Digital Commons Network^™

Independent Reproduction Of The Flash Effect On The Gastrointestinal Tract: A Multi-Institutional Comparative Study, Anet Valdés Zayas, Neeraj Kumari, Kevin Liu, Denae Neill, Abagail Delahoussaye, Patrik Gonçalves Jorge, Reiner Geyer, Steven H Lin, Claude Bailat, François Bochud, Raphael Moeckli, Albert C Koong, Jean Bourhis, Cullen M Taniguchi, Fernanda G Herrera, Emil Schüler

Faculty, Staff and Student Publications

FLASH radiation therapy (RT) is a promising new paradigm in radiation oncology. However, a major question that remains is the robustness and reproducibility of the FLASH effect when different irradiators are used on animals or patients with different genetic backgrounds, diets, and microbiomes, all of which can influence the effects of radiation on normal tissues. To address questions of rigor and reproducibility across different centers, we analyzed independent data sets from The University of Texas MD Anderson Cancer Center and from Lausanne University (CHUV). Both centers investigated acute effects after total abdominal irradiation to C57BL/6 animals delivered by the FLASH …

The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton

Graduate School of Biomedical Sciences Theses and Dissertations

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen known as a major cause of hospital-acquired secondary infections, commonly causing chronic respiratory infections in immunocompromised individuals, especially those with cystic fibrosis, and often found in wound infections. P. aeruginosa uses the quorum sensing pathway to readily form protective biofilms, which reduce the efficacy of antibiotics and access by host immune cells to eradicate the pathogen. Specialized pro-resolving mediators (SPMs) are lipids endogenously produced by the host immune response to infection to aid in infection resolution. One SPM, Lipoxin A4 (LxA4), has been shown to be a robust quorum sensing inhibitor.

The …

Effects Of Diet On Lcn2 Expression And Onset Of Neuroinflammation In An Alzheimer’S Disease Mice Model, Abdirahman A. Hayir

Neuroscience Honors Projects

This project covers the findings regarding the impact of diet on lipocalin 2 (LCN2) and the effects it has on neuroinflammation Alzheimer’s Disease (AD). LCN2 is a protein that is critical to the functionality of mitochondria and inflammatory responses. Evidence has shown that mitochondrial dysfunction is a potential central event in driving AD pathogenesis and contributing to formation of pathological hallmarks such as chronic inflammation. Furthermore, studies have shown that LCN2 can be deficient under metabolic conditions such as high-fat-diet (HFD). This study investigates if HFD induces LCN2 deficiency and increased neuroinflammation in an AD mice model.

Effects Of Coordinated Reset Deep Brain Stimulation Of Subthalamic Nucleus On Parkinsonian Gait In The Non-Human Primate Model, Kanon Nakajima

Neuroscience Honors Projects

Parkinson’s Disease (PD) is a neurodegenerative disorder that affects over 10 million people worldwide. Deep Brain Stimulation (DBS) has been a successful treatment for advanced PD, however, can be accompanied with current spread related side effects. Coordinated Reset (CR) DBS is a novel therapeutic approach that could reduce the risk of side-effects by using lower current. Previous research has shown therapeutic effects of CR DBS on PD motor symptoms including akinesia, bradykinesia, rigidity, and tremor that sustained after stimulation cessation (i.e., carryover effect), however its effect on gait dysfunction is unknown even though it can be one of the most …

Jurisgenerative Tissues: Sociotechnical Imaginaries And The Legal Secretions Of 3d Bioprinting, Roxanne Mykitiuk, Joshua Shaw

Articles & Book Chapters

Three-dimensional ‘bioprinting’ is under development, which may produce living human organs and tissues to be surgically implanted in patients. Like tissue engineering and regenerative medicine generally, the process of bioprinting potentially disrupts experience of the human body by redefining understandings of, and becoming actualised in new practices and regimes in relation to, the body. The authors consider how these novel sociotechnical imaginaries may emerge, having regard to law’s contribution to, as well as its possible transformation by, the process of 3D bioprinting. The authors draw on Gilbert Simondon and corporeal, material feminists to account for these disruptions as ‘ontogenetic,’ in …

Regeneration Of Neurons In Human Brain Tissue; A Revolutionary Concept With Therapeutic Potential, Mackenzie R. Dunn

Biomedical Sciences Undergraduate Research

There is current research to suggest that endogenous neuronal regeneration, exogenous neuronal stem cell transplantation and glial cell reprogramming could be prospective therapeutic treatments for neurodegeneration and traumatic injury. With these conditions, there is significant brain atrophy, loss of neurons and loss of synaptic connections which can have devastating effects on executive functioning, cognition, learning and memory. This review will examine these modern approaches to adult neurogenesis, and assess the viable mechanisms and future outlook of these three therapies for neurological regenerative medicine.

