bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Sedentary Conditions Affect the Number of C1 Neurons in Rat Rostral Ventrolateral Medulla?
Authors: Huber Benjamin , Llewellyn‐Smith Ida J , Mueller Patrick J
Published: June 2021

Cardiovascular disease (CVD) is the leading cause of death in the United States. One of the primary risk factors for CVD is a lack of regular exercise. The brain controls the activity of the autonomic nervous system, which regulates many physiological functions; including blood pressure. The rostral ventrolateral medulla (RVLM) is an important region in the brainstem for blood pressure control because it contains a critical subset of adrenergic (C1) neurons that project to sympathetic preganglionic neurons in the spinal cord. C1 neurons from sedentary rats show more dendritic branching than in active rats, suggesting a novel mechanism by which inactivity could increase sympathetic activity and contribute to hypertension. However, it is also possible that the absolute number of C1 neurons changes along with the number of dendritic branches in sedentary rats. Therefore, the purpose of this study was to test the hypothesis that there are more C1 neurons in the RVLM of rats living under sedentary conditions compared to freely exercising rats. Aiming to understand the mechanisms by which inactivity leads to hypertension, we maintained four‐week old, male Sprague‐Dawley rats for 10–12 weeks under either physically active conditions (running wheels; 410±5.6 km total per rat) or sedentary conditions (no running wheels). Following perfusion and post‐fixation, sections of brainstem were first immunoperoxidase‐stained black for phenylethanolamine N‐methyltransferase (PNMT), a synthetic enzyme and marker of C1 neurons, and then brown for tyrosine hydroxylase (TH), the enzyme that all catecholamine neurons contain. PNMT+TH and TH only neurons in each rat were counted in the 6 sections containing the 600 μm caudal to the caudal pole of the facial nucleus (FN). Sedentary conditions did not produce a difference in the number, or rostrocaudal pattern, of C1 neurons compared to the active group nor an interaction between the two (two way RM ANOVA, p>0.05 ea). Sedentary conditions also did not affect the low number of TH neurons (likely A1 neurons) in the RVLM compared to active rats (2±1 vs. 2±1, respectively). Because the number of RVLM C1 neurons is the same in active and sedentary rats, we can exclude the possibility that an increase in the number of C1 neurons is a cause of increased activation of vasomotor spinal neurons and that structural neuroplasticity in C1 neurons may underlie increased functional excitability of the RVLM in our other studies. Future functional neuroanatomical studies using Fos protein should show whether the overall activation of the population of C1 neurons differs between sedentary and active rats.

Support or Funding Information

(HL096787‐09)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protective actions of angiotensin II type 2 receptors in male mice with muscular dystrophy
Authors: Sabharwal Rasna , Yang Liping , Zimmerman Kathy , Weiss Robert
Published: June 2021

Muscular dystrophies are inherited group of heterogeneous genetic disorders that cause progressive muscle atrophy and dilated cardiomyopathy (DCM). We have identified that the renin‐angiotensin system plays a crucial role in pathogenesis of muscular dystrophy. In particular, we have demonstrated that angiotensin II (Ang II) via type 1 receptors (AT1R) mediate autonomic and skeletal muscle dysfunction at young age (<10 weeks) and predicts onset of DCM at older ages (>45 weeks) in the sarcoglycan delta deficient (Sgcd−/−) mice, an established model of muscular dystrophy [Exp Physiol 2013, 2015]. It is becoming evident that AngII/AT2R can offset the deleterious actions of AngII/AT1R [Curr Opin Nephrol Hypertens 2017; Pharmacol Res 2017]. Therefore, we hypothesized that agonism of AT2R by a non‐peptide small molecule compound 21 (C21; Vicore Pharma) will ameliorate AngII‐induced autonomic and skeletal muscle dysfunction and delay development of DCM in Sgcd−/− mice. Control C57BL6 (n=5–8) and Sgcd−/− (n=6–10) male mice were infused with either vehicle (saline) or C21 (0.03 mg/kg/min, minpump) for eight‐ten weeks, beginning at 3 weeks of age for group 1 (younger‐aged), and at 45 weeks of age for group 2 (older‐aged) experiments. Mean blood pressure (BP), heart rate (HR) and locomotor activity were recorded by telemetry, while cardiac function was assessed by echocardiography. Autonomic indices including baroreflex sensitivity (BRS, sequence technique) and resting cardiac vagal and sympathetic tone (HR responses to atropine and propranolol) were calculated. Group 1: As expected, Sgcd−/− mice exhibit lower BP (105±5 mmHg) and activity (3±1 counts/min), reduced BRS and vagal tone, and increased sympathetic tone (P<0.05 vs. control). C21 improved BRS and restored sympathovagal balance in Sgcd−/− mice; albeit it did not influence these variables in control mice (P<0.05 vs. vehicle). Importantly, C21 normalized locomotor activity and decreased AT1R expression in skeletal muscle of Sgcd−/− mice (P<0.05 vs. vehicle). Group 2: Compared to older‐aged control mice, Sgcd−/− mice exhibit increased left ventricular end‐diastolic and end‐systolic volumes, and reduced ejection fraction (P<0.05). Chronic C21 infusion remarkably improved cardiac function in Sgcd−/− mice (P<0.05 vs. vehicle; NS vs. control). Furthermore, the protective effects of C21 persisted for an additional two weeks after the treatment was discontinued in Sgcd−/− mice. Thus, we conclude that activation of AT2R is a potential novel treatment strategy that alleviates muscular dystrophy phenotype and delays the onset/severity of dilated cardiomyopathy.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Activation of GPR81 Causes Endothelin‐A Receptor‐Dependent Cardiorenal Effects
Authors: Jones Natalie K , Wallenius Kristina , Stewart Kevin , Wiseman John W , Mullins John J , Bailey Matthew A
Published: June 2021

