bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Utility of Cadaver‐Based Approaches for the Teaching of Human Anatomy: A Survey of British and Irish Anatomy Teachers
Authors: Balta Joy Y. , Cronin Michael , Cryan John F. , O'Mahony Siobhain M. 
Published: November 2023

Human cadavers have been used for centuries to learn about the human body. Today they still represent a key anatomy learning tool in most Medical Schools. Using reality anatomy such as dissection and demonstrating using cadavers has been described as a superior way to create meaning. To prevent the decomposition of cadavers and to decrease any health risks, cadavers are embalmed using different chemicals. These chemicals can differentially alter the tissue of the human body which has led to the usage of different processes along the hard to soft‐fixed spectrum of preserved cadavers. However, it is currently unclear what is the perceived utility of the different preservation modalities within anatomy learning environments.To this end we used a questionnaire based approach to gain a better insight into the opinion of anatomists on the use of preserved cadavers for the teaching of human anatomy. We focused on anatomy teachers in the United Kingdom and Ireland. From the 125 participating anatomists, 34.4% were medically qualified, 30.4% had a PhD in a non‐anatomical science and 22.4% had a PhD in an anatomical science, these figures include ten anatomists who had combinations of MD with the two other PhD qualifications. Anatomists with different background had different experiences. Table 1 shows the experiences of participating anatomist.The main findings from the questionnaire were that 61.6% of participants agreed that hard‐fixed formalin cadavers accurately resemble features of a human body while 21.6% disagreed. Moreover, anatomists rated the teaching aids on how accurately resemble features of the human body as follows (Figure 1) : plastic models the least accurate followed by plastinated specimen, and hard fixed cadavers; soft preserved cadavers were considered to be the most accurate when it comes to resembling features of the human body. Friedman test was conducted followed by Post hoc analysis with Wilcoxon signed‐rank tests showing that there was a statistically significant difference in rating between the different teaching aids.With different embalming solutions becoming more commercially available, it is important to remain unbiased and consider the best interest of education and research. Further research is required in order to investigate which techniques or methods provide better teaching tool for a range of anatomical teaching levels and for the sections of the body used in surgical training.
Experience of anatomists teaching in the U.K. and Ireland in surgery, teaching a cadaver based anatomy module, examining the tissue of dissected fresh cadavers and examining the tissue of dissected soft preserved cadavers.

Experience
Yes (%)

Surgery±
34.4%

Cadaver Teaching
98.4%

Examine Fresh Cadaver
52%

Examine Soft Preserved cadaver
56%

relevant to those who chose Medical Degree
How to Support Student Motivation In a Flipped Anatomy Course: Introducing the “mFlip”
Authors: Saltarelli William , Robinson Kristy , Bovee Emily , Beymer Patrick , Linnenbrick‐Garcia Lisa , Roseth Cary 
Published: November 2023

