Digital Commons Network^™

Idh Status Dictates Ohsv Mediated Metabolic Reprogramming Affecting Anti-Tumor Immunity, Upasana Sahu, Matthew P Mullarkey, Sara A Murphy, Joshua C Anderson, Vasanta Putluri, Abu Hena Mostafa Kamal, Jun Hyoung Park, Tae Jin Lee, Alexander L Ling, Benny A Kaipparettu, Ashok Sharma, Nagireddy Putluri, Pamela L Wenzel, Christopher D Willey, E Antonio Chiocca, James M Markert, Balveen Kaur

Faculty, Staff and Student Publications

Identification of isocitrate dehydrogenase (IDH) mutations has uncovered the crucial role of metabolism in gliomagenesis. Oncolytic herpes virus (oHSV) initiates direct tumor debulking by tumor lysis and activates anti-tumor immunity, however, little is known about the role of glioma metabolism in determining oHSV efficacy. Here we identify that oHSV rewires central carbon metabolism increasing glucose utilization towards oxidative phosphorylation and shuttling glutamine towards reductive carboxylation in IDH wildtype glioma. The switch in metabolism results in increased lipid synthesis and cellular ROS. PKC induces ACSL4 in oHSV treated cells leading to lipid peroxidation and ferroptosis. Ferroptosis is critical to launch an …

Diabetic Retinopathy: A Pathophysiological Discussion, Nathanael C. Nicholls

Senior Honors Theses

Diabetic retinopathy is a severe complication of diabetes that is capable of causing vision loss or blindness. As a result of hyperglycemia, the disease increases oxidative stress and activates biochemical processes such as the Hippo pathway and the complement system to cause significant damage to the retina. Overexpression of BTG1 and microRNA-183 enables activation of biochemical pathways that lead to negative effects on the retinal vascular endothelium including angiogenesis and inflammation. Conventional methods of diagnosis for diabetic retinopathy include fundus examination, nucleoside detection, and optical coherence tomography angiography. Photocoagulation and hormonal intravitreal injection are the most popular current treatments, while …

Impact Of Antidiabetic Medication Type On A New Episode Of Depression: A Retrospective Cohort Study In Texas, Usa, Lin-Na Chou, Mukaila A Raji, Holly M Holmes, Yong-Fang Kuo

Faculty, Staff and Student Publications

Objectives: To examine the associations between antidiabetic medication type and a new episode of depression using 100% Texas Medicare database during 2009 and 2018.

Design: A retrospective cohort study.

Setting: A population-based study using the Texas Medicare data.

Interventions: 11 common antihyperglycaemic medication types, alone and in combinations: metformin-only, five non-metformin-containing regimens (dipeptidyl peptidase-4 inhibitor (DPP4i) only, sulfonylureas (SU) only, thiazolidinediones (TZD) only, SU/DPP4i and SU/TZD) and five metformin-containing combination treatments (metformin/DPP4i, metformin/SU, metformin/TZD, metformin/SU/DPP4i and metformin/SU/TZD).

Participants: This study included 59 057 type 2 diabetes (T2D) patients from a cohort of Texas Medicare beneficiaries who were aged ≥66 years, …

Is There Evidence For Changes In Antibiotic Resistance Of Microorganisms Causing Postcataract Surgery Endophthalmitis: A Systematic Review, Christina J Flaxel, Justine R Smith, Nieraj Jain, Leo A Kim, Stephen Jae Kim, Maureen G Maguire, Christina Y Weng, Steven Yeh

Faculty, Staff and Students Publications

Background/aims: To review the evidence for changes in antibiotic resistance patterns before and after cataract surgery since the advent of routine use of intracameral (IC) antibiotic prophylaxis and development of newer topical fluoroquinolones pre- and postcataract surgery.

Methods: Literature searches in the National Library of Medicine PubMed database were conducted between 2019 and 2021 and updated in 2024. There were no date restrictions, and the search was limited to high-quality studies published in English. The initial combined searches yielded 583 articles, and the search update in 2024 yielded 9 articles. Of these 592 articles, 26 presented original research that met …

Tobacco Smoking Functional Networks: A Whole-Brain Connectome Analysis In 24 539 Individuals, Yezhi Pan, Chuan Bi, Zhenyao Ye, Hwiyoung Lee, Jiaao Yu, Luba Yammine, Tianzhou Ma, Peter Kochunov, L Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

Introduction: Nicotine addiction, a multifaceted neuropsychiatric disorder, profoundly impacts brain functions through interactions with neural pathways. Despite its significance, the impact of tobacco smoking on the whole-brain functional connectome remains largely unexplored.