G protein‐coupled receptor 81 (GPR81) is highly expressed in adipocytes and activation by the endogenous ligand lactate or by the specific agonist AZ’55381 inhibits lipolysis. The receptor is also found in non‐adipose tissue2 but the function here is not well understood; recent studies show that GPR81 activation increases blood pressure1.

All animal work was performed in accordance with the UK Home Office Animals (Scientific Procedures) Act of 1986 after ethical review by The University of Edinburgh. Here, we used IV infusion of AZ’5538 in anaesthetised wildtype and GPR81 KO mice to assess the effect of GPR81 activation on blood pressure and renal haemodynamics in vivo. Blood pressure was recorded via a cannula inserted into the carotid artery while renal blood flow was assessed both by a Doppler ultrasound probe placed around the left renal artery or by pulse‐wave Doppler ultrasound in separate experiments. Endothelin‐1 (ET‐1) levels were assessed in plasma samples taken at baseline and post AZ’5538 or vehicle infusion by commercial ELISA.

Data are mean±SD. AZ’5538 increased systolic blood pressure by 14.9±6.5mmHg, whereas the 5% mannitol vehicle had no significant effect (0.7±3.1mmHg, n=6). Renal blood flow was decreased compared to vehicle control in both Doppler flow probe and Doppler ultrasound studies (−0.33±0.23mL/min vs vehicle 0.04±0.02ml/min, P=0.027 and −185±25mm/s vs vehicle −0.4±20mm/s, P<0.01, respectively, n=4). The cardiorenal effects of AZ’5538 were absent in GPR81 null mice, confirming on‐target action. Plasma ET‐1 was increased in drug treated animals compared to vehicle (0.44±0.28pg/mL vs 0.12±0.28pg/mL respectively, n=8, P=0.04). Prior infusion of endothelin‐A receptor (ET‐A) inhibitor BQ‐123 prevented the AZ’5538 mediated blood pressure increase in anaesthetised C57 mice (n=4, P=0.04) where as BQ‐788, a specific endothelin‐B receptor antagonist, did not (n=5, P=0.18).

These data suggest that GPR81 activation influences cardiorenal haemodynamics in an ET‐A receptor mediated manner by stimulating circulating and tissue levels of the potent vasoconstrictor ET‐1. The sensitivity of the renal circulation to GPR81 activation may become physiologically significant when lactate, the endogenous ligand of GPR81, concentration rises, as can occur in ischemic renal disease.

Support or Funding Information

Supported by The British Heart Foundation (FS/15/63/32033) and AstraZeneca (Research Agreement 10028531)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effect of Tempol on Systolic Blood Pressure in Salt‐loaded Hypertensive 129Sv Mice
Authors: Chacko Kevin M. , Liu Lauren P. , Schramm Whitney C. , Malik Zeeshan S. , Alli Abdel A.
Published: June 2021

The underlying mechanisms of salt‐induced hypertension are not completely understood. The purpose of this study was to determine whether oxidative stress contributes to the increase in exosomal MARCKS and ENaC and the increase in blood pressure of 129Sv mice after salt loading. Adult 129Sv mice were salt loaded to induce hypertension and the antioxidant Tempol was infused by osmotic minipump. Blood pressure was measured by tail cuff before and after Tempol infusion. Metabolic cage studies were performed to obtain 24 hour urine collections for the isolation of urinary exosomes and measurement of electrolytes in the urine. Urinary exosomes and kidneys from these mice were processed for protein biochemistry. Western blot analysis showed MARCKS and ENaC proteins are increased in urinary exosomes isolated from salt‐loaded hypertensive 129Sv mice compared to exosomes isolated from urine of the same mice before salt loading. Urinary sodium increased while potassium in the urine decreased after salt loading the 129Sv mice. Tempol infusion ameliorated the salt‐induced hypertension and decreased MARCKS and ENaC proteins in urinary exosomes of salt‐loaded hypertensive 129Sv mice. Taken together, oxidative stress may play an important role in the salt‐induced hypertension and upregulation of MARCKS and ENaC proteins in the kidneys of these animals.

