Medical Sciences Commons^™

Rewired M6a Epitranscriptomic Networks Link Mutant P53 To Neoplastic Transformation, An Xu, Mo Liu, Mo-Fan Huang, Yang Zhang, Ruifeng Hu, Julian A Gingold, Ying Liu, Dandan Zhu, Chian-Shiu Chien, Wei-Chen Wang, Zian Liao, Fei Yuan, Chih-Wei Hsu, Jian Tu, Yao Yu, Taylor Rosen, Feng Xiong, Peilin Jia, Yi-Ping Yang, Danielle A Bazer, Ya-Wen Chen, Wenbo Li, Chad D Huff, Jay-Jiguang Zhu, Francesca Aguilo, Shih-Hwa Chiou, Nathan C Boles, Chien-Chen Lai, Mien-Chie Hung, Zhongming Zhao, Eric L Van Nostrand, Ruiying Zhao, Dung-Fang Lee

Faculty, Staff and Students Publications

N6-methyladenosine (m6A), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of m6A epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas. We find that mutant p53 but not wild-type (WT) p53 physically interacts with SVIL to recruit the H3K4me3 methyltransferase MLL1 to activate the expression of m6A reader YTHDF2, culminating in an oncogenic phenotype. Aberrant YTHDF2 upregulation markedly hampers expression of multiple m6A-marked tumor-suppressing …

Clinical Features And Shared Mechanisms Of Chronic Gastritis And Osteoporosis, Tao Han, Yili Zhang, Baoyu Qi, Ming Chen, Kai Sun, Xiaokuan Qin, Bowen Yang, He Yin, Aili Xu, Xu Wei, Liguo Zhu

Faculty, Staff and Student Publications

Chronic gastritis (CG) and osteoporosis (OP) are common and occult diseases in the elderly and the relationship of these two diseases have been increasingly exposed. We aimed to explore the clinical characteristics and shared mechanisms of CG patients combined with OP. In the cross-sectional study, all participants were selected from BEYOND study. The CG patients were included and classified into two groups, namely OP group and non-OP group. Univariable and multivariable logistic regression methods were used to evaluate the influencing factors. Furthermore, CG and OP-related genes were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified …

Impact Of Testosterone Use On The Vaginal Microbiota Of Transgender Men, Including Susceptibility To Bacterial Vaginosis: Study Protocol For A Prospective, Observational Study, Christina A. Muzny, Olivia T. Van Gerwen, Julia A. Schroeder, Emma Sophia Kay-Duncan, Krishmita Siwakoti, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Jacob H. Elnaggar, Ashutosh Tamhane, Dustin Long, Nicholas Van Wagoner, Evelyn Toh, Christopher M. Taylor

School of Graduate Studies Faculty Publications

Introduction The effect of testosterone (T) therapy on the vaginal microbiota of transgender men (TGM) is not well characterised, although one cross-sectional study comparing the vaginal microbiota of cisgender women to TGM on T≥1 year found that, in 71% of the TGM, the vaginal microbiota was less likely to be Lactobacillus-dominated and more likely to be enriched with >30 other bacterial species, many associated with bacterial vaginosis (BV). This prospective study aims to investigate changes in the composition of the vaginal microbiota over time in TGM who retain their natal genitalia (ie, vagina) and initiate T. In addition, we will …

The Nrf2 Pathway In Depressive Disorders: A Systematic Review Of Animal And Human Studies, Gabriele Sani, Stella Margoni, Andrea Brugnami, Ottavia Marianna Ferrara, Evelina Bernardi, Alessio Simonetti, Laura Monti, Marianna Mazza, Delfina Janiri, Lorenzo Moccia, Georgios D Kotzalidis, Daniela Pia Rosaria Chieffo, Luigi Janiri

