bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural Crest Derived Cardiomyocytes Regulate Cardiac Trabeculation and Adult Heart Function.
Authors: Abdul‐Wajid Sarah , Demarest Bradley , Yost H Joseph 
Published: June 2021

The cardiac neural crest arise from the multi‐potent, migratory neural crest cell population and contribute to cardiovascular development, including contributions to cardiac endothelium and myocardium, formation of the great vessels and their valves, as well as septation of the chambers. However, very little is known about the neural crest contribution to the myocardium. This study aims to selectively decipher the function of the neural crest derived cardiomyocytes (NC‐Cms) without the confounding roles of the contributions of neural crest to other tissues, including endocardium. Zebrafish provide a unique genetic model to study this population because of their developmental transparency and they have a relatively large neural crest contribution of NC‐Cms compared to mammals. By creating Zebrafish transgenic lines that both lineage label and allow for ablation of only NC‐Cms, we find that the embryonic NC‐Cms arrive early in zebrafish heart development, makeup ~10% of the embryonic cardiomyocyte population and are steady state by two days post fertilization (2dpf). A majority of this contribution is to the ventricle in a discrete pattern around the apex of the ventricle. To test the function of NC‐Cms during heart development, we genetically ablated them during their early stages (up to 2dpf) and then observed heart development and phenotype up to 14dpf and into adulthood. Surprisingly embryonic ablation of the NC‐Cms was largely dispensable for heart development with a non‐lethal but significant defect in patterning of ventricle trabeculation. Importantly, embryonic ablation of NC‐Cms yielded adults with hypertrabeculated hearts and impaired performance in cardiac stress tests. We investigated the relation of the NC‐Cms to known Notch and Neuregulin effectors of embryonic trabeculation and speculate on their mechanistic regulation of this pathway. These results present a new model of human left ventricular non‐compaction or hypertrabeculation cardiomyopathy, and adult heart failure. Importantly these results demonstrate how a subtle and relatively minor developmental cell population can have detrimental effects on adult cardiac function.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Interactive Cases using the Medical Stories of a Living Anatomical Donor
Authors: Elzie Carrie , Wellman Laurie , Ortiz Fabian , Clark Russ M. , Goodmurphy Craig W. 
Published: June 2021

Narrative medicine is an important and expanding new field that recognizes the value of storytelling in the acts of doctoring. Narrative competence involves recognizing, absorbing, metabolizing, interpreting and being moved by the stories of illness. Our goal was to incorporate this valuable aspect of medicine into the gross anatomy course with first year medical students. To do so, we have taken the illness stories of one living anatomical donor, Mr. Clark, and transformed them into interactive cases and discussions to teach not only the humanity of medicine, but also the anatomical sciences. Five digital interactive cases were generated combining Mr. Clark's personal narratives of his medical encounters, his own medical records and relevant anatomical content using Articulate Storyline. Students reviewed the cases prior to attending a discussion session with Mr. Clark facilitated by a physician where students were allowed to ask any questions which ranged from personal feelings to medical details to financial implications. Qualitative analysis has shown that the conversation has reflected more compassion and reflection than science and medicine. However, anatomical questions based on the cases have performed equally or better than the traditional anatomical course content. Anatomical reflections since the addition of Mr. Clark, who has participated in every anatomy lab and ultrasound session, have become more empathetic and less egoistic. Focus group feedback and course evaluations have been overwhelmingly positive and reviews have outranked similar cases using virtual patients. Thus we encourage all anatomy programs to reach out to prospective donors, as the addition of their stories, has truly enhanced our anatomy course and our students' 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.
Memantine (a dual α7‐nAChR/NMDAR antagonist) displays anti‐angiogenic activity in human squamous cell lung cancer
Authors: Nolan Nicholas A. , Robateau Zachary , Brown Kathleen C. , Chen Yi Charlie , Egleton Richard D. , Tirona Maria R. , Dasgupta Piyali 
Published: June 2021

