bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine D2 receptor decreases the toxic effects of aristolochic acid in human renal proximal tubule cells.
Authors: Kumar Megha , Ayvazian Nicholas , Gildea John , Felder Robin A. , Jose Pedro A. , Armando Ines 
Published: June 2021

Previous work from our laboratory indicates that the renal dopamine D2 receptor (D2R) has a direct role in regulating renal inflammation and injury and blood pressure. In mice, renal‐selective D2R silencing increased the expression of pro‐inflammatory and pro‐fibrotic factors including TNFα, chemokine CCL‐2, TGFβ, fibronectin 1 (Fn1), and collagen 1α1 (Col1α1). Moreover, the damaging effects of 45‐minute bilateral ischemia/reperfusion on renal expression of profibrotic factors, renal function, and blood pressure in mice were ameliorated by a renal‐selective increase in D2R expression by the retrograde ureteral infusion of a viral vector carrying DRD2. In human renal proximal tubule cells (hRPTCs), D2R silencing increased the expression of TGFβ, Fn1 and Col1α1. We tested the hypothesis that in hRPTCs, D2R agonism decreases the deleterious effects of aristolochic acid, a potent nephrotoxic. hRPTCs were treated with aristolochic acid (5μg/ml, 24 hrs) in the presence or absence of the D2R agonist quinpirole (0.5 μM). Treatment with aristolochic acid increased the mRNA expression of TGFβ (1.3 ± 0.02; n=3; P<0.05), Fn1 (2.6 ±0.4‐fold, n=3, P<0.05), Col1α1 (1.9±0.2‐fold; n=3; P<0.05), and connective tissue growth factor (CTGF, 7.6 ± 0.3‐fold, n=3, P<0.05). Treatment with quinpirole, alone, decreased significantly the mRNA expression of TGFβ (0.7±0.05‐fold, n=3, P<0.05) and Fn1 (0.8±0.01‐fold, n=3, P<0.05) but did not change the expression of Col1α1, or CTCG. However, quinpirole reduced significantly the aristolochic‐mediated increase in the expression of Fn1 by 43% and Col1α1 by 35% but had no significant effect on that of TGFβ or CTGF. Our results indicate that several pathways are involved in the nephrotoxic effects of aristolochic acid and that D2R agonism is able to negatively regulate some but not all of those pathways.Support or Funding InformationThis work was funded by grants from the NIH: R01DK090918, P01HL074940, P01HL068686, R01HL092196, R37HL023081, and R01DK039308.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Buffer Composition and Substrates on Calcium‐stimulated Mitochondrial Respiration and Free Radical Emission
Authors: Duong Quynh , Zhong Katie , Zhang Yizhu , Bazil Jason 
Published: June 2021

Mitochondrial ATP synthesis is tightly coupled to oxygen consumption in a highly regulated process; however, unavoidable byproducts in the form of reactive oxygen species (ROS) are formed. An important regulator of this process is calcium, but the precise relationship between calcium and free radical production is obscure. Therefore, we measured ROS production under a variety of experimental conditions that mimic the pathological environmental setting. The Oroborous oxygraph system was used to simultaneously measure ROS emission and the oxygen consumption rate from isolated cardiac guinea pig mitochondria energized with different substrates and challenged with different calcium concentrations. The Amplex Red assay was used to quantify ROS emission rates. The substrates used utilized a mixture of the carbohydrate and fatty acid dependent metabolic pathways. Two respiration buffers, one lactobionate‐based and the other potassium chloride‐based, were used to quantify the differences in respiration and ROS emission rates. Relative to the potassium chloride‐based respiration buffer, the lactobionate‐based buffer resulted in higher ADP‐stimulated respiration rates and higher ROS emission rates for each substrate combination. On average, the presence of calcium depressed ROS emission rates during the leak respiration, sodium/calcium cycling, and ADP‐stimulated states. The lower respiration rates in the potassium chloride‐based buffer is likely due to the presence of inhibitory levels of chloride. The high chloride levels also appear to depress ROS emission. Overall, these data refute the hypothesis that calcium stimulates ROS emission from isolated mitochondria. Studies are ongoing to further characterize ROS emission from cardiac guinea pig mitochondria and elucidate the relationship between calcium and ROS emission.Support or Funding InformationR00‐HL121160This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Regulated Dephosphorylation of NCC Shapes the Renal Potassium Switch Pathway
Authors: Grimm P. Richard , Li Dimin , Delpire Eric , Welling Paul A. 
Published: June 2021

