Digital Commons Network^™

Deepmicetl: A Deep Transfer Learning Based Prediction Of Mice Cardiac Conduction Diseases Using Early Electrocardiograms, Ying Liao, Yisha Xiang, Mingjie Zheng, Jun Wang

Faculty, Staff and Student Publications

Cardiac conduction disease is a major cause of morbidity and mortality worldwide. There is considerable clinical significance and an emerging need of early detection of these diseases for preventive treatment success before more severe arrhythmias occur. However, developing such early screening tools is challenging due to the lack of early electrocardiograms (ECGs) before symptoms occur in patients. Mouse models are widely used in cardiac arrhythmia research. The goal of this paper is to develop deep learning models to predict cardiac conduction diseases in mice using their early ECGs. We hypothesize that mutant mice present subtle abnormalities in their early ECGs …

Blockchain-Enabled Immutable, Distributed, And Highly Available Clinical Research Activity Logging System For Federated Covid-19 Data Analysis From Multiple Institutions, Jason Chan

Faculty, Staff and Student Publications

OBJECTIVE: We aimed to develop a distributed, immutable, and highly available cross-cloud blockchain system to facilitate federated data analysis activities among multiple institutions.

MATERIALS AND METHODS: We preprocessed 9166 COVID-19 Structured Query Language (SQL) code, summary statistics, and user activity logs, from the GitHub repository of the Reliable Response Data Discovery for COVID-19 (R2D2) Consortium. The repository collected local summary statistics from participating institutions and aggregated the global result to a COVID-19-related clinical query, previously posted by clinicians on a website. We developed both on-chain and off-chain components to store/query these activity logs and their associated queries/results on a blockchain …

Co-Delivery Of Therapeutics And Bioactive Gas Using A Novel Liposomal Platform For Enhanced Treatment Of Acute Arterial Injury, Hyunggun Kim

Faculty, Staff and Student Publications

Atherosclerosis is a complex, multi-stage disease characterized by pathological changes across the vascular wall. Endothelial dysfunction, inflammation, hypoxia, and vascular smooth muscle cell proliferation contribute to its progression. An effective strategy capable of delivering pleiotropic treatment to the vascular wall is essential to limit neointimal formation. Echogenic liposomes (ELIP), which can encapsulate bioactive gases and therapeutic agents, have the potential to deliver enhanced penetration and treatment efficacy for atherosclerosis. In this study, liposomes loaded with nitric oxide (NO) and rosiglitazone, a peroxisome proliferator-activated receptor agonist, were prepared using hydration, sonication, freeze-thawing, and pressurization. The efficacy of this delivery system was …

Influenza C And D Viruses Demonstrated A Differential Respiratory Tissue Tropism In A Comparative Pathogenesis Study In Guinea Pigs, Chithra C. Sreenivasan, Runxia Liu, Rongyuan Gao, Yicheng Guo, Ben M. Hause, Milton Thomas, Ahsan Naveed, Travis Clement, Dana Rausch, Jane Christopher-Hennings, Eric Nelson, Julian Druce, Miaoyun Zhao, Radhey S. Kaushik, Qingsheng Li, Zizhang Sheng, Dan Dan, Feng Li

Nebraska Center for Virology: Faculty Publications

Influenza C virus (ICV) is increasingly associated with community-acquired pneumonia (CAP) in children and its disease severity is worse than the influenza B virus, but similar to influenza A virus associated CAP. Despite the ubiquitous infection landscape of ICV in humans, little is known about its replication and pathobiology in animals. The goal of this study was to understand the replication kinetics, tissue tropism, and pathogenesis of human ICV (huICV) in comparison to the swine influenza D virus (swIDV) in guinea pigs. Intranasal inoculation of both viruses did not cause clinical signs, however, the infected animals shed virus in nasal …

Single-Frame Deep-Learning Super-Resolution Microscopy For Intracellular Dynamics Imaging, Rong Chen, Xiao Tang, Yuxuan Zhao, Zeyu Shen, Meng Zhang, Tiantian Li, Lijuan Zhang, Ji Wang, Binbin Cui, Peng Fei, Yusong Guo, Shengwang Du, Shuhuai Yao

