Ixazomib enhances parathyroid hormone-induced β-catenin/T-cell factor signaling by dissociating β-catenin from the parathyroid hormone receptor.

The anabolic action of PTH in bone is mostly mediated by cAMP/PKA and Wnt-independent activation of β-catenin/T-cell factor (TCF) signaling. β-Catenin switches the PTH receptor (PTHR) signaling from cAMP/PKA to PLC/PKC activation by binding to the PTHR. Ixazomib (Izb) was recently approved as the first orally administered proteasome inhibitor for the treatment of multiple myeloma; it acts in part by inhibition of pathological bone destruction. Proteasome inhibitors were reported to stabilize β-catenin by the ubiquitin-proteasome pathway. However, how Izb affects PTHR activation to regulate β-catenin/TCF signaling is poorly understood. In the present study, using CRISPR/Cas9 genome-editing technology, we show that Izb reverses β-catenin-mediated PTHR signaling switch and enhances PTH-induced cAMP generation and cAMP response element-luciferase activity in osteoblasts. Izb increases active forms of β-catenin and promotes β-catenin translocation, thereby dissociating β-catenin from the PTHR at the plasma membrane. Furthermore, Izb facilitates PTH-stimulated GSK3β phosphorylation and β-catenin phosphorylation. Thus Izb enhances PTH stimulation of β-catenin/TCF signaling via cAMP-dependent activation, and this effect is due to its separating β-catenin from the PTHR. These findings provide evidence that Izb may be used to improve the therapeutic efficacy of PTH for the treatment of osteoporosis and other resorptive bone diseases

Universal Boundary Entropies in Conformal Field Theory: A Quantum Monte Carlo Study

Recently, entropy corrections on nonorientable manifolds such as the Klein bottle are proposed as a universal characterization of critical systems with an emergent conformal field theory (CFT). We show that entropy correction on the Klein bottle can be interpreted as a boundary effect via transforming the Klein bottle into an orientable manifold with nonlocal boundary interactions. The interpretation reveals the conceptual connection of the Klein bottle entropy with the celebrated Affleck-Ludwig entropy in boundary CFT. We propose a generic scheme to extract these universal boundary entropies from quantum Monte Carlo calculation of partition function ratios in lattice models. Our numerical results on the Affleck-Ludwig entropy and Klein bottle entropy for the $q$-state quantum Potts chains with $q=2,3$ show excellent agreement with the CFT predictions. For the quantum Potts chain with $q=4$, the Klein bottle entropy slightly deviates from the CFT prediction, which is possibly due to marginally irrelevant terms in the low-energy effective theory.Comment: 10 pages, 4 figures. Published versio

A novel common triplet profile for GC-rich prokaryotic genomes

AbstractIt has been reported that there is a majority triplet profile among genomes, which was considered as a reflection of general mechanisms of genome evolution (Albrecht-Buehler, 2007). However, there are actually, according to our further analysis and at least among prokaryotic genomes, two common triplet profiles: one is from low-GC content genomes; the other is from high-GC content genomes. Both common profiles would be direct reflections of GC content variations and strand symmetry of genomic sequences

muon g−2g-2 anomaly and μ\mu-τ\tau-philic Higgs doublet with a light CP-even component

We examine the possibilities of accommodating the muon $g-2$ anomaly reported by Fermilab in the 2HDM with a discrete $Z_4$ symmetry in which an inert Higgs doublet field ($H,~A,~H^\pm$) has the lepton flavor violation $\mu$-$\tau$ interactions. We study the case of light $H$ (5 GeV $<m_H<$ 115 GeV) and assume the Yukawa matrices to be real and symmetrical. Considering relevant theoretical and experimental constraints, especially for the multi-lepton searches at the LHC, we find the muon $g-2$ anomaly can be explained within $2\sigma$ range in the region of 5 GeV $<m_H<20$ GeV, 130 GeV $< m_A~(m_{H^\pm})<$ 610 GeV, and 0.005 $<\rho<$ 0.014. Meanwhile, the $\chi^2_\tau$ fitting the data of lepton flavour universality in the $\tau$ decays approaches to the SM prediction.Comment: 12 pages, 4 figures. arXiv admin note: text overlap with arXiv:2104.03227. text overlap with arXiv:1908.0375