In a “flipped classroom,” instructors post lectures online in the hope of using class time for more active learning activities. In theory, students watch the online lectures on their own, then bring questions to class for clarification and deeper understanding. Yet research and practice suggest that reality rarely matches this ideal, particularly in large, introductory courses like college anatomy where many students fail to watch online lectures, much less direct their own learning in a way that adequately prepares them for in‐class activities. To flip successfully, therefore, instructors must also support students’ motivation.PurposeIn this report, we describe the “mFlip,” or a motivationally supportive way of flipping anatomy instruction by awarding points for self‐directed learning, using formative quizzes, and scaffolding in‐class clicker activities.MethodsData was collected over three semesters in a large, undergraduate anatomy course in order to compare traditional lecture instruction (semester 1) with two different versions of flipped instruction (semesters 2 and 3). The results of the semester‐2 flip informed motivationally supportive changes in the semester‐3 flip. Specifically, in semester 3, we awarded points for watching ≥ 80% of the online lectures before class and for attending ≥ 80% of in‐class sessions. We also awarded full points for earning ≥ 80% on weekly lecture quizzes that students could take up to 3 times. In class, the instructor also scaffolded clicker‐based student activities, using fact‐based multiple‐choice questions to support more open‐ended application and synthesis questions. In addition, we also designed in‐class activities to help students develop study strategies for managing the large volume of material in college anatomy.ResultsAfter reviewing results from the traditional flip (semester 2) the researchers made changes designed to support student motivation. Points were added for viewing online recordings (prior to class), class attendance and weekly quizzes. Results suggest that, compared to the conventional flip (semester 2) the “mFlip” (semester 3) has increased viewing of the online lectures by 36% and in‐class attendance by 57%. However, initial analyses suggest that exam scores have not yet changed significantly, with three of five exams still to be completed.ConclusionAs new technologies afford new approaches to teaching and learning, one must also consider the way student motivation affects outcomes. This study highlights the way technology, pedagogy, and course content interacts with student motivation in the successful design of the “mFlip,” a motivationally supportive way of flipping college anatomy instruction. More broadly, this report also highlights the value of collaboration between content experts ‐ e.g., anatomy instructors ‐ and educational psychologists in the design and on‐going refinement of using educational technology in the modern classroom.
Determination of Escherichia coli Genes Involved in Resistance to DNA Alkylating Agents
Authors: Bellou Sirine , Muenter Mark , Travers Meghan , Leifer Becky , Baig Samir , Kramer Caitlin , Qi Macee , Joshi Christopher , Carlson Alyssa , Conway Charles , Beuning Penny 
Published: November 2023

DNA repair is a vital aspect of cellular life that restores DNA from damage often caused by environmental aggressions, such as chemical mutagens. Alkylating agents, a common family of DNA damaging agents that form adducts on DNA, are frequently used for chemotherapy as well as for industrial purposes, thus the importance to deepen our understanding of their mechanisms of damage and the cellular responses to these agents. In order to identify genes that confer resistance to alkylating agents, our research focuses on the ability of twenty‐seven genes in Escherichia coli to confer resistance to chloroacetaldehyde (CAA) and styrene oxide (SO). An assay has been designed to assess survival of the strains, each of which possess a deletion of a specific gene, upon exposure to different concentrations of the alkylating agents relative to the wild‐type strain. Strains in which recJ or nfo were deleted were sensitive to SO, whereas strains lacking recA were sensitive to both SO and CAA. The genes deleted in the strains that show drastic killing were selected for complementation, which would confirm the role of each specific gene in the repair mechanism.Support or Funding InformationAmerican Cancer Society
Functional Significance of Meiotic Proteins in the DNA Repair System of Bdelloid Rotifers
Authors: Dickinson Lauren E , McReynolds Jeanita C , Schurko Andrew M 
Published: November 2023

Bdelloid rotifers are microinvertebrates that repair DNA double‐strand breaks (DSBs) with an efficiency unparalleled in other eukaryotes. These animals inhabit transient aquatic environments and survive frequent desiccation by entering a state of anhydrobiosis. Their DNA repair system is necessary for repairing the DSBs induced by extreme desiccation. Bdelloids have long been considered ancient asexuals that have survived without males and sex for millions of years. Evidence for canonical meiosis and sexual reproduction in bdelloids is absent, although some form of atypical genetic exchange might occur in some populations. Despite the long‐standing absence of meiosis in bdelloids, their genomes contain four genes that encode proteins (HOP1, SPO11, MSH4, and MSH5) known to be specific to meiosis in other eukaryotes. Since bdelloids lack meiosis yet possess a noteworthy DNA repair system, the objective is to investigate the potential role of meiotic proteins during DNA repair. We used real‐time PCR to quantify meiotic gene expression in the bdelloid Adineta vaga following exposure to 280 Gray of ionizing radiation (which induces DSBs). Genes encoding meiotic proteins were upregulated, relative to non‐irradiated A. vaga. Western blots using custom antibodies for HOP1, SPO11, MSH4, and MSH5 from A. vaga revealed that these proteins are produced in bdelloids. To characterize binding partners of these meiotic proteins during DNA repair, we generated 6×histidine‐tagged copies of HOP1, SPO11, MSH4, and MSH5 from A. vaga. Pull‐down assays using the histidine‐tagged proteins were done to identify the proteins that interact with HOP1, SPO11, MSH4, and MSH5 in irradiated and non‐irradiated bdelloids. These findings will shed light on the functional significance of these meiotic proteins in bdelloids. Overall, this study represents the first genetic and proteomic data to address whether meiotic genes in bdelloids have evolved a novel function in DNA repair, which could justify the maintenance of these genes in an ameiotic lineage. Data supporting a role for “meiotic proteins” in DNA repair would be the first evidence of a non‐meiotic function for these genes and could be used to further our understanding of DNA repair in eukaryotes.Support or Funding InformationThis work was supported by grants from the NCRR (5P20RR016460) & NIGMS (8P20GM103429) from the NIH to AMS, and a Summer Undergraduate Research Fellowship from the Arkansas Department of Higher Education to LED.
DNA Repair Proteins XLF and XRCC4 Interact With Telomeric Proteins TRF1 And RAP1
Authors: Castle Eric Anthony , Zaibaq Pilar , Pham Quoc‐Khanh , Aviles Yicenia , Hou Jianyi , Vu Kimberly Thien , Fahmy Nicole , Guirette Melanie , Ruff Aaron , Jain Renu , Jabbur James , Ribes‐Zamora Albert 
Published: November 2023

