bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Intermittent Hypoxia Promotes Glomerular Hyperfiltration, Reductions in Renal Blood Flow, and Upregulation of Renal A2B Receptor Expression
Authors: Kious Kiefer W. , Twohey Stephanie C.E. , Keomanivong Faithe E. , Neidermann Sarah E. , Dirkman Jacob J. , Marcus Noah J.
Published: June 2021

Background/Significance

Sleep apnea (SA) is associated with hypertension and chronic kidney disease. Changes in adenosine signaling associated with chronic intermittent hypoxia (CIH) during apneic episodes may alter glomerular hemodynamics and contribute to hyperfiltration. In addition, increased signaling through the adenosine type 2B receptor (A2B) may promote inflammation and contribute to renal damage and eventual declines in renal function.

Hypothesis

We hypothesized that short‐term exposure to CIH would promote increased glomerular filtration rate and upregulation of A2B, IL‐6, NGAL, and α‐smooth muscle actin (SMA) expression in the kidney.

Methods

Adult male Sprague Dawley rats were exposed to 10 days CIH (60 sec. FiO2 10%, 120 sec. FiO2 21%) for 8h/d. Glomerular filtration rate (GFR) was measured transdermally (Medibeacon) pre‐ and post‐CIH, and post‐CIH (or sham) renal blood flow (RBF) was measured using Transonic flow probes (2% isoflurane, FiO2 21% and 10%). Cortical and medullary expression of A2B, IL‐6, NGAL, and α‐smooth muscle actin (SMA) was measured via western blot.

Results

Weight‐corrected RBF decreased modestly (15%) after 10 days of CIH (1.89±0.13 mL/min/g vs. 1.42±0.16 mL/min/g, p<0.05). In contrast weight‐corrected GFR increased by 80% from pre‐ to post‐CIH measurements (3.1±0.27 mL/min/g vs. 5.5±0.51 mL/min/g, p<0.05). Renal cortical A2B (1.0±0.09 sham vs. 1.42±0.15 CIH, p<0.05) and IL‐6 (1.0±0.11 sham vs. 1.56±0.21 CIH, p<0.05) and medullary NGAL (1.0±0.22 sham vs. 2.68±0.65 CIH, p<0.05) expression was increased in CIH relative to sham tissue. SMA was not significantly different between groups.

Conclusions

Intermittent hypoxia induces glomerular hyperfiltration and upregulation of renal A2B/pro‐inflammatory pathways, which in turn may precede renal injury.

Support or Funding Information

Supported by a grant from NHLBI (R15 HL138600‐01 to NJM)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Postprandial Effects on ENaC‐Mediated Sodium Absorption
Authors: Klemens Christine A , Blass Gregory A , Brands Michael , Palygin Oleg , Staruschenko Alexander
Published: June 2021

Recent studies have suggested that postprandial increases in insulin directly contribute to reduced urinary sodium (Na+) excretion by altering renal Na+ transport. While there are a number of renal transporters that respond to insulin stimulation, which of these transporters are involved in this Na+ sparing mechanism under normal physiological conditions is not fully established. The epithelial sodium channel (ENaC) is the rate limiting step for sodium reabsorption in the distal nephron and its regulation by insulin is well established; however, the regulatory effect of acute hyperinsulinemia (as would result from a meal) on ENaC under normal conditions is still being debated. The main objective of this study was to test the contribution of ENaC as well as other Na+ transporters to the increase in renal Na+ reabsorption following a meal. To test this, we used fasted Sprague Dawley rats that had been given a high carbohydrate supplement to simulate a meal and analyzed changes to ENaC activity as well as expression of other renal transporters involved in sodium homeostasis. Postprandial changes in circulating renin‐angiotensin‐aldosterone system (RAAS) hormones known to enhance ENaC activity were also tested. We found that 4 hours post carbohydrate stimulus, ENaC open probability increased relative to controls in split‐open isolated collecting duct tubules (0.34 ±0.06 vs. 0.70 ± 0.07, n≥5, p<0.01), while the number of channels at the surface and total ENaC α‐ and β‐subunit levels remained unchanged. We also examined expression levels of the Na+‐Cl− cotransporter (NCC), Na+‐K+‐2Cl− cotransporter (NKCC2), and Na+‐K+‐ATPase (NKA). While there were no significant differences in expression of NCC or NKCC2 in either group, NKA expression in the postprandial group was significantly increased (1.0 ± 0.08 vs. 1.62 ± 0.10, n=5, p<0.001). Additionally, using mass spectrometry‐based analysis, we interrogated different metabolites of RAAS signaling between the stimulated and fasted rats and found no significant changes in aldosterone or angiotensin metabolite levels. These results suggest that acute hyperinsulinemia following a meal increases ENaC activity independent of the RAAS signaling cascade. Our study demonstrates that ENaC and NKA regulation via insulin is a likely contributor to an evolutionary mechanism for preserving sodium and volume loss after a meal, and that this regulation is distinct from classical ENaC regulation by RAAS.

