Aspects of the present disclosure include amyloid β (Aβ) peptides. In certain aspects, the Aβ peptides include a chiral substitution at an electrostatic cluster amino acid residue. Also provided are compositions, non-human animals, and kits that include the Aβ peptides. Methods involving the Aβ peptides are also provided.

The present disclosure provides methods of identifying a candidate agent for treating an apoE-associated neurodegenerative disorder. The methods involve contacting a PCSK1 or a PCSK2 polypeptide with an apolipoprotein E polypeptide in the presence of a test agent.

A new, stable trimeric TNFα structure is disclosed with distorted symmetry which can bind to the TNFR1 receptor to attenuate signalling therefrom, which can be used in the treatment and/or prevention of diseases associated with the soluble TNFα/TNFR1 interaction. Membrane-bound TNFα is not affected in its ability to signal through TNFR2, and thus the new structure of TNFα may be used in therapies which do not significantly raise the risk of infection or malignancy.

The present invention in various aspects and embodiments involves pharmaceutical compositions prepared by contacting a candidate α- or β-integrin-binding molecule, or panel thereof, with an integrin heterodimer, and quantifying heterodimer disruption by the candidate molecule. An integrin-binding molecule, or derivative thereof, that disrupts the integrin heterodimer is selected and is formulated into a pharmaceutical composition for administration to a subject, e.g., who has a disease or disorder related to abnormal vascularization.

An anti-Ang2 antibody or an antigen-binding fragment thereof that specifically binds to an angiogenesis-inducing factor Angiopoietin-2 (Ang2) and complexes with a Tie2 receptor and Ang2, and related methods and compositions.

The present disclosure provides Bak binding proteins that change the conformation of Bak and uses thereof.

Methods and compositions for modulation of the activity of alpha thalassemia/mental retardation syndrome X-linked (ATRX), e.g., modulation of DNA-ATRX or RNA-ATRX interactions, and methods for identifying and using compounds that modulate DNA-ATRX or RNA-ATRX interactions, as well as the compounds themselves.

The present invention discloses a method for establishing a colorectal cancer p73 reporter gene cell line, specifically including: first designing a site-specific sgRNA sequence of a p73 gene and cloning same into a plasmid PX459; integrating a homologous recombination sequence of the p73 gene and a green fluorescent protein DNA fragment (EGFP), and transforming the plasmid and the integrated fragment together into a colorectal cancer cell line HCT116 by electroporation; performing signal cell screening through a flow cytometer to obtain EGFP-expressing cells, and amplifying a monoclonal cell line; and identifying a positive p73 reporter gene cell line through PCR identification and Western blot, among screened EGFP-expressing cell lines. The colorectal cancer cell line p73 gene and the EGFP are co-expressed, and the expression level of the EGFP is highly consistent with that of the p73 gene. Therefore, the expression level of the p73 gene can be accurately determined by detecting changes in the expression level of the EGFP. The method for establishing the cell line in the present invention is simple, easy to implement, high in efficiency and precise in gene site positioning.

A family of structurally related proteins has been found to have enzymatic activity. The protein family may comprise DUF1874 proteins. Members of this family can be used to modulate the structure, function and/or activity of a cellular signalling molecule that is associated with a cellular antiviral response. In particular, the proteins described herein exhibit an ability to modulate the function, structure and/or activity of cyclic oligoadenylate (cOA); that is to say they can be used to inhibit, destroy, ablate and/or breakdown cOA activity, structure and/or function. The disclosed proteins (all of which belong to the DUF1874 protein family) are generally referred to as “ring nucleases”.

The present invention relates to a method of determining the capacity of a Cluster 1 mammalian Transcription Factor (TF) for phase separation and/or the capacity for forming a transcriptional condensate in a sample, including a method of determining the presence, localization and/or morphology of a transcriptional condensate comprising said Transcription Factor, and/or of determining the composition of a transcriptional condensate comprising at least one Cluster 1 mammalian TF and/or of determining the transcriptional activity of the TF or a condensate comprising the TF. Further, the present invention relates to an active agent for use in a method of preventing and/or treating a disorder associated with, caused by and/or accompanied with a dysfunction of a biomolecular condensate comprising at least one Cluster 1 mammalian TF.