Faculty, Staff and Student Publications

Single-molecule localization microscopy (SMLM) can be used to resolve subcellular structures and achieve a tenfold improvement in spatial resolution compared to that obtained by conventional fluorescence microscopy. However, the separation of single-molecule fluorescence events that requires thousands of frames dramatically increases the image acquisition time and phototoxicity, impeding the observation of instantaneous intracellular dynamics. Here we develop a deep-learning based single-frame super-resolution microscopy (SFSRM) method which utilizes a subpixel edge map and a multicomponent optimization strategy to guide the neural network to reconstruct a super-resolution image from a single frame of a diffraction-limited image. Under a tolerable signal density and …

Cxcl8/Cxcr2 Signaling Mediates Bone Marrow Fibrosis And Is A Therapeutic Target In Myelofibrosis, Andrew J Dunbar, Dongjoo Kim, Min Lu, Mirko Farina, Robert L Bowman, Young Park, Wenbin Xiao, Zach Zaroogian, Kavi O'Connor, Shoron Mowla, Francesca Gobbo, Paola Verachi, Fabrizio Martelli, Giuseppe Sarli, Lijuan Xia, Nada Elmansy, Maria Kleppe, Zhuo Chen, Yang Xiao, Erin Mcgovern, Jenna Snyder, Aishwarya Krishnan, Corrine Hill, Keith Cordner, Anouar Zouak, Mohamed E Salama, Jayden Yohai, Eric Tucker, Jonathan Chen, Jing Zhou, Timothy Mcconnell, Anna R Migliaccio, Richard Koche, Raajit Rampal, Rong Fan, Ross L Levine, Ronald Hoffman

Faculty, Staff and Student Publications

Proinflammatory signaling is a hallmark feature of human cancer, including in myeloproliferative neoplasms (MPNs), most notably myelofibrosis (MF). Dysregulated inflammatory signaling contributes to fibrotic progression in MF; however, the individual cytokine mediators elicited by malignant MPN cells to promote collagen-producing fibrosis and disease evolution are yet to be fully elucidated. Previously, we identified a critical role for combined constitutive JAK/STAT and aberrant NF-κB proinflammatory signaling in MF development. Using single-cell transcriptional and cytokine-secretion studies of primary cells from patients with MF and the human MPLW515L (hMPLW515L) murine model of MF, we extend our previous work and delineate the role of …

Pou4f1-Tbr1 Transcriptional Cascade Controls The Formation Of Jam2-Expressing Retinal Ganglion Cells

Faculty, Staff and Student Publications

More than 40 retinal ganglion cell (RGC) subtypes have been categorized in mouse based on their morphologies, functions, and molecular features. Among these diverse subtypes, orientation-selective Jam2-expressing RGCs (J-RGCs) has two unique morphologic characteristics: the ventral-facing dendritic arbor and the OFF-sublaminae stratified terminal dendrites in the inner plexiform layer. Previously, we have discovered that T-box transcription factor T-brain 1 (Tbr1) is expressed in J-RGCs. We further found that Tbr1 is essential for the expression of Jam2, and Tbr1 regulates the formation and the dendritic morphogenesis of J-RGCs. However, Tbr1 begins to express in terminally differentiated RGCs around …

The Child Healthcare At Mater Pediatric Study (Champs): A 2-Arm Cluster Randomized Control Trial Of Group Well Child Care For Mothers In Treatment For Opioid Use Disorder And Their Children, Vanessa L. Short, Diane J. Abatemarco, Erica Sood, Dennis J. Hand, Meghan Gannon, Jobayer Hossain, Neera K. Goyal

Department of Pediatrics Faculty Papers

BACKGROUND: Studies suggest that group-based well child care-a shared medical appointment where families come together as a group to receive pediatric primary care-increases patient-reported satisfaction and adherence to recommended care. Evidence supporting the use of group well child care for mothers with opioid use disorder, however, is lacking. The overall objective of the Child Healthcare at MATER Pediatric Study (CHAMPS) trial is to evaluate a group model of well child care for mothers with opioid use disorder and their children.