Support or Funding Information

T32 HL134643; R35 HL135749, HL56259

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
ENaC activation by bile acids depends on specific moieties, but not on membrane permeability
Authors: Wang Xue‐Ping , Im Seohyun Janice , Ertem Merve , Balchak Deidra M , Montalbetti Nicolas , Carattino Marcelo D , Ray Evan C , Kashlan Ossama B
Published: June 2021

The epithelial sodium channel (ENaC) mediates Na+ transport in several epithelia, including the aldosterone‐sensitive distal nephron, distal colon, and biliary epithelium. Numerous factors regulate the activity of the channel, including extracellular ligands, post‐translational modifications, and membrane‐resident lipids. Bile acids are abundant in the biliary tree and intestinal tract, and can be elevated in the urine of patients with advanced liver disease. Using Xenopus oocytes, we found that bile acids both activated and inhibited mouse ENaC, dependent on the bile acid. Whether bile acids were activating or inhibiting depended on the position and stereochemistry of specific moieties. Taurine conjugated bile acids had stronger effects than their more membrane permeant unconjugated counterparts, suggesting that bile acids regulate ENaC extracellularly. Bile acids that increased ENaC currents had a hydroxyl group at position 12, facing the hydrophilic side. Bile acids that decreased ENaC currents had a hydroxyl group at position 6. Bile acid dependent activation of ENaC currents was mildly voltage‐dependent, suggesting that regulation occurs in the outer leaflet of the membrane. Bile acids also regulated ENaC in a cortical collecting duct cell line, mirroring results in Xenopus oocytes. These results suggest that bile acids interact directly with ENaC near the interface between the outer leaflet and the extracellular solution.

Support or Funding Information

This work was supported by NIDDK, National Institutes of Health, Grant R01 DK098204 (to O.B.K), and a grant from the Pittsburgh Liver Research Center. The Pittsburgh Center for Kidney Research was supported by Grant DK P30 DK079307 from NIDDK, National Institutes of Health.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MARCKS Expression and Localization in the Aged Kidney of Hypertensive 129Sv Mice
Authors: Malik Zeeshan S. , Schramm Whitney C. , Liu Lauren P. , Chacko Kevin M. , Alli Abdel A.
Published: June 2021

Essential hypertension remains a major public health problem and there is an increase in its prevalence with age. An upregulation in the expression and activity of the renal epithelial sodium channel (rENaC) plays a key role in the development of essential hypertension. MARCKS protein plays an essential role in the positive regulation of rENaC by stabilizing the actin cytoskeleton and increasing the availability of PIP2 at the apical plasma membrane. The goal of this study was to determine whether MARCKS protein expression and association with the actin cytoskeleton is augmented in the aged kidney of hypertensive 129Sv mice. 129Sv mice were aged for 12 months before being subject to salt loading (8% NaCl) for 4 weeks to induce hypertension. Blood pressure was measured by tail cuff and electrolytes in the urine were measured using an electrolyte analyzer. The kidneys were harvested for proteins and the expression of total MARCKS and phospho‐MARCKS was measured by Western blotting and densitometric analysis. Immunohistochemistry was performed to assess the localization of MARCKS and the actin cytoskeleton protein filamin A. The expression of total MARCKS protein increased while phospho‐MARCKS protein expression decreased in kidney cortex lysates from aged 129Sv mice with hypertension compared to aged 129Sv mice without hypertension. The colocalization between MARCKS and filamin A in kidney tubules was augmented in hypertensive aged mice compared to controls. These data indicate MARCKS expression and its function is augmented in the pathogenesis of hypertension in the aged kidney.

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.
Sex Differences in Aged Hypertensive 129Sv Mice
Authors: Liu Lauren P. , Chacko Kevin M. , Schramm Whitney C. , Malik Zeeshan S. , Alli Abdel A.
Published: June 2021

Salt‐sensitive hypertension has become an enormous public health problem due to the recent increase of dietary salt intake in many countries. It is already known that female sex hormones have a protective effect regarding the increase of blood pressure. However, little is known about sex differences in the aged kidney. The goal of this study was to determine whether or not there are differences in blood pressure, ENaC alpha protein expression, and filamin protein expression in the aged kidneys of salt‐sensitive male mice when compared to female mice after salt loading. Male and female 129Sv mice were aged for 12 months and maintained on a normal salt diet (0.4% NaCl) before being salt loaded (8% NaCl) for 4 weeks. During this time, blood pressure was measured by tail cuff and electrolytes in the urine were measured using an electrolyte analyzer. Protein expression of ENaC alpha and filamin were measured by Western blotting and immunohistochemistry. The difference in blood pressure before and after salt loading was greater in the aged male 129Sv mice compared to the females. Before and after salt loading, the male mice showed higher urinary sodium levels than the female mice. There were no differences observed in urinary potassium levels between the male and female mice. Although ENaC alpha protein expression did not change, filamin A protein expression was augmented in the hypertensive aged male mice compared to the females. This data suggests that there are sex differences in the aged kidneys of hypertensive 129Sv mice that do not involve changes in ENaC alpha protein expression but may involve changes in actin cytoskeleton associated proteins.

