bluuebunny/crossref_metadata_2025 huggingface dataset:
Selenoprotein P and apolipoprotein E receptor‐2 interact at the blood‐brain barrier and within the brain to protect against neurodegeneration (374.6)
Authors: Burk Raymond , Hill Kristina , Motley Amy , Winfrey Virginia , Kurokawa Suguru , Mitchell Stuart , Zhang Wanqi
Published: June 2021

The brain retains selenium under selenium‐deficient (0 Se) conditions better than other tissues. Selenoprotein P (Sepp1) and its receptor apolipoprotein E receptor‐2 (apoER2) are both necessary for this retention. Feeding 0 Se diet to weanling mice with either of these proteins knocked out leads to severe brain injury within 4 weeks. Little is known about the interactions of Sepp1 and apoER2 that protect against brain injury. We studied these proteins and brain selenium in knockout mice. Immunocytochemistry showed that apoER2 mediated Sepp1 uptake by choroid plexus and brain capillaries in the fetus but only by choroid plexus in the adult. ApoER2 mRNA in adult brain was 11% of that in fetal brain, consistent with lesser uptake of Sepp1 at the blood‐brain barrier (BBB) in the adult than in the fetus. Severe brain injury occurred in knockout mice fed 0 Se diet when brain selenium fell to 34‐39 ng/g. However, mice with selective knockout of Sepp1 in hepatocytes fed 0 Se diet for 40 weeks tolerated brain selenium of 12 ng/g without severe brain injury. Thus, Sepp1 within the brain prevents the injury. These results indicate that 2 levels of Sepp1‐apoER2 interaction occur to supply neurons with selenium. One results in selenium uptake at the BBB and the other occurs within the brain. We postulate that Sepp1 synthesized inside the BBB is taken up by neurons through apoER2‐mediated endocytosis, concentrating brain selenium in neurons.

Grant Funding Source: Supported by NIH ES002497
Doctors fail to offer advice about omega‐3s to those who need it most (379.7)
Authors: Bangia Deepika , Palmer‐Keenan Debra
Published: June 2021

A grocery store tour podcast was developed to inform shoppers about the health benefits of omega‐3s (n‐3s) and foods to increase n‐3 consumption. This study specifically examined shoppers who had a history including one of 12 health conditions that may be ameliorated by increased n‐3 consumption (N=223). Participants were recruited from 20 New Jersey grocery stores, and surveyed pre‐intervention to assess if their doctors had ever made them aware of n‐3s’ benefits or advised them to increase their n‐3 consumption. After having listened to the podcast as they shopped, participants were asked to show the researcher any foods they had purchased as a result of listening to the podcast, and the foods were verified to be n‐3 rich foods. Most participants were female (n=173) with a mean age of 52.6±12.4 years. Just over a third of the study population (n=83) had been advised to consume more n‐3s. Notably, those with heart conditions or high‐triglycerides (n=40) were most likely to have been apprised about n‐3s, as about half (n=21, 53%) had been advised by their doctors to consume more. Of the 47 women who were of child bearing age (<45 years), less than one third (n=15) had received any advice from doctors regarding n‐3s to support the birth of healthy babies. As a result of listening to the podcast 108 shoppers (49%) bought at least one n‐3 rich food (mean = 1.2 ± 0.5), and 194 shoppers (88%) indicated they would buy n‐3 rich foods in the future. These results suggest that doctors do not adequately address n‐3s benefits/consumption among patients who would likely most benefit from this advice. Further, it suggests that when offered information regarding the benefits of n‐3s and counseled on foods to purchase via this innovative means of providing nutrition education at the point of purchase, n‐3 rich food purchases increase.

Grant Funding Source: Supported by New Jersey Agricultural Experiment Station
Energy restriction impairs dendritic cell development in C57Bl/6 mice (382.2)
Authors: Duriancik David , Gardner Elizabeth
Published: June 2021

Dendritic cells (DC) are antigen presenting cells and sensitive to nutritional modulation. Energy restriction (ER) is a nutritional intervention shown to extend lifespan in many experimental organisms, but recent data in non‐human primates are contradictory. Immunological outcomes of ER are inconsistent, with several reports demonstrating amelioration of autoimmune disease in ER mice, yet increased susceptibility to some primary infections, such as influenza. In the current study, we hypothesized bone marrow DC development would be increased in ER mice due to glucocorticoid‐associated increased myelopoiesis. The objective of this study was to determine the effects of ER on bone marrow DC progenitor numbers. Multicolor flow cytometry was used to characterize bone marrow DC progenitors. We observed increased myeloid progenitors and monocytes, while common DC progenitors and precursor DC were decreased in bone marrow of ER mice. Injecting recombinant mouse Flt3L was utilized to induce DC development in ER and ad libitum (AL) fed mice. We observed differential effects of rmFlt3L injections on DC subsets in ER mice, relative to that observed in AL mice. The altered developmental pathway of DC subsets may be responsible for contradictory immunological outcomes in ER populations and provide potential targets for improving vaccination, autoimmune conditions, and infectious disease.

Grant Funding Source: Supported by NIA grant to EMG RO1AG034949
Objective score of atopic dermatitis and prebiotic in infant (382.8)
Authors: Ghanei Nila , Siassi Fereydoun , Zandieh Fariborz
Published: June 2021

Background: Atopic dermatitis (AD) is a prevalent medical condition in infants aging from 6 months to 12 years old. Due to changes in life style, the prevalence of AD has been on the rise in recent decades such that nearly 50% of children in the first year of life and 80% in the first five years suffer from it. AD can lead to many complications such as changes in behavior, drowsiness, and susceptibility to viral and bacterial infections. Current standard of care for AD includes treatment with corticosteroids. However, treatment with corticosteroids can lead to many complications. There is a need for alternative treatments with lower risks of side effects. The aim of this study was to determine the effect of prebiotic supplement on objective score of infant with AD.

