Lower Limits on μ→eγ\mu \to e \gamma from new Measurements on Ue3U_{e3}

New data on the lepton mixing angle $\theta_{13}$ imply that the $e\mu$ element of the matrix $m_\nu m_\nu^\dagger$, where $m_\nu$ is the neutrino Majorana mass matrix, cannot vanish. This implies a lower limit on lepton flavor violating processes in the $e\mu$ sector in a variety of frameworks, including Higgs triplet models or the concept of minimal flavor violation in the lepton sector. We illustrate this for the branching ratio of $\mu \to e \gamma$ in the type II seesaw mechanism, in which a Higgs triplet is responsible for neutrino mass and also mediates lepton flavor violation. We also discuss processes like $\mu\to e\bar{e}e$ and $\mu\to e$ conversion in nuclei. Since these processes have sensitivity on the individual entries of $m_\nu$, their rates can still be vanishingly small.Comment: 9 pages, 4 .eps figures; Discussions, 2 new figures and references added, Abstract and text modified, matches with the published version in Physical Review

Re-opening dark matter windows compatible with a diphoton excess

We investigate a simple setup in which an excess in the di-photon invariant mass distribution around $750$ GeV, as seen by the ATLAS and CMS collaborations, is originated through a pair of collimated photon pairs. In this framework a scalar state $s$ decays into two light pseudo-Goldstone bosons $a$, each of which subsequently decays into a pair of collimated photons which are misidentified as a single photon. In a minimal context of spontaneous symmetry breaking, we show that coupling a complex scalar field $\Phi=(s+ia)/\sqrt{2}$ to a fermionic dark matter candidate $\chi$, also responsible for generating its mass, allows for the correct relic density in a large region of the parameter space, while not being excluded by the direct or indirect detection experiments. Moreover, the correct relic abundance can naturally co-exist with a relatively large width for the resonant field $s$.Comment: 29 pages, 11 figures, new references adde

AP-1 binding to sorting signals and release from clathrin-coated vesicles is regulated by phosphorylation

The adaptor protein complex-1 (AP-1) sorts and packages membrane proteins into clathrin-coated vesicles (CCVs) at the TGN and endosomes. Here we show that this process is highly regulated by phosphorylation of AP-1 subunits. Cell fractionation studies revealed that membrane-associated AP-1 differs from cytosolic AP-1 in the phosphorylation status of its β1 and μ1 subunits. AP-1 recruitment onto the membrane is associated with protein phosphatase 2A (PP2A)–mediated dephosphorylation of its β1 subunit, which enables clathrin assembly. This Golgi-associated isoform of PP2A exhibits specificity for phosphorylated β1 compared with phosphorylated μ1. Once on the membrane, the μ1 subunit undergoes phosphorylation, which results in a conformation change, as revealed by increased sensitivity to trypsin. This conformational change is associated with increased binding to sorting signals on the cytoplasmic tails of cargo molecules. Dephosphorylation of μ1 (and μ2) by another PP2A-like phosphatase reversed the effect and resulted in adaptor release from CCVs. Immunodepletion and okadaic acid inhibition studies demonstrate that PP2A is the cytosolic cofactor for Hsc-70–mediated adaptor uncoating. A model is proposed where cyclical phosphorylation/dephosphorylation of the subunits of AP-1 regulate its function from membrane recruitment until its release into cytosol

Macrophage states: there's a method in the madness

Single-cell approaches have shone a spotlight on discrete context-specific tissue macrophage states, deconstructed to their most minute details. Machine-learning (ML) approaches have recently challenged that dogma by revealing a context-agnostic continuum of states shared across tissues. Both approaches agree that 'brake' and 'accelerator' macrophage subpopulations must be balanced to achieve homeostasis. Both approaches also highlight the importance of ensemble fluidity as subpopulations switch between wide ranges of accelerator and brake phenotypes to mount the most optimal wholistic response to any threat. A full comprehension of the rules that govern these brake and accelerator states is a promising avenue because it can help formulate precise macrophage re-education therapeutic strategies that might selectively boost or suppress disease-associated states and phenotypes across various tissues

A predictive computational model reveals that GIV/girdin serves as a tunable valve for EGFR-stimulated cyclic AMP signals.

Cellular levels of the versatile second messenger cyclic (c)AMP are regulated by the antagonistic actions of the canonical G protein → adenylyl cyclase pathway that is initiated by G-protein-coupled receptors (GPCRs) and attenuated by phosphodiesterases (PDEs). Dysregulated cAMP signaling drives many diseases; for example, its low levels facilitate numerous sinister properties of cancer cells. Recently, an alternative paradigm for cAMP signaling has emerged in which growth factor-receptor tyrosine kinases (RTKs; e.g., EGFR) access and modulate G proteins via a cytosolic guanine-nucleotide exchange modulator (GEM), GIV/girdin; dysregulation of this pathway is frequently encountered in cancers. In this study, we present a network-based compartmental model for the paradigm of GEM-facilitated cross-talk between RTKs and G proteins and how that impacts cellular cAMP. Our model predicts that cross-talk between GIV, Gαs, and Gαi proteins dampens ligand-stimulated cAMP dynamics. This prediction was experimentally verified by measuring cAMP levels in cells under different conditions. We further predict that the direct proportionality of cAMP concentration as a function of receptor number and the inverse proportionality of cAMP concentration as a function of PDE concentration are both altered by GIV levels. Taking these results together, our model reveals that GIV acts as a tunable control valve that regulates cAMP flux after growth factor stimulation. For a given stimulus, when GIV levels are high, cAMP levels are low, and vice versa. In doing so, GIV modulates cAMP via mechanisms distinct from the two most often targeted classes of cAMP modulators, GPCRs and PDEs