Aims and methods: We conducted a whole-brain analysis on 24 539 adults aged 40 and above from the United Kingdom Biobank cohort. Subjects were categorized into individuals who use nicotine and those who do not use nicotine based on current and chronic tobacco smoking information. Functional connectivity was assessed using resting-state functional magnetic resonance imaging. We employed a network analysis method to assess the systematic effects of tobacco …

Can The Discovery Of High-Impact Diagnostics Be Improved By Matching The Sampling Rate Of Clinical Diagnostics To The Frequency Domain Of Diagnostic Information?, Steven W Millward, Peng Wei, David Piwnica-Worms, Seth T Gammon

Faculty, Staff and Student Publications

Over the past 30 years, academic and industrial research investigators have developed molecular reporters to visualize cell death in complex biological systems. In parallel, clinical researchers, chemists, biochemists, and molecular biologists have endeavored to translate these molecular tools into clinical imaging agents. Despite these efforts, there are no clinically approved imaging methodologies with which to image cell death consistently and quantitatively. One reason may reside in the intrinsic mismatch between the sampling frequency of translational molecular imaging and the biochemical kinetics that define cell death. Beyond cell death imaging, many active research programs are now attempting to create translational diagnostic …

Swi/Snf Complex-Mediated Znf410 Cooperative Binding Maintains Chromatin Accessibility And Enhancer Activity, Siyuan Xu, Chuxuan Peng, Ren Ren, Haowen Lu, Han Zhao, Sijian Xia, Yijie Shen, Bin Xu, Haoyue Zhang, Xiaodong Cheng, Gerd A Blobel, Xianjiang Lan

Faculty, Staff and Student Publications

The clustering of multiple transcription factor binding sites (TFBSs) for the same TF has proved to be a pervasive feature of cis-regulatory elements in the eukaryotic genome. However, the contribution of binding sites within the homotypic clusters of TFBSs (HCTs) to TF binding and target gene expression remains to be understood. Here, we characterize the CHD4 enhancers that harbor unique functional ZNF410 HCTs genome wide. We uncover that ZNF410 controls chromatin accessibility and activity of the CHD4 enhancer regions. We demonstrate that ZNF410 binds to the HCTs in a collaborative fashion, further conferring transcriptional activation. In particular, three ZNF410 motifs …

Biallelic Fgf4 Variants Linked To Thoracic Dystrophy And Respiratory Insufficiency, Laura M. Watts, Esther Kinning, Donald R. Latner, Marla Johnston, Jessica Patrick-Esteve, Gregory M. Cooper, Stephen R.F. Twigg, Alistair T. Pagnamenta, Jenny C. Taylor

School of Medicine Faculty Publications

The thoracic dystrophies are inherited skeletal conditions where abnormal embryonic development of the thoracic skeleton results in a narrow chest, pulmonary hypoplasia, and respiratory insufficiency, which can be severe or lethal. The majority of thoracic dystrophies are due to biallelic alterations in genes needed for normal ciliary function. However, despite the identification of over 20 genes as causal for the thoracic dystrophy phenotype, around 20% of patients remain without a molecular diagnosis. We present two unrelated families with a clinical diagnosis of thoracic dystrophy with associated respiratory insufficiency without a molecular diagnosis on previous genetic testing. Both harbor rare biallelic …

Dna Methylation Signature Of A Lifestyle-Based Resilience Index For Cognitive Health, Wei Zhang, David Lukacsovich, Juan I Young, Lissette Gomez, Michael A Schmidt, Eden R Martin, Brian W Kunkle, X Steven Chen, Deirdre M O'Shea, James E Galvin, Lily Wang

