bluuebunny/crossref_metadata_2025 huggingface dataset:
CD47 regulates CD11b‐dependent neutrophil transepithelial migration during intestinal inflammation
Authors: Azcutia Veronica , Luissint Anny‐Claude , Flemming Sven , Quiros Miguel , Nusrat Asma , Luscinskas Francis William , Parkos Charles A.
Published: November 2023

Inflammatory bowel disease (IBD), including Crohn's disease and Ulcerative colitis, is a chronic, relapsing disorder of the gastrointestinal tract characterized by neutrophil (PMN) associated bystander tissue damage, crypt abscess formation and mucosal ulceration. It is well appreciated that neutrophil transepithelial migration (TEpM) in the intestine correlates with disease flares in individuals with IBD. While the molecular events regulating PMN TEpM are far from understood, it is now clear that the integrin CD11b/CD18 and CD47 play crucial roles in this process. CD47 is a highly glycosylated protein that associates in cis with β1, β2 and β3 integrins in different cell types while also serving as a receptor for Signal Regulatory Proteins (SIRP‐α and ‐γ) and thrombospondin (TSP). CD47 is involved in regulation of innate and adaptive immune responses. For example, it has been reported that PMN recruitment in CD47−/− mice is reduced in models of peritonitis, lung injury and dermal air pouch inflammation, but the exact mechanism(s) behind CD47 regulation of PMN infiltration into inflamed mucosal tissues is unclear. We have previously reported that CD47 expressed in T‐cells regulates transendothelial migration through its physical and functional association with the β2 integrin CD11a/CD18. In the gut, it has been shown that PMN transmigration across intestinal epithelium is dependent on CD11b/CD18 but not CD11a/CD18. Thus, we hypothesized that CD47 interacts with CD11b/CD18 to regulate PMN chemotaxis and TEpM in the intestine. Here we report that CD47 co‐associates with CD11b/CD18 in PMN as determined by co‐immunoprecipitation and proximal ligation assay (PLA). Flow cytometry analyses of murine PMN deficient in CD47 showed that, despite expressing similar levels of CD11b/CD18 at baseline, there was defective upregulation of CD11b/CD18 upon stimulation with the chemoattractants fMLF or LTB4 compared with WT PMN. Additionally, loss of CD47 in murine PMN resulted in a 25% reduction in LTB4 driven chemotaxis. Furthermore, antibody mediated inhibition of CD11b/CD18 reduced WT PMN migration to similar levels as CD47−/− PMN. In contrast, blocking CD11b on CD47−/− PMN did not further reduce migration, suggesting a functional regulation of integrin‐dependent chemotaxis by CD47. In vivo studies modeling PMN TEpM into the intestinal lumen in response to LTB4 revealed decreased migration in CD47−/− mice (>60% reduction vs. WT; p<0.05). Taken together, our data suggest that CD47 plays an important role in PMN intestinal recruitment through regulation of CD11b/CD18 adhesive function. We suggest that CD47 represents a promising new candidate for therapeutic approaches aimed at dampening pro‐inflammatory signals, reducing PMN influx and improving mucosal wound healing in IBD.

Support or Funding Information

Supported by NIH 5R01DK079392‐12 and R01HL125780
Pyruvate Dehydrogenase Kinase 4‐Deficiency Induces Hepatic Apoptosis by Activating NF‐κB/TNFα Signaling
Authors: Wu Jianguo , Choiniere Jonathon , Lin Matthew , Wang Li
Published: November 2023

Objective

Pyruvate dehydrogenase kinase 4 (PDK4) is a mitochondrial protein and key metabolic regulator of glucose oxidation. However, the role of PDK4 in the development hepatocellular carcinoma (HCC) remains unknown, which is the focus of this study.

Methods

In vivo model: Male 15‐day‐old wild‐type (WT) or Pdk4 knockout (Pdk4−/−) mice given i.p. injections of a single dose of diethylnitrosamine(DEN) (25 mg/kg body weight). In vitro model: PDK4 knockdown Huh7 and Hep3B cells using shRNAs. Cell viability was evaluated by MTS and colony formation assays. Mitochondria function and cell apoptosis were determined by transmission electronic microscopy (EM), Seahorse assay, flow cytometry, and the measurement of caspase activity. Cell death gene expression was profiled with qPCR array and Western blot. TNFα levels were detected by ELISA. NF‐κB activity was determined by immunofluorescence (IF), CHIP assay, qPCR, and luciferase reporter assay. TNFα and NF‐κB signaling were inhibited by shRNAs against TNFR and NF‐κB/p65, respectively. The protein interaction was studied by GST‐pulldown and co‐immunoprecipitation (Co‐IP). Immunohistochemistry (IHC), liver histology, and TUNEL assay were used to detect apoptosis in mouse liver.