Faculty, Staff and Students Publications

There is increasing interest in the involvement of antioxidative systems in protecting from depression. Among these, Nrf2 occupies a central place. We aimed to review the role of Nrf2 in depression. For this reason, we conducted a PubMed search using as search strategy (psychiatr*[ti] OR schizo*[ti] OR psychot*[ti] OR psychos*[ti] OR depress*[ti] OR MDD[ti] OR BD[ti] OR bipolar[ti] OR Anxiety[ti] OR antidepress*[ti] OR panic[ti] OR obsess*[ti] OR compulsio*[ti] OR “mood disord*”[ti] OR phobi*[ti] OR agoraphob*[ti] OR anorex*[ti] OR anorect*[ti] OR bulimi*[ti] OR “eating disorder*”[ti] OR neurodevelopm*[ti] OR retardation[ti] OR autism[ti] OR autistic[ti] OR ASM[ti] OR adhd[ti] OR “attention-deficit”[ti]) AND nrf2, …

Bioinformatic Analysis Predicts Microglial Dysfunction In Murine Aging, Amadu Idrisa Jalloh

USF Tampa Graduate Theses and Dissertations

Age-related disease is a growing concern as the global geriatric population increases. Neurodegenerative diseases scale unfavorably in prevalence with aging and inflict disastrous consequences to human health and well-being. These disorders are challenging to investigate because they arise from complex molecular origins. The neuroimmune system is a common factor among these diseases and microglia play an important role in maintaining homeostasis in the central nervous system. Aging progressively impairs microglia by decreasing their ability to adapt and respond to noxious environmental stimuli or injury. Microglial dysfunction aggravates neurodegenerative pathology when microglia are unable to regulate neuroinflammation effectively. We investigated aging …

Venetoclax For Acute Myeloid Leukemia In Pediatric Patients: A Texas Medical Center Experience, Adriana Trabal, Amber Gibson, Jiasen He, David Mccall, Michael Roth, Cesar Nuñez, Miriam Garcia, Meredith Buzbee, Laurie Toepfer, Aram Bidikian, Naval Daver, Tapan Kadia, Nicholas J Short, Ghayas C Issa, Farhad Ravandi, Courtney D Dinardo, Guillermo Montalban Bravo, Sofia Garces, Andrea Marcogliese, Hana Paek, Zoann Dreyer, Julienne Brackett, Michele Redell, Joanna Yi, Guillermo Garcia-Manero, Marina Konopleva, Alexandra Stevens, Branko Cuglievan

Faculty, Staff and Student Publications

The BCL-2 inhibitor venetoclax improves survival for adult patients with acute myeloid leukemia (AML) in combination with lower-intensity therapies, but its benefit in pediatric patients with AML remains unclear. We retrospectively reviewed two Texas Medical Center institutions' experience with venetoclax in 43 pediatric patients with AML; median age 17 years (range, 0.6-21). This population was highly refractory; 44% of patients (n = 19) had ≥3 prior lines of therapy, 37% (n = 16) had received a prior bone marrow transplant, and 81% (n = 35) had unfavorable genetics KMT2A (n = 17), WT1 (n = 13), FLT3-ITD (n = 10), …

Soybean Gmsaul1, A Bona Fide U-Box E3 Ligase, Negatively Regulates Immunity Likely Through Repressing The Activation Of Gmmpk3, Jun-Mei Li, Mei-Yan Ye, Chaofeng Wang, Xiao-Han Ma, Ni-Ni Wu, Chen-Li Zhong, Yanjun Zhang, Ninghui Cheng, Paul A Nakata, Lirong Zeng, Jian-Zhong Liu

Faculty, Staff and Students Publications

E3 ubiquitin ligases play important roles in plant immunity, but their role in soybean has not been investigated previously. Here, we used Bean pod mottle virus (BPMV)-mediated virus-induced gene silencing (VIGS) to investigate the function of GmSAUL1 (Senescence-Associated E3 Ubiquitin Ligase 1) homologs in soybean. When two closely related SAUL1 homologs were silenced simultaneously, the soybean plants displayed autoimmune phenotypes, which were significantly alleviated by high temperature, suggesting that GmSAUL1a/1b might be guarded by an R protein. Interestingly, silencing GmSAUL1a/1b resulted in the decreased activation of GmMPK6, but increased activation of GmMPK3 in response to flg22, …