Material and methods: Seventy 7‐24 month old infants with AD were enrolled in a double‐blind placebo‐controlled trial and were divided into 2 groups. The prebiotic supplemented group (PS) received fructooligosaccharides‐inulin and the control supplemented group (CS) received maltodextrin powder as placebo for 3 months. At the beginning and at the end of intervention total SCORAD (SCORing for Atopic Dermatitis) questionnaire was completed by a physician and serum levels of IgE were measured. The data were analyzed using SPSS software.

Table: Clinical parameters before and after prebiotic supplementation in atopic dermatitis infants

GROUPvariable
Intervention(PS)N=35
Control(CS)N=35
P value

Objective scoreBeforeafter
55.4±97.73.8±8.1
32.8±16.715.5±9.8
0.180.001

Total SCORAD:Before After
53.9±23.64.3±9.6
43.4±20.919.4±13
0.060.001

Serum IgE level (IU/ml)Beforeafter
160±73107±42.7
158±4093±56
0.340.001

Results: The objective SCORAD consist of just the extent and intensity items. All clinical parameters of the SCORAD decreased significantly in both groups at the end of trial. However, the reduction in the PS group was significantly higher than the CS group (P<0.001). Also Significant negative correlation was found between total SCORAD score and Serum IgE levels (r2=0.20 ; P<0.001).

Conclusion: It seems that prebiotic supplement can effectively reduce clinical signs in AD infants.

Grant Funding Source: supported by Tehran University of Medical Sciences (TUMS)
Associations between the neighborhood and home environments and weight status in pre‐kindergarten children (390.6)
Authors: Partington Susan , Lacombe Donald , Menzies Tim , Cottrell Lesley
Published: June 2021

AIM: To determine if parent perceptions of the neighborhood environment, parenting style and household food purchasing patterns are associated with weight status in pre‐kindergarten children. METHODS: Parents of 114 pre‐kindergarten children, participants in the West Virginia Early Childhood Obesity Prevention Project, completed surveys to assess behavioral and environmental contributors to child weight. Neighborhood and home environments were assessed using the Twin Cities Walking Survey and the Family Food Environment Survey. Household food expenditures over the past 30 days, parent health status and that of the study child and household socio‐demographic characteristics were also reported. Children were weighed and height measured at a home visit or school screening by study staff. Linear regression was used to identify survey items significantly associated with child body mass index (BMI) percentile. RESULTS: Indicators of neighborhood cohesion, walkability and safety, percent of household food purchases made at stores not considered grocery stores, parent feeding style and history of overweight, and child birth weight accounted for about 50% of the variance in BMI percentile for age and gender. CONCLUSION: Characteristics of the neighborhood and home environments may be important contributors to weight status and should be considered in early childhood obesity prevention initiatives.

Grant Funding Source: This project was supported by USDA AFRI grant #2011‐68001‐30049.
New insight into the obesity paradox among older adults with diabetes (391.7)
Authors: Murphy Rachel , Reinders Ilse , Garcia Melissa , Eiriksdottir Gudny , Launer Lenore , Benediktsson Rafn , Jonsson Palmi , Gudnason Vilmundur , Harris Tamara
Published: June 2021

Objective: To investigate relationships between body mass index (BMI) and mortality in diabetes where obesity has been paradoxically associated with lower mortality risk than normal weight and to examine the possible role of muscle, adiposity and function.

Design: Participants aged 66‐96 years with diabetes from self‐report, medication or fasting glucose 蠅7mmol/l in the AGES‐Reykjavik Study. BMI was classified as normal weight (18.5‐24.9kg/m2, N=114) or overweight/obese (蠅25.0kg/m2, N=520). Thigh muscle area, abdominal and thigh adipose depots were assessed with computed tomography. Function was assessed from gait speed and leg strength.

Outcome: Mortality risk (hazard ratios (HR) and 95% confidence intervals (CI)) over a mean of 6.5 years were assessed by Cox models, reference category overweight/obese.

Results: In adjusted models (demographics, diabetes duration, medications, blood pressure, lipids, waist circumference, mid‐life BMI, smoking, microalbuminuria, inflammation and hypertension), normal weight participants had higher mortality risk (HR 1.69 95% CI 1.10‐2.61) than overweight/obese participants. Risk remained with adjustment for adipose depots and strength but was attenuated with adjustment for muscle area (HR 1.33 95% CI 0.86‐2.06) and gait speed (HR 1.54, 95% CI 0.97‐2.43).

Conclusion: Muscle size and function may help explain the obesity paradox among adults with diabetes.

