Digital Commons Network^™

A Novel Missense Variant Located Within The Zinc Finger Domain Of The Gli3 Gene Was Identified In A Vietnamese Pedigree With Index Finger Polydactyly, Thy Ngoc Nguyen, Giang Son Tran, Hai Duc Hoang, Long Giang Nguyen

Faculty, Staff and Student Publications

BACKGROUND: Polydactyly, particularly of the index finger, remains an intriguing anomaly for which no specific gene or locus has been definitively linked to this phenotype. In this study, we conducted an investigation of a three-generation family displaying index finger polydactyly.

METHODS: Exome sequencing was conducted on the patient, with a filtration to identify potential causal variation. Validation of the obtained variant was conducted by Sanger sequencing, encompassing all family members.

RESULTS: Exome analysis uncovered a novel heterozygous missense variant (c.1482A>T; p.Gln494His) at the zinc finger DNA-binding domain of the GLI3 protein within the proband and all affected family members. …

Incidence And Factors In Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice, William Wroe, Ari Dienel, Sungha Hong, Kanako Matsumura, Jose Guzman, Kiara Torres, Angelica Bernal, Hussein A Zeineddine, Peeyush Thankamani Pandit, Spiros L Blackburn, Devin W Mcbride

Faculty, Staff and Student Publications

Background: Delayed cerebral ischemia (DCI) is one of the most feared complications in aneurysmal subarachnoid hemorrhage (SAH). Animal models are crucial to studying the disease mechanisms and potential treatments. DCI in rodents was thought to not exist; herein we examine literature and our experience with DCI in rodents.

Methods: Daily behavioral performance was assessed every day from day 1 to up to 7 days post-SAH on mice from 5 different studies that used the endovascular perforation model. Performance was graded using an 8-test sensorimotor neuroscore previously described. The daily neuroscore was then used to identify the incidence and timing of …

Loss Of Ovol2 In Triple-Negative Breast Cancer Promotes Fatty Acid Oxidation Fueling Stemness Characteristics, Ruipeng Lu, Jingjing Hong, Tong Fu, Yu Zhu, Ruiqi Tong, Di Ai, Shuai Wang, Qingsong Huang, Ceshi Chen, Zhiming Zhang, Rui Zhang, Huiling Guo, Boan Li

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, has a poor prognosis and lacks effective treatment strategies. Here, the study discovered that TNBC shows a decreased expression of epithelial transcription factor ovo-like 2 (OVOL2). The loss of OVOL2 promotes fatty acid oxidation (FAO), providing additional energy and NADPH to sustain stemness characteristics, including sphere-forming capacity and tumor initiation. Mechanistically, OVOL2 not only suppressed STAT3 phosphorylation by directly inhibiting JAK transcription but also recruited histone deacetylase 1 (HDAC1) to STAT3, thereby reducing the transcriptional activation of downstream genes carnitine palmitoyltransferase1 (CPT1A and CPT1B). PyVT-Ovol2 knockout mice develop a …

A Comprehensive Investigation Of The Performance Of A Commercial Scintillator System For Applications In Electron Flash Radiotherapy, Kevin Liu, Shannon Holmes, Emil Schüler, Sam Beddar

Faculty, Staff and Student Publications

Background: Dosimetry in ultra-high dose rate (UHDR) beamlines is significantly challenged by limitations in real-time monitoring and accurate measurement of beam output, beam parameters, and delivered doses using conventional radiation detectors, which exhibit dependencies in ultra-high dose-rate (UHDR) and high dose-per-pulse (DPP) beamline conditions.

Purpose: In this study, we characterized the response of the Exradin W2 plastic scintillator (Standard Imaging, Inc.), a water-equivalent detector that provides measurements with a time resolution of 100 Hz, to determine its feasibility for use in UHDR electron beamlines.

Methods: The W2 scintillator was exposed to an UHDR electron beam with different beam parameters by …

Mesenchymal-Specific Alms1 Knockout In Mice Recapitulates Metabolic Features Of Alström Syndrome, Eleanor J Mckay, Ineke Luijten, Xiong Weng, Pablo B Martinez De Morentin, Elvira De Frutos González, Zhanguo Gao, Mikhail G Kolonin, Lora K Heisler, Robert K Semple

Faculty, Staff and Student Publications

OBJECTIVE: Alström Syndrome (AS), caused by biallelic ALMS1 mutations, includes obesity with disproportionately severe insulin resistant diabetes, dyslipidemia, and fatty liver. Prior studies suggest that hyperphagia is accounted for by loss of ALMS1 function in hypothalamic neurones, whereas disproportionate metabolic complications may be due to impaired adipose tissue expandability. We tested this by comparing the metabolic effects of global and mesenchymal stem cell (MSC)-specific Alms1 knockout.

