neutrino oscillations, we show that all 4 neutrino mixing models, both of 2+2 and 3+1 type, lead to a full thermalization of the sterile neutrino flavor. Moreover such a sterile neutrino production excludes the possibility of an electron neutrino asymmetry generation and we conclude that $\Delta N_{\nu}^{\rm tot}\simeq 1$, in disagreement with the cosmological bound. This result is valid under the assumption that the initial neutrino asymmetries are small. We suggest the existence of a second sterile neutrino flavor, with mixing properties such to generate a large electron neutrino asymmetry, as a possible way out.Comment: 29 pages, 3 figures; to appear on Phys.Rev.D; added discussion (at page 19) and references; typos correcte

Partial wave analysis of J/psi to p pbar pi0

Using a sample of 58 million $J/\psi$ events collected with the BESII detector at the BEPC, more than 100,000 $J/\psi \to p\bar p \pi^0$ events are selected, and a detailed partial wave analysis is performed. The branching fraction is determined to be $Br(J/\psi \to p \bar p \pi^0)=(1.33 \pm 0.02 \pm 0.11) \times 10^{-3}$. A long-sought `missing' $N^*$, first observed in $J/\psi \to p \bar n \pi^-$, is observed in this decay too, with mass and width of $2040_{-4}^{+3}\pm 25$ MeV/c$^2$ and $230_{-8}^{+8}\pm 52$ MeV/c$^2$, respectively. Its spin-parity favors ${3/2}^+$. The masses, widths, and spin-parities of other $N^*$ states are obtained as well.Comment: Add one author nam

Tricritical Behavior in the Extended Hubbard Chains

Phase diagrams of the one-dimensional extended Hubbard model (including nearest-neighbor interaction $V$) at half- and quarter-filling are studied by observing level crossings of excitation spectra using the exact diagonalization. This method is based on the Tomonaga-Luttinger liquid theory including logarithmic corrections which stem from the renormalization of the Umklapp- and the backward-scattering effects. Using this approach, the phase boundaries are determined with high accuracy, and then the structure of the phase diagram is clarified. At half-filling, the phase diagram consists of two Berezinskii-Kosterlitz-Thouless (BKT) transition lines and one Gaussian transition line in the charge sector, and one spin-gap transition line. This structure reflects the U(1) $\otimes$ SU(2) symmetry of the electron system. Near the $U=2V$ line, the Gaussian and the spin-gap transitions take place independently from the weak- to the intermediate-coupling region, but these two transition lines are coupled in the strong-coupling region. This result demonstrates existence of a tricritical point and a bond-charge-density-wave (BCDW) phase between charge- and spin-density-wave (CDW, SDW) phases. To clarify this mechanism of the transition, we also investigate effect of a correlated hopping term which plays a role to enlarge BCDW and bond-spin-density-wave (BSDW) phases. At quarter-filling, a similar crossover phenomenon also takes place in the large-$V$ region involving spin-gap and BKT-type metal-insulator transitions.Comment: 18 pages(REVTeX), 17 figures(EPS(color)), 3 tables, Detailed paper of JPSJ 68 (1999) 3123 (cond-mat/9903227), see also cond-mat/000341

CUORE-0 results and prospects for the CUORE experiment

With 741 kg of TeO2 crystals and an excellent energy resolution of 5 keV (0.2%) at the region of interest, the CUORE (Cryogenic Underground Observatory for Rare Events) experiment aims at searching for neutrinoless double beta decay of 130Te with unprecedented sensitivity. Expected to start data taking in 2015, CUORE is currently in an advanced construction phase at LNGS. CUORE projected neutrinoless double beta decay half-life sensitivity is 1.6E26 y at 1 sigma (9.5E25 y at the 90% confidence level), in five years of live time, corresponding to an upper limit on the effective Majorana mass in the range 40-100 meV (50-130 meV). Further background rejection with auxiliary bolometric detectors could improve CUORE sensitivity and competitiveness of bolometric detectors towards a full analysis of the inverted neutrino mass hierarchy. CUORE-0 was built to test and demonstrate the performance of the upcoming CUORE experiment. It consists of a single CUORE tower (52 TeO2 bolometers of 750 g each, arranged in a 13 floor structure) constructed strictly following CUORE recipes both for materials and assembly procedures. An experiment its own, CUORE-0 is expected to reach a sensitivity to the neutrinoless double beta decay half-life of 130Te around 3E24 y in one year of live time. We present an update of the data, corresponding to an exposure of 18.1 kg y. An analysis of the background indicates that the CUORE performance goal is satisfied while the sensitivity goal is within reach.Comment: 10 pages, 3 figures, to appear in the proceedings of NEUTRINO 2014, 26th International Conference on Neutrino Physics and Astrophysics, 2-7 June 2014, held at Boston, Massachusetts, US

Status of the CUORE and results from the CUORE-0 neutrinoless double beta decay experiments

CUORE is a 741 kg array of TeO2 bolometers for the search of neutrinoless double beta decay of 130Te. The detector is being constructed at the Laboratori Nazionali del Gran Sasso, Italy, where it will start taking data in 2015. If the target background of 0.01 counts/keV/kg/y will be reached, in five years of data taking CUORE will have a 1 sigma half life sensitivity of 10E26 y. CUORE-0 is a smaller experiment constructed to test and demonstrate the performances expected for CUORE. The detector is a single tower of 52 CUORE-like bolometers that started taking data in spring 2013. The status and perspectives of CUORE will be discussed, and the first CUORE-0 data will be presented.Comment: 7 pages, 4 figures, to be published in the proceedings of ICHEP 2014, 37th International Conference on High Energy Physics, Valencia (Spain) 2-9 July 201

Search for Neutrinoless Double-Beta Decay of 130^{130}Te with CUORE-0

We report the results of a search for neutrinoless double-beta decay in a 9.8~kg$\cdot$yr exposure of $^{130}$Te using a bolometric detector array, CUORE-0. The characteristic detector energy resolution and background level in the region of interest are $5.1\pm 0.3{\rm~keV}$ FWHM and $0.058 \pm 0.004\,(\mathrm{stat.})\pm 0.002\,(\mathrm{syst.})$~counts/(keV$\cdot$kg$\cdot$yr), respectively. The median 90%~C.L. lower-limit sensitivity of the experiment is $2.9\times 10^{24}~{\rm yr}$ and surpasses the sensitivity of previous searches. We find no evidence for neutrinoless double-beta decay of $^{130}$Te and place a Bayesian lower bound on the decay half-life, $T^{0\nu}_{1/2}>$~$2.7\times 10^{24}~{\rm yr}$ at 90%~C.L. Combining CUORE-0 data with the 19.75~kg$\cdot$yr exposure of $^{130}$Te from the Cuoricino experiment we obtain $T^{0\nu}_{1/2} > 4.0\times 10^{24}~\mathrm{yr}$ at 90%~C.L.~(Bayesian), the most stringent limit to date on this half-life. Using a range of nuclear matrix element estimates we interpret this as a limit on the effective Majorana neutrino mass, $m_{\beta\beta}< 270$ -- $760~\mathrm{meV}$.Comment: 6 pages, 5 figures, updated version as published in PR