bluuebunny/crossref_metadata_2025_split huggingface dataset:
QTL Analysis of a Trade‐off in Bone Length within the Mouse Zygomatic Arch
Authors: Percival Christopher J. , Green Rebecca , Gatti Daniel M. , Pomp Daniel , Roseman Charles C. , Marcucio Ralph , Hallgrímsson Benedikt 
Published: November 2023

We use a powerful mouse resource to identify candidate genes associated with a negative correlation in the length of bones that contribute to the zygomatic arch. Because system‐wide growth factors contribute to all skeletal dimensions, most skull linear distances are positively correlated with each other. However, the lengths of two adjacent zygomatic arch bones are negatively correlated in our Diversity Outbred (DO) mice. This is evidence for an opposite pleiotropic effect or developmental constraint during zygomatic arch formation, which appears to limit variation in total zygomatic arch length. Determining the basis for this negative correlation will help us understand developmental mechanisms that limit phenotypic variation and underlie variation in how individual bones contribute to overall skull form. We completed high‐resolution genetic mapping with 563 DO mice to identify genomic regions and candidate genes associated with this negative correlation. DO mice are ideal for this, because each mouse carries a high degree of heterozygosity and a unique combination of alleles. We separately mapped 1) jugal bone length, 2) jugal process of maxilla length, and 3) total zygomatic arch length. Analysis was completed on raw linear distances without scaling or removing the allometric component of variation, because these procedures remove variation associated with overall size and artificially create negative associations between linear distance measurements. A genomic interval between 85 and 86 Mb on chromosome 17 was significantly associated with variation in jugal bone length and jugal process length, but not total zygomatic arch length. In addition, founder haplotypes under this peak displayed opposite phenotypic effects on individual bone lengths, suggesting it includes a genetic factor driving relative length of these zygomatic bones, but not total arch length. This interval includes Six2, Six3, and Six3os1, which are expressed in the pharyngeal arches or forebrain during facial development, as well as Camkmt, which is pivotal for calmodulin methylation. Ongoing real‐time PCR will show whether expression of these genes within the maxillary arch at E10.5 in three founder strains is correlated with measured founder haplotype effects. Understanding the genetic and developmental basis for this negative correlation is important because it results in a developmental constraint on total zygomatic arch length, which will act to limit evolvability of this structure.Support or Funding InformationFunding graciously provided by the NIH (U01DE020054, 2R01DE019638, R01DE021708, R01GM070683), NSERC (238992‐12), and to CJP by the Alberta Innovates Health Solutions.
Movement Guided Learning as an Efficacious, Effective, and Evidence‐based Teaching Strategy Within the Undergraduate Anatomy Classroom
Authors: Bentley Danielle Christine 
Published: November 2023

Within the anatomy classroom, physical movements and stretches can turn a student's own body into their personal educational tool. Such direct relevance can be useful for the undergraduate junior learner as they attempt to truly understand musculoskelatal anatomy in a meaningful way. This presentation describes the longitudinal, iterative scholarship that went in to developing, piloting, refining, and experimentally assessing Movement Guided Learning (MGL)©, a self‐directed learning workbook that guides students through applications of musculoskeletal anatomy including physical movements/stretches, surface palpations/visualizations, and extensions of knowledge with case‐based scenarios.Most recently, components of the refined MGL workbook were fully integrated as adjunct teaching activities into a large undergraduate classroom within health sciences. Using a randomized control design, the entire curriculum of muscular anatomy was divided into three equal groups; students received MGL activities for 1/3rd of the taught muscles, students received multiple choice style review questions for 1/3rd of the taught muscles (as an active, time‐matched control), and students received no additional learning material for 1/3rd of taught muscles (as a non‐active control). To facilitate full integration of supplementary teaching materials, the course instructor was been made aware of group allocations, provided with all teaching materials, and embedded those materials during in‐class lecture time and during independent student activities. Final exam scores will be segmented and compared in agreement with the three experimental groups, allowing for an intra‐individual superiority assessment of MGL. Student survey responses will allow for MGL efficacy to be further assessed against student learning preferences as well as self‐reported strategy utilization. To control for inadvertent instructor‐bias, time spent on each muscle will be quantified (using video lecture capture software) and compared across the three groupsThere are currently 187 undergraduate students enrolled in the course with the majority of them enrolled in a global health degree (~75%) in their first year of undergraduate studies (~90%). MGL efficacy will be determined using the aforementioned mixed‐methods assessment strategies following the fall semester final exam. Based on previously reported MGL success, it is hypothesized that the MGL activities will be a useful learning adjunct, especially for students who display kinesthetic learning preferences.Support or Funding Informationnone to declare
Strategies to Help Students Tackle Complicated Anatomical Terminology
Authors: Carnegie Jacqueline 
Published: November 2023

