bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of zinc deficiency and diet restriction on gene expression of hypoxia‐inducible factors in rat's kidney
Authors: Konomi Aki , Yokoi Katsuhiko 
Published: June 2021

We reported that plasma erythropoietin (EPO) concentration, kidney EPO concentration and kidney EPO mRNA level were changed by moderate zinc deficiency or diet restriction. It is not established how moderate zinc deficiency or diet restriction induces these alterations. We investigated whether moderate zinc deficiency or diet restriction affects renal hypoxia‐inducible factor genes expression in rats.Thirty 3‐week‐old male Sprague‐Dawley rats were assigned into 3 dietary groups (n=10 each) and fed on dietary regimens for 4 weeks: control group (AIN‐93G; Control), moderate zinc‐deficient group (4.5 mg Zn/kg) and pair‐fed group (AIN‐93G; diet restriction). Kidney was separated into cortex and medulla for RNA isolation. Quantitative real time‐PCR using TaqMan proves was performed for mRNA measurement of hypoxia‐inducible factor (Hif) genes (Hif‐1a, Hif‐1an and Hif‐3a). Statistical analysis was performed by ANOVA and PLSD with separate variance approach (when normality was satisfied) or the Kruskal‐Wallis and Conover‐Iman tests (when normality was not satisfied). P value less than 0.05 was considered significant. Kidney medulla mRNA expressions per organ weight of Hif‐1a and Hif‐1an were significantly decreased by zinc deficiency or diet restriction compared with Control. Kidney medulla Hif‐3a and cortex Hif‐1a, Hif‐1an and Hif‐3a mRNA expressions per organ weight were not significantly different among all groups.These results suggest that kidney hypoxia‐inducible factor gene expressions are decreased by zinc deficiency and diet restriction.Support or Funding InformationThis work was supported by KAKENHI grant‐in‐aid for Young Scientists (B) (23700928) and (15K16216).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Artificial sweeteners and dietary disaccharides promote the release of glucagon‐like peptide‐1 in GLUTag cells, an in vitro model of the enteroendocrine cell
Authors: Mehat Kirnjot , Corpe Christopher 
Published: June 2021

Due to the rise in diabetes rates across the world, the enteroendocrine cells (EEC) of the small intestine have gathered much interest in recent years because of their roles in secreting the incretin hormones, glucagon‐like peptide 1 (GLP‐1) and glucose‐dependent insulinotropic peptide (GIP) in response to ingested carbohydrates. Both GLP‐1 and GIP promote insulin synthesis and secretion and therefore play an important role in controlling blood glucose levels. While glucose induced incretin secretion by EEC cells has been well established, the response of EEC cells to other dietary carbohydrates, such as the dissacharides, and non‐nutritive sweeteners, such as artificial sweeteners (AS), is less well understood. Thus, to investigate the effects of the AS, aspartame, acesfulfame‐K and Canderel® (1.4% aspartame;0.95% acesulfame‐k) and the disaccharides, maltose, sucrose, trehalose and lactose on GLP‐1 secretion, we used the mouse EEC line, GLUTag, a well established model of the L cell, which is predominantly found in the distal regions of the small intestine. GLUTag cells were incubated with the AS (at 0, 0.25, 0.4 and 5mM), and the disaccharides and glucose (at 0, 0.25, 0.5, 2.5, 5, 12.5, 25 and 50mM) for 2 hours at 37° C and the supernatant collected. GLP‐1 was measured from the supernatant using a GLP‐1 (Active) ELISA assay (EMD Millipore®, UK). Our results showed that at dietary relevant doses (0.25–5mM) the individual AS, aspartame and acesulfame‐k, and the AS mixture, Canderel® significantly induced GLP‐1 secretion in GLUTag cells when compared to baseline (except for 0.25mM acesulfame‐k) and values were similar to glucose‐induced GLP‐1 secretion. Cells incubated in a combination of Canderel® and glucose (0.4mM and 5mM) showed the highest secretion of GLP‐1; indicating a potential synergistic effect of AS and other nutrients in EEC function. Of the disaccharides tested, maltose showed a significant dose‐responsive increase in GLP‐1 secretion from 0–5mM with values nearly similar to glucose induced secretion over the same concentration range. Gene expression studies by RT‐PCR showed the sweet taste receptors (T1R3) and maltase‐glucoamylase (MGAM) gene to be expressed in the cell line; suggesting the potential mechanism behind AS and maltose sensing in EEC. These in vitro results indicate a possible role for AS and the disaccharide maltose in promoting incretin hormone secretion and having an impact on glycaemia.Support or Funding InformationSelf‐funded projectThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Kvβ subunit interacts with NEDD4 leading to decreased mouse skeletal muscle size.
Authors: Tipparaju Srinivas , Tur Jared , Brotto Marco , Chapalamadagu Kalyan 
Published: June 2021