Non‐homologous end‐joining (NHEJ) is the main repair pathway for processing double‐strand DNA breaks in Eukarya. In mammalian cells, NHEJ is mediated by a complex of proteins comprised of the Ku subunits (Ku70 and Ku86), Ligase IV, XRCC4, Artemis, DNA‐PKcs and XLF. Paradoxically, several of these NHEJ proteins are also found at telomeres, despite the fact that one of the main functions of the complex structure at telomeres is to prevent NHEJ proteins from recognizing the natural ends of chromosomes as DSBs. For instance, Ku is present at telomeres through interactions with resident telomeric proteins like TRF1 and TRF2, as is the case for DNA‐PKcs. Currently, the telomeric status of several NHEJ proteins is still unknown. Using protein fragment complementation assays, we have found interactions between two NHEJ proteins, XLF and XRCC4, with TRF1 and RAP1, two proteins present at telomeres. Co‐localization studies with TRF2 indicate that TRF1 interactions with XLF and XRCC4 occur at telomeres, while XLF‐RAP1 and XRCC4‐RAP1 interactions occur throughout the nucleus. Mutations that disrupt XRCC4‐XLF filament formation did not impair XRCC4 or XLF interaction with TRF1. Similarly, XRCC4 mutations in known phosphorylation sites for ATM and DNA‐PKcs did not impair XRCC4‐TRF1 interaction nor did they impair XRCC4 localization at telomeres. Overall, these results suggest that XRCC4 and XLF can localize at telomeres through direct interaction with telomeric resident proteins.Support or Funding InformationSupported by the UST/HCCS STEM Scholars Program (P031C110128‐12) from the US Department of Education and by the University of St Thomas Cullen Smith Chair of Biology
Analysis of nuclease hypersensitive‐equivalent sites in SV40 by Next Generation Sequencing
Authors: Milavetz Barry , Balakrishnan Lata , Woods Benjamin , Christensen Kendra 
Published: November 2023

