bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D Neuroanatomy: Using the HoloLens for an augmented reality approach in neuroanatomy education
Authors: Holman Parker , Bodnar Tamara , Ghomi Mehrdad , Choi Robyn , Moukhles Hakima , Krebs Claudia 
Published: June 2021

The gold standard for neuroanatomy instruction involves the use of human brain specimens and prosections; however, there is still a clear need for innovative visualizations and educational tools that supplement dissection and improve learning outcomes for students in many areas including health related disciplines. With technological advances in computer imaging and display devices, anatomy educators increasingly have a variety of options for delivering educational content. There are limitations to these approaches, which include challenges in accurately representing 3D structures, ease of use for instructors and students, as well as oversimplification or inaccurate information. Students consistently struggle with integrating 2D images into a complex representation of the interconnected brain, and overlaying this understanding with important vascular and clinically relevant information. Increasingly, 3D technologies are being employed to help close this gap in student learning; however, not all 3D technologies are alike, nor do they offer the same instructional value.The goal of the current project was to develop an augmented reality (AR) teaching tool that could be implemented in neuroanatomy instruction, and to evaluate its effectiveness in the classroom. In collaboration with Microsoft (BigPark Vancouver and Microsoft Garage Interns), an interactive lecture was developed using the HoloLens, a mixed reality headset offering the unique ability to blend virtual 3D content with the real world. Specifically, 3D reconstructions of basal ganglia nuclei were obtained from MRI scans and built into the teaching tool deployed on the HoloLens. Taking advantage of the HoloLens gesture recognition input system, interactivity was optimized, allowing the 3D reconstructions to be manipulated with ease and built up separately, as well as to visualize 2D MRI scans juxtaposed against 3D volumes of key brain nuclei. We are evaluating the pedagogical efficacy of this HoloLens teaching tool for undergraduate students, compared to traditional instructional methods. Assessments comprised multiple‐choice questions and structure identification on brain specimens focused on spatial orientation within the CNS as well as the ability to orient a 2D slice to the 3D structure of the brain. Students in both groups received baseline testing to assess both previous content knowledge as well as visuospatial reasoning to control for individual differences.Support or Funding InformationPJH, TSB supported by Mitacs Accelerate Internships in partnership with Microsoft. Equipment donated from Microsoft. MG, RC supported by Emerging Media Lab, UBC Studios.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
RNA and RNP Structures that Contribute to Viral Pathogenesis
Authors: Tolbert Blanton S. 
Published: June 2021

RNA viruses persist to pose serious threats to human health and global economies. Disease progression mediated by viral pathogenesis requires numerous intersections between host proteins and viral RNA (vRNA) elements. Host‐vRNA complexes drive essential processes in the replication cycles of viruses; as such, they represent novel targets for therapeutic intervention. Members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family are cellular proteins often usurped by RNA viruses. My lab studies the molecular mechanisms by which HIV and Enterovirus 71 redirects hnRNPs to control viral gene expression. To that end, we have designed an integrated biophysical framework to elucidate the structures of vRNAs and protein‐vRNA complexes. Here, we describe 3D structures of conserved HIV and EV71 RNA elements that regulate splicing and translation. We further show that conformational adaptation and slow protein motions are fundamental properties by which hnRNP A1 and hnRNP H achieve cognate RNA recognition. To globally identify determinants of specificity, we used High Throughput Sequencing Equilibrium (HTS‐EQ) binding experiments to characterize the complete affinity distribution of human hnRNP A1 bound to the HIV ESS3 stem loop. HTS‐EQ involves competitive binding of hnRNP A1 to a completely randomized pool of ESS3 apical loop variants (n=16,384). Quantitative analysis of the resulting affinity distribution reveals RNA sequence; motif copy number; motif spacing; and secondary structure determine specificity by modulating the rates of productive hnRNP A1‐RNA encounters. Collectively, our work is offering mechanistic insights into the strategies by which viruses coopt cellular RNA binding proteins.Support or Funding InformationNIH R01 GM101979NIH U54 GM103297This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
From Petabytes to Molecular Insights: Building an Operating System for Cancer
Authors: White Kevin 
Published: June 2021