BackgroundThe voltage‐gated potassium channel subunits 1–3 play significant physiological roles in excitable and non‐excitable tissues. However, the precise nature of its expression and functional identify in skeletal muscle remains unknown.HypothesisTherefore we hypothesized that Kvβ subunits play a significant physiological role in the skeletal muscle.Methods and ResultsIn the present study we identified that the voltage gated potassium channel subunit Kvβ interacts with NEDD4 in skeletal muscle. Previous research indicated a possible interaction with Kvβ and NEDD4 through pathway analysis. Utilizing immunoprecipitate pulldown technique, wild type skeletal muscle homogenates were incubated with Kvβ2 coated magnetic beads and run on SDS‐PAGE and immunoblotted with NEDD4 antibody demonstrating a visible band. Using a genetic deletion of kcnab we identified that the size of the major hind limb muscle is significantly decreased in Kvβ KO mice compared with wild type mice. Therefore we explored the underlying causes for this phenotype since Kvβ is ubiquitously expressed in skeletal muscle. Based on our investigation Kvβ plays a major role in muscle differentiation and overall size, however the proliferation aspect in skeletal muscle at least in the in vitro level remains unaffected. We utilized targeted siRNA knockdown approached to confirm these findings. In addition, tissue analysis reveals that the MHCI fiber type is significantly increased in Kvβ KO group compared with wild type.ConclusionOverall, this is the first study demonstrating that Kvβ2 plays a significant role in determining the size of the skeletal muscle and phenotype.Support or Funding InformationThis Research work was funded by National Institutes of Health (NIH) Grant R01‐HL‐102171 (S. M. Tipparaju).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protein Synthesis throughout the Progression of Cancer Cachexia in Tumor‐Bearing Mice
Authors: Brown Jacob Levi , Lee David , Rosa‐Caldwell Megan , Perry Richard , Haynie Wesley , Benson Conner , Washington Tyrone , Wiggs Michael , Greene Nicholas 
Published: June 2021

Cancer cachexia occurs in approximately 80 percent of cancer patients and is a key contributor to cancer‐related death. The mechanisms controlling development of tumor‐induced muscle wasting are not fully elucidated. Specifically, the progression of cancer cachexia is underexplored. We have previously reported that muscle wasting occurs 4 wks following tumor implantation in these mice.PurposeTo examine the rate of muscle protein synthesis throughout the progression of cancer cachexia in tumor‐bearing mice.MethodsLewis Lung Carcinoma (LLC) was injected into the hind‐flank of C57BL6/J mice at 8 wks age with tumor allowed to develop for 1, 2, 3, or 4 wks and compared to PBS injected control. PBS control animals were age matched to the 4 wk tumor bearing group. Cumulative fractional protein synthetic rates (FSR) were determined using deuterium oxide (2H20). Briefly, a (20 μL/g body weight) bolus priming dose of deuterium oxide was injected intraperitoneally approximately 24 hours before tissue collection. Drinking water was thereafter supplemented with 4% deuterium oxide in order to maintain the plasma pool of deuterium oxide. Fractional synthetic rate (FSR) of mixed muscle fraction (soluble, mitochondria, sarcolemmal, and contractile) and myofibrillar (contractile) rich fraction from gastrocnemius muscle were measured us a GC/MS. Data were analyzed by one‐way ANOVA. When significant F‐ratios were found, a SNK post hoc was used to compare differences between experimental groups. Significance was established at p<0.05.ResultsPlasma enrichment of 2H20 for all groups was 2.91 ± 0.073% and no significant differences existed in means between groups. Mixed muscle FSR remained consistent in 1 wk and 2 wk animals and was ~40% lower 4 wks following tumor implantation (p<0.05) when compared to PBS control. The myofibrillar rich fraction of FSR followed a similar pattern, but changes did not reach statistical significance between groups.ConclusionsThese data indicate muscle protein synthesis decreases concomitantly with muscle loss and may be a major contributor of cancer cachexia in tumor‐bearing mice. More research needs to be conducted to analyze the mechanism for the loss of protein synthesis in cachectic mice.Support or Funding InformationThis study was supported by The Arkansas Bioscience Institute and National Institutes of Health R15AR069913.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Participation of Toll‐like Receptor (TLR) 9 in Obesity‐Induced Benign Prostatic Hyperplasia (BPH) in Mice: Implication of Periprostatic Fat
Authors: Calmasini Fabiano Beraldi , McCarthy Cameron G. , Wenceslau Camilla F. , Priviero Fernanda BM. , Antunes Edson , Webb RC 
Published: June 2021