Faculty, Staff and Students Publications

Cognitive resilience (CR) contributes to the variability in risk for developing and progressing in Alzheimer's disease (AD) among individuals. Beyond genetics, recent studies highlight the critical role of lifestyle factors in enhancing CR and delaying cognitive decline. DNA methylation (DNAm), an epigenetic mechanism influenced by both genetic and environmental factors, including CR-related lifestyle factors, offers a promising pathway for understanding the biology of CR. We studied DNAm changes associated with the Resilience Index (RI), a composite measure of lifestyle factors, using blood samples from the Healthy Brain Initiative (HBI) cohort. After corrections for multiple comparisons, our analysis identified 19 CpGs …

The Combined Effect Of High-Intensity Interval Training And Time-Restricted Feeding On The Akt-Igf-1-Mtor Signaling Pathway In The Muscle Tissue Of Type 2 Diabetic Rats, Motahareh Mohebinejad, Fatemeh Kazeminasab, Mahtab Ghanbari Rad, Reza Bagheri, Mazdak Razi, Darryn Willoughby, Fred Dutheil

Faculty, Staff and Students Publications

Background/Objectives: High-intensity interval training (HIIT) and time-restricted feeding (TRF) have shown potential in enhancing glucose metabolism, increasing insulin sensitivity, and promoting muscle health. This study investigates the combined effects of HIIT and TRF on the AKT-IGF-1-mTOR signaling pathway in the muscle tissue of type 2 diabetic (T2D) rats.

Methods: 42 male Wistar rats (4-5 weeks of age) were included in the study. The animals were randomly divided into two groups: 1. Standard diet (SD) non-diabetic (n = 7) and 2. High-fat diet (HFD n = 35) for 4 weeks. T2D was induced by intraperitoneal injection (IP) of streptozotocin (STZ) …

Liposomes As Imaging Agents Of Inflammation And Oxidative Stress In Bone Implants, Delia Danila, Patricia S Pardo, R Devesh Kumar Misra, Aladin M Boriek

Faculty, Staff and Students Publications

Liposomes are tiny, spherical vesicles made from cholesterol and natural phospholipids that are promising imaging agents for detecting medical complications. They can carry fluorescent markers or other imaging agents, making them effective for medical imaging. Furthermore, liposomes can target specific cells involved in inflammation, such as macrophages, and accumulate at inflammation sites when injected. Additionally, liposomes can be designed to respond to oxidative stress, which is often associated with bone implant complications. By detecting areas of stress, liposomes provide valuable information about implant health. However, challenges such as rapid clearance from the body, precise targeting, immune reactions, and high production …

Epidemiology Of Tourette Syndrome, Abdullah Yasir Yilmaz, Joseph Jankovic

Faculty, Staff and Students Publications

Background/Objectives: Tourette syndrome (TS) is a neurodevelopmental disorder, manifested by tics and a variety of behavioral comorbidities that cluster strongly within families, suggesting a combination of genetic and environmental risk factors. The underlying pathophysiology of TS remains to be elucidated. Understanding the incidence and prevalence across different populations provides valuable insights into the etiology and pathogenesis of the condition and aids in the development of effective treatment strategies.

Methods: A comprehensive literature search was conducted on PubMed covering the period from 1 January 2000 to 1 January 2025. The search used the terms "Tourette syndrome", "tics", "tic disorders", "epidemiology", "prevalence", …

Tips For Quality Publishing; Lessons From The Neuroscience Editorial Team, Francesca Cirulli, Rachael Dangarembezi, Victor De Lafuente, Anthony J Hannan, Amanda C Kentner, Tatsuya Mima, Laurel Morris, Sarah J Spencer, Long-Jun Wu, Chen Zhang

The Brown Foundation: Institute of Molecular Medicine

In pursuit of excellence in scholarly publishing, the Neuroscience editorial team shares valuable insights that are essential for authors, reviewers, and the broader scientific community. Firstly, we emphasize that impactful research is built on rigorous study design and execution. Beyond fundamental methodological safeguards such as randomization and blinded analysis, we highlight the importance of thoughtfully selecting study models, with deliberate attention to biological variables like sex and gender, as well as appropriate nomenclature. Secondly, as technological innovations reshape research landscapes, we advocate for combining methodological rigor with suitable analytical tools to ensure robust data collection and transparent reporting. Thirdly, for …

Trends In Celecoxib Prescribing: A Single Institution 16-Month Review, Ivo H Cerda, Helen Jung, Maria C Guerrero, Rodrigo Diez Tafur, Robert Jason Yong, Christopher L Robinson, Jamal J Hasoon

Faculty, Staff and Student Publications

Background/Objectives: Celecoxib, a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID), is widely prescribed for pain management due to its efficacy and improved gastrointestinal safety profile compared to traditional NSAIDs. Understanding prescription trends and their comparison to other NSAIDs provides valuable insight into prescribing behaviors in clinical settings.