Grant Funding Source: Supported by NIH contract N01‐AG012100, the NIA Intramural Research Program, Hjartavernd (the Icelan
Role of infiltrating macrophage in neuroinflammation following infection and obesity in mice (392.1)
Authors: Sheridan Patricia
Published: June 2021

Obesity, inflammation and infections are linked to increased cognitive impairment, anxiety and dementia in later life. Previous data from our lab demonstrate a diet high in saturated fat, leading to obesity, prolongs inflammation in the brains of latently herpes simplex virus (HSV)‐infected mice and results in increases in anxiety behaviors. In this study, we sought to determine the contribution of infiltrating monocytes/macrophage to the prolonged neuroinflammation in the obese, latently infected mice. C57Bl/6 and CCR2RFP/+/CX3CR1GFP/+ mice, which allow for the differentiation of microglia from infiltrating mononuclear cells, were used in this study. Weanling mice were placed on the low fat diet. Five days post weaning, the mice were infected with a low dose of herpes simplex (HSV)‐1. After 14 days half of the mice were moved to the 45% lard/soybean oil diet. At various points following infection, we determined the number and phenotype of infiltrating cells using immunohistochemistry, flow cytometry and FACS sorting. We found that in latently infected mice on the HF diet there was greater infiltration of macrophage and increased microglial activation compared to LF mice. The infiltrating macrophage also produced proinflammatory cytokines demonstrating that along with activated microglia, infiltrating macrophage contribute to neuroinflammation in latently infected obese mice.
Dietary zinc supplementation during Giardia lamblia infection enhances growth performance, zinc status and immune response in CD1 mice (392.5)
Authors: Iñigo‐Figueroa Gemma , Astiazarán‐García Humberto , Quihui‐Cota Luis , Méndez‐Estrada Rosa Olivia , Velázquez‐Contreras Carlos Arturo , Garibay‐Escobar Adriana , Canett‐Romero Rafael
Published: June 2021

The effect of zinc (Zn) supplementation for treating diarrhea in children may vary according to the etiological agent. Since Giardia lamblia (G. lamblia) is an important cause of parasitic diarrheal disease worldwide it was of interest to evaluate the effect of different levels of dietary Zn intake on growth performance, Zn status and immune response during infection. CD1 mice were fed 1 of 4 experimental diets: low Zn (ZnL), adequate Zn (ZnA), supplemented Zn (ZnS1) and highly supplemented Zn (ZnS2) diet containing 10, 30, 223 and 1383 mg Zn/kg respectively. After a 10‐day feeding period, mice were orally inoculated with G. lamblia trophozoites and followed on the assigned diet during the course of infection. Giardia‐free mice fed ZnL or ZnA diet were able to attain normal growth while Giardia‐infected mice presented significant growth retardation and lower serum Zn levels. ZnS1 and ZnS2 diets avoided this weight loss during infection, enhanced the production of anti‐G. lamblia IgG and improved serum Zn levels despite the ongoing infection. Maximum growth rate and antibody mediated response were attained in mice fed ZnS1 diet with no further increases by feeding higher Zn levels (ZnS2). These findings reflect biological effect of Zn that could be of public health importance in endemic areas of infection. (Partially published, Nutrients 2013, 5(9), 3447‐3460)

Grant Funding Source: Supported by CONACyT
Intravenous catheterization and the clinical setting do not impact appetite sensations in children (393.4)
Authors: Gheller Brandon , Montgomery Sarah , Anini Younes , Bellissimo Nick , Hamilton Jill , Glanville N. Theresa , Anderson G. Harvey , Luhovyy Bohdan
Published: June 2021

In the clinical setting children report intravenous procedures as distressing but it is unknown if they affect their appetite sensations. Therefore, the objective of this study was to evaluate the effect of setting and venous blood draws on subjective appetite (SA) and physical comfort (PC) in children. Methods: In two separate studies, 9‐14 y children (5th‐85th BMI percentile) consumed a snack of either yogurt or cookies in random order. One study was conducted non‐invasively at a university laboratory (n=23) and another study was conducted at the hospital (n=11) where children had an intravenous catheter inserted for repeated blood draws over 2 h. In both studies, food intake (FI) was measured at an ad libitum meal 120 min after the snack. SA and PC were measured at 0, 30, 45, 60, 90, 120 and 145 min using visual analogue scale questionnaires. Results: There was no difference between settings for the baseline SA and PC scores. There was an effect of time, but not setting, on two hour average appetite (P<0.01). Children had slightly higher PC scores (12%) in the clinical setting (P<0.01) but PC did not correlate with SA scores or FI in any setting. PC scores were high (0‐100 mm scale) in both the clinical setting (82 mm ± 1.8) and university setting (72 mm ± 1.2) indicating a lack of effect of setting and catheterization on appetite sensations. Conclusion: Venous blood draws performed in the clinical setting do not affect subjective appetite sensations following snacks in children.

Grant Funding Source: Supported by Dairy Farmers of Canada
Alternatively activated monocytes/macropahges support prostate cancer skeletal metastasis (397.6)
Authors: Jones Jacqueline , Soki Fabiana , Morgan Todd , Pienta Kenneth , McCauley Laurie
Published: June 2021

Macrophages play a vital role in maintaining tissue homeostasis, by clearing foreign pathogens and apoptotic tumor cells through phagocytosis (termed eferrcoytosis). The purpose of this study was to determine the bone resident phagocytic macrophage/monocyte(s) that support prostate cancer (PCa) bone metastasis through efferocytosis and TGFβ. Bone marrow macrophages co‐incubated with either apoptotic mimicry beads or apoptotic PCa tumor cells exhibited efferocytosis and displayed a shift to a M2 phenotype. Furthermore, co‐incubation with apoptotic tumor cells resulted in an increase in gene expression of efferocytic markers TGFβ, MERTK and MFG‐E8. From a clinical perspective, patients with malignant PCa expressed higher levels of MFG‐E8, a known efferocytosis facilitator, while co‐localization of CD68+ cells and MFG‐E8 was significantly increased in malignant PCa tissue. Moreover, peripheral blood from patients with PCa bone metastasis showed significantly higher numbers of efferocytic CD68+ and CD14+16‐ monocytes, which significantly correlated with their PSA levels. Together, these results demonstrate that efferocytosis by bone‐derived macrophages elicits a pro‐tumorigenic response that is sufficient to support tumor growth. Moreover, PCa bone metastasis patients exhibit a high alternatively activated efferocytic monocyte population.