METHODS: CHAMPS is a single-site 2-arm cluster randomized controlled trial. A total of 108 mother-child dyads will be enrolled into …

Neutralizing Antibody Formation With Onabotulinumtoxina (Botox®) Treatment From Global Registration Studies Across Multiple Indications: A Meta-Analysis, Patricia Ogilvie, Terry Boodhoo, Mayssa Attar, Swati Gupta, Ritu Singh, John Soliman, Irina Yushmanova, Mitchell F Brin, Jie Shen

Faculty, Staff and Students Publications

Though the formation of neutralizing antibodies (NAbs) during treatment with botulinum neurotoxin is rare, their presence may nonetheless affect the biological activity of botulinum toxin and negatively impact clinical response. The goal of this updated meta-analysis was to evaluate and characterize the rate of NAb formation using an expanded dataset composed of 33 prospective placebo-controlled and open-label clinical trials with nearly 30,000 longitudinal subject records prior to and following onabotulinumtoxinA treatment in 10 therapeutic and aesthetic indications. Total onabotulinumtoxinA doses per treatment ranged from 10 U to 600 U administered in ≤15 treatment cycles. The NAb formation at baseline and …

Deciphering Tumor Ecosystems At Super Resolution From Spatial Transcriptomics With Tesla, Jian Hu, Kyle Coleman, Daiwei Zhang, Edward B Lee, Humam Kadara, Mingyao Li

Faculty, Staff and Student Publications

Cell populations in the tumor microenvironment (TME), including their abundance, composition, and spatial location, are critical determinants of patient response to therapy. Recent advances in spatial transcriptomics (ST) have enabled the comprehensive characterization of gene expression in the TME. However, popular ST platforms, such as Visium, only measure expression in low-resolution spots and have large tissue areas that are not covered by any spots, which limits their usefulness in studying the detailed structure of TME. Here, we present TESLA, a machine learning framework for tissue annotation with pixel-level resolution in ST. TESLA integrates histological information with gene expression to annotate …

Morphology Of The Ventral Process Of The Sixth Cervical Vertebra In Extinct And Extant Equus: Functional Implications, Sharon May-Davis, Robert Hunter, Richard White

Faculty, Staff and Student Publications

In this study, we examined the ventral process of C6 in extinct and extant Equus (sister taxa to Equus ferus caballus only) with the purpose of describing normal morphology and identifying anomalous variations relevant to recent studies describing a congenital malformation in E. ferus caballus. Overall, 83 specimens from 9 museums and 3 research/educational facilities were examined, totalling 71 extinct specimens from 12 species and 12 extant specimens from 5 species. The lateral view revealed that a large convexity exists in the ventral process between the cranial ventral tubercle (CrVT) and the caudal ventral tubercle (CVT) in the earliest …

Full Issue: Volume 1, Issue 1 - May 2023

Bone Bulletin

Contents

i - Editors’ Note by Payton Boere and Ari Clements

ii - Foreword by Dr. Alan Hilibrand

7 - Injuries, Management, and Prevention in the Weekend Warrior by John Paulik

10 - A Practical Guide to Etiquette in the Orthopaedic OR for the Rotating Medical Student by Tyler Radack

13 - New Trends in Orthopaedic Surgery Residency Applications: The Role of Preference Signaling by J. Liam Gibbons

16 - First Job Considerations as an Orthopaedic Surgery Attending: Picking a Practice Setting by Purab Kothari

