The atmospheric pressure that decreases with altitude affects lung physiology. However, these changes in physiology are not usually considered in ventilator design and testing. We argue that high altitude human populations require special attention to access the international supply of ventilators. Humans are naturally adapted to live at low altitude. Yet,~2% of the world's population permanently live at altitudes above 2500 meters 1. The majority of these populations live in areas that are either poor, such as Ethiopia, Ecuador and Bolivia, or highly controlled, such as Tibet 1. The small market size and low economic power of these regions have left them aside in the design of biomedical equipment, which usually does not consider their special environmental conditions and physiological adaptations. Worldwide, there is a shortage of many goods including intensive care unit (ICU) beds, facemasks, and ventilators due to the COVID-19 pandemic 2. This shortage has led to an international "stock market"-like process of bidding for these goods, in which many countries are left at an extreme disadvantage 3. Several international organizations, including the International Monetary Fund, the World Bank, and others, have been encouraged to provide loans to developing countries, but access to these goods is an issue that goes beyond money. Many countries have enacted export restrictions, and small orders are usually rejected to give preference to large purchases from powerful nations 3. This reduces the capability of less-affluent nations in both treating COVID-19 patients and preventing the further spread of the disease. Diverse pathological mechanisms in COVID-19 are under investigation, and respiratory symptoms predominate in the clinic. Physiologically, SARS-COV-2 cell entry is dependent on the cellular expression of ACE2 and TMPRSS2, and SARS-COV-2 likely binds to, and replicates in epithelial cells after entering the nasal cavity 4. SARS-CoV-2 then spreads from the nasal cavity into the lungs where it primarily infects ciliated epithelial cells that line the conducting airways. As ACE2 expression and receptors are also found in cells outside of the lungs 5 and COVID-19 patients have been reported to suffer from non-lung-related illness 6 , it is likely that SARS-CoV-2 infection is not limited to the nasal cavity and lungs. However, the majority of COVID-19 related deaths are caused by pulmonary illness. Therefore, the lungs are the primary focus of COVID-19 treatment efforts. Ventilators are essential to treat COVID-19, as they are the primary equipment needed to assist the breathing and gas exchange of critically ill patients. To this end, ICU ventilators have become an expensive commodity that most countries have fought to access. These fights have left
Cortical function critically depends on inhibitory/excitatory balance. Cortical inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into cortex, where their numbers are adjusted by programmed cell death. Previously, we showed that loss of clustered gamma protocadherins (Pcdhγ), but not of genes in the alpha or beta clusters, increased dramatically cIN BAX-dependent cell death in mice. Here we show that the sole deletion of the Pcdhγc4 isoform, but not of the other 21 isoforms in the Pcdhγ gene cluster, increased cIN cell death in mice during the normal period of programmed cell death. Viral expression of the Pcdhγc4 isoform rescued transplanted cINs lacking Pcdhγ from cell death. We conclude that Pcdhγ, specifically Pcdhγc4, plays a critical role in regulating the survival of cINs during their normal period of cell death. This demonstrates a novel specificity in the role of Pcdhγ isoforms in cortical development.
Project-based learning (PBL) has long been recognized as an effective way to teach complex biology concepts. However, not all institutions have the resources to facilitate effective project-based coursework for students. We have developed a framework for facilitating PBL using remote-controlled internet-connected microscopes. Through this approach, one lab facility can host an experiment allowing simultaneous interaction by many students worldwide. Experiments on this platform can be run on long timescales and with materials that are typically unavailable to high school classrooms. This allows students to perform novel research projects rather than just repeat standard classroom experiments. To investigate the impact of this program, we designed and ran six user studies with students worldwide. All experiments were executed in Santa Cruz and San Francisco, California, with observations and decisions made remotely by the students using their personal computers and cellphones. In surveys gathered after the experiments' conclusion, students reported increased excitement for science and a greater desire to pursue a career in STEM. This framework represents a novel, scalable, and effective PBL approach that has the potential to democratize biology and STEM education around the world.
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