The Renal Potassium Switch pathway stimulates the thiazide‐diuretic sensitive sodium chloride cotransporter (NCC) to limit urinary potassium loss at the expense of retaining sodium and elevating blood pressure. It has been established that Low [K+]o activates the WNK4‐SPAK kinases to drive NCC phosphorylation, but it remains mysterious how NCC is dephosphorylated in response to an acute rise in [K+]o. It has been generally assumed that high [K+]o turns off WNK4 kinase activation, allowing constitutive phosphatase activity to dephosphorylate WNK4 in states of dietary potassium loading. Here, we challenge the prevailing view.Kinase‐activating mutations were introduced in SPAK, the terminal kinase in the WNK signaling pathway, and renal expression of the constitutively active (CA) SPAK mutant was specifically targeted in mice to the early DCT with a DCT‐driven Cre‐recombinase. NCC abundance (tNCC) and phosphorylation (pNCC) were evaluated in vivo and in isolated tubules, together with telemetric blood pressure (BP) measurements in response to changes in dietary potassium and [K+]o. CA‐SPAK were compared to Control mice.CA‐SPAK mice display thiazide‐treatable hypertension, concurrent with NCC hyperphosphorylation. BP remained elevated in CA‐SPAK mice, compared to control, over a wide range of [K+]o, as predicted. However, BP dropped in CA‐mice when [K+]o exceeded 5 mM, and this was coincident with a reduction in pNCC/tNCC, revealing a [K+]‐regulated dephosphorylation mechanism. In isolated control DCT tubules, an acute increase in [K+]o rapidly reduced pNCC with IC50 of ~3.5 mM, indicating [K+]o directly modulates dephosphorylation of the switch pathway. [K+]o–regulated dephosphorylation of pNCC was also observed in DCT isolated from CA‐SPAK mice but the response displayed a rightward shift in the dependence on [K+]o.ConclusionBecause CA‐SPAK drives NCC phosphorylation independent and downstream of WNK, these observations provide strong support for a potassium‐activated phosphatase that directly dephosphorylates NCC. Thus [K+]o–regulated phosphorylation as well as dephosphorylation of NCC shape the Renal Potassium Switch response. Regulated NCC dephosphorylation provides a new mechanism to explain why high dietary K+ consumption alleviates salt‐sensitive hypertension and associated cardiovascular complications.Support or Funding InformationFunding for this project was provided National Institutes of Health Grants DK63049, DK54231, and DK093501This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inflammation Differentially Impacts Phrenic Long‐term Facilitation (pLTF) in Rats with Motor Neuron Death Induced by Intrapleural CTB‐saporin Injections
Authors: Nichols Nicole L. , Tanner Miles A. 
Published: June 2021

