bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medical Student Learning Experiences in Organ System Course Sessions using a Histology and Embryology Team‐taught Integrated Format
Authors: Attardi Stefanie M. , Venuti Judith M. 
Published: June 2021

Medical schools accredited by the Liaison Committee on Medical Education are required to enhance their medical curriculum in a coherent and coordinated manner. Content integration, which is one characteristic of this requirement, involves linking concepts from different subjects and building from them so they can be more deeply understood and applied by students. At the relatively new Oakland University William Beaumont School of Medicine, the preclinical medical curriculum is integrated horizontally within each organ system course. However, the appropriate basic science disciplines are generally presented in separate sessions delivered by different content experts.In an effort to enhance the integration of the basic sciences, histology and embryology sessions were delivered in select organ system courses as integrated, team‐taught lectures for a two‐year period. Histology and embryology professors were both present during the same session to present the content and the relationship between the two disciplines was emphasized with embryological concepts forming a foundation for interpreting histological images.Studies of team teaching in higher education suggest it enhances the learning environment; however, the research is predominately anecdotal, from the instructors' perspectives, and lacks measurement of benefits and costs. This qualitative study aimed to identify variables for measuring outcomes of team‐taught integrated sessions in medical histology and embryology. The specific objectives were to determine why students might prefer the team or traditional segregated format, to compile student‐recommended best practices for team lecturers, and to identify other disciplines that may be conducive to the team‐teaching format. A phenomenological approach to qualitative inquiry was employed, where medical students' perceptions about team lectures were generalized to describe their shared experience of the learning environment. Qualitative data were collected from second year medical students during audio‐recorded focus groups and from organ system course evaluations. Open coding analyses will be performed on the focus group transcripts and course evaluation comments to generate themes and identify variables of interest. This study serves as the first phase of an exploratory sequential mixed methods research project in that the results will drive the development of future quantitative studies on the benefits and costs of team‐taught integrated sessions in medical education.Support or Funding InformationOUWB Fellowship in Medical EducationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
“Exploring the Regulation of Photosynthesis in Single‐Cell Lineages at Sub‐Cellular Resolution”
Authors: Cameron Jeffrey C. 
Published: June 2021

Photosynthesis is regulated in response to many diverse stimuli including light intensity and wavelength, nutrient availability, and temperature. Understanding how photosynthesis is regulated is critical if we are to increase photosynthetic efficiency for the benefit of society and the environment. While decades of research have revealed the structures and mechanisms of isolated photosynthetic complexes at molecular resolution, little is known about how these complexes interact and are regulated in the context of the dynamic cellular environment.To investigate how photosynthesis is regulated in single‐cells, we utilized long‐term, quantitative time‐lapse fluorescence microscopy to visualize the growth dynamics of wild‐type and mutant cyanobacterial strains following diverse environmental, chemical, and genetic perturbations. Quantitative image processing with custom algorithms enabled us to track individual cells across single‐cell derived lineages for multiple generations and monitor cellular physiology at sub‐cellular resolution.Our results suggest that mechanical interactions with the physical environment can lead to attenuation of photosynthesis and can play a major role in governing cellular fitness and productivity in cyanobacteria. The mechanistic basis of this phenomenon was investigated using mathematical modeling, electron microscopy, mutational analysis, and CRISPRi‐based dynamic gene regulation. These results provide insight into how photosynthetic organisms navigate the physical environment and a new perspective on source‐sink regulation of photosynthesis.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CXCR3 Regulates CD4+ T Cell Cardiotropism and Maladaptive Cardiac Remodeling Through Mechanisms Involving ICAM1‐Mediated Adhesion
Authors: Ngwenyama Njabulo , Salvador Ane , Nevers Tania , Velázquez Francisco , Aronovitz Mark , Alcaide Pilar 
Published: June 2021

