Check of a new non-perturbative mechanism for elementary fermion mass generation

We consider a field theoretical model where a SU(2) fermion doublet, subjected to non-Abelian gauge interactions, is also coupled to a complex scalar field doublet via a Yukawa and an irrelevant Wilson-like term. Despite the presence of these two chiral breaking operators in the Lagrangian, an exact symmetry acting on fermions and scalars prevents perturbative mass corrections. In the phase where fermions are massless (Wigner phase) the Yukawa coupling can be tuned to a critical value at which chiral transformations acting on fermions only become a symmetry of the theory (up to cutoff effects). In the Nambu-Goldstone phase of the critical theory a fermion mass term of dynamical origin is expected to arise in the Ward identities of the purely fermionic chiral transformations. Such a non-perturbative mechanism of dynamical mass generation can provide a "natural" (\`a la 't Hooft) alternative to the Higgs mechanism adopted in the Standard Model. Here we lay down the theoretical framework necessary to demonstrate the existence of this mechanism by means of lattice simulations.Comment: 7 pages, 3 figureres, Proceedings for The 34th International Symposium on Lattice Field Theor

Clinical, genetic, epidemiologic, evolutionary, and functional delineation of TSPEAR-related autosomal recessive ectodermal dysplasia 14

TSPEAR variants cause autosomal recessive ectodermal dysplasia (ARED) 14. The function of TSPEAR is unknown. The clinical features, the mutation spectrum, and the underlying mechanisms of ARED14 are poorly understood. Combining data from new and previously published individuals established that ARED14 is primarily characterized by dental anomalies such as conical tooth cusps and hypodontia, like those seen in individuals with WNT10A-related odontoonychodermal dysplasia. AlphaFold-predicted structure-based analysis showed that most of the pathogenic TSPEAR missense variants likely destabilize the b-propeller of the protein. Analysis of 100000 Genomes Project (100KGP) data revealed multiple founder TSPEAR variants across different populations. Mutational and recombination clock analyses demonstrated that non-Finnish European founder variants likely originated around the end of the last ice age, a period of major climatic transition. Analysis of gnomAD data showed that the non-Finnish European population TSPEAR gene-carrier rate is 1/140, making it one of the commonest AREDs. Phylogenetic and AlphaFold structural analyses showed that TSPEAR is an ortholog of drosophila Closca, an extracellular matrix-dependent signaling regulator. We, therefore, hypothesized that TSPEAR could have a role in enamel knot, a structure that coordinates patterning of developing tooth cusps. Analysis of mouse single-cell RNA sequencing (scRNA-seq) data revealed highly restricted expression of Tspear in clusters representing enamel knots. A tspeara-/-;tspearb-/- doubleknockout zebrafish model recapitulated the clinical features of ARED14 and fin regeneration abnormalities of wnt10a knockout fish, thus suggesting interaction between tspear and wnt10a. In summary, we provide insights into the role of TSPEAR in ectodermal development and the evolutionary history, epidemiology, mechanisms, and consequences of its loss of function variants