Balancing Act: an Interdisciplinary Exploration of Trade-offs in Reproducing Females.

Trade-offs resulting from the high demand of offspring production are a central focus of many subdisciplines within the field of biology. Yet, despite the historical and current interest on this topic, large gaps in our understanding of whole-organism trade-offs that occur in reproducing individuals remain, particularly as it relates to the nuances associated with female reproduction. This volume of Integrative and Comparative Biology (ICB) contains a series of papers that focus on reviewing trade-offs from the female-centered perspective of biology (i.e., a perspective that places female reproductive biology at the center of the topic being investigated or discussed). These papers represent some of the work showcased during our symposium held at the 2024 meeting of the Society for Integrative and Comparative Biology (SICB) in Seattle, Washington. In this roundtable discussion, we use a question-and-answer format to capture the diverse perspectives and voices involved in our symposium. We hope that the dialogue featured in this discussion will be used to motivate researchers interested in understanding trade-offs in reproducing females and provide guidance on future research endeavors.

Let's talk about sex: instructor views and hesitancies related to sex and gender in the biology classroom.

There is much current debate in the US regarding how sex and gender are approached in science and medical classrooms. There does not seem to be sufficient consensus around why it must be taught and how it should be implemented. State-enacted restrictions to both education and healthcare in recent years demonstrate the relevance and importance of sex and gender in the college classroom, not only including but especially in the biology classroom. Given the areas comprising the Society for Integrative and Comparative Biology (SICB), these topics of sex and gender in biology instruction are incredibly salient to our members. Thus, this survey aimed to determine instructors' views of and experiences with sex-diverse gender-inclusive biology. College-level biology instructors who are members of SICB were surveyed about their views of science, views of sex and gender, teaching philosophy, and their experiences with inclusive teaching and with sex-diverse gender-inclusive teaching. The resulting data lead us to implore academic biology to provide more sex-diverse and gender-inclusive teaching tools and resources to educators, while minimizing potential fear of retaliation and backlash to instructors who utilize these teaching methods.

Incorporating Sex-Diverse and Gender-Inclusive Perspectives in Higher Education Biology Courses.

Inclusive teaching is teaching in a way that reaches all students in the classroom; this is beneficial for everyone and particularly for those with minoritized identities. Instructors play a critical role in scaffolding how students are exposed to and learn science content in the classroom. In this manuscript we discuss how biology instructors can make their classrooms more inclusive with regard to sex and gender diversity content. Many topics in biology are based on androcentric, heteronormative, and oppressive framing, even though those lenses are more reflective of our own history and culture than they are of the diversity we see in nature. Here, we summarize information presented in the SICB 2024 workshop titled "Incorporating sex diversity and gender inclusivity in biology undergraduate classrooms" and provide instructors with a) rationale for why inclusive teaching matters, b) guidance on how to challenge unscientific views and make their curricula more sex-diverse and gender inclusive, and c) practical and easy-to-implement strategies for discussing "contentious" topics in the classroom. Incorporation of this material will be beneficial for students, for science and medicine, and for accurately representing the diversity found across the tree of life.

Impact of Long-Term Dietary High Fat and Eicosapentaenoic Acid on Behavior and Hypothalamic-Pituitary-Adrenal Axis Activity in Amyloidogenic APPswe/PSEN1dE9 Mice.

INTRODUCTION: Alzheimer's disease (AD) alters neurocognitive and emotional function and causes dysregulation of multiple homeostatic processes. The leading AD framework pins amyloid beta plaques and tau tangles as primary drivers of dysfunction. However, many additional variables, including diet, stress, sex, age, and pain tolerance, interact in ways that are not fully understood to impact the onset and progression of AD pathophysiology. We asked: (1) does high-fat diet, compared to low-fat diet, exacerbate AD pathophysiology and behavioral decline? And, (2) can supplementation with eicosapentaenoic (EPA)-enriched fish oil prevent high-fat-diet-induced changes? METHODS: Male and female APPswePSdE9 mice, and their non-transgenic littermates, were randomly assigned to a diet condition (low-fat, high-fat, high-fat with EPA) and followed from 2 to 10 months of age. We assessed baseline corticosterone concentration during aging, pain tolerance, cognitive function, stress coping, and corticosterone response to a stressor. RESULTS: Transgenic mice were consistently more active than non-transgenic mice but did not perform worse on either cognitive task, even though we recently reported that these same transgenic mice exhibited metabolic changes and had increased amyloid beta. Mice fed high-fat diet had higher baseline and post-stressor corticosterone, but diet did not impact cognition or pain tolerance. Sex had the biggest influence, as female mice were consistently more active and had higher corticosterone than males. CONCLUSION: Overall, diet, genotype, and sex did not have consistent impacts on outcomes. We found little support for predicted interactions and correlations, suggesting diet impacts metabolic function and amyloid beta levels, but these outcomes do not translate to changes in behaviors measured here.