Grant Funding Source: Supported by PO1CA093900‐10
Human pathophysiological concentrations of bile salts induce necrosis in primary human hepatocytes (398.1)
Authors: Woolbright Benjamin , Li Feng , Gholami Parviz , Dorko Kenneth , Kumer Sean , Schmitt Timothy , Forster Jameson , Olyaee Mojtaba , Hagenbuch Bruno , Jaeschke Hartmut
Published: June 2021

Liver injury during cholestasis is thought to develop due to plasma and liver accumulation of toxic bile salts (BS), such as glycochenodeoxycholate (GCDC), which leads to apoptosis. This paradigm relies on the use of cytotoxic concentrations of GCDC to mimic cholestasis in rat hepatocytes or human hepatoma lines. Instead, this study assessed how pathophysiological concentrations of BS measured in cholestatic patients affected primary human hepatocytes (PHH). Individual BS levels were determined by UPLC/MS in 50 patients with extrahepatic cholestasis, with or without concurrent liver injury. Patients with liver injury had increased BS levels in serum, while biliary levels decreased, implicating development of bile infarcts, which were confirmed by histology. Human hepatocytes isolated from resection material, retained functional BS uptake via Na+ ‐dependent and ‐independent transporters, measured by uptake of taurocholate. Exposing PHH to GCDC for 6 hours resulted in little cell death, measured by LDH release, until exposure to concentrations >1mM GCDC. In contrast to data in rat hepatocytes, no dose of GCDC produced an increase in caspase‐3 activity in PHH, and pretreatment with a pan‐caspase inhibitor did not protect. Finally, PHH were treated with complete BS mixtures derived from patient serum or bile. While serum values resulted in no increase in cell death for up to 24 hours after application, bile mixtures caused direct toxicity. These data suggest PHH are more resistant to human BS concentrations than rat hepatocytes, and die by necrosis. Moreover, biliary concentrations of BS are required for acute cell death, implicating biliary infarction as the initiator of injury.
All omega 3 fatty acids improve serum lipid profiles and decrease aortic plaque buildup in LDLr‐/‐ mice fed an atherogenic diet (40.1)
Authors: Pepper‐Yowell Amanda , Wang Shu , Byelashov Oleksandr , Sellers Matthew , Liang Rowdy , Ballou Michael
Published: June 2021

Although the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on vascular disease markers have been well studied, the effect of docosapentaenoic acid omega‐3 (DPAn3) has been studied less. The objective of this study was to compare the effects of DPAn3, EPA, DHA, and commercial combinations of EPA, DPAn3, and DHA on serum lipid profiles and the development of atherosclerosis in mice. Male LDLr‐/‐ mice were assigned to one of six atherogenic (42% kcal from fat) dietary treatments (n=8) that had 3.5% of total fatty acids (FA) replaced with milk fat, DHA, DPAn3, EPA, or a commercial n3 fatty acid preparation. Blood samples were taken at 0, 10, and 20 weeks into the study; serum was isolated and probed for lipid classes and glucose. Aortic arches were harvested from all mice and total, free, and esterified cholesterol are reported. Serum lipid profiles and glucose in mice increased over the study, but supplementing n3 polyunsaturated fatty acids (PUFA) decreased (P<0.05) serum cholesterol, triglyceride, and non‐esterified fatty acid concentrations compared to the milk fat control. Mice supplemented with all n3 PUFA had decreased aortic total cholesterol (P<0.10) and cholesterol ester (P<0.05) compared to the control mice. The results of this study suggest that EPA, DPA, and DHA may equally (P>0.10) improve serum lipid profiles and decrease aortic plaque buildup in a mouse model prone to atherosclerosis.

Grant Funding Source: Supported by Omega Protein Corporation
Effect of modifying the n‐3 and n‐6 content of the Total Western Diet on the acute inflammatory response to lipopolysaccharide in C57BL mice (40.2)
Authors: Xu Tao , Hintze Korry , Lefevre Michael , Ward Robert
Published: June 2021

To objective of this study was to determine if physiologically relevant levels of omega‐6 (n6) and omega‐3 (n3) fatty acids in the Total Western Diet (TWD) affect the acute inflammatory response in C57 mice challenged with LPS. The TWD is a new rodent diet that was formulated to match the macronutrient and micronutrient intakes of Americans and is based on data collected in 2009‐2010 in NHANES. Thirty‐two mice were randomly assigned to one of four versions of the TWD differing in n6 and n3 content. Based on NHANES, a typical Western Diet contains 7% kcal from n6 and 0.7% kcal n3. The diets used in this 2 x 2 design reflected the 10th and 90th percentile of n6 and n3 intakes. All diets contained 34% kcal from fat with the following n6 and n3 compositions (all in kcal): HH (10.4% n6, 1.1% n3 (10:1 ratio)), HL (10.4% n6, 0.4% n3 (26:1 ratio)), LH (5.1% n6, 1.1% (5:1 ratio)) and LL (5.1% n6, 0.4% n3 (13:1)). After 28d mice were challenged with 10mg/kg of an intraperitoneal injection of lipopolysaccharide (LPS), sacrificed after 24 h and plasma and tissues were collected. Fatty acids were measured in erythrocytes using gas chromatography and plasma cytokines were measured using a multiplexed bead assay. Mice fed the HH diet gained more 29% more weight than LH diet and 39% more than those fed the LL diet. The erythrocyte fatty acid profile indicated the LH group had significant more DHA and DPA than other diet groups, and higher EPA than HL and LL groups. Arachidonic acid, on the other hand, was not different between groups. Despite the differences in PUFA intakes there were no significant difference between the groups in the pro‐inflammatory and anti‐inflammatory cytokines in plasma. According to these results, dietary n6 and n3 PUFA at intakes physiologically relevant to the US diet did not affect the acute inflammatory response to LPS.

