Developing Hypoimmunogenic Human iPSC-Derived Oligodendrocyte Progenitor Cells as an Off-The-Shelf Cell Therapy for Myelin Disorders.

Demyelinating disorders are among the most common and debilitating diseases in neurology. Canavan disease (CD) is a lethal demyelinating disease caused by mutation of the aspartoacylase (ASPA) gene, which leads to the accumulation of its substrate N-acetyl-l-aspartate (NAA), and consequently demyelination and vacuolation in the brain. In this study, hypoimmunogenic human induced pluripotent stem cell (iPSC)-derived oligodendrocyte progenitor cells (OPC) are developed from a healthy donor as an "off-the-shelf" cell therapy. Hypoimmunogenic iPSCs are generated through CRISPR/Cas9 editing of the human leukocyte antigen (HLA) molecules in healthy donor-derived iPSCs and differentiated into OPCs. The OPCs are engrafted into the brains of CD (nur7) mice and exhibit widespread distribution in the brain. The engrafted OPCs mature into oligodendrocytes that express the endogenous wildtype ASPA gene. Consequently, the transplanted mice exhibit elevated human ASPA expression and enzymatic activity and reduced NAA level in the brain. The transplanted OPCs are able to rescue major pathological features of CD, including defective myelination, extensive vacuolation, and motor function deficits. Moreover, the hypoimmunogenic OPCs exhibit low immunogenicity both in vitro and in vivo. The hypoimmunogenic OPCs can be used as "off-the-shelf" universal donor cells to treat various CD patients and many other demyelinating disorders, especially autoimmune demyelinating diseases, such as multiple sclerosis.

Systemic racism: Pharmacists' role and responsibility.

Systemic racism is a public health emergency and disproportionately impacts communities of color, specifically black Americans. Pharmacists took an oath to protect the welfare of humanity and protect our patients. As such, to practice truly patient-centered care, pharmacists must recognize racism as a root cause of social determinants of health and use their privilege to educate themselves and their colleagues around dismantling structural racism.

Development of the User Requirements for the Canadian WildFireSat Satellite Mission.

In 2019 the Canadian Space Agency initiated development of a dedicated wildfire monitoring satellite (WildFireSat) mission. The intent of this mission is to support operational wildfire management, smoke and air quality forecasting, and wildfire carbon emissions reporting. In order to deliver the mission objectives, it was necessary to identify the technical and operational challenges which have prevented broad exploitation of Earth Observation (EO) in Canadian wildfire management and to address these challenges in the mission design. In this study we emphasize the first objective by documenting the results of wildfire management end-user engagement activities which were used to identify the key Fire Management Functionalities (FMFs) required for an Earth Observation wildfire monitoring system. These FMFs are then used to define the User Requirements for the Canadian Wildland Fire Monitoring System (CWFMS) which are refined here for the WildFireSat mission. The User Requirements are divided into Observational, Measurement, and Precision requirements and form the foundation for the design of the WildFireSat mission (currently in Phase-A, summer 2020).

Systemic Racism: Pharmacists' Role and Responsibility.

Systemic racism is a public health emergency and disproportionately impacts communities of color, specifically Black Americans. Pharmacists took an oath to protect the welfare of humanity and protect our patients. As such, to practice truly patient-centered care, pharmacists must recognize racism as a root cause of social determinants of health and use their privilege to educate themselves and their colleagues around dismantling structural racism.

Mycorrhiza-Induced Resistance in Potato Involves Priming of Defense Responses Against Cabbage Looper (Noctuidae: Lepidoptera).

Most plants form mutualistic associations with arbuscular mycorrhizal (AM) fungi that are ubiquitous in soils. Through this symbiosis, plants can withstand abiotic and biotic stresses. The underlying molecular mechanisms involved in mediating mycorrhiza-induced resistance against insects needs further research, and this is particularly true for potato (Solanum tuberosum L. (Solanales: Solanaceae)), which is the fourth most important crop worldwide. In this study, the tripartite interaction between potato, the AM fungus Rhizophagus irregularis (Glomerales: Glomeraceae), and cabbage looper (Trichoplusia ni Hübner) (Lepidoptera: Noctuidae) was examined to determine whether potato exhibits mycorrhiza-induced resistance against this insect. Plant growth, insect fitness, AM fungal colonization of roots, and transcript levels of defense-related genes were measured in shoots and roots after 5 and 8 d of herbivory on mycorrhizal and nonmycorrhizal plants. AM fungal colonization of roots did not have an effect on potato growth, but root colonization levels increased by herbivory. Larval weight gain was reduced after 8 d of feeding on mycorrhizal plants compared with nonmycorrhizal plants. Systemic upregulation of Allene Oxide Synthase 1 (AOS1), 12-Oxo-Phytodienoate Reductase 3 (OPR3) (jasmonic acid pathway), Protease Inhibitor Type I (PI-I) (anti-herbivore defense), and Phenylalanine Ammonia Lyase (PAL) transcripts (phenylpropanoid pathway) was found during the tripartite interaction. Together, these findings suggest that potato may exhibit mycorrhiza-induced resistance to cabbage looper by priming anti-herbivore defenses aboveground. This study illustrates how mycorrhizal potato responds to herbivory by a generalist-chewing insect and serves as the basis for future studies involving tripartite interactions with other pests.

Disruption of INOS, a Gene Encoding myo-Inositol Phosphate Synthase, Causes Male Sterility in Drosophila melanogaster.

Inositol is a precursor for the phospholipid membrane component phosphatidylinositol (PI), involved in signal transduction pathways, endoplasmic reticulum stress, and osmoregulation. Alterations of inositol metabolism have been implicated in human reproductive issues, the therapeutic effects of drugs used to treat epilepsy and bipolar disorder, spinal cord defects, and diseases including diabetes and Alzheimer's. The sole known inositol synthetic enzyme is myo-inositol synthase (MIPS), and the homolog in Drosophilia melanogaster is encoded by the Inos gene. Three identical deletion strains (inosΔDF /CyO) were constructed, confirmed by PCR and sequencing, and homozygotes (inosΔDF /inosΔDF ) were shown to lack the transcript encoding the MIPS enzyme. Without inositol, homozygous inosΔDF deletion fertilized eggs develop only to the first-instar larval stage. When transferred as pupae to food without inositol, however, inosΔDF homozygotes die significantly sooner than wild-type flies. Even with dietary inositol the homozygous inosΔDF males are sterile. An inos allele, with a P-element inserted into the first intron, fails to complement this male sterile phenotype. An additional copy of the Inos gene inserted into another chromosome rescues all the phenotypes. These genetic and phenotypic analyses establish D. melanogaster as an excellent model organism in which to examine the role of inositol synthesis in development and reproduction.