Results

Pdk4−/− mice injected with DEN died within a week, whereas WT‐DEN showed no visible abnormalities. Pdk4−/−‐DEN had significantly decreased liver/body weight ratio and displayed disrupted liver structure. Pdk4−/−‐DEN liver exhibited severe apoptosis as determined by TUNEL staining, which was accompanied by increased caspase 3 activity, PARP1 cleavage, TNFα expression, and NF‐kB activity, as compared to WT‐DEN. Knockdown of PDK4 in Huh7 and Hep3B cells also caused a marked decrease in cell viability and increased apoptosis and caspase activities. Interestingly, EM revealed apoptotic body formation as well as mitochondria vacuolization in shPDK4 cells. Seahorse revealed marked increases in basal mitochondria respiration, and ATP and ROS production in shPDK4 cells. qPCR array identified a common upregulation of TNFα, BIRC3, and CCDC103 in shPDK4 Huh7 and Hep3B cells. At the molecular level, PDK4 protein sequestrated p65 and p50 in cytoplasm via direct protein‐protein interactions and knockdown of PDK4 resulted in their dissociation thus increased p65/p50 nuclear translocation. This in turn increased binding of p65 to TNFα, BIRC3, and CCDC103 promoters and the activation of their gene transcription.

Conclusions

Our study elucidated PDK4 as a crucial new modulator of NF‐κB‐TNFα mediated apoptosis signaling in HCC.

Support or Funding Information

Grant support: L.W. is supported by NIH R01DK104656, R01DK080440, R01ES025909, R21AA022482, R21AA024935, VA Merit Award 1I01BX002634, P30 DK34989 (Yale Liver Center) and the National Natural Scientific Foundation of China (Grant No. 81572443).
Role of MET and EGFR Signaling in Hepatomegaly and Hepatocyte Proliferation Induced by TCPOBOP (1,4‐Bis [2‐(3,5‐Dichloropyridyloxy)] Benzene) in Mice
Authors: Bhushan Bharat , Haynes Meagan M. , Mars Wendy M. , Orr Anne , Bowen William C. , Paranjpe Shirish , Michalopoulos George K.
Published: November 2023

Growth factor receptors MET and EGFR are known to play a critical role in liver regeneration after partial hepatectomy. TCPOBOP (1,4‐Bis [2‐(3,5‐Dichloropyridyloxy)] benzene), a CAR agonist, induces robust hepatocyte proliferation and hepatomegaly without any injury or tissue loss. The underlying mechanisms are considered to be different compared to the mechanisms of liver regeneration after partial hepatectomy with no evidence of involvement of cytokine and receptor tyrosine kinase signaling. Role of signaling via growth factor receptors, MET and EGFR, in TCPOBOP‐induced direct hyperplasia is not yet investigated. Here we report that both MET and EGFR are rapidly activated after TCPOBOP treatment in mice preceding any substantial increase in hepatocyte proliferation and liver mass. This was accompanied by concomitant activation of downstream ERK1/2 and AKT signaling pathways. Systemic elimination of MET (MET KO) in mice resulted in a moderate decrease in TCPOBOP‐induced hepatomegaly. However, treatment with Canertinib, an EGFR inhibitor (EGFRi), did not significantly alter TCPOBOP‐induced liver growth. Interestingly, combined elimination of MET and EGFR signaling (MET KO + EGFRi‐treatment) dramatically reduced TCPOBOP‐induced hepatomegaly and remarkably attenuated hepatocyte proliferation. In conclusion, our study revealed a novel role of signaling via EGFR and MET receptors in hepatomegaly and hepatocyte proliferation induced by TCPOBOP.
Active Methodologies Improve the Performance of Medical Students in Physiology Assessments
Authors: Montrezor Luís Henrique
Published: November 2023

Why evaluate? How to evaluate? When to evaluate? What to evaluate? Evaluations are constantly employed in the classroom to assist students in the learning process and to help teachers improve the teaching process. The use of active methodologies encourages students to participate in the learning process, encourages interaction with their peers, and stimulates thinking about physiological mechanisms. This study examined the performance of medical students on physiology over four semesters, with and without active engagement methodologies. The study was conducted with 200 medical school students from four different classrooms. The students were divided according to their semester of attendance: second (group 1), third (group 2), seventh (group 3) and eighth (group 4). Our medical classrooms are composed of 50 students and all of them participated in the study (n = 50 per group). Each group was randomly divided into two subgroups: a subgroup (n = 25) that completed activities with active methodologies before the Cognitive Monitoring Test (CMT) and Integrative Cognitive Test (ICT) and a subgroup (n = 25) that did not perform such activities. Four activities were used: a puzzle on the cardiac cycle in the second semester; a board game on membrane potential and action potential in the third semester; a debate on the physiological basis of electrocardiography, the cardiac cycle and blood pressure control in the seventh semester and a video presented in the eighth semester on neurology and focused on membrane potential and action potential. The activities involving active methodologies lasted 90–120 minutes. The CMT is composed of five questions: two open questions and three multiple‐choice questions. Students had 30 minutes for CMT. The ICT consists of open and multiple‐choice questions (an average of 40 questions) based on clinical cases (case‐based learning). Students had 4 hours for ICT. The results show that engaging in activities with active methodologies before physiology CMT significantly improved student performance compared with not performing the activities. All of the students were also evaluated using the ICT and obtained better grades than the students in the control groups We integrate the use of these methodologies with classic lectures, and this integration appears to improve the teaching‐learning process in the discipline of physiology and improves the integration of physiology with cardiology and neurology. In addition, students enjoy the activities and perform better on their evaluations when they use them.
Ontogenetic Changes in the Terrestrial Locomotion of the American Alligator (Alligator mississippiensis)
Authors: Manfredi Kevin , Georgi Justin
Published: November 2023