IntroductionClinical and experimental studies indicate a strong correlation between obesity and benign prostatic hyperplasia (BPH)[1]. Recently, prostatic inflammation and innate immune system have been shown to play a pivotal role in BPH pathogenesis/progression [2]. In the present study we explored the presence and participation of TLR9 signaling pathway on obesity‐induced BPH in mice.MethodsUsing prostate from C57BL6/JUnib mice, we performed immunofluorescence analysis for TLR9 localization. We also evaluated the effects of the in vitro TLR9 activation by ODN 2395 on functional (concentration‐response curves) and molecular (MYD88, TRAF6 and COX2 ‐ TLR9 pathway protein expression) protocols. Besides, male C57BL6/JUnib (Wild type) and TLR9 mutant mice were fed for 12 weeks with either a standard chow or high‐fat diet (HFD) to induce obesity. Fasting glucose levels and body, epididymal and periprostatic fat weight were evaluated. Concentration‐response curves to phenylephrine (PE; α1‐adrenoceptor agonist) and potassium chloride (KCl; depolarizing agent), as well as neurogenic contractions produced by electrical‐field stimulation (EFS; 1–32 Hz, 50 V, 10 s) were also obtained.ResultsThe immunofluorescence assay revealed the presence of TLR9 in epithelial layer of the mouse prostate. The in vitro TLR9 activation with ODN 2395 (TLR9 agonist; 5 μM) led to a significant decrease (P<0.05) in prostate smooth muscle (PSM) contractions to PE and EFS along with increases in MYD88, TRAF6 and COX2 protein expression in prostate from C57BL6/JUnib mice. After 12 weeks of HFD, the TLR9 mutant obese mice exhibited the same body weight compared with WT obese group, however, fasting glucose (FG) and epididymal fat (EF) were reduced on TLR9 mutant obese mice. Despite improvements in FG and EF, TLR9 mutant obese group showed increases in prostate weight and PSM reactivity to PE, KCl and EFS compared with WT and TLR9 mutant lean group. Interestingly, the periprostatic fat (PF) showed augmented (P<0.001) in TLR9 mutant lean group compared with WT lean group. Under obesity conditions, an increase in PF was seen in WT obese group, which was further increased in TLR9 mutant obese group.ConclusionDespite amelioration in fasting glucose and reduction in epididymal fat, TLR9 mutant obese mice still exhibit BPH, which can be, at least in part, due to augmented periprostatic fat.Support or Funding InformationFinancial support: FAPESP (2016/20592‐8); NIH (NHLBI 001961)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
STAT1 (Signal Transducer and Activator of Transcription 1) Deficiency in T Cells Upregulates MHC Class II and Co‐stimulation Receptors, Suggesting that STAT1 deficiency in T Cells May Increase the Plasticity and Convert in to Atypical Antigen Presenting Cells
Authors: Yang William Y. , Shen Haitao , Wu Na , Nanayakkara Gayani K. , Fu Hangfei , Drummer Charles , Shao Ying , Wang LuQiao , Yang Qian , Xu Keman , Hu Wenhui , Choi Eric T. , Wang Hong , Yang Xiaofeng 
Published: June 2021

