Summer Research Internships Prepare High School Students for 21st Century Biomedical Careers.

STEM internships for both high school and college students provide early opportunities for students to discover careers of interest and career paths they may not otherwise experience. For over 25 years, the University of Alabama at Birmingham's (UAB) Center for Community OutReach Development (CORD) has provided rising high school seniors with opportunities to conduct research in federally-funded laboratories under the mentorship of UAB faculty. This paper evaluates CORD's High School Summer Science Institute III Program (SSI III) and its impact on participants' STEM career trajectories. Outcomes were tracked for SSI III participants over an eight-year period, and former interns' perceptions of the program reported. Over 99% of surveyed interns (N=102) chose a STEM undergraduate major, and 97% of the former interns reported they were pursuing STEM careers. Nearly all interns indicated their SSI-III experience was very positive and influenced their career decision. Over half of the interns matriculated into an undergraduate STEM major at UAB, providing the university with return as more excellent students for their investment in the program. These results highlight the importance of high school student involvement in STEM internships as a pathway that leads towards STEM careers.

Effectively Adapting and Implementing In-Person Teacher Professional Development to a Virtual Format.

A year of COVID-19 quarantine required educators to switch from in-person to virtual learning platforms, causing a dramatic reimagining of their daily praxis. Their experiences are likely to influence new norms for K-12 education. While virtual learning can be effective, student engagement, student retention, and student attention can be challenging. This paper discusses how we adapted a materials-heavy, hands-on, annual summer teacher professional development (PD) program from an in-person to a virtual platform in the initial months of the pandemic. We successfully maintained effective and hands-on components, giving authentic learning experiences to the participants. The 2020 virtual version of the program effectively engaged in-service teachers with high daily participation and retention rates. Nearly all participants rated the workshops as very good or excellent, and an assessment of participants' learning outcomes was comparable to that of the highly-rated in-person 2018 version of the program. Following the PD session, teachers reported feeling more prepared to facilitate their students' learning, increased inquiry-based science teaching knowledge and skills, and their enthusiasm for utilizing workshop strategies. While there are challenges to implementing virtual learning, virtual teacher PD can be widely adaptable and replicable for many institutions, especially in situations in which distance or finances deter in-person participation.

Distinct effects of early-life experience and trait aggression on cardiovascular reactivity and recovery.

We previously demonstrated independent effects of early-life experience (ELE) and trait aggression (TA) on resting heart rate (HR) and mean arterial pressure (MAP) in rats. The present study examined the effects of TA and ELE on stress-evoked cardiovascular reactivity and recovery. Pups born to Wistar-Kyoto dams were exposed to daily 180-min periods of maternal separation (MS) during the first two weeks of life, and aggression was assessed in adult offspring using the resident-intruder test. Radiotelemetry was then used to record stress-evoked HR and MAP responses in response to: strobe light, novel environment, intruder rat, or restraint. Maximal HR and MAP responses were quantified as indices of reactivity, and exponential decay curves were fitted to determine decay constants as a measure of recovery. Strobe light was the weakest stressor, evoking the lowest increases in MAP and HR, which were significantly greater in MS-exposed rats irrespective of TA. In contrast, reactivity to and recovery from exposure to a novel environment or an intruder were significantly influenced by TA, but not ELE. TA animals exhibited greater reactivity in both of these paradigms, with either decreased (novel environment) or increased (intruder) recovery. Restraint stress induced the largest changes in HR and MAP with the slowest recovery, and these responses were shaped by a significant ELE x TA interaction. These data indicate that cardiovascular reactivity and recovery are influenced by ELE, TA, or ELE x TA interaction depending on stressor aversiveness as well as its physical and psychological dimensions.

Preparing 8th Grade Students to Excel in Physical Science: HandsOn Physics (HOP)!

