Abstract: A transplantation method to increase the establishment rate of human tumors in immunodeficient mice. A pocket is created in the mouse and the tumor and surrounding tissues are implanted in the pocket. The pocket is left open to oxygenate the tumor and surrounding tissues.

Abstract: 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.

Abstract: Genetically encoded calcium indicator (GECI) polypeptides and the nucleic acid molecules encoding such polypeptides are provided. In addition, methods of using such nucleic acids and polypeptides in methods of screening for agonists or antagonists of G-protein coupled receptor (GPCR) or ion channels and methods of monitoring neural activity also are provided.

Abstract: An objective of the present invention is to provide non-human animal models of cancer pathology, which mimic the hierarchical organization, cancer progression process, or biological property of human cancer tissues, and uses thereof. To achieve the objective described above, first, the present inventors transplanted cells of NOG-established cancer lines into NOG mice and morphologically observed the resulting tissue organization. As a result, the non-human animal models were demonstrated to exhibit pathologies (the hierarchical organization, cancer progression process, or biological properties of the cancer cells) similar to that of human cancer. Specifically, the present inventors succeeded in preparing non-human animal models exhibiting pathologies more similar to a human cancer, and cell culture systems using NOG-established cancer cell lines where the in vitro cell morphology is more similar to that of human cancer.

Abstract: The invention provides a genetically modified non-human animal that comprises in its genome unrearranged T cell receptor variable gene loci, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified non-human animal and methods of making the same. Various methods of using the genetically modified non-human animal are also provided.

Abstract: The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD40, and methods of use thereof.

Abstract: The present application relates to a method for reestablishing stem cells capable of forming chimeras, and cells obtained by the method. The method of the present invention is a technique for monocloning stem cells, for example, capable of forming chimeras from a heterogeneous cell population to obtain high-quality stem cells.

Abstract: A system for identifying and enumerating cross-body degradations, the system comprising a computing device, wherein the computing device is configured to receive biological extraction data. Computing device may generate a first body degradation function, using a machine-learning model trained with data that correlates biological extraction data with rates of biological degradation of the body. Computing device may determine, using a machine-learning process and the first body degradation function, a second body degradation function, wherein the second body degradation function describes a rate of biological degradation that is statistically associated with a first body degradation function. Computing device identify, using the first body degradation function and the second body degradation function, a predictive relationship between the first body degradation function and the second body degradation function according to the biological extraction datum.

Abstract: Nucleic acid constructs and methods for rendering modifications to a genome are provided, wherein the modifications comprise null alleles, conditional alleles and null alleles comprising COINs. Multifunctional alleles (MFA) are provided, as well as methods for making them, which afford the ability in a single targeting to introduce an allele that can be used to generate a null allele, a conditional allele, or an allele that is a null allele and that further includes a COIN. MFAs comprise pairs of cognate recombinase recognition sites, an actuating sequence and/or a drug selection cassette, and a nucleotide sequence of interest, and a COIN, wherein upon action of a recombinase a conditional allele with a COIN is formed. In a further embodiment, action of a second recombinase forms an allele that contains only a COIN in sense orientation. In a further embodiment, action by a third recombinase forms an allele that contains only the actuating sequence in sense orientation.

Abstract: A system is provided comprising a plurality of C. elegans cultures, where each culture comprises a transgenic C. elegans strain that models a mammalian disease or condition. Methods of using a system, e.g., for characterizing microbial strains of a mammalian microbiome and determining whether such microbial strains affect a mammalian disease or disorder.

Abstract: Provided is a method for preparing a PD-1 gene-modified humanized animal model. The method utilizes the CRIPSR/Cas9 technique to replace partial fragments of a mouse PD-1 gene with fragments of a human PD-1 gene using homologous recombination by constructing a targeting vector, thereby preparing a gene-modified humanized mouse. This mouse can normally express a PD-1 protein containing the functional domain of the human PD-1 protein, and can be used as an animal model for mechanism research regarding PD-1, PD-L1 and other signals, for screening regulators, and for toxicological research. The method has an important and high application value in studies on functions of the PD-1 gene and in the development of new drugs.