Chromatin fragments obtained by sonication or Micrococcal nuclease digestion of SV40 minichromosomes or disrupted virions were analyzed by Next Generation Sequencing (NGS) to determine the location of regions of the SV40 genome differentially sensitive to either treatment. Both treatments yielded samples which upon analysis allowed us to identify regions of hypersensitivity and moderate sensitivity. With sonication all of the samples contained regions of hypersensitivity centered on nucleotides 141 and 221 and regions of moderate sensitivity surrounding these sites which included the 21 base pair repeat regions and enhancers. Following Micrococcal nuclease treatment Hypersensitive sites were found in minichromosomes centered on nucleotides 30 and 92 and in chromatin from disrupted virions centered at nucleotide 106. Micrococcal nuclease also generated a pattern of peaks and valleys based upon the number of reads at each nucleotide consistent with the location of nucleosomes. While the pattern was very similar throughout most of the SV40 genome in minichromosomes and chromatin from disrupted virions, the pattern differed significantly in the regulatory region. In minichromosomes we observed a nucleosome‐free region extending from approximately nucleotide 5000 to nucleotide 250 encompassing most of the early and late transcription regulatory sequences and the origin of replication. In chromatin from disrupted virions we observed a very small open region which at most included only the enhancers.Support or Funding InformationThis work was supported by grants from NIH AI094441 (to BM) and NIH GM098328 (to LB)
Target Discrimination in the Nonsense‐Mediated Decay Pathway Requires ATPase‐dependent Release of Upf1
Authors: Lee Suzanne Rebecca , Pratt Gabriel , Martinez Fernando , Yeo Gene W , Lykke‐Andersen Jens 
Published: November 2023

RNA binding proteins (RBPs) play key roles in gene expression, involved in every aspect of RNA metabolism. RBPs are generally thought to identify their target RNAs through affinity for specific RNA elements or bound proteins. However, this mechanism of target recognition has limited utility for RBPs functioning in RNA quality control pathways, which target aberrant RNAs that have the potential to vary greatly in sequence and associated proteins. Here we present several lines of evidence suggesting that in the nonsense‐mediated decay (NMD) quality control pathway, target discrimination involves the selective release of the RNA helicase Upf1 from non‐target mRNAs, rather than Upf1‐target specific affinity. By examining Upf1 association with reporter mRNAs and the mRNA transcriptome, we found that Upf1 mutations preventing ATP hydrolysis eliminate target discrimination, elevating the association of NMD factor complexes with both target and non‐target mRNAs. Conversely, Upf1 mutants with enhanced ATPase activity are severely compromised in association with both targets and non‐targets. Moreover, ATP hydrolysis‐dependent release of Upf1 from non‐target mRNA is faster than release from target mRNAs in cell extracts. Intriguingly, known modulators of NMD depend on the ATPase activity of Upf1 to limit Upf1‐non‐target association. Together, our findings suggest that mRNP‐regulated ATP hydrolysis‐dependent release is a previously unappreciated mechanism by which a regulatory RBP can achieve target specificity. This mechanism may be particularly advantageous for RNA quality control pathways, which need to continuously survey the RNA population for those that deviate from the norm.Support or Funding InformationThis study was supported by a Helen HayWhitney Postdoctoral Fellowship to S.R.L., NIH grant R01GM099717 to J.L.‐A.; NIH grants NS075449, HG004659, HG007005, to G.W.Y.; ; and a National Science Foundation Predoctoral Fellowship to G.A.P. F.J.M. is supported in part by a University of California, San Diego, Genetics training grant from the National Institute of General Medical Sciences (T32 GM008666).
Compulsive Grooming and Hyperactivity in Nicastrin Conditional Knockout Mice
Authors: Dries Daniel R. , Zhu Julia , Birnbaum Shari G. , Yu Gang 
Published: November 2023

The gamma‐secretase complex is a proteolytic machine of four subunits and is involved in the generation of the pathogenic and neurotoxic beta‐amyloid peptides found in the brains of Alzheimer's patients. Germline deletion of any of the four gamma‐secretase components results in embryonic lethality, necessitating tissue‐ and/or age‐specific deletion. Conditional deletion of presenilin (the catalytic subunit) or nicastrin (the substrate receptor subunit) from neurons in the mouse forebrain results in mild cognitive defects and neuronal loss. Here, we asked whether gamma‐secretase activity in other brain cell types (i.e. glia) also contributes to behavioral phenotypes. To this end, we have developed a conditional knockout mouse in which nicastrin has been specifically eliminated from oligodendrocytes, the myelinating cells of the brain. These mice are hyperactive and display reduced anxiety. Adult mice appear do not display gross brain pathology, although adult mice do have hypomyelination in the central nervous system. The work presented suggests that elimination of gamma‐secretase activity from oligodendrocytes may result in altered neuronal circuitry to elicit behaviors consistent with obsessive‐compulsive disorder and attention‐deficit‐hyperactivity disorder, as well as some of the non‐cognitive symptoms of Alzheimer's disease.Support or Funding InformationThis work was supported by NIH grants F32 AG031625, R01 AG023104, R01 AG029547, the Welch Foundation (I‐1566), the Hartwell Foundation, and the Alzheimer's Association.
Global Ubiquitylome Profiling for the Identification of Drug Targets in Cancer
Authors: Udeshi Namrata D , Kronke Jan , Fink Emma , Svinkina Tanya , Schenone Monica , Ebert Benjamin , Carr Steven A 
Published: November 2023

