TDP-43 proteinopathies including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by aggregation and mislocalization of the nucleic acid-binding protein TDP-43 and subsequent neuronal dysfunction. This mouse model is an endogenous model of sporadic TDP-43 proteinopathy based on the principle that disease-associated TDP-43 acetylation at lysine 145 (K145) alters TDP-43 conformation, impairs RNA-binding capacity, and induces downstream mis-regulation of target genes. Expression of acetylation-mimic TDP-43K145Q results in stress-induced nuclear TDP-43 foci and loss of TDP-43 function. Mice harboring the TDP-43K145Q mutation recapitulated key hallmarks of FTLD, including progressive TDP-43 phosphorylation and insolubility, TDP-43 mis-localization, transcriptomic and splicing alterations, and cognitive dysfunction. This mouse is available from the Mutant Mouse Resource and Research Centers (MMRRC) Cat #: MMRRC 068119-UNC TDP43KQ (C57BL/6J-Tardbpem1Toco/Mmnc). https://www.mmrrc.org/catalog/sds.php?mmrrc_id=68119

BALB/c mice are commonly used for B cell hybridoma development because of their predictable B cell responses to various antigens. Our investigators have developed the tg801 transgenic mouse line, (BALB/c latency mice), as an alternative to the commonly used BALB/c or BALB/c/FcgR2b KO mouse that are often used for studying B cell immunobiology. These BALB/c latency mice express genes from the Kaposi sarcoma-associated herpesvirus that are associated with the long-term latency period of infection. These mice develop hyperglobulinemia, plasmacytosis and B cell hyperplasia. When these mice are exposed to viruses, such as Zika virus, they exhibit enhanced antibody response and infection clearance relative to wild type BALB/c mice. These mice are ideal for studying B cell immunobiology and production of monoclonal antibodies. If you are an academic institution or nonprofit organization interested in this research tool for non-commercial purposes, this mouse is available from Jackson Laboratories (Stock No. 032639) https://www.jax.org/strain/032639  

This mouse line, Ube3a-INSG, was generated by CRISPR/Cas9 knock-in of an IRES-Nanoluciferase-T2A-Sun1-sfGFP cassette downstream of the endogenous Ube3a stop codon, allowing dual allele-specific reporters to be expressed without modifying the UBE3A protein itself. UBE3A protein levels, brain/body weight, and behavior were unchanged from wild-type, despite a modest reduction in Ube3a transcript abundance. Maternal inheritance drove strong, allele-matched Nluc and Sun1-sfGFP expression, while paternal inheritance showed the expected neuronal silencing, with residual signal restricted to immature neurons in neurogenic zones. Compared with the existing Ube3a-YFP model, Sun1-sfGFP gave sharper, nuclear-restricted signal enabling single-cell and whole-brain quantification, and also enabled flow cytometry (FANS) capabilities. The Nluc enabled high-throughput screening and in vivo bioluminescence imaging. The line reliably reported both pharmacological unsilencing of paternal Ube3a and ASO-mediated knockdown of maternal Ube3a, supporting its use for therapeutic development in Angelman syndrome and Dup15q syndrome. If you are an academic institution or nonprofit organization interested in this research tool for noncommercial purposes, please contact the researcher directly to inquire about availability.