Abstract: A TRPM8 related peptide fragment, comprising amino acid sequence as shown in SEQ ID No: 1-18 is provided. Furthermore, application of TRPM8 protein, TRPM8 related peptide fragment and their antibodies in preparing diagnostic reagent for chronic prostatitis/chronic pelvic pain syndromes (CP/CPPS) is provided. By detecting level of TRPM8 protein molecule, TRPM8 related peptide fragment and their antibodies, the chronic prostatitis/chronic pelvic pain syndromes (CP/CPPS) is effectively diagnosed, and the present invention is capable of effectively making a distinction between CP/CPPS and other diseases of prostate.

Abstract: The present disclosure relates to a method of screening an anti-NRP1 antibody or an antigen-binding fragment thereof by use of patient-derived tumor spheroids overexpressing NRP1 and an animal model comprising the same, and more particularly to a method of screening an antibody or an antigen-binding fragment thereof through in vitro and in vivo panning by use of a patient-derived tumor spheroid containing NRP1 and an animal model transplanted with the same, respectively.

Abstract: A method of inhibiting inflammation with milk oligosaccharides or glycoconjugates containing the oligosaccharides.

Abstract: Provided is a method of detecting neural activity, including inducing neurons of a subject to express two or more polypeptides each comprising an amino acid sequence represented by one of SEQ ID NOs:13-24, wherein inducing comprises stimulating interneuronally different relative levels of expression of the two or more polypeptides; applying coelenterazine to the subject; applying a first stimulation of neural activity to the subject; detecting a first spatiotemporal and spectral pattern of electromagnetic radiation emitted by neurons of the subject in response to the first stimulation; recording the first spatiotemporal and spectral pattern of electromagnetic radiation in a computer memory; applying a second stimulation of neural activity to the subject; detecting a second spatiotemporal and spectral pattern of electromagnetic radiation emitted by neurons of the subject in response to the second stimulation; comparing the second spatiotemporal and spectral pattern of electromagnetic radiation to the first spa

Abstract: The present application provides a novel drug screening platform designed to identify drugs that favorably modulate cellular bioenergetics in the human brain of a zebrafish which has been modified by altering a teleost gene that corresponds to a human gene associated with a brain dysfunction disorder (such as epilepsy). The drug screening platform are also useful for determining a mutation in a human gene associated with a brain dysfunction disorder that is associated with a human individual responsive to the treatment of a compound. Also provided are modified teleosts useful for the methods described herein.

Abstract: The present disclosure provides methods of modulating a feature of a behavioral state. The methods involve inhibiting or activating the activity of a bed nucleus of stria terminalis (BNST) neuron, a BNST subnucleus, or a neuronal output to or from a BNST neuron. Animals encounter environmental conditions that require rapid switching among different behavioral states to increase the likelihood of survival and reproduction.

Abstract: The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD47, and methods of use thereof.

Abstract: Provided is a method for preparing a PD-1 gene-modified humanized animal model. The method utilizes the CRIPSR/Cas9 technique to replace partial fragments of a mouse PD-1 gene with fragments of a human PD-1 gene using homologous recombination by constructing a targeting vector, thereby preparing a gene-modified humanized mouse. This mouse can normally express a PD-1 protein containing the functional domain of the human PD-1 protein, and can be used as an animal model for mechanism research regarding PD-1, PD-L1 and other signals, for screening regulators, and for toxicological research. The method has an important and high application value in studies on functions of the PD-1 gene and in the development of new drugs.

Abstract: The present invention is in the field of stem cell biology, in particular in the field of developmental and regenerative biology. The invention generally relates to a method of generating cells capable of differentiating to a multicellular organoid unit that morphologically and/or functionally resembles the terminal ductal-lobular unit. More precisely, said cells are generated by dissociating mammary epithelial tissue, thereby gaining cells and culturing said cells in presence of a compound which elevates cAMP levels in a collagen gel. Under said culturing conditions said cells form a multicellular organoid unit facilitating to obtain a breast stem cell by isolating a single cell from said multicellular organoid unit. The present invention also relates to enriching said cells and differentiating them to a multicellular organoid that morphologically and/or functionally resembles the terminal ductal-lobular unit and use of said cells or said multicellular organoid in testing a compound.