This study describes a program that the University of Alabama at Birmingham (UAB) carried out in partnership with Birmingham City Schools (BCS) to test an educational intervention, i.e., Hands-On Physics (HOP), among 8th grade students in predominantly minority schools. It also evaluated teachers' demographics and educational backgrounds. The students conducted four physics experiments during a three day period. They performed better on post-tests. The actual and the percent gains in knowledge for each school were essentially equal for the schools that had passing versus failing grades in annual state assessment (20.4±5.6/49.0±5.6%, 20.4±2.7/48.4±8.3%, respectively). Most students (53%) stated that they were comfortable with science, 88% indicated that they were planning to enter higher education, and 86% agreed that higher education was very important for their future. The students' major perceived obstacles to higher education were education cost and low grades. The teachers were primarily between 40-59 years old (60%), female (80%) and African-American (93%), and 87% majored in biology (93%). Forty percent had a bachelor's degree and 60% had a master's degree. They reported that they needed more support teaching physics and reported that a lack of materials and time were the main obstacles to provide the highest quality science educational experiences.

Taurine Supplementation Reduces Renal Nerve Activity in Male Rats in which Renal Nerve Activity was Increased by a High Sugar Diet.

This study tests the hypothesis that taurine supplementation reduces sugar-induced increases in renal sympathetic nerve activity related to renin release in adult male rats. After weaning, male rats were fed normal rat chow and drank water containing 5% glucose (CG) or water alone (CW) throughout the experiment. At 6-7 weeks of age, each group was supplemented with or without 3% taurine in drinking water until the end of experiment. At 7-8 weeks of age, blood chemistry and renal nerve activity were measured in anesthetized rats. Body weights slightly and significantly increased in CG compared to CW groups but were not significantly affected by taurine supplementation. Plasma electrolytes except bicarbonate, plasma creatinine, and blood urea nitrogen were not significantly different among the four groups. Mean arterial pressure significantly increased in both taurine treated groups compared to CW, while heart rates were not significantly different among the four groups. Further, all groups displayed similar renal nerve firing frequencies at rest and renal nerve responses to sodium nitroprusside and phenylephrine infusion. However, compared to CW group, CG significantly increased the power density of renin release-related frequency component, decreased that of sodium excretion-related frequency component, and decreased that of renal blood flow-related frequency component. Taurine supplementation completely abolished the effect of high sugar intake on renal sympathetic activity patterns. These data indicate that in adult male rats, high sugar intake alters the pattern but not firing frequency of sympathetic nerve activity to control renal function, and this effect can be improved by taurine supplementation.

Abnormal autonomic nervous system function in rural Thai men: A potential contributor to their high risk of sudden unexplained nocturnal death syndrome.

BACKGROUND: Rural compared to urban Thai populations have a higher incidence of sudden unexplained nocturnal death syndrome (SUNDS). This study tests the hypothesis that compared to young urban Thai men, the young rural northeast Thai men display autonomic system dysfunction that may contribute to their relatively high risk to develop SUNDS. METHODS: Forty-seven healthy second and third year students from Khon Kaen University (20-22years old) were divided into central, urban northeastern, and rural northeastern groups, based on the locality in which they had grown up and in which their parents had lived prior to their birth. RESULTS: Body weight, body height, serum sodium, serum potassium, fasting blood sugar, glucose tolerance, resting mean arterial pressure, resting heart rate, ulnar nerve conduction velocity, and sympathetic and parasympathetic nervous system activity were not significantly different among the three groups. In contrast, compared to urban northeasterners and central Thais, rural northeasterners displayed low sympathetic and high parasympathetic responses to cold stress and oral saline load; however, baroreflex sensitivity and the autonomic nervous system responses to upright tilt were not significantly different among the three groups. In addition, respiratory rates at rest and in response to upright tilt, cold stress, and oral saline load were not significantly different among the three groups. CONCLUSIONS: These data indicate that compared to central or urban, individuals from rural origin display decreased sympathetic and increased parasympathetic responses to stresses. These altered responses could predispose the individuals to inappropriate autonomic control during the stresses, including those resulting in SUNDS.

Neonatal maternal separation stress elicits lasting DNA methylation changes in the hippocampus of stress-reactive Wistar Kyoto rats.

