bluuebunny/crossref_metadata_2025 huggingface dataset:
Leveraging mouse liver co‐expression networks and human lipid GWAS data to identify and validate cholesterol metabolism genes
Authors: Parks Brian Wesley , Li Zhonggang , Nguyen Jenny , Leyva‐Jaimes Fernanda
Published: June 2021

Genetic factors play an important role in contributing to variation in plasma lipid levels across the human population. Large genome‐wide association studies (GWAS) in humans have identified more than 100 loci significantly associated with plasma levels of low‐density lipoprotein (LDL) cholesterol, high‐density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol (TC). To prioritize genes that are involved in cholesterol metabolism we developed a systematic approach to leverage genome‐wide liver transcriptomic and proteomic data from multiple mouse reference populations along with human lipid GWAS data. We constructed global co‐expression networks from 12 distinct mouse liver datasets and identified a conserved module of genes highly enriched for cholesterol biosynthetic processes. Based on replication across mutiple datasets we prioritized 112 unique genes. Intersection with human GWAS data for LDL, HDL, TC, and triglycerides identified 54 of these genes to be within 100 kilobases of a significant or suggestive significant single nucleotide polymorphism (SNP). 29 of the 54 prioritized genes have well documented biological roles in cholesterol metabolism, such as LDLR, PCSK9, and INSIG1. With the 25 identified genes with no documented role in cholesterol metabolism, we tested for sensitivity to cholesterol modulation and performed a functional screen by siRNA knockdown. From this analysis we identified, Sestrin1, as a candidate gene that is responsive to cholesterol manipulation and capable of modulating cellular cholesterol levels. Using Sestrin1 targeted mice we show that Sestrin1 heterozygous or homozygous knockout mice have elevated levels of plasma cholesterol when fed a diet enriched in cholesterol. Collectively, through a systematic approach we have identified 25 highly prioritized genes that have no documented role in cholesterol metabolism. One of these genes, Sestrin1, we validate in vivo and in vitro as a modulator of cholesterol metabolism.

Support or Funding Information

BWP is supported by NIH R00‐HL123021

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protein kinase R modulates NLRP3 inflammasome in cardiac fibroblasts in sepsis
Authors: Xu Xuemei , Tao Aibin , Kao Raymond , Martin Claudio , Rui Tao
Published: June 2021

Background

We have reported that sepsis leads to an activation of NLRP3 inflammasome in cardiac fibroblasts (CF) resulting in IL‐1β maturation and extracellular release. Increase in IL‐1β by the CF induces myocardial dysfunction. The aim of the present study is to identify a modulation pathway that activates NLRP3 inflammasome in the CF.

Materials and Methods

CF were isolated and cultured from adult mouse hearts. The CF were primed with LPS (1 μg/ml) for 6 hrs followed by 30 min of ATP (3 mM) treatment to activate NLRP3 inflammasome. PKR activation was assessed by PKR phosphorylation (Western). NLRP3 inflammasome activation was assessed by detecting CF caspase‐1 p20 (Western) and IL‐1β release (ELISA).

Results

LPS priming of CF resulted in PKR activation as indicated by increase in PKR phosphorylation at Thr451, and increase in NLRP3 and pro‐IL‐1β protein expression. Inhibition of PKR (PKR inhibitor and siRNA) prevented the LPS‐induced NLRP3 and pro‐IL‐1β expression in the CF. Inhibition of PKR in CF primed with LPS before ATP showed no effect on NLRP3 and pro‐IL‐1β expression, but prevented the NLRP3 inflammasome activation as indicated by abolishing the caspase‐1 activation and IL‐1β releasing. In addition, pretreatment of CF with peroxynitrite (ONOO−) decomposition catalyst, FeTPPs, before LPS, prevented the LPS induced PKR phosphorylation, NLRP3 and pro‐IL‐1β expression in CF. Furthermore, pretreatment of CF with FeTPPs before ATP prevented the NLRP3 inflammsome activation in CF.

Conclusion

our results indicate that ONOO−/PKR pathway modulates priming and activation of NLRP3 inflammasome in CF in sepsis.

Support or Funding Information

IRF of Lawson Health Research Institute (IRF 2014–25); The Natural Science Foundation of Jiangsu Province, China (BK2015‐1332).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identification of a Novel Phenotype of Myeloid Cells in Classical Hodgkin Lymphoma
Authors: Post Ginell R. , Yuan Youzhong , Post Steven R.
Published: June 2021