Cigarette smoking accounts for 85% of squamous cell lung cancer (SCC‐L) in patients. Since SCC‐L is a highly angiogenic tumor, anti‐angiogenic therapies like Avastin have been investigated for the treatment of SCC‐L. However, the drawback of these therapies has been the incidence of pulmonary hemorrhage and extensive hemoptysis in SCC‐L patients. Nicotine, the addictive component of cigarettes, promotes angiogenesis in lung cancer via the α7‐nicotinic acetylcholine receptor (α7‐nAChR) subunit in human lung endothelial cells. Therefore, we conjectured that α7‐nAChR‐antagonists should display potent anti‐angiogenic and antitumor activity in SCC‐Ls. We observed that the α7‐nAChR is robustly expressed on human microvascular endothelial cells of the lung (HMEC‐Ls) and SCC‐L associated endothelial cells (STACE). With this background in mind, we tested the anti‐angiogenic activity of memantine (dual α7‐nAChR/NMDAR antagonist) in SCC‐Ls. Receptor binding assays have shown that the affinity of Memantine for α7‐nAChR is greater than NMDAR. Here we show that memantine attenuates nicotine‐induced angiogenesis in human microvascular endothelial cells of the lung (HMEC‐Ls). Furthermore, the α7‐nAChR antagonist memantine displayed potent antiangiogenic activity in the chicken chorioallantoic membrane (CAM) model. Memantine is an FDA approved drug, used in clinical practice to treat mild‐moderate Alzheimer's disease. It is well tolerated by patients and has a favorable side effect profile. Our studies are unique and innovative because they study, for the first time, the application of memantine in a non‐neuronal disease, namely lung cancer.Support or Funding InformationFunding for our study was supported by an NIH R15‐AREA Grant (2R15CA161491‐02), Edwards Cancer Center Pilot grant, Cabell Huntington Hospital, Marshall University. This work was supported in part by the West Virginia IDeA Network of Biomedical Research Excellence (WV‐INBRE) grant GM103434 (PI: Dr. G. Rankin).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva – How Does One Tissue Become Another?
Authors: Shore Eileen M. 
Published: June 2021

The development and maintenance of tissues and organ systems depend on precise coordination of cellular events and mechanisms. During embryonic development, the induction of bone formation is spatially and temporally regulated to specify the skeletal elements. After birth, new bone formation is normally limited to regeneration during fracture repair, a process that is also precisely regulated.Fibrodysplasia ossificans progressiva (FOP) is a rare human genetic disease in which extensive and progressive heterotopic ossification – the formation of bone outside of the normal skeleton – occurs in soft connective tissues such as skeletal muscle. At birth, there is usually little indication of the disease, except for a characteristic malformation of the great toes. However during early childhood, episodes of bone formation that are frequently associated with swelling and inflammation begin within soft tissues. In most patients examined to date, FOP is caused by a single nucleotide change in the BMP type I receptor ACVR1 (Activin A receptor, type 1; alias, ALK2) that causes enhanced pathway activation. All patients with a classic clinical presentation of the disease possess a recurrent heterozygous c.617G>A (R206H) mutation.Heterotopic ossification in FOP frequently forms in response to tissue injury, although also develops in the absence of overt tissue trauma. Within the tissue, heterotopic bone formation in FOP patients progresses through well‐described changes in affected tissue: initial catabolic events are followed by an anabolic stage and formation of endochondral bone. In vivo mouse models have been instrumental in providing a more detailed understanding of the tissue, cellular, and molecular impact of the ACVR1 R206H mutation and the structural changes in the soft connective tissues that are transitioning to cartilage and bone. In response to injury, initial steps of wound healing in mutant tissue appear to be normal, including an early immune response that leads to tissue degradation and removal of damaged tissue. However this tissue repair trajectory rapidly diverges and, instead of repairing and regenerating the injured muscle tissue, ectopic cartilage and bone are formed. Our investigations of these events are providing a more detailed understanding of the tissue, cellular, and molecular impact of the ACVR1 R206H mutation and of the mechanisms that regulate tissue maintenance, repair, and regeneration.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 Postdoctoral Fellowship in Anatomy Education – Is it Needed?
Authors: Schaefer Audra 
Published: June 2021

With an increasing demand for anatomy faculty members, a number of graduate programs have been implemented to train individuals to be able to teach the various anatomical disciplines. Such programs offer instruction in pedagogy, scholarly teaching and educational research. Although there are increasing numbers of masters and doctoral level programs that have emerged, anatomy education focused postdocs are nearly nonexistent. In this study, members of the American Association of Anatomists were surveyed to determine whether they perceived that a postdoctoral fellowship emphasizing educational research and pedagogy training in the anatomical sciences would be a worthy endeavor. Initially, a pilot survey was conducted, inviting 27 early to mid‐career anatomy faculty to participate. For the second administration of the survey, an open invitation was posted in a public forum on Anatomy Connected, a platform open to all AAA members. Follow‐up interviews were conducted with eight respondents from the pilot survey. Quantitative and qualitative analysis of the survey results, as well as thematic analysis of the interviews revealed that most individuals, regardless of their own completion of a postdoctoral fellowship, see value in a well‐designed anatomy education postdoctoral fellowship experience. Perceived potential benefits include mentorship to enhance their own pedagogy, gain additional teaching experiences, and development of educational research skills. There are concerns regarding the funding support for such a position, as well as the potential exploitation of an individual in such a position. Still, as a whole, the survey and interview results suggest that developing anatomy education postdoctoral fellowships have a strong potential to aid the development of our future anatomy educators and educational researchers, particularly for individuals earning doctorates from programs that do not offer explicit training in pedagogy and/or educational research.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inflammation and Innate Immune Activation During Ex‐Vivo Heart Perfusion
Authors: Qi Xiao , Hatami Sanaz , White Christopher , Himmat Sayed , Aboelnazer Nader , Ondrus Martin , Kinnear Alxe , Wu Yilun , Nagendran Jayan , Freed Darren H. 
Published: June 2021

