This article proposes a brief overview of the history of automated sign language interpretation and identifies trends. The history suggests that human interpreters will be the gold standard for the ...foreseeable future.
Social distancing and online education demands have had an immediate impact on the delivery of biochemistry curriculum to meet the student, faculty, and institutional needs. During the Fall 2020 and ...2021 semesters, one model of hybrid online flipped learning was applied to an introduction to biochemistry lecture course. Normal classroom lectures were turned into voice‐over PowerPoint videos. Students were expected to have watched the lecture videos before coming to class. After gaining experience with the flipped classroom and social distancing model, student learning shifted from passive to active engagement by applying their knowledge during in person classroom activities including question response, board problems, 3D molecular modeling kits, and think pair share exercises. Students self‐reported that they liked the flexibility of watching the lecture videos before class and the ability to rewind and pause the videos. Students also commented in student evaluations that the in‐class activities and practice problems were helpful in applying their understanding. Compared to the previous six years, the withdrawal rate heavily decreased in Fall 2020 using this flipped learning style decreasing from a usual 30% to 10%. In addition, no students earned a D or an F for Fall 2020 and Fall 2021 in the introduction to biochemistry course compared to previous years where 10% of the class normally would be in this grade range. This preliminary assessment of the Fall 2020/2021 grade distributions and withdrawal number supports that flipped learning and focus on application of the lecture material in class can be a powerful combination for improved understanding. This is especially relevant to the threshold concepts identified by the ASBMB. Out of class recorded lectures can introduce topics and in class time can be spent focusing on the more difficult concepts and understanding in biochemistry.
Type A γ-aminobutyric acid (GABAA) receptors are pentameric ligand-gated ion channels and the main drivers of fast inhibitory neurotransmission in the vertebrate nervous system1,2. Their dysfunction ...is implicated in a range of neurological disorders, including depression, epilepsy and schizophrenia3,4. Among the numerous assemblies that are theoretically possible, the most prevalent in the brain are the α1β2/3γ2 GABAA receptors5. The β3 subunit has an important role in maintaining inhibitory tone, and the expression of this subunit alone is sufficient to rescue inhibitory synaptic transmission in β1-β3 triple knockout neurons6. So far, efforts to generate accurate structural models for heteromeric GABAA receptors have been hampered by the use of engineered receptors and the presence of detergents7-9. Notably, some recent cryo-electron microscopy reconstructions have reported 'collapsed' conformations8,9; however, these disagree with the structure of the prototypical pentameric ligand-gated ion channel the Torpedo nicotinic acetylcholine receptor10,11, the large body of structural work on homologous homopentameric receptor variants12 and the logic of an ion-channel architecture. Here we present a high-resolution cryo-electron microscopy structure of the full-length human α1β3γ2L-a major synaptic GABAA receptor isoform-that is functionally reconstituted in lipid nanodiscs. The receptor is bound to a positive allosteric modulator 'megabody' and is in a desensitized conformation. Each GABAA receptor pentamer contains two phosphatidylinositol-4,5-bisphosphate molecules, the head groups of which occupy positively charged pockets in the intracellular juxtamembrane regions of α1 subunits. Beyond this level, the intracellular M3-M4 loops are largely disordered, possibly because interacting post-synaptic proteins are not present. This structure illustrates the molecular principles of heteromeric GABAA receptor organization and provides a reference framework for future mechanistic investigations of GABAergic signalling and pharmacology.Type A γ-aminobutyric acid (GABAA) receptors are pentameric ligand-gated ion channels and the main drivers of fast inhibitory neurotransmission in the vertebrate nervous system1,2. Their dysfunction is implicated in a range of neurological disorders, including depression, epilepsy and schizophrenia3,4. Among the numerous assemblies that are theoretically possible, the most prevalent in the brain are the α1β2/3γ2 GABAA receptors5. The β3 subunit has an important role in maintaining inhibitory tone, and the expression of this subunit alone is sufficient to rescue inhibitory synaptic transmission in β1-β3 triple knockout neurons6. So far, efforts to generate accurate structural models for heteromeric GABAA receptors have been hampered by the use of engineered receptors and the presence of detergents7-9. Notably, some recent cryo-electron microscopy reconstructions have reported 'collapsed' conformations8,9; however, these disagree with the structure of the prototypical pentameric ligand-gated ion channel the Torpedo nicotinic acetylcholine receptor10,11, the large body of structural work on homologous homopentameric receptor variants12 and the logic of an ion-channel architecture. Here we present a high-resolution cryo-electron microscopy structure of the full-length human α1β3γ2L-a major synaptic GABAA receptor isoform-that is functionally reconstituted in lipid nanodiscs. The receptor is bound to a positive allosteric modulator 'megabody' and is in a desensitized conformation. Each GABAA receptor pentamer contains two phosphatidylinositol-4,5-bisphosphate molecules, the head groups of which occupy positively charged pockets in the intracellular juxtamembrane regions of α1 subunits. Beyond this level, the intracellular M3-M4 loops are largely disordered, possibly because interacting post-synaptic proteins are not present. This structure illustrates the molecular principles of heteromeric GABAA receptor organization and provides a reference framework for future mechanistic investigations of GABAergic signalling and pharmacology.