It is well known that antigen presenting cells (APC) express co‐stimulation receptors (CSR) and co‐inhibition receptors (CIR) that play important roles in modulating T cell activation status. The CSR and CIR can affect priming, T‐helper (Th) cell differentiation, effector and memory function of T‐cells. However, the issue of whether the types and number of APCs vary across different tissues is not known. Therefore, we hypothesize that the types and number of APCs vary across different tissues, which create different stimulatory/suppressive environments depending on the tissues and determine the four functional aspects of T cells mentioned above. Therefore, to validate this hypothesis, we conducted an extensive data mining study. In our analysis, we included 14 CSRs and 14 CIRs. Our study revealed following interesting findings. 1) The CSRs and CIRs are differentially expressed in human tissues. Amongst all the co‐stimulation receptors included in our analysis, CSRs such as CD40, CD48, HVEM and B7‐H2 are highly expressed in many types of human tissues. SEMA4A is the only CIR that is highly expressed in human tissues. Moreover, lymph node, placenta, thymus and trachea had the highest co‐stimulation and co‐inhibition potential. 2) Two CSRs including CD40 and CD70 can affect all the four functional aspects of T‐cells. CSRs such as CD48, CD58, TL1A, OX40L, LGHT, B7‐H2 and one co‐inhibition receptor (CIR) Galectin 9 regulates only three functions of T‐cells. 3) Co‐signaling potential varies between tissues, therefore T‐cell functions may undergo differential regulation. 4) Human tumors have increased co‐stimulation potential than correlated healthy human tissues. This may predict the improved prognosis of patients with tumor. 5) Inflammasome components and tissue hyper‐/hypo‐methylation status can significantly regulate the expression of co‐stimulation receptors in the tissues. 6) STAT1 deficiency in T cells upregulates MHC class II and co‐stimulation Receptor. This suggest that STAT1 deficiency in T cells may increase the plasticity and promote the conversion of T‐cells into APCs. Based on our findings, we conclude that tissue environment can regulate the expression of co‐stimulation receptors, and thereby significantly affect the functions of T‐cells; and key transcription factors such as STAT1 not only plays important roles in regulating cytokine pathways and T cell function, but also determine T cell identity and roles of atypical T cells in immune responses.Support or Funding InformationRO1 ‐ HL132399‐01A1This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Redesigning a Physiology Course Using Core Concepts and Active Learning Methods
Authors: Jensen Murray , Malmquist Sarah , Hull Kerry 
Published: June 2021

The findings of discipline based education research support the transition away from lecture, towards active learning, and away from details, towards core concepts. In response, a junior level physiology course at the U of Minnesota has been transformed in terms of where it is taught, how it is taught, and what is taught.In 2013 the course was moved from a large auditorium to an active learning classroom. This physical change, however, was not sufficient to induce transformation. Lecture remained the primary mode of instruction, reflecting the instructors' unfamiliarity with teaching methods required to facilitate active learning as well as the lack of active learning curriculum materials for physiology.In August 2017, the course was assigned to two professors who were familiar with Process Oriented Guided Inquiry Learning (POGIL), a well‐established teaching and learning method that utilizes guided inquiry and small cooperative groups. The instructors developed relevant curriculum materials; some were modified forms of existing POGIL curriculum, but most were new. The course now features regular group activities, with minimal class time devoted to traditional lecture.The instructors modified the course content as well as the classroom practices, bypassing the traditional body systems approach in favor of the Core Concepts of Physiology developed by Michael et al. They used core concepts such as homeostasis, flux, and communication to introduce topics such as blood pressure regulation, blood flow dynamics, neuronal physiology, and endocrine regulation. While students took the Homeostasis Concept Inventory on a pre‐ and post‐ basis, the detected learning gains were quite modest because of their strong scores in the pretest.In anonymous open‐ended surveys, students voiced concern about the emphasis on group work over traditional lecture and the lack of reliable study materials. Several expressed their preference for PowerPoint slides over information derived via group activities. Students also remarked that the summative assessments (primarily multiple choice exams) were not reflective of the course practices and content, since they seemed to address information that was not covered in class.While the instructors in the course will continue to use the modified format, they note the importance of better alignment between the core concepts‐based curricular materials and the assessments. The lack of alignment noted by the students largely reflects the difficulty of constructing conceptually‐based assessments. Thus, question databases testing core concepts as well as validated concept inventories are clearly needed to facilitate increased incorporation of core concepts into physiology courses.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Student Perspectives on Active Learning Activities in a Human Anatomy and Physiology Course
Authors: DiFrancesca Heidi M. 
Published: June 2021