Support or Funding Information

This project was funded by the U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (Grant K01 DK099617; to A.A.A.) and the University of Florida College of Medicine.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
In vivo effects of renal Npt2a inhibition
Authors: Thomas Linto , Xue Jianxiang , Rieg Jessica Ann Dominguez , Rieg Timo
Published: June 2021

Hyperphosphatemia is common in patients with chronic kidney disease and associated with increased mortality. Oral phosphate binders and dietary phosphate restriction are the current management protocols for patients with hyperphosphatemia; however, their effectiveness is insufficient. In the kidney, the sodium‐phosphate cotransporter Npt2a is responsible for bulk uptake of phosphate in the proximal tubule. Recently, an orally bioavailable selective Npt2a inhibitor (Npt2a‐I, PF‐06869206) has been described to reduce phosphate uptake in HEK cells transfected with mouse or rat Npt2a. So far, its physiological in vivo function has not been tested. Based on in vitro IC50 concentrations, we chose to study 30 mg/kg (oral gavage, 1% of body weight) in short‐term (3 hours) metabolic cage experiments in C57BL/6J mice. Compared to vehicle (n=14), bolus administration of Npt2a‐I (n=12) caused significantly higher (~4‐fold) urinary phosphate excretion (104±8 vs 27±6 μmol*min−1, P<0.05). Similarly, urinary phosphate/creatinine ratios were also significantly higher (32±2 vs 8±2 mmol*mmol−1, P<0.05). In addition, Npt2a‐I caused higher urinary excretion of calcium (9±1 vs 3±1 μmol*min−1, P<0.05), sodium (316±37 vs 113±24 μmol*min−1, P<0.05), and chloride (277±31 vs 91±24 μmol*min−1, P<0.05), as well as their respective creatinine ratios (Ca2+: 2.5±0.2 vs 0.8±0.1; Na+: 92±9 vs 31±6; Cl−: 81±8 vs 25±6 mmol*mmol−1; all P<0.05). In contrast, urinary flow rate, urinary potassium excretion, potassium/creatinine ratio, and urinary pH were not significantly different between vehicle and Npt2a‐I. In a different set of mice, we studied the effect of Npt2a‐I on plasma phosphate and calcium. Under baseline conditions, plasma phosphate and calcium levels were not significantly different between the vehicle and Npt2a‐I groups. Oral bolus administration of vehicle did not significantly change plasma phosphate (Δ 0.06±0.08 mmol/L, NS) or calcium (Δ −0.04±0.02 mmol/L, NS) 3 hours after application. In contrast, administration of Npt2a‐I caused a significant decrease in plasma phosphate (Δ −0.5±0.05 mmol/L, P<0.05) without affecting plasma calcium (Δ 0.01±0.03 mmol/L, NS). In summary, our study demonstrates for the first time that in vivo application of a novel Npt2a inhibitor efficiently increases urinary phosphate excretion leading to a decrease in plasma phosphate levels. Thus, inhibiting Npt2a might be a useful treatment strategy for hyperphosphatemia.

Support or Funding Information

TR is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK110621). JX was supported by an American Heart Association Predoctoral Fellowship (18PRE33990236) and LT by a Postdoctoral Fellowship (19POST34400026).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of NHE3 and dietary phosphate in lithium pharmacokinetics
Authors: Valdez Alexandria , Thomas Linto , Xue Jianxiang , Rieg Jessica Ann Dominguez , Rieg Timo
Published: June 2021

Lithium (Li+) is one of the mainstays for the treatment of bipolar disorder despite its side effects on the endocrine, neurological, and renal systems. Experimentally, Li+ has been used to determine proximal tubule (PT) reabsorption based on the assumption that Li+ and Na+ transport go in parallel in the PT. However, the exact mechanism by which Li+ is reabsorbed remains elusive. The majority of PT Na+ reabsorption is directly or indirectly mediated by the Na+‐H+ exchanger 3 (NHE3). In addition, Na+‐phosphate cotransporters (Npt2a/c) have been implicated in renal Li+ reabsorption. We hypothesized that either NHE3 and/or Npt2a/c are mediating Li+ reabsorption. We studied Li+ pharmacokinetics in: i) tubule‐specific NHE3 knockout mice (NHE3loxloxPax8Cre), and ii) mice challenged with low or high phosphate diets. Intravenous (LiCl 5 mmol/kg, 2 μl/g BW) or oral administration (5 mmol/kg, 1% of BW via oral gavage) of LiCl did not result in differences in Li+ bioavailability (~80% in all groups), half‐life or urinary Li+/creatinine ratios between control and NHE3loxloxPax8Cre mice. After one week of dietary phosphate challenges, Li+ bioavailability was ~30% lower on low vs high dietary phosphate (64±4 vs 93±3%, P<0.05), possibly the consequence of a smaller area under the curve after oral administration (21±1 vs 25±1 mmol × L−1 × h, P<0.05). This was associated with lower urinary Li+/creatinine ratios on low vs high dietary phosphate (15±2 vs 47±7 mmol/mmol, P<0.05). Our data indicate that renal NHE3 does not play a role in Li+ pharmacokinetics; however, dietary phosphate has an indirect effect on Li+ bioavailability and Li+ disposition.