Classical Hodgkin lymphoma (cHL) characteristically shows few malignant cells in a microenvironment comprised of inflammatory cells. Although cHL is associated with a high cure rate, recent studies have associated poor prognosis with increased macrophages in involved lymph nodes (LN). It was recently reported that in cHL patients with relapsed disease post‐allotransplant, tumor‐infiltrating macrophages are derived from circulating monocytes and not resident macrophages. Thus, the role of monocytic infiltration and differentiation in cHL may be more relevant to defining prognosis in cHL patients and potentially have therapeutic implications. Most studies identify tumor associated macrophages using markers (e.g., CD68) that detect the entire myeloid lineage. In contrast to other myeloid markers, SR‐A is expressed by tissue macrophages but not monocytic precursors. In this study, we examined expression of the Class A Scavenger Receptor (SR‐A/CD204) in cHL LNs. We confirmed a high prevalence of cells that stained with the myeloid markers CD68, CD163, and CD14 in cHL LNs. However, SR‐A protein expression determined by immunohistochemistry was limited to macrophages localized in sclerotic bands characteristic of nodular sclerosing cHL. In contrast, SR‐A protein was readily detectable in solid tumor metastasis to LNs and in resident macrophages in control tissue (spleen, lung, liver). The results of SRA protein expression paralleled the expression of SR‐A message determined by quantitative RT‐PCR indicating transcriptional regulation of SR‐A expression. These data provide evidence for a unique macrophage phenotype, perhaps reflecting altered differentiation of myeloid cells, in LNs of cHL patients.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Patient‐derived and cell line xenograft growth in the B6;129‐Rag2tm1FwaIL2rgtm1Rsky/DwlHsd (R2G2) mouse model
Authors: Naden Jamie
Published: June 2021

Immunodeficient mouse models are helping to advance the field of oncology. A new model on the market, the B6;129‐Rag2tm1FwaIL2rgtm1Rsky/DwlHsd (R2G2) knockout mouse, lacks responsiveness to common gamma chain cytokines, including IL‐2, IL‐4, IL‐7, IL‐9 and IL‐15. In addition, this model exhibits defects in lymphoid development and so lacks mature lymphocytes of the B, T, and natural killer (NK) cell lineages. Herein we describe growth of multiple patient‐derived (PDX) and tumor cell line xeno‐ (CDX) and allo‐grafts in the R2G2 immunodeficient mouse model. The PDXs examined include colorectal and head and neck cancers. The CDXs studied include esophageal (OE33 and FLO1) and stomach cancer (AGS). Tumor growth data was also collected from two allografts of murine colorectal cancer (CT26) and B‐cell lymphoma (A20) cells. Colorectal PDX tissue was subcutaneously implanted bilaterally into five male R2G2 and five male NSG mice. Growth was comparable between the R2G2 and the NSG mouse models, however the standard error was much lower in the R2G2 strain. Head and neck PDX 626 and 635 was transplanted in 2.2 mm2 tissues into 4 sections of each of 2 R2G2 mice each (n=2/PDX), and 100% of mice developed either one or two tumors. The human esophageal adenocarcinoma OE33 cells were implanted into the left and right flanks of three each of R2G2, Athymic Nude and SCID mice. There was a 100% take rate in R2G2 mice, 0% in SCID mice and 17% in Athymic Nude mice. The human esophageal adenocarcinoma FLO1 cells were examined in two studies. In both studies, cells were injected into both flanks of R2G2 and SCID mice. Study A also examined growth in Athymic Nude mice. In study A, no tumor growth was seen in Athymic Nude or SCID mice, whereas the take rate was 100% in R2G2 mice. In study B, the take rate was 100% in both the R2G2 and the SCID mice, although differences were seen in growth rate. Human gastric adenocarcinoma AGS cells were implanted in both flanks of four each of R2G2 and SCID mice. The take rate was 75% in R2G2 mice and 0% in SCID mice. Head and neck squamous cell carcinoma SQ20b cells were implanted in twenty R2G2 mice and take rate was 90%. Growth of two allogeneic tumor lines was also examined. The mouse colon carcinoma CT26 cells were implanted in ten R2G2 mice and took in 100% of the mice. Mouse B‐cell lymphoma A20 cells were implanted in ten R2G2 mice and take rate was 100%. Both allografts grew to 1000mm3 by 13 days post implantation. These data provide evidence that the R2G2 mouse model is a valuable tool for oncology programs including cell line tumor models research, with high take rates and quick growth of allogeneic models.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Significant Reduction in Full Metabolic Syndrome in Saudi Subjects with Elevated Fasting Glucose through an Intensive Lifestyle Monitoring Programme of 12 months
Authors: Alfawaz Hanan A. , AL‐Daghri Nasser M.
Published: June 2021

Background

The present interventional study in adult Saudi subjects with elevated fasting glucose was aimed to determine the health benefits, in terms of reduction in full metabolic syndrome, of a 12‐month intensive lifestyle monitoring programme with emphasis on lowering dietary fat intake; exercise and increasing sunlight exposure.

Methods

Between April‐2012 and March‐2017, 300 Saudi subjects with baseline fasting glucose at 5.6 to 6.9mmol/l were screened and randomly divided into 3 groups: 1) General advice (GA) group who received a standard lifestyle change advice at recruitment and at 6‐months, 2) Intensive lifestyle monitoring programme (ILMP) group who was followed with a rigorous lifestyle modification support and 3) Metformin (GA+Met) group who was advised to take 3 tablets/day of 500 mg metformin hydrochloride. Basic anthropometric, glycemic, and lipid estimations were obtained at baseline and after 6‐months and 12‐months. The data for 85(GA), 73(ILMP) and 59(GA+Met) subjects was analyzed after removing those lost in follow‐up etc. The percentages of full metabolic syndrome and its five components were calculated for all three groups at different time points.

