bluuebunny/crossref_metadata_2025_split huggingface dataset:
Student‐developed learning resources for the anatomical sciences (719.12)
Authors: Eastwood Jennifer , Doubleday Alison 
Published: June 2021

The process of creating learning resources provides students with opportunities to explore information, create study aids, and identify learning gaps prior to an examination. We present two examples of activities for the anatomical sciences that engage students through resource building and provide formative assessment opportunities.At UIC first‐year dental students produce video narrations in the anatomy laboratory. Videos are created on instructor‐controlled devices and viewable online via a password‐protected link on a secure site. Students review videos and instructors correct inaccuracies in subsequent classes. All students and instructors can comment on videos within the secure site. Students find that the process of taking videos helps them organize their thoughts and students can better prepare for the laboratory by viewing other groups’ videos.At OUWB, first and second year medical students develop practice practical questions in histology lab. Students select and capture images from virtual histology slides and use presentation software to develop image‐based questions. The instructor compiles, corrects, and posts slides for the class. Misconceptions can be quickly identified and addressed with students prior to summative assessment. Students find these practice questions valuable and frequently approach the instructors with questions generated from the use of this resource.
Students as anatomy peer teachers ő a new course to develop teaching skills in a flourishing community of learning (721.11)
Authors: Barash Alon , Reis Shmuel , Dickman Nomy , Biswas Sima , Karasik David 
Published: June 2021

Objective: In response to shortage of doctors in Israel, a new medical faculty was set up at Bar Ilan University in Galilee. Basic Science and clinical teachers were recruited overseas and locally, but junior faculty, such as teacher assistants (TA), were difficult to find in this remote locale. Thus, a peer teacher course for students was designed to develop anatomy teaching skills.Method: Students participated in the 5‐day Teaching Assistant course, set up by the departments of Medical Education &amp; Anatomy. 20 preclinical students attended the course. Topics covered included the basics of didactics and pedagogic approaches, small group teaching skills, and advanced practical skills in cadaveric dissection.Results: On the Likert scale the overall rating for the course was 3.85. Learning prosection and anatomy demonstration skills scored 4.3 and 4.15, respectively. TA Students appeared at ease in the dissecting room amongst their peers. They were able to prepare and lead a Case‐Based Learning session with more confidence.Conclusion: Students as peer teachers can make a great contribution to the teaching faculty. Personal gain in terms of confidence, focus and motivation are at least as important as practical dissection and teaching skills. Among the lessons learned for the future are: a need to provide a radiological hands‐on experience (e.g. CT, MRI &amp; US) and the necessity to emphasise on ethical values, since these TAs will be facing such questions from their peers.
Through the eyes of future medical student teachers: the growing role of teaching assistants in medical education (721.13)
Authors: Laitman Benjamin , Maffucci Patrick , Shaw Phyllis , Mak Ki , Eddleman Keith , Lerner Susan , Reidenberg Joy , Laitman Jeffrey 
Published: June 2021

As much of the education of medical students in their clinical years is now conducted by residents, it is becoming increasingly important that medical students at all levels learn the importance of various aspects of teaching, from in‐class instruction to conducting evaluations. The following report will discuss the changes implemented in our first year medical school “Structures” course, a new entity at the Icahn School of Medicine at Mount Sinai consisting of Gross Anatomy, Histology, and Embryology.Approximately 70 TAs take part in teaching for this course, with roles ranging from organizing review sessions, to assisting in the preparation of exams and in‐lab assessment of students. In an effort to integrate TAs more into the teaching process, Structures TAs became responsible for organizing weekly review sessions, comprehensive midterm and final exam review sessions, and, especially of note, became a larger part of the course’s evaluations. Over the past few years, the anatomy course at Mount Sinai has adopted an assessment strategy called “table conferences” in place of practical examinations. Traditionally, in these table conferences, a group of five or six students are questioned about aspects of their dissection, both practical and conceptual, by an evaluator. While historically done by faculty members, this year, in Structures, Senior TAs became responsible for conducting the majority of these table conferences.Overall, we found that increased TA involvement in all aspects of the course has been an overwhelmingly positive experience for students, TAs, and faculty alike. It is our hope to completely shift table conferences to Senior TAs and to further increase the involvement of both Senior TAs and second year TAs in the course in the future. We believe participating in this TA paradigm will play a major role in shaping our students as educators.
Use of Peer Instruction in an interactive medical histology laboratory (721.16)
Authors: Balch Maria , Hawes Sara , Borges Nicole , Ream Larry 
Published: June 2021