Methods: This retrospective study analyzed celecoxib prescriptions written by three pain management physicians in a single institution over a 16-month period from 1 January 2023 to 30 April 2024. Prescription data were collected and grouped into four 4-month intervals to assess temporal trends. Additionally, we compared celecoxib prescriptions to other commonly prescribed NSAIDs, including …

Neural And Behavioral Changes In Consecutive Errors, Nabeel Bhimani

Research Honors

Consecutive failures in any task have been understudied in electrophysiology and neuroscience. Research identifies that single-errors tend to slow our response time to identify feedback and respond accordingly to ensure a correct response for the next task. However, evidence is limited regarding what the commission of consecutive errors does in relation to not only behavior, but also in relation to adaptations in attention or self-regulation. Electroencephalography (EEG) studies have revealed two important components of neural activity that can assess this self-regulatory activity with similar morphology and topography. The error positivity (Pe) is a positive wave that peaks due to the …

Rnase1-Driven Alk-Activation Is An Oncogenic Driver And Therapeutic Target In Non-Small Cell Lung Cancer, Zhengyu Zha, Chunxiao Liu, Meisi Yan, Cong Chen, Cheng Yu, Yaohui Chen, Chenhao Zhou, Lu Li, Yi-Chuan Li, Hiro Yamaguchi, Leiguang Ye, Tong Liu, Ying-Nai Wang, Heng-Huan Lee, Wen-Hao Yang, Li-Chuan Chan, Baozhen Ke, Jennifer L Hsu, Lieming Ding, Dong Ji, Peng Pan, Yiran Meng, Yue Pu, Lunxu Liu, Mien-Chie Hung

Faculty, Staff and Student Publications

Targeted therapy has achieved significant success in the treatment of non-small cell lung cancer (NSCLC), particularly in patients harboring common oncogenic driver mutations such as EGFR, KRAS, and ALK rearrangement. However, ~35-50% of NSCLC patients without tyrosine kinase mutation or rearrangement (non-mutated) cannot benefit from these targeted treatments, highlighting the urgent need for novel therapeutic strategies for this patient population. In this study, we report a non-canonical role of human secretory ribonuclease 1 (RNase1), which binds to and activates wild-type ALK in lung cancer cells, thereby triggering its downstream signaling pathway. RNase1-driven ALK-activation (RDAA) cells exhibit enhanced cell proliferation, migration, …

Association Between B-Cell Marker Expression And Runx1 Lesions In Acute Myeloid Leukemia, Beyond Runx1::Runx1t1 Fusion: Diagnostic Pitfalls With Mixed-Phenotype Acute Leukemia—B/Myeloid, Giby V George, Malgorzata Kajstura, Audrey N Jajosky, Hong Fang, Fatima Zahra Jelloul, Andrew G Evans, W Richard Burack, John M Bennett, L Jeffrey Medeiros, Wei Wang, Siba El Hussein

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with RUNX1::RUNX1T1 fusion is well known to often demonstrate aberrant upregulation of CD19 expression. We studied the clinicopathologic and genetic features of 16 cases of AML with various RUNX1 lesions, including mutations, copy number gains, and translocations other than fusions with RUNX1T1. Most of these cases were classified as AML-myelodysplasia-related or AML-post-cytotoxic therapy based on the cytogenetic and molecular work-up. These neoplasms showed partial expression of one or more B-cell antigens by flow cytometry and/or immunohistochemistry, fulfilling the criteria for mixed-phenotype acute leukemia (MPAL)-B/myeloid (i.e., ≥20% blasts expressing B and myeloid lineage antigens) …