Ontogenetic changes in the musculoskeletal system, ecological niche, and feeding habits of the American alligator (Alligator mississippiensis) have all been hypothesized to relate to similar ontogenetic shifts in locomotion. Anecdotal evidence of the loss of galloping in some crocodilian taxa lends some support to this hypothesis. This study represents the first systematic evaluation of terrestrial locomotor mechanics across an ontogenetic series of crocodilian in order to evaluate if there is an identifiable change. American alligators representing 23 different sizes (ranging in length from 0.63 to 1.64 m in total length) were tracked with a VICON motion tracking system as they moved across a packed dirt floor. For all walking strides that included less than 20° of direction change, stride length, stride duration and duty factor were calculated from the 3D data. These stride parameters were compared to a geometric mean of skull measurements to calculate scaling factors. In addition to overall scaling patterns, the data were sorted into two large (n=11) and small (n=12) groups, correlating to the difference between juveniles and adults (less than or greater than approximately 1 m in length). Scaling patterns between these groups were then compared.

Across all specimens, length and duration showed significant positive correlation with size (p << 0.001 and p = 0.016 respectively), but duty factor did not (p = 0.079). In only smaller alligators, length exhibited a positive correlation with size (p << 0.001), duty factor a strong negative correlation (p = 0.002) and duration no correlation (p = 0.288). In contrast, larger alligators demonstrated a different pattern with length and duty factor both showing positive correlations with size (p = 0.002 and p = 0.001 respectively) and no correlation between duration and size (p = 0.204). Comparisons between the large and small groups found significantly different scaling factors for both length (p = 0.008) and duty factor (p = 0.007). Thus, we have shown that there is a major shift in the scaling of the fundamental parameters of alligator locomotion at approximately the sub‐adult stage. This transition decreases the scaling factor of stride length from positive allometry (slope = 1.64) to negative (slope = 0.54) and completely reverses the scaling trend of duty factor from decreasing duty factor (slope = −0.18) to increasing duty factor (slope = 0.40).
Modeling Complex Cranial Joints in Varanus exanthematicus
Authors: Wilken Alec T. , Middleton Kevin M. , Sellers Kaleb C. , Cost Ian N. , Davis Julian L. , Holliday Casey M.
Published: November 2023

In contrast to humans and other mammals which have relatively few mobile cranial joints, most lizards exhibit cranial kinesis, intracranial movement between bones, which they inherited from their amniote ancestors. Although the tissue‐level structure of kinetic joints has been described, how these joints are loaded during feeding remains relatively poorly known. Finite element analysis previously has been used to estimate joint loading; however, these studies have not modeled mobile joints, instead fusing bones across joints, creating a solid model. We have developed a new method of modeling mobile cranial joints, in which joint spaces are filled with materials that have the properties of cartilage, ligaments, and other tissues that are known to contribute to joint structure. Because their skulls house many different types of structurally and compositionally different joints, ranging from sutural to synovial, lizards make excellent model organisms for studying the relationship between the composition and loading of cranial joints. We created a 3D finite element model of the cranium of an individual of Varanus exanthematicus, a species with intermediate levels of kinesis for which comparative feeding data is available. Intracranial joints were modeled as flexible interfaces between bones and material properties of those joints could be assigned independently. Muscle force magnitudes were calculated from physiological cross‐sectional area estimates and oriented toward mandibular attachment sites. These forces and orientations mimicked feeding behavior. For each simulation, we changed the properties of the joint material to (1) cartilage, (2) ligament, and (3) bone, which represents a fused morphology. Comparisons among these models show lower overall strain energy when joints are modeled using ligament and cartilage, whereas joints modeled with bone showed areas of high stress concentrations. Modeling joints as non‐bony soft‐tissues produced deformations that more closely approximated in vivo feeding kinematics. This concordance affirms the model's ability to recreate feeding mechanics; therefore, the methods used to develop the varanid model can be used to more accurately model the feeding mechanics of fossils, which cannot be directly checked against in vivo feeding kinematics.

Support or Funding Information

National Science Foundation IOS 1457319
Comparative Anatomy and Biomechanics of the Feeding Apparatus of Parrots (Aves: Psittaciformes)
Authors: Cost Ian N. , Middleton Kevin M. , Witmer Lawrence M. , Echols M. Scott , Holliday Casey M.
Published: November 2023