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.
A single residue substitution confers thiazide sensitivity to the European eel thiazide‐resistant NaCl cotransporter, NCCb isoform
Authors: Vega‐Mateos Antonio , Moreno Erika , Plata Consuelo , Vazquez Norma , Pacheco‐Alvarez Diana , Gamba Gerardo
Published: June 2021

The thiazide sensitive Na‐Cl cotransporter (NCC) is the major pathway for salt reabsorption in the distal convoluted tubule of the mammalian kidney and is the receptor for the thiazide diuretics, which constitute one of the baseline therapies for arterial hypertension worldwide. Yet, the binding site for thiazides at the NCC is still unknown. In the eel the NCC gene is duplicated. The NCCα is an orthologue for mammalian NCC and is expressed at the eel's kidney, while the duplicated gene, the NCCβ is expressed along the intestine and is not present in mammals. We recently reported that the NCCβ of the European eel (eNCCβ) is a thiazide‐resistant NaCl cotransporter (Moreno et al, JBC 2016).

Here, we used “clustal omega” software to analyze all the NCC sequences known to this moment and compared them to the eNCCβ, searching for residues that are conserved in all NCCs, except in the eNCCβ. Using site‐directed mutagenesis we substituted specific amino acid residues in the sequence of eNCCβ, for those that are highly preserved in all other NCC sequences. The mutant cDNAs were sequenced to avoid unwanted mutations. Assessment of the functional expression was performed in Xenopus laevis oocytes, microinjected with cRNA from the wild‐type and mutated eNCCβ, by measuring the tracer 22Na+ uptake in the absence or presence of extracellular chloride or of hydrochlorothiazide.

Sixteen different amino acid residues of the eNCCβ, localized at the first seven transmembrane regions (TM), were individually substituted for the corresponding residue in rat NCC. The wild type eNCCβ cRNA injection induced after two days of incubation the expression of Na‐influx pathway that was chloride dependent, but not affected by thiazide diuretics, up to 10‐3 M concentration. In 15 out of 16 mutant clones, NaCl transport activity was present, but no thiazide sensitivity was observed. However, the substitution of a phenylalanine for a tyrosine at the position 174 (eNCCβ‐F174Y), which is localized at the extracellular loop that binds TM1 to TM2, conferred over 90% of inhibition with hydrochlorothiazide, with an IC50 of about 10‐7 M. In addition, the tracer 22Na+ uptake induced by eNCCβ‐F174Y was inhibited by five different thiazide diuretic tested, but not by furosemide.

A substitution of a phenylalanine for tyrosine residue at position 174 of the eel NCCβ isoform confers sensibility to thiazide diuretics in the eel NCCβ cotransporter.

Support or Funding Information

Supported by Conacyt grant numbers 222918 and 188712 to EM and GG, respectively

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 HORMONES PRODUCED DURING PROESTROUS AND ESTROUS EXERT A REGULATORY EFFECT ON NESFATIN‐1 MRNA LEVELS AND AUTONOMIC FUNCTION IN FEMALE CYCLING RATS
Authors: Pate Alicia Nicole , Schnell Abigayle L. , Samson Willis K , Yosten Gina LC
Published: June 2021

Nesfatin‐1/NUCB2 is a protein derived from the nucleobindin‐2 precursor originally localized in different appetite controlling areas of the brain, such as the hypothalamic PVN, ARC, SON, LHA and NTS, and is thought to be regulated in a sex‐specific manner. It has recently been suggested that nesfatin‐1 might play an important metabolic role during pregnancy and fetal development (2) and the expression of nesfatin‐1/NUCB2 is regulated by progesterone and 17b‐estradiol in mouse pituitary gland (1). We investigated Nesfatin‐1 mRNA expression in female, cycling rats across the estrous cycle and observed a decrease in Nesfatin‐1 mRNA during Proestrous, corresponding to a period of increased levels of Estradiol. We therefore hypothesized that the ability of centrally administered Nesfatin‐1 to raise mean arterial pressure (MAP) in conscious, cycling, freely moving female rats would no longer be seen during the Proestrous day of the estrous cycle. We, therefore, monitored MAP changes across estrous cycle with central Nesfatin‐1 administration. We found that the ability of Nesfatin‐1 to increase MAP is no longer prevalent in female, cycling rats on proestrous and estrous days. We then monitored MAP changes in ovariectomized females with and without estradiol supplementation. We found that the ability of Nesfatin‐1 to increase MAP is no longer prevalent in female rats that were pretreated with estradiol, suggesting that sex‐specific hormones produced during proestrous and estrous exert a regulatory effect on the Nesfatin‐1 mRNA levels and autonomic function.