Results

The mean fasting glucose at baseline, 6‐months and 12‐months respectively was 5.97±0.4, 6.07±0.7 and 5.92±0.9 (p=0.49) for GA group; 6.06±0.4, 5.66±0.8 and 5.67±0.8 (p<0.01) for ILMP group; and 6.57±0.5, 6.01±1.3 and 5.76±1.7 (p<0.01) for GA+Met group. 37.3 %( N=22) in GA+Met group were able to reduce their weight by atleast 5% from baseline while this number was 11 %( N=8) and 10.6 %( N=9) in ILMP and GA respectively. Full Metabolic syndrome at end of study compared to the baseline was 64.7%(N=55) vs 72.9%(62) (% change: Δ= −8.2%, p=not significant) for GA group; 35.6%(26) vs 61.6%(45) (Δ= −26%, p<0.01) for ILMP group and 64.4%(38) vs 83.1%(49) (Δ= −18.7%, p<0.01) for GA+Met group.

Conclusions

This study highlights the clinical potency of intensive lifestyle modification programme versus other anti‐diabetic management options in reducing full metabolic syndrome in Saudi adults with elevated fasting glucose.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Type‐I interferon‐mediated Akt/mTORC2 signaling regulates autophagy and inflammasome activation in mouse liver injury/sepsis model
Authors: Wells Jakob , Kader Muhamuda , Tamama Kenichi , Yates Cecelia , Scott Melanie , Ismail Nahed
Published: June 2021

Background

: Sepsis is a clinical syndrome due to dysregulated systemic immune response to infection and tissue injury that causes life‐threatening multiple organ failure. In murine model of sepsis and hepatic inflammatory injury induced by infection with Ehrlichia, an obligate intracellular bacteria targeting liver that compromises the immune system, we have shown that type I interferon (IFN‐I) signaling triggered liver injury, excessive inflammation, and impaired bacterial clearance. We and others have also showed that Ehrlichia exploits autophagy proteins for their own survival and replication. This study was designed to investigate the role of IFN‐I signaling in the regulation of autophagy and inflammatory responses in immune and non‐immune cells such as macrophages and hepatocytes, respectively, during sepsis.

Results

: In this study, we found that IFN‐I signaling promotes autophagy and activates non‐canonical inflammasome pathway mediated by caspase 11 in primary murine macrophages and hepatocytes. Enhancement of autophagy in hepatocytes and macrophages via IFN‐I stimulation or rapamycin treatment increased bacterial replication. Conversely, inhibition of autophagy in macrophages using type III Phosphatidylinositol 3‐kinases (PI‐3K) inhibitor (3‐MA) or blocking IFN‐I receptor (IFNAR) signaling attenuated autophagy, abrogated caspase 11 activation, and decreased intracellular bacteria. These data suggest that IFN‐I signaling impair anti‐bacterial immunity via induction of autophagy. Further, IFN‐I signaling also induced secretion of several chemokines and growth factors (e.g. MIP1alpha, MCP‐1, RANTES, KC, GM‐CSF and VEGF) by hepatocytes that are known to promote excessive infiltration of immune and inflammatory cells into the liver. Finally, microarray analysis identified mTORC2, rapamycin‐insensitive companion of mTOR, and WNT, elevated in sepsis, signaling components to be enhanced in IFN‐I stimulated and infected hepatocytes, which may play a role in IFN‐mediated enhancement of autophagy and inflammation.

Conclusions

: Together, our novel findings identify the IFN‐1‐mediated Akt/autophagy axis as a key regulator of innate inflammatory response in the mouse liver cells. By identifying molecular mechanisms of IFN‐1‐mediated Akt/autophagy/mTORC2 signaling during sepsis, our study provides a rationale for therapeutic approaches to manage inflammation and liver injury during sepsis.

Support or Funding Information

This work was supported by grants from NIAMS, NIGMD, and NIAID (AR68317 CCY, 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.
Critical Role of Plasmin in Macrophage Activation During Liver Injury
Authors: Roth Katherine , Joshi Nikita , Albee Ryan , Luyendyk James P. , Copple Bryan
Published: June 2021