Albumin has a number of important physiologic functions, which include maintaining oncotic pressure, transporting various agents (fatty acids, bile acids, cholesterol, metal ions, and drugs), ...scavenging free oxygen radicals, acting as an antioxidant, and exerting an antiplatelet effect. Hypoalbuminemia in adults, defined by an intravascular albumin level of <3.5 g/dL, is associated with poor postoperative outcomes in patients undergoing surgical intervention. Although the relationship of hypoalbuminemia and poor surgical outcome has been known for many years, the pathophysiology behind the relationship is unclear. Three theoretical constructs might explain this relationship. First, albumin might serve as a nutritional marker, such that hypoalbuminemia represents poor nutritional status in patients who go on to experience poor postoperative outcomes. Second, albumin has its own pharmacologic characteristics as an antioxidant or transporter, and therefore, the lack of albumin might result in a deficiency of those functions, resulting in poor postoperative outcomes. Or third, albumin is known to be a negative acute phase protein, and as such hypoalbuminemia might represent an increased inflammatory status of the patient, potentially leading to poor outcomes. A thorough review of the literature reveals the fallacy of these arguments and fails to show a direct cause and effect between low albumin levels per se and adverse outcomes. Interventions designed solely to correct preoperative hypoalbuminemia, in particular intravenous albumin infusion, do little to change the patient's course of hospitalization. While surgeons may use albumin levels on admission for their prognostic value, they should avoid therapeutic strategies whose main endpoint is correction of this abnormality.
Type-A γ-aminobutyric (GABA
) receptors are ligand-gated chloride channels with a very rich pharmacology. Some of their modulators, including benzodiazepines and general anaesthetics, are among the ...most successful drugs in clinical use and are common substances of abuse. Without reliable structural data, the mechanistic basis for the pharmacological modulation of GABA
receptors remains largely unknown. Here we report several high-resolution cryo-electron microscopy structures in which the full-length human α1β3γ2L GABA
receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA (γ-aminobutyric acid), and the classical benzodiazepines alprazolam and diazepam. We describe the binding modes and mechanistic effects of these ligands, the closed and desensitized states of the GABA
receptor gating cycle, and the basis for allosteric coupling between the extracellular, agonist-binding region and the transmembrane, pore-forming region. This work provides a structural framework in which to integrate previous physiology and pharmacology research and a rational basis for the development of GABA
receptor modulators.
Type-A γ-aminobutyric receptors (GABA
A
Rs) are ligand-gated chloride channels with a very rich pharmacology. Some of their modulators, including benzodiazepines and general anaesthetics, are among ...the most successful drugs in clinical use and common substances of abuse. Without reliable structural data, the mechanistic basis for pharmacological modulation of GABA
A
Rs remains largely unknown. Here we report high-resolution cryoEM structures of the full-length human α1β3γ2L GABA
A
R in lipid nanodiscs, bound to the channel blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA and the classical benzodiazepines alprazolam (Xanax) and diazepam (Valium), respectively. We describe the binding modes and mechanistic impacts of these ligands, the closed and desensitised states of the GABA
A
R gating cycle, and the basis for allosteric coupling between the extracellular, agonist-binding, and the transmembrane, pore-forming, regions. This work provides a structural framework to integrate decades of physiology and pharmacology research and a rational basis for development of novel GABA
A
R modulators.
We demonstrate a new method for the generation of beams with rapidly tunable orbital angular momentum (OAM). This method is based on using a single-axis scanning galvanometer mirror to add a phase ...tilt on an elliptical Gaussian beam that is then wrapped to a ring using optics that perform a log-polar transformation. This system can switch between modes in the kHz range and use relatively high power with high efficiency. This scanning mirror HOBBIT system was applied to a light/matter interaction application using the photoacoustic effect, with a 10 dB enhancement of the generated acoustics at a glass/water interface.
In the United States, cancer is the second leading cause of death after heart disease and hundreds of thousands of people pass away each year due to this deadly disease. Many treatments for cancer ...are nonselective and do not provide long‐lasting immunity in case of recurrence. Gold nanoparticles can provide a more targeted radiation therapy and better effectiveness through heat generation and formation of reactive oxygen species via hydrolysis reaction which can cause DNA damage in the tumor. Unfortunately, gold particles have low photothermal transduction efficiency and must be aggregated to improve performance. To achieve this, positively charged gold nanoparticles were aggregated with MDA MB 231 cancer cell DNA to increase gold nanoparticle aggregation, to elicit higher photothermal efficiency, and to stimulate an immune response. In vitro analysis demonstrated DNA size and concentration dependent gold nanoparticle aggregation, which varied little in the pH range of 5.5 to 8.6. Furthermore, these aggregates elicited an immune response via delivery of DNA for direct transfection of antigen presenting cells. Tumor necrosis factor alpha released from mouse RAW macrophages increased in the presence of the cancer cell DNA aggregated gold particles. This work suggests that the promise of combination therapy using cancer cell DNA not only can improve photothermal therapy of gold nanoparticles, but also can elicit an immune response in cancer treatment.
Beams with fast and continuously-tunable orbital angular momentum (OAM) have potential applications in classical and quantum optical communications, sensing, and in the study of beam propagation ...through turbulence. An acousto-optical deflector (AOD) is a sophisticated, well-studied device that continuously and rapidly tunes the deflection angle of an output beam. The log-polar HOBBIT setup can generate beams with OAM by wrapping elliptically shaped Gaussian beams with linear phase tilt to a ring. By combining the linear tilted output from the AOD with the OAM generation capabilities of the HOBBIT system, the generated OAM modes become continuously tunable at high speeds measured on the order of 400 kHz.
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