The study of anatomy involves the acquisition of a new language as students familiarize themselves with the names of the components of organs and organ systems. Many of these names derive from Latin and Greek, languages with which students have limited experience and they struggle with the pronunciation and spelling of each new term. Furthermore, students gain little experience in actively recalling, speaking and writing this terminology (they are provided with PowerPoint (PPT) lecture slides) and high enrolments (250–300 students per course) make weekly laboratory sessions impossible. Interactive learning strategies are needed to enrich their educational experience. Videos narrated by peers allow students to hear the names of bones and muscles while simultaneously using visual pathways to situate their study of musculoskeletal (MSK) anatomy within applied contexts such as a fractured wrist or the assumption of a yoga pose. Interactive PPT‐based Hangman games (PPTAlchemyR) require students to both recall functional anatomy content and to focus on the letters composing a muscle's name when assigning letters to spaces. Indeed, gamification is a new educational trend that promotes interactive learning by giving students low‐stakes opportunities to practice and to learn from their errors. A final approach, the development of content‐specific crossword puzzles using EclipseCrosswordR, also uses clues to stimulate recall and forces students to focus on word structure. But these puzzles have the additional advantages of accommodating words of unlimited length (word limit for PPT‐based Hangman is 15 letters), alerting students to an answer with the wrong number of letters, allowing students to identify spelling errors following puzzle submission, and motivating students to produce a finished product. Despite the fact that marks were not assigned to these interactive activities, tracking data shows that they were well used by students when preparing for summative evaluation. Students in two undergraduate courses in MSK anatomy (n = 233 and 235) presented with a series of four yoga videos over the three weeks leading up to summative exams watched each video an average of 1.92–2.70 times with most students being sufficiently engaged to view the entire series at least once. Preliminary data tracking student use of crossword puzzles in a first‐year anatomy and physiology course (n = 296) revealed a high level of interest when each puzzle was released (immediately accessed by over 25% of students) and that many students (at least 25–30%) returned to try the puzzles more than once. These studies involving students of anatomy show that educational strategies that combine audio with visual and/or use interactive word‐based games can enrich learning and are welcomed by students tackling a new language.Support or Funding InformationUniversity of Ottawa Undergraduate Research Opportunity Program
Expansion of the Functional Border of the Audiovisual Cortex Following Partial Hearing Loss in Adulthood
Authors: Allman Brian 
Published: November 2023

Following damage to a major sense (e.g., hearing loss), crossmodal plasticity occurs whereby there is an increased responsiveness in the deprived cortex to the remaining, intact senses. Using a rat model and single‐unit electrophysiological recordings, our recent studies on hearing‐impaired animals have revealed that crossmodal plasticity is not restricted to the core auditory cortex; higher‐order auditory regions as well as visual and audiovisual cortices show differential effects following noise‐induced hearing loss. To our surprise, the cortical area showing the greatest relative degree of multisensory convergence transitioned away from the normal audiovisual area toward a neighboring, predominantly auditory area. Thus, our collective results suggest that crossmodal plasticity induced by adult‐onset hearing impairment manifests in higher‐order cortical areas as an expansion in the functional border of the audiovisual cortex. Our ongoing studies seek to determine the implications of this crossmodal plasticity on the rats' ability to perceive the precise timing of audiovisual stimuli using novel behavioral tasks that are consistent with studies of perceptual judgement in humans.Support or Funding InformationSupport provided by an NSERC Discovery Grant
Changes in Oligodendroglial and Microglial Cell Populations in the Embryonic Rat Spinal Cord Following Maternal Immune Activation
Authors: McDermott Kieran W , Anderson Rebecca C , Foley Tara , Radford Jay , O'Halloran Sophie , O'Keeffe Gerard W 
Published: November 2023