Abstract: The present disclosure provides pharmaceutical compositions including a plurality of IgG2 anti-CGRP antagonist antibodies comprising a high content of particular IgG2 disulfide isomers, and methods of using the same.

Abstract: The invention relates to novel libraries of linear and cyclic peptides, and methods of generating and screening such libraries for biological, pharmaceutical and other uses.

Abstract: Transgenic non-human animals, e.g., rodents, e.g., mice comprising genomic mutations that inactive all of the serpin1A genes and thus lack any functional serpinA1 genes. As a result of the genomic mutations, the animals express no hepatic or circulatory AAT protein. Also provided herein are cells and tissues derived from the transgenic mice.

Abstract: Methods are provided for stimulating ovarian preantral and antral follicles in a mammal.

Abstract: Provided herein, inter alia, are non-human animals comprising nucleic acid sequences encoding a C3 protein that comprises a human sequence as well as transgenic non-human animals comprising a C3 gene that is human in whole or in part as well as methods for using the same to screen for candidate therapeutic molecules to treat complement-related nephropathies. Also provided herein are methods for improving kidney function in an individual diagnosed with or thought to have a complement-related nephropathy.

Abstract: A method of identifying individual zebrafish (Danio rerio), containing the steps of: observing a striped pattern for each of an anal fin and a caudal fin of each individual of two or more zebrafish in side view; determining characteristics of each individual from the observed striped pattern; and identifying each individual on the basis of the characteristics obtained.

Abstract: The ?4?2 neuronal nicotinic acetylcholine receptor (nAChR) plays a crucial role in nicotine addiction. The invention studied the effect of subunit phosphorylation on ?4?2 nAChR function and expression, and eleven residues located in the M3-M4 cytoplasmic loop were mutated to alanine and aspartic acid. When nicotine was used as an agonist, four mutations exhibited a statistically significant hypersensitivity to nicotine (S438D, S469A, Y576A, and S589A). Additionally, two mutations (S516D and T536A) that displayed normal activation with ACh displayed remarkable reductions in sensitivity to nicotine. The invention provides a knock-in mutant construct for the development of a transgenic mouse line with reduced nicotine sensitivity to be used in future studies.

Abstract: The invention generally relates to optical methods for the diagnosis of neuronal condition by converting a cell from a patient into a neuron and optically evaluating action potentials of that cell in vitro. The cell is transformed with an optical reporter and exhibits an optical signature in response to neural stimulation. Using genome-editing, a control cell can be made that is isogenic but-for a known mutation and a control signature obtained from the control cell. Thus, methods of the invention reveal potential neurodegenerative effects of a mutation as manifested in a patient's genetic context. The optical signature of the cell, or the difference between the signature and the control signature, is correlated to a diagnosis of the neurodegenerative disease.

Abstract: Microbiota restoration therapy compositions and methods for manufacturing, processing, and/or delivering microbiota restoration therapy compositions are disclosed. An example method for manufacturing a microbiota restoration therapy composition may include collecting a human fecal sample and adding a diluent to the human fecal sample to form a diluted sample. The diluent may include a cryoprotectant. The method may also include mixing the diluted sample with a mixing apparatus and filtering the diluted sample. Filtering may form a filtrate. The method may also include transferring the filtrate to a sample bag and sealing the sample bag.

Abstract: Methods for diagnosing and treating conditions associated with life-threatening neurological complications are provided. The methods involve in some aspects the identification of oxLDL and LOX-1 as critical players in pregnant subjects and in some cases subjects having severe preeclampsia (early onset preeclampsia). Related products and kits are also provided.

Abstract: Microbiota restoration therapy compositions and methods for manufacturing, processing, and/or delivering microbiota restoration therapy compositions are disclosed. An example method for manufacturing a microbiota restoration therapy composition may include collecting a human fecal sample and adding a diluent to the human fecal sample to form a diluted sample. The diluent may include a cryoprotectant. The method may also include mixing the diluted sample with a mixing apparatus and filtering the diluted sample. Filtering may form a filtrate. The method may also include transferring the filtrate to a sample bag and sealing the sample bag.