Left ventricular (LV) dysfunction and heart failure (HF) progression are associated in humans and mice with increased levels of circulating chemokines CXCL9 and CXCL10, and increased frequency of T cells expressing their receptor CXCR3. CXCR3 signaling upon chemokine recognition in T cells results in integrin activation and T cell adhesion to endothelial cells. We recently reported that the integrin ligand ICAM1 is significantly upregulated in the LV endothelium of mice with HF, and that Icam1−/− mice have decreased LV T cell recruitment and HF. Additionally, we reported that Th1 cells, which highly express CXCR3, are major drivers of maladaptive cardiac remodeling. Thus, we hypothesized that chemokine signaling through CXCR3 regulates integrin dependent adhesion to ICAM1 and contributes to Th1 cell recruitment to the LV and HF. We used the mouse model of Transverse Aortic Constriction (TAC) to induce LV remodeling and HF in WT and CXCR3−/− mice, and in vitro adhesion studies to evaluate WT and CXCR3−/− Th1 cell chemokine‐mediated integrin‐dependent adhesion to ICAM1. WT mice expressed increased levels of CXCL9 and CXCL10 in the LV during the course of TAC. Activation of CD4+ T cells occurred in the mediastinal lymph nodes (mLN), which drain the heart, of both WT and CXCR3−/− mice; however T cell infiltration in the LV only occurred in WT but not CXCR3−/− mice, and heart infltrated T cells expressed high levels of CXCR3 and the ligand of ICAM‐1, LFA1. Moreover, CXCR3−/− TAC mice did not develop cardiac fibrosis, hypertrophy or inflammation and had preserved systolic and diastolic function as compared to WT TAC mice. Mechanistically, both CXCL9 and CXCL10 induced Th1 cell adhesion to ICAM1 under shear flow conditions in vitro in a CXCR3‐dependent manner. Our data support a CXCL9/CXCL10‐CXCR3‐ICAM1 axis regulating CD4+ T cell LV recruitment, and may represent a novel pathway potentially targetable in non‐ischemic HF.Support or Funding InformationNIH R01 HL123658‐01, T32AI007077‐34This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Muscle‐specific regulation of right ventricular transcriptional responses to chronic hypoxia induced heart failure by the Muscle Ring Finger‐1 (MuRF1) ubiquitin ligase in vivo
Authors: Willis Monte S. , Oakley Robert H. , Parry Traci L. , Cidlowski John A. , Campen Matthew J. 
Published: June 2021

BackgroundWe recently identified a role for the muscle‐specific ubiquitin ligase MuRF1 (Muscle Ring Finger‐1) in right‐sided heart failure secondary to pulmonary hypertension induced by chronic hypoxia (CH). MuRF1−/− challenged to chronic hypoxia for three weeks were resistant to CH induced changes in right ventricle (RV) weight, ejection fraction, and volume (systolic and diastolic) and provided significantly increased perfusion to skeletal muscle. In contrast, MuRF1 Tg+ mice exhibited significant decreases in RV weight and ejection fraction indicative of a maladaptive dilated phenotype (heart failure), consistent with the significant decreases in skeletal muscle perfusion observed. The present study was undertaken to understand the underlying transcriptional alterations in the right ventricle of MuRF1−/− and MuRF1 Tg+ mice using microarray analysis.ResultsAfter three weeks of chronic hypoxia (15% O2) exposure, right ventricular total RNA was isolated, labeled, and hybridized to microarray chips. Microarray analysis of the MuRF1−/− right ventricle identified 37,095 defined genes with signals, with 590 found to be significantly different (p<0.01) from WT controls. Analysis of the 70 top differentially expressed genes (>2 fold or <−2 fold) revealed their function in 1) transcriptional regulation; and 2) oxidoreductase function. Analysis of these differentially expressed genes for common transcription factor promoter regions identified homeobox (HOX) D12 and HOXC13 transcription factors, along with RREB‐1. Microarray analysis of the MuRF1 Tg+ right ventricle identified 37,095 defined genes with signals, with 150 found to be significantly different (p<0.01) from WT controls. Analysis of the 46 top differentially expressed genes (>3 fold or <−3 fold) revealed their function in 1) oxidoreductase‐metabolic regulation, 2) glycoprotein‐transmembrane integral protein structure, and 3) alternative splicing / splice variants.ConclusionsThe differentially expressed genes in MuRF1−/− and MuRF1 Tg+ RV after CH exposure have common functional annotations related to oxidoreductase (including antioxidant) and transmembrane component functions. Moreover, the functionally‐enhanced MuRF1−/− hearts regulate genes related to transcription, homeobox proteins, and kinases/phosphorylation. These studies also reveal potential indirect effects MuRF1 may have with known substrates such as SFR and PPARalpha by regulating RREB‐1 and reveal for the first time mechanisms by which MuRF1 may transcriptionally regulate anti‐oxidant systems in the face of right heart failure.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Feeding in Marine Mammals: An Integration of Evolution and Ecology through Time
Authors: Berta Annalisa , Lanzetti Agnese 
Published: June 2021

