LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival.

Epithelial dysfunction and crypt destruction are defining features of inflammatory bowel disease (IBD). However, current IBD therapies targeting epithelial dysfunction are lacking. The nuclear receptor LRH-1 (NR5A2) is expressed in intestinal epithelium and thought to contribute to epithelial renewal. Here we show that LRH-1 maintains intestinal epithelial health and protects against inflammatory damage. Knocking out LRH-1 in murine intestinal organoids reduces Notch signaling, increases crypt cell death, distorts the cellular composition of the epithelium, and weakens the epithelial barrier. Human LRH-1 (hLRH-1) rescues epithelial integrity and when overexpressed, mitigates inflammatory damage in murine and human intestinal organoids, including those derived from IBD patients. Finally, hLRH-1 greatly reduces disease severity in T-cell-mediated murine colitis. Together with the failure of a ligand-incompetent hLRH-1 mutant to protect against TNFα-damage, these findings provide compelling evidence that hLRH-1 mediates epithelial homeostasis and is an attractive target for intestinal disease

LRH-1 drives colon cancer cell growth by repressing the expression of the <i>CDKN1A</i> gene in a p53-dependent manner

Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor that has been implicated in the progression of breast, pancreatic and colorectal cancer (CRC). To determine mechanisms underlying growth promotion by LRH-1 in CRC, we undertook global expression profiling following siRNA-mediated LRH-1 knockdown in HCT116 cells, which require LRH-1 for growth and in HT29 cells, in which LRH-1 does not regulate growth. Interestingly, expression of the cell cycle inhibitor p21 (CDKN1A) was regulated by LRH-1 in HCT116 cells. p21 regulation was not observed in HT29 cells, where p53 is mutated. p53 dependence for the regulation of p21 by LRH-1 was confirmed by p53 knockdown with siRNA, while LRH-1-regulation of p21 was not evident in HCT116 cells where p53 had been deleted. We demonstrate that LRH-1-mediated p21 regulation in HCT116 cells does not involve altered p53 protein or phosphorylation, and we show that LRH-1 inhibits p53 recruitment to the p21 promoter, likely through a mechanism involving chromatin remodelling. Our study suggests an important role for LRH-1 in the growth of CRC cells that retain wild-type p53

Linguistic Structures and Economic Outcomes

Linguistic structures have recently started to attract attention from economists as determinants of economic phenomena. This paper provides the first comprehensive review of this nascent literature and its achievements so far. First, we explore the complex connections between language, culture, thought and behaviour. Then, we summarize the empirical evidence on the relationship between linguistic structures and economic and social outcomes. We follow up with a discussion of data, empirical design and identification. The paper concludes by discussing implications for future research and policy

Persistent currents with long-range hopping in 1D single-isolated-diffusive rings

We show from exact calculations that a simple tight-binding Hamiltonian with diagonal disorder and long-range hopping integrals, falling off as a power $\mu$ of the inter-site separation, correctly describes the experimentally observed amplitude (close to the value of an ordered ring) and flux-periodicity ($hc/e$) of persistent currents in single-isolated-diffusive normal metal rings of mesoscopic size. Long-range hopping integrals tend to delocalize the electrons even in the presence of disorder resulting orders of magnitude enhancement of persistent current relative to earliar predictions.Comment: 4 pages, 3 figure

Holographic entanglement thermodynamics for higher dimensional charged black hole

In this paper, we have investigated the entanglement thermodynamics for $d$-dimensional charged $AdS$ black hole by studying the holographic entanglement entropy in different cases. We have first computed the holographic entanglement entropy in extremal and non-extremal cases in two different regimes, namely, the low temperature and high temperature limits. We then obtain the first law of entanglement thermodynamics for boundary field theory in the low temperature regime in $d$-dimensions.Comment: 28 pages Late

An Experimental Realization of Quantum-vacuum Geometric Phases by Using the Gyrotropic-medium Optical Fiber

The connection between the quantum-vacuum geometric phases (which originates from the vacuum zero-point electromagnetic fluctuation) and the non-normal product procedure is considered in the present Letter. In order to investigate this physically interesting geometric phases at quantum-vacuum level, we suggest an experimentally feasible scheme to test it by means of a noncoplanarly curved fiber made of gyrotropic media. A remarkable feature of the present experimental realization is that one can easily extract the nonvanishing and nontrivial quantum-vacuum geometric phases of left- and/or right- handed circularly polarized light from the vanishing and trivial total quantum-vacuum geometric phases.Comment: 4 pages, Late