IntroductionHeart transplantation remains the standard treatment for advanced heart failure. However, waiting lists for donor heart continue to rise all over the world due to the discrepancy between the demand and supply of suitable organs. Ex‐vivo heart perfusion (EVHP) has been proposed as a means improving heart preservation and expanding the donor pool. The clinically available EVHP performs in non‐working mode (NWM). Alternatively, EVHP in working mode (WM) may be better in terms of function assessment and preservation.ObjectivesThe generation of circulating mediators of inflammation during EVHP has not been previously investigated. We hypothesized that inflammatory mediators will be activated during EVHP and that the inflammatory response would play a role in declining of donor heart function.MethodsThe procured porcine hearts were perfused ex vivo in a beating state for 12 hours (normothermic, whole blood‐based perfusate, no steroids) on a custom EVHP apparatus. Group 1 hearts (n=9) were perfused in a working mode (left atrial pressure=6 mmHg, heart rate=100 beats/minutes) for the entire EVHP interval. Group 2 hearts (n=6) were briefly transitioned into a working mode at hours T1, T5, and T11 for inflammatory and functional assessment, but were otherwise perfused in a non‐working mode (left atrial pressure=0 mmHg). In vivo hearts (n=4) without perfusion were treated as baseline control. Cardiac functional parameters were compared between two perfusion modes groups. The pro‐inflammatory cytokine levels in the perfusate and myocardial tissue were measured by ELISA and western blot and compared between two groups.ResultsMyocardial function declined over time but the function parameters were better preserved in WM (T11 cardiac index (mL/minute/gram): WM=6.9±1.0 vs NWM=2.0±1.2, p=0.02; LV stroke work (mm Hg·mL): WM=1012.5±245.7 vs NWM=303.4±121.6, p=0.03). The perfusate concentration of pro‐inflammatory cytokines TNF‐α, IL‐6, IL‐8, IL‐1α, IL‐1β, IL‐18 increased significantly during the 12‐hour perfusion interval (p<0.05), but were not significantly different between WM and NWM groups. The IL‐6 and TNF‐α increased in the left ventricular tissue after perfusion compared to baseline myocardial samples (p<0.05), with no significant difference between WM and NWM.ConclusionsA significant pro‐inflammatory cytokine response is generated during prolonged EVHP in the perfusate and left ventricular tissue, independent of perfusion mode. The inflammatory responses may play role in declining of cardiac function. Further studies are warranted to elucidate the stimulants, consequences of inflammatory responses (I.E. on energy metabolism), and methods to mitigate these effects.Support or Funding InformationCanadian National Transplant Research Program, Canadian Institute of Health Research Grant
Elucidating Epigenetic Readers of H3T45ph in S. cerevisiae
Authors: Grant Patrick , Lee Christina , Pray‐Grant Marilyn , Bekiranov Stefan 
Published: June 2021

The phosphorylation of histone H3 threonine 45 (H3T45ph) in S. cerevisiae and mammalian cells occurs at the N‐terminal alpha‐helix and aligns at the precise location of DNA points of entry and exit on the nucleosome. The phosphorylation peaks during S‐phase and is mediated by the DNA replication kinase Cdc7, which is dependent on forming a complex with Dbf4 to phosphorylate the residue. Loss of T45ph leads to greater sensitivity to replicative stress, but it is not required for cell survival. ChIP‐seq was used to identify the genomic sites of H3T45ph in asynchronous and hydroxyurea (HU) treated cells and RT‐qPCR to determine the mark's influence on transcription. These studies revealed that H3T45ph is located at both origins of replication and at the sites of highly transcribed genes responsible for protein synthesis and glycolysis. Here we aim to elucidate the reader(s) of the H3T45ph mark to aid in understanding the possible roles H3T45ph may play in regulating chromatin structure, the recruitment of transcription factors, or the recruitment of the DNA replication or repair machinery. Our research supports the identification of readers of the mark, which perform a wide variety of functions and are classically associated with DNA damage repair pathways and stabilizing stalled replication forks, as well as differentially regulating rapamycin‐mediated transcription. We hypothesize that these factors act as transcription factors that regulate ribosome biogenesis and cell growth, as well as aid in DNA replication. We speculate this pathway is crucial for efficient DNA replication fork stability and the activation of growth genes, coordinating DNA replication and gene expression in highly proliferating cells.Support or Funding InformationThis work is supported by NIH Grant 5R01GM111911.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 structural role for the C‐terminal conserved LSA motifs in Arabidopsis LARP6 proteins
Authors: Toner Chelsea , Chovanec Lindsay , Foster Corina , Foster Jessica , Otte‐Petrill Courtney , Betancourt Francisco , Billey Elodie , Bousquet‐Antonelli Cécile , Lewis Karen 
Published: June 2021

