bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocytic localization of supraoptic serine racemase and its potential participation in NMDA‐stimulated vasopressin responses in hypothalamo‐neurohypophysial explants (1182.9)
Authors: Valdez Joe , Valdez Matt , Kim Simon , González Gwendolyn , Fernández Ruben , Gutiérrez Robert , Currás‐Collazo Margarita 
Published: June 2021

Our lab has previously shown that vasopressinergic magnocellular neuroendocrine cells (MNCs) express various NMDA receptor subunits including the obligatory NR1. Other reports show that NMDA receptors (NMDAr) mediate osmotically‐induced vasopressin (VP) release from the hypothalamo‐neurohypophysial system (HNS). Recently, Panatier et al 2006 revealed that D‐serine is the endogenous coagonist for NMDAr in MNCs of the supraoptic nucleus (SON). Therefore, we investigated the role of D‐serine in NMDAr‐mediated VP release from acutely dissected HNS explants taken from adult male C57BL/6 mice and incubated in a perifusion chamber from which samples were analyzed for vasopressin (VP) using EIA (Gregg &amp; Sladek 1984). After a 4 hr incubation, explants were treated with 5‐100 uM NMDA for 1 hr in the presence and absence of SR inhibitor, L‐Aspartic acid β‐hydroxamate (LA‐βH; 3 mM). We found that NMDAr‐mediated VP release was reduced by LA‐βH suggesting that SR activity and D‐serine signaling are required. In immunohistochemical experiments using adult SON sections, we found marked colocalization of green SR immunoreactivity (ir) with either of two astrocyte specific markers, glial fibrillary acidic protein (GFAP) and glial excitatory amino acid transporter GLT‐1 labeled red. In other experiments animals were injected with Evans Blue (EB), which retrogradely labels VP and oxytocin‐producing MNCs projecting to the posterior pituitary with red fluorescence (excitation/emission maxima ~540/680 nm). SR ir was examined under two osmotic states: hyperosmotic (3.5M NaCl) or normosmotic (0.9% NaCl; 0.6cc/100g bw, i.p.). EB‐positive MNCs showed little or no SR ir, which was redistributed in hyperosmotic animals. We hypothesize that a significant proportion of SR is expressed in astrocytes and that D‐serine gliotransmission contributes to VP responses in SON MNCs.Grant Funding Source: Supported by APS STRIDE summer fellowship (JV), APS Porter fellowship (MV), and MARC (GG, RF, RG).
Middle cerebral artery mean flow velocity changes to non‐pharmacologically induced hypertension and hypotension in humans (1184.6)
Authors: Brassard Patrice , Paquette Myriam , Le Blanc Olivier , Gaudreau Alexandra , Moreau Pascale‐Renée , Clément Andrée‐Anne , Thibault Guy 
Published: June 2021

Asymmetrical responses of cerebral blood flow in response to elevating vs. falling blood pressure has been reported using cyclic inflation and deflation of thigh cuffs in head injury patients and pharmacologically in healthy volunteers. Whether this phenomenon exists with non‐pharmacologically induced hypertension and hypotension is unknown. In this study, we examined the relative changes in cerebrovascular conductance index (CVCi), defined as percent changes in middle cerebral artery mean flow velocity / percent changes in mean arterial pressure, during transient hypertension vs. hypotension in 10 healthy male volunteers {age [median (range)]: 24 (22‐35 yrs), body weight [mean±SD: 72±12 kg]; maximal oxygen uptake: 55±5 ml/kg/min}. Transient hypertension and hypotension were induced via squat‐stand manoeuvres executed at 0.025, 0.05 and 0.1 Hz. The CVCi responses to hypertension (squat) compared to hypotension (stand) were attenuated at 0.05 Hz (0.57±0.38 vs. 1.84±0.56 %/%) and 0.1 Hz [0.83±0.41 vs. 1.59±0.57 %/%; all p<0.01), but not at 0.025 Hz [0.86±0.30 vs. 1.12±0.31 %/%; p=0.1). These results suggest that the human cerebrovascular function is better adapted to combat non‐pharmacologically and physiologically relevant transient hypertension than transient hypotension.Grant Funding Source: Supported by a research contract from the Ministère de l’Éducation, du Loisir et du Sport (Québec)
Induction of autophagy by zinc during acute ethanol exposure (122.1)
Authors: Liuzzi Juan , Menzel Lorenzo , Yoo Changwon 
Published: June 2021