Mechanisms of action for drugs targeting ubiquitin E3 ligases that show efficacy in disease treatment have been extremely difficult to establish. Through advances in proper utilization of ubiquitin enrichment reagents and instrumentation, we now routinely characterize unprecedented numbers of ubiquitylation sites in disease relevant samples to reveal cancer‐relevant substrates. Lenalidomide is a highly effective drug for treatment of multiple myeloma but the precise mechanism of action has not been established. Previous work found that thalidomide, an analogue of lenalidomide, binds and modulates the activity of the CRBN‐DDB1 E3 ligase. We hypothesized that the pleiotropic effects of lenalidomide may be caused by altered ubiquitination of targets. Quantitative proteomics using SILAC revealed that transcription factors IKZF1 and IKZF3 have altered abundance and ubiquitination status upon lenalidomide treatment in multiple myeloma cells. Protein interaction analyses showed that IKZF1 and IKZF3 bind to CRBN and that binding is enhanced in the presence of lenalidomide. Multiple myeloma cells were found to be dependent on IKZF1 and IKZF3 expression. Knockdown of these proteins inhibited cell growth while expression of the lenalidomide‐resistant IKZF3 conferred lenalidomide resistance of MM1S cells. Here we present findings that reveal that lenalidomide modulates the CRBN‐DDB1 ligase to increase ubiquitination of two transcription factors that would otherwise be considered “undruggable.” Our findings reveal a novel mechanism of action for a therapeutic agent; alteration of ligase activity leading to selective degradation of specific targets. This work will further discuss the mechanism of action for Lenalidomide in MDS 5q‐.Support or Funding InformationThis work was supported by funding from the NIH (R01HL082945, P01 CA108631), Leukemia and Lymphoma Society, Evans Foundation, Starr Cancer Consortium, SPARC consortium, National Human Genome Research Institute (RL1‐HG004671) and by the German Research Foundation (DFG, Kr‐3886/1‐1).
Measurements of Endogenous Opioid Peptides in the Rat Brain Using Online‐Preservation Microdialysis with Mass Spectrometry
Authors: Robles Dagoberto , Laude Nicholas D. , Kramer Catherine , Lemister Eric , Meske Diana , Navratilova Edita , Heien Michael , Porreca Frank 
Published: November 2023

In the mammalian central nervous system, opioid receptors and their endogenous ligands are involved in mediating reinforcing effects of natural rewards such as food. Endogenous opioid system also plays an important role in pain and analgesia. Human neuroimaging studies have demonstrated that endogenous opioid peptides (EOPs) are released in cortical and subcortical regions of the brain during appetitive food consumption, as well as following an acute pain stimulus. Dynamic monitoring of EOPs in laboratory animals, however, has been limited due to the low concentration of EOPs that are released and their high susceptibility to degradation. To address these issues, on‐line preservation microdialysis with nano liquid chromatography and tandem mass‐spectrometry (nano LC‐M) has been developed to facilitate measurements of EOPs and prevent peptide degradation. By using this method, in vivo ultra‐trace measurements of leucine and methionine enkephalins was successfully achieved in conscious and freely moving rats. This approach serves as a powerful tool to quantitatively monitor endogenous opioids in cortical and subcortical regions of the brain in behaving rats.Support or Funding Information: Department of Pharmacology, Arizona Health Sciences Center, University of Arizona, Tucson, AZ, 85721, USA Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA