The invention relates to a genetically modified mouse comprising a heterozygous mutation of Tardbp (TDP-43) gene in that the Asn at amino acid 390 in TDP-43 is substituted with an amino acid that is different from Asn, wherein the genetically modified mouse exhibits Amyotrophic lateral sclerosis (ALS)-like phenotypes, TDP-43 proteinopathies and/or motor neuron degeneration. The invention also so relates to an isolated spinal cord motor neuron differentiated from an embryonic stem cell (ESC) that is obtained from an offspring of a genetically modified mouse according to the invention. Methods for identifying an agent alleviating and/or suppressing ALS-TDP pathogenesis are also disclosed.

Herein is reported a method for determining the concentration of a therapeutic antibody in a tissue of an experimental animal to whom the therapeutic antibody had been administered, wherein the interference from residual blood in a tissue sample of the experimental animal, which is used for determining the concentration of the therapeutic antibody in said tissue, is reduced, wherein the concentration of the therapeutic antibody in the tissue of the experimental animal is calculated with the following formula:

[00001]$C_{\mathrm{tmAb},\mathrm{tissue}}=\frac{C_{tmAb,\mathrm{tissue},\det .}}{C_{tis\mathrm{sue},\mathrm{sample}}}-\frac{\frac{C_{refmAb,\mathrm{tissue},\det .}}{C_{tis\mathrm{sue},\mathrm{sample}}}}{C_{refmAb,\mathrm{plasma}.\det .}}*C_{tmAb,\mathrm{plasma},\det }.$

wherein C.sub.tmAb,tissue,det.=obtained by determining the concentration of the therapeutic antibody in the tissue sample of the experimental animal, C.sub.tmAb,plasma,det.=obtained by determining the concentration of the therapeutic antibody in a blood sample of the experimental animal directly prior to taking the tissue sample, C.sub.refmAb,tissue,det.=obtained by determining the concentration of the inert reference antibody in the tissue sample of the experimental animal, C.sub.refmAb,plasma,det.=obtained by determining the concentration of an inert reference antibody in

A production method for a cerebral organoid having amyloid plaques is provided, the method including a step (a) of forming, in the presence of a SMAD inhibitor, an embryoid body from a pluripotent stem cell having a mutation in an Alzheimer's disease-related gene; a step (b) of embedding the embryoid body after the step (a) in an extracellular matrix and three-dimensionally culturing the embedded embryoid body in the presence of a SMAD inhibitor and a glycogen synthase kinase 3β (GSK3β) inhibitor to form an organoid; and a step (c) of removing the organoid after the step (b) from the extracellular matrix and subjecting the removed organoid to stirring culture in a medium, where at least a part of the step (c) is carried out in the presence of leukemia inhibitory factor (LIF).

In some aspects, the disclosure provides compositions and methods for detecting and monitoring the activity of proteases in vivo using affinity assays. The disclosure relates, in part, to the discovery that biomarker nanoparticles targeted to the lymph nodes of a subject are useful for the diagnosis and monitoring of certain medical conditions (e.g., metastatic cancer, infection with certain pathogenic agents).

An ex vivo tissue composition comprising an isolated tissue explant and tissue graft is provided. Methods of making and using the tissue composition are also provided.

The present invention discloses a method for diagnosing cancer comprising a step of detecting active protein kinase Cα in urine.

Disclosed herein are methods for obtaining endometrial stromal fibroblast cells from pluripotent stem cells, such as induced pluripotent stem cells. The present disclosure also provides methods of obtaining a three-dimensional, multilayered endometrial tissue composition. Methods of using the cells and tissue compositions in drug screening and therapeutic applications are also provided.

An apparatus includes a housing having an aperture extending through a wall of the housing, a carbon dioxide delivery device coupled to the housing through the aperture, a non-biological skin substitute substrate, and a heater coupled to the substrate.

In some aspects, the present invention provides chimeric transferrin receptor (TfR) polynucleotides and polypeptides. In other aspects, this invention provides chimeric TfR transgenic animal models and methods of using the animal models to identify therapeutics that can cross the blood-brain barrier.

The present disclosure provides a substrate for cell culture. Systems comprising the substrate, and methods for using and manufacturing the substrate are also disclosed herein.