Grant Funding Source: USDA‐NIFA
Dietary patterns and plasma adipokines and inflammatory markers in healthy Chinese men (40.3)
Authors: Takata Yumie , Xiang Yong‐Bing , Villegas Raquel , Li Honglan , Yang Gong , Murff Harvey , Zheng Wei , Cai Qiuyin , Shu Xiao‐Ou
Published: June 2021

We investigated associations of dietary patterns with plasma levels of adipokines and inflammatory markers [i.e., adiponectin, resistin, leptin, tumor necrosis factor (TNF)‐alpha, interleukin (IL)‐6, IL‐8, monocyte chemoattractant protein‐1 (MCP‐1) and plasminogen activator inhibitor‐1 (PAI‐1)] in 3,636 non‐diabetic Chinese men who are participants of the Shanghai Men’s Health Study. Using the interviewer‐administered, validated food frequency questionnaire data, three dietary patterns were derived by principal component analysis (i.e., “Vegetable”, “Fruit and Milk”, and “Meat” patterns). We evaluated the correlation of the dietary pattern scores with adipokines and inflammatory markers while adjusting for covariates. The mean age and body mass index of the participants were 50.9 years and 23.4 kg/m2, respectively. Nearly three‐quarters of the participants were current smokers. The Vegetable pattern was inversely correlated with resistin (r=‐0.04, P=0.02), but positively correlated with MCP‐1 (r=0.04, P=0.02). The Fruit and Milk pattern was inversely correlated with IL‐8 (r=‐0.07, P=0.0001), MCP‐1 (r=‐0.04, P=0.03) and PAI‐1 (r=‐0.05, P=0.003). The Meat pattern was positively correlated with MCP‐1 (r=0.04, P=0.03) and PAI‐1 (r=0.07, P=0.0001). Our study sheds light on potential biological mechanisms underlying the dietary patterns and chronic disease associations.

Grant Funding Source: This work was supported by the National Institutes of Health (R01 CA082729).
Increased platelet‐activating factor accumulation in the endothelium in response to cigarette smoke may contribute to breast cancer metastasis (405.5)
Authors: Kispert Shannon , Marentette John , German Konstantin , McHowat Jane
Published: June 2021

Cancer deaths are more often caused by distant metastases than by growth of the primary tumor. We have previously demonstrated that endothelial cell platelet‐activating factor (PAF) production results in increased adherence of breast cancer cells to the endothelium and may play a role in cancer cell migration to locations distant to the primary tumor. In this study, we used cigarette smoke extract (CSE) to inhibit endothelial cell PAF‐acetylhydrolase (PAF‐AH, hydrolyzes and inactivates PAF) activity and determined whether this results in increased endothelial cell PAF production and breast cancer cell adherence. Incubation of human lung microvascular endothelial cells (HMVEC‐L) with CSE (20 µg/ml) for up to 24 hours resulted in a significant inhibition of PAF‐AH activity that was accompanied by increased PAF production and adherence of highly invasive MDA‐MB‐231 breast cancer cells. Pretreatment of HMVEC‐L with (S)‐bromoenol lactone to inhibit calcium‐independent phospholipase A2β (iPLA2β, initiates endothelial cell PAF production) prior to CSE exposure resulted in complete inhibition of MDA‐MB‐231 cells. Likewise, pretreatment of MDA‐MB‐231 cells with the PAF receptor antagonist Ginkgo biloba resulted in inhibition of adherence to the endothelium. Western blot analysis revealed increased PAF receptor expression in MDA‐MB‐231 cells with CSE exposure. Histological samples of human breast carcinoma show that PAF receptor expression is increased in tumor regions when compared to the surrounding epithelium. Taken together, our data indicate that CSE exposure increases endothelial cell PAF production resulting in enhanced adherence of breast tumor cells. Our in vitro data indicate that increased tumor cell adherence would lead to enhanced metastasis formation in smokers. Potential therapeutic targets include endothelial cell iPLA2β or the tumor cell PAF receptor.
Synaptic selection by dopamine neurotransmission (468.3)
Authors: Sulzer David
Published: June 2021

Electrophysiological and electrochemical recordings provide time resolution sufficient to measure quantal neurotransmission at CNS synapses, but do not resolve activity of individual synapses within populations. Modulation at the level of individual synapses, however, may be required in habit learning and decision making.

