bluuebunny/crossref_metadata_2025 huggingface dataset:
Time dynamics of cerebral blood flow during LBNP (1183.11)
Authors: Kasprowicz Magdalena , Czosnyka Marek , Diehl rolf , Haubrich christina
Published: June 2021

Background: The time constant (τ) estimates how fast the arterial part of cerebral vascular bed is filled with blood volume during the cardiac systole. We have demonstrated previously that τ provides new insights into time dynamics in different cardiovascular diseases and during CO2 challenge in normal subjects. In this study we aimed to investigate time dynamics of cerebral blood flow using τ during progressive lower body negative pressure (LBNP) test.

Material and Methods:Simultaneous recordings of TCD cerebral blood flow velocity (CBFV) in MCA, Finapres arterial blood pressure (ABP) and heart rate (HR) along with end‐tidal CO2 (EtCO2) were performed in 38 healthy volunteers (26 ± 4 years) during LBNP test. τ and τ*HR [beat] were estimated during lower body negative pressure ‐ using mathematical transformation of ABP and CBFV pulse waveforms. The analysis of variance (ANOVA) with Bonferroni post‐hoc test were used to compare the differences in hemodynamic variables between the stages of LBNP test. The level of significance was set as 0.05.

Key Results / Statistics: From baseline to maximal LBNP before the onset of presyncope the gradual shortening of τ by 74±6% (mean ±95%CI) of baseline was observed with no further decrease in τ at presyncope (76±8%) ‐ see figure 1. The τ*HR did not change significantly in the course of LBNP up to the presyncope when it increased by 119±11% of baseline (p<0.0013). At presyncope reduction in ABP was by 90±5% of baseline, in CBFV by 77±3% of baseline, and in EtCO2 by 81±5% of baseline whereas HR increased by 162±9% of baseline.

Conclusion: The time constant Tau sheds light onto a new aspect of the pathophysiology of presyncope. Although the heart systole contributes an increasing part to the cerebral circulation the failure of cerebral circulation cannot be prevented. Tau*HR indicates a significant downslow of the cerebral circulation during LBNP just before the occurrence of presyncopal complaints.
Influence of cholinergic blockade on the cerebral blood flow response to exercise in humans (1183.3)
Authors: Braz Igor , Shantsila Alena , Adlan Ahmed , Secher Niels , Fisher James
Published: June 2021

Administration of the muscarinic cholinergic receptor blocker glycopyrrolate reportedly attenuates the exercise‐induced increase in middle cerebral artery mean blood velocity. We sought to determine the cholinergic contribution to blood flow in the internal carotid artery (ICA; duplex Doppler ultrasound) during low (42±9 Watts; mean±SE) and moderate (110±11 Watts) intensity leg cycling in seven young male subjects (21±1 yr). Mean arterial pressure (MAP) and heart rate (HR; ECG) were continuously monitored. Stroke volume (SV) was determined offline using Modelflow and cardiac output calculated (CO=HR×SV). Exercise trials were conducted under control (no drug) conditions and after cholinergic blockade by administration of glycopyrrolate. Cholinergic blockade increased resting CO (6.8±0.4 to 8.7±0.5 L/min; P<0.05) and MAP (79±2 to 89±3 mmHg), while the responses to exercise were similar. ICA blood flow increased similarly from rest during low and moderate intensity exercise under control (271±34, 333±27 and 361±28 mL/min, respectively, P<0.05) and cholinergic blockade conditions (315±43, 384±33 and 390±38 mL/min, respectively), with ICA blood flow always being higher with cholinergic blockade (P<0.05). These findings indicate that the cholinergic contribution to the internal carotid artery blood flow responses to dynamic exercise in humans is minimal.
Increases in sympathetic activity during cold pressor test does not cause cerebral vasoconstriction (1183.8)
Authors: Serrador Jorge , Blatt Melissa , Ghobreal Bemin , Falvo Michael
Published: June 2021

The objective of this work was to determine whether increased sympathetic activity results in cerebral vasoconstriction. To assess the role of sympathetic activity, 10 healthy individuals participated in a cold pressor test in which they immersed their hand in ice cold water for 57.5±16.6 seconds. We continuously monitored beat‐by‐beat blood pressure, cerebral flow velocity in the middle (MCA) and anterior cerebral artery (ACA), common carotid artery (CCA) flow and end tidal CO2. As expected the cold pressor test produced a significant increase in sympathetic outflow causing mean arterial pressure to increase from 104±7 to 117±10 mmHg, P=0.005. In contrast CCA diameter did not change (6.7±0.2 to 6.7±0.2 mm), and flow increased slightly but non‐significantly (+6.0±6.2%). Similarly, we saw slight increases in flow velocity in the MCA (+3.0±6.7 %) and ACA (+7.5±4.9 %) but non‐significant. End tidal CO2 values did not change from baseline to end of cold pressor (40.3±1.1 vs 40.0±1.2 mmHg). In contrast, cerebrovascular resistance increased in the MCA (+9.7±5.7 %) and ACA (+11.5±5.0 %), likely due to the cerebral autoregulatory response to the increase mean arterial pressure. These data demonstrate that increased sympathetic activity was associated with a slight increase in common carotid, middle and anterior cerebral flow, all ~5%, indicating there was no cerebral vasoconstriction to reduce flow. The increase in cerebral flow was likely in response to increased neural activation due to pain and sensory inputs. Our finding that CCA flow increased the same amount as MCA and ACA supports the concept that sympathetic activity does not cause vasoconstriction at either the arteriolar or MCA level.