Support or Funding Information

This work was funded through a President's Research Fund grant (Saint Louis University) to GLCY. WKS and GLCY are supported by a grant from the National Institutes of Health, HL‐121456

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of maternal obesity on body weight regulation and sleep time in offspring
Authors: Moak Sydney P. , Dai Xuemei , Hall John E. , da Silva Alexandre A. , do Carmo Jussara M.
Published: June 2021

Mississippi Center for Obesity Research, University of Mississippi Medical Center – Jackson, MS. There is limited understanding of the mechanisms that link parental obesity to adverse metabolic outcomes in their offspring. In this study we examined factors that influence body weight regulation and sleep time in mice fed a high fat diet after weaning (HFD, n=5) that were offspring of dams also fed a HFD (45% fat) and compared them to HFD fed mice (n=5) from dams on a control diet. Food intake was measured daily and body weight and body composition (EchoMRI) were measured weekly. Energy expenditure (EE), oxygen consumption (VO2), motor activity (MA) and sleep time (Sable System 40 sec criterion) were monitored for 5 consecutive days at 22 weeks of age. There were no significant differences in calorie intake (17.3±0.7 vs. 16.2±0.8 kcal/day), fasting blood glucose (170±13 vs. 187±16 mg/dL), total EE (5.7±0.6 vs. 5.7±0.2 kcal/hr), VO2 (1.5±0.1 vs. 1.7±0.1 ml/min) or MA (57±6 vs. 65±5 m/day) in offspring from dams fed a HFD compared to offspring from dams fed a control diet. However, there were significant increases in body weight (47.3±1.5 vs. 42.4±1.1 g) and fat mass (19.8±0.6 vs. 15.7±1.6 g), and decreased sleep time (8.6±0.2 vs. 9.7±0.2 hr/day, p=0.005) in offspring of dams fed a HFD. These results suggest that maternal obesity increases body weight and fat mass in offspring fed a HFD, and reduces sleep time without altering food intake, VO2, EE, MA, or fasting glucose levels in adult mice (NHLBI PO1HL51971, NIGMS P20GM104357 and NIGMS U54GM115428)

Support or Funding Information

NHLBI PO1HL51971, NIGMS P20GM104357 and NIGMS U54GM115428

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Interrelationships among perceived stress, food addiction, and body mass index
Authors: Lin Yi‐Syuan , Yeh Jhih‐Han , Chien Yi‐wen
Published: June 2021

The degree of perceived stress affects the emotional response of humans, leads to behavioral changes, and is more likely to trigger physical illness. Many studies have indicated that the level of stress and amount of stressors are related to overeating and unhealthy eating behavior, which will cause obesity in the long run. According to the statistics in Ministry of Health and Welfare, the number of visits for mentally stressful diseases in Taiwan has doubled year by year, and adults who are overweight and obese have continued to grow after reaching 43% in 2014. An assumption about whether perceived pressure is a factor affecting the obesity has made and whether food addiction is posing as an intermediate factor has yearn more and more attention in oversea studies. Therefore, the purpose of this study is to explore whether perceived stress affects the development of food addiction and body mass index. The study was conducted through online questionnaire, composed of the basic data form, the Perceived Stress Scale, the Beck Depression Inventory‐Short Form and the Yale Food Addiction Scale. We analyzed 1019 valid questionnaire. The results showed 132 participants met the food addiction criteria, accounting for 12.95% of the total sample. Among them, there were 54 overweight and obese people, accounting for 40.91% of the food addiction participants. Moreover, there were 22 people with mild depression among the samples meeting the food addiction criteria, 54 with moderate depression and 42 with severe depression, in which presented as proportion of 16.67%, 40.91% and 31.82%. By dividing the sum score of the perceived stress scale with the quartile method, 83.3% of the food addiction sample met the top quartile. The study expects that perceived stress level is positively correlated with the prevalence of food addiction, food addiction is positively correlated with BMI, and those with higher perceived stress but lower degree of depression have greater tendency of food addiction and greater BMI values than those with higher perceived stress and higher degree of depression.

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 differences in the physiological response to coconut oil based high fat diets in C57BL/6J mice
Authors: Sitnick Mitchell , Wang Shari , den Hartigh Laura J
Published: June 2021

It is well established that diets containing a high percentage of calories from fat leads to a myriad of metabolic issues from obesity, insulin resistance, and diabetes to an impaired skeletal muscle growth response. With the growing percentage of individuals considered overweight or obese, it is of critical importance that we understand the effect of fats on human physiology. One response to the rise in obesity is an increased promotion of products believed to promote weight management. This is true in the case of coconut oil. Products containing coconut oil have become popular due to a perceived benefit to human health which includes an ability to help control body weight an effect attributed to high levels of short‐ and medium‐chain fatty acids in the oil. While these classes of fatty acids on their own have been shown to be beneficial, the actual health benefits of dietary coconut oil remains unclear.

In order to test the possible health benefits of coconut oil rich diets we fed both male and female, C57Bl/6J mice standard chow or a diet that contained either 10% (LFC) or 45% (HFC) kcal from coconut oil. Mice were fed for either 14 weeks or 30 weeks and multiple physiological parameters were measured. In response to the diets, preliminary analyses suggests that that while HFC led to a significant alterations in body and tissue weights compared to LFC, gender had a significant moderation effect on weight (β = −7.052, p<0.05) and other parameters (Subcutaneous fat, β =−1.926, P<0.027, Tibialis Anterior mass, β = 0.036, p<0.05).