Developing A Bacterial Panel For The Evaluation Of Novel Anti-Infective Compounds, Clare Euteneuer

UNO Student Research and Creative Activity Fair

Antibiotic resistance is one of the leading causes of concern for the world health community. Drugs used to stop various infections for years are now becoming easier for bacteria to resist due to mutations and plasmids conferring resistance. To combat this problem, new drug can help alleviate this concern. We developed an assay that allows us to screen novel drug-like compounds against bacteria in an effort to identify promising new anti-infective compounds. Our assay was designed using known drugs against a panel of gram positive and negative bacilli and cocci including S. epidermidis, P. mirabilis, N. mucosa, and E. …

Impact Of Passive Leg Movement On Lower Limb Vascular Function In Patients With A Spinal Cord Injury, Christian D. Sanchez Tato, Elizabeth J. Pekas, Michael F. Allen, Cody P. Anderson, Song-Young Park

UNO Student Research and Creative Activity Fair

Background: Individuals with spinal cord injuries (SCI) are at a greater risk for developing cardiovascular diseases. Of note, post injury mediated increases in physical inactivity leads to muscle atrophy, which also results in vascular dysfunction in this population. Although a growing body of evidence suggests that passive leg movement (PLM) may be a useful exercise modality to improve peripheral blood flow and skeletal muscle activation in individuals with limited mobility, few studies have examined the impact of PLM on local skeletal muscle blood flow. Therefore, there is a need to examine the impact of PLM on lower limb vascular function …

Impact Of Sex On Macrovascular Endothelial Function During Prolonged Sitting With A Mild Hypercapnic Environemnt, Andres Benitez-Albiter, Michael Allen, Elizabeth J. Pekas, Cody P. Anderson, Song-Young Park

UNO Student Research and Creative Activity Fair

IMPACT OF SEX ON MACROVASCULAR ENDOTHELIAL FUNCTION DURING PROLONGED SITTING WITH A MILD HYPERCAPNIC ENVIORNMENT

Andres Benitez-Albiter¹, Michael F. Allen¹, Elizabeth J. Pekas¹, Cody P. Anderson¹, and Song-Young Park¹

1 - School of Health & Kinesiology University of Nebraska Omaha, Omaha, NE

Introduction: Prolonged sitting (PS), defined as sitting for 2+ hours at a time[SYP1] , has been identified as an independent risk factor for cardiovascular disease. It has been well-documented that an acute PS bout can impair macro- and microvascular dysfunction in healthy young individuals. Recently, we reported that …

Med25 Limits Master Regulators That Govern Adipogenesis, Jasmine Saunders, Kunal Sikder, Elizabeth Phillips, Anurag Ishwar, David Mothy, Kenneth B. Margulies, Jason C. Choi

Department of Medicine Faculty Papers

Mediator 25 (Med25) is a member of the mediator complex that relays signals from transcription factors to the RNA polymerase II machinery. Multiple transcription factors, particularly those involved in lipid metabolism, utilize the mediator complex, but how Med25 is involved in this context is unclear. We previously identified Med25 in a translatome screen of adult cardiomyocytes (CMs) in a novel cell type-specific model of LMNA cardiomyopathy. In this study, we show that Med25 upregulation is coincident with myocardial lipid accumulation. To ascertain the role of Med25 in lipid accumulation, we utilized iPSC-derived and neonatal CMs to recapitulate the in vivo …