Progesterone Signaling In Oviductal Epithelial Cells Modulates The Immune Response To Support Preimplantation Embryonic Development, Emily A Mcglade, Jiude Mao, Kalli K Stephens, Ryan M Marquardt, Feyza Nur Arguc, Peter F Lais, San-Pin Wu, Sarayut Winuthayanon, Haval Shirwan, Esma S Yolcu, Mark I Hunter, James K Pru, John P Lydon, Francesco J Demayo, Wipawee Winuthayanon

Faculty, Staff and Students Publications

More than 60% of pregnancy losses occur during the first trimester, highlighting the need to understand the role of the oviduct in early pregnancy. In this study, we conditionally ablated the classical progesterone receptor (Pgr) in oviductal epithelial cells, called the Pgrd/d mouse model. We found that 40% of embryos collected from Pgrd/d females were nonviable or developmentally delayed, indicating that epithelial PGR expression is crucial for embryonic development. Single-cell RNA sequencing revealed up-regulation of proinflammatory genes, including interleukin-22 (IL-22), in the epithelial cells of Pgrd/d females. Pharmacological inhibition of inflammation using nonsteroidal anti-inflammatory drugs …

Robust Sex Determination In The Caenorhabditis Nigoni Germ Line, Jonathan P Harbin, Yongquan Shen, Shin-Yi Lin, Kevin Kemper, Eric S Haag, Erich M Schwarz, Ronald E Ellis

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sexual characteristics and reproductive systems are dynamic traits in many taxa, but the developmental modifications that allow change and innovation are largely unknown. A leading model for this process is the evolution of self-fertile hermaphrodites from male/female ancestors. However, these studies require direct analysis of sex-determination in male/female species, as well as in the hermaphroditic species that are related to them. In Caenorhabditis nematodes this has only become possible recently, with the discovery of new species. Here, we use gene editing to characterize major sex-determination genes in C. nigoni, a sister to the widely studied hermaphroditic species C. briggsae. These …

Comparison Of Total Oxidative State, Total Antioxidative State , Serum Paraoxonase Activity, And Thiol Levels Before And After 6 Months Of Treatment In Patients With Multiple Sclerosis Who Have Been Recently Started On New Therapy Agents, Emel Başar, Hasan Bayindir, Hati̇ce Ferhan Kömürcü, Ebru Bi̇lge Di̇ri̇k, Ömer Anlar, Özcan Erel

Turkish Journal of Medical Sciences

Background/aim: The objective of this study was to establish the oxidative stress determiners as a total oxidative state (TOS), total antioxidative state (TAS), paraoxonase (PON) activity, oxidative stress index (OSI), and thiol/disulfide levels before and after 6 months of immunomodulator therapy in patients who were diagnosed according to the revised McDonald Criteria.

Materials and methods: Thirty-nine patients were included in our study who were diagnosed according to the revised McDonald Criteria, approved to participate in the study, and had been treated in the neurology inpatient clinic or presented in the neurology outpatient clinic of Ankara Yıldırım Beyazıt University Atatürk Training …

Can Mac-2 Binding Protein Glycosylation Isomer Serve As A Biomarker For Predicting Pulmonary Arterial Pressure And Pulmonary Hypertension In Systemic Sclerosis?, Ridvan Mercan, Di̇lara Bulut Gökten, Sonat Pinar Kara, Nesli̇han Meli̇k Üzüm, Savaş Güzel

Turkish Journal of Medical Sciences

Background/aim: This study aimed to explore the role of Mac-2 binding protein glycosylation isomer (M2BPGi) serum levels as a biomarker that could contribute to understanding organ involvement and the overall disease process in systemic sclerosis (SSc).

Materials and methods: The cross-sectional study examined 108 patients with SSc. Seventy-two people were included in the control group. Demographic and clinical characteristics of the patients, laboratory and radiological findings, pulmonary function tests and echocardiography results, and presence of pulmonary hypertension (PHT) based on echocardiographic evaluation were recorded. Venous blood samples of 5 mL were collected from individuals. Human M2BPGi levels in the samples …

Comparative Vasorelaxant Effects Of Atorvastatin And Rosuvastatin In Rat Aorta:Investigating The Role Of Perivascular Adipose Tissue, Deni̇z Kaleli̇ Durman, Meryem Aras, Gülsüm Ruveyda Aktaş, Bi̇rsel Sönmez Uydeş Doğan

Turkish Journal of Medical Sciences

Background/aim: Statins are known to display pleiotropic effects on the vascular system, beyond their lipid-lowering properties. Studieson isolated vascular preparations have demonstrated their acute relaxant effects on vascular tone. Considering the increased evidence inregard to the contribution of perivascular adipose tissue (PVAT) in the regulation of vascular homeostasis, we aimed to investigate thepossible modulatory role of PVAT in the vascular effects of atorvastatin and rosuvastatin in isolated rat aorta.