The Effects Of Exercise On The Lipid Profile Of Extracellular Vesicles, Tesha Kerr

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

We sought to ascertain the effect of different types of exercise (aerobic training and resistance training) on the lipid profile of extracellular vesicles. Thus, we had participants perform bouts of AT and RT and rest (control) and collected blood samples from them immediately after (timepoint 0) and 30 minutes after (timepoint 30) exercise. Small extracellular vesicles (sEVs) were isolated from plasma of participants using cushioned-density gradient ultracentrifugation (C-DGUC). Small EV size, morphology, and protein markers were determined using nanoparticle tracking analysis, transmission electron microscopy, and western blot, respectively. Additionally, we performed untargeted lipidomics on the sEV isolate. We found that …

The Revolutionary Genome Editor: Crispr-Cas9 Systems, Grace Spade

Senior Honors Theses

Genetic engineering is the modification of an organism's genetic material to alter its traits through adding, deleting, or changing specific genes. CRISPR-Cas9 systems are groundbreaking tools for genetic engineering, in short utilizing a molecule called RNA to guide a protein called Cas9 to a specific location in DNA to add, delete, or replace genes. The history of how the CRISPR-Cas9 systems came into existence, how it was adapted from a natural defense system in bacteria, and its mechanism of action in both are explained. Its applications, both present and future, competing genetic modifiers, advantages and disadvantages, and the ethical dilemmas …

In Vitro Gametogenesis: A Research Timeline And Implications For The Future Of Assisted Reproductive Technology, Nicole Buckley

Senior Honors Theses

The novel reproductive technology, In Vitro Gametogenesis (IVG), includes the process of obtaining mature viable germ cells from pluripotent stem cells. To do so, embryonic stem cells and induced pluripotent stem cells are specified to primordial germ cells and differentiated to form gametes that undergo further maturation, which subsequently may undergo in vitro fertilization to form an embryo. With this capability, IVG holds the power to provide a novel treatment option for human infertility. As of now, research has been conducted on mice successfully, and with limited success in humans. Future research will likely focus on discovering the species-specific differences …

Investigating The Effects Of Sex And Carvedilol On Ischemia Preconditioning Protective Effect, Casey Jc Miller

Honors Thesis

Many studies have been done on ischemic preconditioning and its protective effects using the murine model with overwhelmingly consistent and promising results. However, many clinical trials have failed to demonstrate the protective effects of ischemic preconditioning. The causes of the inconsistency are unknown. The effect of sex on ischemic preconditioning protection is largely unclear, which may be a contributing factor. Additionally, in clinical trials, the recruited patients were most likely taking some medications. This project aimed to test the differences in sex on preconditioning protection and the effect of a common β-blocker medication, Carvedilol, on preconditioning protection. Tourniquet-induced unilateral hindlimb …

The Non-Coding Rna Journal Club: Highlights On Recent Papers—12, Patrick K.T. Shiu, Mirolyuba Ilieva, Anja Holm, Shizuka Uchida, Johanna K. Distefano, Agnieszka Bronisz, Ling Yang, Yoh Asahi, Ajay Goel, Liuqing Yang, Ashok Nuthanakanti, Alexander Serganov, Suresh K. Alahari, Chunru Lin, Barbara Pardini, Alessio Naccarati, Jing Jin, Beshoy Armanios, Xiao Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, André P. Gerber, He Lin, Simon J. Conn, Doha Magdy Mostafa Sleem

School of Graduate Studies Faculty Publications

No abstract provided.