Marine mammals are a key component of aquatic ecosystems. Four major feeding strategies: suction, biting, filter feeding and grazing are identified in extant marine mammals (cetaceans, pinnipeds, sirenians, marine otters, and the polar bear) and associated with anatomical specializations of the head (e.g. rostrum, palate, temporomandibular joint, teeth/baleen, and mandible). Genetic and ontogenetic evidence of skull and tooth morphology provide the mechanisms that underlie patterns of feeding diversity. Based on a comprehensive diversity data set we provide an integrated analysis of the evolution of feeding, trophic structure and habitat (e.g. marine, riverine, estuarine) in fossil and extant marine mammals. We explore the origin and timing of particular feeding strategies over the last 50 million years. We find that the greatest diversity of pinnipedimorphs, cetaceans and extinct desmostylians occurred during the middle Miocene (11–15 million years ago, Ma). Sirenians reached their greatest diversity slightly earlier during the early Miocene (16–23 Ma). These historical data are used as a framework to inform the structure and trophic interactions of past, present and future marine ecosystems. We show that marine mammal generic diversity tracks diet with the greatest diversity of carnivores and herbivores in the middle Miocene. The drivers of diet and feeding patterns are both environmental (e.g. sea level fluctuations, climate change) and biotic (e.g. anatomical specializations, competition, predator‐prey) changes. The influence of these different processes on paleodiversity varies depending on taxonomic group, timing and geographic scale.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Therapeutic inhibition of RIP1 improves metabolic dysfunction and inhibits atherosclerosis in mouse models of cardiometabolic diseases
Authors: Karunakaran Denuja , Nguyen My Anh , Geoffrion Michele , Lister Zachary , Kandiah Joshua , Wyatt Hailey , Mompeon Ana , deKemp Ella , Lee Richard , Rayner Katey 
Published: June 2021

IntroductionChronic activation of the innate immune system drives inflammation and contributes directly to obesity, insulin resistance and atherosclerosis. Previously we showed that necroptosis, a pro‐inflammatory form of programmed cell death, is activated in the vessel wall and drives atherosclerosis via activation of RIP3 and MLKL. We sought to determine upstream genetic regulators of necroptosis in atherosclerosis and metabolic disease, and hypothesized that gene expression of RIP1, a key regulatory kinase upstream of NFkB activation, apoptosis and necroptosis, drives macrophage inflammation in cardiometabolic diseases.MethodsRIP1 anti‐sense oligonucleotides (ASOs, 2 unique sequences) were used to reduce RIP1 expression in 2 mouse models: i) atherosclerotic model [ApoE−/− mice fed a western diet for 8wks] and ii) diet‐induced obesity (DIO) model [C57Bl/6 male mice fed a high fat diet for 24 wks]. Mice were given weekly injections of RIP1 ASOs (50 or 100mg/kg) or control ASO (non‐targeting).ResultsRIP1 ASO treated ApoE−/− mice had a marked reduction in aortic sinus and en face lesion areas (47.2% or 58.8% decrease relative to control, p<0.01) and plasma inflammatory cytokines (IL‐1a, IL‐17A, p<0.05). RIP1 knockdown in macrophages decreased inflammatory gene expression (NFkB, TNFa, IL‐1a) and in vivo LPS‐induced NFkB activation. In obese mice, RIP1 ASOs strikingly decreased body weight (25% decrease versus control p<0.001) and total fat mass (50–65% decrease versus control, p<0.001). Further, insulin resistance was improved in RIP1 ASO treated mice (fasted blood glucose: 10.9mM in control versus 8.5±mM in RIP1 ASO, p<0.001; GTT and ITT both p<0.001). In humans, we identified 5 novel SNPs in strong linkage disequilibrium in or nearby RIP1 gene exon 5. Notably, in a cohort of >1,800 people, individuals carrying the minor allele of these RIP1 SNPs have a 75–89% increase in the risk of developing obesity (adjusted odds ratios: 1.75–1.89, p<10−5) and a significant increase in RIP1 mRNA expression in adipose tissue (eQTL association in METSIM cohort, p=10−23).Conclusions: We have identified RIP1 as central a driver of insulin resistance, obesity, and atherosclerosis and demonstrate the potential of RIP1 as a novel therapeutic target.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Synthesis of bioorthogonal muramyl glycans that illuminate and track bacterial peptidoglycan
Authors: DeMeester Kristen E. , Liang Hai , Jones Zachary , Taylor Jenny A. , Siegrist M. Sloan , Salama Nina R. , Leimkuhler‐Grimes Catherine L. 
Published: June 2021

