Chatbot responses suggest that hypothetical biology questions are harder than realistic ones.

The biology education literature includes compelling assertions that unfamiliar problems are especially useful for revealing students' true understanding of biology. However, there is only limited evidence that such novel problems have different cognitive requirements than more familiar problems. Here, we sought additional evidence by using chatbots based on large language models as models of biology students. For human physiology and cell biology, we developed sets of realistic and hypothetical problems matched to the same lesson learning objectives (LLOs). Problems were considered hypothetical if (i) known biological entities (molecules and organs) were given atypical or counterfactual properties (redefinition) or (ii) fictitious biological entities were introduced (invention). Several chatbots scored significantly worse on hypothetical problems than on realistic problems, with scores declining by an average of 13%. Among hypothetical questions, redefinition questions appeared especially difficult, with many chatbots scoring as if guessing randomly. These results suggest that, for a given LLO, hypothetical problems may have different cognitive demands than realistic problems and may more accurately reveal students' ability to apply biology core concepts to diverse contexts. The Test Question Templates (TQT) framework, which explicitly connects LLOs with examples of assessment questions, can help educators generate problems that are challenging (due to their novelty), yet fair (due to their alignment with pre-specified LLOs). Finally, ChatGPT's rapid improvement toward expert-level answers suggests that future educators cannot reasonably expect to ignore or outwit chatbots but must do what we can to make assessments fair and equitable.

Making the case for prophylactic use of betaine to promote brain health in young (15-24 year old) athletes at risk for concussion.

Betaine supplementation in the context of human nutrition, athletic performance, and clinical therapy demonstrate that the osmolyte and methyl donor, betaine, is cytoprotective and beneficial to human health. These studies also demonstrate that betaine supplementation in healthy humans is straight-forward with no reported adverse effects. Here, we explore betaine uptake in the central nervous system (CNS) and contribute to evidence that betaine may be uniquely protective to the brain. We specifically describe the therapeutic potential of betaine and explore the potential implications of betaine on inhibition mediated by GABA and glycine neurotransmission. The influence of betaine on neurophysiology complement betaine's role as an osmolyte and metabolite and is consistent with clinical evidence of betaine-mediated improvements to cognitive function (reported in elderly populations) and its anti-convulsant properties. Betaine's therapeutic potential in neurological disorders including epilepsy and neurodegenerative diseases combined with benefits of betaine supplementation on athletic performance support the unique application of betaine as a prophylaxis to concussion. As an example, we identify young athletes (15-24 years old), especially females, for prophylactic betaine supplementation to promote brain health and resilience in a cohort at high risk for concussion and for developing Alzheimer's disease.

Betaine in the Brain: Characterization of Betaine Uptake, its Influence on Other Osmolytes and its Potential Role in Neuroprotection from Osmotic Stress.

Betaine (N-trimethylglycine), a common osmolyte, has received attention because of the number of clinical reports associating betaine supplementation with improved cognition, neuroprotection and exercise physiology. However, tissue analyses report little accumulation of betaine in brain tissue despite the presence of betaine/GABA transporters (BGT1) at the blood brain barrier and in nervous tissue, calling into question whether betaine influences neuronal function directly or indirectly. Therefore, the focus of this study was to determine what capacity nervous tissue has to accumulate betaine, specifically in the hippocampus, a region of the brain associated with learning and memory and one that is particularly susceptible to damage (e.g., seizure activity). Here we report that hippocampal slices actively accumulate betaine in a time, dose and osmolality dependent manner, resulting in peak intracellular concentrations four times extracellular concentrations within 8 h. Our data also indicate that betaine uptake differentially influences the accumulation of other osmolytes. Under isosmotic conditions, betaine uptake minimally impacted some osmolytes (e.g., glycerylphosphorylcholine and glutamate) while significantly reducing others (taurine, creatine, and myo-inositol). Under osmotic stress (hyperosmotic) conditions, we observed dramatic changes in osmolytes like glycine and glutamine-key players in inhibitory neurotransmission-and little change in osmolytes such as taurine, creatine and myo-inositol when betaine was available. These data suggest that betaine may influence pathways of inhibitory neurotransmitter production/recycling in addition to serving as an osmolyte and metabolic intermediate. In sum, our data provide detailed characterization of betaine uptake in the hippocampus that implicates betaine in the modulation of hippocampal neurophysiology and neuroprotection.

Inhibition and interneuron distribution in the dentate gyrus of p35 knockout mice.

The p35 knockout (p35-/-) mouse is an animal model of temporal lobe epilepsy that recapitulates key neuroanatomic abnormalities-granule cell dispersion and mossy fiber sprouting-observed in the hippocampal formation of humans, as well as spontaneous seizure activity. It is a useful model in which to study the relationship between the abnormal neuronal structure and seizure activity to further our understanding of cortical dysplasia in epileptogenesis. Our previous work using this mouse model characterized the anatomic features of the dentate granule cells and the functional implications of these abnormalities on increased recurrent excitation. These data also suggested that there might be compromised inhibition in this animal model. We pursued this possibility, focusing our investigation on inhibitory circuitry. In preliminary investigations using neuroanatomic tools (immunocytochemistry, camera lucida reconstructions of individually labeled interneurons, and electron microscopy) combined with intracellular electrophysiology, we observed no significant reduction in the number of symmetric versus asymmetric synaptic contacts on dentate granule cell somata, and no statistically significant changes in evoked early or late inhibition. Although there were some abnormalities in the morphology/distribution of inhibitory interneurons (as well as a larger population of dentate granule cells) of the dentate gyrus, overall inhibition in the p35 knockout mouse appeared to be largely intact.