Consensus-Based Evaluation Of Outcome Measures In Pediatric Stroke Care: A Toolkit, Samantha J Feldman, Lauren A Beslow, Ryan J Felling, Laura A Malone, Michaela Waak, Stuart Fraser, Nihal Bakeer, Jo Ellen M Lee, Victoria Sherman, Melissa M Howard, Beth Anne Cavanaugh, Robyn Westmacott, Lori C Jordan

Faculty, Staff and Student Publications

Following a pediatric stroke, outcome measures selected for monitoring functional recovery and development vary widely. We sought to develop a toolkit of outcome measures that are currently available to clinicians, possess strong psychometric properties, and are feasible for use within clinical settings. A multidisciplinary group of clinicians and scientists from the International Pediatric Stroke Organization comprehensively reviewed the quality of measures in multiple domains described in pediatric stroke populations including global performance, motor and cognitive function, language, quality of life, and behavior and adaptive functioning. The quality of each measure was evaluated using guidelines focused on responsiveness and sensitivity, reliability, …

Model-Constrained Reconstruction Accelerated With Fourier-Based Undersampling For Hyperpolarized [1-13c] Pyruvate Imaging, Zhan Xu, Keith A Michel, Christopher M Walker, Collin J Harlan, Gary V Martinez, Jeremy W Gordon, Hsin-Yu Chen, Daniel B Vigneron, James A Bankson

Faculty, Staff and Student Publications

PURPOSE: Model-constrained reconstruction with Fourier-based undersampling (MoReFUn) is introduced to accelerate the acquisition of dynamic MRI using hyperpolarized [1-

METHODS: The MoReFUn method resolves spatial aliasing using constraints introduced by a pharmacokinetic model that describes the signal evolution of both pyruvate and lactate. Acceleration was evaluated on three single-channel data sets: a numerical digital phantom that is used to validate the accuracy of reconstruction and model parameter restoration under various SNR and undersampling ratios, prospectively and retrospectively sampled data of an in vitro dynamic multispectral phantom, and retrospectively undersampled imaging data from a prostate cancer patient to test the fidelity …

De Novo Mutations Disturb Early Brain Development More Frequently Than Common Variants In Schizophrenia, Toshiyuki Itai, Peilin Jia, Yulin Dai, Jingchun Chen, Xiangning Chen, Zhongming Zhao

Faculty, Staff and Student Publications

Investigating functional, temporal, and cell-type expression features of mutations is important for understanding a complex disease. Here, we collected and analyzed common variants and de novo mutations (DNMs) in schizophrenia (SCZ). We collected 2,636 missense and loss-of-function (LoF) DNMs in 2,263 genes across 3,477 SCZ patients (SCZ-DNMs). We curated three gene lists: (a) SCZ-neuroGenes (159 genes), which are intolerant to LoF and missense DNMs and are neurologically important, (b) SCZ-moduleGenes (52 genes), which were derived from network analyses of SCZ-DNMs, and (c) SCZ-commonGenes (120 genes) from a recent GWAS as reference. To compare temporal gene expression, we used the BrainSpan …

Hyperphosphorylated Tau In Mesial Temporal Lobe Epilepsy: A Neuropathological And Cognitive Study, Eliana C B Toscano, Érica L M Vieira, Lea T Grinberg, Natalia P Rocha, Joseane A S Brant, Regina S Paradela, Alexandre V Giannetti, Claudia K Suemoto, Renata E P Leite, Ricardo Nitrini, Milene A Rachid, Antonio L Teixeira

Faculty, Staff and Student Publications

Temporal lobe epilepsy (TLE) often courses with cognitive deficits, but its underlying neuronal basis remains unclear. Confluent data suggest that epilepsy share pathophysiological mechanisms with neurodegenerative diseases. However, as most studies analyze subjects 60 years old and older, it is challenging to rule out that neurodegenerative changes arise from age-related mechanisms rather than epilepsy in these individuals. To fill this gap, we conducted a neuropathological investigation of the hippocampal formation of 22 adults with mesial TLE and 20 age- and sex-matched controls (both younger than 60 years). Moreover, we interrogated the relationship between these neuropathological metrics and cognitive performance. Hippocampal …

Myosin Light-Chain 4 Gene-Transfer Attenuates Atrial Fibrosis While Correcting Autophagic Flux Dysregulation, Yuan Zhong, Kai Tang, Stanley Nattel, Ming Zhai, Shiyu Gong, Qing Yu, Yanxi Zeng, Guangxi E, Nuerbiyemu Maimaitiaili, Jun Wang, Yawei Xu, Wenhui Peng, Hailing Li

Faculty, Staff and Student Publications

OBJECTIVES: To determine the role of MYL4 regulation of lysosomal function and its disturbance in fibrotic atrial cardiomyopathy.

BACKGROUND: We have previously demonstrated that the atrial-specific essential light chain protein MYL4 is required for atrial contractile, electrical, and structural integrity. MYL4 mutation/dysfunction leads to atrial fibrosis, standstill, and dysrhythmia. However, the underlying pathogenic mechanisms remain unclear.