Intrapleural injection of cholera toxin B fragment conjugated to saporin (CTB‐SAP) selectively kills respiratory motor neurons, and mimics aspects of neuromuscular disorders and neurodegenerative diseases including phrenic motor neuron death, decreased phrenic motor output, and increased microglial cell number. Our previous results demonstrated unexpectedly that respiratory plasticity is not only observed 7 days (d) after CTB‐SAP delivery, but that it is actually enhanced compared to control treatments. At 28d, however, respiratory plasticity is comparable to control levels, suggesting that the underlying mechanisms of plasticity at both time points may differ. Because inflammation is a hallmark of all neurodegenerative diseases, and it is known to prevent the development of acute intermittent hypoxia‐induced phrenic long‐term facilitation (pLTF), we predicted that inflammation would impair pLTF in CTB‐SAP‐treated rats and thus, anti‐inflammatory drugs would enhance pLTF at both time points. Using anesthetized, paralyzed and ventilated CTB‐SAP‐treated adult Sprague Dawley rats, we studied acute intermittent hypoxia (AIH; 3, 5 min bouts of 10.5% O2) induced pLTF following intrathecal C4 delivery of the nonsteroidal anti‐inflammatory drug ketoprofen to rats that received bilateral, intrapleural injections of: 1) CTB‐SAP (25μg), or 2) un‐conjugated CTB and SAP (control) in rats treated 7d or 28d prior. Surprisingly, preliminary results indicate that ketoprofen attenuates pLTF in 7d CTB‐SAP‐treated rats, but enhances it in the 28d CTB‐SAP‐treated rats. These observations suggest that inflammation potentially contributes to pLTF in 7d CTB‐SAP‐treated rats, whereas it may undermine pLTF in 28d CTB‐SAP‐treated rats. Studies are underway to assess cervical spinal levels of both pro‐inflammatory and anti‐inflammatory and neurotrophic molecules at both time points, and their cellular source. Future studies will investigate the potential contributions of microglia to the mechanisms whereby inflammation differentially impacts pLTF in CTB‐SAP‐treated rats. Results from this project will increase our understanding of how inflammation and microglial activities influence respiratory plasticity following motor neuron death, and will have broad implications for therapies restoring ventilatory function in many disorders in which motor neuron death is associated.Support or Funding InformationNIH K99/R00 HL119606This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protection against hypoxia‐induced pulmonary hypertension in CX3CR1‐deficient mice correlates with decreased microglia activation
Authors: Oliveira Aline Cristina , Aquino Victor , Sharma Ravindra K. , Lobaton Gilberto , Harrison Jeffrey K. , Richards Elaine M. , Raizada Mohan K. 
Published: June 2021

BackgroundMicroglia are key modulators of the immune response in the brain and can be activated very early in pathology. Our previous studies have indicated that activation of microglial cells and neuro‐inflammation in autonomic brain regions plays a critical role in pulmonary hypertension (PH), possibly by increasing sympathetic activity. Microglial activation is regulated by the chemokine fractalkine, CX3CL1, and its receptor CX3CR1. Lack or deficiency of CX3CR1 was shown to significantly reduce inflammation, and suppress activation and neurotoxicity of microglia/macrophages in experimental ischemic stroke.AimThis study was designed to explore the role of CX3CR1 in microglial activation in PH induced by hypoxia.MethodsCX3CR1‐deficient (CX3CR1GFP/GFP) mice and Wild‐type (WT) mice (C57BL/6J) were exposed to 3 weeks of hypoxia (H:10%O2) in a ventilated chamber (n=5–8/group). On day 21, animals were anesthetized and a Millar pressure catheter was inserted into the jugular vein and threaded down into the right ventricle to measure right ventricular systolic pressure (RVSP), dP/dt and collect data for spectral analysis, a measure of sympathetic activity. After measuring hemodynamic parameters, blood and tissues were collected and animals were perfused for histological analyses.ResultsChronic hypoxia induced PH in WT mice, but not in CX3CR1GFP/GFP as demonstrated by hemodynamic analysis (shown in the table below) and sympathetic activity (LF/HF: WT‐N: 0.23 ± 0.8; WT‐H:1.19 ± 0.8; CX3CR1GFP/GFP‐N: 0.19 ± 0.1; CX3CR1GFP/GFP‐H: 0.29 ± 0.05; p<0.001). PH is associated with increase in activated microgial cells in the autonomic brain areas, predominantly in the paraventricular nucleus (PVN). However, exposure of the CX3CR1GFP/GFP mice to hypoxia did not change microglia activation in the PVN (CX3CR1GFP/GFP‐N: 1441 ± 51; CX3CR1GFP/GFP‐H: 1541 ± 68). Furthermore, a positive correlation between microglia and RVSP was also observed (R square: 0.4619 p=0.03).ConclusionThese data demonstrate a relationship between RVSP and PVN microglia and suggest that microglia activation and neuroinflammation in the autonomic brain areas may be involved in development of PH.Support or Funding InformationThis research is supported by NIH grant HL102033.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Self‐Directed Learning Modules Enhance Mastery of Diagnostic Imaging in a Dissection‐Based Anatomy Course for Physician Assistant Students
Authors: Zhang Guiyun , Fenderson Bruce A. , Zuo Xuan 
Published: June 2021

