Advances in tooth agenesis and tooth regeneration

The lack of treatment options for congenital (0.1%) and partial (10%) tooth anomalies highlights the need to develop innovative strategies. Over two decades of dedicated research have led to breakthroughs in the treatment of congenital and acquired tooth loss. We revealed that by inactivating USAG-1, congenital tooth agenesis can be successfully ameliorated during early tooth development and that the inactivation promotes late-stage tooth morphogenesis in double knockout mice. Furthermore, Anti- USAG-1 antibody treatment in mice is effective in tooth regeneration and can be a breakthrough in treating tooth anomalies in humans. With approximately 0.1% of the population suffering from congenital tooth agenesis and 10% of children worldwide suffering from partial tooth loss, early diagnosis will improve outcomes and the quality of life of patients. Understanding the role of pathogenic USAG-1 variants, their interacting gene partners, and their protein functions will help develop critical biomarkers. Advances in next-generation sequencing, mass spectrometry, and imaging technologies will assist in developing companion and predictive biomarkers to help identify patients who will benefit from tooth regeneration

Anti–USAG-1 therapy for tooth regeneration through enhanced BMP signaling

先天性無歯症に対する分子標的薬の開発 --USAG-1を標的分子とした歯再生治療--. 京都大学プレスリリース. 2021-02-15.Uterine sensitization–associated gene-1 (USAG-1) deficiency leads to enhanced bone morphogenetic protein (BMP) signaling, leading to supernumerary teeth formation. Furthermore, antibodies interfering with binding of USAG-1 to BMP, but not lipoprotein receptor–related protein 5/6 (LRP5/6), accelerate tooth development. Since USAG-1 inhibits Wnt and BMP signals, the essential factors for tooth development, via direct binding to BMP and Wnt coreceptor LRP5/6, we hypothesized that USAG-1 plays key regulatory roles in suppressing tooth development. However, the involvement of USAG-1 in various types of congenital tooth agenesis remains unknown. Here, we show that blocking USAG-1 function through USAG-1 knockout or anti–USAG-1 antibody administration relieves congenital tooth agenesis caused by various genetic abnormalities in mice. Our results demonstrate that USAG-1 controls the number of teeth by inhibiting development of potential tooth germs in wild-type or mutant mice missing teeth. Anti–USAG-1 antibody administration is, therefore, a promising approach for tooth regeneration therapy

Spin-wave spectrum in La2CuO4 -- double occupancy and competing interaction effects

The recently observed spin-wave energy dispersion along the AF zone boundary in La2CuO4 is discussed in terms of double occupancy and competing interaction effects in the $t-t'$ Hubbard model on a square lattice.Comment: 4 pages, 2 figure

Spin Excitations in La2CuO4: Consistent Description by Inclusion of Ring-Exchange

We consider the square lattice Heisenberg antiferromagnet with plaquette ring exchange and a finite interlayer coupling leading to a consistent description of the spin-wave excitation spectrum in La2CuO4. The values of the in-plane exchange parameters, including ring-exchange J_{\Box}, are obtained consistently by an accurate fit to the experimentally observed in-plane spin-wave dispersion, while the out-of-plane exchange interaction is found from the temperature dependence of the sublattice magnetization at low temperatures. The fitted exchange interactions J=151.9 meV and J_{\Box}=0.24 J give values for the spin stiffness and the Neel temperature in excellent agreement with the experimental data.Comment: 4 pages, 1 figure, RevTe

High-energy magnon dispersion in the half-filled Hubbard model: A comparison with La2_2CuO4_4

We use quantum Monte Carlo methods and single-mode approximation to study the magnon dispersion in the 2D half-filled Hubbard and phonon-coupled Heisenberg models. We find that in the Hubbard model with $U/t< 8$, high-energy magnon dispersion is similar to those observed in inelastic neutron scattering experiments in ${La}_2{CuO}_4$. On the other hand, our studies of a 2D Heisenberg model coupled to dynamic optical bond phonons, fails to reproduce the experimental dispersion. These results can be interpreted as evidence for intermediate $U/t$ and charge fluctuations in the cuprate materials

How to detect fluctuating order in the high-temperature superconductors

We discuss fluctuating order in a quantum disordered phase proximate to a quantum critical point, with particular emphasis on fluctuating stripe order. Optimal strategies for extracting information concerning such local order from experiments are derived with emphasis on neutron scattering and scanning tunneling microscopy. These ideas are tested by application to two model systems - the exactly solvable one dimensional electron gas with an impurity, and a weakly-interacting 2D electron gas. We extensively review experiments on the cuprate high-temperature superconductors which can be analyzed using these strategies. We adduce evidence that stripe correlations are widespread in the cuprates. Finally, we compare and contrast the advantages of two limiting perspectives on the high-temperature superconductor: weak coupling, in which correlation effects are treated as a perturbation on an underlying metallic (although renormalized) Fermi liquid state, and strong coupling, in which the magnetism is associated with well defined localized spins, and stripes are viewed as a form of micro-phase separation. We present quantitative indicators that the latter view better accounts for the observed stripe phenomena in the cuprates.Comment: 43 pages, 11 figures, submitted to RMP; extensively revised and greatly improved text; one new figure, one new section, two new appendices and more reference

Non-strange Dibaryon Resonances Observed in the γd→π0π0d\gamma d\to \pi^0\pi^0 d Reaction

Coherent double neutral-pion photoproduction on the deuteron, $\gamma{d}${$\to$}$\pi^0\pi^0{d}$, has been experimentally studied at incident photon energies ranging from 0.75 to 1.15 GeV. The total cross section as a function of the $\gamma{d}$ center-of-mass energy shows resonance-like behavior, which peaks at approximately 2.47 and 2.63 GeV. The measured angular distribution of deuteron emission is rather flat, which cannot be reproduced by the kinematics of quasi-free $\pi^0\pi^0$ production with deuteron coalescence. In $\pi^0d$ invariant-mass distributions, a clear peak is observed at $2.14{\pm}0.01$ GeV$/c^2$ with a width of $0.09{\pm}0.01$ GeV$/c^2$. The spin-parity of this state is restricted to $1^+$, $2^+$ or $3^-$ from the angular distributions of the two $\pi^0$s. The present work shows strong evidence for the existence of an isovector dibaryon resonance with a mass of 2.14 GeV$/c^2$. The $2^+$ assignment is consistent with the theoretically predicted ${\cal{D}}_{12}$ state, and also with the energy dependence of the $\pi{d}$ partial-wave amplitude $^3\!P_2$ for the $\pi^{\pm}d${$\to$}$\pi^{\pm}d$ and $\pi^+d${$\to$}${pp}$ reactions.Comment: 12 pages, 6 figure