This virtual educational seminar series was created by clinicians from the UNC Adams School of Dentistry. The seminars are well suited to complement the coursework for anesthesia with nitrous oxide or benzodiazepines that are taught in Dental Hygiene, Dental Assisting, Dental Student, Medical Student, or Clinical Graduate Training programs. The individual seminars can be viewed alone or in combination. The seminar topics and the learning objectives for each are as follows: Seminar One: Depths of Sedation/ Anesthesia and the Central Nervous System How anesthesia evolved  Differentiate among the changes in the CNS with sedation/anesthesia drugs Seminar Two: Routes for Drug Administration, Pharmacology of Nitrous Oxide, and Benzodiazepines Compare sedation and general anesthesia by physiologic outcomes  Compare drug administration by access, control of dosage  Relate drug administration to elimination; alpha half-life (redistribution) and beta half-life (elimination)  Describe possible clinical outcomes associated with choice of drug administration Seminar Three: Pulmonary/Respiratory Physiology: A Review Discuss relationship between lung function and gas exchange at the alveolus  Discuss relationship between monitoring with pulse oximetry and arterial oxygen levels  Compare monitoring: pulse oximetry vs. capnography   Describe how sedative drugs might affect blood oxygen levels Seminar Four: Evaluation of patients for sedation/anesthesia Classify patients by health status Assess patients specifically as candidates for inhalation anesthetics Seminar Five: Anesthesia / Monitoring Equipment Sequence technical steps for administration of N2O  Select monitoring protocol for individual patient  Compare clinical uses of pulse oximetry and capnography Seminar Six: Administration of Nitrous Oxide Prepare patient for planned anesthesia: diet, caregiver responsibility  Decide levels of anesthesia based on the patient’s responses  Sequence steps if patient becomes agitated, disoriented, nauseated  Sequence steps if airway blocked  Implement discharge protocol after anesthesia Seminar Seven: Side Effects / Hazards to Staff of Nitrous Oxide Evaluate patients for high risk of nausea/vomiting  Evaluate patients for high risk of vitamin B12 deficiency  Explain hazards to staff  Understand mechanisms of reducing N2O in ambient air A preview of the seminar series can be found by downloading the preview document on the right. This preview contains links for viewing the Introduction and Seminar One videos, as well as a course outline, and learning objectives, references, and an evaluation for Seminar One. The seminar series is available for licensing for educational use. All the material needed for implementing the seminar series in a course is provided (seminar videos, course outline, learning objectives, and seminar evaluations). The seminar material, which contains links for streaming the seminar videos, will be available for download following acceptance of the terms of the license agreement and payment of the license fee.   Offerings Add Offering Name                                                                                                                 Price           Shipping    Currency Nitrous Oxide_Benzodiazepines Anesthesia - 21-0069                                    $500.00         $0.00           USD Demo Nitrous Oxide/Benzodiazepines Anesthesia - 21-0069                           $0.00             $0.00          USD

Macrophages are central drivers of chronic inflammation and provide robust cellular readouts for inflammation and immune activation. For applications ranging from small-molecule or pathway-based screening to mechanistic dissection of inflammatory processes, the zebrafish molecular sensor based on a precise GFP knock-in reporter at the immunoresponsive gene 1 (IRG1) locus (also known as the aconitate decarboxylase 1 (ACOD1) enables precise visualization and quantification of immune activation. In this zebrafish line, macrophage activation is reported by transcriptional induction of the endogenous IRG1, quantified by GFP expression levels. Notably, IRG1 is highly conserved across species, including humans and zebrafish, where it similarly marks activated macrophages during inflammation. This tool can be coupled with any type of fluorescence microscopy imaging or analysis, FACS sorting, histological analyses, transcriptomics, proteomics, and live in vivo dynamic imaging and experimentation. If you are an academic institution or nonprofit organization interested in this research tool for noncommercial purposes, please contact the researcher directly to inquire about availability

Abstract G protein-coupled receptors (GPCRs) are essential mediators of cellular signaling and are important targets of drug action, with over one third of prescribed medications targeting the non-olfactory class of these receptors.  GPCRs have a large diversity in their signal transduction cascades necessitating the use of numerous functional assays to identify agonists or inhibitors of these receptors. Assessment of GPCR-ß-arrestin interactions offers a way to universally assay a large variety of GPCRs. Transcriptional activation following arrestin translocation (TANGO) assays allow for effective high throughput screening of GPCR activity by assessing ß-arrestin-GPCR activity independent of coupling of ß-arrestin to a G-protein. This allows for interrogation of so-called “orphan” GPCRs for whom the receptor’s ligand and/or its coupled G-protein may not be known.   Researchers at UNC have developed open-source resource that provides the capacity to interrogate the druggable human GPCR-ome via a G-protein-independent ß-arrestin recruitment assay. This method is termed is termed PRESTO-TANGO (Parallel Receptor-ome Expression and Screening via Transcriptional Output - TANGO). Researchers have applied this unique platform to more than 120 nonorphan human GPCR targets, and demonstrate its utility for discovering new ligands for orphan human GPCRs.     These PRESTO-TANGO plasmids are available for academic institutions or nonprofit organizations interested in utilizing this research tool for noncommercial purposes, at Addgene (Roth Lab PRESTO-Tango GPCR Kit, Kit # 1000000068). https://www.addgene.org/kits/roth-gpcr-presto-tango/ Benefit ·       The PRESTO-Tango Kit can be used to measure receptor activation for more than 300 GPCRs via a modified Tango beta-arrestin recruitment assay. ·       Facilitates the rapid, efficacious, parallel, and simultaneous profiling of biologically active compounds across essentially the entire human druggable GPCR-ome. ·       PRESTO-TANGO is sensitive, easily executed, and amenable to both HTS and simultaneous parallel screening at many GPCRs. ·       Particularly suited for “first-pass” screening of compound libraries for identifying ligands of orphan receptors, since knowledge of the G protein partners of each GPCR is not required  

