Disclosed herein are Pifithrin compounds, methods of treating Rett Syndrome, brain fusion organoids comprising a fusion between a cerebral cortex (Cx) organoid and the ganglionic eminence (GE) organoid, one of which comprises, consists essentially of, or consists of neural cells having a loss of function mutation in the Methyl-CpG Binding Protein 2 (MECP2) gene, and methods of using the brain fusion organoid to screen for candidate compounds that treat, reduce, or inhibit the abnormal neural activities caused by MECP2-mutations.

The present disclosure provides methods of processing or analyzing a sample. A method for processing a sample may comprise hybridizing a probe molecule to a target region of a nucleic acid molecule (e.g., a ribonucleic acid (RNA) molecule), barcoding the probe-nucleic acid molecule complex, and performing extension, denaturation, and amplification processes. A method for processing a sample may comprise hybridizing first and second probes to adjacent or non-adjacent target regions of a nucleic acid molecule (e.g., an RNA molecule), linking the first and second probes to provide a probe-linked nucleic acid molecule, and barcoding the probe-linked nucleic acid molecule. One or more processes of the methods described herein may be performed within a partition, such as a droplet or well. One or more processes of the methods described herein may be performed on a cell, such as a permeabilized cell.

The disclosure provides for multilayered organ-on-a-chip systems that can be used to generate topographic neural organoids, and uses thereof, including as models to study neurological disorders.

The invention concerns uses of anti-KLβ agents, and detection of KLβ and/or FGF19 and/or FGFR4.

Provided is a measurement device including a mounting unit in which a flow channel device is attachably and detachably mounted, the flow channel device including a first flow channel, a second flow channel having a communicating portion that communicates with a part of the first flow channel, and a cell sheet in which a plurality of cultured cells are arranged in such a manner that the cells are bound to each other and which partitions between the first flow channel and the second flow channel at the communicating portion; and a detection unit that optically distinguishes and detects a leakage state of each of a plurality of types of tracers having different sizes and leaking out from the first flow channel into the second flow channel through a defect occurring in the cell sheet in a case where an evaluation liquid is fed into the first flow channel.

The present invention provides compositions, systems, and methods for barcoding cells, beads, and secreted proteins in discrete entities (e.g. droplets) to allow sequencing data from such components that are separated during processing to be associated via the common barcodes. In some embodiments, the barcodes are tethered to the cell surface via a lipid, cholesterol, or antibody, or are attached to a surface molecule that moves from one cell to another via trogocytosis. In certain embodiments, such methods allow cell-cell interactions or secreted proteins in the discrete entity to be monitored.

Novel therapeutic agents, particularly those capable of activating (GPR)124/RECK/Frizzled/lipoprotein receptor-related protein (LRP)-mediated Wnt signaling, while not activating Frizzled/LRP-mediated Wnt signaling in the absence of RECK and/or GPR124. The agents are particularly useful for the prevention or treatment of neurovascular disorders or central nervous system (CNS) disorders including neurovascular dysfunction.

The invention concerns uses of anti-KLβ agents, and detection of KLβ and/or FGF19 and/or FGFR4.

The present disclosure provides compositions, methods, systems, and devices for polynucleotide processing and analyte characterization from a single cell. Such polynucleotide processing may be useful for a variety of applications. The compositions, methods, systems, and devices disclosed herein generally describe barcoded oligonucleotides, which can be bound to a bead, such as a gel bead, useful for characterizing one or more analytes including, for example, protein (e.g., cell surface or intracellular proteins) and chromatin (e.g., accessible chromatin).

The present disclosure provides compositions, methods, systems, and devices for polynucleotide processing and analyte characterization from one or more cells. Such polynucleotide processing may be useful for a variety of applications, including generation of labeled macromolecules, including major mistocompatability complex (MHC) molecules, dextramers, etc. Labeled macromolecules may be generated using an in vitro transcription reaction. Labeled macromolecules may be generated in one or more partitions.