La Related Protein 6 (LARP6) is a sub‐family of the RNA‐binding La‐Related Proteins superfamily (LARPs). In vertebrates, LARP6 is known to bind to the 5′ untranslated region of mRNAs that encode for collagen type I. In contrast, the ligands and biological function of the three LARP6 paralogs in plant LARP6 (LARP6a, LARP6b and LARP6c) remain to be determined. Of the three variations of the LARP6 protein in Arabidopsis thaliana, LARP6b and LARP6c contain a PAM2 motif in the N terminal region of the protein, while LARP6a does not. All three LARP6 paralogs contain the conserved LSA motif, which is a distinguishing feature of the LARP6 subfamily and has been implicated in biologically relevant protein‐protein interactions. We have successfully expressed and purified full‐length LARP6a, LARP6b, and LARP6c proteins from Arabidopsis thaliana as recombinant proteins in E. coli. Mutant forms of the Arabidopsis LARP6 proteins were generated using site‐directed mutagenesis to test the role of conserved sequence motifs. The deletion of the PAM2 motif from LARP6c does not negatively impact the structural stability of the full‐length protein. However, deletion of the LSA from LARP6c does appear to destabilize the recombinant protein during biosynthesis. We hypothesize that the LSA motif in plant LARP6 proteins contributes to the global structure and/or the thermodynamic stability of the proteins. These studies using highly purified recombinant protein, with protein stability measured by differential scanning calorimetry, provide novel insight into the potential structure and function of the uncharacterized LSA motif that characterizes the LARP6 subfamily of RNA‐binding proteins.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Toxic effect of resveratrol induced by energy restriction on mitochondrial dysfunction in mouse hepatocytes
Authors: CAMACHO LILLIAN , GOMEZ MINERVA RAMOS , PEREZ LUIS ALBERTO MADRIGAL , LORÍA JORGE LUIS ROSADO 
Published: June 2021

Resveratrol (RSV) is a polyphenol classified as a phytoalexin, which occurs naturally and in response to a mechanical injury or biotic and abiotic factors. RSV has been shown to reduce cell viability of pathogenic organisms, probably through inhibition of the electron transport chain (ETC) and F1F0‐ATPase (which is referred to as oxidative phosphorylation in general), generating a decreased synthesis of energy, causing, in turn, a mitochondrial dysfunction. Interest in RSV has increased in recent years due to the beneficial health effects shown by this stilbene. However, such beneficial effects have been observed only at high concentrations of glucose or lipids, without considering those with adequate or low consumption in which the beneficial effect could be neglected and even show toxic effects. Therefore, the objective of the investigation was to determine whether the amount of glucose modulates the effects of RSV on mitochondrial dysfunction in mouse hepatocytes (Hepa1c1c7). Hepa1c1c7 cells were supplemented with both RSV (0.1 to 1000 μM) and glucose (0.5 to 30 mM). According to the MTT assay, at high concentration of RSV (1000 μM) cell viability significantly decreased by 91% at low glucose concentrations (0.5 to 1 mM), while normal glucose concentration (5 mM) decreased cell viability by 63%, relative to control cells. Furthermore, RSV had no effect on cell viability at high glucose concentrations (20 and 30 mM); this indicates that there is a RSV‐dependent relationship with the energetic state of the cell. Subsequently, mitochondrial dysfunction was determined using membrane potential, reactive oxygen species (ROS) production, and ADP/ATP ratio. In the ROS production experiment, a decrease in ROS release was observed at the highest glucose concentrations (10, 20 and 30 mM) in cells supplemented with 10, 100 and 1000 μM of RSV, which indicates that RSV inhibits ROS overproduction in a dose‐dependent manner, demonstrating its antioxidant effect. Interestingly, under energy restriction concentrations (glucose 0.5 and 1 mM) at concentrations greater than 10 μM of RSV, an increase of ROS release was observed, which corroborates the fact that under restraint energy RSV exerts a toxic effect. Besides, an increase in both mitochondrial membrane potential and ADP/ATP ratio was observed; therefore, it was suggested that RSV is interrupting the flow of electrons, altering the CTE, with a subsequent decrease in ATP production. Altogether, these data support the hypothesis that the toxic effects of RSV are dependent on the cellular energy restriction condition as a result of mitochondrial dysfunction.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.