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1.
Isr Med Assoc J ; 23(7): 401-407, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34251120

ABSTRACT

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic forced drastic changes in all layers of life. Social distancing and lockdown drove the educational system to uncharted territories at an accelerated pace, leaving educators little time to adjust. OBJECTIVES: To describe changes in teaching during the first phase of the COVID-19 pandemic. METHODS: We described the steps implemented at the Technion-Israel Institute of Technology Faculty of Medicine during the initial 4 months of the COVID-19 pandemic to preserve teaching and the academic ecosystem. RESULTS: Several established methodologies, such as the flipped classroom and active learning, demonstrated effectiveness. In addition, we used creative methods to teach clinical medicine during the ban on bedside teaching and modified community engagement activities to meet COVID-19 induced community needs. CONCLUSIONS: The challenges and the lessons learned from teaching during the COVID-19 pandemic prompted us to adjust our teaching methods and curriculum using multiple online teaching methods and promoting self-learning. It also provided invaluable insights on our pedagogy and the teaching of medicine in the future with emphasis on students and faculty being part of the changes and adjustments in curriculum and teaching methods. However, personal interactions are essential to medical school education, as are laboratories, group simulations, and bedside teaching.


Subject(s)
COVID-19 , Education, Distance , Education, Medical , Physical Distancing , COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control/methods , Education, Distance/methods , Education, Distance/organization & administration , Education, Medical/organization & administration , Education, Medical/trends , Humans , Needs Assessment , Organizational Innovation , Outcome Assessment, Health Care , SARS-CoV-2 , Schools, Medical , Teaching/trends
2.
mBio ; 11(5)2020 10 13.
Article in English | MEDLINE | ID: mdl-33051367

ABSTRACT

Arginine homeostasis in lysosomes is critical for the growth and metabolism of mammalian cells. Phagolysosomes of macrophages are the niche where the parasitic protozoan Leishmania resides and causes human leishmaniasis. During infection, parasites encounter arginine deprivation, which is monitored by a sensor on the parasite cell surface. The sensor promptly activates a mitogen-activated protein kinase 2 (MAPK2)-mediated arginine deprivation response (ADR) pathway, resulting in upregulating the abundance and activity of the Leishmania arginine transporter (AAP3). Significantly, the ADR is also activated during macrophage infection, implying that arginine levels within the host phagolysosome are limiting for growth. We hypothesize that ADR-mediated upregulation of AAP3 activity is necessary to withstand arginine starvation, suggesting that the ADR is essential for parasite intracellular development. CRISPR/Cas9-mediated disruption of the AAP3 locus yielded mutants that retain a basal level of arginine transport but lack the ability to respond to arginine starvation. While these mutants grow normally in culture, they were impaired in their ability to develop inside THP-1 macrophages and were ∼70 to 80% less infective in BALB/c mice. Hence, inside the host macrophage, Leishmania must overcome the arginine "hunger games" by upregulating the transport of arginine via the ADR. We show that the ability to monitor and respond to changes in host metabolite levels is essential for pathogenesis.IMPORTANCE In this study, we report that the ability of the human pathogen Leishmania to sense and monitor the lack of arginine in the phagolysosome of the host macrophage is essential for disease development. Phagolysosomes of macrophages are the niche where Leishmania resides and causes human leishmaniasis. During infection, the arginine concentration in the phagolysosome decreases as part of the host innate immune response. An arginine sensor on the Leishmania cell surface activates an arginine deprivation response pathway that upregulates the expression of a parasite arginine transporter (AAP3). Here, we use CRISPR/Cas9-mediated disruption of the AAP3 locus to show that this response enables Leishmania parasites to successfully compete with the host macrophage in the "hunger games" for arginine.


Subject(s)
Arginine/metabolism , Host-Parasite Interactions , Leishmania/growth & development , Leishmania/metabolism , Macrophages/parasitology , Animals , CRISPR-Cas Systems , Female , Leishmaniasis/metabolism , Leishmaniasis/parasitology , Lysosomes/parasitology , Macrophages/physiology , Membrane Transport Proteins/genetics , Mice , Mice, Inbred BALB C , Phagosomes/parasitology , Phagosomes/physiology
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