bluuebunny/crossref_metadata_2025_split huggingface dataset:
Course Evaluations ‐ Are We Gaining Insight, or Feeding Egos? Using Novel Evaluations to Uncover Value
Authors: Brewer‐Deluce Danielle , Palombella Andrew , Rockarts Jasmine , Wainman Bruce C. 
Published: June 2021

Assessment is generally the evaluation of student learning and competency. But, when the roles are reversed, and we ask students for their perspective, assessment has the potential to improve a course. Unfortunately in practice however, there are some limitations. In particular, asking students to rate their experience on ubiquitous Likert scale evaluations imposes a ceiling effect, which limits utility. So while top notch evaluations feel great, and often support tenure, promotion and hiring decisions, constructive change seldom results.Over the past 7 years the Education Program in Anatomy at McMaster University has focussed on understanding learner profiles in an interprofessional education (IPE)/anatomy dissection course using multiple evaluation strategies. By employing Likert‐scales, qualitative ratings and Q method, students were asked about what they valued in the course. Specifically through Q method's factor analysis, individuals were grouped based on similarities in their rankings of common preferences/viewpoints: three previously unknown independent learner groups (Anatomy IPE Enthusiasts, Practical IPE Advocates and Skeptical IPE Anatomists) were identified for which common challenges could be addressed. Conversely, qualitative and Likert‐based analyses provided less granular information which was not directly useful for course evolution.With the above study serving as an exemplary template, we will challenge value of current course evaluation practices, and further explore Q methodology as a viable and valuable alternative. In all, session attendees can expect to learn methods for better understanding the types of students in our classrooms which will support strategies for more refined student‐centred 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.
Growth Factor Expression by Cardiac Tissues in the Leopard Gecko (Eublepharis macularius)
Authors: Jacyniak Kathy , Vickaryous Matthew Kenneth 
Published: June 2021

Tissue homeostasis is a dynamic process involved in the maintenance of tissue structure and function in response to physiological fluctuations in biochemistry, metabolism, and physical conditions. Despite the profound role that growth factors play in homeostasis of organs such as the heart, constitutive patterns of expression are only known for a handful of species. Here, we investigated growth factor expression in the heart of a representative reptile, the leopard gecko (Eublepharis macularius; hereafter, ‘gecko’). We focused our investigation on three major classes known to be expressed by mammalian cardiac tissues: transforming growth factor β (TGFβ); vascular endothelial growth factor A (VEGF); and basic fibroblast growth factor (FGF‐2). Similar to other squamates (snakes and lizards), geckos have a three‐chambered heart with two atria and one ventricle. The ventricular myocardium includes a trabeculated or spongy‐like inner compartment, and a thin, compact cortical layer. We determined that cardiac cells in both compartments of the gecko myocardium (trabeculated and compact) constitutively express a diverse panel of growth factor ligands and receptors commonly associated with wound healing and repair, including: TGFβ1, activin‐βA, and phosphorylated SMAD2; FGF‐2; and VEGF, VEGF receptor 1 (VEFGR1), VEGFR2, and phosphorylated VEGFR2. Using double immunofluorescence, we observed co‐localization of VEGF/VEGFR2 and VEGFR1/VEGFR2, indicating that – similar to mammals – reptilian cardiomyocytes may use paracrine and autocrine signalling. Taken together, these findings indicate a homeostatic role for these growth factors in the heart that is conserved across reptiles and mammals.Support or Funding InformationNatural Sciences and Engineering Research Council (NSERC) Discovery Grant 400358 (to MV); Ontario Veterinary College Scholarship (to KJ)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex‐specific Conditions Affecting Vascular Tone, Cerebral Blood Flow and Cognition
Authors: Barnes Jill N. 
Published: June 2021

