Blended Learning Improves Science Education.

Blended learning is an emerging paradigm for science education but has not been rigorously assessed. We performed a randomized controlled trial of blended learning. We found that in-class problem solving improved exam performance, and video assignments increased attendance and satisfaction. This validates a new model for science communication and education.

A Stem Cell-Based Screening Platform Identifies Compounds that Desensitize Motor Neurons to Endoplasmic Reticulum Stress.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease selectively targeting motor neurons in the brain and spinal cord. The reasons for differential motor neuron susceptibility remain elusive. We developed a stem cell-based motor neuron assay to study cell-autonomous mechanisms causing motor neuron degeneration, with implications for ALS. A small-molecule screen identified cyclopiazonic acid (CPA) as a stressor to which stem cell-derived motor neurons were more sensitive than interneurons. CPA induced endoplasmic reticulum stress and the unfolded protein response. Furthermore, CPA resulted in an accelerated degeneration of motor neurons expressing human superoxide dismutase 1 (hSOD1) carrying the ALS-causing G93A mutation, compared to motor neurons expressing wild-type hSOD1. A secondary screen identified compounds that alleviated CPA-mediated motor neuron degeneration: three kinase inhibitors and tauroursodeoxycholic acid (TUDCA), a bile acid derivative. The neuroprotective effects of these compounds were validated in human stem cell-derived motor neurons carrying a mutated SOD1 allele (hSOD1A4V). Moreover, we found that the administration of TUDCA in an hSOD1G93A mouse model of ALS reduced muscle denervation. Jointly, these results provide insights into the mechanisms contributing to the preferential susceptibility of ALS motor neurons, and they demonstrate the utility of stem cell-derived motor neurons for the discovery of new neuroprotective compounds.

Incorporation of metabolically stable ketones into a small molecule probe to increase potency and water solubility.

Introducing a reactive carbonyl to a scaffold that does not otherwise have an electrophilic functionality to create a reversible covalent inhibitor is a potentially useful strategy for enhancing compound potency. However, aldehydes are metabolically unstable, which precludes the use of this strategy for compounds to be tested in animal models or in human clinical studies. To overcome this limitation, we designed ketone-based functionalities capable of forming reversible covalent adducts, while displaying high metabolic stability, and imparting improved water solubility to their pendant scaffold. We tested this strategy on the ferroptosis inducer and experimental therapeutic erastin, and observed substantial increases in compound potency. In particular, a new carbonyl erastin analog, termed IKE, displayed improved potency, solubility and metabolic stability, thus representing an ideal candidate for future in vivo cancer therapeutic applications.

Group Problem Solving in Class Improves Undergraduate Learning.

Developing methods for improving student learning is a long-standing goal in undergraduate science education. However, the extent to which students working on problems in small groups versus individually results in improved learning among undergraduate science students has not been evaluated in a randomized controlled trial. We have performed such a trial with 80 students in an undergraduate biochemistry class, in which students were randomized to either learning in groups or learning individually. All students participated in the same class, which consisted of a lecture with periodic breaks for students to solve problems using an audience response system. Students in the individual learning condition answered these questions on their own, but students in the group-based learning condition answered these questions in an assigned group of four students. At the end of the class, all students then took the same exam as individuals. The exam had two types of questions-recall questions, in which students had to simply recall information provided to them, and predict questions, in which students had to apply their new knowledge to a new context. Students in the individual and group-based learning conditions performed similarly well on recall questions. However, students who had been in the group-based learning condition performed significantly better as individuals on the predict questions. This suggests that learning in groups may be more effective than individual learning for undergraduate science students, particularly for applying their knowledge to new contexts; this highlights the potential need for pedagogical approaches in undergraduate science courses that incorporate learning in groups.