METHODS AND RESULTS: Rats subjected to knock-in of a pathogenic MYL4 mutant (p.E11K) developed fibrotic atrial cardiomyopathy. Proteome analysis and single-cell RNA sequencing indicate enrichment of autophagy pathways in mutant-MYL4 atrial dysfunction. Immunofluorescence and electron microscopy revealed undegraded autophagic vesicles accumulated in MYL4

CONCLUSIONS: …

The Glycoprotein Cd147 Defines Mirna-Enriched Extracellular Vesicles That Derive From Cancer Cells, Song Yi Ko, Wonjae Lee, Melanie Weigert, Eric Jonasch, Ernst Lengyel, Honami Naora

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) are ideal for liquid biopsy, but distinguishing cancer cell‐derived EVs and subpopulations of biomarker‐containing EVs in body fluids has been challenging. Here, we identified that the glycoproteins CD147 and CD98 define subpopulations of EVs that are distinct from classical tetraspanin+ EVs in their biogenesis. Notably, we identified that CD147+ EVs have substantially higher microRNA (miRNA) content than tetraspanin+ EVs and are selectively enriched in miRNA through the interaction of CD147 with heterogeneous nuclear ribonucleoprotein A2/B1. Studies using mouse xenograft models showed that CD147+ EVs predominantly derive from cancer cells, whereas the majority of tetraspanin+ EVs are not …

Emerging Role Of Tak1 In The Regulation Of Skeletal Muscle Mass, Anirban Roy, Vihang A Narkar, Ashok Kumar

Faculty, Staff and Student Publications

Maintenance of skeletal muscle mass and strength throughout life is crucial for heathy living and longevity. Several signaling pathways have been implicated in the regulation of skeletal muscle mass in adults. TGF-β-activated kinase 1 (TAK1) is a key protein, which coordinates the activation of multiple signaling pathways. Recently, it was discovered that TAK1 is essential for the maintenance of skeletal muscle mass and myofiber hypertrophy following mechanical overload. Forced activation of TAK1 in skeletal muscle causes hypertrophy and attenuates denervation-induced muscle atrophy. TAK1-mediated signaling in skeletal muscle promotes protein synthesis, redox homeostasis, mitochondrial health, and integrity of neuromuscular junctions. In …

2023 Research Day Program, Lincoln Memorial University

Research Day

This program contains abstracts and presentation summaries from LMU's 2023 Annual Research Day conference.

Somatostatin Regulates Central Clock Function And Circadian Responses To Light, Deborah A.M. Joye, Kayla E. Rohr, Kimberlee Suenkens, Alissa Wuorinen, Thomas Inda, Madeline Arzbecker, Emma Mueller, Alec Huber, Harshida Pancholi, Murray G. Blackmore, Vania Carmona-Alcocer, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Daily and annual changes in light are processed by central clock circuits that control the timing of behavior and physiology. The suprachiasmatic nucleus (SCN) in the anterior hypothalamus processes daily photic inputs and encodes changes in day length (i.e., photoperiod), but the SCN circuits that regulate circadian and photoperiodic responses to light remain unclear. Somatostatin (SST) expression in the hypothalamus is modulated by photoperiod, but the role of SST in SCN responses to light has not been examined. Our results indicate that SST signaling regulates daily rhythms in behavior and SCN function in a manner influenced by sex. First, we …

Leukocyte Tyrosine Kinase (Ltk) Is The Mendelian Determinant Of The Axolotl Melanoid Color Variant, Mirindi Kabangu, Raissa Cecil, Lloyd Strohl Ii, Nataliya Y. Timoshevskaya, Jeramiah James Smith, Stephen Randal Voss

Markey Cancer Center Faculty Publications

The great diversity of color patterns observed among amphibians is largely explained by the differentiation of relatively few pigment cell types during development. Mexican axolotls present a variety of color phenotypes that span the continuum from leucistic to highly melanistic. The melanoid axolotl is a Mendelian variant characterized by large numbers of melanophores, proportionally fewer xanthophores, and no iridophores. Early studies of melanoid were influential in developing the single-origin hypothesis of pigment cell development, wherein it has been proposed that all three pigment cell types derive from a common progenitor cell, with pigment metabolites playing potential roles in directing the …

Outcomes Among Heart Failure Patients Hospitalized For Acute Pulmonary Embolism And Covid-19 Infection: Insight From The National Inpatient Sample, Bruce Adrian Casipit, Sahana Tito, Isaac Ogunmola, Abiodun Idowu, Shivaraj Patil, Kevin Lo, Behnam Bozorgnia

