damage states  (MedChemExpress)

Journal: iScience

Article Title: Compensatory responses to glaucoma pathology in the dorsolateral geniculate nucleus

doi: 10.1016/j.isci.2026.115176

Figure Lengend Snippet: Pharmacology of inhibition indicates decreased activation of extrasynaptic GABA A receptors in DBA/2J TC neurons (A) Example peak-normalized IPSCs from TC neurons from D2 and D2-control mice evoked by stimulation with an aCSF-filled patch pipette positioned approximately 25 microns from the recorded TC neuron in the presence of CNQX (20 μM) and D-AP5 (50 μM). Traces show before (gray) and after (black) bath application of 10 μM DS2. (B) Relative effect of DS2 application on peak response of the IPSC (n.s., p = 0.16 via nested t test) and area (∗∗∗ p = 0.0010 via nested t test) of D2 (red) and D2-control (black) mice ( n = 8 cells, four mice [D2-control] and n = 16 cells, six mice [D2]). Bar graphs and error bars show mean ± SEM. (C) Example peak-normalized traces of IPSCs from D2 and D2-control mice before (gray) and after (black) application of SNAP5114 (60 μM). IPSCs were evoked as in A. (D) Relative effect of SNAP5114 application on peak response (n.s., p = 0.70 via nested t test) and area (n.s., p = 0.91 via nested t test) of D2 (red) and D2-control (black) mice ( n = 16 cells, six mice [D2] and n = 14 cells, five mice [D2-control]). Bar graphs and error bars show mean ± SEM.

Article Snippet: DS2 , Tocris , Cat # 3679.

Techniques: Inhibition, Activation Assay, Control, Transferring

Journal: eBioMedicine

Article Title: Rational design of respiratory syncytial virus dimeric F-subunit vaccines in protein and mRNA forms

doi: 10.1016/j.ebiom.2025.105902

Figure Lengend Snippet: Rational design of RSV F protein monomer A and scDimer AA at pre-fusion state and their immunogenicity assessment. (A) Schematic diagram and design rationale of monomer A. The design of monomer A was outlined (top). Substitutions unique to monomer A and DS2 are labelled in black and grey, respectively. Substitutions shared among DS-Cav1, DS2, and monomer A are coloured in red, and those shared between DS2 and monomer A are coloured in blue. The dashed squares indicated the deleted residues. In the pre-F structure (PDB: 5k6i ), Epitope I, II, III, IV, V, and Ø were labelled in magenta, green, purple, red, yellow, and blue, respectively and their neutralising sensitivities are indicated. (B) Binding affinities of monomer A (top) and scDimer AA (bottom) with MAbs targeting six epitopes. Actual and fitted curves were represented by red and black lines, respectively. K D values were listed as mean ± SD of three experiments. (C) Endpoint titres of immunised antigen-binding IgG in murine sera were measured by ELISA. Groups of mice (n = 4∼5) were intramuscularly immunised with 3 or 10 μg of monomer A or scDimer AA at 0, 3, and 6 weeks with Alhydrogel® adjuvant. Serum samples were collected on day 56 (two weeks after the 3rd immunisation) and subjected for ELISA test. (D) Neutralisation of RSV A2 strain in murine sera on day 56 was assessed. (E) Design of scDimer AA. Two truncated monomers A were tandemly linked, with the latter one starting at N27 residue. (F) Crystal structure of scDimer AA, with epitopes labelled as in panel A. Dotted lines represented areas with uncharacterised structures due to the flexibility of the regions. In (C) and (D), dotted lines indicated the lower limit of detection (LLD). Any value less than the LLD was assigned a value of 1⁄2 the LLD. Data were derived from two technical replicates of a single experiment, with bars indicating mean ± SD. P values were determined using Two-way ANOVA (ns indicated P > 0.05; ∗ indicated P < 0.05; ∗∗∗∗ indicated P < 0.0001).

Article Snippet: DS-Cav1, a representative pre-F stabilised by introducing a disulfide bond and two cavity-filling substitutions, is adopted in the approved GSK protein-based vaccine, Arexvy., An enhanced version, DS2, with additional disulfide bonds and substitutions, was also adopted in Moderna's licenced mRNA vaccine (mRNA-1345, mRESVIA).

Techniques: Immunopeptidomics, Binding Assay, Enzyme-linked Immunosorbent Assay, Adjuvant, Residue, Derivative Assay