Grant Funding Source: Supported by Dept of Veteran Affairs and NIH R21 DC009900
Maternal mortality dynamics in Kazakhstan (1185.1)
Authors: Kamalbekova G. , Magzumova R.
Published: June 2021

In Kazakhstan, over the period since 2000‐2011, maternal mortality reduced per 100,000 live births, from 60.9 to 17.4 cases per year.

Results: The analysis of indicators by regions in the Republic of Kazakhstan demonstrates the most favorable situation of reducing maternal mortality, what was observed in Mangistau region (from 160.5 to 24.7) in the Atyrau region (from 108.6 to 6.6) in Kostanai region (from 92.9 to 15.7) in the North‐Kazakhstan region (from 66.2) and in Astana (from 65 to 10.4). In the analysis of the absolute number of deaths during pregnancy, childbirth and postpartum periods on the pregnants on the period since 2008‐2011 in Kazakhstan, up to 12 weeks ‐ in average of 3.5 cases of death per year in the period 13‐21 weeks‐6.5 cases per year of 22 weeks or more‐6.5 cases per year, women in labor and puerperal‐77.5 cases per year.

During the period since 2008‐2011 an average cause maternal mortality 40.7 for extragenital diseases, 18.5 cases‐obstetric hemorrhage, 13,7‐from preeclampsia 10.7‐from abortion, 4.7‐from uterine rupture, 3,5‐from sepsis, 075‐from an ectopic pregnancy.

During the period since 2008‐2011 in South Kazakhstan region recorded 40 maternal deaths from extragenital diseases, 13 cases‐from obstetric hemorrhage, 9 cases‐from Gestoses, total‐82 cases.

For recent 6 months in 2013 in Kazakhstan demonstrates decrease in the maternal mortality rate ‐ 15.1% compared to the same period in 2012.
The effect of increasing the protein content of breakfasts on satiety and cognitive function in undergraduate students (120.2)
Authors: Hutchison Christine , West Robert , Hollis James
Published: June 2021

The effect of protein consumption at breakfast on appetite and cognitive performance was investigated using a randomized, cross‐over study design. Following an overnight fast, 33 healthy, college undergraduates (aged = 22±2 yrs, BMI = 23.5±1.7. kg/m2) were provided one of four breakfast treatments: no breakfast, CHO‐only, high‐CHO/low protein and low‐CHO/high protein. Baseline appetite questionnaires and plasma samples were collected and cognitive performance tests were administered at regular intervals for 240 minutes following breakfast. An ad libitum lunch meal was provided 240 minutes after breakfast, and the amount eaten recorded. Following the lunch meal, participants were allowed to leave the laboratory and food intake was recorded using a food log and hourly appetite questionnaires completed for the rest of the day. Eating breakfast reduced subjective appetite compared to eating no breakfast (p<0.05). While food intake at the lunch meal was lowest after the HP breakfast (p<0.05) total daily energy intake was lowest when participants consumed no breakfast (p<0.05). The macronutrient composition of the breakfast meal had no effect on subjective appetite or food intake (p>0.05). Analysis of plasma samples revealed a significantly lower glucose following the low CHO/high protein treatment as compared to the CHO only breakfast. (p<0.05). Plasma insulin concentration was lowest following the no breakfast condition (p<0.05) but did not differ following the different breakfast meals (p>0.05). Proactive interference in delay memory was sensitive to treatment (p = .056), the low CHO/high protein treatment reducing interference. Verbal fluency was sensitive to overall treatment (p < .05), and reflected a stronger effect of the low CHO/high protein breakfast over time. Verbal fluency was marginally sensitive to the treatment (p = .068), with the two protein treatments leading to continued improvement over time.

Grant Funding Source: Supported by the National Pork Board
Tart cherries improve glucose tolerance and insulin signaling in obese Zucker rats (121.4)
Authors: Stull April , Kirakosyan Ara , Elks Carrie
Published: June 2021

The objective of this study was to evaluate the therapeutic efficacy of tart cherries on insulin sensitivity (intraperitoneal insulin tolerance test; IPITT), glucose tolerance (intraperitoneal glucose tolerance test; IPGTT), and intracellular signaling (gastrocnemius skeletal muscle) in obese Zucker rats. The rats consumed either a control (n=11) or tart cherry (n=11; 4% cherry powder) diet for 8 wk. Their body weight, fat pad weight, food intake, and fasting glucose and insulin concentrations were not altered by tart cherries. The IPGTT and IPITT were conducted at the end of study and blood glucose concentrations were measured over a 2‐h period. During the IPGTT, the area under the curve for glucose was significantly lower in the cherry group when compared to the control group (16,630 ± 2,181 vs 21,025 ± 1,994 mg/dl•120min; p 蠄 0.05). However, there were no group differences in glucose concentrations during the IPITT. In the skeletal muscle, the serine phosphorylation of AKT was higher in the cherry group than control group. Also, there were no differences between the groups in the phosphorylation of AMP‐activated protein kinase (AMPK; insulin‐independent protein). These results suggest that tart cherry supplementation improves glucose tolerance and enhances the activation of the intracellular signaling protein AKT in obese Zucker rats.