20 - A Day in the Life of an Orthopaedic Surgeon with Dr. Rachel Shakked …

Biologic Augmentation In Osteochondral Lesions Of The Talus, Yashas Reddy

Bone Bulletin

Introduction

Osteochondral lesions of the talus (OLT) are injuries involving damage to the cartilage and bone associated with the talar dome. They occur in up to 50% of ankle sprains and 73% of ankle fractures, varying in stability and severity.¹ Standard weightbearing ankle radiographs may allow for visualization of the lesions if substantial bone fragmentation is involved but CT and MRI are more sensitive for subchondral bone damage and purely cartilaginous lesions, respectively (Figure 1). The majority of patients with OLT are active individuals in their 20s and 30s, and often present after sustaining an acute inversion injury.^{2 …}

A Day In The Life Of An Orthopaedic Surgeon With Dr. Rachel Shakked, Anne Cohen

Bone Bulletin

From a young age, Dr. Shakked knew she wanted to be a doctor and started medical school with an interest in pursuing medical oncology. As a third year, she did her surgery rotation with low expectations but ended up loving it and discovering the field of orthopaedics. After completing her fellowship in 2016, she is now a foot and ankle specialist at the Rothman Institute where she experiences a mix of both private and academic practice. This conversation was born from her desire to show students what life is like beyond medical school and residency, and the importance of living …

Association Of Brain Age, Lesion Volume, And Functional Outcome In Patients With Stroke, Sook-Lei Liew, Nicolas Schweighofer, James H. Cole, Artemis Zavaliangos-Petropulu, Bethany P. Lo, Laura K.M. Han, Tim Hahn, Lianne Schmaal, Miranda R. Donnelly, Jessica N. Jeong, Zhizhuo Wang, Aisha Abdullah, Jun H. Kim, Alexandre Hutton, Giuseppe Barisano, Michael R. Borich, Lara A. Boyd, Amy Brodtmann, Cathrin M. Buetefisch, Winston D. Byblow, Jessica M. Cassidy, Charalambos C. Charalambous, Valentina Ciullo, Adriana Bastos Conforto, Rosalia Dacosta-Aguayo, Julie A. Dicarlo, Martin Domin, Adrienne N. Dula, Natalia Egorova-Brumley, Wuwei Feng, Fatemeh Geranmayeh, Chris M. Gregory, Colleen A. Hanlon, Kathryn Hayward, Jess A. Holguin, Brenton Hordacre, Neda Jahanshad, Steven A. Kautz, Mohamed Salah Khlif, Hosung Kim, Amy Kuceyeski, David J. Lin, Jingchun Liu, Martin Lotze, Bradley J. Macintosh, John L. Margetis, Maria Mataro, Feroze B. Mohamed, Emily R. Olafson, Gilsoon Park, Fabrizio Piras, Kate P. Revill, Pamela Roberts, Andrew D. Robertson, Nerses Sanossian, Heidi M. Schambra, Na Jin Seo, Surjo R. Soekadar, Gianfranco Spalletta, Cathy M. Stinear, Myriam Taga, Wai Kwong Tang, Greg T. Thielman, Daniela Vecchio, Nick S. Ward, Lars T. Westlye, Carolee J. Winstein, George F. Wittenberg, Steven L. Wolf, Kristin A. Wong, Chunshui Yu, Steven C. Cramer, Paul M. Thompson

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in …

Traf4-Mediated Nonproteolytic Ubiquitination Of Androgen Receptor Promotes Castration-Resistant Prostate Cancer, Lance Edward V Lumahan, Steven Nguyen, Hong Shen, Subhamoy Dasgupta, Li Qin, Dileep Karri, Bokai Zhu, Feng Yang, Cristian Coarfa, Bert W O'Malley, Ping Yi

Faculty, Staff and Students Publications

Castration-resistant prostate cancer (CRPC) poses a major clinical challenge with the androgen receptor (AR) remaining to be a critical oncogenic player. Several lines of evidence indicate that AR induces a distinct transcriptional program after androgen deprivation in CRPCs. However, the mechanism triggering AR binding to a distinct set of genomic loci in CRPC and how it promotes CRPC development remain unclear. We demonstrate here that atypical ubiquitination of AR mediated by an E3 ubiquitin ligase TRAF4 plays an important role in this process. TRAF4 is highly expressed in CRPCs and promotes CRPC development. It mediates K27-linked ubiquitination at the C-terminal …