COVID-19 as a chronic stressor and the importance of individual identity: A data-driven look at academic productivity during the pandemic.

The COVID-19 pandemic impacted personal and professional life. For academics, research, teaching, and service tasks were upended and we all had to navigate the altered landscape. However, some individuals faced a disproportionate burden, particularly academics with minoritized identities or those who were early career, were caregivers, or had intersecting identities. As comparative endocrinologists, we determine how aspects of individual and species-level variation influence response to, recovery from, and resilience in the face of stressors. Here, we flip that framework and apply an integrative biological lens to the impact of the COVID-19 chronic stressor on our endocrine community. We address how the pandemic altered impact factors of academia (e.g., scholarly products) and relatedly, how factors of impact (e.g., sex, gender, race, career stage, caregiver status, etc.) altered the way in which individuals could respond. We predict the pandemic will have long-term impacts on the population dynamics, composition, and landscape of our academic ecosystem. Impact factors of research, namely journal submissions, were altered by COVID-19, and women authors saw a big dip. We discuss this broadly and then report General and Comparative Endocrinology (GCE) manuscript submission and acceptance status by gender and geographic region from 2019 to 2023. We also summarize how the pandemic impacted individuals with different axes of identity, how academic institutions have responded, compile proposed solutions, and conclude with a discussion on what we can all do to (re)build the academy in an equitable way. At GCE, the first author positions had gender parity, but men outnumbered women at the corresponding author position. Region of manuscript origin mattered for submission and acceptance rates, and women authors from Asia and the Middle East were the most heavily impacted by the pandemic. The number of manuscripts submitted dropped after year 1 of the pandemic and has not yet recovered. Thus, COVID-19 was a chronic stressor for the GCE community.

Acute stressors do not impair short-term memory or attention in an aged mouse model of amyloidosis.

Memory impairment in Alzheimer's disease patients is thought to be associated with the accumulation of amyloid-beta peptides and tau proteins. However, inconsistent reports of cognitive deficits in pre-clinical studies have raised questions about the link between amyloid-beta and cognitive decline. One possible explanation may be that studies reporting memory deficits often involve behavioral assessments that entail a high stress component. In contrast, in tasks without a high stress component transgenic mice do not consistently show declines in memory. The glucocorticoid cascade hypothesis of aging and the vicious cycle of stress framework suggest that stress exacerbates dementia progression by initiating a cycle of hypothalamic-pituitary-adrenal axis activation and subsequent brain deterioration. Using the APPswe/PS1dE9 mouse model of amyloidosis, we assessed whether stressor exposure prior to testing differentially impaired cognitive performance of aged male and female mice. As part of a larger study, mice performed a delayed match-to-position (DMTP) or a 3-choice serial-reaction time (3CSRT) task. Unexpectedly, these mice did not exhibit cognitive declines during aging. Therefore, at 73 and 74 weeks of age, we exposed mice to a predator odor or forced swim stressor prior to testing to determine if stress revealed cognitive deficits. We predicted stressor exposure would decrease performance accuracy more robustly in transgenic vs. non-transgenic mice. Acute stressor exposure increased accuracy in the DMTP task, but not in the 3CSRT task. Our data suggest that acute stressor exposure prior to testing does not impair cognitive performance in APPswe/PS1dE9 mice.

Longitudinal assessment of cognitive function in the APPswe/PS1dE9 mouse model of Alzheimer's-related beta-amyloidosis.