Autophagy is an important catabolic process for the clearance of damaged or superfluous proteins and organelles. The role of ethanol in the regulation of autophagy remains controversial, with some studies showing induction of autophagy by ethanol while others show inhibition. Nevertheless, the view that maintenance of adequate levels of autophagy protects against ethanol induced damage is widely supported. We investigated the role of zinc in the modulation of autophagic flux in human hepatoma cells VL‐17A. LC3II/LC3I ratio, p62 and Beclin‐1 expression and autophagosomes number were analyzed in cells incubated in medium containing 0, 10, 20 or 40µM of zinc with or without 100 mM of ethanol, in presence or absence of the autophagy inhibitor chloroquine. The effect on autophagic flux of co‐incubation with lipopolysaccharide was also investigated. Lastly, labile zinc was analyzed in cells exposed to ethanol and the autophagy inhibitor 3‐methyladenine. Excess zinc had an additive effect on the induction of autophagy by ethanol and lipopolysaccharide. In addition, 3‐methyladenine treatment decreased labile zinc in cells. Our results indicate that zinc is a positive regulator of autophagic flux and support the notion that zinc protective effects against ethanol induced damage are mediated by autophagy.Grant Funding Source: Supported by NIH 1R03AA022451‐01
Associations between tissue retinol binding protein‐4, visfatin and vaspin protein concentrations and blood triglyceride and cholesterol levels in morbidly obese subjects (133.3)
Authors: Goktas Zeynep , Wang Shu , Besler Tanju 
Published: June 2021

Background: Obesity is associated with insulin resistance, diabetes, and cardiovascular diseases. Retinol binding protein‐4 (RBP‐4), visfatin and vaspin are known to have some effect on insulin resistance although their effects on cardiovascular diseases are not clear. Our research focuses on tissue secretions of RBP‐4, visfatin and vaspin proteins and their relationships to blood lipids.Methods: Thirty eight morbidly obese (BMI 蠅40) subjects had the subcutaneous, omental, and mesenteric adipose, liver and muscle tissue samples taken at the time of Roux‐n‐Y surgeries. Total proteins were extracted with RIPA solution and measured with ELISA kits (Adipogen, Korea). Blood triglycerides and cholesterols levels were measured using standard methods. Results were analyzed using Pearson correlation with p <0.05 being significant.Results: Omental adipose tissue visfatin protein concentrations were positively correlated with blood total cholesterol levels (r = 0.382, p = 0.018). Muscle tissue visfatin protein concentrations were negatively correlated with blood HDL cholesterol levels (r = ‐0.384, p = 0.017). Omental adipose tissue RBP‐4 protein concentrations were positively correlated with blood triglyceride levels (r = 0.404, p = 0.012). Mesenteric adipose tissue vaspin concentrations were positively correlated with blood total cholesterol levels (r = 0.429, p = 0.007).Conclusions: Our findings indicate that tissue RBP‐4, visfatin and vaspin protein concentrations might have effects related to dyslipidemia during obesity.
Lipocalin2 regulates the p38MAPK‐PGC1α‐UCP1 pathway to activate the thermogenic program in subcutaneous white adipocytes via a non‐adrenergic mechanism (133.5)
Authors: Deis Jessica , Guo Hong , Chen Xiaoli 
Published: June 2021