We will discuss means to resolve the modulation of subgroups of individual synapses using fluorescent false neurotransmitters (FFNs) that act as synaptic vesicle transporter substrates as well as endocytic probes. These optical approaches indicate not only presynaptic release probability and reuptake kinetics but also new forms of presynaptic plasticity, including the rapid movement of presynaptic release sites, and transfer between silent and active states. We will show how such selection of corticostriatal synapses by dopamine and cannabinoid might enable normal motor function.
Association between sleep patterns and food choices among adolescents (47.7)
Authors: Clarke Abigail , Phang Chen‐Chen , Sirirat Rawiwan , Heskey Celine , Siapco Gina , Sabate Joan
Published: June 2021

Inadequate sleep has been associated with poor food choices which may increase one’s risk for obesity. This study investigated the relationship between sleeping patterns (sleep duration and bedtime) and food group choices in adolescents. This cross‐sectional study consisted of 581 adolescents (53% female) ages 11‐19 years from 10 schools in Southern California and Michigan. Participants completed a self‐administered web‐based survey containing a semi‐quantitative food frequency questionnaire, and items on demographics and lifestyle behaviors including physical activity and sleeping habits. Anthropometric measurements were obtained at clinic visits held at school sites. Data was analyzed using descriptives, t‐tests, χ2, ANOVA and ANCOVA with adjustment for confounders. Male subjects with shorter sleep duration (<8 hrs) consumed less fruits (p=0.0001) and more fat (p=0.0019). Females who sleep 8‐9 hrs per night consumed less added sugar (p=0.01) when compared to those who sleep >9 hours or <8 hours. Bedtime was not significantly associated with food intake among females. Male subjects who went to bed before 9 pm had a greater intake of fruits (p=0.0012) and a lower intake of starchy vegetables, snacks and added fat (p<0.01). Shorter sleep duration and later bedtimes influence food choices, which may have implications for adolescent future weight status.
Characterizing anemia due to malnutrition in roux‐en‐y gastric bypass surgery patients (47.8)
Authors: Wright Breanne , Gletsu‐Miller Nana
Published: June 2021

Roux‐en‐y gastric bypass surgery (RYGB) is effective for weight loss, but is commonly associated with anemia. Anemia may be caused by decreased dietary intake and intestinal absorption of nutrients, and changes in systemic inflammation following surgery. Objectives were to investigate the nutritional causes of anemia within a RYGB cohort (anemia prevalence, 17%). Systemic concentrations of hemoglobin, ferritin, serum transferrin receptor (sTfR), total iron binding capacity (TIBC), copper (Cu), vitamins B1, B6 and B12, folate, zinc (Zn), and C‐reactive protein (CRP) were determined using reference methods. Iron deficiency equaled having 蠅 2 abnormalities in: ferritin, sTfR, sTfR:ferritin, or TIBC. Subjects (N=23) were female, age 51 ± 2 years, 6 ± 1 years post surgery, and 74% Caucasian. Anemia was most commonly associated with iron deficiency (34.8%), either in isolation (17.4%) or combined with other nutrient deficiencies (B6, B12 and/or Zn, 17.4%). 26.1% of anemia was explained by combinations of deficiencies in Zn, Cu, B12, B6, B1 or folate; none of these nutrients caused anemia in isolation. Inflammation accounted for 4.3% of anemia and 34.8% of anemia remained unexplained. This study supports iron deficiency as a leading cause of anemia in RYGB patients and highlights the role of several other nutrients, emphasizing the importance of comprehensive nutritional assessment following RYGB.

Grant Funding Source: Supported by International Copper Association
Integrating instruction of population genetics and mathematics common core standards using Stella® (530.5)
Authors: Meystrik Jacob , Muller Bradley , West Lori , Mimbs Debra
Published: June 2021

Increasing integration of mathematics and biological concepts is an area of intense focus in both secondary and higher education. Our goal was to develop a platform through which high school mathematics and biology instructors could collaborate with one another in order to demonstrate to their students the connectedness of the two disciplines. Our focus was to apply mathematics common core standards to biological phenomena. One strategy was to show how principles of mathematical modeling could be used to solve population genetics problems. In order to do so, we instructed teachers on how population genetics problems could be modeled and solved using the software, Stella®. We first taught instructors basic functions of the software and then demonstrated how Stella® could be used to answer problems in population genetics. Based on feedback from the instructors, we feel that this provided them with a unique experience that they will be able to use in their classrooms.

Grant Funding Source: Supported by the Tennessee Higher Education Commission
A millennial perspective of Physiology as discipline (531.7)
Authors: Poteracki James , Wehrwein Erica
Published: June 2021

Numerous recent editorials have focused on the state of the discipline of Physiology and stressed the importance of a systems‐level approach. These editorials were authored by established leaders in the discipline. The purpose of this study was to assess the perspective on the discipline of Physiology from the eyes of senior undergraduates majoring in Physiology. We sought to discern whether millennial students are “‐omics”‐focused or have strong interest in systems‐level concepts. Undergraduate students (n=40, 29 males and 11 females) at Michigan State University were asked to provide a free response answer on where their interests lie along the continuum of molecular‐to‐integrative physiology. A vast majority (72.5%) of students prefer learning about integrative and systems‐level physiology over cell and molecular physiology (17.5%). Ten percent of students enjoyed both equally. Students expressed interest specifically in environmental and exercise physiology (27.5%) and pathology (12.5%). Organ‐system preferences, of those noted by students who had a preference, were as follows: cardiovascular (25%), musculoskeletal (19.6%), nervous system (17.9%), respiratory (8.9%), endocrine (7.1%), digestive (7.1%), renal (5.4%), blood/immune (5.4%), and reproduction (1.8%). These data reveal strong preferences for systems/integrative physiology among millennial students. This is important information in light of the recent discussion about the state of the field. It also allows us to better design curricula to engage students with topics in system‐level physiology and integrative function.
Role of EST2/ETV5 as transcription factors in the regulation of SHH by FGF (541.3)
Authors: Townsend Dominique , Brier‐Jones Justin , Pira Charmaine , Oberg Kerby
Published: June 2021

During limb development, fibroblast growth factors (FGFs) from the apical ectodermal ridge (AER) regulate the expression of Sonic hedgehog (SHH) in the underlying posterior distal mesoderm. The molecules or pathways involved in the regulation of SHH by FGF are unknown. A recent study suggests that ETS and ETV, members of the ETS transcription factor family, are intermediate regulators in the Fgf to Shh cascade and directly interact with the limb‐specific Shh regulatory region in the murine limb model.