Traf4-Mediated Nonproteolytic Ubiquitination Of Androgen Receptor Promotes Castration-Resistant Prostate Cancer, Lance Edward V Lumahan, Steven Nguyen, Hong Shen, Subhamoy Dasgupta, Li Qin, Dileep Karri, Bokai Zhu, Feng Yang, Cristian Coarfa, Bert W O'Malley, Ping Yi

Faculty, Staff and Students Publications

Castration-resistant prostate cancer (CRPC) poses a major clinical challenge with the androgen receptor (AR) remaining to be a critical oncogenic player. Several lines of evidence indicate that AR induces a distinct transcriptional program after androgen deprivation in CRPCs. However, the mechanism triggering AR binding to a distinct set of genomic loci in CRPC and how it promotes CRPC development remain unclear. We demonstrate here that atypical ubiquitination of AR mediated by an E3 ubiquitin ligase TRAF4 plays an important role in this process. TRAF4 is highly expressed in CRPCs and promotes CRPC development. It mediates K27-linked ubiquitination at the C-terminal …

Review Of Gynaecological Cancer Among Aboriginal And/Or Torres Strait Islander People In Australia, Aime Powell, Ami Morseu-Diop, Maya Morton Ninomiya, Uday Narayan Yadav, Emily Phillips, Devendra Raj Singh, Tamara Butler, Emma Allanson, Lisa J. Whop

Journal of the Australian Indigenous HealthInfoNet

Gynaecological cancers bear a significant burden on the health of Australians. Whilst Australia has made great strides in reducing the overall gynaecological cancer burden nationally, Aboriginal and/or Torres Strait Islander women continue to experience disproportionately high rates of gynaecological cancers.

This review focuses on the social, cultural, and historical contexts that contribute to inequitable gynaecological cancer rates among Aboriginal and/or Torres Strait Islander women. An in-depth discussion on cervical cancer, ovarian cancer, and uterine cancer are described; including the incidence, mortality, survival, and management of these diseases for Aboriginal and/or Torres Strait Islander women.

It highlights both the persistent barriers …

From Bugs To Drugs: Bacterial 3-Iaa Enhances Efficacy Of Chemotherapy In Pancreatic Cancer, Y David Seo, Jennifer A Wargo

Faculty, Staff and Student Publications

Tintelnot et al. identified enrichment of indole-3-acetic acid (3-IAA), a tryptophan metabolite produced by gut microbiota, as a predictor of chemotherapy response in pancreatic adenocarcinoma. Recapitulated in mouse models, 3-IAA represents a novel potential therapeutic approach for chemotherapy sensitization.

Sarcopenia And Cardiovascular Diseases, Manish Kumar, Wayne B Batchelor, Daniel E Forman, Michael W Rich, James Kirkpatrick, Ashok Krishnaswami, Karen P Alexander, Gary Gerstenblith, Peggy Cawthon, Christopher R Defilippi, Parag Goyal

Faculty, Staff and Student Publications

Sarcopenia is the loss of muscle strength, mass, and function, which is often exacerbated by chronic comorbidities including cardiovascular diseases, chronic kidney disease, and cancer. Sarcopenia is associated with faster progression of cardiovascular diseases and higher risk of mortality, falls, and reduced quality of life, particularly among older adults. Although the pathophysiologic mechanisms are complex, the broad underlying cause of sarcopenia includes an imbalance between anabolic and catabolic muscle homeostasis with or without neuronal degeneration. The intrinsic molecular mechanisms of aging, chronic illness, malnutrition, and immobility are associated with the development of sarcopenia. Screening and testing for sarcopenia may be …

Next-Generation Boron Drugs And Rational Translational Studies Driving The Revival Of Bnct, Sunil Krishnan