Einstein Health Papers

There is paucity of data regarding the outcomes of hospitalized acute pulmonary embolism (PE) patients with heart failure (HF) and Coronavirus Disease 2019 (COVID-19) infection. We utilized the 2020 National Inpatient Sample (NIS) Database in conducting a retrospective cohort study to investigate the outcomes of hospitalized acute PE patients with HF and COVID-19, looking at its impact on in-hospital mortality, thrombolysis, and thrombectomy utilization as well as hospital length of stay (LOS). A total of 23,413 hospitalized acute PE patients with HF were identified in our study, of which 1.26% (n = 295/23,413) had COVID-19 infection. Utilizing a stepwise survey …

The Effect Of A Pharmaceutical Ghrelin Agonist On Lifespan In C57bl/6j Male Mice: A Controlled Experiment, Kathryn A Kaiser, Inga Kadish, Thomas Van Groen, Daniel L Smith, Stephanie Dickinson, Beate Henschel, Erik S Parker, Andrew W Brown, David B Allison

Children’s Nutrition Research Center Staff Publications

Interventions for animal lifespan extension like caloric restriction (CR) have identified physiologic and biochemical pathways related to hunger and energy-sensing status as possible contributors, but mechanisms have not been fully elucidated. Prior studies using ghrelin agonists show greater food intake but no effect on lifespan in rodent models. This experiment in male C57BL/6J mice tested the influence of ghrelin agonism for perceived hunger, in the absence of CR, on longevity. Mice aged 4 weeks were allowed to acclimate for 2 weeks prior to being assigned (N = 60/group). Prior to lights off daily (12:12 cycle), animals were fed a ghrelin …

Aerosolized Immunotherapeutic Nanoparticle Inhalation Potentiates Pd-L1 Blockade For Locally Advanced Lung Cancer, Yang Liu, William N Crowe, Lulu Wang, W Jeffrey Petty, Amyn A Habib, Dawen Zhao

Faculty, Staff and Student Publications

Despite therapeutic advancements, the prognosis of locally advanced non-small cell lung cancer (LANSCLC), which has invaded multiple lobes or the other lung and intrapulmonary lymph nodes, remains poor. The emergence of immunotherapy with immune checkpoint blockade (ICB) is transforming cancer treatment. However, only a fraction of lung cancer patients benefit from ICB. Significant clinical evidence suggests that the proinflammatory tumor microenvironment (TME) and programmed death-ligand 1 (PD-L1) expression correlate positively with response to the PD-1/PD-L1 blockade. We report here a liposomal nanoparticle loaded with cyclic dinucleotide and aerosolized (AeroNP-CDN) for inhalation delivery to deep-seated lung tumors and target CDN to …

Dietary Intake Of Total, Heme And Non-Heme Iron And The Risk Of Colorectal Cancer In A European Prospective Cohort Study, Elom K Aglago, Amanda J Cross, Elio Riboli, Veronika Fedirko, David J Hughes, Agnes Fournier, Paula Jakszyn, Heinz Freisling, Marc J Gunter, Christina C Dahm, Kim Overvad, Anne Tjønneland, Cecilie Kyrø, Marie-Christine Boutron-Ruault, Joseph A Rothwell, Gianluca Severi, Verena Katzke, Bernard Srour, Matthias B Schulze, Clemens Wittenbecher, Domenico Palli, Sabina Sieri, Fabrizio Pasanisi, Rosario Tumino, Fulvio Ricceri, Bas Bueno-De-Mesquita, Jeroen W G Derksen, Guri Skeie, Torill Enget Jensen, Marko Lukic, Maria-Jose Sánchez, Pilar Amiano, Sandra Colorado-Yohar, Aurelio Barricarte, Ulrika Ericson, Bethany Van Guelpen, Keren Papier, Anika Knuppel, Corinne Casagrande, Inge Huybrechts, Alicia K Heath, Konstantinos K Tsilidis, Mazda Jenab

Faculty, Staff and Student Publications

BACKGROUND: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.

METHODS: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.