Support or Funding Information

TR is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK110621). JX was supported by an American Heart Association Predoctoral Fellowship (18PRE33990236) and LT by a Postdoctoral Fellowship (19POST34400026).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Uncoupling Protein 3 Deficiency Prevents Whitening of Brown Fat and Preserves Insulin Sensitivity in High‐Fat Fed Rats
Authors: Lomax Tyler M. , Ashraf Sadia , Wiseman Jessica M. , Edwards Kristin S. , Harmancey Romain
Published: June 2021

Uncoupling protein 3 (UCP3), a mitochondrial anion carrier promoting fatty acid oxidation in myocytes, is down‐regulated in animal models with obesity, insulin resistance and type 2 diabetes. Although mutations in UCP3 have been linked to obesity in humans, their contribution to increased adiposity and insulin resistance is still unclear. The goal of this study was to investigate the effect of UCP3 loss on the development of high‐fat diet‐induced obesity. UCP3‐deficient rats were generated using CRISPR‐Cas9 genome editing, and male littermates were maintained on a high‐fat diet (HFD) for 14 weeks starting at 8 weeks of age. Compared with wild type control animals, UCP3‐deficient rats experienced a reduction in total body weight gain and body fat percentage. Perirenal fat depots were also lighter and overall contained smaller adipocytes. High‐fat feeding markedly induced whitening of subscapular brown fat depots in wild type rats, which was characterized at the subcellular level by an accumulation of large lipid droplets. Interestingly, whitening of brown fat was reduced in UCP3‐deficient rats. Preservation of brown fat structure in the UCP3 knockout rats was associated with a dramatic change in mitochondrial cristae organization. Although plasma triacylglycerol, free fatty acids, and total cholesterol levels were not different from that of wild type rats, UCP3 deficiency led to a reduction in circulating levels of tumor necrosis factor‐α, improved systemic insulin sensitivity, and improved glucose tolerance. In conclusion, loss of UCP3 unexpectedly reduces fat mass gain and preserves insulin sensitivity under high‐fat feeding in rats. We propose that the improvement of insulin sensitivity is due to decreased fat accumulation in adipose tissue and subsequent reduction of chronic inflammation driven by increased mitochondrial function in brown adipose tissue.

Support or Funding Information

This work was supported by NIH Grants R01HL136438, R00HL112952, P01HL051971, and P20GM104357

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Differential Transcription of CD95 in Abdominal and Lower‐Body Subcutaneous Fat Depot–Implications for Regional Differences in Adipose Tissue Function
Authors: Singh Prachi , Zhang Yuebo , Somers Virend K
Published: June 2021

Background

Abdominal (ABD) and lower‐body (LB) fat depots exert opposing effects on cardiometabolic risk factors. However, molecular mechanisms underlying these differences are not completely understood. Studies suggest an inflammatory role of CD95 in obesity‐associated adipose tissue inflammation and dysfunction. Also, leptin deficiency is associated with increased CD95 expression.

Objective

To examine the expression of CD95 in the ABD and LB fat depots and to investigate leptin‐dependent CD95 regulation.

Methods

Transcription of CD95 and other adipokines was determined in paired subcutaneous abdominal (ABD) and lower‐body (femoral, LB) fat samples obtained from 29 healthy individuals (10 females, age: 29.4 ± 7.6 years, BMI: 24 ± 4.1 kg/m2). The underlying mechanisms and down‐stream effects of altered CD95 expression were evaluated using differentiated human white preadipocytes (dHWP).

Results

Reduced mRNA expression of CD95 was apparent in adipose tissue obtained from LB fat depot [ABD: 4.30 (13.91 – 0.06), LB: 2.49 (10.88 – 0.04), p = 0.01]. mRNA expression of MCP1 [ABD: 0.51 (1.35 – 0.34), LB: 0.51 (1.21 – 0.28), p = 0.51], CCL5 [ABD: 6.60 (43.45 – 1.40), LB: 4.44 (11.28 – 1.27), p = 0.20], TNFα [ABD: 1.10 (6.14 – 0.03), LB: 0.07 (5.84 – 0.03), p = 0.30], and leptin [ABD: 21.86 (31.33 – 14.6), LB: 27.23 (41.69 – 20.35), p = 0.08] was not different between the two fat depots. A positive relationship between CD95 mRNA and other inflammatory cytokines was evident in both ABD (MCP1: ρ = 0.79, p < 0.001; CCL5: ρ = 0.83, p < 0.001; TNFα: ρ = 0.87, p < 0.001) and LB fat depot (MCP1: ρ = 0.87, p < 0.001; CCL5: ρ = 0.78, p < 0.001; TNFα: ρ = 0.83, p < 0.001). Furthermore, leptin‐dependent decreases in CD95 mRNA (p = 0.04) and protein expression (p = 0.03) was seen in dHWP. Also, 24 hour pre‐treatment of dHWP with leptin protected cells from FasL (p = 0.03) induced apoptosis.

Conclusions

Compared to ABD adipose tissue, LB fat has reduced transcription of CD95. Additionally, expression of CD95 mRNA was associated with increased expression of inflammatory cytokines in both ABD and LB subcutaneous fat. Moreover, we show that leptin may mediate decreases in CD95 expression thereby protecting adipose tissue from FasL mediated apoptosis. Our studies suggest that the decreased CD95 mRNA expression in LB fat depot may be related to higher localized leptin expression and possibly contribute to depot specific alterations in adipose tissue function and consequent cardiometabolic risk.

Support or Funding Information

Prachi Singh is supported by AHA grant‐in‐Aid 17GRNT33660138.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Leptin Signaling Defects in Offspring of Dams Having Received Vertical Sleeve Gastrectomy
Authors: Deer Evangeline M. , Welch Bradley A. , Grayson Bernadette E.
Published: June 2021

The global incidence of obesity continues to rapidly increase and is a public health concern. Obesity poses substantial risks for hypertension, diabetes mellitus, osteoarthritis, coronary artery disease and hyperlipidemia, collectively known as Metabolic Syndrome (MetS). A long‐term, successful weight loss treatment in morbidly obese individuals is vertical sleeve gastrectomy (VSG), which resects 80% of the stomach creating a tube linking the esophagus to the duodenum. Because most VSG recipients are women of childbearing age, it is important to understand the impact of the surgery on their offspring.

