Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues

Dose-dependency of Immune Response.

<p>L-Plastin immunohistochemical staining on rostral telencephalon of PolyD (200 μM, A), PolyR (100 μM, B; 150 μM, D; 200 μM, F), and Trans (100 μM, C; 150 μM, E; 200 μM, G) peptide-injected brains. (H) Quantification of L-Plastin-positive cells. DAPI is used for nuclear counterstaining (blue). Scale bars = 100 μm, n = 4, data are mean + s.e.m.</p

Quantification of Cell Death upon Peptide Injection.

<p>(A) TUNEL staining on rostral telencephalon of stab-lesioned brain, used as control. Lesioned hemisphere left and unstabbed contralateral hemisphere right. (B) DAPI counterstaining on A. (C) Magnified medial ventricular region of B. (D) TUNEL upon PolyD injection and DAPI counterstaining (E). (F) High magnification of medial ventricular region of E. (G) TUNEL staining on PolyR-injected brain and DAPI counterstaining (H). (J) TUNEL on Trans-injected brain. (K) DAPI counterstaining on J and high magnification of medial ventricular region (L). (M) Quantification of TUNEL-positive cells per telencephalic hemisphere. Scale bars = 100 μm, n = 3, data are mean + s.e.m.</p

Overview of Peptide Translocation in the Telencephalon upon 100 μM Injection, and Dose-dependence.

<p>(A) Reaction scheme for the coupling of 5(6)-carboxyfluorescein to peptides. Fluorescein immunohistochemistry (IHC) on rostral telencephalon of peptide (B) control PolyD, (C) PolyR, (D) Antp, (E) Tat 49–57, (F) Trans and (G) CendRP injected brains. Graphs depict the average area of peptide translocation in one telencephalic hemisphere, upon 100 μM dose injection (H) and upon 200 μM dose injection of CPPs (I). Scale bars: 200 μm, n = 3, data are mean ± s.e.m.</p

Immune Response after Peptide Injection.

<p>(A) L-Plastin immunohistochemistry (IHC) on PBS injected brain, used as control. (B) DAPI counterstaining on A. (C) Magnified medial ventricular region of B. (D) L-Plastin IHC upon PolyD injection and DAPI counterstaining (E). (F) High magnification of medial ventricular region of E. (G) L-Plastin IHC on PolyR injected brain and DAPI counterstaining (H). (J) L-Plastin IHC on Trans injected brain. (K) DAPI counterstaining on J and high magnification of medial ventricular region (L). (M) Graph depicts the quantification of L-Plastin-positive cells per telencephalic hemisphere. Scale bars: 100 μm, n = 3, data are mean + s.e.m.</p

Synthesized Peptides used for CVMI-based Translocation Experiments.

<p>Shown are the name and sequence of the peptides. All peptides were synthesized using standard FMOC chemistry and coupled to 5-Carboxyfluorescein to allow detection in the tissue.</p><p>Synthesized Peptides used for CVMI-based Translocation Experiments.</p

Delivery of Plasmid DNA with PolyR.

<p>(A) GFP immunohistochemistry (IHC) and DAPI staining on brains injected with PolyR-coupled GFP-expression plasmid. (A’) Green channel alone. (B) GFP immunohistochemistry (IHC) and DAPI staining on brains injected with uncoupled GFP-expression plasmid. (B’) Green channel alone. (C) Surface plot projection of the fluorescence intensity in brains injected with uncoupled plasmid. (C’) Surface plot projection of the fluorescence intensity in brains injected with PolyR-coupled plasmid.</p