A Randomized Phase I/Ii Safety And Immunogenicity Study Of The Montanide-Adjuvanted Sars-Cov-2 Spike Protein-Rbd-Fc Vaccine, Aks-452, Eline A Feitsma, Yester F Janssen, Hendrikus H Boersma, Yannick Van Sleen, Debbie Van Baarle, David G Alleva, Thomas M Lancaster, Thillainaygam Sathiyaseelan, Sylaja Murikipudi, Andrea R Delpero, Melanie M Scully, Ramya Ragupathy, Sravya Kotha, Jeffrey R Haworth, Nishit J Shah, Vidhya Rao, Shashikant Nagre, Shannon E Ronca, Freedom M Green, Ari Aminetzah, Frans Sollie, Schelto Kruijff, Maarten Brom, Gooitzen M Van Dam, Todd C Zion

Faculty, Staff and Students Publications

BACKGROUND: Previous interim data from a phase I study of AKS-452, a subunit vaccine comprising an Fc fusion of the respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (SP/RBD) emulsified in the water-in-oil adjuvant, Montanide™ ISA 720, suggested a good safety and immunogenicity profile in healthy adults. This phase I study was completed and two dosing regimens were further evaluated in this phase II study.

METHODS: This phase II randomized, open-labelled, parallel group study was conducted at a single site in The Netherlands with 52 healthy adults (18 - 72 years) receiving AKS-452 subcutaneously at one 90 µg …

Defects In Lipid Homeostasis Reflect The Function Of Tango2 In Phospholipid And Neutral Lipid Metabolism, Agustin Leonardo Lujan, Ombretta Foresti, Conor Sugden, Nathalie Brouwers, Alex Mateo Farre, Alessio Vignoli, Mahshid Azamian, Alicia Turner, Jose Wojnacki, Vivek Malhotra

Faculty, Staff and Students Publications

We show that TANGO2 in mammalian cells localizes predominantly to mitochondria and partially at mitochondria sites juxtaposed to lipid droplets (LDs) and the endoplasmic reticulum. HepG2 cells and fibroblasts of patients lacking TANGO2 exhibit enlarged LDs. Quantitative lipidomics revealed a marked increase in lysophosphatidic acid (LPA) and a concomitant decrease in its biosynthetic precursor phosphatidic acid (PA). These changes were exacerbated in nutrient-starved cells. Based on our data, we suggest that TANGO2 function is linked to acyl-CoA metabolism, which is necessary for the acylation of LPA to generate PA. The defect in acyl-CoA availability impacts the metabolism of many other …

Calpain Activity Is Negatively Regulated By A Kctd7-Cullin-3 Complex Via Non-Degradative Ubiquitination, Jaiprakash Sharma, Shalaka Mulherkar, Uan-I Chen, Yan Xiong, Lakshya Bajaj, Byoung-Kyu Cho, Young Ah Goo, Hon-Chiu Eastwood Leung, Kimberley F Tolias, Marco Sardiello

Faculty, Staff and Students Publications

Calpains are a class of non-lysosomal cysteine proteases that exert their regulatory functions via limited proteolysis of their substrates. Similar to the lysosomal and proteasomal systems, calpain dysregulation is implicated in the pathogenesis of neurodegenerative disease and cancer. Despite intensive efforts placed on the identification of mechanisms that regulate calpains, however, calpain protein modifications that regulate calpain activity are incompletely understood. Here we show that calpains are regulated by KCTD7, a cytosolic protein of previously uncharacterized function whose pathogenic mutations result in epilepsy, progressive ataxia, and severe neurocognitive deterioration. We show that KCTD7 works in complex with Cullin-3 and Rbx1 …

Health-Related Quality Of Life In Adolescents And Young Adults With Cancer Who Received Radiation Therapy: A Scoping Review, Kelsey L Corrigan, Bryce B Reeve, John M Salsman, Elizabeth J Siembida, Lauren M Andring, Yimin Geng, Ramez Kouzy, J Andrew Livingston, Susan K Peterson, Andrew J Bishop, Grace L Smith, Jillian R Gunther, Susan K Parsons, Michael Roth

Faculty, Staff and Student Publications

Purpose: Radiation therapy (RT) is a critical component of treatment for adolescents and young adults (AYAs, age 15-39 years old) diagnosed with cancer. Limited prior studies have focused on AYAs receiving RT despite the potentially burdensome effects of RT. We reviewed the literature to assess health-related quality of life (HRQOL) in AYAs with cancer who received RT.