Over the last decade there has been a confluence of technological advances in the computational and biological sciences that set the stage for large‐scale improvements in how cancers are diagnosed and treated, leading to a new vision for advancing precision oncology. As part of this vision we have taken steps to develop technological solutions and novel approaches to the challenge of integrating massive datasets and validating discoveries. In this context I will describe a series of proof‐of‐principle projects that our team has made to highlight basic discoveries and applications in cancer diagnostics and therapeutics. With these and many other efforts as a backdrop for what can be done, I will also describe our recent efforts at Tempus Labs to engineer and industrialize a systematic solution that is allowing physicians to treat patients enabled by a real‐time learning system that condenses petabytes of data into actionable information matched uniquely to each patient.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Suppression of Chemotherapy‐induced Cytokine/Eicosanoid Storm and Ovarian Tumor Growth by a Dual COX‐2/sEH Inhibitor
Authors: Gartung Allison , Yang Jun , Fernandes Djanira , Chang Jaimie , Hwang Sung Hee , Huang Sui , Kieran Mark , Hammock Bruce , Panigrahy Dipak 
Published: June 2021

While chemotherapy remains a mainstay in cancer treatment, growing evidence indicates that it may stimulate tumor growth. Other cancer therapies including radiation, immunotherapy, and stem cell transplantation may also trigger the release of pro‐inflammatory and pro‐tumorigenic cytokines in the tumor stroma. We recently demonstrated that although cancer therapy reduces tumor burden by killing tumor cells, the resulting dead cells, or ‘debris', can promote tumor growth by stimulating the release of cytokines. Chemotherapy fails to generate remission in over 70% of patients with ovarian cancer, is rarely curative, and simultaneously creates tumor cell debris. Thus, cancer therapy is inherently a double‐edged sword and targeting a single cytokine or pathway may not prevent therapy‐induced cancer. Soluble epoxide hydrolase (sEH) inhibitors have been shown to stimulate the resolution of inflammation by promoting the synthesis of pro‐resolving mediators and counter‐regulating pro‐inflammatory cytokines. In this study, tumor cell debris was prepared in vitro by treating either murine or human ovarian tumor cells with first‐line platinum or taxane‐based cytotoxic chemotherapies used for treating ovarian cancer (e.g. cisplatin, carboplatin, or paclitaxel). Chemotherapy‐generated tumor cell debris stimulated ovarian tumor growth in both immunocompetent and immunocompromised hosts. Debris triggered macrophage production of a series of pro‐inflammatory and pro‐angiogenic cytokines. Further, LC‐MS‐MS–based oxylipin profiling of tumor cell debris generated by chemotherapy revealed a pathological release of tumor‐promoting bioactive lipids (‘eicosanoid storm’) including cyclooxygenase (COX)‐derived prostaglandins, lipoxygenase‐derived HETEs, CYP450‐derived DiHOMEs and EpOMEs. We hypothesize that dual COX‐2/sEH inhibition may be a novel modality in suppressing ovarian tumor growth by stimulating the natural debris‐clearing process. A dual COX‐2/sEH inhibitor, PTUPB, suppressed debris‐induced cytokines (e.g. TNFα, CCL2, CCL4, CXCL2, G‐CSF, ICAM‐1, MMP‐9, and PAI‐1) and eicosanoids (e.g. PGF2a, PGD2, and PGJ2). PTUPB also delayed the onset of debris‐stimulated tumor growth in an ovarian cancer (ID8) model, achieving sustained survival over 80 days post‐injection. It is imperative to overcome the predicament between killing tumor cells and the inherent tumor‐promoting activity of the debris. Thus, dual inhibition of COX‐2/sEH may be a novel approach in cancer therapy to suppress the therapy‐induced cytokine/eicosanoid storm and debris‐stimulated tumor growth.Support or Funding InformationNational Cancer Institute grant RO1 01CA170549‐02; ROCA148633‐01A4; NIEHS Superfund Research Program RO1This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hypoxanthine as a Checkpoint Metabolite in Epithelial Energy Modulation and Barrier Function
Authors: Lee J Scott , Wang Ruth , Alexeev Erica , Lanis Jordi , Colgan Sean 
Published: June 2021