Parrots occupy varied dietary niches that require an agile, mobilized but sturdy feeding apparatus. Cranial kinesis, flexibility among intracranial joints, has a central role in the unique feeding apparatus of parrots. Parrots possess a highly mobile, streptostylic quadrate that drives the kinetic assemblage by moving the rod‐like pterygoids. The pterygoids, in turn, act as levers and rostrally actuate the tall, thin palatine bones which possess a robust articulation with the rostrum. This palatomaxillary system of articulation rotates the rostrum about the synovial craniofacial hinge, leading to extensive prokinetic movement between the frontal and nasal bones. In this study we analyze the size and orientations of jaw and palatal muscles as well as the biomechanical environment of the kinetic palate of five species of parrots: Psittacus erithacus, Eclectus roratus, Brotogeris jugularis, Strigops habroptilus, and Nestor notabilis. We compared feeding apparatuses across species using 3D data derived from muscle resultants, 3D modeling, and finite element analysis to identify shared patterns of cranial form and function. We digitally mapped jaw muscles onto the models, calculated 3D moments about multiple joints using BoneLoad, and evaluated force propagation through and strain patterns in the models using finite element analysis. Quantitative muscle orientations were visualized and compared using 3D spatial orientations. These data show relationships between muscle orientations and loading of cranial elements during feeding behaviors and highlight the morphological and dietary diversity of the parrot feeding apparatus. We found a wide diversity of orientations among parrot cranial muscles, however, jaw and palate muscles in the parrot species studied are highly specialized for cranial kinesis. Our results show that parrots have appreciably altered the conservative environment of the feeding apparatus by radically expanding their range of cranial kinesis. Understanding how parrot joint articulations work in a highly mobilized system can be applied to skull biomechanics, behavior, and our understanding of avian cranial kinesis. This new understanding will be applied to parrots of various morphologies with similar diets in future studies to assess the abilities of novel morphologies in performing similar tasks. More broadly, these new methods can be applied across other vertebrates to assess morphological performance capabilities of biomechanical tasks.

Support or Funding Information

We thank the National Science Foundation (NSF IOS‐1457319), Missouri Research Board, Missouri Research Council, and the Department of Pathology and Anatomical Sciences for funding this research.
Telequantum Medical Technologies Taught, Practiced, and Assessed by Medical Students in a Millennial Anatomy Lab Developing Telemedicine Skills
Authors: Benninger Brion , Chen Wilson
Published: November 2023

Introduction

Medical school basic science curriculum is formally attempting a facelift from traditional curricula better preparing trainees to succeed in todays changing healthcare arena. Evolving technologies and patient care have created logical behavioral changes for both patient and physician. Teleporting units have continued to develop and evolve into better quality audiovisual transmissions with friendlier interfaces. Third/fourth year medical students(MS) and junior residents arrive with no or minimal formal training skills interacting with teleporting, tele‐emotion and telemedicine technology skills(TTS).

Objective

Telequantum medical technologies(TqMedTech) successfully integrated into a millennial anatomy lab resulting in TTS.

Methods

TqMTech were taught, used and assessed in a millennial anatomy lab during 1st year anatomy course. MS(n=103) participated with the following TqMTechs, Sectra cross‐sectional and 3D visualization table, PercuVision catheterization, SKY‐EYE camera system, Ultrasound Triple feedback technique, finger probe and 3D/4D ultrasound, robotic OPUS ultrasound simulator, C‐Link and novel scopes, Otoscope teleporting and Google Glass.

Results

MS successfully used all technologies as revealed by timed hands‐on assessment results(>80%) from anatomy lab examinations. Likert scale scores ranged 3.8–4.5 from questions addressing instruction, hands‐on time and perceived importance.

Discussion

Telemedicine is growing and appears to have an invaluable contribution in today's health care system. Ideally suited for use between 7pm–7am weekdays and weekends when virtually all family practices are closed. MS appear to have the acumen to integrate TTS during basic science curriculum. MS incorporated TqMTech, skills, education and clinical benefits to improve.

Conclusion

This pilot study successfully integrated telequantum medical technologies, skills and clinical uses demonstrated by MS in a millennial anatomy lab.

Support or Funding Information

With the cordial support of Jim & Heather McDaniel and Dr. Jeff Heatherington, as well as the gracious donors who donated themselves for science.
A Formal Interprofessional Ultrasound Curriculum between Medical and Physical Therapy Students in the First Year Gross Anatomy Course
Authors: Gibbs Christopher M , Knight Jennifer A , Van Nuland Sonya E , Bhagra Anjali , Hellyer Nathan J , Langley Natalie R
Published: November 2023

Ultrasound has been used more frequently in the anatomical sciences to reinforce core anatomy concepts in the classroom and introduce commonly applied imaging technologies encountered in a clinical setting. Interprofessional Education (IPE) is being incorporated into health sciences training as a learning model for real world interactions. The primary objective of the current study was to determine the impact of an IPE ultrasound curriculum on students' anatomy and ultrasound knowledge, as well as attitudes towards interprofessional collaboration. We hypothesized that students who participated in an IPE experience would have improved recall of anatomical and ultrasound concepts as well as improved attitudes and perceptions towards IPE when compared to students who did not participate in an IPE session. First year medical students (MD, n = 40) and first year physical therapy students (PT, n = 25) were randomly assigned to PT‐only, MD‐only, or mixed PT‐MD ultrasound instruction groups studying the shoulder. Students were assessed using an anatomy and ultrasound knowledge test and University of the West of England Interprofessional Questionnaire (UWEIPQ) prior to and following the session. The results of this study suggest that while ultrasound instruction significantly improves ultrasound post‐test scores when compared to pre‐test scores regardless of group assignment (PT‐only: p < 0.001; MD‐only: p = 0.007; PT‐MD: p < 0.001), learning in an interprofessional PT‐MD group did not significantly impact knowledge recall of ultrasound concepts when compared to non‐IPE groups. Interestingly, students in PT‐MD groups had significantly higher anatomy post‐test scores when compared to the MD‐only groups (PT‐MD post‐test = 93.2%; MD‐only post‐test = 84.1%; p = 0.041), but not when compared to the PT‐only groups. Additionally, the results of the UWEIPQ are consistent with the impression that students who participate in an IPE experience are more likely to be cognizant of inherent biases in the interactions between different health professionals as well as demonstrate increased confidence in their interprofessional relationships. In conclusion, our study reinforces that IPE programs should quantify knowledge recall in order to assess the effectiveness of a specific program. Furthermore, such endeavors should assess important competencies including communication, teamwork, and interdisciplinary respect that are necessary to succeed in a multidisciplinary health care team.