Faculty, Staff and Student Publications

BNCT is a high-linear-energy transfer therapy that facilitates tumor-directed radiation delivery while largely sparing adjacent normal tissues through the biological targeting of boron compounds to tumor cells. Tumor-specific accumulation of boron with limited accretion in normal cells is the crux of successful BNCT delivery. Given this, developing novel boronated compounds with high selectivity, ease of delivery, and large boron payloads remains an area of active investigation. Furthermore, there is growing interest in exploring the immunogenic potential of BNCT. In this review, we discuss the basic radiobiological and physical aspects of BNCT, traditional and next-generation boron compounds, as well as translational …

Evaluation Of 89zr-Labeled Anti-Pd-L1 Monoclonal Antibodies Using Dfo And Novel Hopo Analogues As Chelating Agents For Immuno-Pet, Bhasker Radaram, Sarah E Glazer, Ping Yang, Chia-Wei Li, Mien-Chie Hung, Mian Alauddin

Faculty, Staff and Student Publications

Programmed death ligand 1 (PD-L1) is a type 1 transmembrane immunosuppressive protein that is expressed on a wide range of cell types, including cancer cells. Anti-PD-L1 antibodies have revolutionized cancer therapy and have led to improved outcomes for subsets of cancer patients, including triple-negative breast cancer (TNBC) patients. As a result, PET imaging of PD-L1 protein expression in cancer patients has been explored for noninvasive detection of PD-L1 expressing tumors as well as monitoring response to anti-PD-L1 immune checkpoint therapy. Previous studies have indicated that the in vivo stability and in vivo target detection of antibody-based radio-conjugates can be dramatically …

Improved Synthesis And Anticancer Activity Of A Potent Neuronal Nitric Oxide Synthase Inhibitor, Dhananjayan Vasu, Cory T. Reidl, Eric Wang, Sun Yang, Richard B. Silverman

Pharmacy Faculty Articles and Research

An improved synthesis of 4-methyl-7-(3-((methylamino)methyl)phenethyl)quinolin-2-amine (1) is reported. A scalable, rapid, and efficient methodology was developed to access this compound with an overall yield of 35%, which is 5.9-fold higher than the previous report. The key differences in the improved synthesis are a high yielding quinoline synthesis by a Knorr reaction, a copper-mediated Sonogashira coupling to the internal alkyne in excellent yield, and a crucial deprotection of the N-acetyl and N-Boc groups achieved under acidic conditions in a single step rather than a poor yielding quinoline N-oxide strategy, basic deprotection conditions, and low yielding copper-free conditions that …

Adenoviral-Vectored Epigraph Vaccine Elicits Robust, Durable, And Protective Immunity Against H3 Influenza A Virus In Swine, Erika M. Petro-Turnquist, Matthew J. Pekarek, Nicholas Jeanjaquet, Cedric Wooledge, David J. Steffen, Hiep Vu, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Current methods of vaccination against swine Influenza A Virus (IAV-S) in pigs are infrequently updated, induce strain-specific responses, and have a limited duration of protection. Here, we characterize the onset and duration of adaptive immune responses after vaccination with an adenoviral-vectored Epigraph vaccine. In this longitudinal study we observed robust and durable antibody responses that remained above protective titers six months after vaccination. We further identified stable levels of antigen-specific T cell responses that remained detectable in the absence of antigen stimulation. Antibody isotyping revealed robust class switching from IgM to IgG induced by Epigraph vaccination, while the commercial comparator …

Cardiac Pericytes Mediate The Remodeling Response To Myocardial Infarction, Kamal Ss Kolluri, David Wong, Kevin D Shih, Kai Fang, Arash Pezhouman, Lingjun Wang, Ali Daraei, Matthew D Tran, Elle M Rathbun, Kimberly N Burgos Villar, Maria L Garcia-Hernandez, Thanh Td Pham, Charles J Lowenstein, M Luisa Iruela-Arispe, S Thomas Carmichael, Eric M Small, Reza Ardehali

Faculty, Staff and Students Publications

Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling. Deleting TGF-β receptor 1 in chondroitin sulfate proteoglycan 4-expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading to a transient improvement in the cardiac …