A primary function of intestinal epithelial cells (IECs) is to provide a selectively permeable barrier to protect the host from luminal microbiota and antigens, and to mediate the flux of nutrients, fluid, and waste across that barrier. Loss of intestinal barrier function is a hallmark of inflammatory bowel disease (IBD). Dysregulation of IEC barrier in IBD coincides with profound shifts in metabolic energy, especially in the colon, which exists in an energetically‐vulnerable state of physiologic hypoxia. The precise mechanism(s) by which metabolic pathways contribute to and control inflammation have yet to be elucidated. To delineate barrier‐related energy flux, an HPLC‐based profiling method was developed to track changes in energy and adenylate metabolites during intestinal epithelial barrier development and restitution. Cultured epithelia demonstrated a remarkable capacity to maintain ATP and phosphocreatine during barrier development. Further epithelial cell profiling identified a significant capacity for cultured human IECs to salvage hypoxanthine (Hpx) and shift their metabolic equilibrium toward the production of ATP and phosphocreatine. In a consistent manner, we have demonstrated that Hpx‐mediated shifts in metabolism result in enhanced epithelial barrier formation, increased epithelial restitution, and improved wound healing. Modulation of cellular energetics by Hpx were recapitulated with in vivo murine models, where orally‐delivered Hpx increased colonic ATP levels. Guided by an unbiased microarray analysis of Hpx treated human IECs, we identified a number of target genes important in mucosal differentiation, energy metabolism, and reactive oxygen species mediation. As the ATP consumed by IECs under energetic stress is shuttled to and pooled as Hpx, it appears not only as a central energy metabolite, but also as a regulator of gene expression. Taken together, our ongoing studies provide strong evidence that Hpx functions as a central, checkpoint energy metabolite in IEC function.Support or Funding InformationNIH/NIDDKThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Desmoglein Binding Properties are Regulated by Plakophilins
Authors: Vielmuth Franziska , Fuchs Michael , Foresti Marco , Keil Rene , Hatzfeld Mechthild , Spindler Volker , Waschke Jens 
Published: June 2021

Desmosomes are highly organized protein complexes required for strong intercellular adhesion of keratinocytes. To maintain desmosome integrity, desmosomal cadherins provide intercellular mechanical coupling with their extracellular domains whereas plaque proteins such as plakophilins (Pkp), plakoglobin and desmoplakin mediate the anchorage to the intermediate filament cytoskeleton. In addition, Pkp isoforms are involved in the regulation of desmosomal turnover and several signaling pathways and are thereby crucial for desmosomal adhesion. However, their contribution to binding properties of desmosomal cadherins has not been elucidated yet. Here, we used murine keratinocytes lacking either Pkp1 or Pkp3 (Pkp1 k.o. / Pkp3 k.o.) and characterized Dsg1 and 3 binding properties in comparison to wildtype cells (Pkp wt). Both, Pkp1 and 3 k.o. cells showed compromised intercellular adhesion and reduced membrane levels of Dsg1 and Dsg3. Consistent with these findings, the amount of Dsg3 oligomers detected by membrane‐impermeable extracellular crosslinking was drastically reduced in both, Pkp1 and 3 k.o. cell lines. Along the same line, binding frequencies of both, Dsg1 and Dsg3‐dependent binding events as well as binding strength and the step position of Dsg3 interaction, the latter of which represents a measure for cytoskeletal anchorage, were drastically reduced in Pkp1 and 3 k.o. cell lines. Further, Dsg1 binding frequency was higher at cell borders compared to cell surface in wt but not in Pkp1 and Pkp3 k.o. cells, indicating a Pkp‐dependent control of Dsg1 membrane positioning. Moreover, alteration of p38MAPK signaling, a central signaling pathway for the regulation of desmosomal adhesion, correlated with intercellular adhesion in all cell lines. However, Pkp3 k.o. cells showed reduced activity of p38MAPK under untreated conditions as well as a diminished response to the p38MAPK activator anisomycin, indicating an important role of Pkp3 for p38MAPK signaling. Taken together, these data suggest (1) that Pkps are important for localization and binding of desmosomal cadherins and (2) that Pkp3 may participate in the regulation of desmosomal adhesion via p38MAPK signaling.Support or Funding InformationFunding Information: Supported by Else‐Kröner‐Fresenius‐Stiftung (2016_A157).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Deficiency of miR‐1954 promotes cardiac remodeling
Authors: Gupta Sudhiranjan , Chisson Valorie 
Published: June 2021