Our previous study exploring the use of an Audience Response System (ARS) to promote active learning and group interactivity in a medical school histology laboratory determined the method to be effective in stimulating discussion, enhancing peer interaction, and applying the material. Separately, the instructional strategy known as Peer Instruction (PI) provides a model for student interaction using a controlled questioning process. Upon implementation of PI, published studies report increases in students’ conceptual reasoning and quantitative problem solving skills. Our study seeks to further develop the concept of ARS in a histology course by implementing the use of PI in a medical histology laboratory setting.Presenting clinically‐relevant questions associated with microscope images using the PI model provides a system through which visual learning, pattern recognition, group interaction, and clinical application are simultaneously addressed. The benefits of Peer Instruction Laboratory Sessions (PILS) are evaluated by obtaining individual student assessments from the PILS using ARS data and comparing them to corresponding student laboratory exam scores. This data comparison thus helps to quantify the impact of PILS on visual application and long term material retention.
Methods used in the gross anatomy lab to facilitate learning by first‐year students in a new Physician Assistant Program (722.1)
Authors: Syed Mohsin , Akhter Noor , Hayes Helen , Davies David 
Published: June 2021

The University of Arkansas for Medical Sciences opened a new Physician Assistant (PA) Program in its College of Health Professions in the summer of 2013 with 26 students. This small class size ensured more individualized faculty‐student interaction that greatly facilitated the learning. Unlike most gross anatomy courses that use a regional approach, the PA students were taught with a system‐based approach. During the weekly 3‐hour lab sessions, anatomical structures were demonstrated on four prosected cadavers. Four second‐year medical students were enlisted to prepare these prosections, each of which required about 100 hours of dissection time. During scheduled lab sessions the PA students identified relevant structures using the prescribed atlas and with the help of 3 faculty members. A dedicated lab area (740 sq. ft.) was designated for the study of anatomical models, bones, previously dissected regional specimens and cross sections. A lab incentive program (LIP) was introduced to keep the students focused. Four computers loaded with anatomical tables, charts and images were accessible in the lab for self‐directed study. At the end of each organ system unit, major concepts, important structures and their clinical relevance were reviewed in the lab before proceeding to another organ system. Briefly, the effectiveness of these lab‐teaching strategies is quantitatively evidenced by the strong performance of students on examinations.Supported by: Dept. of Neurobiology and Developmental Sciences, UAMS
The mismatch repair pathway maintains genomic stability in human pluripotent stem cells (735.1)
Authors: Lin Bo , Heinen Christopher 
Published: June 2021

The mismatch repair (MMR) pathway repairs polymerase errors to help maintain genome stability and prevent tumorigenesis. In addition to repair, MMR is also involved in the induction of cell cycle arrest and apoptosis in response to certain forms of DNA damage. The role of MMR in preserving genome integrity in human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) has not been previously examined. Accumulation of mutation in pluripotent stem cells (PSCs) would be detrimental to the developing organism so we hypothesize that these cells have a robust MMR pathway. We find that ESCs and iPSCs express high levels of MMR proteins and demonstrate strong mismatch repair activity. PSCs are also hypersensitive to DNA damage, showing a high level of apoptosis after treatment with a DNA alkylating agent that is MMR dependent. However, the specific response observed differs from that seen in HeLa or other cancer or primary cells. In these other cells, a permanent G2/M cell cycle arrest is induced in the second cell cycle after damage, however, PSCs directly undergo apoptosis in the first cell cycle. Interestingly, there is no activation of cell cycle checkpoint kinases CHK1 or CHK2, although phosphorylation of H2AX is increased. This more immediate apoptotic response suggests a separate molecular mechanism by which the MMR pathway can induce a response to DNA damage in PSCs.Grant Funding Source: Supported by NIH CA 115783 and CT Stem Cell 13‐SCB‐UCHC‐06
Investigating the role of DNA repair enzymes in DNA replication and recombination (735.3)
Authors: Speed Clayton , Wiese Claudia , Parplys Ann , Hatherill J. Robert 
Published: June 2021