Preclinical models of Alzheimer's disease (AD)-related cognitive decline can be useful for developing therapeutics. The current study longitudinally assessed short-term memory, using a delayed matching-to-position (DMTP) task, and attention, using a 3-choice serial reaction time (3CSRT) task, from approximately 18 weeks of age through death or 72 weeks of age in APPswe/PS1dE9 mice, a widely used mouse model of AD-related amyloidosis. Both transgenic (Tg) and non-Tg mice exhibited improvements in DMTP accuracy over time. Breaks in testing reduced DMTP accuracy but accuracy values quickly recovered in both Tg and non-Tg mice. Both Tg and non-Tg mice exhibited high accuracy in the 3CSRT task with breaks in testing briefly reducing accuracy values equivalently in the 2 genotypes. The current results raise the possibility that deficits in Tg APPswe/PS1dE9 mice involve impairments in learning rather than declines in established performances. A better understanding of the factors that determine whether deficits develop will be useful for designing evaluations of potential pharmacotherapeutics and may reveal interventions for clinical application.

Do categorically distinct stressors alter the attention to visual food cues?

Stressor exposure affects food intake as well as the preference for high or low palatability foods, but little is known about how stressor types impact the visual attention to food images. We used eye tracking methodology in humans to determine if activation of the hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system is associated with changes in attention to food images as determined by measuring changes in oculomotor activity. Specifically, we tested two questions: 1) Do categorically distinct stressors alter aspects of visual attention to food images as determined by oculomotor activity (i.e., saccade latency, gaze duration, and saccade bouts)? 2) Do categorically distinct stressors differentially affect visual attention to food images of high or low palatability? A total of sixty participants were randomly divided into one of three test groups: controls, an anticipatory stressor group, or a reactive stressor group. We measured salivary cortisol and salivary alpha-amylase (sAA) before and after stressor exposure to confirm activation of the HPA axis and sympathetic nervous system, respectively. Following stressor exposure participants performed an eye-tracking test using a standardized food picture database (Food-pics). We analyzed saccade latency, gaze duration, and saccade bouts in balanced pairs of food and non-food images. Salivary cortisol was elevated by both stressors, although the elevation in salivary cortisol to the reactive stressor was driven by women only. sAA was elevated only by the anticipatory stressor. There were main effects of image type for all three eye-tracking variables, with initial saccades of shorter latency to food images and longer gaze duration and more saccade bouts with food images. Participants exposed to the reactive stressor reduced gaze duration on food images relative to controls, and this affect was not linked to palatability or salivary cortisol levels. We conclude that the reactive stressor decreased time spent looking at food, but not non-food, images. These data are partly consistent with the idea that reactive stressors reduce attention to non-critical visual signals.

Eicosapentaenoic Acid Protects against Metabolic Impairments in the APPswe/PS1dE9 Alzheimer's Disease Mouse Model.

BACKGROUND: Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by amyloid-ß (Aß) plaques. Systemic inflammation and obesity may exacerbate AD pathogenesis. We previously reported anti-inflammatory and anti-obesity effects of EPA in mice. OBJECTIVES: We aimed to determine whether EPA reduces obesity-associated metabolic dysfunctions and Aß accumulation in AD amyloidogenic mice. METHODS: Two-mo-old APPswe/PS1dE9 transgenic (TG) mice and non-TG littermates were randomly assigned to low fat (LF; 10% kcal fat), high fat (HF; 45% kcal fat), or EPA (36 g/kg)-supplemented HF diets. Body composition, glucose tolerance, and energy expenditure were measured, and serum and brain metabolic markers were tested 38 wk postintervention. Outcomes were statistically analyzed via 3-factor ANOVA, modeling genotype, sex, and diet interactions. RESULTS: HF-fed males gained more weight than females (Δ = 61 mg; P < 0.001). Compared with LF, HF increased body weights of wild-type (WT) males (Δ = 31 mg; P < 0.001). EPA reduced HF-induced weight gain in WT males (Δ = 24 mg; P = 0.054) but not in females. HF mice showed decreased glucose clearance and respiratory energy compared with LF-fed groups (Δ = -1.31 g/dL; P < 0.001), with no significant effects of EPA. However, EPA conferred metabolic improvements by decreasing serum leptin and insulin (Δ = -2.51 g/mL and Δ = -0.694 ng/mL, respectively compared with HF, P ≤ 0.05) and increasing adiponectin (Δ = 21.6 ng/mL; P < 0.001). As we expected, TG mice expressed higher serum and brain Aß than WT mice (Δ = 0.131 ng/mL; P < 0.001 and Δ = 0.56%; P < 0.01, respectively), and EPA reduced serum Aß1-40 in TG males compared with HF (Δ = 0.053 ng/mL; P ≤ 0.05). CONCLUSIONS: To our knowledge, this is the first report that EPA reduces serum Aß1-40 in obese AD male mice, warranting further investigations into tissue-specific mechanisms of EPA in AD.