Cardiac remodeling due to hemodynamic overload is associated with significant morbidity and mortality. In response to stress, cardiomyocyte (CM) become hypertrophied whereas cardiac fibroblasts convert into myofibroblasts. The phenomenon leads to the development of cardiac hypertrophy, fibrosis and impair cardiac function. Previously, we have shown the pivotal role of miRNA (a new class of post‐transcriptional regulators) in cardiac remodeling, but, loss of miRNA contributing to the onset of cardiac remodeling remains elusive. Using next generation miRNA sequencing, we discovered a panel of novel dysregulated miRNAs from read‐data, secondary structure and miRPara classification score analysis in wild‐type mice (WT) infused with Angiotensin II (Ang II). Among them, one was identified as miR‐1954, a novel miRNA which was significantly reduced in Ang II‐infusion and transverse aortic constriction (TAC). Following an unbiased approach, we confirmed that Sp1‐Gata4‐Col I‐Tsp1‐axis is the bona‐fide targets. Our hypothesis is that deficiency of miR‐1954 exacerbates cardiac remodeling leading to hypertrophy and fibrosis through paracrine mechanism; and overexpression of miR‐1954 mitigates the cardiac damage and abrogates remodeling by modulating Sp1‐Gata4‐Col I‐Tsp1‐axis. Our data demonstrated that depletion of miR‐1954 in CM triggers hypertrophic response by modulating Sp1 and Gata4; releases soluble factors (Tgfb1) that triggers cardiac fibroblasts proliferation; upregulation of thrombospondin 1 (Tsp1) and collagen I (Col I). Overexpression of miR‐1954 in CM reverses these processes implicated a cellular cross‐talk. Cardiac‐specific overexpression of pre‐miR‐1954 transgenic mice (miR‐1954 Tg) showed reduced cardiac mass and improved function compared to WT littermate after Ang II treatment. Inhibition of miR‐1954 by locked nucleic acid of anti‐miR‐1954 exacerbates cardiac hypertrophy and fibrosis. Our findings provide evidence that loss of miR‐1954 promotes cardiac remodeling by targeting Sp1‐Gata4‐Col I‐Tsp1‐axis and, overexpression of miR‐1954 reverses the process. We conclude that miR‐1954 could be a triggering factor in cardiac remodeling and providing new mechanistic information for therapeutic benefit.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Intersectional Genetic Approaches for Studying Dopaminergic Subpopulations
Authors: Bateup Helen 
Published: June 2021