The bacterial cell wall is composed of a thick, web‐like polymer known as peptidoglycan (PG). This structure is critical for bacterial survival, as it protects the cell from changes in osmotic pressure and environmental insults. PG structures are essential for complex chemical and biological processes related to human health, as antibiotics are designed to target its destruction while the innate immune system responds to small molecules teased out of the PG network. While the overall chemical composition of PG is conserved throughout all species of bacteria, specifically peptides and two carbohydrate units N‐acetyl glucosamine (NAG) and N‐acetyl muramic acid (NAM), the glycan immunoactivating molecular calling cards derived from this polymer vary among pathogenic and commensal strains of bacteria. Immune misrecognition of these PG fragments can lead to the development of inflammatory bowel diseases. Information regarding the biological identity and the generation of these NAM‐containing fragments, either via host or pathogen machinery, and the cellular location of these events is limited. We sought out to developed new tools that may be used to uncover NAM containing immunostimulatory PG molecules. We recently report methodology to synthetically and chemoenzymatically access bioorthogonal NAM PG building blocks, which were then metabolically incorporated into the PG and subsequently labeled via in both gram positive and negative bacterial cells. We are currently expanding this methodology into both pathogenic and commensal strains of bacteria and utilizing the bioorthogonal handle to install fluorescent affinity tags to track and identify innate immune processing of NAM containing PG derivatives produced by these bacteria both in the presence and absence of macrophages. This work summarizes efforts toward illuminating host‐microbial molecular space by taking a multidisciplinary organic and chemical biology approach to access bioorthogonal NAMs and utilizing these substrates to metabolically label commensal and pathogenic bacterial PG in whole to fluorescently track innate immune processing of NAM containing PG derivatives produced by bacteria in the microbiome.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Regulation of HMGB1 in Hepatocytes by MyD88 and Type‐I interferon (IFN‐I) During Ehrlichia‐induced acute liver injury.
Authors: Kader Muhamuda , Scott Melanie , Yates Cecelia , Ismail Nahed 
Published: June 2021