Methods: The MEDLINE, EMBASE, and Web of Science databases were searched in January 2022 to identify studies that analyzed HRQOL measured by patient-reported outcomes in AYAs who received RT. After title (n = 286) and abstract (n = 58) screening and full-text review …

Convergent Deployment Of Ancestral Functions During The Evolution Of Mammalian Flight Membranes, Charles Y Feigin, Jorge A Moreno, Raul Ramos, Sarah A Mereby, Ares Alivisatos, Wei Wang, Renée Van Amerongen, Jasmin Camacho, John J Rasweiler, Richard R Behringer, Bruce Ostrow, Maksim V Plikus, Ricardo Mallarino

Faculty, Staff and Student Publications

Lateral flight membranes, or patagia, have evolved repeatedly in diverse mammalian lineages. While little is known about patagium development, its recurrent evolution may suggest a shared molecular basis. By combining transcriptomics, developmental experiments, and mouse transgenics, we demonstrate that lateral Wnt5a expression in the marsupial sugar glider (Petaurus breviceps) promotes the differentiation of its patagium primordium. We further show that this function of Wnt5a reprises ancestral roles in skin morphogenesis predating mammalian flight and has been convergently used during patagium evolution in eutherian bats. Moreover, we find that many genes involved in limb development have been redeployed during …

Cervicovaginal Microbiota Profiles In Precancerous Lesions And Cervical Cancer Among Ethiopian Women, Brhanu Teka, Kyoko Yoshida-Court, Ededia Firdawoke, Zewditu Chanyalew, Muluken Gizaw, Adamu Addissie, Adane Mihret, Lauren E Colbert, Tatiana Cisneros Napravnik, Molly B El Alam, Erica J Lynn, Melissa Mezzari, Jhingran Anuja, Eva Johanna Kantelhardt, Andreas M Kaufmann, Ann H Klopp, Tamrat Abebe

Faculty, Staff and Student Publications

Although high-risk human papillomavirus infection is a well-established risk factor for cervical cancer, other co-factors within the local microenvironment may play an important role in the development of cervical cancer. The current study aimed to characterize the cervicovaginal microbiota in women with premalignant dysplasia or invasive cervical cancer compared with that of healthy women. The study comprised 120 Ethiopian women (60 cervical cancer patients who had not received any treatment, 25 patients with premalignant dysplasia, and 35 healthy women). Cervicovaginal specimens were collected using either an Isohelix DNA buccal swab or an Evalyn brush, and ribosomal RNA sequencing was used …

Exploration Of Data Science Toolbox And Predictive Models To Detect And Prevent Medicare Fraud, Waste, And Abuse, Benjamin P. Goodwin, Adam Canton, Babatunde Olanipekun

SMU Data Science Review

The Federal Department of Health and Human Services spends approximately $830 Billion annually on Medicare of which an estimated $30 to $110 billion is some form of fraud, waste, or abuse (FWA). Despite the Federal Government’s ongoing auditing efforts, fraud, waste, and abuse is rampant and requires modern machine learning approaches to generalize and detect such patterns. New and novel machine learning algorithms offer hope to help detect fraud, waste, and abuse. The existence of publicly accessible datasets complied by The Centers for Medicare & Medicaid Services (CMS) contain vast quantities of structured data. This data, coupled with industry standardized …

Design And Preclinical Evaluation Of A Universal Sars-Cov-2 Mrna Vaccine, Jane Qin, Ju Hyeong Jeon, Jiangsheng Xu, Laura Katherine Langston, Ramesh Marasini, Stephanie Mou, Brian Montoya, Carolina R Melo-Silva, Hyo Jin Jeon, Tianyi Zhu, Luis J. Sigal, Renhuan Xu, Huabin Zhu