Thermogenic activity in adipocytes is negatively correlated with obesity. Adrenergic activation of p38 mitogen‐activated protein kinase (p38MAPK) mediated thermogenesis is well established. Recently, non‐adrenergic regulation of thermogenesis has gained interest. Lipocalin 2 (Lcn2) is a novel adipokine whose deficiency induces cold intolerance in mice. Herein, we explored the thermogenic effect of Lcn2 and its underlying mechanism in subcutaneous white adipocytes. Inguinal stromal‐vascular cells were collected from wild‐type (WT) and Lcn2‐/‐ mice and differentiated to adipocytes. Lcn2‐/‐ mice had a downregulation of uncoupling protein 1 (UCP1) expression in inguinal adipose tissue (iWAT) compared to WT mice on a high fat diet. Lcn2‐/‐ inguinal adipocytes showed significantly lower UCP1 and peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC1α) expression as well as p38MAPK phosphorylation when compared to WT cells. However, norepinephrine‐induced UCP1 and PGC1α transcription, lipolysis and p38MAPK phosphorylation remained unchanged in Lcn2‐/‐ adipocytes. Additionally, Lcn2 recombinant markedly upregulates UCP1 and PGC1α transcription, and increases p38MAPK phosphorylation in Lcn2‐/‐ inguinal adipocytes. This effect is more pronounced under insulin‐stimulated conditions, suggesting Lcn2 synergizes with insulin to activate thermogenic programming. Moreover, a p38MAPK inhibitor attenuated Lcn2‐induced UCP1 expression. In conclusion, Lcn2 has a significant role in promoting iWAT thermogenesis by upregulating the p38MAPK‐PGC1α‐UCP1 pathway via a non‐adrenergic mechanism.Grant Funding Source: Supported by NIDDK
Adipogenesis and glycemic improvement can be concurrent, yet independent (133.7)
Authors: Hegde Vijay , Dubuisson Olga , Dhurandhar Nikhil 
Published: June 2021

Although excessive adiposity is linked with impaired glycemic control, in some animal models transgenic manipulations that increase adiposity, paradoxically improve glycemic control. In mice, Ad36, ‐a human adenovirus, promotes adipogenesis, and enhances glycemic control. The E4orf1 gene of Ad36 is sufficient to improve diet induced hyperglycemia in mice, which offers therapeutic potential. Studies indicate that via E4orf1, Ad36 increases Ras to up‐regulate PPARγ and Glut4 signaling, leading to adipogenesis and better glycemic control, respectively. Our objective was to determine if the adipogenic and glycemic signaling pathways induced by E4orf1 are interdependent. PPARγ null mouse embryonic fibroblasts were transfected with vector expressing E4orf1 or a null vector. Compared to cells transfected with the null vector, E4orf1 expression significantly increased glucose uptake despite a complete absence of PPARγ or adipogenesis, and significantly enhanced Ras activation and the protein abundance of glucose transporters Glut4, Glut1 and adiponectin. Thus, E4orf1 can enhance the signaling underlying glucose disposal, independent of adipogenic signaling. This offers the possibility to harness the anti‐diabetic property of E4orf1, without its adipogenic effect. Moreover, conceptually, these results suggest that adipogenesis and glycemic improvement can be concurrent, yet independent.Grant Funding Source: Vital Health Interventions
DHA regulates the expression of 15‐PGDH through miR 26 a/b in cholangiocarcinoma (144.12)
Authors: Yao Lu , Han Chang , Wu Tong 
Published: June 2021