Hypothalamic-pituitary-adrenal (HPA) axis activity and anxiety-like behavior during aging: A test of the glucocorticoid cascade hypothesis in amyloidogenic APPswe/PS1dE9 mice.

Alzheimer's disease (AD) is a progressive, dementing, whole-body disorder that presents with decline in cognitive, behavioral, and emotional functions, as well as endocrine dysregulation. The etiology of AD is not fully understood but stress- and anxiety-related hormones may play a role in its development and trajectory. The glucocorticoid cascade hypothesis posits that levels of glucocorticoids increase with age, leading to dysregulated negative feedback, further elevated glucocorticoids, and resulting neuropathology. We examined the impact of age (from 2 to 10 months) and stressor exposure (predator odor) on hormone levels (corticosterone and ghrelin), anxiety-like behavior (open field and light dark tests), and memory-related behavior (novel object recognition; NOR), and whether these various measures correlated with neuropathology (hippocampus and cortex amyloid beta, Aß) in male and female APPswe/PS1dE9 transgenic and non-transgenic mice. Additionally, we performed exploratory analyses to probe if the open field and light dark test as commonly used tasks to assess anxiety levels were correlated. Consistent with the glucocorticoid cascade hypothesis, baseline corticosterone increased with age. Predator odor exposure elevated corticosterone at each age, but in contrast to the glucocorticoid cascade hypothesis, the magnitude of stressor-induced elevations in corticosterone levels did not increase with age. Overall, transgenic mice had higher post-stressor, but not baseline, corticosterone than non-transgenic mice, and across both genotypes, females consistently had higher (baseline and post-stressor) corticosterone than males. Behavior in the open field test primarily showed decreased locomotion with age, and this was pronounced in transgenic females. Anxiety-like behaviors in the light dark test were exacerbated following predator odor, and female transgenic mice were the most impacted. Compared to transgenic males, transgenic females had higher Aß concentrations and showed more anxiety-like behavior. Performance on the NOR did not differ significantly between genotypes. Lastly, we did not find robust, statistically significant correlations among corticosterone, ghrelin, recognition memory, anxiety-like behaviors, or Aß, suggesting outcomes are not strongly related on the individual level. Our data suggest that despite Aß accumulation in the hippocampus and cortex, male and female APPswePS1dE9 transgenic mice do not differ robustly from their non-transgenic littermates in physiological, endocrine, and behavioral measures at the range of ages studied here.

Aversive Self-Focus and Alcohol Consumption Behavior in Women with Sexual Identity-Uncertainty: Changes in Salivary Cortisol Stress Response Among Those who Drink-to-Cope.

Background: Individuals who report sexual identity-uncertainty are at-risk for heavy alcohol consumption and alcohol use disorder symptomology. The current study examined the impact of states of aversive self-focus on subsequent consumption of ostensibly alcohol-containing beverages among a sample of women in early adulthood with varying levels of sexual identity-uncertainty (N = 75). Methods: Utilizing a 2 (self-focus: negative vs. neutral) × 2 (attribution for any psychological discomfort: external vs. none given) between-subjects design with 3 within-person assessments of salivary cortisol, both a moderation model and mixed-effects general linear model were tested. Results: States of aversive self-focus caused increases in overall consumption among women higher in sexual identity-uncertainty. Findings suggested consumption of ostensibly alcohol-containing beverages was more likely among women higher in sexual identity-uncertainty who also reported consuming beverages to cope with distress. Among women who reported higher levels of sexual identity-uncertainty and drinking-to-cope motives, salivary cortisol concentrations dampened more quickly over time, as they supposedly consumed alcohol. Conclusion: Findings demonstrate that, among women reporting sexual identity-uncertainty who are motivated to consume alcohol to forget about troubles or worries, situations which evoke states of aversive self-focus may contribute to differences in alcohol consumption in early adulthood.

Relations among CRFR1 and FKBP5 genotype, cortisol, and cognitive function in aging humans: A Project FRONTIER study.