Department of Microbiology and Immunology Faculty Papers

Because of the rapid mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective vaccine against SARS-CoV-2 variants is needed to prevent coronavirus disease 2019 (COVID-19). T cells, in addition to neutralizing antibodies, are an important component of naturally acquired protective immunity, and a number of studies have shown that T cells induced by natural infection or vaccination contribute significantly to protection against several viral infections including SARS-CoV-2. However, it has never been tested whether a T cell-inducing vaccine can provide significant protection against SARS-CoV-2 infection in the absence of preexisting antibodies. In this study, we designed and evaluated …

Botulinum Neurotoxin Injections In Children With Self-Injurious Behaviors, Mariam Hull, Mered Parnes, Joseph Jankovic

Faculty, Staff and Students Publications

Self-injurious behaviors are repetitive, persistent actions directed toward one's body that threaten or cause physical harm. These behaviors are seen within a broad spectrum of neurodevelopmental and neuropsychiatric conditions, often associated with intellectual disability. Injuries can be severe and distressing to patients and caregivers. Furthermore, injuries can be life-threatening. Often, these behaviors are challenging to treat and require a tiered, multimodal approach which may include mechanical/physical restraints, behavioral therapy, pharmacotherapy, or in some cases, surgical management, such as tooth extraction or deep brain stimulation. Here, we describe a series of 17 children who presented to our institution with self-injurious behaviors …

Aberrant Function Of Pathogenic Stat3 Mutant Proteins Is Linked To Altered Stability Of Monomers And Homodimers, Moses M Kasembeli, Efiyenia Kaparos, Uddalak Bharadwaj, Ahmad Allaw, Alain Khouri, Bianca Acot, David J Tweardy

Faculty, Staff and Student Publications

STAT3 mutations, predominantly in the DNA-binding domain (DBD) and Src-homology 2 domain (SH2D), cause rare cases of immunodeficiency, malignancy, and autoimmunity. The exact mechanisms by which these mutations abrogate or enhance STAT3 function are not completely understood. Here, we examined how loss-of-function (LOF) and gain-of-function (GOF) STAT3 mutations within the DBD and SH2D affect monomer and homodimer protein stability as well as their effect on key STAT3 activation events, including recruitment to phosphotyrosine (pY) sites within peptide hormone receptors, tyrosine phosphorylation at Y705, dimerization, nuclear translocation, and DNA binding. The DBD LOF mutants showed reduced DNA binding when homodimerized, whereas …

A Phase 2 Study Of Interleukin-22 And Systemic Corticosteroids As Initial Treatment For Acute Gvhd Of The Lower Gi Tract, Doris M Ponce, Amin M Alousi, Ryotaro Nakamura, John Slingerland, Marco Calafiore, Karamjeet S Sandhu, Juliet N Barker, Sean Devlin, Jinru Shia, Sergio Giralt, Miguel-Angel Perales, Gillian Moore, Samira Fatmi, Cristina Soto, Antonio Gomes, Paul Giardina, Leeann Marcello, Xiaoqiang Yan, Tom Tang, Kevin Dreyer, Jianmin Chen, William L Daley, Jonathan U Peled, Marcel R M Van Den Brink, Alan M Hanash

Faculty, Staff and Student Publications

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality following allogeneic hematopoietic transplantation. In experimental models, interleukin-22 promotes epithelial regeneration and induces innate antimicrobial molecules. We conducted a multicenter single-arm phase 2 study evaluating the safety and efficacy of a novel recombinant human interleukin-22 dimer, F-652, used in combination with systemic corticosteroids for treatment of newly diagnosed lower gastrointestinal acute GVHD. The most common adverse events were cytopenias and electrolyte abnormalities, and there were no dose-limiting toxicities. Out of 27 patients, 19 (70%; 80% confidence interval, 56%-79%) achieved a day-28 treatment response, meeting the prespecified primary endpoint. Responders …