Hypothesis: A mutant DNA repair protein (DSS1) will be unable to facilitate Homologous Recombination Repair (HRR) within osteosarcoma cell lines. Also depletions in the DNA repair enzyme RAD51AP1 will hinder the cells ability to rescue stalled replication forks and repair replication associated Double Strand Breaks (DSB), along with causing a S‐phase check point defect in cells. In this study DNA damage was induced via exogenous and endogenous stresses, to test the fitness of cells. To gain insight into the role DNA repair proteins play after DNA damage, mutant osteosarcoma cell lines were exposed to high intensity X‐rays. The ability for cells to faithfully repair double strand breaks was assessed by fluorescent activated cell sorting and immunocytochemistry. The levels of S phase check point activation by the phosphorylation of check point kinase1 was assessed by infrared Western blot analysis. We also depleted the DNA interacting enzymes and studied the effects on DNA damage, DNA replication, and the cell cycle. It was concluded that human RAD51AP1 expressed in chicken DT40 cells caused a checkpoint defect, leading to the cells inability to arrest after damage. This phenotype has been recently validated in human cell lines. The overall goal of this research was to determine the roles DSS1 and RAD51AP1 play in DNA repair and the interaction with other recombination mediators and effectors.Grant Funding Source: NSF ATE DUE 1205059
Mapping modified cytosines in the epitranscriptome of Trypanosoma brucei using sodium bisulfite sequencing (745.1)
Authors: Ackerman Sarah , Chen Leanne , Mandarano Alexandra , Valentine Erika , Militello Kevin 
Published: June 2021

This study characterized the presence and location of modified cytosines in the tRNAs of Trypanosoma brucei, a parasitic protozoan. We are interested in these modifications, specifically 5‐methylcytosine (5mC), as a first step in characterizing the epitranscriptome. We used sodium bisulfite sequencing to determine the location of modified cytosines in procyclic form tRNAAsp(GUC), tRNAGly(GCC), tRNAVal(AAC), and tRNATyr(GUA). Our data show that all analyzed tRNAs have 1 to 4 modified cytosines. Each tRNA has a modification at C48 in the TψC stem and there is partial modification T C40 present in tRNAGly(GCC) in the anticodon stem. There are no modifications at C38, which is a common site in higher eukaryotes. tRNATyr(GUA), the only spliced tRNA in T. brucei, possess the same cytosine modification pattern in both unspliced and spliced molecules. In addition, the intron did not contain any cytosine modifications. Thus methylation can occur before splicing and it is unlikely that methylation is involved in splicing. We are now examining bloodstream form parasites for potential changes in methylation sites or levels. We are also determining if there is a correlation between the tRNA levels and modification levels. Elucidating the presence of these modifications has developed our understanding of the epitranscriptome in T. brucei and we hope to determine the global distribution and purpose of these modifications.Grant Funding Source: NIH R15AI074035
Investigating the targeting and regulation of Ded1, a DEAD‐box ATPase, in returning repressed mRNAs to translation (749.9)
Authors: Hilliker Angie 
Published: June 2021

Translation regulation is important, especially during stress, in neurons, and in early development, where many mRNAs are stored in translationally repressed states. These repressed mRNAs can be returned to translation, but this process is poorly understood. We have previously shown evidence that the RNA helicase, Ded1, performs two sequential functions to return a repressed mRNA back to translation in an ATP‐dependent manner. First, Ded1 promotes the formation of a “pre‐48S mRNP” that includes the initiation factors eIF4F and Pab1. Then, Ded1 hydrolyzes ATP, allowing the mRNA to become translated. We hypothesize that Ded1 acts as an ATP‐dependent switch to return mRNAs back to the translating pool.We are investigating how Ded1 forms this pre‐48S intermediate by investigating the importance of its interaction with translation initiation factors and with the mRNA. Additionally, we are exploring the role of post‐translational modifications on the function of Ded1.
Function analysis of the different S6Ks isoforms (752.8)
Authors: Pavan Isadora , Ferreira Flávia , de Freitas Lidia , Tavares Mariana , Simabuco Fernando 
Published: June 2021