RESULTS: Of 450,105 participants (318,680 women) followed for 14.2 …

Effect Of The Physical Fibrillated Sweet Potato (Ipomoea Batatas) Stem On The Plant-Based Patty Analogues, Suyoon Lee, You Young Lee, Yang Kim, Seung Hwan Ham, Min Gyu Lee, Jungwoo Hahn, Young Jin Choi

Faculty, Staff and Student Publications

In this study, a dietary fiber extracted from sweet potato stems (Ipomoea batatas, PS) was evaluated for its ability to improve the quality of vegetable patty analogues. A patty analogues containing 0–50 wt% dietary fiber were prepared to analyze the utilized dietary fiber's performance. To evaluate the manufactured patty analogues, texture profile analysis, color analysis, emulsion stability, and microstructural analysis were conducted. As the PS increased, the hardness decreased, while the total expressible fluids tended to increase. The color analysis revealed that the a* value, which represents red, declined as the PS content increased, and heterogeneous colors showed …

Clinical Outcomes Of Immune Checkpoint Inhibitor Diabetes Mellitus At A Comprehensive Cancer Center, Rebecca Jeun, Priyanka C Iyer, Conor Best, Victor Lavis, Jeena M Varghese, Sireesha Yedururi, Veronica Brady, Isabella C Glitza Oliva, Ramona Dadu, Denai R Milton, Kristy Brock, Sonali Thosani

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a rare adverse event. In this study, we characterize clinical outcomes of patients with ICI-DM and evaluate survival impact of this complication on melanoma patients.

Research design & methods: We conducted a retrospective review of 76 patients diagnosed with ICI-DM from April 2014 to December 2020.

Results: 68% of patients presented in diabetic ketoacidosis, 16% had readmissions for hyperglycemia, and hypoglycemia occurred in 70% of patients after diagnosis. Development of ICI-DM did not impact overall survival or progression-free survival in melanoma patients.

Conclusion: Development of ICI-DM is associated with long-term insulin dependence …

An Antibody-Drug Conjugate Targeting Gpr56 Demonstrates Efficacy In Preclinical Models Of Colorectal Cancer, Joan Jacob, Liezl E Francisco, Treena Chatterjee, Zhengdong Liang, Shraddha Subramanian, Qingyun J Liu, Julie H Rowe, Kendra S Carmon

Faculty, Staff and Student Publications

Background: Long-term prognosis remains poor for colorectal cancer (CRC) patients with advanced disease due to treatment resistance. The identification of novel targets is essential for the development of new therapeutic approaches. GPR56, an adhesion GPCR, is highly expressed in CRC tumours and correlates with poor survival. Here, we describe the generation and preclinical evaluation of a novel ADC consisting of an anti-GPR56 antibody (10C7) conjugated with the DNA-damaging payload duocarmycin.

Methods: RNA-seq dataset analysis was performed to determine GPR56 expression in CRC subtypes. The specificity of binding, epitope mapping, and internalisation of 10C7 was examined. 10C7 was conjugated to payload …

Sensing Fear: Fast And Precise Threat Evaluation In Human Sensory Cortex, Wen Li, Andreas Keil

Faculty, Staff and Student Publications

Animal models of threat processing have evolved beyond the amygdala to incorporate a distributed neural network. In human research, evidence has intensified in recent years to challenge the canonical threat circuitry centered on the amygdala, urging revision of threat conceptualization. A strong surge of research into threat processing in the sensory cortex in the past decade has generated particularly useful insights to inform the reconceptualization. Here, synthesizing findings from both animal and human research, we highlight sensitive, specific, and adaptable threat representations in the sensory cortex, arising from experience-based sculpting of sensory coding networks. We thus propose that the human …

Augmentation Of Bmp Signaling In Cranial Neural Crest Cells Leads To Premature Cranial Sutures Fusion Through Endochondral Ossification In Mice, Hiroki Ueharu, Haichun Pan, Xia Liu, Mamoru Ishii, Jessica Pongetti, Anshul K Kulkarni, Folasade E Adegbenro, Jaden Wurn, Robert E Maxson, Hongchen Sun, Yoshihiro Komatsu, Honghao Zhang, Jingwen Yang, Yuji Mishina

Faculty, Staff and Student Publications

Craniosynostosis is a congenital anomaly characterized by the premature fusion of cranial sutures. Sutures are a critical connective tissue that regulates bone growth; their aberrant fusion results in abnormal shapes of the head and face. The molecular and cellular mechanisms have been investigated for a long time, but knowledge gaps remain between genetic mutations and mechanisms of pathogenesis for craniosynostosis. We previously demonstrated that the augmentation of bone morphogenetic protein (BMP) signaling through constitutively active BMP type 1A receptor (caBmpr1a) in neural crest cells (NCCs) caused the development of premature fusion of the anterior frontal suture, leading to craniosynostosis in …