Abstract: Embodiments described herein relates to compositions and methods of preventing and/or treating itch in a subject using a therapeutically effective amount of a MRG receptor antagonist. e.g., a tripeptide QWF. In one embodiment, the itch is a non-histamine mediated itch.

Abstract: The present invention provides mammalian cell lines that have been genetically engineered causing such cell lines to be resistant to viral entry and/or propagation, and provides methods of using said cell lines to reduce or prevent viral contamination of biologic production systems.

Abstract: The following discloses mammalian cells lines that stably express functional nematode acetylcholine receptor subunits. The resulting expression of functional ion channels has been made possible by the stable co-expression of the chaperone protein, RIC3. These cell lines are extremely useful for the high throughput screening (HTS) of compounds, to identify new candidate parasiticidal, including nematocidal, active ingredients.

Abstract: Provided is a non-human animal that is highly practical as a hyperuricenia model, the non-human animal being the following: (a) a non-human animal obtained by producing a primary chimeric non-human animal by transplantation of human hepatocytes to an immunodeficient non-human animal with liver dysfunction; and subsequently administering a purine base-containing substance to the primary chimeric non-human animal, or (b) a non-human animal obtained by producing a serially transplanted chimeric non-human animal via two steps, a first step being a step of producing a primary chimeric non-human animal by transplantation of human hepatocytes to an immunodeficient non-human animal with liver dysfunction, a second step being a step of transplanting the human hepatocytes grown in the body of the primary chimeric non-human animal to an immunodeficient non-human animal with liver dysfunction, the second step being performed one or more times; and subsequently administering a purine base-containing substance to the seri

Abstract: Embodiments of the invention are directed to compositions and methods related to Tau oligomers and Tau oligomer specific antibodies and their use in detecting and/or treating traumatic brain injury or chronic traumatic encephalopathy.

Abstract: Transgenic non-human animals, e.g., rodents, e.g., mice comprising genomic mutations that inactive all of the serpin1A genes and thus lack any functional serpinA1 genes. As a result of the genomic mutations, the animals express no hepatic or circulatory AAT protein. Also provided herein are cells and tissues derived from the transgenic mice.

Abstract: The present invention pertains to a dendritic cell-based vaccine against rh-?-Syn, ?-synuclein specific peptide antibodies and related vaccines, and methods of treating, preventing, and/or vaccinating against Parkinson's Disease (PD), or symptoms thereof.

Abstract: Disclosed herein are 1,4-naphthoquinone analogs, pharmaceutical compositions that include one or more of such 1,4-naphthoquinone analogs, and methods of treating and/or ameliorating diseases and/or conditions associated with a cancer, such as prostate cancer with such 1,4-naphthoquinone analogs. Also included are combination therapies wherein a 1,4-naphthoquinone analog disclosed herein, and a hormone therapy agent are provided to a subject suffering from a condition such as cancer.

Abstract: In some aspects, described herein is a DNA methylation reporter. In some aspects, the DNA methylation reporter comprises a promoter whose activity can be affected by exogenous methylation changes without being independently regulated by the DNA methylation machinery, operably linked to a DNA sequence that encodes a reporter molecule. In some embodiments the DNA methylation reporter comprises (i) a promoter derived from a mammalian imprinted gene promoter; and (ii) a sequence that encodes a reporter molecule that is detectable in individual mammalian cells, wherein the promoter is operably linked to the sequence that encodes the reporter molecule. Also described are nucleic acids that comprise the DNA methylation reporter, cells that have the DNA methylation reporter integrated into their genome, and non-human mammals comprising cells that have the DNA methylation reporter integrated into their genome.

Abstract: Methods are provided for stimulating ovarian preantral and antral follicles in a mammal.

