Background: NARC 1/PCSK9 encodes a novel serine proteinase known to play a role in cholesterol homeostasis. NARC 1 mRNA expression in cerebellar granule neurons (CGNs) was discovered to be induced following an apoptotic injury. Coregulation of known apoptotic mediators (caspase-3 and death receptor 6) raises the possibility that NARC 1 might be involved in the propagation of apoptotic signaling in neurons. Methods: CGNs were transfected with EGFP-fusion constructs of wild-type and mutant NARC 1, and a laser scanning cytometry-based method of scoring cell death in transfectants was applied. Use of the poly-caspase inhibitor BAF allowed assessment of the caspase-dependence of the NARC 1 proapoptotic effect. Results: Wild-type NARC 1 was found to have substantial proapoptotic effects that were only partially reversible by BAF. Mutation of the active site serine or deletion of the catalytic domain resulted in a reduced level of cell death, consistent with loss of the BAF-sensitive component of cell death. NH 2 -terminal deletion constructs of NARC 1

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The type II seesaw model is a well-motivated new physics scenario to address the origin of the neutrino mass issue. We show that this model can easily accommodate an absolutely stable vacuum until the Planck scale, however with strong limit on the exotic scalar masses and the corresponding mixing angle. We examine the model prediction at the current and future high luminosity run of the Large Hadron Collider (LHC) for the scalar masses and mixing angles fixed at such high-scale valid region. Specifically, we device the associated and pair production of the charged scalars as a new probe of the model at the LHC. We show that for a particular signal process the model can be tested with 5σ signal significance even at the present run of the LHC.

In the context of a left-right symmetric model, we introduce one full generation of vectorlike lepton doublets (both left and right-handed) together with their mirror doublets. We show that the lightest vectorlike neutrino in the model is right-handed, and can serve as the dark matter candidate. We find that the relic density as well as the direct and indirect DM detection bounds are satisfied for a large range of the parameter space of the model. In accordance with the parameter space, we then explore the possibility of detecting signals of the model at both the LHC and the ILC, in the pair production of the associated vectorlike charged leptons which decay into final states including dark matter. A comprehensive analysis of signal and backgrounds shows that the signals at the ILC, especially with polarized beams are likely to be visible for light vectorlike leptons, even with low luminosity, rendering our model highly predictable and experimentally testable.

We study the $$S_3$$ S 3 -symmetric two Higgs doublet model by adding two generations of vector like leptons (VLL) which are odd under a discrete $$Z_2$$ Z 2 -symmetry. The lightest neutral component of the VLL acts as a dark matter (DM) whereas the full VLL set belongs to a dark sector with no mixings allowed with the standard model fermions. We analyse the model in light of dark matter and collider searches. We show that the DM is compatible with the current relic density data as well as satisfying all direct and indirect dark matter search constraints. We choose some representative points in the model parameter space allowed by all aforementioned dark matter constraints and present a detailed collider analysis of multi-lepton signals viz. the mono-lepton, di-lepton, tri-lepton and four-lepton along with missing transverse energy in the final state using both the cut-based analysis and multivariate analysis respectively at the high luminosity 14 TeV LHC run.