Support or Funding Information

Department of Anatomy, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, MN; Social Science and Humanities Research Council, Government of Canada
Physical Models Dominate: The Pirate Patch Study
Authors: Wolak Liliana K. , Pukas Giancarlo A. , Zheng Yu Hang , Norman Geoffrey R. , Monteiro Sandra D. , Wainman Bruce C.
Published: November 2023

Prior studies have shown physical models are superior learning tools compared to interactive‐two‐dimensional models (3D images on 2D surfaces) and key views of the specimen when tested on a cadaver. Additionally, we have shown that haptic feedback and transfer‐appropriate processing do not contribute to the superiority of the physical model. In the current study, we explored the role of stereopsis in the same context. During the learning phase, we compared a condition with both eyes uncovered to a condition with the non‐dominant eye covered, removing stereopsis. The results further validate that physical models are superior to the interactive 2D model. Participants in the physical model group performed significantly better than those in the interactive 2D group on structure identification on the cadaveric pelvis (64% vs 47%, p < 0.001). Furthermore, the use of two eyes was superior to one eye (62% vs 49%, p < 0.01). However, there were no interactions, suggesting that stereopsis had no differential effect in the 2D model. Ultimately, these results further support the superiority of the physical model for anatomy education.
Tutor Group Assessments (TGAs): Criteria Based Monitoring of Medical Student Performance, Participation and Behavior in Small (Tutor) Group Sessions in a Problem Based Learning Curriculum
Authors: Viscomi Natalie S , DiLalla Lisabeth F , Henry Nancy , Clough Rich W
Published: November 2023

Southern Illinois University School of Medicine developed and initiated a Problem Based Learning (PBL) curriculum 27 years ago, in 1990, for ½ of the medical school class. Owing to success, this approach was expanded to the entire class in year 2000 and we have maintained the PBL approach to date. In our theme‐based PBL curricular units, students are placed into faculty‐facilitated small groups of 6–8 (~Tutor Group, TG) for the entirety of any particular Unit (approx. 3 months). Students, and their faculty tutor, meet 3h/3x/week across approximately 2 years to develop learning issues, discuss clinical and basic science topics, generate and refine differential diagnoses, etc., and learn about the process of doctoring through electronic simulated patient cases. Participation of each student in TG is essential and expected. Moreover, participation is highly valuable to inculcate professionalism, seek, gain and offer knowledge, develop communication skills, develop diagnostic reasoning, etc. Accordingly, we have developed an assessment tool to monitor student performance in the TG process. Periodic TGAs (Tutor Group Assessments) allow students to both provide and receive feedback about performance and other attributes of TG participation. Initially, our TGAs were open‐ended forms that gave both the students and the tutor a forum to discuss any aspect of the tutor group process. This resulted in inconsistencies between groups and curricular units and complacency in the process, and it sometimes left students unsure of what is expected from them. In an effort to standardize TGAs and provide a more consistent method of evaluation between the different groups and units, we created a rubric style TGA form to evaluate the most critical components of tutor group performance. We modeled our new TGAs after the ACGME's rubrics for residency milestones because we wanted students to more accurately and objectively characterize their own, and their peers', performance in TG. This style of assessment is more robust than before because it combines a Likert scale with subjective comments, providing objective context to assessment categories for students and faculty (tutors) to evaluate performance. In conclusion, since adopting the new TGA approach, our students are now more aware of their specific strengths and/or deficiencies (apart from test scores) and can use the TGAs to better target improvements in their group performance. The new TGA also provides a more consistent longitudinal measurement of student performance throughout the curriculum and provides valuable insights into student behavior over time.

Support or Funding Information

Supported by SIU School of Medicine
Improved Medical Student Perception of Ultrasound Using a Paired Anatomy Teaching Assistant and Clinical Instructor Model
Authors: Smith Jacob , Kendall John , Royer Danielle
Published: November 2023

BACKGROUND

Ultrasound (US) is an important component of modern clinical practice, creating the need for US exposure and training during medical school. Incorporating US into medical education allows trainees to develop fundamental skills that help ensure that they are adequately prepared for residency.

GOAL

This study describes and evaluates a new teaching model for US training during medical gross anatomy at the University of Colorado School of Medicine.