Materials and methods: Thoracic aortas isolated from young male Wistar rats were divided into two groups: rings with intact PVAT(+) and rings without PVAT (-), and then mounted in an isolated …

The Effects Of Liraglutide On Expressions Of Insulin Secretion And Beta Cell Survive Associated Gpcr Genes In Pancreatic Beta Cells, Meli̇kenur Türkol, Türker Bi̇lgen

Turkish Journal of Medical Sciences

Background/aim: Liraglutide as a long-acting glucagon-like peptide drug has anti-hyperglycemic and antiobesity effects. G protein-coupled receptors (GPCRs) are well- known drug target molecules that conduct critical signaling pathways related with diseases. Research has confirmed the role of many GPCRs genes in the regulation of pancreatic beta cell functions and insulin secretion. Liraglutide dependent expressional changes in GPCR genes may let us determine new drug targets.

Materials and methods: Therefore, we investigated the changes in expression of GPR75, GPR56, GLP1R, M3R, and CB1R genes, which are the GPCR family members, in response to liraglutide treatment in the NIT-1 mouse pancreatic beta …

Acute Effects Of Virtual Reality-Based Relaxation And Exergaming On Primary Dysmenorrhea Symptoms, Muhammed Şeref Yildirim, Merve Çoğ, Büşra Mehder Akbaş, Si̇nem Salar, Hi̇lal Kekli̇cek

Turkish Journal of Medical Sciences

Background/aim: Primary dysmenorrhea (PD) is a menstrual disorder with significant physical and psychological impacts. Physical activity and relaxation techniques are proven methods for managing PD. Advances in virtual reality (VR) suggest that immersive relaxation and exergaming could provide new avenues for symptom relief. This study aimed to investigate the acute effects of VR-based interventions on PD symptoms and compare them with a control group receiving Jacobson’s Relaxation

Materials and methods: A randomized, controlled, single-blind trial was conducted with 43 female participants aged 18–30 years with regular menstrual cycles and PD. Participants were allocated to three groups: (I) immersive VR relaxation, …

Benzyl Alcohol Improves Ang Ii-Induced Vascular And Renal Injury, Qi Hua, Zhenyu Gu

Turkish Journal of Medical Sciences

Background/aim: The etiology of hypertension in pediatric populations is complex and multifactorial, with metabolic abnormalitiesplaying a fundamental role in the pathogenesis of the condition. This study investigates the therapeutic effects of Benzyl alcohol (BA),identified through metabolomics analysis of pediatric hypertension serum, on Angiotensin II (Ang II)-induced vascular and renalinjury in murine models.

Materials and methods: Male C57BL/6 mice were used to establish a vascular remodeling model by continuous 4-week Ang II infusionusing a subcutaneous osmotic pump. Bioinformatics was used to identify target metabolites. The tail artery, common carotid arterydiastolic, and systolic pressures in mice were determined with a blood pressure …

Humanized Saccharomyces Cerevisiae Provides A Facile And Effective Tool To Identify Damaging Human Variants That Cause Exosomopathies, Khondakar Sayef Ahammed, Milo B Fasken, Anita H Corbett, Ambro Van Hoof

Faculty, Staff and Student Publications

The RNA exosome is an evolutionarily conserved, multiprotein complex that is the major RNase in 3' processing and degradation of a wide range of RNAs in eukaryotes. Single amino acid changes in RNA exosome subunits cause rare genetic diseases collectively called exosomopathies. However, distinguishing disease-causing variants from nonpathogenic ones remains challenging, and the mechanism by which these variants cause disease is largely unknown. Previous studies have employed a budding yeast model of RNA exosome-linked diseases that relies on mutating the orthologous yeast genes. Here, we develop a humanized yeast model of exosomopathies that allows us to unambiguously assess damaging effects …