Midbrain dopamine neurons project to numerous targets throughout the brain to modulate various behaviors and brain states. Within this small population of neurons exists significant heterogeneity based on circuitry, physiology, and disease susceptibility. Recent studies have shown that dopamine neurons can be subdivided based on gene expression; however, the extent to which genetic markers define functionally relevant dopaminergic sub‐types has not been determined. To address this, we performed single cell RNA‐sequencing of midbrain dopamine neurons and identified genes that define dopaminergic subpopulations. Using a combination of anatomy, circuit tracing, and electrophysiology we have defined the projection targets, cellular properties, and disease vulnerability of two groups of dopamine neurons. Our current efforts are aimed at generating intersectional mouse genetic tools that will allow us to selectively target and manipulate dopaminergic subpopulations to understand their functional roles. This approach will allow us to dissect the complexity of the dopaminergic system, thereby furthering our understanding of how specific dopaminergic circuits control behavior in both normal and disease states.Support or Funding InformationThis work is supported by a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation and a fellowship from the Alfred P. Sloan Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cerebellar Neuron Diversity in the Zebrafish: More atoh1 Genes for More atoh1 Fates?
Authors: Moens Cecilia B. , Kidwell Chelsea U. 
Published: June 2021

During mammalian cerebellar development, a single Atoh1 basic‐helix‐loop‐helix transcription factor is required sequentially for the specification of multiple neuron types. The zebrafish genome encodes three paralagous atoh1 genes, atoh1a, atoh1b and atoh1c with overlapping but distinct spatio‐temporal expression patterns in the developing cerebellum. (The presence of extra paralogs in fish genomes is due to a whole‐genome duplication at the base of the teleost lineage). We have studied the roles of zebrafish atoh1 paralogs using transgenic reporters to mark atoh1c‐and atoh1a‐specified neurons, as well using CRISPR/Cas9‐generated mutant alleles in all three genes. Our analysis suggests that additional atoh1 genes are the source of additional neuronal diversity in the zebrafish cerebellum. atoh1c‐expressing cells are organized in two distinct domains: an early expression domain at the mid‐hindbrain boundary gives rise to an extracerebellar population in rhombomere 1 and an upper rhombic lip domain gives rise to granule cells that populate the four granule neuron territories of the fish cerebellum. Atoh1a‐expressing cells at the URL give rise to a separate population of granule neurons that do not overlap with the atoh1c populations. Consistent with this, atoh1a and atoh1c are both required for the specification of the full complement of granule neurons. These results suggest that zebrafish atoh1 duplicates generate granule neuron diversity that is not detected in mammals.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reconstructing Jaw Movement and Musculature in the Xenacanth Shark Orthacanthus texensis
Authors: Bronson Allison Whitney , Heers Ashley 
Published: June 2021

Most of the shark fossil record consists of teeth, due to their relative abundance, decay‐resistant enameloid, and the poor preservation potential of cartilaginous skeletons. However, rare cartilage fossils have changed our understanding of chondrichthyan evolution. Sharks have traditionally been considered primitive vertebrates, but new paleontological information demonstrates that chondrichthyans are actually a highly specialized group of fishes. In addition to valuable phylogenetic characters from fossil cartilage, three‐dimensionally preserved specimens allow us to explore functional morphology in extinct taxa. Here, we reconstruct jaw movement and musculature of the xenacanth Orthacanthus texensis. The cranium and jaws of Orthacanthus have been previously described, but a complete three‐dimensional specimen from the Permian of Texas (MCZ 12872) has never been addressed in its entirety. To better understand xenacanth anatomy, we took three‐dimensional surface scans of Orthacanthus skeletal elements by laser scanning, and articulated each element in Maya. We reconstructed musculature based on comparisons with several dissections of extant taxa, and then used Software for Interactive Musculoskeletal Modeling (SIMM) and OpenSim to assess muscle moment arms, potential functions, and optimal positioning for increasing bite forces. We find that Orthacanthus had large, extensive adductor muscles. To our knowledge, this is the first time SIMM has been used to model extinct chondrichthyan musculature. Computer modeling is an important method for this type of study, as xenacanths are not closely related to any modern sharks, so dissection of extant taxa alone is inadequate for modeling xenacanth musculature.Support or Funding InformationRichard Gilder Graduate School at the American Museum of Natural HistoryThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.