While further testing is needed, this data partially supports the idea that, in moderation, coconut oil could potentially serve as a beneficial fat source for certain populations. Further, these results provide additional evidence in support of the current initiative to account for sex as a biological variable in basic physiological studies.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High Saturated and Unsaturated Fat Diets Yield Different Disease Phenotypes in Mice
Authors: DeWitt Elizabeth , Dysinger Ian , Larmer Zachary , Kolwicz Stephen C
Published: June 2021

Excessive consumption of unsaturated or saturated fatty acids have adverse effects on certain health parameters, namely increased risk of obesity, diabetes, and cardiovascular disease. Specifically, saturated fats are linked to increased cardiovascular risk while unsaturated fats are suggested to protect against cardiovascular disease. Our previous work suggested that various high fat diets have differential effects on cardiac hypertrophy and function. However, it was not clear whether a high saturated fat diet (HSFD) or high unsaturated fat diet (HUFD) could elicit different disease phenotypes. Therefore, the purpose of this study was to evaluate the effects of HSFD or HUFD on the development of obesity, diabetes, and cardiac lipotoxicity in mice. Male, C57BL/6J mice received normal chow (CON, n=12), HSFD (n=15) or HUFD (n=15) for 12 weeks. Body weight and food intake were measured weekly. After 12 weeks, the adipose tissue and heart were removed and weighed. Glucose, fatty acids, and cholesterol were analyzed in serum using biochemical assays. Cardiac triglycerides (TG) were measured in heart tissue extracts. Both HSFD and HUFD significantly increased body weight above CON. Interestingly, body weight increased by ~63% in the HUFD while the HSFD increased ~41% (P<0.05). Adipose tissue mass was increased 5‐fold in both HFD groups and was ~10% greater in the HUFD. Surprisingly, caloric intake was higher in the HSFD (15.3±0.8) compared to HUFD (12.8±0.1) and CON (11.9±0.7). Serum cholesterol levels were elevated in both HSFD and HUFD. Blood glucose was significantly increased only in the HUFD while serum fatty acids were increased only in the HSFD. Cardiac hypertrophy, assessed by the heart weight to tibia length ratio, was increased in the HSFD but not HUFD group. Cardiac TGs were ~25% higher in HSFD but <10% in HUFD compared to CON. These data show that excess consumption of saturated or unsaturated fats increased body weight and adiposity in mice. However, high consumption of unsaturated fatty acids resulted in a pronounced increase in body weight, body fat, and hyperglycemia, consistent with an obese and diabetic phenotype. Conversely, high consumption of saturated fatty acids caused elevated serum lipids, cardiac hypertrophy, and cardiac lipid accumulation, consistent with cardiac lipotoxicity. In conclusion, the fatty acid composition of diets may be critical in the development of disease phenotypes resulting from high fat feeding in mice.

Support or Funding Information

This work was supported by funding from the American Heart Association and Ursinus College.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Maternal and Sex‐Specific Fetal Characteristics of Three Different Mouse Models for Fetal Programming by Preeclampsia
Authors: Plösch Torsten , Dijkstra Dorieke J. , Stojanovska Violeta , Verkaik‐Schakel Rikst Nynke , Scherjon Sicco A.
Published: June 2021

Epidemiological data shows that preeclampsia increases the susceptibility for cardiovascular and metabolic diseases later in life in mother and offspring. This is usually referred to as “fetal programming” or “epigenetic programming”. However, conclusive data on causative factors and molecular mechanisms is lacking. This could potentially be examined in animal models, but preeclampsia is a multifactorial disease for which the perfect animal model does not exist. Here we compare the maternal and fetal status at the end of preeclamptic pregnancy in several mouse models, in order to unravel the mechanisms possibly involved in long‐term programming of health.

We employed three C57Bl/6 mouse models mimicking specific parts of the phenotype of preeclampsia: the sFlt+LPS model, a combination of an antiangiogenic and a proinflammatory factor; the L‐NAME model, where vasoconstriction is induced; and the LXR agonist model, which is shown to induce metabolic distortion and antiangiogenesis. Interventions took place at gestational day 8 or 10. Right before delivery, at gestational day 18, we compared maternal and fetal phenotypes between the models.

Elevated maternal systolic blood pressure was found in sFlt+LPS and L‐NAME dams, while to our surprise blood pressure was decreased in the LXR agonist model. Albuminurea was only found in the sFlt+LPS model. Maternal circulating insulin, an important fetal growth factor, was found decreased in the LXR agonist model, while no changes were found in free thiols, a measure of oxidative status.