There are sex and sex‐hormone specific differences in autonomic nervous system control of blood pressure. The sympathetic nerve fibers of the autonomic nervous system innervate skeletal muscle blood vessels, initiating vasoconstriction, and thus regulate blood flow and vascular tone. This regulation of vascular tone is different between men and women, such that estrogen increases the activity of the b2‐adrenergic receptor activity (causing vasodilation) which offset sympathetically‐mediated vasoconstriction and results in lower blood pressure values in young women. Higher sympathetic nerve activity is associated with greater augmented aortic blood pressure in young men, but lower augmented aortic blood pressure in young women. Such differences in blood pressure regulation will likely have effects that extend beyond blood pressure, affecting blood flow, and ultimately tissue structure and function. For example, higher aortic blood pressure and greater arterial stiffness of the central arteries are associated with white matter hyperintensity fraction in normotensive postmenopausal women and older adults. In addition, there are conditions unique to women, menopause and pregnancy, that further affect blood pressure and blood flow regulation. Pregnancy constitutes a stress that challenges the regulation of blood pressure and blood flow in women. Hypertensive conditions of pregnancy, such as preeclampsia, carry life‐long risk for developing cardiovascular and cerebrovascular diseases. We evaluated the influence of pregnancy history in postmenopausal women on vascular function, cerebral blood flow, and cognition 35 years after pregnancy. Aortic blood pressure was associated with lower cognitive function scores in women with a history of preeclampsia. Additionally, women with a history of preeclampsia had lower cerebral blood flow responses to a vasodilatory stimulus and this was associated with greater intravascular cellular activation. Furthermore, women with a history of preeclampsia and with late‐life hypertension had atrophy in specific regions of the brain, suggesting that pregnancy history may later impact brain structure. Therefore, conditions that a woman may experience during pregnancy may be informative for future risk of disease. In summary, understanding sex‐specific physiological mechanisms, and how this may change over the lifespan is crucial for identification and treatment of individuals at accelerated risk of cardiovascular and cerebrovascular disease.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex Differences in Remodeling of the Failing Heart
Authors: Kararigas Georgios 
Published: June 2021

Heart failure (HF) is a leading cause of hospitalization and death and can be characterized by either reduced or preserved ejection fraction. Cardiomyopathies like Takotsubo and HF manifest differently between men and women. More men have maladaptive remodeling underlain by higher induction of pro‐fibrotic pathways, while women repress inflammatory pathways. Sex and menopause‐related differences in the incidence and the prognosis of cardiovascular disease have pointed to the sex hormone 17β‐estradiol (E2) and its receptors (ER α and β). Employing the transverse aortic constriction model in mice to study E2‐ and sex‐specific regulation of pressure overload‐induced left ventricular hypertrophy and HF, the E2/ER axis is considered cardioprotective in females. In contrast, E2 exerts deleterious effects in male hearts and cardiac cells. Detailed characterization of the regulation of cardiac (patho)physiology by sex and E2 and elucidation of the underlying mechanisms may lead to the identification of novel therapeutic targets, which may have a wide implication in the development of new and personalized therapies.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Stem Cell Biology of Airway Submucosal Glands during Development and Disease
Authors: Engelhardt John F. 
Published: June 2021