Kras Hijacks The Mirna Regulatory Pathway In Cancer

Faculty, Staff and Students Publications

Extensive studies have focused on the misregulation of individual miRNAs in cancer. More recently, mutations in the miRNA biogenesis and processing machinery have been implicated in several malignancies. Such mutations can lead to global miRNA misregulation, which may promote many of the well-known hallmarks of cancer. Interestingly, recent evidence also suggests that oncogenic Kristen rat sarcoma viral oncogene homolog (KRAS) mutations act in part by modulating the activity of members of the miRNA regulatory pathway. Here, we highlight the vital role mutations in the miRNA core machinery play in promoting malignant transformation. Furthermore, we discuss how mutant KRAS can simultaneously …

Correction Of T-Cell Repertoire And Autoimmune Diabetes In Nod Mice By Non-Myeloablative T-Cell Depleted Allogeneic Hsct, Rakefet Sidlik Muskatel, Bar Nathansohn-Levi, Shlomit Reich-Zeliger, Michal Mark, Liat Stoler-Barak, Irit Milman-Krentsis, Robert Pete Gale, Nir Friedman, Yair Reisner

Faculty, Staff and Student Publications

The induction of partial tolerance toward pancreatic autoantigens in the treatment of type 1 diabetes mellitus (T1DM) can be attained by autologous hematopoietic stem cell transplantation (HSCT). However, most patients treated by autologous HSCT eventually relapse. Furthermore, allogeneic HSCT which could potentially provide a durable non-autoimmune T-cell receptor (TCR) repertoire is associated with a substantial risk for transplant-related mortality. We have previously demonstrated an effective approach for attaining engraftment without graft versus host disease (GVHD) of allogeneic T-cell depleted HSCT, following non-myeloablative conditioning, using donor-derived anti-3rd party central memory CD8 veto T cells (Tcm). In the present study, we investigated …

An Opportunity To Increase Collaborative Science In Fetal, Infant, And Toddler Neuroimaging, Dustin Scheinost

Faculty, Staff and Student Publications

The field of fetal, infant, and toddler (FIT) neuroimaging research—including magnetic resonance imaging (MRI), electroencephalography (EEG), magnetoencephalography, and functional near-infrared spectroscopy, among others—offers pioneering insights into early brain development and has grown in popularity over the past 2 decades. In broader neuroimaging research, multisite collaborative projects, data sharing, and open-source code have increasingly become the norm, fostering big data, consensus standards, and rapid knowledge transfer and development. Given the aforementioned benefits, along with recent initiatives from funding agencies to support multisite and multimodal FIT neuroimaging studies, the FIT field now has the opportunity to establish sustainable, collaborative, and open science …

Effects Of Prenatal Pesticide Exposure On The Fetal Brain And Placenta Transcriptomes In A Rodent Model, Randy Williams, Jia Chen

Faculty, Staff and Student Publications

Organophosphate and pyrethroid pesticides are among the most extensively used insecticides worldwide. Prenatal exposures to both classes of pesticides have been linked to a wide range of neurobehavioral deficits in the offspring. The placenta is a neuroendocrine organ and the crucial regulator of the intrauterine environment; early-life toxicant exposures could impact neurobehavior by disrupting placental processes. Female C57BL/6 J mice were exposed via oral gavage to an organophosphate, chlorpyrifos (CPF) at 5 mg/kg, a pyrethroid, deltamethrin (DM), at 3 mg/kg, or vehicle only control (CTL). Exposure began two weeks before breeding and continued every three days until euthanasia at gestational …

Structural Insights Into Ligand Recognition And Selectivity Of Somatostatin Receptors, Guizhen Fan, Eugenia Mileykovskaya, William Dowhan

Faculty, Staff and Student Publications

Cardiolipin is a hallmark phospholipid of mitochondrial membranes. Despite established significance of cardiolipin in supporting respiratory supercomplex organization, a mechanistic understanding of this lipid-protein interaction is still lacking. To address the essential role of cardiolipin in supercomplex organization, we report cryo-EM structures of a wild type supercomplex (IV