Consequences for fetuses were model‐ and sex‐specific. LXR agonist and sFlt+LPS fetuses were growth restricted, with brain sparing taking place in male fetuses only. Placental efficacy, as measured by body weight/placenta ratio, was lower for male LXR agonist and L‐NAME fetuses. Disturbed fetal growth is known to have long‐lasting metabolic consequences for the fetus.

To conclude, we show here that different animal models for preeclampsia result in different maternal and fetal characteristics, with the sFlt+LPS model showing the most resemblance with clinical preeclampsia. A long‐term study in the sFlt+LPS model will give insight in programming effects and programming mechanisms of preeclampsia for both mother and offspring.

Support or Funding Information

This work was supported by the Netherlands Organization for Health Research and Development (ZonMW, grant number 91211053 to T.P.).

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 Computational Models for Blood Pressure Regulation in the Rat
Authors: Ahmed Sameed , Leete Jessica , Hernandez Francisco Lopez , Layton Anita
Published: June 2021

Renal hemodynamics play a critical role in blood pressure regulation, while renal autoregulatory mechanisms maintain kidney function for varying blood pressure. Computational models have been developed of the cardiovascular system to simulate blood pressure regulation in humans, including the seminal model by Guyton et al. (Ann Rev Physiol 1972). Although the Guyton model and its many variants represent mechanisms for renal autoregulation, they appear to fail to adequately maintain glomerular filtration rate for a sufficiently wide range of blood pressure. Additionally, while such human models have clinical values in that they can be used to assess the effects and reveal mechanisms of hypertensive therapeutic treatments, rodent models would be more useful in assisting the interpretation of animal experiments. Finally, despite well‐known sexual dimorphism in blood pressure regulation, all published models are gender neutral Given these observations, the goal of this project is to develop the first sex‐specific computational models of blood pressure regulation for the rat. The resulting models represent the interplay between cardiovascular function, renal hemodynamics, and kidney function. They also include the actions of the renal sympathetic nerve activity and the renin‐angiotensin‐aldosterone system. We applied the models to investigate the cardiovascular effects of antihypertensive treatments including diuretics, angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blocker (ARB), and of nonsteroidal anti‐inflammatory drugs (NSAIDs). Simulations were conducted to identify risks factors for acute kidney injury following the administration of a combination of these treatments.

Support or Funding Information

This research was supported by the Canada 150 Research Chair program and by the National Institutes of Health: National Institute of Diabetes and Digestive and Kidney Diseases, grant R01DK106102.

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 synthetic flavagline FL3 suppresses intestinal tumorigenesis in APCMin/+ mice
Authors: Jackson Dakota N , Abou‐Hamdan Hussein , Cook Beth N , Desaubry Lauent , Souza Rhonda F , Theiss Arianne L
Published: June 2021

Introduction

Flavaglines are natural plant products shown to have anti‐inflammatory and anti‐cancer effects. FL3 is a synthetic derivative of the flavagline Silvestrol, lacking its structural components linked to causing multidrug resistance and suboptimal absorption and metabolism. Ongoing studies in our lab have shown that FL3 inhibits the Wnt/β‐catenin pathway in colon cancer cell lines. This is especially important since in most colorectal cancer cases aberrant activation of the carcinogenic Wnt pathway occurs via inactivation of the adenomatous polyposis coli (APC) tumor suppressor gene or activating mutations in CTNNB1 encoding b‐catenin. To assess in vivo action of FL3, we used the APCMin/+ mouse model of spontaneous intestinal tumorigenesis driven by enhanced β‐catenin activation via the loss of heterozygosity mutation in the APC gene.

Methods

Male and female APCMin/+ mice were administered FL3 (0.1 mg/kg) or vehicle by intraperitoneal injection twice weekly from ages 15 to 20 weeks of age. To assess whether FL3 affected the normal intestine, wild‐type (WT) littermates were injected with FL3 alongside APCMin/+ mice. The entire small intestine and colon were excised and adenoma distribution, size, and number were quantitated using a dissecting microscope. Swiss‐rolled intestines and colons were used for histology and severity of dysplasia or villus/crypt measurements in WT mice. Proliferation was measured by PCNA expression and Ki67 immunostaining in adenomas. Apoptosis was measured by Cleaved Caspase 3 expression and TUNEL immunostaining in adenomas.

Results

FL3‐treated WT mice exhibited normal intestinal and colon histology, villus/crypt measurements, and no dysplasia. FL3 injection decreased the number and size of adenomas in APCMin/+ mice. TUNEL staining and Cleaved Caspase‐3 expression were increased in adenomas in APCMin/+ mice treated with FL3. FL3 did not alter cell proliferation.. Adenomas in APCMin/+ mice treated with FL3 exhibited increased TUNEL staining and Cleaved Caspase‐3 expression and had no changes in cell proliferation compared to APCMin/+ mice not treated with FL3..