Previously, we reported that the adult offspring of VSG dams had increased adiposity and were glucose intolerant in comparison to adult offspring of sham dams after animals were challenged with a high‐saturated fat diet. However, no mechanism for this was identified. Leptin is an adipocyte‐derived hormone that conveys the level of stored nutrition in the form of adiposity to the brain and periphery. Here we test the overall hypothesis that leptin signaling is dysregulated in VSG offspring, thus driving metabolic dysfunction. Female Long Evans rats were made obese on a 40% saturated fat diet for 4 weeks. They then received either Sham or VSG surgery and recovered on chow. Six weeks after surgery, they were mated and gave birth naturally. The offspring were weaned on postnatal day 21 (PND21) on to chow. Food intake studies began to be conducted starting at PND60. Chow was pulled at 4 h prior to lights out. Rats were given either intraperitoneal injections of saline or leptin (1mg/kg, PeproTech, Inc., Rocky Hill, NJ) just prior to lights off. Hoppers were returned and food measured at 30 min, 1, 2, 3, 4 and 24 h following injection. A crossover study was performed 1 week later. Leptin administration reduced food intake at all time points in Sham male and female offspring (p<0.05). However in VSG males and females, leptin did not reduce food intake at any time point measured. We fasted animals for 6 hours and then collected blood to measure leptin. No differences in leptin by surgery were measured, only by sex. We conclude that leptin signaling in VSG offspring PND60 is not functioning appropriately. Further work is being conducted to determine which arm of leptin signaling is dysregulated in VSG offspring (i.e. p/STAT, p/AKT, mTOR, SOCS3 and PTB1). This work will inform us of the long‐term impact of maternal bariatric surgery on the metabolic health of offspring.

Support or Funding Information

Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number P20GM104357.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Association between Parental Weight Status and Risk of Hypertension in Children Aged 6 to 12 Years: A Cross‐sectional Study in Shanghai, China
Authors: Lu Liping , Chen Cheng , Cai Wei , Wang Jialu , Jiang Ying , Tang Molian , He Ka , Wan Yanping
Published: June 2021

Background

Parents may play important roles in the regulation of children's weight status and consequently risk of childhood HTN. However, data relating parental dietary/lifestyle characteristics to risk of HTN in their children is sparse.

Objective

Using parental weight status as a marker of their dietary and lifestyle habits, we aimed to examine the association between parental weight status and risk of hypertension (HTN) in their children.

Methods

A total of 1,949 children aged 6 to 12 years (1,012 girls) and their parents were enrolled. Information on demographics, anthropometrics, lifestyle, diet, and medical history were obtained from the participants and their parents through self‐administered questionnaires. Multivariable‐adjusted odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of prevalent HTN in children in relation to parental weight status are presented.

Results

The HTN prevalence in children was 8.4%, with no significant gender difference (9.0% in boys vs. 7.8% in girls, P=0.36). After adjusting for potential confounders, parental overweight was significantly associated with risk of HTN in children. Compared with children who had both parents being normal weight, the risk of childhood HTN was increased by 94% (OR=1.94; 95% CI: 1.08, 3.50) for children with only father being overweight and 109% (OR=2.09; 95% CI: 1.26, 3.46) for children with both parents being overweight. The observed association was attenuated after further adjustment for children's body mass index.

Conclusions

Findings from this cross‐sectional study suggest that parental BMI levels were associated with higher prevalence of HTN in their children through the mediation of children's BMI. Because parental weight status is a marker of the dietary and lifestyle choices in a family, actions focusing on improving health awareness and changing unhealthy habits among parents may exert critical influence on the risk of childhood HTN.

Support or Funding Information

This work was partially supported by a grant from the NIH (R01ES021735).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of early weaning on proliferation and differentiation of intestinal mucosa
Authors: da Costa Aline Vasques , Rattes Isadora Campos , Silva Kethleen Mesquita , Rigonati Cruz Alberto Mendoza , Gama Patricia
Published: June 2021