Decoupling Body Shape And Mass Distribution In Birds And Their Dinosaurian Ancestors, Sophie Macaulay, Tatjana Hoehfurtner, Samuel R.R. Cross, Ryan D. Marek, John R. Hutchinson, Emma R. Schachner, Alice E. Maher, Karl T. Bates

School of Medicine Faculty Publications

It is accepted that non-avian theropod dinosaurs, with their long muscular tails and small forelimbs, had a centre-of-mass close to the hip, while extant birds, with their reduced tails and enlarged wings have their mass centred more cranially. Transition between these states is considered crucial to two key innovations in the avian locomotor system: crouched bipedalism and powered flight. Here we use image-based models to challenge this dichotomy. Rather than a phylogenetic distinction between ‘dinosaurian’ and ‘avian’ conditions, we find terrestrial versus volant taxa occupy distinct regions of centre-of-mass morphospace consistent with the disparate demands of terrestrial bipedalism and flight. …

Catalyzing Next-Generation Artificial Intelligence Through Neuroai, Anthony Zador, Sean Escola, Blake Richards, Bence Ölveczky, Yoshua Bengio, Kwabena Boahen, Matthew Botvinick, Dmitri Chklovskii, Anne Churchland, Claudia Clopath, James Dicarlo, Surya Ganguli, Jeff Hawkins, Konrad Körding, Alexei Koulakov, Yann Lecun, Timothy Lillicrap, Adam Marblestone, Bruno Olshausen, Alexandre Pouget, Cristina Savin, Terrence Sejnowski, Eero Simoncelli, Sara Solla, David Sussillo, Andreas S Tolias, Doris Tsao

Faculty, Staff and Students Publications

Neuroscience has long been an essential driver of progress in artificial intelligence (AI). We propose that to accelerate progress in AI, we must invest in fundamental research in NeuroAI. A core component of this is the embodied Turing test, which challenges AI animal models to interact with the sensorimotor world at skill levels akin to their living counterparts. The embodied Turing test shifts the focus from those capabilities like game playing and language that are especially well-developed or uniquely human to those capabilities - inherited from over 500 million years of evolution - that are shared with all animals. Building …

Cc16 Augmentation Reduces Exaggerated Copd-Like Disease In Cc16-Deficient Mice, Joselyn Rojas-Quintero, Maria Eugenia Laucho-Contreras, Xiaoyun Wang, Quynh-Anh Fucci, Patrick R Burkett, Se-Jin Kim, Duo Zhang, Yohannes Tesfaigzi, Yuhong Li, Abhiram R Bhashyam, Zhang Li, Haider Khamas, Bartolome Celli, Aprile L Pilon, Francesca Polverino, Caroline A Owen

Faculty, Staff and Students Publications

Low Club Cell 16 kDa protein (CC16) plasma levels are linked to accelerated lung function decline in patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke-exposed (CS-exposed) Cc16-/- mice have exaggerated COPD-like disease associated with increased NF-κB activation in their lungs. It is unclear whether CC16 augmentation can reverse exaggerated COPD in CS-exposed Cc16-/- mice and whether increased NF-κB activation contributes to the exaggerated COPD in CS-exposed Cc16-/- lungs. CS-exposed WT and Cc16-/- mice were treated with recombinant human CC16 (rhCC16) or an NF-κB inhibitor versus vehicle beginning at the midpoint of the exposures. COPD-like disease and NF-κB activation were …

Interleukins, Chemokines, And Tumor Necrosis Factor Superfamily Ligands In The Pathogenesis Of West Nile Virus Infection, Emna Benzarti, Kristy O Murray, Shannon E Ronca

Faculty, Staff and Students Publications

West Nile virus (WNV) is a mosquito-borne pathogen that can lead to encephalitis and death in susceptible hosts. Cytokines play a critical role in inflammation and immunity in response to WNV infection. Murine models provide evidence that some cytokines offer protection against acute WNV infection and assist with viral clearance, while others play a multifaceted role WNV neuropathogenesis and immune-mediated tissue damage. This article aims to provide an up-to-date review of cytokine expression patterns in human and experimental animal models of WNV infections. Here, we outline the interleukins, chemokines, and tumor necrosis factor superfamily ligands associated with WNV infection and …