Conclusions

FL3 protects against in vivo tumorigenesis driven by aberrant activation of the Wnt/b‐catenin pathway in APCMin/+ mice. FL3 suppressed tumorigenesis by increasing rates of apoptosis without affecting rates of proliferation in neoplasias. This proof‐of‐principle study suggests that FL3 is effective in combating tumorigenesis in a pre‐clinical animal model of aberrant Wnt/b‐catenin pathway activation.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exercise Physiology: more PhUn than just play
Authors: Perez‐Cardona Enrique U. , Rodríguez‐Graciani Keishla Marie
Published: June 2021

Physiology is an unknown scientific discipline in high schools in Puerto Rico. In the past few years the chapter of the American Physiological Society in Puerto Rico at the Medical Sciences Campus has designed and implemented a Physiology Understanding Week (PhUn Week) to introduce high school students to basic concepts of neurophysiology, cardiovascular physiology and respiratory physiology, all separately. This year we decided to use Exercise Physiology as a tool to integrate basic concepts in physiology and to show students how these concepts are relevant to our daily lives. Unlike previous PhUn Week events, this year, we introduced the skeletal muscle system and movement concepts that would illustrate better the idea of integration of physiological systems. We used the example of climbing stairs to show the students how the cardiovascular and respiratory systems are activated and interact during an acute effort. In addition, we compared a student not involved in exercise training with a physically trained student to demonstrate the differences in the cardiovascular and respiratory responses to the acute demands of physical effort and exercise. In this case, we also integrated relevant neurophysiological concepts. At the end of the PhUn week integrative session, the students understood that these systems interact with each other and can adapt positively to the demands of exercise training. We concluded that exercise physiology is a fun way to learn basic concepts of neurophysiology, cardiovascular physiology and respiratory physiology.

Support or Funding Information

Physiology Understanding Week is sponsored by the American Physiological Society. Enrique U. Pérez‐Cardona was supported by the UPR MSC RISE Program under the NIH grant R25 GM061838.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
An Active Learning and Draft‐Revision Approach to Teaching Scientific Writing to Undergraduate Physiology Students
Authors: Weaver Chelsea C , Taylor Jessica C , Osborn Jeffrey L
Published: June 2021

The comprehension and communication of scientific literature are critical in training prospective scientists, yet undergraduate students are rarely exposed to these concepts in their STEM courses. To this end, we designed and implemented a series of mini‐workshops focusing on scientific evaluation and writing. Five undergraduates participated in these pilot workshops during weekly lab meetings. The first workshop taught students how to select and critically evaluate a peer‐reviewed paper for journal club. Students discussed the guidelines for authorship, the importance of assessing the quality of a journal, and how to concisely skim the article prior to choosing it for presentation. The second focused on abstract writing using active learning techniques. The students engaged in a discussion on scientific writing, including formatting, word choice, and style. They were introduced to the required sections of an abstract: title, introduction, animal model, hypothesis, methods, results, discussion, and conclusions. Laminated, cutout headers of each of the abstract components, along with single sentence snippets from a previously published abstract that was unknown to the students were provided for the exercise. As a group, they were tasked with classifying each of the sentences under the section headers. Afterward, students put the sentence cutouts together in a coherent fashion to form the complete abstract. The third workshop had the students use the scientific method to design an experiment. Students were given sample data and asked to write an abstract individually. The workshop leader provided a draft revision including comments and suggested edits. Writing an abstract required students to utilize knowledge from both the first and second workshops, including conducting a literature search, reviewing articles, and writing each portion of an abstract to complete the assignment. These reading and writing workshops elicited positive feedback from the students. They stated that they enjoyed working as a group and felt more prepared to write an abstract. The workshops also improved participation amongst lab members during weekly meetings. Overall, this was a quick, engaging strategy for preparing novice science students for scientific writing. We plan to expand this technique to a larger group of junior‐level physiology students in the spring. This will allow us to compare abstract quality amongst students who participate in the workshops with students who do not participate. From this, we will obtain a better understanding of the effectiveness of this technique as a method of introducing scientific communication to undergraduate physiology students.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reflective writing as a learning tool to improve exam performance in a clinical physiology course
Authors: Anderson Lisa C
Published: June 2021

Reflective writing is a process that allows the writer to give serious consideration to an experience. The act of reflecting can, not only give the writer insights into that experience but, also, be the vehicle of further learning. Given the value of reflection as a learning tool, reflective writing assignments have been incorporated into a two course Clinical Physiology series. Reflective writings are assigned after a two‐part exam. Part one is a multiple‐choice exam completed by each student individually. Part two is a group exam in which an assigned interdisciplinary group completes the same exam given in part one. During the group exam, students discuss each question until they reach a consensus about the correct answer. In previous work, student writings were analyzed using a reflective rubric adapted from the work of Learman (1). The analysis of student writings from the 2015–2016 academic year was used to refine the rubric and analysis for writings from the 2016–2017 academic year was used to perform inter‐rater reliability testing. For the 2017–2018 academic year, the adapted reflection rubric was included in the course syllabi for the purpose of guiding the student's reflective writings. Exam scores from academic year 2016–17 (pre‐rubric) were compared to exam scores from academic year 2017–2018 (post‐rubric). The following hypothesis was tested: students would benefit from having a rubric to guide their reflective writing and would therefore score higher on multiple choice exams than students who were not provided the rubric (since it had not yet been developed). There was not statistical difference between the exam averages on the first exam of the year, but in subsequent exams, the 2017–2018 students performed significantly better on individual exams, supporting the hypothesis. Data from academic year 2018–2019 is currently being collected and analyzed.