Grant Funding Source: Cherry Marketing Institute
Giant pterosaurs and the limits of animal flight (13.3)
Authors: Habib Michael
Published: June 2021

Pterosaurs appear to have had a particular propensity for the evolution of large size compared with other flying animals: at least eight genera of pterosaurs included species with wingspans in excess of 4 meters. I present a launch constraints model that accurately predicts size trends in pterosaurs. Azhdarchid pterosaurs evolved a suite of traits associated with improved terrestrial ability and rapid launch, including an expanded and curved deltopectoral crest, expanded coracoid flange, elongate metacarpal IV, and a reinforced fourth metacarpal‐phalangeal joint. This pattern explains why the largest pterosaurs were members of the Azhdarchidae. Most other “giant” pterosaurs were marine, and may have been more constrained in size than azhdarchids as a result of water launching requirements. Large marine pterosaurs, such as anhanguerids, tended to possess an expanded scapula, reinforced scapular‐notarial joint, warped deltopectoral crest, exceptionally broad wing pivot joint, expanded posterior brachial musculature, and reduced hind limbs. These traits are predicted as specializations to water launching. Pneumaticity, forelimb hypertrophy, and quadrupedal launch, combined with selection for low energy loitering and/or extended range, explains the repeated evolution of large size in pterosaurs.
Decision of breastfeeding or formula feeding among low‐income women in Mississippi (131.5)
Authors: Mitra Amal
Published: June 2021

To evaluate factors in decision making of breastfeeding, pregnant women, certified for WIC, visiting health department clinics of 18 selected counties were surveyed. Data were collected by face‐to‐face interview of 694 women by using a 2‐page questionnaire. The major variables included demographics, women’s perceptions on barriers to breastfeeding, and other data relevant to breastfeeding behavior. The outcome variable was women’s intention to breastfeeding. Women’s desired feeding pattern was classified into three groups: 1) exclusive breastfeeding, if planned to breastfeed only; 2) partial breastfeeding, if planned to breastfeed at the start and then used mix breastfeeding and formula milk, or if used mix formula and breastfeeding right from the start; and 3) formula feeding only. The majority (57%) of the study subjects was African American (AA). The proportion of AAs who opted for exclusive breastfeeding (10% vs. 24%, p <0.0001) or any breastfeeding (38% vs. 67%, p <0.0001) was significantly lower than those for whites. AA women who decided to bottle feed their babies had significantly larger family size (p = 0.02) and higher number of children (p = 0.01) compared with whites. A decision to bottle feed was associated with poor previous breastfeeding experience, significantly more often among AAs than whites (95% vs. 88%, p = 0.036). A large proportion of the women had not received breastfeeding information either from a counselor (75%) or from the mass media (56%). Community based educational programs are needed to reach low‐income women for the promotion of breastfeeding.
Establishment and characterization of in vitro model of human beige adipocytes using adenoviral delivery of BMP7 (133.1)
Authors: Okla Meshail , Ha Jung‐Heun , Lee Meeae , Chung Soonkyu
Published: June 2021

Browning of white adipose tissue is an attractive target to facilitate weight loss and improve metabolic health. Bone morphogenic protein 7 (BMP7) is known to stimulate brown adipogenesis, but the molecular identity and metabolic characteristics are unknown. To establish in vitro model of human beige adipocytes, human adipose stem cells (hASCs) were first infected with adenoviral (Ad)‐BMP7 followed by adipogenic differentiation. Delivery of Ad‐BMP7 to hASCs was associated with 1) positive correlation with PPARγ (r2=0.9), 2) a robust increase of UCP1, Cidea, ADR3, and DIO2, and 3) a significant increase of beige‐specific markers, including CD137 and TMEM26. The uptake of 2‐deoxy‐3H‐glucose and 14C‐oleic acid was significantly higher in adipocytes infected with Ad‐BMP7 compared to Ad‐GFP. Moreover, cAMP‐stimulated lipolysis was augmented in Ad‐BMP7 infected adipocytes compared to Ad‐GFP group. Taken together, we demonstrated that delivery of Ad‐BMP7 to hASCs induced beige adipocytes that expressed beige‐selective markers and resembled brown fat metabolic characteristics. Therefore, our human beige adipocyte model would serve as an important tool for the development of new strategies against obesity.

Grant Funding Source: Supported in part by the NIH and NCRR
Dietary phenolic compounds modify glutathione redox homeostasis and cytokine release in human T lymphocytes (134.1)
Authors: Richardson Sian , Ford Christopher , Crozier Alan , Lotito Silvina , McArdle Francis , McArdle Anne , Jackson Malcolm
Published: June 2021

Polyphenols and phenolic acids are abundant in fruits and vegetables. Twenty‐nine dietary phenolic compounds were screened for effects on cytokine release (interleukin 2 (IL2), interleukin 8 (IL8), and tumour necrosis factor α (TNFα)) by Jurkat T‐lymphocytes. Cells were treated with phenolic compounds for 48h, with or without stimulation with 25ng/ml phorbol myristate acetate and 5μg/ml phytohaemagglutinin (PMA/PHA) to induce cytokine release at the 24h time point.