Here we use the glucocorticoid cascade hypothesis framework to address the role of baseline cortisol on changes in cognitive function over a 3-year span in non-demented rural Americans. We also determine if genotype at 4 different single nucleotide polymorphisms (SNPs) relates to change in cognitive function. We predicted 1) over time, increases in baseline cortisol will be associated with decline in cognitive function, 2) individuals homozygous for 3 CRFR1 SNP rare alleles (AA rs110402, TT rs7209436, and TT rs242924 vs. others) will show less cognitive decline and this will be particularly pronounced in those with lower baseline cortisol, and 3) FKBP5 T carriers (TT or CT vs. CC homozygotes) will have decreased cognitive performance and this will be particularly pronounced in individuals with higher baseline cortisol. Collectively, our data do not robustly support the glucocorticoid cascade hypothesis. In several cases, higher baseline cortisol related to better cognitive performance over time, but within individuals, increased cortisol over time related to decreased performance on some cognitive domains over time. Contrary to our predictions, individuals with the rare CRFR1 haplotype (AA, TT, TT) performed worse than individuals with the common haplotype across multiple domains of cognitive function. FKBP5 genotype status had minimal impacts on cognitive outcomes. Genotype effects were largely not dependent on cortisol. The Project FRONTIER dataset is supported by Texas Tech University Health Sciences Center Garrison Institute on Aging.

From panic to pedagogy: Using online active learning to promote inclusive instruction in ecology and evolutionary biology courses and beyond.

The rapid shift to online teaching in spring 2020 meant most of us were teaching in panic mode. As we move forward with course planning for fall and beyond, we can invest more time and energy into improving the online experience for our students. We advocate that instructors use inclusive teaching practices, specifically through active learning, in their online classes. Incorporating pedagogical practices that work to maximize active and inclusive teaching concepts will be beneficial for all students, and especially those from minoritized or underserved groups. Like many STEM fields, Ecology and Evolution shows achievement gaps and faces a leaky pipeline issue for students from groups traditionally underserved in science. Making online classes both active and inclusive will aid student learning and will also help students feel more connected to their learning, their peers, and their campus. This approach will likely help with performance, retention, and persistence of students. In this paper, we offer broadly applicable strategies and techniques that weave together active and inclusive teaching practices. We challenge instructors to commit to making small changes as a first step to more inclusive teaching in ecology and evolutionary biology courses.

Tectal CRFR1 receptor involvement in avoidance and approach behaviors in the South African clawed frog, Xenopus laevis.

Animals in the wild must balance food intake with vigilance for predators in order to survive. The optic tectum plays an important role in the integration of external (predators) and internal (energy status) cues related to predator defense and prey capture. However, the role of neuromodulators involved in tectal sensorimotor processing is poorly studied. Recently we showed that tectal CRFR1 receptor activation decreases food intake in the South African clawed frog, Xenopus laevis, suggesting that CRF may modulate food intake/predator avoidance tradeoffs. Here we use a behavioral assay modeling food intake and predator avoidance to test the role of CRFR1 receptors and energy status in this tradeoff. We tested the predictions that 1) administering the CRFR1 antagonist NBI-27914 via the optic tecta will increase food intake and feeding-related behaviors in the presence of a predator, and 2) that prior food deprivation, which lowers tectal CRF content, will increase food intake and feeding-related behaviors in the presence of a predator. Pre-treatment with NBI-27914 did not prevent predator-induced reductions in food intake. Predator exposure altered feeding-related behaviors in a predictable manner. Pretreatment with NBI-27914 reduced the response of certain behaviors to a predator but also altered behaviors irrelevant of predator presence. Although 1-wk of food deprivation altered some non-feeding behaviors related to energy conservation strategy, food intake in the presence of a predator was not altered by prior food deprivation. Collectively, our data support a role for tectal CRFR1 in modulating discrete behavioral responses during predator avoidance/foraging tradeoffs.

Comparison of contingent and noncontingent access to therapy dogs during academic tasks in children with autism spectrum disorder.

This study compared contingent and noncontingent access to therapy dogs during educational tasks for children with autism spectrum disorder using a multielement design. The experimenters assessed whether initial preference for the dog predicted reinforcer efficacy and how preference changed across time. A higher response rate during contingent dog sessions than baseline sessions occurred for 4 out of 5 participants, suggesting that the dog functioned as a reinforcer. One participant engaged in a high rate of responding in both contingent and noncontingent dog conditions. Preference assessments revealed idiosyncrasies, suggesting that further research is needed into the predictive nature of initial preference assessments with animals as part of the stimulus array. The experimenters also analyzed salivary cortisol before and after sessions to determine if learning about the upcoming interaction with a dog reduced salivary cortisol in children. Cortisol was variable across participants, with only some deriving a potential physiological benefit from expecting to interact with the dog.