Lineage‐tracing studies in the mouse lung suggest that multiple region‐specific progenitors contribute to regenerative plasticity of the airway epithelium. Airway submucosal glands (SMGs) are thought to house stem cell niches for the surface airway epithelium; however, the phenotype of the SMG‐derived progenitor cells remains unclear. SMGs are tubuloacinar structures embedded within the mesenchyme beneath the surface of all cartilaginous airways in humans and the proximal trachea of mice. These structures secrete important factors that regulate airway clearance and maintain sterility at homeostasis and in response to injury and infection. Secretory functions of SMGs are severely affected in cystic fibrosis, a genetic disease caused by mutation in the cystic fibrosis transmembrane conductance regulator, and disease‐associated alterations in neuropeptide (CGRP) expression alter the slowly cycling stem cell niches of SMGs. In this context, CGRP acts as both a secretagogue to stimulate gland secretion following injury—a response defected in cystic fibrosis—and a mitogen of glandular progenitor cells. To better define the contribution of SMG stem cells in airway regeneration and abnormalities to these processes in cystic fibrosis, we have dissected Wnt‐regulated mechanism that control both the formation of glandular stem cell niches during development and lineage‐commitment of glandular stem cells during airway regenerative responses following injury. Using lineage tracing in mice, we demonstrate that multipotent glandular myoepithelial cells form very early during SMG development in a Wnt/TCF‐dependent manner. In the adult mouse trachea, SMG myoepithelial cells can give rise to seven cell types in the proximal airway following severe injury. Similar to the stem cell program adopted during SMG development, Wnt/TCF signals appear to control self‐renewal and lineage commitment of glandular myoepithelial stem cells following injury. These studies clarify important stem cell targets for therapy in the cystic fibrosis lung.Support or Funding InformationNIDDKThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Myofascial Pathologies, Their Treatment, and the Importance of Patient Education
Authors: Schabacker Kara 
Published: June 2021

The importance of healthcare provider understanding and patient education in the foundational principles governing the fascia of the human body cannot be overstated. What the fascia is, what it does, and what purpose it serves (i.e., What's the point of this vast structural framework?) versus what patients usually “think” is going on in their bodies are often vastly different. There exists a myriad of fascial pathologies in which the fascia goes awry and results in people ending up on the clinical massage therapy table. These include long term and chronic physical issues, short term injuries, and even emotional stress. There are techniques through which the fascia can be manipulated and released to alleviate the physical, emotional, and mental stressors and the patterns behind them. This presentation will elaborate on exactly how the fascial system stores, processes, and (with intervention) releases these holding patterns either with self care or the help of a licensed massage therapist. It will include vignettes from the clinician perspective including humans of all life stages and activity levels (from infant to elderly, from sedentary to professional athlete) and other animal models such as dogs and horses. The emphasis of this presentation will be on the practical and real‐world application of interventions focused on fascia and it's roles in both containment and communication within the body.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Precisely heterogeneous ‐ the making of N‐glycoproteins
Authors: Aebi Markus 
Published: June 2021

Two dedicated organelles, the Endoplasmic Reticulum (ER) and the Golgi contain the synthetic machinery that generates N‐linked glycans, the most divers modification of proteins. The ER pathway generates a structurally highly conserved oligosaccharide that is transferred to selected asparagine residues of nascent polypeptide chains. These oligosaccharides are essential for the folding and the quality control process of glycoproteins. The subsequent trimming and remodeling of N‐linked glycans in the Golgi compartment follows a completely different regime and generates a heterogeneous assembly of N‐glycans in a species‐, protein‐ and site‐specific manner.We have established MS‐based analytical systems for the site‐specific quantification of N‐linked glycans and combined it with expression systems of model glycoproteins (such as IgG) in different cell lines. We quantified the site‐specific glyco‐heterogeneity and showed that the interaction of the glycan with the protein surface defined the processing in a given setting of hydrolases and glycosyltransferases. We hypothesized that this site‐dependent processing requires a kinetic control of glycan remodeling in the Golgi, which, in turn, is the cause for the well‐known microheterogeneity of N‐glycans.We have experimentally addressed this concept of glycan processing and followed the time‐course of intracellular N‐glycan processing in vivo using time‐resolved SILAC experiments. In addition, we assessed site‐specific N‐glycan processing in vitro using purified glycosyltransferases and hydrolases. We conclude that the compartmentalization of glycosyltransferases and hydrolases in the different Golgi stacks is a prerequisite for site‐specific N‐glycan processing. The lamellar structures of the Golgi cisternae is necessary to provide the high concentration of processing enzymes that can act only for a short time on secreted substrates.Support or Funding InformationSupported by the Swiss National Science Foundation and ETH ZurichThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mapping the O‐GlcNAc‐Cytoprotective network
Authors: Zachara Natasha , Groves Jennifer , Guo Chenxu , Martinez Marissa , Fahie Kamau , McKen Cathrine , Maduka Austin , O'Meally Robert , Cole Robert 
Published: June 2021