Polyphenols had more anti‐inflammatory effects than phenolic acids. In unstimulated cells, 1μM resveratrol decreased IL2 by 42±7% and IL8 by 32±8%, compared with vehicle controls (p<0.05). For PMA/PHA stimulated cells, 1μM isorhamnetin reduced IL2 by 50±4%, IL8 by 58±6% and TNFα by 63±7%, and curcumin reduced IL2 by 43±14%, IL8 by 30±7% and TNFα by 22±5 (p<0.05). Compounds that significantly modulated cytokine release were investigated for effects on glutathione redox status. Cells treated with 1µM epigallocatechin gallate (EGCG) or pyrogallol increased total and reduced glutathione compared with vehicle controls and reduced glutathione redox potentials from ‐211±3mV (controls) to ‐216±2mV (EGCG) and ‐221±2mV (pyrogallol; p<0.05). Polyphenols demonstrating anti‐inflammatory and redox modulating effects will be further investigated using proteomics to identify cellular pathways responsive to treatments with polyphenols.

Grant Funding Source: Supported by BBSRC DRINC and Unilever
Protective effects of camel’s milk in tri‐nitrobenzensulfonic acid‐induced colitis in rats: modulation of inflammatory cytokines and oxidative stress (134.6)
Authors: Arab Hany , Salama Samir , Eid Ahmed , Omar Hany , Arafa El‐Shaimaa , Maghrabi Ibrahim
Published: June 2021

Current treatment strategies for inflammatory bowel diseases (IBD) are associated with several adverse effects, and thus, the search for effective agents with minimal side effects merits attention. Camel’s milk (CM) is endowed with antioxidant/anti‐inflammatory features and has been reported to protect against diabetes and hepatic injury, however, its effects on IBD have not been previously explored. In the current study, we aimed to investigate the potential alleviating effects and the underlying mechanisms of CM against tri‐nitrobenzensulfonic acid‐induced colitis in rats. CM (10 ml/kg b.i.d. by oral gavage) effectively suppressed the severity of colon injury as evidenced by amelioration of macroscopic damage, histopathological alterations, leukocyte influx and myeloperoxidase activity. Administration of CM mitigated the upregulated inflammatory response via inhibition of TNF‐α and IL‐10 cytokines and caspases‐3 as an apoptotic marker. The attenuation of CM to colon injury was also associated with suppression of oxidative stress via reduction of lipid peroxides and nitric oxide along with boosting the antioxidant defenses through restoration of colon glutathione and total anti‐oxidant capacity. Together, our study highlights evidences for the promising alleviating effects of CM in colitis. Thus, CM may be an interesting complementary approach for the management of IBD.
Plasma folate levels are inversely associated with natural killer cell degranulation in mice (135.1)
Authors: Warzyszynska Joanna , Sohn Kyoung‐Jin , Spring Christopher , Duan Angela , Kim Sung‐Eun , Carlyle James , Kim Young‐In
Published: June 2021

High intake and plasma levels of folic acid (FA), the synthetic form of the B‐vitamin folate, were associated with reduced natural killer (NK) cell cytotoxicity in post‐menopausal women. This observation has not yet been confirmed. Thus, we examined the relationship between dietary FA intake/plasma folate levels and NK cell activity in an animal model. Post‐weaning C57BL/6 mice were randomized to receive diets containing 2 (control) or 20 mg FA/kg diet for 3 months. A flow cytometry based CD107a and IFN‐γ detection assay was used to assess splenic NK cell activity. Plasma folate levels were significantly higher (p < 0.0001) in the high FA group. Plasma folate levels were significantly and inversely associated with the frequency of NK cell degranulation (%CD107a+ NK cells) in response to stimulation with the mouse T‐cell lymphoma YAC‐1 and cytokines (rs = ‐0.520; p = 0.035) but not in response to mitogenic stimulation with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. Plasma folate levels were not associated with IFN‐γ production (%IFN‐γ+ NK cells) in response to either YAC‐1 and cytokine or PMA/ionomycin stimulation. Our findings corroborate an inverse association between high FA levels and NK cell cytotoxicity and suggest that reduced target cell recognition, evidenced by reduced degranulation in response to cancer cell targets but not in response to mitogenic stimulation, is a likely mechanism behind this inverse association. Our data suggest that impaired NK cell function may be a mechanism behind the purported tumor‐promoting effect associated with high FA supplementation.

Grant Funding Source: Supported by CIHR MOP #14126
Regulation of the protein degradation pathways by amino acids and insulin in skeletal muscle of neonatal pigs (137.1)
Authors: Suryawan Agus , Nguyen Hanh , Parada Rosemarie , Davis Teresa
Published: June 2021

The rapid gain in lean mass in neonates requires greater rates of protein synthesis than degradation. We previously delineated the molecular mechanisms by which insulin (Ins) and amino acids (AA), especially leucine (leu), modulate protein synthesis in skeletal muscle and how this changes with development. These studies aimed to determine whether Ins, AA or Leu alter the abundance and activation of ubiquitin‐proteasome, i.e., atrogin‐1 (MAFbx) and muscle RING‐finger protein‐1 (MuRF1), and autophagy‐lysosome, i.e., microtubule‐associated protein light chain 3 (LC3) and lysosomal‐associated membrane protein 2 (Lamp‐2), protein degradation systems and whether the responses change with age. In study 1, overnight fasted 6‐ and 26‐d‐old pigs were infused with saline or with insulin or AA to achieve fed levels. In study 2, overnight fasted 6‐d‐old pigs were infused with Leu while Ins and AA were kept at fasting levels. Abundance of atrogin‐1, but not MuRF1, was greater in 26‐ than in 6‐day‐old pigs (P<0.05) and was not affected by Ins, AA, or Leu. Abundance of LC3 was higher in younger pigs and not affected by treatment (P<0.05). LC3‐II/LC3‐I ratio was reduced by Ins, AA, and Leu (P<0.05). This response was more profound in younger pigs. Abundance of Lamp‐2 was not affected by treatment or development. In conclusion, Ins, AA, and, in particular, Leu act as signals to modulate muscle protein degradation in neonates.