Homeostasis of intestinal epithelial tissue is essential for the completion of digestion, absorption and barrier protection mediated by specialized epithelial cells. Growth and regeneration are controlled by stem cell niche located at the base of the crypts. The complete functional and morphological development of the intestine occurs during the weaning period, however, it is still unknown how this niche stem cells and the proliferative population behave in face of alterations in dietetic pattern. By considering that breastfeeding has important roles during the development of intestinal mucosa, we hypothesized that early weaning (EW) might induce changes in proliferation and differentiation processes. In order to determine the influence of EW in mucosal morphology and integrity, we studied the size of crypt–villus axis, cell proliferation, the distribution of goblet cells, and the expression of genes involved in intestinal functions and renewal. Wistar rats were separated into groups: suckling control (S) and early‐weaned (EW) at 15d (Ethical Committee 18/2015; 115/2017). Samples from middle jejunum were collected at 15, 18 and 60d for morphological analyses of cells stained with hematoxylin and eosin (HE); quantification of goblet cell after Periodic Acid‐Schiff (PAS) reaction; determination Ki‐67 proliferative index (PI), and RNA extraction for qPCR. We observed that the villus height was significantly decreased by EW at 18 d, showing an evident atrophy. However, at 60 d we did not detect differences between S and EW groups, suggesting a recovery of villus compartment during growth and ageing periods. The number of goblet cells in the villi was significantly reduced in EW group compared to S animals, without recovery at 60 days. In the crypt compartment, goblet cells were not altered by EW, increasing only as a function of villus growth. The PI (%) decreased in EW pups (18 d), and the effect was maintained in adults (60 d). The target genes for growth and functions were analyzed according to their immediate and late effect, and different responses were detected. Our preliminary findings suggest that EW affects cell proliferation, gene expression and the number of goblet cells immediately after interruption of suckling (18 d), but the effects are sustained to adulthood, indicating the priming of epithelial cells by EW.

Support or Funding Information

This study was financed in parts by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Brazil (CAPES) – Finance Code 001; FAPESP grant 2018/07782‐8 and fellowship 2018/07409‐5.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
What Traits Characterize Expert Biomedical Educators?
Authors: Dumas Kenneth D , Kibble Jonathan D
Published: June 2021

It is well known across different cognitive domains that there are differences in the knowledge, skills and actions of experts compared to novices (1). The goal of the present study was to identify traits of expert biomedical educators, with a view to informing future faculty development activities. Two approaches were used. Firstly, a literature review was undertaken using the PubMed and ERIC databases to catalogue expert traits and thereby create a codebook of important themes. A total of 15 articles from higher education settings met search criteria, with five of them focusing on the clinical aspect of teaching, seven on medical education/basic science education specifically, and three on characteristic of all educators. Second, we performed qualitative analysis through a line‐by‐line coding of all available essays from teachers who have been recognized by the American Physiological Society, either as the Arthur C. Guyton Physiology Educator of the Year or as the Claude‐Bernard Distinguished lecturer. Results show that while the literature and the expert essays reported similar qualities, the frequencies differed between two with the top characteristics stressed by leading physiology educators being: student‐centered, active environment, and self‐reflection compared to the literature's frequent terms of: content knowledge, pedagogical competency, and ability as an assessor. These traits were also stratified into 3 more broad categories of: in‐classroom activities, outside‐of‐class activities, and trait of personality or philosophy. In most cases the identified traits are likely to require time on task to develop expertise but others such as student‐centered philosophy and reflective practice could be learned more quickly through deliberate practice.

Support or Funding Information

No Funding

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role‐play: An innovative immune response simulation session enhances understanding of abstract principles of immunology
Authors: Dil Nyla
Published: June 2021

Undergraduate medical education is moving towards engaging students in active learning as opposed to heavily relying on traditional lecture based pedagogy. Immunology is a complex discipline to comprehend and most entering medical students have little to no prior knowledge of this intricate discipline. We developed a novel hands‐on “immune response simulation” session to engage students in active learning of immunological principles and improve integration with medical microbiology.

Students are taught didactic immunology lectures followed by this active learning session where groups of students utilize their immunology knowledge to stimulate an immune response scenario to five major classes of pathogens. Students prepare short enactments playing roles of a host immune cell or a pathogen. Faculty facilitates this learning session and administers the assessment tools. The session outcomes are evaluated by administering pre‐ and post‐immunology tests.

Preliminary results indicate that there is a significant increase in immunology knowledge gained and that students were highly engaged in learning immunology through this innovative pedagogy. Our results indicate that Immune response simulation is an effective pedagogical novelty where students are actively engaged in learning complex immunological principles in a fun, hands on experiential learning session. This novel pedagogical intervention might prove valuable in engaging students in learning other physiological principles.

Support or Funding Information

No funding was received for this project.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Creating and Using “Choose‐your‐own‐experiment” Case Studies in Large Lecture Courses
Authors: Hines Justin K
Published: June 2021

“Choose‐your‐own‐experiment” cases make use of an in‐class iterative cycle in which students choose from a set of experimental options, followed by the immediate acquisition of data, and subsequent discussion before repeating the cycle with another decision. Cases involving iterative decision‐making and evidence gathering are common in medical education and games, but uncommon in undergraduate science education. Notably this game‐like experience is implementable in regular large‐lecture courses. An additional layer of complexity can be added by limiting the ability of students or groups to gather all the data, creating a “jig‐saw” type activity and an opportunity for genuine collaboration toward a common goal. I will present an example of one such case study which is currently published and freely available for immediate use. This original case was created to increase retention and deepen learning by teaching “scientific inquiry” in life science courses. I will also discuss how this method can be easily implemented in other courses and contexts and suggest methods for other practitioners to write their own cases, drawing on my own experiences writing six cases of this type for biology and biochemistry courses. Thus the goal of this session is to aid others in the creation and implementation of content‐specific inquiry‐driven activities in the health sciences to foster increased student retention in these programs.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Acid‐Base Balance: Back to Basics
Authors: Shavit Ayal , Janssen Herb
Published: June 2021