The virtues of using computer‐based learning modules as an alternative to traditional didactic lectures were tested in a human anatomy course for Physician Assistant (PA) students. Self‐directed learning modules on diagnostic imaging were created using Articulate™ software and provided online as homework assignments for PA students taking a human anatomy lecture and dissection laboratory course. These interactive self‐learning modules replaced the content of traditional didactic lectures on the same topics that had been given in previous years. For the PA class of 2016 (n=104), diagnostic imaging was taught via traditional lectures, whereas for the PA class of 2017 (n=100), students studied the same content online using self‐learning modules. An identical set of 21 questions on diagnostic imaging was used for both lecture (2016) and self‐learning (2017) groups of students, and student performance on these examinations was compared between the two groups. Our results indicate that PA students with access to online self‐learning modules performed as well or significantly better on the diagnostic imaging questions (p<0.05 for 5 of 21 questions). Moreover, the average on the diagnostic imaging questions improved from 86.29 (class of 2016) to 89.19 (class of 2017). The overall course grade for students using self‐learning modules for diagnostic imaging was also higher (class mean 87.76) than that of students receiving lectures for diagnostic imaging (class mean 86.08), suggesting that self‐learning modules may have a positive influence on students' overall understanding of the anatomical material. Our results indicate that online self‐study modules are highly effective teaching tools for pre‐clinical basic science medical education.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.
Anatomy in a New Curriculum: Using Digital Media to Facilitate the Learning of Anatomy in the Medical Curriculum
Authors: Oberoi Vishesh , Hosseini Farshad , Doroudi Majid , Vo Lien 
Published: June 2021

IntroductionThe advances in technology have allowed teachers to develop new ways to teach their course materials to their students. This has ranged from using educational videos to developing online learning modules that students may complete at their pace and time. Although these advances in enhancing student knowledge have been made in many subjects, there are limited resources available to students for the purposes of learning anatomy. One area that needs to be expanded is one of educational anatomy video tutorials/lessons.ObjectivesThis project was designed to create an educational video tutorial/lesson that provides a step by step tutorial that the students can follow to complete their anatomy lab. The video is designed to complement the lab component rather than replace it as we have realized that there is no substitute to viewing the material first hand. The video would allow students to prepare for the lab and upon its completion, they may refer back to the video and use it as a study tool.MethodsTo begin the cadaver was dissected and prepared so that the anatomical structures that needed to be identified were properly exposed for the filming. The filming was done in a stepwise manner, where the anatomical structures were identified and commented on throughout the video. During the editing, process animations were added to tag key anatomical structures and a quiz was added towards the end to allow students to test their knowledge of the materials in the video.ResultsTo gather the efficacy of the videos and receive feedback we gave the students a survey to conduct prior to and after their lab. The results showed that more than 95% of students felt that the video helped them prepare for the upcoming lab dissection. While 98.9% of students felt that they would like to have a similar lab video for labs in the future. Also, 93% of the students stated that they would like to use the videos to study for their exams.ConclusionDue to the positive responses received it can be concluded that the use of video tutorials in teaching anatomy is an effective tool that can be implemented alongside the lecture material and cadaver dissections to enhance the learning of students.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of a Radiological Anatomy‐Based Intervention on Students in a Medical Gross Anatomy Course
Authors: Larsen Roxanne J. , Engle Deborah L. 
Published: June 2021