DHA, the primary effector molecule of omega‐3 polyunsaturated fatty acids, may ameliorate inflammatory diseases and prevent carcinogenesis. However, the precise mechanisms by which DHA influence hepatic carcinogenesis have not been elucidated. Here we report DHA regulates PGE2 deactivator‐15‐PGDH expression through miR26a/b in cholangiocarcinoma. Human cholangiocarcinoma cell lines (CCLP‐1 and TFK‐1) treated with DHA or stably transfected with Fat‐1 gene significantly enhanced 15‐PGDH protein expression while had little effect on its mRNA level. MiR26a/b, which putatively binds to 15‐PGDH 3’UTR, are significantly down‐regulated in DHA‐treated or Fat‐1 expression cells. MiR26a/b overexpression greatly reduced 15‐PGDH protein level. Since miR26a/b locate in intron region of gene family CTDSP, their expression is intensely correlated and regulated by transcription factor C‐myc. We found significant consistency between C‐myc expression and CTDSPL, CTDSP1 gene or miR26a/b levels. Tumor growth assays, in vitro and in vivo, showed Fat‐1 undermined tumor growth while miR26a/b had a reverse effect. This phenomenon could be attributed to that those two factors regulate the 15‐PGDH expression and further affect the PGE2 production. Taken together, our data provide important mechanistic insights and therapeutic implications for utilizing omega‐3 PUFAs for the treatment of human cholangiocarcinoma.Grant Funding Source: NIH/NCI
Autophagic flux alters hepatic iNOS protein accumulation, functional form, and localization (151.8)
Authors: Loughran Patricia , Sun Qian , Scott Melanie , Stolz Donna , Mastroberardino Pier , Friedman Peter , Watkins Simon , Billiar Timothy 
Published: June 2021

The hepatic iNOS response to different stressors varies with the amount, duration, cell type and source of nitric oxide. Autophagy is known to be regulated by inducible nitric oxide synthase (iNOS) and nitric oxide (NO), but little is known about how autophagic flux impacts iNOS protein levels. Regulation of iNOS accumulation is important to understand as many metabolic processes are influenced by oxygenation/nitrosylation mediated by iNOS/NO during inflammation. We have also previously shown that iNOS binding to ezrin radizin moesin binding phosphoprotein 50 (EBP50) allows transport of iNOS to peroxisomes and then degradation via pexophagy. The aim of this study was to identify the role of alterations of autophagic flux on iNOS in hepatocytes after stimulation with cytokine mix (CM: TNF[500U/ml]; IL1[200U/ml]; IFN [100U/ml]). Rat hepatocytes were stimulated with CM +/‐ autophagic inhibitors for 8h. Cells were analyzed by Griess, immunoblot, and confocal microscopy to determine the localization, functional form and accumulationof iNOS. iNOS peroxisomal localization is maximal with the inclusion of 3MA and to a lesser degree the NO inhibitor, L‐NIO. This form of iNOS was determined by immunoblot to be monomeric. Accumulation of iNOS and its reactive products at the various stages of autophagic sequestration is of interest due to the shift of metabolic processes that rely on heme proteins susceptible to modification by oxygen and nitrogen radicals characteristic in surgical models generated in inflammation.Grant Funding Source: R37‐GM044100 awarded to TRB
Designing an interprofessional learning curriculum for medical and physical therapy students in gross anatomy curriculum (18.5)
Authors: Euerle Terin , Haller Elizabeth , Lachman Nirusha , Pawlina Wojciech , Youdas James , Hellyer Nathan , Krause David 
Published: June 2021

Interprofessional collaboration in healthcare is crucial for quality patient care. While it continues to be an expected competency, most educational programs lack interprofessional learning (IPL) experiences. We administered the five‐point Likert Readiness of Interprofessional Learning Scale (RIPLS) to first year medical (MD) and physical therapy (PT) students to evaluate attitudes toward IPL. Students agreed that “For small group learning to work, students need to trust and respect each other” (average of 4.6 out of five points). They also disagreed that learning with other healthcare students is a waste of time or unnecessary (averages of 1.91 and 1.98 respectively).Clearly students desire IPL experiences, and with this in mind, we established an IPL curriculum for their gross anatomy courses. Students were first grouped into interprofessional teams at a social event. In dissection lab, PT students taught upper limb and MD students taught thorax anatomy. We also conducted IPL anatomy based problem solving sessions in a classroom setting.Anatomy courses provide an ideal platform for IPL opportunities. Lab and classroom activities enable students to work together through a shared experience of understanding anatomical concepts from different perspectives. By establishing an IPL curriculum, we hoped to increase interprofessional collaboration early in students’ medical education. Our results indicate positive student attitude toward the learning experience.
Mixed methods evaluation of an online undergraduate systemic human anatomy course with laboratory (211.1)
Authors: Attardi Stefanie , Barnett John , Rogers Kem 
Published: June 2021