Epidemiological studies suggest that maternal immune activation (MIA) may contribute to the development of neurological disorders such as cerebral palsy, schizophrenia, autism, epilepsy and potentially, neurodegenerative diseases. These studies, and those in animal models, have suggested that the effects of MIA on the developing nervous system, and thus the longer term consequences for the offspring, may be spatially and temporally regulated. However, much work remains in order to elucidate fully the CNS regions, cell populations and timing of gestational vulnerability.The in vivo effects of MIA on cellular development in the spinal cord (SC) at embryonic day (E)12, 14 and 16 were investigated in this study. Dams received a single intraperitoneal injection of 50μg/kg lipopolysaccharide (LPS), 100 μg/kg LPS, or saline. Embryos were sacrificed either 5 hours post‐injection or, following their delivery, two weeks postnatally(P). Embryos and pups were fixed and frozen prior to cryosectioning at 15μm. Rostral, intermediate and caudal SC sections were immunofluorescently stained with Olig‐2 (an oligodendrocyte marker), Iba‐1 (a microglial marker), nestin (a radial glial marker) and reelin antisera.Olig2‐positive cells were counted in white matter (WM) and grey matter (GM) regions of the SC. Olig2‐positive cell number in E16 embryos decreased 5 hours following treatment with 100μg/kg LPS but not with treatment with 50μg/kg LPS. At E14 Olig2‐positive cells showed no change at 5 hours in response to 50μg/kg LPS treatment.Iba‐1+ cells decreased in GM and WM of the E16 SC 5Hr post treatment with 100μg/kg LPS.Reelin fluorescence intensity is decreased in the GM of the E16 SC 5 hours after 100μg/kg LPS treatment. Reelin fluorescence intensity is unaltered in E16 spinal cord in response to 50μg/kg LPS. Reelin appears to co‐localise with a specific population of neurons at E16 and P14.In conclusion, MIA appears to have an acute effect on the development of key cell populations at specific time points. Ongoing work is extending these analyses and will seek to identify how such perturbations affect ongoing SC development into the early postnatal period.Support or Funding InformationAnatomical SocietyGraduate Entry Medical School University of Limerick
Orphan Nuclear Receptor, GCNF, Is Required for Early Neural Crest Cell Induction and Survival
Authors: Munoz William A , Bhatt Shachi , Crane‐Dennis Jennifer , Achilleos Annita , Sakai Daisuke , Cooney Austin , Trainor Paul 
Published: November 2023

Neural crest cells (NCC) are considered to be a vertebrate innovation that significantly contributed to the evolution, predation, radiation and adaptation of vertebrates to most niches of the planet. NCC comprise a unique vertebrate cell population that is frequently termed the “fourth germ layer” because they form in conjunction with the other germ layers and give rise to a diverse array of cell types and tissues including most of the craniofacial skeleton, peripheral nervous system, and pigment cells amongst many others. NCC development is dependent on gene regulatory network (GRN) control of several cellular mechanisms including induction, migration and differentiation. Defects in these processes result in clinical manifestations termed neurocristopathies.In contrast to aquatic and avian species, we currently have a very poor understanding of the factors that regulate mammalian neural crest cell induction and specification. Here we describe molecular analyses in mouse models that reveal a critical role for the orphan nuclear receptor, Germ cell nuclear factor (Gcnf/Nr6a1) in mammalian neural crest cell formation and survival. Comparison of null and conditional Gcnf mutant embryos indicates that Gcnf is required prior to E8.0 for proper neural crest cell specification and induction. Furthermore, Gcnf functions as a bimodal switch to repress neural stem cell fate and promote the acquisition of neural crest cell identity. Thus our findings have identified a novel regulator of mammalian neural crest cell development and defined a temporal window for mammalian neural crest cell formation which is earlier than previously thought and raises important questions regarding the appropriateness of Wnt1Cre in studies of mammalian neural crest cell specification and induction.Support or Funding InformationThis work in the Trainor lab is supported by the Stowers Institute for Medical Research, the March of Dimes (#6‐FY08‐265) and the National Institute of Health ‐ National Institute for Dental and Craniofacial Research (DE016082). WIM is further supported by the American Association of Anatomist Postdoctoral Fellowship.
LHX2 is a necessary intermediate in FGF‐induced SHH expression during limb development
Authors: Watson Billy A. , Pira Charmaine U. , Oberg Kerby C. 
Published: November 2023