Grant Funding Source: Supported by NIH AR444474 and USDA/ARS 6250‐51000‐055
Energizing your educational scholarship: What are the hot topics? (14.1)
Authors: Uijtdehaage Sebastian
Published: June 2021

We compiled a list of 10 hot topics in medical education that we vetted with medical education researchers across the country. In this short presentation we provide an overview of issues and challenges that health sciences educators currently debate and that may suggest focus areas for educational scholarship. The list is phrased in terms of research questions and spans topics ranging from challenges of national significance (e.g., changes in healthcare delivery) to local issues (e.g., flipped classroom).
Tissue resident macrophages regulate IL‐23‐dependent granulopoiesis (146.7)
Authors: Mackey Lantz , Perez Eliezer , Rose Jason , Homeister Jonathon
Published: June 2021

Mice deficient in α(1,3)‐fucosyltransferases 4 and 7 (FUT‐/‐) lack selectin ligand activity and selectin‐dependent leukocyte trafficking, resulting in altered IL‐23‐dependent granulopoiesis. It is not clear if this granulopoiesis is regulated by bone marrow‐derived macrophages (BMMC) or a distinct population of tissue resident macrophages (TRM). We hypothesized that the loss of FUT‐dependent trafficking reduces the number of neutrophils able to infiltrate tissues, undergo apoptosis, and be phagocytosed by TRMs, altering IL‐23 production. Primary Kupffer cells (pKC) and BMMC were isolated from FUT‐/‐ and WT mice, stimulated in vitro with LPS, and assessed for IL‐23 production. WT mice were irradiated and their hematopoietic system was reconstituted with 1x106 bone marrow cells isolated from WT or FUT‐/‐ mice. Six weeks after reconstitution, circulating WBC counts were assessed. There was no difference in gene expression levels of IL‐23 between WT and FUT‐/‐ pKCs or BMMCs, indicating that IL‐23 production from FUT‐/‐ macrophages is intact. WT mice reconstituted with FUT‐/‐ bone marrow show a pronounced neutrophilia similar to that seen in FUT‐/‐ mice. These results confirm that FUT‐dependent neutrophil trafficking is required for the regulation of granulopoiesis and suggest that the TRM populations are responsible for clearing apoptotic neutrophils and regulating IL‐23 production in granulopoiesis.

Grant Funding Source: R01‐HL090823, T32‐HL069768
Micromechanical forces regulate vascular patterning in the chick chorioallantoic membrane (15.3)
Authors: Belle Janeil , Ysasi Alexandra , Bennett Robert , Ackermann Maximilian , Wagner Willi , Konerding Moritz , Tsuda Akira , Mentzer Steven
Published: June 2021

Mechanical forces have been implicated in blood vessel growth associated with diverse activities such as organ development and wound healing; however, the link between mechanical forces and network structure remains elusive. To test the hypothesis of a direct effect of mechanical force on axial blood vessel growth, we studied ex ovo chick embryo chorioallanotic membranes (CAMs) between embryonic development days 10 to 13. Uniaxial stretch was applied to CAMs for 72 hours using computer‐controlled servomotors to provide a reproducible stretch field. Sholl analysis of fluorescent micrographs of CAM vasculature and scanning electron microscopy (SEM) of vascular corrosion casts were used to characterize vascular structure. Distinct vessel branching was observed across the stretch field and among stretch and control CAMs. Vessel bifurcation angles were significantly lower in stretched CAMs (30.8°; 69.2°, p< 0.01). Mean interbranch length was longer in stretched compared to control CAMs (2.63 mm ± 0.58; 0.93 mm ± 0.33, p< 0.01). Corrosion casting and SEM demonstrated marked sprouting and intussusceptive angiogenesis in the capillary plexus in stretched areas of CAM. Mechanical stretch in the CAM may stimulate axial growth of conducting vessels and both sprouting and intussusceptive angiogenesis in gas exchange capillaries. These results indicate that mechanical force may have vessel‐specific influences on vascular patterning.

Grant Funding Source: Supported by NIH 5T32‐CA009535
Estradiol activates AMPK through interaction with extrogen receptor beta (15.4)
Authors: Lipovka Yulia , Konhilas John P.
Published: June 2021

The susceptibility and progression of cardiovascular disease (CVD) increases in post‐menopausal women. AMP‐kinase (AMPK) has emerged as prominent player as a cellular energetic regulator that is known to modify both metabolic and contractile function in the heart. Our on‐going studies indicate that AMPK activation is down‐regulated during menopause and that this may play a role in the increased risk of CVD in post‐menopausal women. The aim of this study is to determine the mechanistic link between estrogen (Estradiol) and AMPK activation. We show that Estradiol (E2) increases AMPK activity in c2c12 myotubes, as well as in human ductal breast epithelial tumor cells (T47D). Further, AMPK activity is potentiated by chemical as well as siRNA inhibition of the individual Estrogen Receptors (ERα or ERβ), suggesting an antagonistic effect of the two Estrogen Receptors (ER) on AMPK activation. Next, we hypothesized that E2 regulates AMPK through a direct interaction of ER and AMPK. Using co‐immunoprecipitation in neonatal rat cardiomyocytes and female mice hearts, we show a direct interaction of ERβ with AMPK and MO25, a component of the upstream AMPK activation complex. We conclude that E2 can activate the AMPK through a direct interaction of ERβ with members of the AMPK kinase complex.

Grant Funding Source: Supported by R01 HL098256A
Mixed proteome analysis for clarification of the mechanism of infectious candidiasis (152.6)
Authors: Kitahara Nao , Morisaka Hironobu , Aoki Wataru , Kuroda Kouichi , Ueda Mitsuyoshi
Published: June 2021

Candida albicans is an opportunistic pathogen that causes fatal disease in immunocompromised hosts. Host resistance against pathogenic fungus such as C. albicans relies on the ingestion and elimination by macrophage. However, once inside the macrophage, C. albicans can break through it and spread around the body. In this study, using mixed proteome analysis, we have investigated the response of C. albicans to phagocytosis by macrophage. Unlike previous works, mixed proteome analysis does not require any additional prefractionation of two organisms prior to the separation and detection by nanoLC‐MS/MS system. This system is equipped with a monolithic silica capillary column (500 cm long), which offers high separation efficiency to the tryptic peptides in highly complex samples [1,2]. We cultivated C. albicans with macrophages for 0, 3, and 5 h, and determined 499 and 1273 proteins for C. albicans and macrophage, respectively. Pathway analyses of C. albicans proteins and macrophage proteins were carried out. From these results, a model of the interaction of C. albicans with macrophage was constructed [3].
Modeling cranial biomechanics in archosaurs using 3D computational methods (17.5)
Authors: Holliday Casey , Sellers Kaleb , Davis Julian , Tea Juliann , Miller‐Phillips Chanel , Witmer Lawrence
Published: June 2021

Accurately modeling cranial function in vertebrates remains a challenging yet important tool for ecologists, functional morphologists, and paleobiologists. Three‐dimensional computational methods now offer new approaches for reconstructing jaw muscle anatomy and the cranial biomechanical environment so that evolutionary and functional hypotheses can be tested. Here we present several examples that reconstruct muscle forces, joint moments and bite forces in extant and extinct archosaurs using 3D modeling techniques. 1) We compared modeled bite forces in an ontogenetic sample of Alligator mississippiensis with published in vivo bite forces to validate whether the method is applicable to diapsid vertebrates. 2) We modeled bite forces and joint moments within the skulls of the non‐avian dinosaurs Tyrannosaurus rex and Edmontosaurus regalis to test the sensitivity of input parameters with force estimates. 3) Using these latter taxa, we compared moments about joints implicated in cranial kinesis to identify functional patterns. These models will enable us to test for coevolution between bite force and dietary correlates in fossil archosaurs, estimate loading patterns within cranial joints, and determine patterns in jaw muscle anatomy and function among tetrapods.
Importance of interprofessional approaches in medical education (18.1)
Authors: Kirch Darrell
Published: June 2021

Today’s political, economic and health realities present significant opportunity to shape the United States health care system so that it provides better care to more people at reasonable cost. To sustain such improvements in health care, academic health centers must train future health professionals differently. For example, physicians trained in a model that emphasizes autonomy and hierarchy will find it difficult to practice patient‐centered medicine in a high‐functioning health care team. In recognition of the needs of future physicians, many of our nation’s medical schools and teaching hospitals are implementing innovative programs that promote the importance of interprofessional collaboration and team‐based health care. Dr. Kirch will highlight some of these innovations and discuss additional educational initiatives, including ways in which interprofessional education can reshape our approach to basic sciences and our teaching of anatomy, to ensure an adequate supply of future‐oriented health professionals.
RNA and small molecule probes of hiPSC‐cardiomyocyte differentiation and physiology (207.1)
Authors: Mercola Mark
Published: June 2021

There is an urgent need for therapies that reverse the course of ventricular dysfunction in heart failure, which is a leading cause of morbidity and mortality. We have performed high throughput chemical and functional genomics screens probing cardiomyocyte differentiation and contractility, and used the results to construct protein‐protein interaction networks controlling these complex biological processes. To measure cardiac contractility in high throughput, we have used an automated microscopy platform (Vala Sciences) that optically measures heart muscle cell action potential and calcium transient kinetics and morphology. By screening static and kinetic endpoint assays against whole genome microRNA libraries, we have reconstructed microRNA:protein networks that control myocyte differentiation and contractility. This approach has revealed a number of microRNAs that direct differentiation and modulate physiological function, including microRNAs that adversely affect heart function in vivo. Targeting one of microRNAs with an antisense RNA is able to enhance echocardiographic and hemodynamic indices of heart function in vivo and halt the progression of established heart failure in a mouse pressure overload model.
Generation of insulin‐producing cells from human stem cells (207.3)
Authors: Hebrok Matthias
Published: June 2021

Recent advances in directing human embryonic stem cells (hESC) towards endodermal organs have identified conditions under which hESC differentiate into pancreatic progenitor cells in cell culture. Transplantation of these progenitor cells into immune compromised mice allows for the generation of insulin‐producing, ß‐like cells capable of restoring normoglycemia in diabetic mice. However, the generating of functional ß‐cells under cell culture conditions has proven difficult. Using a combination of 2D and 3D culture methods and optimized culture conditions we have generated single hormone‐positive, ß‐like cells that show signs of glucose responsive insulin secretion. Furthermore, I will discuss efforts related to identifying signals provided by the pancreatic mesenchyme that guide ß‐cell formation and can be used to optimize cell culture conditions.
Controlling the dynamics of differentiation: regulation of cardiac outflow tract assembly (210.1)
Authors: Yelon Deborah
Published: June 2021