To determine whether this was a conserved function of ETS/ETV transcription factors, we used the chick model and examined ETS2/ETV5 expression by in situ hybridization following ectopic application of FGF in the posterior limb bud, an assay known to induce SHH.

ETV5 is expressed in the distal mesoderm sub‐adjacent to the AER and overlaps the SHH expression domain. ETS2 expression is most prominent in the developing chick zeugopod and appears to correlate with the condensing radius and ulna. The posterior expression of ETS2 is more robust than its anterior expression. Both factors show increased expression around ectopically applied FGF2‐laden beads at 24 hours after bead implantation.

These data demonstrate expression patterns that spatially complement and overlap the SHH expression domain. Furthermore, both factors are upregulated by ectopic FGF prior to or coincident with SHH upregulation. These data support a role for ETS transcription factors in the regulation of SHH by FGF.
Anomalous pattern of the cerebral arterial circle, associated with an aneurysm: a case report (543.12)
Authors: Enache Alexandra , Zahoi Delia , Sztika Dorina , Baderca Flavia , Daescu Ecaterina
Published: June 2021

The cerebral arterial circle plays a crucial role in the blood circulation within the cortical area. Its’ morphological variability and potential for the formation of aneurysms are well documented and constitute significant mortality risks.

Within the Forensic Medicine Department, several anomalies within the area were identified during the autopsy of a 29 year old male. The observations included anomalous origins of the arteries constituting the cerebral circle (anterior and posterior parts), left/right vascular asymmetry and the presence of an aneurysm which had ruptured spontaneously and was identified as the cause of death.

On the anterior part of the circle, both cerebral arteries originate from the left internal carotid artery, through a 2cm common trunk. The 0.3‐0.4cm saccular aneurysm was located at the bifurcation of this trunk. The right anterior cerebral artery anastomosed with the the middle homolateral cerebral artery through a 4.5cm long and 0.2cm in diameter branch. On the posterior part of the circle, agenesis of the right posterior communicating artery was highlighted.

Through their effect on hemodynamics, morphological anomalies in vessels such as those identified in this case may constitute causal factors in the development of aneurysms.
Difference between hemoglobin‐based oxygen carrier and non‐oxygen carrying plasma expander on cardiac function during hemorrhagic shock resuscitation (545.1)
Authors: Ao‐ieong Eilleen , Cabrales Pedro
Published: June 2021

Study aimed to establish the role of acellular hemoglobin (Hb) based oxygen carrier on cardiac function during anemia. Anesthetized Golden Syrian hamsters under mechanical ventilation with air were hemorrhage 30% of the animal’s blood volume followed by equal volume resuscitation with polymerized albumin (pHSA), or polymerized Hb (pHb, Hemopure, OPK Biotech, Boston, MS). Blood oxygen saturation of >90% was maintained throughout experiment. Cardiac function was assessed through the use of a miniaturized conductance catheter inserted into the left ventricle with continuous pressure‐volume readings. All groups had an increase in stroke work, cardiac output, and ejection fraction compared to baseline. The ratio between dP/dtmax and end diastolic volume, an index of contractility, recovered to 94±33% from baseline for the pHSA, and decreased to 55± 13% from baseline for pHb one hour after resuscitation. To further elucidate the difference in contractility, the intrinsic effects of oxygenation will be investigated by the histology of hypoxic tissue using pimonidazole staining. Hemorrhage and resuscitation resulted in an increased in cardiac function for both treatments.

Grant Funding Source: NIH R01 HL52684, R01 HL064395 and R01 HL062318 and ARMY: W81XWH‐11‐2‐0012
Rapid vasodilation in response to passive leg movement with age: the role of nitric oxide and the impact of perfusion pressure (546.6)
Authors: Groot H , Trinity Joel , Layec Gwenael , Rossman Matthew , Ives Stephen , Richardson Russell
Published: June 2021

We sought to elucidate the contribution of NO, with and without posture‐induced increases in femoral perfusion pressure (FPP), on the rapid (first 7 sec) vasodilatory response to passive leg movement (PLM) with age. PLM was performed in 8 young (24±1 yrs) and 7 old (75±3 yrs) healthy males, with (blk) and without (ctrl) NO synthase (NOS) inhibition, in both the supine and upright‐seated posture. Peripheral hemodynamic responses were determined with Doppler ultrasound. In the supine posture, NOS inhibition had no effect on the rapid vasodilation (leg vascular conductance slope/time) in either the young (ctrl: 0.78 ± 0.10; blk: 0.71 ± 0.16 ml/min/mmHg/sec; p>0.05) or on the already attenuated response in the old (ctrl: 0.25 ± 0.06; blk: 0.33 ± 0.07 ml/min/mmHg/sec; p>0.05). However, in the upright‐seated posture, which similarly increased FPP in both groups (~7mmHg), NOS inhibition significantly attenuated the posture‐induced augmentation of rapid vasodilation in the young (ctrl: 1.25 ± 0.23; blk: 0.74 ± 0.11 ml/min/mmHg/sec; p<0.05), with no effect in the old (ctrl: 0.38 ± 0.05; blk: 0.26 ± 0.05 ml/min/mmHg/sec; p>0.05). PLM‐induced rapid vasodilation in the supine posture is NO‐independent and this response is attenuated with age. In the young, elevated FPP increases the role of NO in this rapid vasodilatory response, but has no effect in the old, likely due to decreased NO bioavailability in this population.