Activation of hepatic macrophages is critical for liver repair after injury. The mechanism by which liver injury stimulates macrophage activation is not fully understood. We tested the hypothesis that the fibrinolytic enzyme, plasmin, is critical for macrophage activation after liver injury. To test this hypothesis, mice were exposed to a hepatotoxic dose of acetaminophen followed by treatment with tranexamic acid (1200 mg/kg i.p., administered twice daily), a drug that inhibits the conversion of plasminogen to plasmin. Exposure of mice to acetaminophen stimulated rapid macrophage activation, increasing cytokine production and macrophage‐mediated phagocytosis of necrotic cells. This activation was reduced by plasmin inhibition, leading to impaired liver repair. Next, we determined whether plasmin directly activates macrophages. Treatment of either bone marrow‐derived macrophages or Kupffer cells with plasmin increased expression of the proinflammatory cytokines Cxcl1, Cxcl2, and tumor necrosis factor‐α in an Erk1/2 and p38‐dependent manner. Studies have indicated a role for high‐mobility group B1 protein (HMGB1), a damage‐associated molecular pattern molecule, in the activation of macrophages. Therefore, we determined whether HMGB1 affects plasmin‐mediated activation of macrophages. While HMGB1 alone at concentrations that are detected in the serum of acetaminophen‐treated mice did not increase expression of proinflammatory cytokines in macrophages, it synergistically enhanced plasmin‐mediated upregulation of cytokines. Furthermore, necrotic hepatocytes from wild‐type mice enhanced plasmin‐mediated activation of macrophages, whereas necrotic hepatocytes from hepatocyte‐specific HMGB1 knockout mice did not. Collectively, these studies demonstrate that plasmin is an important activator of macrophages after liver injury. Further characterization of this pathway could lead to the development of novel therapies aimed at enhancing macrophage‐mediated liver repair in patients suffering from acute liver injury.

Support or Funding Information

NIH grant 2 R01 DK073566

NIH Training Grant T32 ES007255

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hepatocyte specific ablation of β and γ‐catenin leads to altered hepatocyte polarity and microvillae association
Authors: Pradhan Tirthadipa , Adebayo Adeola , Molina Laura , Monga Satdarshan Pal
Published: June 2021

Liver is the largest organ in a vertebrate body which is structurally and functionally complex and is considered second to the brain in its complexity. It is highly heterogeneous in nature and consists of various cell types. Hepatocytes are the predominant type of cells present in liver which is responsible for its many important functions including bile production, detoxification, cholesterol synthesis etc. Like any other epithelial cell, hepatocytes are polarized towards the apico‐basal axes. Polarization of hepatocytes is necessary for many functions and requires carefully orchestrated cooperation between cell adhesion molecules, extracellular matrix, cell junctions, cytoskeleton, and intracellular trafficking machinery. Loss of hepatocyte polarity is associated with various liver diseases including cholestasis.

Recently, we have shown that absence of adherent junctional protein β and γ catenin in the liver leads to cholestatic liver disease. However, the molecular mechanism that leads to cholestasis in the absence of β‐ γ‐catenin is not known. Therefore, we developed a hepatocyte specific conditional knockout of β and γ catenin to further characterize their role in this disease. TEM and SEM analysis of β‐ γ‐catenin knockout liver showed aberrant tight junctional and adherent junctional structurers. Permeability assay confirmed that barrier function of tight junctions is completely lost in these mice resulting in mixing of the bile with the blood. We also found that bile canaliculi, which is apically located in hepatocytes designated for bile storage is strongly dilated with significant reduction in microvilli inside them. Further analysis revealed that loss of β‐ γ‐catenin leads to reduced expression of HNF4α target genes. Remarkably, we found that loss of HNF4α phenocopies β‐ γ‐catenin knockout liver causing aberrant tight and adherent junctional structure. Studies designed to address the molecular mechanism behind the regulation of β; γ‐catenin in maintaining hepatocyte polarity and association of β; γ‐catenin and HNF4α in promoting hepatocyte polarity are currently underway. Profound understanding of the regulation of hepatocyte polarity by both β ‐and γ‐catenin will be useful in the context of liver development and pathophysiology.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Proton‐Coupled Electron Transfer in Soybean Lipoxygenase: Hydrogen Tunneling, Electrostatics, and Conformational Motions
Authors: Hammes‐Schiffer Sharon
Published: June 2021

The enzyme soybean lipoxygenase (SLO) serves as a prototype for hydrogen tunneling reactions because of its unusually large deuterium kinetic isotope effect (KIE) of 80 for the wild‐type enzyme and over 500 for a double mutant. The proton‐coupled electron transfer (PCET) reaction catalyzed by SLO has been studied with a vibronically nonadiabatic PCET theory that includes the quantum mechanical effects of the electrons and the transferring proton, as well as the proton donor‐acceptor and solvent motions. The calculations reproduced the experimentally observed magnitude and temperature dependence of the KIE for wild‐type SLO and a series of single mutants. The large KIE was found to arise from the small overlap between the reactant and product proton vibrational wave functions. Theoretical modeling of the double mutant illustrated that the colossal KIE of over 500 arises from a combination of a non‐optimal active site conformation corresponding to longer equilibrium donor‐acceptor distances and reduced sampling of shorter donor‐acceptor distances. Recent quantum mechanical/molecular mechanical (QM/MM) free energy simulations using a finite temperature string method combined with umbrella sampling have provided additional insights about the conformational motions, as well as the significance of electrostatics in this enzymatic reaction. These calculations highlight the critical roles of hydrogen tunneling, electrostatics, and protein conformational motions in enzyme catalysis.