Early-life stress (ELS) can alter neurodevelopment in variable ways, ranging from producing deleterious outcomes to stress resilience. While most ELS studies focus on its harmful effects, recent work by our laboratory and others shows that ELS elicits positive effects in certain individuals. We exposed Wistar Kyoto (WKY) rats, known for a stress reactive, anxiety/depression-like phenotype, to maternal separation (MS), a model of ELS. MS exposure elicited anxiolytic and antidepressant behavioral effects as well as improved cardiovascular function in adult WKY offspring. This study interrogates an epigenetic mechanism (DNA methylation) that may confer the adaptive effects of MS in WKY offspring. We quantified global genome methylation levels in limbic brain regions of adult WKYs exposed to daily 180-min MS or neonatal handling from postnatal day 1-14. MS exposure triggered dramatic DNA hypermethylation specifically in the hippocampus. Next-generation sequencing methylome profiling revealed reduced methylation at intragenic sites within two key nodes of insulin signaling pathways: the insulin receptor and one of its major downstream targets, mitogen-activated protein kinase kinase kinase 5 (Map3k5). We then tested the hypothesis that enhancing DNA methylation in WKY rats would elicit adaptive changes akin to the effects of MS. Dietary methyl donor supplementation improved WKY rats' anxiety/depression-like behaviors and also improved cardiovascular measures, similar to previous observations following MS. Overall, these data suggest a potential molecular mechanism that mediates a predicted adaptive response, whereby ELS induces DNA methylation changes in the brain that may contribute to successful stress coping and adaptive physiological changes in adulthood.

Independent effects of early-life experience and trait aggression on cardiovascular function.

Early-life experience (ELE) can significantly affect life-long health and disease, including cardiovascular function. Specific dimensions of emotionality also modify risk of disease, and aggressive traits along with social inhibition have been established as independent vulnerability factors for the progression of cardiovascular disease. Yet, the biological mechanisms mediating these associations remain poorly understood. The present study utilized the inherently stress-susceptible and socially inhibited Wistar-Kyoto rats to determine the potential influences of ELE and trait aggression (TA) on cardiovascular parameters throughout the lifespan. Pups were exposed to maternal separation (MS), consisting of daily 3-h separations of the entire litter from postnatal day (P)1 to P14. The rats were weaned at P21, and as adults were instrumented for chronic radiotelemetry recordings of blood pressure and heart rate (HR). Adult aggressive behavior was assessed using the resident-intruder test, which demonstrated that TA was independent of MS exposure. MS-exposed animals (irrespective of TA) had significantly lower resting HR accompanied by increases in HR variability. No effects of MS on resting blood pressure were detected. In contrast, TA correlated with increased resting mean, systolic, and diastolic arterial pressures but had no effect on HR. TA rats (relative to nonaggressive animals) also manifested increased wall-to-lumen ratio in the thoracic aorta, increased sensitivity to phenylephrine-induced vascular contractility, and increased norepinephrine content in the heart. Together these data suggest that ELE and TA are independent factors that impact baseline cardiovascular function.

Electromyographic evidence in support of a knock-in mouse model of DYT1 Dystonia.

INTRODUCTION: DYT1 dystonia is an autosomal-dominant movement disorder characterized by abnormal, often repetitive, movements and postures. Its hallmark feature is sustained or intermittent contractions of muscles involving co-contractions of antagonist muscle pairs. The symptoms are relieved with the anticholinergic drug trihexyphenidyl. The primary mutation is a trinucleotide deletion (ΔGAG) in DYT1/TOR1A, which codes for torsinA. Previous studies showed that (1) heterozygous Dyt1 ΔGAG knock-in mice, which have an analogous mutation in the endogenous gene, exhibit motor deficits and altered corticostriatal synaptic plasticity in the brain and (2) these deficits can be rescued by trihexyphenidyl. However, brain imaging studies suggest that the Dyt1 knock-in mouse models nonmanifesting mutation carriers of DYT1 dystonia. The aim of this work was to examine the hallmark features of DYT1 dystonia in the Dyt1 knock-in mice by analyzing muscular activities. METHODS: Wireless telemetry devices with biopotential channels were implanted to the bicep and the rectus femori muscles in Dyt1 knock-in mice, and muscular activities were recorded before and after trihexyphenidyl administration. RESULTS: (1) Consistent with DYT1 dystonia patients, Dyt1 knock-in mice showed sustained contractions and co-contractions of the antagonistic bicep femoris and rectus femoris. (2) The abnormal muscle contractions were normalized by trihexyphenidyl. CONCLUSION: The results suggest that the motor deficits in Dyt1 knock-in mice are likely produced by abnormal muscle contractions, and Dyt1 knock-in mice can potentially be used as a manifesting disease model to study pathophysiology and develop novel therapeutics. © 2016 International Parkinson and Movement Disorder Society.