Support or Funding Information

NA

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Enhancing Student Outcomes in Large Lecture Courses
Authors: Co Elizabeth , Spilios Kathryn
Published: June 2021

Critical thinking, active learning, enhancing metacognition, problem‐based learning: there are many pedagogical efforts that we can make to enhance learning in biology and physiology classrooms. At large, research‐focused universities there are many challenges to embracing these techniques. Here we present data on effective strategies for enhancing student outcomes in large lecture courses.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evolution of the proboscis in the moose, Alces alces: Evidence from Morphology and Ecology
Authors: Pagano Anthony Santino , Laitman Jeffrey T. , Albertine Kurt , Marquez Samuel
Published: June 2021

Among living cervids, the moose or elk (Alces alces) is among the most distinctive for its enlarged proboscis. Despite over a century of scientific inquiry into the ecology and evolution of this species, the origin and function of its proboscis remain unclear. An ability conferred by the proboscis is closure of its nares, which the North American moose performs while diving for sodium‐rich aquatic vegetation. This is found in combination with elongated metapodials and long, splayed phalanges for walking on soft, marshy ground and cylindrical shape of the femoral head for greater mobility of the hip joint when walking over uneven surfaces as in closed swampland habitats. We investigated the anatomical basis and evolutionary history of the proboscis among moose by examining the soft‐ and hard‐tissue morphology of extant (i.e., dissected head and dry skulls) and extinct material (fossil Cervalces crania). The moose head was provided as a result of a vehicular accident while dry and fossil crania were studied from osteological collections from the Division of Vertebrate Paleontology and Mammalogy of the American Museum of Natural History. Results suggest that, rather than being a direct adaptation to aquatic foraging, the proboscis likely arose in a multi‐step process initiated when ancestral moose populations lost their rhinarium as an adaptation to selective browsing, freeing the external nose from the now mobile upper lip. Further selective pressures influencing ancestral moose populations in closed, marshy environments with poor visibility may have favored enhanced olfactory acuity provided by the proboscis, which appears to separate inspiratory airflow into superior olfactory and inferior respiratory columns via an elongated cartilaginous ridge emerging from the lateral wall of the anterior nasal cavity and meeting the inferior concha. Enhanced olfaction would be adaptive for predator avoidance among calving females and perceiving sociosexual signals during rutting season. Further analysis of the nasal cavity morphology and airflow dynamics of the moose is warranted.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Tissue quantification of neutral and acid mucins in the mucosa of the colon submitted to 10 days of gastric restriction in an animal model
Authors: Akamatsu Flávia Emi , Fontes Luiz Gustavo , Itezerote Ana Maria , Saleh Samir , Teodoro Walcy Rosolia , Hojaij Flávio , Andrade Mauro , Pereira José Aires , Martinez Carlos Augusto Real , Jacomo Alfredo Luiz
Published: June 2021

Background

Obesity and its related comorbidities have detrimental effects for the affected individual and pose a major challenge on public health systems worldwide.

However, mechanisms of surgical weight loss and long‐term consequences of bariatric surgery remain unclear. Gastric reduction procedures are currently employed to treat morbid obesity and there are few reports concerning the consequent effects in large intestine.

Purpose

To quantify the expression of neutral and acids mucins in mucosa of the colon in animal model and correlate this to gastric restriction

Methods

Experimental model of gastric restriction was devised using rats. The animals were submitted to surgical gastrostomy and a cylindrical loofah was inserted into the stomach. We studied 30 adult male Wistar rats divided in three groups: the stomach reduction group (R10), the sham group (S10), which underwent the same procedure except for the loofah insertion and the control group (C10). Animals were fed and kept in separate cages. They were weighed every other day until being sacrificed on day 10. The expression of neutral and acid mucins was evaluated using the histochemical techniques of Periodic Acid Schiff and Alcian Blue, respectively and Picrosirius Red. The tissue mucins and collagen expression were quantified by computer‐assisted image analysis software.

Goblet cells and protein content were presented by groups as mean, median, minimum and maximum and it was compared between groups using generalized estimation equations (GEE) with normal distribution and identity link function supposing exchangeable correlation matrix between fields. Bonferroni's multiple comparison was applied to identify differences between groups. The results are described by the mean value with respective standard deviation. We used Spearman correlation to verify correlation between weight, height of the crypt and cells quantity. All tests were applied with 5% significance level.

Results

There was increased expression of neutral mucins and acid mucins as well as Goblet cells in the R10 group. Picrosirius Red enhanced total collagen in restriction group.

Conclusions

Gastric restriction for 10 days in animal model increased neutral mucins and acid mucins as well as collagen content with trophic maintenance.

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