In the 30 years since the discovery of nucleocytoplasmic glycosylation, O‐GlcNAc has been demonstrated to regulate protein function by modulating characteristics that include protein folding, localization, degradation, activity, post‐translational modifications, and interactions. The cell coordinates these molecular events, on thousands of cellular proteins, in concert with environmental and physiological cues to fine‐tune epigenetics, transcription, translation, signal transduction, the cell cycle, and metabolism. The cellular stress response is no exception: diverse forms of injury result in dynamic changes to the O‐GlcNAc sub‐proteome that promote survival. To date, the majority of studies have focused on identifying proteins and pathways regulated by O‐GlcNAc that combat cytotoxicity. Currently, little is known about the regulation of the two enzymes that write and erase the O‐GlcNAc‐modification, the O‐GlcNAc transferase (OGT) and the O‐GlcNAcase (OGA). To provide insight into the regulation of OGA, the enzyme that catalyzes the removal of O‐GlcNAc, proximity biotin ligation (BioID) in combination with Stable Isoptope Labeling of Amino Acids in Cell Culture (SILAC) was used to define the basal and stress‐induced interactome of OGA. This analysis revealed 90 interaction partners of OGA, many of which exhibited increased binding to OGA upon stress. The associations of OGA with fatty acid synthase, OGT, heat shock cognate 70 kDa protein (HSC70), filamin‐A, and heat shock protein 27 (HSP27) were confirmed by co‐immuno‐precipitation. Furthermore, the pool of OGA bound to FAS demonstrated a substantial reduction in specific activity (~85%), suggesting that FAS is a novel protein inhibitor of OGA. Consistent with these observations, overexpression of FAS augmented O‐GlcNAcylation of a subset of cellular proteins. Collectively, these data support a model in which protein interactors of OGA, such as FAS, regulate its local activity and thus lead to remodeling of the O‐GlcNAc‐sub proteome in a manner consistent with cell survival.Support or Funding InformationThis work was supported by grants from the NIH National Heart, Lung, and Blood Institute (P01HL107153), the NIH National Institute on Aging (F31AG047724), and the NIH National Institute of General Medical Sciences (MARC U‐STAR; T34GM008663). Core Facility support was provided NIH Grant S10 RR024550 ‐ Research Resources (JHUSOM Microscope Facility) and NIH Grant 2P30 CA006973 ‐ National Cancer Institute (JHUSOM Mass Spectrometry and Proteomics Facility).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Corralling Pancreatic Cancer through Epigenetic Reprogramming
Authors: Evans Ronald M. , Antal C. , Truitt M. , Liang G. , Sherman M. , O'Dwyer P. , Drebin J. , Downes M. , Tuveson D. 
Published: June 2021

Pancreatic ductal adenocarcinoma (PDAC) occurs in the context of an exuberant desmoplastic response that produces a ‘living chimera’ of tumor and activated stromal components. We have shown that the vitamin D receptor (VDR) is expressed at high levels in activated human pancreatic stellate cells (PSCs) and, in response to ligand, reprograms PSCs to the quiescent state. In vivo, a synthetic VDR agonist (Cal) similarly remodels tumor stroma, enhancing the anti‐tumor effects of gemcitabine and reducing tumor growth.We will describe the use of a three‐dimensional culture system to dissect the adaptive impact of the stromal secretome on the cancer cell. This integrative approach identified the rapid mobilization of more than a dozen gene networks (cell cycle, steroid biosynthesis, metabolic pathways, DNA replication, etc.), as well as a commensurate adaptive metabolome.In examining chromatin adaptation, our work uncovers a molecular ‘and‐gate’ such that tumor activation is the consequence of mutant Ras and the TME. To mediate this molecular handshake, we find that BRD2 (but not BRD4) in the epithelial compartment transduces stromal cues at the genomic level. This response is blocked by the BET bromodomain inhibitor JQ1 and reduces pancreatic tumor growth in vivo. Collectively, we describe a novel molecular connection between the stroma and a driver oncogene that offers new insights into the role of the TME in the treatment of ras‐driven tumor.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Metabolism, Inflammation, and Tumor Progression
Authors: Simon M. Celeste 
Published: June 2021