Grant Funding Source: VA Merit Grant E6910R and PPG Grant
Early myocardial changes in experimental chick model of hypoplastic left heart syndrome (547.10)
Authors: Pesevski Zivorad , Kockova Radka , Buffinton Christine , Hedgeland Mark , Svatunkova Jarmila , Sedmera David
Published: June 2021

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart defect in which the left ventricle of the heart is critically underdeveloped and unable to effectively supply blood to the body. Early reloading of the hypoplastic left ventricle can induce its growth and maturation and lead to rescue. To analyze the early changes during development of HLHS, we used an experimental chick model of left atrial ligation (LAL). Fertilized eggs were incubated at 37.5 °C. Partial ligation of the left atrium of chick embryonic hearts was performed at the ED4. At ED6, we performed ultrasound biomicroscopy examination of control and ligated hearts, followed by confocal microscopy 3D reconstruction of the left ventricle. Only those LAL hearts with clear phenotype, defined as apex‐forming right ventricle, were included in the quantitative evaluation. The hypoplastic left ventricle was significantly smaller in cross‐section with a total tissue volume less than half that of matched controls. In ovo analysis of circumferential strain from ultrasound showed no difference between the control and LAL group. This data indicate that although there is a clear morphological phenotype at this stage, the myocardial performance is still within normal limits, strengthening the point of early, possibly fetal, intervention for HLHS.

Grant Funding Source: Supported by PRVOUK‐P35/LF1/5, RVO: 67985823, GACR P302/11/1308, and Bucknell University PUR grant
In vivo two‐photon microscopy for imaging leukocytes in atherosclerotic plaques (547.16)
Authors: McArdle Sara , Koltsova Ekaterna , Ley Klaus
Published: June 2021

Atherosclerosis is characterized by chronic inflammation of the walls of large and medium arteries that have been infiltrated by macrophages, dendritic cells (DCs), T cells, and other leukocytes. Disease progression is determined in part by a variety of cell functions that are regulated by the cell’s motility, including recruitment, transmigration, egress, phagocytosis, and interaction between multiple cell types. In vivo imaging is necessary to better understand leukocyte activity during atherosclerosis within the native plaque microenvironment.

Two‐photon microscopy is emerging as a valuable tool to image live, fluorescent cells in explants or certain organs in vivo. However, new technical challenges are introduced when imaging tissues that move within the body, such as arteries, which expand with every heart beat. In‐frame and between‐frame motion cause still images to be distorted and movies to appear unsteady, making cell tracking infeasible.

We engineered an integrated hardware and software system for in vivo two‐photon imaging of large arteries. To ensure that the artery is in the same position for every picture, a trigger mechanism was constructed which links image acquisition to the mouse’s heartbeat via pulse oximetry. To minimize distortions, a method was developed to acquire only a fraction of a frame during each heart beat and then stitch the resulting small strips together to form a larger frame. A custom stage was built to precisely position the mouse under the microscope objective in 3 dimensions in coordination with the trigger mechanism. The resulting 3D movies will be used to track cell motion. This system can be used to study multiple questions involving cell motility in vivo, including leukocyte recruitment from blood, antigen presentation, phagocytosis, chemokine function, and the role of cell subsets in disease progression.

Grant Funding Source: Supported By the AHA (11PRE7580009), HHMI (56005681), and NHLBI (T32HL007089‐35)
Activation of TGF‐β mediated SMAD pathway induces cardiac fibrosis in mice carrying targeted disruption of guanylyl cyclase/natriuretic peptide receptor‐A gene (547.17)
Authors: Subramanian Umadevi , Gogulamudi Venkateswara , Chen David , Pandey Kailash
Published: June 2021

Mice carrying targeted‐disruption of the natriuretic peptide receptor‐A (GC‐A/NPRA) gene (Npr1) have demonstrated cardiac hypertrophy with increased collagen deposition and fibrosis. The objective of this study was to determine the mechanisms regulating the development of fibrosis in Npr1 gene‐disrupted mice hearts. The Npr1 null mutant (Npr1‐/‐, 0‐copy), heterozygous (Npr1+/‐, 1‐copy), and wild‐type (Npr1+/+, 2‐copy) mice were orally administered with transforming growth factor‐β1 receptor inhibitor GW788388 (2 mg/kg/day) for 28 days, and the hearts were isolated and used for quantification of fibrotic markers using real time quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and Western blot analyses. Npr1‐/‐ null mutant mice showed 6‐fold induction of fibrosis in the hearts compared to wild‐type controls. Moreover, the expression of fibrotic markers such as connective tissue growth factor (CTGF), α‐smooth muscle actin (α‐SMA) and TGF‐βRI, TGF‐βRII and SMAD proteins were upregulated in Npr1‐/‐ mice hearts compared with age‐matched wild‐type controls. Whereas, treatment with TGF‐β inhibitor, GW788388, significantly prevented the cardiac fibrosis and potentially down‐regulated the expression of fibrotic markers and SMAD proteins in Npr1‐/‐ mice hearts. The results of the present study suggest that, induction of cardiac fibrosis in Npr1‐/‐ gene‐disrupted mice is majorly through TGF‐β mediated SMAD‐dependent pathway.

Grant Funding Source: NIH