"Sickle cell anemia: tracking down a mutation": an interactive learning laboratory that communicates basic principles of genetics and cellular biology.

"Sickle cell anemia: tracking down a mutation" is a full-day, inquiry-based, biology experience for high school students enrolled in genetics or advanced biology courses. In the experience, students use restriction endonuclease digestion, cellulose acetate gel electrophoresis, and microscopy to discover which of three putative patients have the sickle cell genotype/phenotype using DNA and blood samples from wild-type and transgenic mice that carry a sickle cell mutation. The inquiry-based, problem-solving approach facilitates the students' understanding of the basic concepts of genetics and cellular and molecular biology and provides experience with contemporary tools of biotechnology. It also leads to students' appreciation of the causes and consequences of this genetic disease, which is relatively common in individuals of African descent, and increases their understanding of the first principles of genetics. This protocol provides optimal learning when led by well-trained facilitators (including the classroom teacher) and carried out in small groups (6:1 student-to-teacher ratio). This high-quality experience can be offered to a large number of students at a relatively low cost, and it is especially effective in collaboration with a local science museum and/or university. Over the past 15 yr, >12,000 students have completed this inquiry-based learning experience and demonstrated a consistent, substantial increase in their understanding of the disease and genetics in general.

Spinophilin Is Indispensable for the α2B Adrenergic Receptor-Elicited Hypertensive Response.

The α2 adrenergic receptor (AR) subtypes are important for blood pressure control. When activated, the α2A subtype elicits a hypotensive response whereas the α2B subtype mediates a hypertensive effect that counteracts the hypotensive response by the α2A subtype. We have previously shown that spinophilin attenuates the α2AAR-dependent hypotensive response; in spinophilin null mice, this response is highly potentiated. In this study, we demonstrate that spinophilin impedes arrestin-dependent phosphorylation and desensitization of the α2BAR subtype by competing against arrestin binding to this receptor subtype. The Del301-303 α2BAR, a human variation that shows impaired phosphorylation and desensitization and is linked to hypertension in certain populations, exhibits preferential interaction with spinophilin over arrestin. Furthermore, Del301-303 α2BAR-induced ERK signaling is quickly desensitized in cells without spinophilin expression, showing a profile similar to that induced by the wild type receptor in these cells. Together, these data suggest a critical role of spinophilin in sustaining α2BAR signaling. Consistent with this notion, our in vivo study reveals that the α2BAR-elicited hypertensive response is diminished in spinophilin deficient mice. In arrestin 3 deficient mice, where the receptor has a stronger binding to spinophilin, the same hypertensive response is enhanced. These data suggest that interaction with spinophilin is indispensable for the α2BAR to elicit the hypertensive response. This is opposite of the negative role of spinophilin in regulating α2AAR-mediated hypotensive response, suggesting that spinophilin regulation of these closely related receptor subtypes can result in distinct functional outcomes in vivo. Thus, spinophilin may represent a useful therapeutic target for treatment of hypertension.

Second-hand eating? Maternal perception of the food environment affects reproductive investment in mice.

OBJECTIVE: Little information exists on how perception of the food (or "energetic") environment affects body composition and reproductive investment. The hypothesis was tested that female mice, who are themselves consuming standard chow diets but who are exposed to conspecifics eating a rich "cafeteria diet," will exhibit altered weight gain and reproductive investment. METHODS: Female C57BL/6 mice were raised on a cafeteria diet. At maturity, subjects were switched to a standard chow diet, and their cage-mates were assigned to consume either a cafeteria diet (treatment, n = 20) or standard chow (control, n = 20). Subjects were mated and pups raised to weaning. Subjects and pups were analyzed for body composition. RESULTS: Treatment had no discernable effect on dam body weight or composition but caused pups to have lower body weight (P = 0.036) and less fat mass (P = 0.041). A nearly significant treatment effect on "time to successful reproduction" (avg. 55 versus 44 days), likely due to increased failed first pregnancies, (14/19 versus 8/19, P = 0.099) was found. CONCLUSIONS: These data indicate that perceived food environment (independent of the diet actually consumed) can produce small pups with less body fat and possibly induce difficulties in pregnancy for dams. Replication and mechanistic studies should follow.