METHODS

During gross anatomy, students participated in five 1‐hour, small‐group, peer scanning sessions: introduction to US, musculoskeletal, cardiothoracic, abdominopelvic, and head and neck. In the 2014 academic year (AY), US sessions were led by a single clinical instructor; in the 2015 AY, the sessions used a new teaching model comprised of an anatomy teaching assistant (TA) paired with a clinical instructor. Both cohorts (N = 184 each) were invited to complete an IRB‐exempt anonymous questionnaire with five Likert‐scale items (1 = strongly disagree; 4 = strongly agree) measuring perceptions of US and anatomy. Ratings were compared using the Mann‐Whitney U test. The 2015AY questionnaire also solicited student views on the effectiveness of the anatomy TAs using three Likert‐scale items (1 = strongly disagree; 5 = strongly agree).

RESULTS

Response rates were 89% (2014AY) and 80% (2015AY). Ratings for “US advanced my ability to learn anatomy” increased significantly from 2.91±0.77 in 2014AY to 3.35±0.68 in 2015AY (p<0.0001). Similarly, responses to the statement “Incorporating US increased my interest in anatomy” increased significantly from 3.05±0.84 in 2014AY to 3.50±0.71 in 2015AY (p<0.0001). There was a significant increase from 3.36±0.63 in 2014AY to 3.54±0.53 in 2015AY for the statement “US is relevant to my current educational needs” (p=0.015), and also a significant increase in students agreeing that US training should start in Phase I (2014AY = 3.36±0.71, 2015AY = 3.56±0.59; p=0.010). However, student responses for “US is a valuable tool for my future medical practice” were not significantly different between cohorts (2014AY = 3.75±0.52, 2015AY = 3.73±0.46; p=0.536). 86% of students who experienced the new teaching model agreed or strongly agreed that the anatomy TAs were sufficiently proficient in US (mean = 4.24±0.86), 85% that the TAs enhanced their understanding of anatomy during US (mean = 4.18±0.86), and 85% that TAs were a valuable aspect of the US sessions (mean = 4.23±0.89).

CONCLUSIONS

The significant improvement in student perception of US as a tool to enhance anatomy education is attributed to the new teaching model utilizing anatomy TAs paired with clinical instructors. Furthermore, medical students viewed the TAs as knowledgeable in both anatomy and US, and considered them a valuable addition to the US sessions. The anatomy TA‐clinical instructor pair is a simple yet powerful teaching model that can improve student learning of anatomy through US.
Teaching Chemical Biology at a Primarily Undergraduate Institution
Authors: Danowitz Amy M
Published: November 2023

Chemical biology is a cutting edge subject that is constantly turning out new advances. Many of these advances are particularly interesting as they involve interdisciplinary science and give rise to novel solutions to traditional problems. As chemical biology becomes more established as a field, classes teaching the important concepts of the discipline are needed. Herein is described a chemical biology course that is offered at a primarily undergraduate institution (PUI) and that is aimed at third and fourth year students majoring in chemistry, biochemistry, and biology. The material for this course is derived entirely from the primary literature and follows current trends in the field. Currently, the course is divided into four units that reflect four important topics in chemical biology: observing and characterizing protein‐protein interactions involved in transcription, modifying genes and gene expression, bioorthogonal tag and capture studies, and studies involving bacterial quorum sensing. These topics are used to give students a thorough grounding in the types of questions chemical biologists ask, and serve as a basis for introducing students to the techniques that are central to chemical biology. A blended lecture/seminar style is used in this course to accomplish three major course goals: introducing students to relevant techniques in chemical biology, increasing students' ability to read and analyze the current chemical biology literature, and increasing students' ability to present and discuss science with their peers. A discussion of the details of the course (including specific topics covered, assignments given, and grading metrics), and the tactics that have been employed in bringing a traditionally graduate‐level course to an undergraduate setting will be given. Data gathered from student performance and feedback indicate that chemical biology is a valuable and enjoyable course that can be successfully taught to undergraduates at PUIs.
Using an Alternate Reality Learning Experience (ARLE) to Teach Molecular Biology Techniques and Concepts in a Genetics Laboratory
Authors: Clauson‐Kozina Cheryl L. , Borden Jeff D. , Rheinschmidt Steven , Kunzweiler Greg
Published: November 2023

Alternate reality learning experiences (ARLEs) are curriculum integration (sometimes called interdisciplinary or multi‐disciplinary) events that give participants a chance to learn via activities that provide real‐life experiences in a parallel, but fictional setting. In the ARLE, “The Trial of the Century,” students from many disciplines were brought together, including: biology, criminal justice, cyber forensics, public relations/professional writing, sociology and theater courses to play the various roles. The trial involved a fictitious crime with students serving as witnesses, news reporters, attorneys, public relations professionals, jury members, criminals and, of particular interest, forensics experts. The goal of this research was to measure the impact of an ARLE on Fundamentals of Genetics laboratory students in comparison to Fundamentals of Genetics laboratory students that did not participate in the ARLE. The participating students were tasked with analyzing forensic data (DNA evidence) from a crime scene and four “suspects” following restriction digestion and gel electrophoresis of the samples. All students in the ARLE section of lab wrote an “evidence report” and all ARLE students assisted in preparing those students that wished to act as expert DNA witnesses during the mock trial. Five students were deposed by the prosecution or the defense teams prior to the trial. On the day of the trial, three students acted as witnesses for either the prosecution or the defense team and presented the gel electrophoresis data to a jury of their peers. Those students that were not in the ARLE group completed the same lab activity (restriction digestion and gel electrophoresis), but completed a lab report in lieu of an evidence report and trial participation. This research aimed to determine the value of the ARLE approach in impacting: 1) student understanding of the course material, 2) student confidence in presentation of scientific information to peers in both written and oral communications, and 3) student desire to pursue a career in science.
Integration of literature‐based activities to enhance the learning of content, scientific process, and quantitative analysis in biochemistry courses
Authors: Masuda Hisako
Published: November 2023