Heart assembly requires input from two populations of progenitor cells ‐ the first and second heart fields ‐ that differentiate at distinct times and create different cardiac components. The cardiac outflow tract (OFT) is built through recruitment of late‐differentiating, second heart field (SHF)‐derived cardiomyocytes to the arterial pole of the heart. Mechanisms responsible for selection of an appropriate number of OFT cells from the SHF remain unclear. Here, we find that cell adhesion molecule 4 (cadm4) is essential for restricting the size of the zebrafish OFT. Knockdown of cadm4 causes dramatic OFT expansion, and overexpression of cadm4 results in a greatly diminished OFT. Moreover, cadm4 activity limits the number of OFT progenitor cells and the duration of their accumulation at the arterial pole. Together, our data are the first to suggest a critical role for cell adhesion in restraining SHF deployment to the OFT, perturbation of which could cause congenital OFT defects.
Genetic analysis of the Hippo signaling pathway in mammalian liver development and disease (210.2)
Authors: Johnson Randy
Published: June 2021

The Hippo signaling pathway is an emerging growth control and tumor suppressor pathway. Our laboratory has been using a genetic approach in mice to study the role of Hippo signaling in regulating liver progenitor cell growth and differentiation. Hippo signaling is dynamically modulated during liver development to ensure proper maturation of two major cell types of the liver: hepatocytes and biliary epithelial cells. In addition, Hippo signaling is required in the adult liver to maintain quiescence and to repress activation of resident liver stem cells. These and other recent findings from our laboratory will be discussed.
Student peer teaching in the anatomy lab enhances anatomy performance in the lowest quartile of allied health students (211.5)
Authors: Gottlieb Samuel , Martin Charys , Nichols Carol , Edmondson Anna
Published: June 2021

The gross anatomy lab provides an opportunity for reciprocal peer teaching (RPT), which enables students to develop communication skills and enhance content understanding. Students alternate dissections and are responsible for providing a review of their dissection to the opposite dissection group. This study examines whether students who led reviews do better on exam questions related to their review topic compared to students who did not lead reviews. It is hypothesized that lower performing students will do better on questions that pertain to their review topic, while higher performing students will do well regardless of providing a review. To assess the influence of RPT, students were divided by grade into four quartiles: 66‐80.6, 80.7‐84.3, 84.4‐90.6, 90.7‐99%. Preliminary results suggest that students in the lowest quartile do better on exam questions that pertain to their review topic (72.3%) compared to students in the quartile who did not give a review (65.2%). For students in the upper three quartiles, there was no difference in performance on questions related to their review topic compared to students within their quartile who did not perform a review. Thus, RPT may be more beneficial to students who may otherwise perform at a lower level. Further investigation, including data collected from other reviews, may increase the sample size and establish significance within other quartiles.
Quantitative and qualitative examination of 2D versus 3D technologies in teaching anatomy (211.7)
Authors: Peterson Diana
Published: June 2021

The primary purpose of the study was to identify whether three‐dimensional technologies significantly improved the knowledge and comprehension levels of students within a gross anatomy curriculum compared to the traditional two‐dimensional figures. We hypothesized that the use of 3D technologies would dramatically enhance the comprehension and retention of students.

We tested our hypotheses in a graduate and undergraduate level gross anatomy curriculum. Students were presented 2D images and 3D study materials (atlases, videos, and animations). All material was presented to the students over blackboard; and individual student usage of all material was tracked throughout the semester (# views, time of viewing, and dates of usage).

Subjective measures of student opinion were taken using student surveys. To provide a quantitative measure of student interest, the number of views for each type of study material was calculated. This calculation was then compared with the subjective student evaluations.

To provide a quantitative measure for learning comprehension, half of the test questions were presented from the 2D and the other half from the 3D study materials. Test scores for questions covering 2D versus 3D material were then compared within each student and between students to determine whether the student’s opinion about their learning improvements was substantiated with their test results.

Subjective results indicate that students were much more interested and engaged with the 3D study materials. Although they prefer 3D materials verbally, students tended to rely more heavily on 2D materials when studying prior to tests and 3D materials when not cramming. Preliminary test results indicate that the student scores on 3D material were better than that of 2D material. As expected, student usage of all study materials increased an individual’s overall scores. Given this bias, the percentage of time utilizing 2D versus 3D study materials, was also positively correlated with improved score.

Grant Funding Source: Supported by Iowa State University Miller Fellowship
Big shifts in anatomy education (215.1)
Authors: Wade Patricia Ann
Published: June 2021

Anatomy instruction is evolving. For some courses, this means fewer lectures, more pre‐class assignments, more in‐class small group activities, and more online and computer‐delivered learning activities. What is the rationale behind these changes in anatomy instruction? Which changes in instruction result in increased mastery of the course material? How does an instructor select the best learning tools and teaching methods for their students? By participating in this session, you will be able to: * Describe the key features of active learning, supporting theories, and evidence.

* Discuss various types of active learning, including the flipped classroom format and independent study methods for anatomy courses.

* List several types of instructional strategies and learning tools for courses in anatomy and other basic science courses.