BackgroundLiver is the major target organ in Human Monocytic ehrlichiosis (HME), an undifferentiated febrile illness that is life‐threatening and caused by intracellular bacterial pathogen, Ehrlichia, that target liver and infect macrophages, hepatocytes and endothelial cells. Severe Hepatic inflammation is the common cause of acute liver injury following systemic infection with Ehrlichia. Our previous studies have shown that Myeloid differentiation primary response gene 88 (MYD88) and type I IFN (IFN‐I) promotes excessive inflammation and liver damage following fatal Ehrlichia infection. In this study, we explored the role of the MyD88 and IFN‐I in liver inflammation.ResultsIn this study, we provide evidence to support that high mobility group box 1 (HMGB1), a chromosomal protein and damage‐associated molecular patterns (DAMPs), plays a role in the regulation of innate responses and autophagy during Ehrlichia infection. Wild‐type (WT) mice infected with virulent Ehrlichia develop sepsis and liver injury marked by excessive systemic production of pro‐inflammatory cytokines and chemokines as well as HMGB1. To determine the cellular source of HMGB1 and regulatory mechanisms, we infected hepatocytes (HC) from WT and MYD88−/− knockout mice with virulent Ehrlichia. To mimic paracrine effect of IFN‐I cytokines produced by immune cells on HC response to Ehrlichia infection, we cultured infected HC in the presence or absence of IFN‐β (100 IU/mL). Our data indicate that in‐vitro infected HC produces low levels of IFN‐beta compared to uninfected cells. Exogenous stimulation of infected HC with IFN‐β induced elevated expression and cytoplasmic translocation of HMGB1 in WT‐HC. This was associated with increased autophagy and higher expression of IL‐23R, IFNAR, and heightened JAK/STAT signaling. Importantly, the effect of high dose IFN‐I on autophagy and HMGB1 was MYD88‐dependent. Interestingly, infection of MYD88−/− HC with Ehrlichia, in the absence of exogenous IFN‐β, enhanced autophagy induction and cytosolic translocation of HMGB1, suggesting that MYD88 negatively regulate HMGB1 and autophagy in HC in the absence of the paracrine effect of IFN‐β.ConclusionTogether, our data suggest that autophagy regulation and HMGB1 response in hepatocytes during Ehrlichia‐induced sepsis is controlled by the strength of IFN‐I signaling and dependent on interplay between MYD88 and IFN‐I pathways.Support or Funding InformationThis work was supported by grants from NIAMS, NIGMD, and NIAID (AR68317 CCY, RO1‐GM102146 MS, and R56A1097679 NI)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 discovery platform to identify novel beneficial bacteria
Authors: Darby Trevor , Owens Joshua , Saeedi Bejan , Luo Liping , Robinson Brian , Jones Rheinallt 
Published: June 2021

The use of beneficial bacteria known as ‘probiotics' to promote health is widely practiced. However, experimental evidence corroborating the efficacy of many bacteria promoted with such claims remains limited. We directly address this gap by establishing a discovery platform to identify novel beneficial bacteria that dampen intestinal inflammation and limit tissue damage. We employed the Drosophila animal model to assess the capacity candidate beneficial bacteria to defend the fly gut from induced oxidative damage. From this screen, we identified a number of novel bacteria that elicited potent cytoprotective activity in the gut. In addition, using the murine model, we also demonstrate that the same strains confers powerful anti‐inflammatory activity in a gut colitis model, and cytoprotective influences against radiological damage. Importantly, the beneficial activities of these strains in the murine intestine were substantially stronger in comparison to other currently marketed beneficial bacteria. In summary, we demonstrate that capacity of beneficial bacteria to elicit potent anti‐inflammatory and cytoprotective properties in the gut, and propose that newly discovered probiotic strains of bacteria may be used as a therapeutic interventions to promote intestinal health.Support or Funding InformationNIH Grants R01DK098391This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Picosecond Active‐Site Dynamics Correlate with the Temperature Dependence of KIEs in Enzyme‐Catalyzed Hydride Transfer
Authors: Cheatum Christopher M. 
Published: June 2021

Picosecond time scale motions in enzymes have often been invoked to explain the temperature dependence of primary kinetic isotope effects (KIE) in enzyme‐catalyzed hydride transfer reactions, but these experiments come short of actually measuring the dynamics in these systems on timescales relevant to the making and breaking of bonds. Similar to other enzymes, wild‐type Formate dehydrogenase (FDH) from Candida boidinii exhibits a temperature independent KIE that becomes temperature dependent when space is opened up in the active site via mutation of the V123 residue to alanine and glycine. Transition state analog complexes of FDH bound to azide offer a unique opportunity to investigate how these mutations influence active site dynamics. With a combination of 2D IR spectroscopy, X‐ray crystallography, and molecular dynamic simulations, we report a comprehensive view of fast motions of the active site and their relationship to the hydride transfer. Azide bound to FDH exhibits oscillatory frequency fluctuations on the ps timescale, and the amplitude of these fluctuations increases when the active site space increases in correlation with the temperature dependence of the KIE. Both the kinetic and dynamic phenomena can be modeled computationally. These results provide the first means of directly connecting temperature dependence of KIE's to dynamic motion in the active site in an enzyme‐catalyzed reaction.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.