Support or Funding Information

National Institutes of Health Grant GM056207

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
How Hormonal Contraceptive Use Impacts Laparoscopic Skill Acquisition in Biologically Female Medical Students
Authors: Olive Elizabeth J. , Klei Jennifer , Roach Victoria A.
Published: June 2021

INTRODUCTION

Hormonal contraceptive use is commonplace among biological females of reproductive age. Biological females typically have lower testosterone levels than males, and hormonal contraceptive use lowers that testosterone level even further. Higher testosterone levels are shown to be positively correlated with spatial ability and, ultimately, with better performance in surgical skill acquisition. Biological females, particularly those using hormonal contraceptives, may then be at a disadvantage for learning new surgical skills. However, the relationship between hormonal contraceptive use and surgical skill acquisition is not yet understood, and will be examined in this study.

METHODS

Participants (anticipated n=50) are students of Oakland University William Beaumont School of Medicine and are participating under approval of the university's Institutional Review Board. This study makes use of laparoscopic box trainers and the peg transfer task from the MISTELS (McGill Inanimate System for Training and Evaluation of Laparoscopic Skills) battery of tests. The control and treatment groups are divided based on biologically female participants who do not use hormonal contraceptives, and those who do, respectively. Both groups perform several screening tasks regarding demographics, handedness, video game usage, mental rotation ability, and ovulation status. Participants then train on the peg transfer task, recording their times for each attempt until proficiency is reached. An ANCOVA, 2 (cycle/static) × 1 (frequency of repetitions) with spatial ability as a covariate, with appropriate post‐hocs as necessary, will be used to statistically analyze differences in the learning curves between naturally cycling participants and those using hormonal contraceptives.

ANTICIPATED RESULTS

Compared to the naturally cycling group, the group using hormonal contraceptives is expected to require greater time and number of attempts to reach proficiency on the peg transfer task.

SIGNIFICANCE

The results are expected to support the hypothesis that hormonal contraceptive use is negatively correlated with surgical skill acquisition. This may have implications for informing contraceptive choices of biological females pursuing careers in surgery. In addition, it may inform future curriculum design for graduate medical programs, to maximize learning opportunities for aspiring surgeons.

Support or Funding Information

Department of Biomedical Sciences Research Seed Fund, Oakland University William Beaumont 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.
Formative Assessments in Anatomy: Two‐year Quality Improvement Study of Self‐Assessment Resources for Didactic Material
Authors: Lee Vaughan H. , Pomeroy Brian , Schneider Brandt L.
Published: June 2021

Formative assessments provide one component of resources to support self‐directed learning activities in many disciplines of education. At the Texas Tech University Health Sciences Center/School of Medicine we have previously reported a collection of formative assessments for didactic and laboratory concepts to improve the efficiency of anatomical education in the Clinically Oriented Anatomy course. More recently in 2017–18 access to study materials presented by Firecracker was provided to students and integrated with the objectives of the course. This included weekly formative quizzes created with Firecracker questions and unit formative written exams constructed by the faculty. Preliminary evaluation of this initiative reveals: 1) Both weekly and unit formative assessments yielded moderate correlations to students' summative performance; 2) The level of correlation for these formative assessments were comparable between 2016–17 and 2017–18; and 3) Analysis of student effort by Firecracker provided good correlation with students' final grades. Students' perceptions of these formative written assessments and Firecracker resources were very favorable, 4.42 and 4.02 (5pt Likert), respectively. Detailed analyses of data, outcomes, limitations and future plans for continuous quality improvement will be presented.

Support or Funding Information

This project was funded by the Texas Tech University Health Sciences Center/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.
Mastering Anatomy: Using Cerego as a Teaching Tool
Authors: Warshaw Johanna , Lopez Elisabeth N. , Baker Eric W. , Cunningham Elena P.
Published: June 2021

At the New York University College of Dentistry, lab conference hours for the review of anatomy in preparation for the National Board Dental Examination Part I (NBDE Part I) were reduced due to an increase in incoming class size in 2015. Tasked with providing students an effective means to review material that could now not be covered in the given lab hours, we identified the online platform Cerego as a way to provide a self‐guided anatomy study tool. Use of Cerego replaced what would otherwise have been 96 faculty hours of instruction.

We initially created three anatomy topic modules in Cerego, each of which included a combination of images, identifications, associations, and short text passages. Creation of modules in Cerego was intuitive and straightforward. The platform, with algorithms based on principles of retrieval learning and spaced practice, guides the student through individualized iterations of review in multiple formats, and provides the student with prompts for the most effective timing for return to the material. In addition, both student and instructor have access to fine grained performance analytics.