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes outbreaks of debilitating acute and chronic arthralgia in humans. There are currently no approved vaccines and few therapies against CHIKV. This antigen preparation is derived from a full length molecular clone based on a contemporary clinical CHIKV isolate and can be used to generate diagnostic reagents against CHIKV. Inactivated whole virion CHIKV antigen has the potential to screen patient or animal serum for the presence of CHIKV specific antibodies, act as an antigen for generating CHIKV specific monoclonal antibodies, or produce an inactivated vaccine against CHIKV. If you are an academic institution or nonprofit organization interested in this research tool for noncommercial purposes, please contact the researcher directly to inquire about availability.

Purified virus-like particles of norovirus that can be used to generate anti-norovirus hybridomas and antibodies. If you are an academic institution or nonprofit organization interested in this research tool for noncommercial purposes, please contact the researcher directly to inquire about availability.

Modeling and Measuring Shear Shock Waves in Traumatic Brain Injury A pioneering software platform capable of simulating and measuring shear shock waves in the brain using high frame-rate ultrasound imaging Background Traumatic brain injury (TBI) affects over 1 million people in the United States each year and has been linked to severe neurodegenerative diseases such as Chronic Traumatic Encephalopathy (CTE) and Alzheimer’s. While there is already software commercially available to analyze shock waves in the brain after a traumatic injury, none of these programs model the biomechanics of shear shock formation in the brain. Shear shock has recently been hypothesized to be a major contributing factor to TBI, however, conventional imaging techniques, such as magnetic resonance elastography (MRE) and optical imaging, are not sensitive enough to capture these waves due to their slow frame rates and shallow depths of penetration. High frame-rate (3000 images/second) ultrasound imaging is able to fully capture the nonlinearity of shear shock waves at the depth in which they occur in the brain. Currently, the challenges in measuring and modeling these shear shock waves by high frame-rate ultrasound imaging are two-fold. Firstly, the heterogenous acoustical properties of biological structure in the brain result in poor image quality. Secondly, the high attenuation of shear waves makes it difficult to decipher wave formation in such short time scales. This highlights the need for new software systems that can model and measure shear shock waves in the brain to better inform injury diagnosis and safety measures.  Technology Overview Researchers in the Department of Biomedical Engineering at the University of North Carolina at Chapel Hill have developed novel software that can simulate and measure shear shock waves in the brain using ultrasound imaging. The method combines high frame-rate ultrasound imaging techniques with motion tracking sequences to capture for the first time, critical parameters in brain injury biomechanics, acceleration and strain-rate. Using a phantom with properties that mimic the human brain, displacements smaller than 1 µm at physiologically relevant depths were measured after a simulated collision using adaptive and tracking algorithms. The researchers discovered that prior estimates of acceleration and strain-rate in the brain after traumatic injury are more than an order of magnitude higher when taking into account shear shock formation. This is due to the observed local accelerations and strain-rates deep inside the brain in areas as small as a grain of rice. By directly observing the actions of shear shock waves, this simulation and measurement software has the potential to advance technology in injury diagnosis and safety. Further Details: Espindola, D., Lee, S., Pinton, G. (2017). Shear shock waves are observed in the brain. Phys. Rev. Applied 8, 044024. https://doi.org/10.1103/PhysRevApplied.8.044024 Tripathi, B. B., Chandrasekaran, S., Pinton, G. (2012). Super-resolved shear shock focusing in the human head. Brain Multiphysics, 2, 100033. https://doi.org/10.1016/j.brain.2021.100033 Benefits First-in-class software platform to simulate and measure shear shock waves in the brain Compatible with high frame-rate ultrasound imaging. High accuracy compared to prior plane-wave methods. Applications The simulation application of this software can be used for research and development purposes to better inform how to identify and treat brain injuries. The measurement application of this software could be applied to contact sports, where sensors installed in a helmet are used to monitor players in real-time during practices or games, to decide when a player needs to rest or seek medical attention after an impact. Other potential markets for this technology are the automotive crash-testing industry, helmet manufacturing, construction, and fall assessment.

Wild-type HM175 strain human hepatitis A virus has been passed multiple times in mice with defective innate immunity, resulting in a viral inoculum that reliably establishes acute hepatitis A infection in Ifnar1 knockout mice.