Upper level biochemistry courses are a gateway to many different career paths. Students enroll in these courses in preparation for graduate school, professional school or immediately joining the work force. Regardless of their career interests, the application of knowledge into practice is important, but can be challenging to some students.

At Indiana University Kokomo, Biochemistry I and II are the only major specific courses that students complete before their senior seminar course which requires students to prepare a mock research proposal. Therefore, one of the learning goals of the Biochemistry courses is to practice the higher order objectives in Bloom's taxonomy of learning, such as evaluation and synthesis of knowledge. In previous years, students expressed difficulties interpreting quantitative data, understanding experimental approaches and reading and finding appropriate research articles, which are all required skills in order to construct a proposal.

Several in‐class and homework activities to practice such skills were developed. In collaboration with the science librarian at IUK, flipped lessons to effectively identify articles using NCBI and other databases were developed and tailored for students who lacked any experience in reading and writing scientific articles. Group discussions on a protein purification paper were followed by individual assignments to search for and comprehend articles describing methods such as protein purification, enzyme kinetics, and regulation. Students learned various aspects of a specific protein that they chose at the beginning of the semester. In particular, a protein with a known single amino acid substitution that leads to a genetic disease was suggested as a topic for selection to pique student's interest. Students presented their finding as a poster presentation at the end of semester. In the second semester, students were asked to formulate case study problems based on the reading to lead a discussion on each metabolic pathway. In parallel, students proposed and conducted a simple enzyme activity assay for the uncharacterized protein in laboratory sessions. These activities seemed to have reinforced the lecture material. Moreover, their understanding of the experimental approach and data analysis seemed to have improved. Positive effects of such activities on student learning, as well as current challenges will be discussed.
Modeling Interdisciplinary Collaborations Through a Course‐Based Undergraduate Research Experience (CURE)
Authors: Roberts Rebecca , Koeppe Julia , Price Simara , Allwein Benjamin , Anderson Trevor , Daubner Susan Colette , Irby Stefan , Mills Jeffrey , Pikaart Michael , Craig Paul
Published: November 2023

Interdisciplinary collaborations are often essential to answer multi‐faceted questions, yet they present with many challenges such as understanding the information, methodologies, and norms of another field and effective communication between team members. We must begin to provide young scientists with the skills necessary for success as the call for more interdisciplinary science expands. We have modelled an interdisciplinary collaboration at the undergraduate level through a Course‐based Undergraduate Research Experience (CURE). Students in upper‐level Biochemistry and Structural Biology courses collaborated to assign functions to proteins “of unknown function” in the Protein Data Bank (PDB). The Structural Biology students used bioinformatics tools including the ProMOL plugin to the PyMOL molecular graphics environment, along with BLAST, Pfam, and Dali to predict protein functions. In parallel, the Biochemistry students expressed and purified the proteins and carried out in vitro testing, informed by the in silico‐predicted enzyme function. Students came together in cross‐disciplinary teams throughout the project to share progress, explain their discipline‐specific methodologies, and discuss next steps. They each presented an oral progress report on the entire project, which required that they not only understand their own work but that of their collaborators. Interdisciplinary teams presented final posters to the campus community and students prepared future directions documents. We had students fill out a pre‐ and post‐assessment. The assessment had two foci: the effectiveness of the cross‐course collaboration model and assessment of content learning. While a second iteration of the CURE will be necessary for a full statistical analysis, we see a trend that students learned the information and methodologies of both their own discipline and that of their collaborators. Moreover students appear to have increased their ability to communicate to and learn from their collaborators.

Support or Funding Information

This project is supported by NSF IUSE 1503811.
Transition to a Course‐based Undergraduate Research Experience (CURE)
Authors: Craig Paul Alfred , Mills Jeffrey L. , Roberts Rebecca , Pikaart Michael , Daubner Colette , Irby Stefan , Anderson Trevor
Published: November 2023