Perinatal taurine exposure affects adult arterial pressure control.

Taurine is an abundant, free amino acid found in mammalian cells that contributes to many physiologic functions from that of a simple cell osmolyte to a programmer of adult health and disease. Taurine's contribution extends from conception throughout life, but its most critical exposure period is during perinatal life. In adults, taurine supplementation prevents or alleviates cardiovascular disease and related complications. In contrast, low taurine consumption coincides with increased risk of cardiovascular disease, obesity and type II diabetes. This review focuses on the effects that altered perinatal taurine exposure has on long-term mechanisms that control adult arterial blood pressure and could thereby contribute to arterial hypertension through its ability to program these cardiovascular regulatory mechanisms very early in life. The modifications of these mechanisms can last a lifetime and transfer to the next generation, suggesting that epigenetic mechanisms underlie the changes. The ability of perinatal taurine exposure to influence arterial pressure control mechanisms and hypertension in adult life appears to involve the regulation of growth and development, the central and autonomic nervous system, the renin-angiotensin system, glucose-insulin interaction and changes to heart, blood vessels and kidney function.

Acute and Chronic Kudzu Improves Plasma Glucose Tolerance in Non-Diabetic CD-1 Mice.

Previous studies demonstrate that kudzu root extract and its major isoflavone (puerarin) improve glucose metabolism in animal models of insulin resistance and type 2 diabetes; however, these beneficial effects have not been investigated in normal glycemic mice. The present study investigates the effect of acute and chronic kudzu root extract supplementation on glucose tolerance in normoglycemic CD-1 mice. Male, adult CD-1 mice were fed a phytoestrogen-free diet containing 0.2% or 0.0% kudzu root extract for 6 weeks. Thereafter, they were acutely administered kudzu root extract (75 mg/kg BW; oral) or vehicle followed by a glucose challenge (2 g/kg BW; oral). In control fed mice, the acute glucose challenge increased blood glucose ~300% after 30 minutes, and acute kudzu root extract administration significantly blunted this response by ~50%. In mice chronically fed a kudzu-supplemented diet, glucose tolerance was improved, and acute treatment caused no additional improvement. Irrespective of treatment, all mice were normoglycemic at the start of each glucose challenge. Administration of insulin resulted in a larger decrease in blood glucose in chronic kudzu-supplemented compared to control mice. Co-administration of phloridzin (a specific inhibitor of SGLT-mediated glucose uptake), improved glucose tolerance in acutely kudzu-treated mice but had no significant effect on glucose tolerance in chronically treated mice. These results indicate that both acute and chronic administration of kudzu root extract improves glucose tolerance in a normal glycemic mouse strain and that the effects of chronic kudzu feeding may be mediated, in part, by enhanced insulin sensitivity (chronic) and inhibition of sodium dependent glucose transport.

Taurine supplementation in spontaneously hypertensive rats: Advantages and limitations for human applications.

Taurine (2-aminoethanesulfonic acid) is a ß-amino acid found in many tissues particularly brain, myocardium, and kidney. It plays several physiological roles including cardiac contraction, antioxidation, and blunting of hypertension. Though several lines of evidence indicate that dietary taurine can reduce hypertension in humans and in animal models, evidence that taurine supplementation reduces hypertension in humans has not been conclusive. One reason for the inconclusive nature of past studies may be that taurine having both positive and negative effects on cardiovascular system depending on when it is assessed, some effects may occur early, while others only appear later. Further, other consideration may play a role, e.g., taurine supplementation improves hypertension in spontaneously hypertensive rats on a low salt diet but fails to attenuate hypertension on a high salt diet. In humans, some epidemiologic studies indicate that people with high taurine and low salt diets display lower arterial pressure than those with low taurine and high salt diets. Differences in techniques for measuring arterial pressure, duration of treatment, and animal models likely affect the response in different studies. This review considers both the positive and negative effects of taurine on blood pressure in animal models and their applications for human interventions.