mTOR signaling pathway has been related to several human diseases and disorders, including obesity, diabetes and many types of cancer. In the cell, mTOR signaling is responsible to induce cell growth and metabolism upon activation by signals from nutrients processing, such as insulin, ATP and amino acids. S6Ks, the known kinases of ribosomal small subunit S6 protein, are effectors of mTOR response. S6K family is composed of two genes (encoding S6K1 and S6K2) and different isoforms from alternative translation initiation (p70‐S6K1, p85‐S6K1, p54‐S6K2, p56‐S6K2) and alternative splicing (p31‐S6K1). The main function of S6Ks, upon activation, is to lead to increased protein synthesis. Nevertheless, one of the main questions in this field is to address the specific roles of the different S6Ks isoforms. In this study, we overexpressed p70‐S6K1, p85‐S6K1, p54‐S6K2, p31‐S6K1 in human cells and analyzed by immunoprecipitation followed by mass spectrometry identification the possible and different interacting partners of those S6Ks isoforms. The different roles of S6Ks isoforms was then evaluated in an adipocyte model and in cancer cell lines. Our study may provide new functions to the different S6Ks isoforms which may help the understanding of their roles in the mTOR signaling pathway.Grant Funding Source: Suported by FAPESP #2012/13558‐7
A Tale of Two Distinct Mechanisms for IRE1 RNase (752.9)
Authors: Niwa Maho 
Published: June 2021

IRE1, an ER transmembrane receptor kinase, is a component of the Unfolded Protein Response (UPR) pathway, and acts as an endoribonuclease (RNase) to cleave the intron from XBP1/HAC1 mRNA coding an UPR‐specific transcription factor. Interestingly, recent reports have revealed that UPR also induces a decrease in levels of ER‐associated mRNAs, including INSULIN mRNA in an IRE1‐dependent manner1, which has been termed Regulated IRE1 Dependent Decay (RIDD). While XBP1/HAC1 splicing and RIDD are proposed to be carried out by IRE1, the mechanism by which IRE1 differentiates between XBP1/HAC1 and RIDD substrate mRNAs has not been investigated. Major differences in the cleavage of the HAC1/XBP1 intron and of RIDD RNA include RNA sequences at the cleavage sites, and that HAC1/XBP1 mRNA cleavage occurs at the ends of the intron whereas certain RIDD substrate RNA are cleaved at multiple sites. In addition, HAC1/XBP1 exon cleavage must be coordinated with tRNA ligase activity while RIDD RNA fragments should be shielded from tRNA ligase to promote their degradation.Upon development of a robust in vitro RIDD RNase assay with purified recombinant IRE1 expressed in baculovirus or E. coli, we examined the molecular mechanisms by which IRE1 cleaves either HAC1/XBP1 or RIDD RNA substrates. We have found that IRE1 engaged in cleavage of HAC1/XBP1 RNA cannot be competed by addition of cold RIDD RNA, while HAC1/XBP1 RNA can be effectively competed by excess cold HAC1/XBP1. The converse was true for IRE1 engaged in RIDD cleavage. Further analyses revealed that IRE1 oligomer constitutes the site for RNA substrate binding and catalysis, while IRE1 that acts on RIDD RNA does not require oligomerization. Our study provides a molecular basis for designing strategies to differentially activate (inhibit) one of the Ire1 RNase activities without affecting the other which may lead to new strategies for treating diseases associated with IRE1 activation.#1: Hollien, J., Science 313, 104 (2006), Han, D., Cell 138, 562 (2009)
Effects of lysine mutations on the structure and function of hemolysin A from Proteus mirabilis (755.4)
Authors: Adamczak Kyle , Weaver Todd 
Published: June 2021