Multimeric Transcription Factor Bcl11a Utilizes Two Zinc-Finger Tandem Arrays To Bind Clustered Short Sequence Motifs, John R Horton, Meigen Yu, Jujun Zhou, Melody Tran, Rithvi R Anakal, Yue Lu, Robert M Blumenthal, Xiaotian Zhang, Yun Huang, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

BCL11A, a transcription factor, is vital for hematopoiesis, including B and T cell maturation and the fetal-to-adult hemoglobin switch. Mutations in BCL11A are linked to neurodevelopmental disorders. BCL11A contains two DNA-binding zinc-finger arrays, low-affinity ZF2-3 and high-affinity ZF4-6, separated by a 300-amino-acid linker. ZF2-3 and ZF4-5 share 73% identity, including five out of six DNA base-interacting residues. These arrays bind similar short sequence motifs in clusters, with the linker enabling a broader binding span. Crystallographic structures of ZF4-6, in complex with oligonucleotides from the β-globin locus region, reveal DNA sequence recognition by residues Asn756 (ZF4), Lys784 and Arg787 (ZF5). A …

A Deep Learning Strategy To Identify Cell Types Across Species From High-Density Extracellular Recordings, Maxime Beau, David J Herzfeld, Francisco Naveros, Marie E Hemelt, Federico D'Agostino, Marlies Oostland, Alvaro Sánchez-López, Young Yoon Chung, Michael Maibach, Stephen Kyranakis, Hannah N Stabb, M Gabriela Martínez Lopera, Agoston Lajko, Marie Zedler, Shogo Ohmae, Nathan J Hall, Beverley A Clark, Dana Cohen, Stephen G Lisberger, Dimitar Kostadinov, Court Hull, Michael Häusser, Javier F Medina

Faculty, Staff and Students Publications

High-density probes allow electrophysiological recordings from many neurons simultaneously across entire brain circuits but fail to reveal cell type. Here, we develop a strategy to identify cell types from extracellular recordings in awake animals and reveal the computational roles of neurons with distinct functional, molecular, and anatomical properties. We combine optogenetics and pharmacology using the cerebellum as a testbed to generate a curated ground-truth library of electrophysiological properties for Purkinje cells, molecular layer interneurons, Golgi cells, and mossy fibers. We train a semi-supervised deep learning classifier that predicts cell types with greater than 95% accuracy based on the waveform, discharge …

A Nuclear Rna Degradation Code Is Recognized By Paxt For Eukaryotic Transcriptome Surveillance, Lindsey V Soles, Liang Liu, Xudong Zou, Yoseop Yoon, Shuangyu Li, Lusong Tian, Marielle Valdez, Angela M Yu, Hong Yin, Wei Li, Fangyuan Ding, Georg Seelig, Lei Li, Yongsheng Shi

Faculty, Staff and Students Publications

The RNA exosome plays critical roles in eukaryotic RNA degradation, but how it specifically recognizes its targets remains unclear. The poly(A) tail exosome targeting (PAXT) connection is a nuclear adaptor that recruits the exosome to polyadenylated RNAs, especially transcripts polyadenylated at intronic poly(A) sites. Here, we show that PAXT-mediated RNA degradation is induced by the combination of a 5' splice site (ss) and a poly(A) junction (PAJ) but not by either sequence alone. These sequences are bound by U1 small nuclear ribonucleoprotein particle (snRNP) and cleavage/polyadenylation factors, which, in turn, cooperatively recruit PAXT. As the 5' ss-PAJ combination is typically …

Investigating The Effects Of Palmitoylation In Ovcar3 Cells, Bethany Knopp, Emu Suzuki

Undergraduate Research Symposium 2025

Ovarian cancer is a disease characterized by the abnormal growth of cells in the ovaries often due to mutations in our DNA. Because ovarian cancer is typically diagnosed at advanced stages, the survival rate is less than 40% over a five-year period. One significant influence of this cancer is palmitoylation - a post- translational modification in which fatty acid chains are added to specific cysteine residues in proteins. This modification alters protein localization, stability, and function. When dysregulated, as seen in ovarian cancer, palmitoylation can promote irregular cell growth, mutations, and ultimately cancer. However, the role of palmitoylation in cancer …