Abstract: We explore a dark matter model extending the standard model particle content by one fermionic SU(2)L triplet and two fermionic SU(2)L quadruplets, leading to a minimal realistic UV-complete model of electroweakly interacting dark matter which interacts with the Higgs doublet at tree level via two kinds of Yukawa couplings. After electroweak symmetry-breaking, the physical spectrum of the dark sector consists of three Majorana fermions, three singly charged fermions, and one doubly charged fermion, with the lightest neutral fermion χ10 serving as a dark matter candidate. A typical spectrum exhibits a large degree of degeneracy in mass between the neutral and charged fermions, and we examine the one-loop corrections to the mass differences to ensure that the lightest particle is neutral. We identify regions of parameter space for which the dark matter abundance is saturated for a standard cosmology, including coannihilation channels, and find that this is typically achieved for (Formula presented.) TeV. Constraints from precision electroweak measurements, searches for dark matter scattering with nuclei, and dark matter annihilation are important, but leave open a viable range for a thermal relic.

Cardiac regeneration involves the generation of new cardiomyocytes from cycling cardiomyocytes. Understanding cell-cycle activity of pre-existing cardiomyocytes provides valuable information to heart repair and regeneration. However, the anatomical locations and in situ dynamics of cycling cardiomyocytes remain unclear. Here we develop a genetic approach for a temporally seamless recording of cardiomyocyte-specific cell-cycle activity in vivo. We find that the majority of cycling cardiomyocytes are positioned in the subendocardial muscle of the left ventricle, especially in the papillary muscles. Clonal analysis revealed that a subset of cycling cardiomyocytes have undergone cell division. Myocardial infarction and cardiac pressure overload induce regional patterns of cycling cardiomyocytes. Mechanistically, cardiomyocyte cell cycle activity requires the Hippo pathway effector YAP. These genetic fate-mapping studies advance our basic understanding of cardiomyocyte cell cycle activity and generation in cardiac homeostasis, repair, and regeneration.

Coxsackievirus A6 (CVA6) has recently emerged as a major cause of hand, foot and mouth disease in children worldwide but no vaccine is available against CVA6 infections. Here, we demonstrate the isolation of two forms of stable CVA6 particles-procapsid and A-particle-with excellent biochemical stability and natural antigenicity to serve as vaccine candidates. Despite the presence (in A-particle) or absence (in procapsid) of capsid-RNA interactions, the two CVA6 particles have essentially identical atomic capsid structures resembling the uncoating intermediates of other enteroviruses. Our near-atomic resolution structure of CVA6 A-particle complexed with a neutralizing antibody maps an immune-dominant neutralizing epitope to the surface loops of VP1. The structure-guided cell-based inhibition studies further demonstrate that these loops could serve as excellent targets for designing anti-CVA6 vaccines.Coxsackievirus A6 (CVA6) causes hand, foot and mouth disease in children. Here the authors present the CVA6 procapsid and A-particle cryo-EM structures and identify an immune-dominant neutralizing epitope, which can be exploited for vaccine development.