For decades students have struggled to understand the complexities of acid‐base balance. Facts must be learned, but more importantly concepts must be mastered. To complicate this issue, the student must appreciate the interactions between respiratory physiology, renal physiology, and the complexities involved in acid dissociation and buffering capability. The Davenport diagram provides a graphic representation of the Henderson‐Hasselbalch equation giving students a visual tool useful in understanding these complex interactions. One of the least understood components of this graph is the buffer line. The slope of the buffer line is determined by the amount of fixed buffers in the body which can decrease the extent to which new hydrogen ions alter pH. A rapid decrease in ventilation adds additional CO2 and produces acute respiratory acidosis. As can be seen on the ordinate of the Davenport diagram, the bicarbonate ion concentration can easily increase 3–4mEq/l. As this occurs, an equal amount of hydrogen ion is also produced. If it was not for the presence of fixed buffers, this would result in plasma pH≈3. The current teaching approach employs the van't Hoff Equation and the accepted rate of CO2 production in a normal individual. Using these values, it can be demonstrated that the amount of bicarbonate ions produced by reduced respiration is capable of increasing plasma bicarbonate ion by 3–4 mEq/l in several minutes. This increase in bicarbonate is independent of renal function.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Deltoid muscle innervation in cadaveric specimens: A statistical analysis of the axillary nerve entering sites—preliminary results
Authors: Hara Lucas , Akamatsu Flávia Emi , Lima Larissa Barbosa , Itezerote Ana Maria , Hojaij Flávio , Andrade Mauro , Jacomo Alfredo Luiz
Published: June 2021

Proximal humeral fractures are relatively common in the elderly, especially when osteoporosis is present. Surgical therapy includes deltopectoral and deltoid‐splitting approaches. There was sign of denervation of the axillary nerve, in 12,5% and 25% of the patients when subjected to the deltopectoral and deltoid‐splitting approaches, respectively, even in the absence of clinical symptoms, according to one study.

Another study found irreversible increase, as well as histological damage, to the axillary nerve when performing the deltoid‐splitting approach in cadavers specimens.

The exact placement of the axillary nerve into the deltoid muscle in not fully comprehended. Our objective in this study is to provide a statiscal analysis for the entry points of the axillary nerve to the deltoid muscle in cadaver specimens, which could possibly have further applications in surgical therapy.

The axillary nerve and deltoid muscle were dissected in 5 cadavers, exposing the entry of the axillary nerve into the deltoid muscle. The points where the axillary nerve penetrated the deltoid muscle were collected and transposed to a cartesian graph, divided in 4 quadrants, each one representing a topographic muscular area.

Generalized estimation equations were assessed to compare mean points in deltoids with Poisson distribution and identity link function assuming exchangeable correlation matrix. Bonferroni multiple comparisons were used to identify differences between every 2 regions.

We have concluded innervation of the deltoid innervation comes predominantly from areas 1 and 3, without significative statistical difference between right and left deltoid muscle or gender.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Using Digital Multimedia to Learn the Human Gross Anatomy: A Virtual Guide to the Musculoskeletal System
Authors: Hosseini Farshad , Oberoi Vishesh , Doroudi Majid , Vo Lien
Published: June 2021

Objectives

With the goal of improving students' gross anatomy learning experience, we created a visual, interactive presentation of gross anatomy of the gluteal and posterior thigh region. Our specific objectives were to provide students with some background knowledge prior to attending the lab, as well as allowing them to use the videos during the lab, and as a study resource after labs to enhance their learning and exam preparation.

Methods

The video discuss all the key anatomical structures of the gluteal and posterior thigh as defined by the first year medical undergraduate curriculum learning objectives. It also uses interactive labelling, commentary, and questions to enhance the student learning experience.

Results

Surveys were distributed amongst 290 medical students before and after they completed the lab to determine whether the videos were helpful. Over 95% of the students felt that the videos made them more prepared for the labs and enhanced their learning in the lab. They also endorsed the need for more videos for future gross anatomy labs.

Conclusion

Given the positive feedback, we conclude that this visual guide served to enhance the students' gross anatomy experience, and implementing more of such resources would help with their learning and understanding of the material.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A book of VINCENT and GOIFFON on the anatomy of the horse, in 1779, Alfort (France)
Authors: LE FLOCH‐PRIGENT Patrice , NGUYEN Juliette , GILLOT Jean‐Bernard
Published: June 2021

Antoine VINCENT and Georges GOIFFON published in 1779: “Mémoire artificielle des principes relatifs à la fidelle représentation des animaux”, (=Artificial memory of the relative principles for the representation of the animals”, in the “Ecole royale vétérinaire” (= Royal veterinarian school) of Alfort (near Paris, France). The Alain Brieux’ bookstore owned in 2018 the first and third volumes (without the second one) of the original edition of this seminal book. Georges GOIFFON cooperate only to the second volume so these two ones were entirely written and drawn by Antoine VINCENT. there were 23 large folded plates showing the anatomy and the different types of motion in the horse. The authors gave four different shapes for the horseshoes in the horse, determining by the ear and the examination of the ground prints a kind of musical scope that they named “odochronometrical” representing the successive layings and their duration. So it is a prefiguration of the works of Marey with its chronophotography. Marey recognised his scientifical debt to the works of Vincent and Goiffon. The further parts concerning other animals were never published.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hypertelorism of Efnb1 Null Mice Occurs Independently of Changes to Underlying Brain Shape
Authors: Percival Christopher J , Devine Jay , Niethamer Terren , Bush Jeffrey
Published: June 2021