An online section of a Systemic Human Anatomy course was offered for the first time in 2012/13. Lectures for face‐to‐face (F2F) students (n=365) were broadcast in live and archived format to online students (n=40) using virtual classroom software (Blackboard Collaborate). Labs were delivered online by a teaching assistant who manipulated 3D computer models in the virtual classroom. A mixed methods approach is being used to determine the effectiveness of the online format. Student performance measures (4 tests, 24 lab quizzes) were statistically identical between sections. Incoming grade averages were strongly correlated to overall anatomy grade in both F2F (r = 0.70, p < 0.01) and online (r = 0.63, p < 0.01) sections, suggesting that prior academic performance, and not course format, predicts performance in anatomy. Interviews (22 online; 38 F2F students) and surveys (270 F2F students) regarding perceptions of the learning experience were conducted following a cross‐over period that exposed students to both formats. Survey results indicate that while students preferred online lectures (52%), F2F labs were preferred (85%). Online lectures gave students the benefit of reviewing archived sessions, while F2F labs allowed for better student‐teacher communication. A content analysis of interview transcripts is being undertaken to generate grounded theory about the strengths and weaknesses of the online course.Grant Funding Source: Departmental funding
The anti‐inflammatory effects of manniflavanone extracted from Garcinia buchananii bark in obesity‐induced mice model (259.3)
Authors: Bibi Shima , Balemba Onesmo , Carrion‐Rabanal Rocio , Nyavor Yvonne , Noratto Giuliana 
Published: June 2021

The stem bark of Garcinia buchananii trees is used traditionally to treat diarrhea, dysentery, weight control, and diabetes in Africa. We investigated the anti‐inflammatory and antioxidant activity of the stem bark extracts and identified manniflavanone (Mf) as the most active antioxidant and anti‐inflammatory phenolic compound among the isolated bark phenolics. Seven‐week‐old C57Bl/6 J mice (4 groups) were fed a standard chow (SC) diet and high fat (HF) diet with Mf (SCMf, HFMf) extract (0.164 mg/day) for 3 weeks. Mice were terminated after 8 weeks, fecal and colon tissue was collected for analysis of inflammatory markers and microbiota. Results showed that body mass index (BMI) of mice on SCMf was lower (3.3 Kg/m2) than mice on SC (3.75 Kg/m2). Colon IL‐8, NF‐ĸB and TNF‐α mRNA levels were downregulated in SCMf to 0.69‐, 0.68‐ and 0.49‐fold of SC control, respectively, while IL‐8 and NF‐ĸB were downregulated in the HFMf to 0.27‐ and 0.53‐fold of HF control, respectively. These results indicate that the underlying anti‐inflammatory effects of Mf are related to inhibition of NF‐ĸB and NF‐ĸB‐target genes and we are currently investigating the link with changes in fecal microbiota.Grant Funding Source: wheat project
Consumption of vegetable oils with different unsaturated fatty acid profiles increases cholesterol efflux from THP‐1 macrophages (269.4)
Authors: Liu Xiaoran , Kris‐Etherton Penny , West Sheila , Lamarche Benoît , Couture Patrick , Jenkins David , Fleming Jennifer , Vanden Heuvel Jack , Jones Peter 
Published: June 2021