It will always remain a goal of an undergraduate biochemistry laboratory course to engage students hands‐on in a wide range of biochemistry laboratory experiences. In 2006, our research group initiated a project for in silico prediction of enzyme function based only on the 3D coordinates of the more than 3800 proteins “of unknown function” in the Protein Data Bank (PDB), many of which resulted from the Protein Structure Initiative. Students have used the ProMOL plugin to the PyMOL molecular graphics environment along with BLAST, Pfam, and Dali to predict protein functions. As young scientists, these undergraduate research students wanted to see if their predictions were correct and so they developed an approach for in vitro testing of predicted enzyme function that included literature exploration, selection of a suitable assay and the search for commercially available substrates. Over the past two years, a team of faculty members from seven different campuses (California Polytechnic San Luis Obispo, Hope College, Oral Roberts University, Rochester Institute of Technology, St. Mary's University, and Ursinus College) have transferred this approach to the undergraduate biochemistry teaching lab as a Course‐based Undergraduate Research Experience. A series of ten course modules and eight instructional videos have been created (www.promol.org/home/basil‐modules‐1) and the group is now expanding these resources, creating assessments and evaluating how this approach helps student to grow as scientists. The focus of this presentation will be the logistical implications of this transition on campuses that have different cultures, expectations, schedules and student populations.

Support or Funding Information

This project is supported by NSF IUSE 1503811.
Approaching Undergraduate Research with Students who are Deaf and Hard of Hearing
Authors: Gehret Austin U. , Trussell Jessica W. , Michel Lea V.
Published: November 2023

An undergraduate research experience can provide a unique opportunity for students to learn and grow as scientists; when positive, this experience is often transformative in helping motivate students to pursue post‐graduate degrees and/or careers in STEM. Conversely, a negative research experience can sour a student's opinion of research, propagate misconceptions of graduate school, and turn students away from careers in STEM. Negative research experiences can be equally as devastating for faculty mentors and likely result in refusal to mentor future research students. Although d/Deaf and hard‐of‐hearing (DHH) students learn differently than their hearing peers, their experiences in undergraduate research mirror that of their hearing counterparts. Up until recently, most researchers have focused on how to understand and improve the learning environments for DHH students in the classroom. Here, we discuss several challenges and strategies derived from survey results associated with the undergraduate research experience for DHH students who were actively involved in undergraduate research. The challenges and strategies outlined aim to shape future mentoring and training efforts of DHH students with the goals of enriching their research experiences, increasing their engagement with research, and improving their pursuit of graduate STEM degrees and/or careers in STEM.

Support or Funding Information

This research was supported by the Camille and Henry Dreyfus Special Grant Program in the Chemical Sciences (Awarded to L.V. M.)
A Novel Protein Interaction Between The Cardiac Desmosome and COP9 Signalosome Complex Reveals A New Mechanism Underlying Sudden Death
Authors: Sheikh Farah , Liang Yan , Lyon Robert , Pellman Jason , Mezzano Valeria , Gu Yusu , Dalton Nancy , Lee Mong‐Hong , Iwakuma Tomoo , Nigam Vishal , Peterson Kirk
Published: November 2023

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic based cardiomyopathy, characterized by ventricular dysfunction, fibrofatty replacement of the ventricle and ventricular arrhythmias leading to sudden cardiac death in young people. ARVC is termed a “disease of the desmosome”; however, limited information exists on how desmosomal protein dysregulation/loss triggers ARVC. To identify novel protein targets that impact desmosomal biology and the desmosomal disease, ARVC, we performed a yeast‐two‐hybrid screen using the desmosomal gene, desmoplakin (DSP) as bait to screen an adult human heart cDNA library. We identified subunit 6 of the COP9 signalosome (CSN6) as a novel DSP‐interacting protein, localizing at the cardiac intercalated disc (ICD) in both adult mouse and human heart. Well‐known functions of CSN are to regulate protein degradation via ubiquitination; however, the role of CSN6 in the heart and ARVC has not been defined. We show that CSN6 levels are dramatically reduced at the ICD in a mouse model of ARVC (cardiac‐specific DSP knockout mice (DSP‐cKO)) and a human ARVC patient harboring a novel DSP and known plakophilin‐2 mutation. Yeast‐two‐hybrid assays revealed that this novel DSP mutation in the ARVC patient specifically abrogated binding of DSP to CSN6. DSP‐cKO heart also displayed underlying protein degradation defects associated with loss of CSN6, including a striking accumulation of autophagy markers and autophagosomes at the ICD. Importantly, generation of novel cardiac‐specific CSN6 knockout models using the alpha‐myosin heavy chain (MHC)‐Cre (CSN6‐cKO) and alpha‐MHC‐MerCreMer (CSN6‐iKO) mouse lines revealed that loss of CSN6 in mice was sufficient to elicit premature death, which was associated with early ventricular depolarization delay and a biventricular form of cardiomyopathy, reminiscent of ARVC. Ultrastructurally, CSN6‐iKO hearts displayed loss of cardiac architecture associated with an accumulation of autophagosomes at the ICD, similar to our mouse model of ARVC. At the molecular level, CSN6‐iKO heart exhibited early loss of DSP (prior to heart dysfunction) and recapitulated the protein degradation defects observed in our mouse model of ARVC. We highlight the importance of CSN6 at the cardiac desmosome in maintaining desmosomal protein turnover (“desmophagy”), and suggest that loss of CSN6 and desmosomal protein turnover as new underlying mechanisms driving ARVC and sudden death.

Support or Funding Information

F.S. is supported by grants from National Institutes of Health (NHLBI), American Heart Association and Tobacco Related Disease Research Program.