* Select instructional methods and learning tools that will enhance motivation and mastery of anatomy for students in your classroom.
Making three dimensional human colored skin by using Muse cells, a novel type of non‐tumorigenic pluripotent stem cells (216.3)
Authors: Dezawa Mari
Published: June 2021

We found mesenchymal tissues such as the dermis, bone marrow and adipose tissue and commercially available cultured mesenchymal cells such as fibroblasts hold Multilineage differentiating Stress Enduring (Muse) cells, non‐tumorigenic pluripotent stem cells. We show that human dermal fibroblast‐derived Muse cells are readily reprogrammable into melanin pigment‐producing functional melanocytes by use of certain combinations of factors. Muse cells expressed melanocyte markers including tyrosinase and MiTF and to show positivity for the L‐DOPA reaction, an indicator of melanin production. We then tried to artificially construct colored human skin tissue incorporated with Muse‐derived melanocytes in 3D culture. The dermis was constructed by human fibroblasts and extracellular matrix, and the epidermis by human keratinocytes and Muse‐derived melanocytes. Muse‐derived melanocytes localized themselves in the basal layer of the epidermis and produced melanin in the same manner as authentic melanocytes. This 3D constructed human artificial skin also maintained their melanin production even after the tissue was transplanted to immunodeficient mice back skin. This technique may contribute to autologous transplantation for melanocyte dysfunctions such as vitiligo as well as substituting animal experiments for cosmetic development and drug test.

Grant Funding Source: NEDO, Japan
MOOCing STEM courses: for what purpose and which audiences? (221.1)
Authors: Green Kenneth
Published: June 2021

The continuing campus, public, and even state legislature conversations about the big (massive!) enrollments in the first waves of MOOCs, coupled with a course inventory that includes lots of higher end (upper‐division and graduate‐level) STEM courses, has served as a catalyst for great aspirations and broad discussion about using MOOCs to transform the delivery and the learner experience in STEM courses. Yet a careful examination of several key issues, including content development, instructional infrastructure, and assessment/certification, suggests that any effort “to MOOC” core STEM courses will require the significant investment of time, money, and other resources on the part of professors, instructional support personnel, and academic programs. Moreover, credit remains the coin of the realm in academe: awarding credit and certifying competency pose real challenges for those who wish to leverage MOOCs to advance and enhance STEM education.

BIO: Kenneth C. Green is the founding director of The Campus Computing Project, the largest continuing study of eLearnng and information technology in American higher education. From 1983‐89 Green was the associate director of UCLA's Higher Education Research Institute where he was involved in research on STEM pipeline issues.
MOOCs for hard to find AP courses (221.3)
Authors: Klawe Maria
Published: June 2021

This talk describes two MOOCs (Massive Open Online Courses) being created at Harvey Mudd College for two Advanced Placement courses that are not available at many high schools across the country, namely Introduction to Computer Science and Physics C (Mechanics with Calculus). While individual students will be able to take a course and then receive credit by writing an AP exam, our primary goal is to assist less experienced teachers in offering one of these courses at their own school. Each MOOC will showcase faculty‐student interaction and provide automatic grading for assignments. We also plan to feature a diverse group of students in order to attract more under‐represented groups to STEM education.
Epigenetic mechanisms in reward conditioning (222.1)
Authors: Sweatt David
Published: June 2021

Epigenetic mechanisms typically involve alterations in chromatin structure, which in turn regulate gene expression. “Epigenetics” is functionally equivalent to the mechanisms allowing stable maintenance of gene expression that involve physically“marking” DNA or its associated proteins through post‐translational modification. Thus, regulation of chromatin structure and regulation of direct methylation of DNA are the principal mechanisms of epigenetic regulation. This presentation will address the idea that conservation of epigenetic mechanisms for information storage represents a unifying model in biology, with epigenetic mechanisms being utilized for cellular memory at levels from behavioral memory to development to cellular differentiation. Do epigenetic mechanisms operate in behavioral memory formation, including reward‐based learning? We have generated several lines of evidence that support this idea that I will discuss. 1. Contextual fear conditioning and reward conditioning trigger alterations in hippocampal DNA methylation and histone post‐translational modifications. 2. Inhibitors of DNA methylation block both hippocampal LTP and associative learning in vivo. 3. Remote contextual fear memory is associated with persisting changes in DNA methylation in the Anterior Cingulate Cortex, and DNMT inhibition can reverse established remote memory. 4. Histone acetylation increases in memory formation, and histone deacetylase (HDAC) inhibitors enhance both memory formation and hippocampal long‐term potentiation.
Membrane protein stability as the energy sink for sorting in the periplasm (224.3)
Authors: Fleming Karen
Published: June 2021

We will present novel measurements of folding free energies for the transmembrane proteins PagP and OmpW from E. coli. Our data were collected in the same lipid bilayer and buffer system we previously employed to determine those parameters for E. coli OmpLA. From a biophysical perspective, our results suggest that the stabilities of these proteins may be strongly correlated to the water‐to‐bilayer transfer free energy of the lipid‐facing residues in their transmembrane regions. From a biological perspective, our findings suggest that the folding free energies for these membrane proteins may be the thermodynamic sink that establishes an energy gradient across the periplasm. This potential thus drives the sorting of outer membrane proteins by chaperones to the outer membranes in living bacteria. Binding free energies of these outer membrane proteins with periplasmic chaperones support this energy sink hypothesis.