Cholesterol efflux (CEx) from peripheral tissues is thought to be cardioprotective. Vegetable oils with different unsaturated fatty acid (UFA) profiles and low in saturated fatty acids (SFA) (<10g /100g) may enhance CEx from lipid laden macrophages. The Canola Oil Multicentre Intervention Trial was a double‐blind, randomized, 5‐period crossover, controlled feeding (weight maintenance) study designed to evaluate the efficacy of five vegetable oil treatments on CEx in individuals at risk for Mets with central obesity. These treatment oils were canola oil (62.8% MUFA, 29.3% PUFA: 19.5% LA, 10% ALA), high oleic canola oil (72% MUFA, 17% PUFA: 15% LA, 2% ALA), high oleic canola oil with DHA (63.8% MUFA, 13% LA, 6% DHA), corn/safflower oil (69.3% LA, 17.6% MUFA), and flax/safflower oil (69.4% PUFA: 37.5% LA, 32% ALA, 17.9% MUFA). Subjects (n=100: 51 women, 49 men) were fed isocaloric, heart healthy diet (50% CHO, 15% PRO, 35% FAT, SFA < 7%) containing one of the five treatment oils incorporated in a smoothie for 4 weeks followed by a 2‐4 week break between diets. CEx was measured via a high‐throughput assay using THP‐1 macrophages incubated with human sera from baseline or post diet treatment. At the end of each treatment, canola oil, high oleic canola oil with DHA, corn/safflower oil and flax/safflower oil increased CEx by 28.5%, 31.6%, 20.7%, 20.1% respectively, compared to baseline values (p<0.05). The increase in CEx following high oleic canola oil consumption was 8% (NS). Predictors of CEx capacity in subjects at risk for MetS with central obesity include gender, weight status and baseline CEx. In summary, vegetable oils high in UFA and low in SFA increase CEx from macrophages.Grant Funding Source: Supported by: Canola Council of Canada
Site‐and promoter‐specific epigenetic alterations by a common dietary compound (271.5)
Authors: Dey Moul , Liu Yi 
Published: June 2021

Effects of dietary compounds on site‐specific histone modifications, which are key epigenetic regulators of gene expression impacting cancer etiology, remain relatively unexplored. Phenethylisothiocyanate (PEITC) is a common dietary compound derived from cruciferous vegetables. Our previous research have shown promising anti‐inflammatory and chemo preventive properties of PEITC. The present study reports novel, dynamic, site‐specific chemical changes to histone H3 in a gene‐promoter‐specific manner, associated with PEITC exposure in human colon tumor‐derived epithelial cells. The time‐and concentration‐dependent effects of PEITC on histone modifications (di‐and tri‐methylations of lysine‐9 and lysine‐27 and acetylation) and gene expression changes were achieved at low, non‐cytotoxic concentrations, in contrast to the higher concentrations necessary to halt cancer cell proliferation likely mediated by caspase‐dependent apoptotic signaling. Increased understanding of specific epigenetic alterations by dietary compounds may provide molecular predictors for improved preventive strategies for reducing the healthcare burden of cancer and other human diseases.Grant Funding Source: The work is supported by the National Institutes of Health grant R00AT4245 and SDAES grant 328100/31
Comparative bioavailability of omega‐3 fatty acids from four different omega‐3 supplements (272.6)
Authors: Laidlaw Maggie , Cockerline Carla , Rowe William 
Published: June 2021

This was an open‐label cross‐over study. Thirty‐five healthy subjects were randomized to consume one of four products for four weeks, followed by a four‐week washout. The four products and daily doses (as recommended on the product labels) were: Nordic Naturals ProOmega® Concentrated Triglyceride fish oil: EPA of 650 mg, DHA of 450 mg Minami MorEPA® Platinum Ethyl Ester fish oil: EPA of 756 mg, DHA of 228 mg Source Naturals ArcticPure® Phospholipid krill oil: EPA of 150 mg, DHA of 90 mg New Chapter Wholemega® Triglyceride (TG) salmon oil: EPA of 180 mg, DHA of 220 mg This schedule continued until participants had consumed each product for four weeks, in random order. Blood samples before and after supplementation were quantified for whole blood fatty acids by gas chromatography flame ionization, followed by statistical analyses using ANOVA for repeated measures.At the prescribed daily dose, concentrated TG fish oil was statistically superior to all of its comparators in the bioavailability of EPA+DHA, and of DHA alone. Its EPA percentage increase was more than four times that of krill oil and TG salmon oil. At an extrapolated dose of 1,000 mg/day of omega‐3 fatty acid of interest, concentrated TG fish oil maintained its superiority over all three comparators for the whole blood EPA, DHA and EPA+DHA increases over 28 days of supplementation. For patients, type and dose of omega‐3 supplementation may be clinically important.