Analysis of Thisbe and Pyramus functional domains reveals evidence for cleavage of Drosophila FGFs

Background: As important regulators of developmental and adult processes in metazoans, Fibroblast Growth Factor (FGF) proteins are potent signaling molecules whose activities must be tightly regulated. FGFs are known to play diverse roles in many processes, including mesoderm induction, branching morphogenesis, organ formation, wound healing and malignant transformation; yet much more remains to be learned about the mechanisms of regulation used to control FGF activity. Results: In this work, we conducted an analysis of the functional domains of two Drosophila proteins, Thisbe (Ths) and Pyramus (Pyr), which share homology with the FGF8 subfamily of ligands in vertebrates. Ths and Pyr proteins are secreted from Drosophila Schneider cells (S2) as smaller N-terminal fragments presumably as a result of intracellular proteolytic cleavage. Cleaved forms of Ths and Pyr can be detected in embryonic extracts as well. The FGF-domain is contained within the secreted ligand portion, and this domain alone is capable of functioning in the embryo when ectopically expressed. Through targeted ectopic expression experiments in which we assay the ability of full-length, truncated, and chimeric proteins to support cell differentiation, we find evidence that (1) the C-terminal domain of Pyr is retained inside the cell and does not seem to be required for receptor activation and (2) the C-terminal domain of Ths is secreted and, while also not required for receptor activation, this domain does plays a role in limiting the activity of Ths when present. Conclusions: We propose that differential protein processing may account for the previously observed inequalities in signaling capabilities between Ths and Pyr. While the regulatory mechanisms are likely complex, studies such as ours conducted in a tractable model system may be able to provide insights into how ligand processing regulates growth factor activity

Higgsogenesis

In addition to explaining the masses of elementary particles, the Higgs boson may have far-reaching implications for the generation of the matter content in the Universe. For instance, the Higgs plays a key role in two main theories of baryogenesis, namely electroweak baryogenesis and leptogenesis. In this letter, we propose a new cosmological scenario where the Higgs chemical potential mediates asymmetries between visible and dark matter sectors, either generating a baryon asymmetry from a dark matter asymmetry or vice-versa. We illustrate this mechanism with a simple model with two new fermions coupled to the Higgs and discuss associated signatures.Comment: 5 pages, 2 figures; v2: Intro and conclusion improved, clarifications added, results unchanged. Compared to the PRL version, this arxiv version contains two extra plots, one additional table and a slightly longer conclusio

Direct Detection Portals for Self-interacting Dark Matter

Dark matter self-interactions can affect the small scale structure of the Universe, reducing the central densities of dwarfs and low surface brightness galaxies in accord with observations. From a particle physics point of view, this points toward the existence of a 1-100 MeV particle in the dark sector that mediates self-interactions. Since mediator particles will generically couple to the Standard Model, direct detection experiments provide sensitive probes of self-interacting dark matter. We consider three minimal mechanisms for coupling the dark and visible sectors: photon kinetic mixing, Z boson mass mixing, and the Higgs portal. Self-interacting dark matter motivates a new benchmark paradigm for direct detection via momentum-dependent interactions, and ton-scale experiments will cover astrophysically motivated parameter regimes that are unconstrained by current limits. Direct detection is a complementary avenue to constrain velocity-dependent self-interactions that evade astrophysical bounds from larger scales, such as those from the Bullet Cluster.Comment: 18 pages, 7 figure

Self-interacting Dark Matter Benchmarks

Dark matter self-interactions have important implications for the distributions of dark matter in the Universe, from dwarf galaxies to galaxy clusters. We present benchmark models that illustrate characteristic features of dark matter that is self-interacting through a new light mediator. These models have self-interactions large enough to change dark matter densities in the centers of galaxies in accord with observations, while remaining compatible with large-scale structure data and all astrophysical observations such as halo shapes and the Bullet Cluster. These observations favor a mediator mass in the 10 - 100 MeV range and large regions of this parameter space are accessible to direct detection experiments like LUX, SuperCDMS, and XENON1T.Comment: 4 pages, white paper for Snowmass 2013; v2: finalized version, figures correcte