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We report a facile method to prepare polymer-grafted plasmonic metal nanoparticles (NPs) that exhibit pH-responsive surface-enhanced Raman scattering (SERS). The concept is based on the use of pH- responsive polymers, such as poly(acrylic acid) (PAA) and poly(allylamine hydrochloride) (PAH), as multi- dentate ligands to wrap around the surface of NPs instead of forming polymer brushes. Upon changing the solvent quality, the grafted pH-responsive polymers would drive reversible aggregation of NPs, leading to a decreased interparticle distance. This creates numerous hot spots, resulting in a secondary enhancement of SERS as compared to the SERS from discrete NPs. For negatively charged PAA-grafted NPs, the SERS response at pH 2.5 showed a secondary enhancement of up to 104-fold as compared to the response for discrete NPs at pH 12. Similarly, positively charged PAH-grafted AuNPs showed an oppo- site response to pH. We demonstrated that enhanced SERS with thiol-containing and charged molecular probes was indeed from the pH-driven solubility change of polymer ligands. Our method is different from the conventional SERS sensors in the solid state. With pH-responsive polymer-grafted NPs, SERS can be performed in solution with high reproducibility and sensitivity but without the need for sample pre-con- centration. These findings could pave the way for innovative designs of polymer ligands for metal NPs where polymer ligands do not compromise interparticle plasmon coupling. 

We construct the Schwarzschild dynamical models for 11 early-type galaxies with the SAURON and Mitchell stellar IFUs out to 2–4Re, and construct dynamical models with combined stellar and H i kinematics for a subsample of four galaxies with H i velocity fields out to 10Re obtained from the Westerbork Synthesis Radio Telescope, thus robustly obtaining the dark matter content out to large radii for these galaxies. Adopting a generalized-NFW dark matter profile, we measure an NFW-like density cusp in the dark matter inner slopes for all sample galaxies, with a mean value of 1.00 ± 0.04 (rms scatter 0.15). The mean dark matter fraction for the sample is 0.2 within 1Re, and increases to 0.4 at 2Re, and 0.6 at 5Re. The dark matter fractions within 1Re of these galaxies are systematically lower than the predictions of both the TNG-100 and EAGLE simulations. For the dark matter fractions within 2Re and 5Re, 40 and 70 per cent galaxies are 1σ consistent with either the TNG-100 or the EAGLE predictions, while the remaining 60 and 30 per cent galaxies lie below the 1σ region. Combined with 36 galaxies with dark matter fractions measured out to 5Re in the literature, about 10 per cent of these 47 galaxies lie below the 3σ region of the TNG-100 or EAGLE predictions.

 

Immune checkpoint inhibitors can stimulate antitumor immunity but can also induce toxicities termed immune-related adverse events (irAEs). Colitis is a common and severe irAE that can lead to treatment discontinuation. Mechanistic understanding of gut irAEs has been hampered because robust colitis is not observed in laboratory mice treated with checkpoint inhibitors. We report here that this limitation can be overcome by using mice harboring the microbiota of wild-caught mice, which develop overt colitis following treatment with anti-CTLA-4 antibodies. Intestinal inflammation is driven by unrestrained activation of IFNγ-producing CD4⁺T cells and depletion of peripherally induced regulatory T cells through Fcγ receptor signaling. Accordingly, anti-CTLA-4 nanobodies that lack an Fc domain can promote antitumor responses without triggering colitis. This work suggests a strategy for mitigating gut irAEs while preserving antitumor stimulating effects of CTLA-4 blockade.

 

The detection of site-specific phosphorylation in the microtubule-associated protein tau is emerging as a means to diagnose and monitor the progression of Alzheimer’s Disease and other neurodegenerative diseases. However, there is a lack of phospho-specific monoclonal antibodies and limited validation of their binding specificity. Here, we report a novel approach using yeast biopanning against synthetic peptides containing site-specific phosphorylations. Using yeast cells displaying a previously validated phospho-tau (p-tau) single-chain variable region fragment (scFv), we show selective yeast cell binding based on single amino acid phosphorylation on the antigen. We identify conditions that allow phospho-specific biopanning using scFvs with a wide range of affinities (KD = 0.2 to 60 nM). Finally, we demonstrate the capability of screening large libraries by performing biopanning in 6-well plates. These results show that biopanning can effectively select yeast cells based on phospho-site specific antibody binding, opening doors for the facile identification of high-quality monoclonal antibodies.