During limb development, Fibroblast growth factors (FGFs) from the apical ectodermal ridge (AER) promote limb outgrowth and proximal‐distal patterning. The zone of polarizing activity, a cluster of mesodermal cells in the distal posterior limb bud, secretes Sonic hedgehog (SHH) which promotes anterior‐posterior outgrowth and patterning. Coordination of patterned development between these axes is facilitated by a reciprocal feedback loop and is necessary for normal limb formation as well as redevelopment/regeneration. The molecular mechanisms governing this feedback loop, however, are poorly understood, particularly the intermediates downstream of FGF that induce/maintain SHH expression. In order to elucidate potential target genes, we performed a DNA microarray analysis in SHH‐competent chicken limb bud cells following FGF treatment. The analysis identified a candidate intermediate molecule, the Lim homeobox 2 (LHX2) transcription factor, that displayed a robust response to FGF (>5 fold upregulation). Via comparative genomics, we found LHX2 to be highly conserved across vertebrate species. Additionally, the endogenous expression of LHX2 is in an FGF‐responsive domain which overlaps that of SHH. Thus, we hypothesize that LHX2 is an intermediate molecule downstream of FGF in the regulation of SHH expression.To confirm FGF induction of LHX2, we performed in situ hybridization on chicken embryos implanted with FGF‐soaked beads. LHX2 is upregulated within 3 hours of bead implantation. Using cyclohexamide to globally block protein translation, we observed that LHX2's upregulation via ectopic FGF persisted. We therefore identified LHX2 as a primary response target of FGF signaling. Studies are underway to determine which of the canonical signaling pathways (MAPK/ERK1/2 or AKT) are involved in LHX2 induction.In an effort to assess LHX2's ability to regulate SHH expression in the context of FGF signaling, we knocked‐down LHX2 protein around an FGF bead which lead to a decrease in SHH expression around the bead. We also overexpressed LHX2 in the presence of ectopic FGF and observed an increased in SHH expression. LHX2 alone, however, was insufficient to upregulate SHH expression.Taken together, these data suggest that LHX2 is an intermediate factor downstream of FGF that is necessary but not sufficient for SHH expression in the FGF‐SHH arm of the reciprocal feedback loop.Support or Funding InformationDepartment of Pathology and Human Anatomy
Propagating the Ovarian Cancer Stem Cells by Reprogramming the Tumor Cells
Authors: Chen Yu‐An , Lu Chen‐Yu , Cheng Wen‐Fang , Ho Hong‐Nerng , Cheng Hsin‐Fu 
Published: November 2023