We found that Cerego is well suited to fact memorization, and effective as a means to learn material within the time‐frame of a single semester. However, full mastery using the Cerego program – leading to long‐term retention – is achieved over a more extended period. A survey after the termination of the NBDE Part I course in 2015, as well as informal discussions with students, has indicated high student satisfaction with Cerego as a study tool. In addition, results for the anatomy portion of the board exam demonstrates student success, with NYU Dentistry students as a whole achieving a 97.1–100% first‐time pass rate, and performing at 1.4–2.6 standard deviations above the mean for all dental schools in anatomy in the years 2015–2017. Given the success of our initial Cerego use, we have now incorporated this platform into the Head and Neck Anatomy and Basic Tissues courses within the Department of Basic Science and Craniofacial Biology, and other departments at NYU Dentistry have also adopted the use of this tool.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Difficulty of Dissection: Which Anatomical Regions Are Hardest For Medical Students To Dissect?
Authors: Williams Sutton Ross , Thompson Kenneth , Notebaert Andrew , Sinning Allan
Published: June 2021

Cadaveric dissection in gross anatomy courses has long been considered the gold‐standard for instruction, but the difficulty associated with some dissections may lead to negative learning outcomes for those students adversely impacted by dissection experiences. Therefore, this investigative study aimed to identify medical students' perception of the difficulty associated with each dissection completed during a 16‐week medical gross anatomy course. The purpose of this study was to provide better insight into the relationship between the difficulty associated with dissecting anatomical regions and student performance on practical examination questions pertaining to those regions. To answer this question, 10‐point Likert scale surveys with values ranging from 1 (easy) to 10 (difficult) were utilized to ascertain the perceived difficulty of each dissection completed during the course. The surveys were distributed to the students (n=160) prior to each of the block examinations given throughout the course. Following collection of the difficulty surveys, student responses were analyzed in order to determine if any of the dissections were rated as significantly more or less difficult than others. Difficulty rankings were also compared to previously collected data from the same course to determine if there is a relationship between the difficulties associated with dissecting each region, and how medical students have historically performed on questions pertaining to each region analyzed. Preliminary results indicate that medical students' perception of the difficulty associated with completing different dissections varies significantly. The average perceived difficulty of the dissections was 4.6 (SD=2.3), the minimum mean dissection difficulty reported was 2.9 (SD=2.0) and corresponded to the knee dissection, while the maximum mean dissection difficulty reported was 7.5 (SD=2.3) and corresponded to the axilla dissection. Concurrently, results from the difficulty survey were compared to historical records of medical student performance on practical examination questions. Preliminary results from these comparisons seem to indicate a relationship between the difficulty associated with dissecting anatomical regions and the ability of medical students to learn structures related to the dissection. Students have historically performed worse on practical examination questions pertaining to structures from difficult dissections and better on questions pertaining to structures from easy dissections. As such, it is important for anatomy educators to consider the difficulty of each dissection they require their students to complete, and the potential impact each dissection has on the students' ability to learn the material.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cardioprotective effect of camel milk against carbon tetrachloride induced toxicity
Authors: UGOCHUKWU CHIOMA , IHENTUGE CHURCHILL , IHENTUGE PHOEBE
Published: June 2021

Camel milk a nutritional supplement has been known to have anti oxidant properties and has been used for more than a century for treatment of diseases. Twenty adult wistar rats weighing between 150g and 200g were used in the study to determine the protective effective of camel milk on carbon tetrachloride (CCl4) induced cardio‐toxicity in rats. The rats were divided into 5 groups (A, B, C, D and E) of 4 animals each and were fed with rat feed and water for 30days. Control groups (A and B) were injected intraperitoneally (i/p) with 1ml/kgbw of paraffin oil on the 1st and 2nd days, and in addition group B was fed with camel milk for the remaining days. Groups C and D were injected i/p with CCl4 (1ml/kgbw) for 2 consecutive days and group D fed with camel milk for the remaining period. Group E were fed with camel milk and were injected i/p with CCl4 on the last two days.

Results showed a decrease in mean body weight of group C significant at p<0.05% while A and B; D and E showed increase in mean body weight. Macroscopically there was loss of normal pericardial outline in group C when compared with the normal. The Histomorphic appearance of cardiac cells in group C showed presence of inflammatory cells, scattered vacuoles and focal areas of necrosis with loss of intercalated disc. The control groups (A and B) and other experimental groups (D and E) appear normal with the preservation of the myocytes.

This shows that camel milk is capable of protecting the heart against Carbon tetrachloride Induced toxicity and should be recommended for stress induced disorders.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Morphological Variation in the Posterior Margin of the Frontal Process of the Zygomatic Bone
Authors: Wharton Benjamin L. , Teaff Noah J. , McGowan Branigan L. , Russell Michelle L. , Zdilla Matthew J.
Published: June 2021