Proteus mirabilis (HpmA), a Gram‐negative bacterium, implements the two‐partner secretion pathway to produce a hemolytically active exoprotein. The full‐length HpmA was cloned and truncated to contain the first 265 amino acids (HpmA265) in order analyze the structure and function more readily. In the native crystal structure, a dimer was observed to form via on‐edge stacking of carboxy‐terminal parallel beta‐strands. A series of carboxy‐terminal lysine mutants were investigated in this study. Specifically, Phe241, Met245 and Leu263 were altered with the polar charged lysine residue to disrupt the non‐polar carboxy‐terminal dimer and thereby, induce monomer formation. The resultant HpmA265 mutants were analyzed via template‐assisted hemolysis assay, dynamic light scattering and circular dichroism. The results indicate that the loss of hemolytic activity can be correlated with replacement of the most carboxy‐terminal amino acid, Leu263. Additionally, there appears to be less well‐defined beta‐sheet structure in each of the HpmA265 carboxy‐terminal mutants. Further study will aim to conclude whether the HpmA265 monomer or dimer acts as the functional template during hemolysis.Grant Funding Source: Supported by NSF‐RUI 1050435
Protective role of the mitochondrial Lon protease in homeostasis, oxidative stress‐adaptation, disease, and aging (756.6)
Authors: Davies Kelvin 
Published: June 2021

The targeted removal of damaged proteins by proteolysis is crucial for cell survival. We have shown that the product of the human lon gene, the Lon protease, selectively degrades oxidized mitochondrial proteins, thus preventing their aggregation and cross‐linking. Decreasing Lon levels, by knock‐down, causes accumulation of oxidized mitochondrial proteins, compromised mitochondrial function, and increased mitophagy. We also show that lon is a stress‐responsive gene, whose protease product is a stress‐responsive protein that is induced by multiple stressors, including heat shock, serum starvation, and oxidative stress. Lon induction, by pre‐treatment with low‐level stress, protects against oxidative protein damage, diminished mitochondrial function, and loss of cell proliferation, induced by toxic levels of hydrogen peroxide and other metabolic, environmental, or drug oxidants. Blocking oxidant‐induced Lon induction, with lon siRNA, also blocks this induced protection. Lon protein levels can increase as much as eight‐fold in response to stress‐stimulation, yet mRNA levels increase only about 50%. Our studies indicate that a translational activation mechanism may underlie Lon’s extensive and rapid stress‐inducibility. Lon All of these results were obtained in young, healthy cells. Older animals (mice) show a marked decline in Lon levels, particularly in skeletal muscles. Interestingly, in both senescent cells, and in older postmitotic cells, Lon levels and activity decline, and adaptational responses become sluggish or even ineffectual. Studies in animals and humans now suggest that declining Lon activity and, perhaps, declining responsiveness to stress, may contribute to the ageing process, and to various age‐associated diseases. We propose that Lon is a generalized stress‐protective enzyme whose decline may contribute to the increased levels of protein damage, mitochondrial dysfunction, and mitophagy observed in ageing and various age‐related diseasesGrant Funding Source: NIH/NIEHS ES003598
Quantitative analysis of mitochondrial dynamics illuminates links between mitochondrial dynamics and cell function, and allows single organelle localisation microscopy (759.2)
Authors: Saunter Christopher , Chalmers Susan , Girkin John , McCarron John 
Published: June 2021

Mitochondrial structure is believed to be important to the normal function of cells. However, remarkably, in fully differentiated cells understanding of how mitochondrial structure controls cell function is preliminary. An ability to generate high resolution, high speed images of mitochondrial structure simultaneously with measurements of cell function is required. We present a suite of quantitative bio‐imaging tools developed for the measurement and analysis of mitochondrial dynamics from high speed fluorescence imaging of live cells, including the measurement and quantification of mitochondrial motion to sub‐diffraction limits, Single Organelle Localisation Microscopy, the use of transient depolarisation's of the mitochondrial membrane to segment physically and optically crowded clusters of mitochondria, and the co‐localization of mitochondria and Ca2+ signalling . We present the algorithmic basis of these tools and highlight their use in the context of changing mitochondrial dynamics in cellular proliferation and hypertension, with an emphasis on the generation of quantified measurements to yield insight into the different cellular states. These tools present a powerful combination of experimental procedures that give an unobstructed open view of new, previously hidden, mechanisms that control mitochondrial dynamics and cell function.Grant Funding Source: Wellcome Trust; British Heart Foundation; EPSRC