Stellettin B Renders Glioblastoma Vulnerable To Poly (Adp-Ribose) Polymerase Inhibitors Via Suppressing Homology-Directed Repair, Xin Peng, Yingying Wang, Shaolu Zhang, Zhennan Tao, Yuxiang Dai, Francois X Claret, Moshe Elkabets, Hou-Wen Lin, Zhe-Sheng Chen, Dexin Kong

Faculty, Staff and Student Publications

No abstract provided.

Potential Mitigation Of Environmental Impacts Of Intensive Plum Production In Southeast China With Maintenance Of High Yields: Evaluation Using Life Cycle Assessment, Xiaojun Yan, Delian Ye, Yafu Tang, Muhammad Atif Muneer, Peter Christie, Congyue Tou, Weidong Xu, Bingrong Shen, Jinxian Xu, Jiangzhou Zhang

Faculty, Staff and Student Publications

INTRODUCTION: Intensive plum production usually involves high yields but also high environmental costs due to excessive fertilizer inputs. Quantitative analysis of the environmental effects of plum production is thereby required in the development of optimum strategies to promote sustainable fruit production.

METHODS: We collected survey questionnaires from 254 plum production farms in Zhao'an county, Fujian province, southeast China to assess the environmental impacts by life cycle assessment (LCA) methodology. The farms were categorized into four groups based on yield and environmental impacts, i.e., LL (low yield and low environmental impact), LH (low yield but high environmental impact), HL (high yield …

Large Scale Crowdsourced Radiotherapy Segmentations Across A Variety Of Cancer Anatomic Sites, Kareem A Wahid, Diana Lin, Onur Sahin, Michael Cislo, Benjamin E Nelms, Renjie He, Mohammed A Naser, Simon Duke, Michael V Sherer, John P Christodouleas, Abdallah S R Mohamed, James D Murphy, Clifton D Fuller, Erin F Gillespie

Faculty, Staff and Student Publications

Clinician generated segmentation of tumor and healthy tissue regions of interest (ROIs) on medical images is crucial for radiotherapy. However, interobserver segmentation variability has long been considered a significant detriment to the implementation of high-quality and consistent radiotherapy dose delivery. This has prompted the increasing development of automated segmentation approaches. However, extant segmentation datasets typically only provide segmentations generated by a limited number of annotators with varying, and often unspecified, levels of expertise. In this data descriptor, numerous clinician annotators manually generated segmentations for ROIs on computed tomography images across a variety of cancer sites (breast, sarcoma, head and neck, …

Glia-Neuron Coupling Via A Bipartite Sialylation Pathway Promotes Neural Transmission And Stress Tolerance Iglia-Neuron Coupling Via A Bipartite Sialylation Pathway Promotes Neural Transmission And Stress Tolerance In Drosophila, Hilary Scott, Boris Novikov, Berrak Ugur, Brooke Allen, Ilya Mertsalov, Pedro Monagas-Valentin, Melissa Koff, Sarah Baas Robinson, Kazuhiro Aoki, Raisa Veizaj, Dirk J Lefeber, Michael Tiemeyer, Hugo Bellen, Vladislav Panin

Duncan NRI Faculty and Staff Publications

Modification by sialylated glycans can affect protein functions, underlying mechanisms that control animal development and physiology. Sialylation relies on a dedicated pathway involving evolutionarily conserved enzymes, including CMP-sialic acid synthetase (CSAS) and sialyltransferase (SiaT) that mediate the activation of sialic acid and its transfer onto glycan termini, respectively. In Drosophila, CSAS and DSiaT genes function in the nervous system, affecting neural transmission and excitability. We found that these genes function in different cells: the function of CSAS is restricted to glia, while DSiaT functions in neurons. This partition of the sialylation pathway allows for regulation of neural functions via …