Based on the observation that some crania exhibit a pronounced marginal tubercle, whereas others do not, this study assessed the contour of the zygomatic bone hypothesizing that female and male crania would exhibit different contours. The study included 616 norma lateralis images of a mixed sample of female (n=252) and male (n=318) cranial sides. Images from crania of questionable sex and were excluded from analysis between sexes. The linear distance from the zygomaticofrontal suture to the jugale was calculated in addition to the length of the posterior border of the frontal process of the zygomatic bone to determine the degree of deviation from a straight line. The contour length between males and females did not differ (t=1.577(593); p=0.12) nor did the degree of deviation from a straight line (t=1.808(593); p=0.07). Independent of sex, however, there were significant differences in the aforementioned parameters with regard to side (t=5.589(614); p<0.0001 and t=3.742(614); p=0.0002, respectively). Procrustes superimposition demonstrated the average contour which can be given as y≈44.074x4 + 0.7995x3 −2.6286x2 −0.0122x + 0.0182. Principle component analysis explained 74.6% of shape variation with the first two principle components (PC1=48.8%; PC2=25.8%). With regard to differences in the shape of the contour between sides or sexes, discriminant function analysis revealed no significant shape difference (T2=338.7; p=0.15 and T2=244.3; p=0.94, respectively). However, canonical variate analysis demonstrated statistically significant shape differences among sexes with regard to side. Female right and left sides demonstrated the most shape difference (Mahalanobis distance=2.33) whereas the least shape difference was found among right sides between males and females (Mahalanobis distance=1.83). The results of this study reveal morphological variation in the posterior margin of the frontal process of the zygomatic bone that distinguishes crania based upon sex and laterality.

Support or Funding Information

WV Research Challenge Fund [HEPC.dsr.17.06] and [HEPC.dsr.14.13]

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 NEW ASPECT OF TRICEPS BRACHII MUSCLE INSERTION
Authors: Akamatsu Flávia Emi , Negrão José Renato , Saleh Samir Omar , Hojaij Flávio , Andrade Mauro , Jacomo Alfredo Luiz
Published: June 2021

Anatomy of the triceps tendon insertion has been subject of recent investigations.

The purpose of this cadaveric study was to elucidate a question raised by previous studies whether the triceps brachialis tendon has a double or single insertion in the ulna.

Thirty‐three elbows from 29 male and 4 female fixed cadavers were dissected in order to assess details of the triceps brachii insertion. The triceps tendon near its insertion in the olecranon constantly displayed a thinner and translucent area related to the attachment of the fibers of the long head of the triceps brachii muscle into the tendon. We measured the longitudinal length of this area and found a coefficient of variation of less than 10% for all measurements.

This area, not previously described, may account for some misdiagnosis in imaging studies of the elbow and its knowledge may be essential to avoid incorrect diagnosis and unnecessary therapeutic approaches.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Classifying novel variations of a rare muscle: the sternalis
Authors: Prall Cristina R. , Azzouz Lyna , Connolly Christopher , Gutierrez Marc , Moreno Natalie , Olumolade Oluyemi , Alsup B. Kathleen , Fox Glenn M.
Published: June 2021

Knowledge and publication of human anatomic variations has become increasingly emphasized in the clinical setting with the intent of decreasing the occurrence of misdiagnosis and surgical complications. We report a previously undocumented variant of sternalis muscle. The sternalis muscle is an anatomical variation of the anterior thoracic wall that is rare, though well‐documented. This inconstant muscle is typically parasternal and superficial to pectoralis major muscle, with its fibers running vertically. Dissection of the anterior thoracic wall on an 83‐year‐old female cadaver revealed bilateral sternalis muscles. The right sternalis muscle has a single belly and can be classified using the Snosek et al. (2014) classification system as a simple type, left single. The left sternalis muscle presented with three muscle bellies, each having a unique pattern of superior attachments. This variation is previously undocumented, and we propose the addition of a new subtype of sternalis classification, as well as a modification to the Snosek et al. (2014) classification scheme to include classifying different muscle bellies when multiple are present.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ultrasound Assessment of the Zygapophyseal Joints Before and After Spinal Manipulation
Authors: Cramer Gregory David , Settergren Roy , Miller Nathan , Dexheimer Jennifer
Published: June 2021

This IRB‐approved pilot/feasibility study used diagnostic ultrasound (US) to quantify L3/L4 zygapophyseal (Z) joint space separation (therapeutic gapping) before and after spinal manipulation (SM). Previous work in our lab demonstrated Z joint space gapping using magnetic resonance imaging. US has the advantage of assessing Z joint gapping in real‐time and allows measurements to be made before SM, and multiple measurements to be made after SM, using the data from a single imaging session.

Methods

six (3 male and 3 female) healthy subjects were enrolled. Z joint gapping was determined by the difference (gapping difference) between US joint space measurements taken pre‐ and post‐SM. SM was performed in the side‐posture (recumbent) position and pre‐ and post‐SM images were obtained while the subject was in the side‐posture position. Post‐SM US images were taken immediately after SM, and at 16 pre‐determined time intervals between 5–180 sec post‐SM. Gapping differences were compared for up‐side (contact side for SM) pre‐SM and all post‐SM values. Primary outcomes were maximum gapping difference for each subject and post‐SM time when maximum gapping was measured.

Results

Z joint gapping continued to increase for 10–15 seconds after SM and then gapping diminished toward immediately post‐SM values. The average maximum gap was 0.8 mm and the average time to maximum gap was 11.25 sec. Maximum gapping was achieved most frequently at 10 sec post‐SM.