Abstract: The present invention relates to transgenic mice and isolated transgenic mouse cells, the mice and mouse cells comprising a disrupted H2 class I gene, a disrupted H2 class II gene, a functional HLA class I transgene, and a functional HLA class II transgene. In embodiments, the transgenic mouse or mouse cells are deficient for both H2 class I and class II molecules, wherein the transgenic mouse comprises a functional HLA class I transgene and a functional HLA class II transgene. In embodiments, the transgenic mouse or mouse cell has the genotype HLA-A2+HLA-DR1+?2m°IA?°. The invention also relates to methods of using a transgenic mouse of the invention.

Abstract: Genetically encoded calcium indicator (GECI) polypeptides and the nucleic acid molecules encoding such polypeptides are provided. In addition, methods of using such nucleic acids and polypeptides in methods of screening for agonists or antagonists of G-protein coupled receptor (GPCR) or ion channels and methods of monitoring neural activity also are provided.

Abstract: The present invention provides a transgenic mouse which comprises a deficiency for murine T lymphocytes, B lymphocytes and NK cells, a deficiency for murine MHC class I and MHC class II molecules, and a functional xenogenic SIRP? transgene. This mouse is useful for in vivo screening of various compounds, including immuno-therapeutic agents and vaccines. The said mouse is also useful for testing the in vivo metabolism of xenobiotic compounds.

Abstract: The disclosure relates to genetically modified swine wherein at least one allele of a SIGLEC1 gene has been inactivated and/or at least one allele of a CD163 gene has been inactivated. Genetically modified swine having both alleles of the SIGLEC1 gene and/or both alleles CD 163 gene inactivated are resistant to porcine reproductive and respiratory syndrome virus (PRRSV). Methods for producing such transgenic swine are also provided.

Abstract: The invention relates to the control of gene expression. Specifically, the invention provides compositions and methods for the production and use of recombinant nucleic acid molecules that have the ability to specifically downregulate an expressed target gene in vivo. In some aspects, the invention provides methods for producing a hairpin DNA molecule where part of the molecule is derived from an mRNA that is a target for a small interfering RNA (siRNA) derived from the hairpin. In other aspects, the invention provides synthetic hairpin adapter oligonucleotides that are used in the construction of siRNA-producing cassettes. In other aspects, the invention provides methods for testing for the presence or absence of specific inhibitory activity of an RNAi trigger molecule, and in still other aspects, the invention provides methods for identifying an active RNAi trigger molecule from a library of RNAi trigger molecules.

Abstract: Provided is a gene in drosophila designated as dSLC5A1. This gene is responsible for taste independent nutrient sensing. Activation of neurons expressing this gene results in hunger behavior. Provided are compositions and methods for identifying agents that can interfere with hunger behavior.

Abstract: A lentiviral vector was used to produce non-human animals that express human sFLT1 specifically in the murine placenta, to provide model animals of diseases such as pregnancy-induced hypertension syndrome that are close to the clinical conditions, methods for producing the model animals, methods of screening for candidate compounds as therapeutic agents for diseases such as pregnancy-induced hypertension syndrome by using the model animals, and therapeutic agents for diseases such as pregnancy-induced hypertension syndrome. As a result, the model animals were found to exhibit symptoms that are very close to the clinical conditions in human, which are presentation of hypertension as well as placental insufficiency, intrauterine growth retardation, glomerulosclerosis, and proteinuria during pregnancy, and improvement of those symptoms postpartum.

Abstract: Described herein are recombinant integral membrane proteins having multiple transmembrane domains that have been engineered to be less hydrophobic, through alteration of the amino acid sequence of the native protein, but retain the ability to bind their natural ligand. The decreased hydrophobicity of the described proteins makes them more water soluble than the native protein, which allows the described proteins to be expressed in bacteria in large quantities and isolated in the absence of membranes, all while retaining the ability to interact with known ligands.

Abstract: This invention relates to, in part, methods and compositions that are useful for the diagnosis, treatment, or prevention of a blinding eye disease, including in the discovery of drugs that are efficacious against these diseases. Diseases include, for example, age related macular degeneration and reticular pseudodrusen disease, and the methods described herein include, for example, the method named delayed near infrared analysis (DNIRA).