Abstract: The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/B1N, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2retmlWjl/SzJ (NSG), NOD.Cg-Rag1tm1Mom Il2rgtmlWjl/SzJ (NRG) and NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice.

Abstract: A NOD.Cg-PrkdcscidH2rgtm1 Wjl/SzJ.(NOD-scid-IL2r?null, NSG) mouse which is genetically modified such that the en NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present, invention. According to specific aspects the genetically modified NSG mouse, is a NOD.Cg-PrkdcscidH2-K1tml Bpe H2-Ab1eml Mvw H2-D1tml Bpe H2rgtm Wjl/SzJ (NSG-Kb Db)null(IAnull)) mouse, NSG-RIP-DTR (Kb Db)null(IAnull) mouse, or a NOD.Cg-B2mtmlUnePrKdcscidH2dlAb1-E?H2rgtm1 Wjl/SzJ (NSG-B2Mnull(IA IEnull)) mouse. Human, immune cells and/or human: tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice.

Abstract: Provided herein are, inter alia, compositions and methods for demethylating and methylating a target DNA sequences in a mammalian cell. The compositions and methods are, useful for activity modulation of a targeted gene, or to create a gene regulatory network.

Abstract: Certain pressure sensor devices are much smaller than prior art devices, yet are at least as sensitive as the prior art devices. A capacitive pressure sensor can include a flexible substrate that permits bending of a pressure sensing region without significantly affecting operation thereof. The pressure sensor can include a flexible membrane in which an electrode is sandwiched between two layers of polymeric material. The sandwiched electrode can be extremely close to a reference electrode so as to provide for highly sensitive capacitance readings, yet the membrane can be restricted from contacting the reference electrode under high pressure condition.

Abstract: Genetic variations associated with a patient’s cancerous tumors can be indicative of potential effective treatments for treating the patient. Systems and methods for determining relationships between gene variants of a gene, the gene variants being related to one or more cancers and being correlated to a treatment response of the one or more cancers to one or more medications, are provided. The method includes accessing, using at least one processor, a database comprising information about the gene variants, the information including at least information indicative of a treatment response of a first gene variant of the gene variants to one or more treatments; categorizing the information about the gene variants within a plurality of groups; and generating hierarchical relationships between each group of the plurality of groups. In some embodiments, a patient may be treated using a treatment selected based on the generated hierarchical relationships.

Abstract: The present disclosure provides methods and compositions for high frequency, targeted mammalian transgenesis using, for example, a two-step, two-stage process that enables integrating anywhere in the mammalian genome large pieces of nucleic acid in single generation.

Abstract: The present disclosure provides an immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG™) mouse models that comprise an inactivated mouse Flt3 allele, a nucleic acid encoding human interleukin 3 (IL3), a nucleic acid encoding human granulocyte/macrophage-stimulating factor (GM-CSF), a nucleic acid encoding human stem cell factor (SCF), and a HLA-A2/H2-D/B2M transgene encoding (i) a human B2-microglubulin (B2M) covalently linked to MHC class 1, alpha 1, and alpha2 binding domains of a human HLA-A2.1 gene and (ii) alpha3 cytoplasmic and transmembrane domains of murine H2-db.

Abstract: An arrangement for reducing intraocular pressure includes a pulse signal source, a probe coupling, and at least one electrode. The probe coupling is configured to be supported on a portion of a living eye. The electrodes are supported on the probe coupling. The electrodes are operably coupled to receive a pulse signal from the pulse signal source.

Abstract: The present disclosure provides a transgenic, immunocompromised mouse engineered to express a human angiotensin converting enzyme 2 (huACE2) sequence. The huACE2 sequence may be operably linked to a human keratin 18 (hKRT18) promoter or the endogenous mouse angiotensin converting enzyme 2 (mACE2) promoter. Transgenic immunocompromised mice of the present disclosure may be utilized in methods of evaluating a test agent for reducing or preventing SARS-CoV-2 infection.

Abstract: Provided herein, in some embodiments, are methods for modulating expression and/or activity of transient receptor potential cation channel subfamily C, member 3 (TRPC3), as well as methods of treating Alzheimer's disease.

Abstract: The present disclosure relates to genetically modified non-obese diabetic (NOD) mice deficient in murine class I MHC molecules, class II molecules, or both class I and class II MHC molecules. The MHC knockout transgenic mice provided herein are useful, for example, for developing therapies for diabetes.

Abstract: Provided herein, in some embodiments, are methods, compositions, and systems for identifying alternatively spliced tumor-specific exon inclusion and exclusion events that can be used for survival prognosis.

Abstract: The present disclosure provides methods of inducing EBV early lytic cycle genes with high specificity. These methods slow or stop cancer cell growth in vitro and in vivo.

Abstract: The invention, in part, relates to assessing interactions between gene transcription enhancers and gene transcription repressor, identifying agents that modulate transcription, and use of methods and identified agents to prevent and treat diseases and conditions, such as cancers.

Abstract: The present disclosure provides an admixture of Staphylococcus (S.) epidermidis cells selected from S. epidermidis Type I cells, S. epidermidis Type II cells, S. epidermidis Type III cells, S. epidermidis Type Mvb cells, and S. epidermidis Type IV cells capable of modified expression of virulence factor genes and other genes that contribute to virulence, such as nitrogen respiration genes, ureases activity genes, carbohydrate metabolism genes, iron uptake genes, sulfur metabolism genes. The present disclosure also provides methods of treating or preventing skin disease and reducing the risk of recurrent skin disease in a subject by administering the admixtures of S. epidermidis cell types.

Abstract: The invention described herein provides compositions and reagents for assembling a tripartite complex at a specific location of a target DNA. The invention also provides methods for using the complex to, for example, label a specific genomic locus, to regulate the expression of a target gene, or to create a gene regulatory network.

Abstract: Provided herein are methods and compositions for the treatment or prevention of certain disorders and conditions, for example, addiction using an agent to modulate 5-hydroxytryptamine 1D receptor (HTR1D) activity and/or expression. Also provided are methods for screening a candidate to determine if the candidate is suitable for the therapies disclosed herein.

Abstract: A method and system for developing a predictive model for diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in a human are disclosed. The method comprises receiving immune system data for each member of a population comprising healthy humans and humans with ME/CFS; extracting a set of features from the immune system data; and training a machine learning algorithm using the set of features to classify a human as healthy or having ME/CFS to obtain a predictive model. The system comprises a processor; and a memory storing computer executable instructions, which when executed by the processor cause the processor to perform operations of said method.

Abstract: Methods for identifying MS in a subject based on an analysis of the strength of the immune-microbial homeostatic relationship based on the immune profile and the gut microbiome profile are described. In addition, methods of identifying MS patients likely to seek disease-modifying treatment within six months based on an analysis of the relative abundance of Barnesiella spp. based on the gut microbiome profile are described.

Abstract: Provided herein, in some embodiments, are methods and compositions for the treatment of Charcot-Marie-Tooth disease.