Conclusions

The methods were effective in assessing Z joint gapping before and after SM. Still images and live images were captured. Future work should include establishing the reliability of US Z joint measurements, and continuing to assess video capture of real‐time SM assessment and the time to maximum Z joint gapping following SM.

Support or Funding Information

Partial funding: NIH/NCCIH Grant # 3R01AT000123‐06S2

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Vulnerability of the Temporomandibular Joint in Recent Northern China Populations
Authors: Wang Qian , Zhang Qun , Han Tao , Sun Zhichao , Kesterke Matthew J. , Zhu Hong , Dechow Paul C. , Zhang Quanchao
Published: June 2021

During recent human evolution, the shortening of the facial skeleton and the gracilization of the skull has been related to the high prevalence of dental anomalies, such as dental crowding. However, little attention has is given to temporomandibular joint (TMJ) disorders from an evolutionary perspective, and the evaluation of TMJ in archaeological populations remains scarce. In this study, TMJ vulnerability in recent Northern Chinese human populations, dated to between 3800 B.C. and A.D. 100, is assessed using a model based on the “triangle of support” hypothesis. The results demonstrate that TMJ vulnerability negatively correlates with maxillary dental arch size and biting efficiency, suggesting that populations or individuals with a smaller dental arch and high biting efficiency could more easily injure the TMJ during unilateral loadings, which may explain the higher prevalence of TMJ disorders in modern humans, especially in women. The males in the pastoral group had broader and more orthognathic faces, shorter maxillary dental arch lengths, wider maxillary dental arches, yet overall smaller maxillary dental arch sizes, larger TMJ sizes, larger distances between condylar and coronoid processes, and higher indices of TMJ vulnerability than males in the agricultural group, indicating different adaptation strategies used in different life styles. These findings indicate either coupled consequences of recent human evolution or an inadvertent tradeoff between biting efficiency and TMJ vulnerability, and reflect the impact of diachronic changes of the masticatory apparatus and life style and their impact on oral health during recent human history.

Support or Funding Information

Jilin University Foreign Experts Project Foreign Scholar Award

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chamber specific expression of Myosin heavy chain 7b in the heart of vertebrates
Authors: López‐Unzu Miguel A. , Durán Ana Carmen , Soto‐Navarrete María Teresa , Fernández Borja
Published: June 2021

In extant vertebrates, myosin heavy chain (MyHC) 6 and 7 are the main isoforms of atrial and ventricular myocardium respectively, whereas MyHC7b has been proposed to be an ancient cardiac isoform only expressed during embryonic development in modern species. The MYHC7b DNA sequence has an intronic miRNA thought to be a regulator of slow‐twitch versus fast‐twitch muscle differentiation.

The pan‐MyHC antibodies MF20 and A4.1025 are commonly used to highlight the myocardium in histomorphological studies. In preliminary immunohistochemical studies of the heart of the lesser spotted dogfish (Scyliorhinus canicula; Chondrichthyes), we have observed that while MF20 labels homogeneously all the myocardium, A4.1025 labels the inflow cardiac segments (sinus venosus and atrium) but not the outflow segments (ventricle and conus arteriosus). In order to interpret these results, we have performed western and slot blots from samples of dogfish and hamster (Mesocricetus auratus) hearts, HPLC‐ESI‐MS/MS from dogfish samples, and immunohistochemistry in hearts of representative species of vertebrates, namely elasmobranchs, polypteriforms, acipenseriforms, teleosts and mammals, using MF20 and A4.1025 antibodies.

Western and slot blot results confirmed the specificity of MF20 and A4.1025 for MyHC in dogfish, as well as their differential reactivity against different myocardial segments. HPLC‐ESI‐MS/MS using protein databases from Callorhinchus milii (Chondrichthyes) and Chordata revealed the presence of MyHC6 and 7 in all the dogfish myocardial segments, and of MyHC7b only in the outflow segments. Immunohistochemistry showed that while MF20 signals were homogeneous in all the myocardial segments of all the species studied, A4.1025 signals were restricted to the inflow myocardial segments in elasmobranchs, homogeneous in teleosts and acipenseriforms, and low in the ventricle of polypteriforms.

From our results it can be inferred that the A4.1025 antibody, as opposed to MF20, has a low affinity for MyHC7b, at least in the dogfish. In addition, we show that MyHC distribution in the cardiac chambers has changed during the evolution of gnathostomes. We raise the hypothesis that in early diverged groups of gnathostomes, MyHC6 and 7 were distributed in all the myocardial segments, whereas MyHC7b was specific for the outflow myocardium. In derived gnathostomes, MyHC6 and 7 became mainly restricted to the atrium and ventricle respectively, whereas MyHC7b disappeared from the heart, acquiring a regulatory role in cardiac and extracardiac myogenesis through its intronic miRNA.

Support or Funding Information

This study was supported by CGL2014‐52356‐P and FPU15/03209

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.