An inverted (flipped) teaching model is a blended‐learning pedagogical approach that focuses on learner‐centered instruction. Active learning strategies that facilitate collaboration‐based discussion and small group work that ask students to engage in higher order thinking are paramount to the learner‐centric classes. Evidence that supports the effectiveness of a learner‐centered approach on student learning is well established, and a growing body of research has shown this approach to have a positive impact on student engagement, motivation, and retention. Thus, learner‐centered instruction using a blended‐learning model has gradually become a fundamental part of higher education. Yet, only recently has this approach become a more widely used pedagogy strategy in pre‐health professions and STEM classrooms. Few studies have reported on how students feel about the use of active learning activities as it relates to their learning. Therefore, the purpose of this study was to gather student perspectives on active learning techniques used in an inverted classroom. Undergraduate students (n=88) enrolled in an undergraduate Human Anatomy and Physiology II course taught by one instructor during three separate semesters were asked to evaluate their perception on how various activities impacted their understanding of concepts and helped them to learn. Analysis of the reflection data revealed that 73.86% (n=65) felt strongly that the activities enhanced their learning, while 13.64% (n=12) and 15.9% (n=14) felt that the activities either enhanced their learning slightly or not at all. The results indicate that significantly more students had a positive perspective on how collaboration‐based discussion and small group activities improved their learning (p< 0.000344). Thus, these results support the use of active learning strategies as a way to help increase student learning.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Dynamic Spatio‐Temporal Expression Pattern of FGFR Isoforms During Scleral Ossicle Development
Authors: Kumar Shruti , Franz‐Odendaal Tamara A. 
Published: June 2021

Fibroblast growth factors (FGFs) are an important family of proteins that play several roles during early vertebrate development. The FGF ligands bind to their membrane bound receptors (FGFRs) and activate downstream signalling pathways. Although the role of FGFRs has been widely studied in the development of endochondral bones, little is known about their role in the development of neural crest derived intramembranous bones. Scleral ossicles are a ring of 13–15 neural crest derived intramembranous bones in the eye of the chicken (Gallus gallus) and have been identified as a model for intramembranous bone formation. These bones are induced by a corresponding ring of epithelial thickenings, the conjunctival papillae. Using whole mount in situ hybridization, the spatio‐temporal expression patterns of ‘b’ and ‘c’ isoforms of FGFRs1–3 were determined during the stages of conjunctival papillae (HH30–33) as well as scleral ossicle development (HH34–37). The expression of both ‘b’ and ‘c’ isoforms of FGFRs1–3 were observed during conjunctival papillae development and their downregulation was observed during the stages of scleral ossicle induction. ImageJ was further used to study changes in the intensity of expression and to give a more precise indication of the stages of downregulation for each gene. Additionally, although all FGFRs were expressed in the epithelium, only FGFRs 1c, 2c, 3b and 3c were observed in the mesenchyme. The dynamic spatio‐temporal expression pattern of the FGFR isoforms during conjunctival papillae development implicates several FGF ligands in conjunctival papillae induction. This research will further our understanding of the signalling pathways potentially involved in the scleral ossicle system. FGF signaling is likely to interact with the Bone Morphogenetic Protein and Hedgehog pathways, already identified to play a role in the scleral ossicle system.Support or Funding InformationThis research was funded by the Natural Sciences and Engineering Research Council of CanadaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.