Altered tumor cell metabolism is now firmly established as a hallmark of human cancer. Downstream of oncogenic events, metabolism is re‐wired to support cellular energetics and supply the building blocks for biomass. Rapid, uncontrolled proliferation results in tumor growth beyond the reach of existing vasculature and triggers cellular adaptations to overcome limiting nutrient and oxygen delivery. However, oncogenic activation and metabolic re‐programming also elicit cell intrinsic stresses, independent of the tumor microenvironment. To ensure metabolic robustness and stress resistance, pro‐growth signals downstream of oncogene activation or tumor suppressor loss simultaneously activate homeostatic processes. Here, I will summarize adaptive mechanisms co‐opted by common oncogenes, including mTOR, MYC, and RAS. Recurrent themes include: (1) coordination of oncogene‐induced changes in protein and lipid metabolism to sustain endoplasmic reticulum homeostasis, (2) maintenance of mitochondrial functional capacity to support anabolic metabolism, (3) adaptations to sustain intracellular metabolite concentrations required for growth, and (4) prevention of oxidative stress. Ultimately, an understanding of the adaptations required by both tumor cells and recruited inflammatory cells could reveal targetable metabolic vulnerabilities.Support or Funding InformationR35 CA197602 (Outstanding Investigator Award)Title: “Metabolic Tumor Suppressors in Renal Cancer: Unprecedented Roles in Disease Progression”3 P01 CA 104838Title: “Cancer Cell Adaptation to Metabolic Stress”This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dynamic mechanisms of Xist RNA localization in female lymphocytes: a new form of X‐chromosome Inactivation maintenance
Authors: Anguera Montserrat C. , Syrett Camille 
Published: June 2021

Females mount stronger immune responses and clear pathogens faster than males, yet they are more susceptible to autoimmune and inflammatory disorders. One important biological factor underlying this sex bias is the X‐chromosome, which is enriched for immunity‐related genes. Female mammals use X‐Chromosome Inactivation (XCI) to generate a transcriptionally silent inactive X‐chromosome enriched with heterochromatic modifications and the long noncoding RNA Xist, which equalizes gene expression between the sexes. We have discovered that XCI is maintained differently in female lymphocytes from mice and humans, where Xist RNA and heterochromatic modifications dynamically associate with the inactive X‐chromosome. Mature naïve B cells are missing Xist RNA and heterochromatin marks on the inactive X, and these marks return to most cells with in vitro stimulation. We found that the chromatin of the inactive X changes during early B cell commitment, at the pro‐B cell stage, initiated by the loss of Xist RNA localization. In mature lymphocytes, we found evidence of biallelic expression and increased dosage of immunity‐related X‐linked genes including TLR7 and CXCR3, in support of relaxed transcriptional silence from the inactive X. During B cell activation, Xist RNA is relocalized to the inactive X by the transcription factor YY1, in a novel two‐step process unique to B cells. YY1‐mediated relocalization of Xist RNA during B cell stimulation is necessary for enrichment of heterochromatin modifications and maintenance of X‐linked gene silencing. Furthermore, we examined lymphocytes from patients with systemic lupus erythematosus, an autoimmune disorder with a strong female bias, and observed mislocalized XIST RNA transcripts and evidence of biallelic expression of immunity‐related genes from both X‐chromosomes. We propose that the Xi in female lymphocytes is predisposed to become partially reactivated and to overexpress immunity‐related genes, providing the first mechanistic evidence for the female‐specific enhanced immune responses and increased susceptibility for autoimmunity.Support or Funding InformationR21 AI1240845K12 HD085848‐03This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.