Human gross anatomy is an integral aspect of medical education and serves as an important transition into the medical profession. Radiological imaging modalities serve as the link between gross anatomy content and clinical practice. At Duke University School of Medicine, anatomy faculty and radiologists collaborated to introduce radiological anatomy images into our gross anatomy course with the aim of reinforcing student learning of basic science content. We then investigated the effectiveness of this intervention from several perspectives.MethodsIn order to assess the impact of the radiological intervention, we administered: 1) a 12‐question pre‐test/post‐test, 2) an evaluation of the effectiveness of radiology‐based presentations, and 3) an evaluation of the usefulness of the radiology images used. Pre‐test/post‐test questions were selected from a previously validated question bank and were mapped to levels of cognitive processing as adapted from Bloom's Taxonomy. These questions spanned the content covered in our course (thorax, abdomen, pelvis, limbs, head/neck) and the radiological modalities learners would most likely be exposed to during their clinical training (X‐ray, MR, CT). At the conclusion of the course, Likert‐type questions were used to evaluate the learners' perceptions of the usefulness and effectiveness of the radiology presentations and images.ResultsOf 119 eligible learners, a total of 55 participants (46%) volunteered to take both the pre‐test and post‐test. Results of the paired t‐test showed there was a significant difference between the pre‐test (mean = 13.2%, SD = 8.9%) and post‐test (mean = 38.6%, SD = 17.7%) mean scores (t(54) = 9.9, p < 0.0001). Learners were most successful when questions included anatomy of the thorax and abdomen and MR or CT images, and on questions that were mapped to the analyze process. Additionally, survey feedback of all learners indicated all radiology presentations were rated as “adequately effective” (mean rating of 3 on a 5 point scale), and 65% of learners rated the radiological images as useful for studying in the course.ConclusionsResults of this study suggest that the introduction of radiological images was an effective intervention and may have contributed to participants' increased knowledge of gross anatomy content. Given the success of this intervention as evidenced here, we continued to integrate radiological images into gross anatomy instruction for the 2017 cohort. More broadly, this work adds to the growing area of research that supports the integration of clinically relevant applications into basic science courses.Support or Funding InformationSupport and funding provided by the Office of Curricular Affairs and Duke Academy for Health Professions Education and Academic Development, Duke University School of Medicine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterization and Quantification of Osteoarthritis in Cadaveric Elbow and Wrist Joints Using 3D Modeling
Authors: Anderson Jena Louise , Salmon Ciara , Lewis Christina 
Published: June 2021

Osteoarthritis (OA) is the most common chronic disorder of the joints, affecting 10–13% of the U.S. population. OA can interfere with the quality of life by limiting the ability to participate in activities of daily living (ADLs) due to dysfunction and disability caused by reduced mobility and significant acute and chronic pain. While many OA studies have focused on the weight‐bearing joints of the lower limb, OA involving joints of the upper limb (UL), including those of the elbow and wrist, can just as significantly impact the quality of life, yet are underdeveloped. The purpose of the current study is to gain insight regarding the prevalence and patterns of OA in the distal joints of the UL, and to determine if there are relationships among frequency, location, and severity of occurrence, as well as an individual's sex, age, and prior occupations. For these purposes, the elbow and wrist joints were harvested bilaterally from 15 embalmed cadavers (7F, 8M; ages 63–100, with mean of 84 yo ±10.1), dissected, and the articulations examined. The articulating surfaces for the distal humerus, proximal and distal radius and ulna, and the scaphoid, lunate, and triquetrum carpal bones were each examined. Pitting and degeneration of both cartilage and bone of the articulating surfaces were digitized using the Microscribe 3D Digitizer, and3D models were created and subsequently analyzed via Rhinoceros 5 software. Quantitative analyses of the OA at each articulating surface was used to construct a descriptive comparison of the severity of degeneration on a 4‐point scale (i.e., 0 to 3) ranging from no arthritis to severe arthritis. Our preliminary data indicate that the presence and severity of OA typically affected multiple articulation sites, rather than single surfaces, suggesting that the pathogenesis of OA in any given individual may be more complex than is typically appreciated. Additionally, our assessments indicate that OA is present in significant degrees and on multiple surfaces of the elbow joints, and this region is not well explored in the current literature. Ongoing studies seek to include additional specimens and ad hoc analyses of OA patterns with sex, age, and prior occupations. In conclusion, the present study provides additional characterization and description of OA affecting the UL, and this information may guide therapeutic approaches to occupational therapy regimes.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.