Efnb1+/− heterozygous mice phenocopy many craniofacial characteristics of craniofrontonasal syndrome (CFNS), a disorder caused by heterozygous EFNB1 loss of function mutations. Because ephrin‐B1 is expressed strongly throughout the developing telencephalon in mice, we hypothesized that hypertelorism (increased distance between the eyes) in Efnb1+/− mice could be secondary to early changes in the form of the underlying cerebral cortex. This stems from the common expectation that intramembranously ossified bones surrounding the brain can accommodate unusual patterns of brain growth. We quantified the effect of the heterozygous null mutation on early facial and brain morphology from computed tomography (CT) images of iodine stained E14.5 Efnb1+/− (n=17) and control embryos (n=18). Facial size and shape were measured from manually placed landmarks using geometric morphometrics. Differences in general and local brain size were quantified across soft tissue contrasted CT image volumes using Jacobian determinants derived from the nonlinear registrations required align all specimen images. This analysis indicated that major portions of the forebrain, midbrain, and hindbrain are reduced in size in Efnb1+/− embryos compared with controls. After accounting for differences in overall brain size, we noted a particularly strong local reduction in the subpallium of the forebrain (progenitor of the basal ganglia). To test whether facial changes were secondary to brain dysmorphology in Efnb1+/− mice, we measured facial shape from CT images of unstained E14.5 embryo controls (n=20), embryos with conditional expression in neural crest derived facial tissues (Efnb1lox/+; Sox10Cre−) (n=10), and in neural tissues including the telencephalon (Efnb1lox/+ ; Sox1Cre) (n=10). Although brain size changes are evident in Efnb1+/−, there is no facial shape dysmorphology in mice with neural tissue specific Efnb1 heterozygosity. However, the facial dysmorphology in mice with neural crest Efnb1 heterozygosity are similar in direction and strength to the dysmorphology noted within the Efnb1+/− mice. Our results indicate that strong facial dysmorphology in Efnb1+/− mice is the primary result of heterozygous expression within neural crest‐derived facial tissues. While brain‐skull tissue interactions are critical during development, we should not necessarily assume that skull dysmorphology is secondary when both are affected.

Support or Funding Information

This work is supported by the NIH/NIDCR R01DE023337 and Stony Brook University startup funds to CJP.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex‐Specific Gene Expression in Isolated Human Cardiomyocytes under Pressure Overload
Authors: Kararigas Georgios , Lehmann Daniel , Knosalla Christoph , Gaignebet Lea
Published: June 2021

Cardiac hypertrophy manifests differently between men and women and there are pronounced sex differences in disease progression and outcome. To better understand remodeling and elucidate underlying mechanisms, most approaches have been limited to animal models or multicellular tissue samples. However, little is known about the role of biological sex in remodeling of human cardiomyocytes. We aimed at studying gene expression in isolated human cardiomyocytes under pressure overload hypothesizing significant sex differences. Cardiomyocytes were isolated from the left ventricular (LV) septum of aortic stenosis patients (n = 34; 50% men; 67.5 ± 9.6 years old) undergoing surgical aortic valve replacement. Patients underwent 2D‐guided M‐mode transthoracic echocardiography during the week before surgery and 20.06 ± 9.7 days after surgery. We measured with qRT‐PCR structural genes, as they are involved in cardiac hypertrophy and remodeling, thereby influencing cardiac function. The study was conducted in conformance with the Basic Principles of the Declaration of Helsinki. There was no significant difference between men and women in age, body mass index, systolic and diastolic blood pressure, co‐morbidities and medication. Preoperative posterior wall thickness (P = 0.02), LV end diastolic diameter (P = 0.007) and mass index (P = 0.03) were higher in men than women. At similar levels of aortic valve area index between the sexes, preoperative ejection fraction (EF) was significantly lower in men than women (P = 0.01). Postoperative EF levels improved in men reaching those of women. Male cardiomyocytes had significantly higher levels of ACTC1 (P = 0.03), CTGF (P = 0.03), GATA4 (P = 0.03), GJA1 (P = 0.03), MYH6 (P = 0.02), MYL4 (P = 0.03), NFKB1 (P = 0.01), NPPA (P = 0.03) and NPPB (P = 0.05) than female cardiomyocytes. Next, we asked whether there is an association between gene expression and postoperative EF. The expression of GATA4 (r = −0.77, P = 0.01), GJA1 (r = −0.69, P = 0.03), MYH6 (r = −0.69, P = 0.04), MYH7 (r = −0.82, P = 0.008), MYL4 (r = −0.71, P = 0.03), NPPA (r = −0.9, P = 0.001) and NPPB (r = −0.79, P = 0.01) was negatively correlated with postoperative EF in men only. In conclusion, gene expression is regulated in a sex‐specific manner in isolated cardiomyocytes of aortic stenosis patients. Compared with women, men had higher levels of maladaptive remodeling factors, which may be part of the molecular mechanisms underlying the observed sex differences in cardiac function, i.e. EF. Given the male‐specific changes in EF postoperatively, cardiomyocyte‐specific gene regulation at the time of surgery might inform disease progression.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.