Drug resistance and metastasis are considered to be the major factors leading to tragic prognosis and high rate of mortality in cancer patients. Recent evidences suggest that cancer stem cells (CSCs) possess the essential property of self‐protection from chemotherapy, exhibit the ability to self‐renew and generate cancer cells by asymmetric cell division. Nevertheless, the currently known mechanisms likely explain only the tip of an iceberg about CSC property, acquisition and maintenance. The information from data mining is still limited due to the rarity of CSCs in clinical samples. Ovarian cancer is the most lethal malignancy of the female reproductive system. CSCs in ovarian cancers are considered to acquire the molecular armaments of stem cells, which carry stem cell property and can determine the level of malignant potential of the cancer cells, similar to the findings in other cancer cell types.To overcome the limitation and assess the underlying mechanism, we introduced a set of defined factors (OCT3/4, SOX2, KLF4 and c‐Myc) into human serous ovarian cancer cells, which is one of the most frequently encountered ovarian cancer type in female, through Sendai virus reprogramming, aiming to induce CSC properties in the cancer cells. We then evaluated the CSC properties in the cells. In preliminary data, we observed that the ovarian cancer cells transduced with the four Yamanaka factors showed significantly enhanced pluripotent stem cell properties and drug resistance. We thus named the cells with CSC properties as induced ovarian CSCs (iOCSCs). These iOCSCs could be maintained and expanded up to at least 40 passages.Notably, consistent with the original ovarian cancer cells, iOCSCs could be differentiated into ovarian lineage cells, displaying markers as CA125 and CK‐7, shows that we generate generated iOCSCs with lineage specificity directly from cancer cells. In addition, we also confirmed that the phenotypes of our iOCSCs were reproducible in organoid culture and serial transplantation. The next, we are going to analysis the gene expression, transcriptome and metabolomics in iOCSCs to fully understand CSCs and find out new therapies target. Intriguingly, iOCSCs also acquired the ability to differentiate into cells belonging to the three embryonic germ layers, similar to human iPS cells or ES cells, this finding is probably the dawn of uncovering the stem cell tumorigenecity.It is worth to emphasize again, this great value present approach thus makes it feasible to obtain abundant CSCs to support our understanding and in‐depth research into CSCs and hopefully can help in developing new therapeutic strategies to treat ovarian cancers.Support or Funding InformationNational Science Council of the Republic of China (NSC) and National Taiwan University Hospital (NTUH), Taiwan
SPARC and Hevin in Mustard‐Induced Skin Wound Healing
Authors: Chang Yoke‐Chen , Chang Hui‐Ying , Hahn Rita , Svobada Kathy K. , Gordon Marion K , Gerecke Donald R. 
Published: November 2023

Sulfur mustard (SM) and its analog nitrogen mustard (NM) are potent bifunctional alkylating agents that induce skin blisters. They crosslink proteins and DNA and alter cell adhesion of basement membrane molecules. Dermal toxicity of the mustard agents includes separation of the epidermis and dermis, a strong inflammatory response, and prolonged wound healing. Matricellular proteins (MPs) including SPARC and hevin (aka SPARC‐like 1) are secreted proteins that are incorporated into the provisional matrix upon injury. MPs act as temporally dynamic signaling molecules to modulate cell‐matrix interactions during healing. Hevin can be cleaved by proteinase ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4). This cleavage produces a SPARC‐like fragment (SLF) which is essential to tissue development and wound healing. The expression and removal of MPs is controlled in normal healing, but may persist in chronic skin wounds. The temporal and spatial expression of MPs may play a role in the delayed repair of mustard injury. SPARC, hevin, ADAMTS4, and the basement membrane zone (BMZ) marker, laminin 332 (LM332), were examined over the course of 10 days after exposure of mouse dorsal skin to 5 μmoles NM. In unexposed controls, immunofluorescence (IF) analysis of LM332 showed continuous staining across the BMZ, with minimal staining of SPARC, and hevin. At 1 day post NM‐exposure, H & E staining showed characteristic dermal‐epidermal separations, while IF showed a spotty discontinuous pattern for LM332. Strong staining of SPARC appeared throughout the BMZ. Hevin staining was less intense than SPARC at this time point. Hevin became more apparent in the hyperplastic epidermis at 3 days post‐NM. By days 7–10, hevin stained throughout the hyperplastic epidermis. WB analysis confirmed the sequential deposition of SPARC and hevin in NM injured skin. SPARC showed a 43 kDa band at 1 day, and hevin showed both full length (130 kDa) and fragments (75, 66, and 43 kDa) at 1–10 days post NM exposure. In addition, activated forms of ADAMTS4 were observed in NM exposed skin samples with bands at 75, 60, and 50 kDa by WB. Dual IF staining showed ADAMTS4 co‐localized with hevin in the BMZ and in the basal keratinocytes. This suggests hevin may be processed by ADAMTS4 to produce SLF for wound repair in our injury model. Overall, we observed sequential expression of SPARC and hevin in the BMZ of NM induced skin wounds. This may play a role in modulating the delayed wound healing of vesicant induced injury.Support or Funding InformationES005022, T32ES007148, and NIAMS U54AR055073