METHODS: Global Alms1 knockout (KO) mice were generated by crossing floxed Alms1 and CAG-Cre mice. A Pdgfrα-Cre driver was used to abrogate Alms1 function selectively in MSCs and their descendants, including preadipocytes. We combined …

Pharmacokinetic Analysis Of A Phenobarbital Overdose Treated With Urinary Alkalinization Alone, Justin Seltzer, Jeremy Hardin, Henrik Galust, Nathan Friedman, Bryan Corbett, Richard F Clark

Faculty, Staff and Student Publications

Phenobarbital is a long-acting barbiturate used to treat alcohol withdrawal and epilepsy. Acute overdoses present with varying levels of central nervous system depression and large overdoses can be life threatening. Phenobarbital is an attractive candidate for enhanced elimination using urinary alkalinization given it is a weak acid with a long half-life and extensive urinary elimination. Limited human data exist regarding use of urine alkalinization for the treatment of phenobarbital overdose. We present a fourteen-year-old female who was treated with urinary alkalinization alone following an intentional ingestion of 3800 mg (84.4 mg/kg) of phenobarbital tablets. Urine drugs of abuse screening was …

Multidisciplinary Training In Dermatology: Exploring The Spectrum Of Board Certifications Among Physicians Practicing Dermatology In Texas, Rebecca H Lee, Jason Lee, Jonny Hatch, Lilian Zhan, Braden Van Alfen, Mark Conley, Tracy Zhao, Carlos Gomez-Meade

Faculty, Staff and Students Publications

Dermatology, a medical specialty focused on skin, hair, and nail conditions, often overlaps with various medical specialties. Although most physicians practicing dermatology are board-certified in dermatology, there are physicians practicing dermatology who are board-certified in a variety of different medical specialties. This cross-sectional study examines the board certifications of physicians who reported practicing dermatology in Texas. Data were sourced from the Texas Medical Board database updated in August 2023. The data showed that out of 1,614 practicing physicians declaring dermatology as a specialty in Texas, 1,080 (66.91%) physicians had one board certification, 200 (12.39%) had two, and 15 (0.93%) had …

Persistent ∆Fosb Expression Limits Recurrent Seizure Activity And Provides Neuroprotection In The Dentate Gyrus Of App Mice, Gabriel S Stephens, Jin Park, Andrew Eagle, Jason You, Manuel Silva-Pérez, Chia-Hsuan Fu, Sumin Choi, Corey P St Romain, Chiho Sugimoto, Shelly A Buffington, Yi Zheng, Mauro Costa-Mattioli, Yin Liu, A J Robison, Jeannie Chin

Faculty, Staff and Student Publications

Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer's disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity. However, the suppression of calbindin in conditions of neuronal hyperexcitability has been demonstrated to provide neuroprotection …

Purkinje Cell Dysfunction Causes Disrupted Sleep In Ataxic Mice, Luis E Salazar Leon, Amanda M Brown, Heet Kaku, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Purkinje cell dysfunction disrupts movement and causes disorders such as ataxia. Recent evidence suggests that Purkinje cell dysfunction may also alter sleep regulation. Here, we used an ataxic mouse model generated by silencing Purkinje cell neurotransmission (L7Cre;Vgatfx/fx) to better understand how cerebellar dysfunction impacts sleep physiology. We focused our analysis on sleep architecture and electrocorticography (ECoG) patterns based on their relevance to extracting physiological measurements during sleep. We found that circadian activity was unaltered in the mutant mice, although their sleep parameters and ECoG patterns were modified. The L7Cre;Vgatfx/fx mutant mice had decreased wakefulness and rapid eye movement (REM) sleep, …

A Multicenter, Randomized, Doubleblind, Placebo-Controlled Trial Of Amantadine To Stimulate Awakening In Comatose Patients Resuscitated From Cardiac Arrest, Patrick J Coppler, David J Gagnon, Katharyn L Flickinger, Jonathan Elmer, Clifton W Callaway, Francis X Guyette, Ankur Doshi, Alexis Steinberg, Cameron Dezfulian, Ari L Moskowitz, Michael Donnino, Teresa L May, David B Seder, Jon C Rittenberger

Faculty, Staff and Students Publications

OBJECTIVE: We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest.

METHODS: We performed a prospective, randomized, controlled pilot trial, randomizing subjects to amantadine 100 mg twice daily or placebo for up to 7 days. The study drug was administered between 72 and 120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome …

Anti-Α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (Ampa) Receptor Antibody Encephalitis In An Immunosuppressed Patient With Myasthenia Gravis Post-Thymoma Treatment, Suyuan Tan, Heitor Frade, Kian S Abdul-Baki, Samantha De Gannes, Puneet Singh, Ernesto Lopez Valencia, Anand Kumar, Aimalohi Esechie, Chilvana Patel

Faculty, Staff and Students Publications

Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is a rare form of autoimmune encephalitis. We report a case of a patient with myasthenia gravis post-thymoma treatment who presented with deteriorating mental status. She was found to have positive AMPA receptor titers in her cerebrospinal fluid and subsequently attained full recovery. Of the limited number of cases that were documented, we report the only case of a patient who was previously immunocompromised to develop the condition. Even though autoimmune encephalitis is an emerging condition, its early differentiation from other causes of encephalitis is crucial in the prognosis of the patient.

Quantitative Assessment Of The Trocarwash™ System For Automated Laparoscopic Camera Cleaning, Maaz Ahmed, Ashok Gowda, Fatemeh Alavi Naini, Alexander Le, John Treffalls, Robin Torres, Bryan M Burt

Faculty, Staff and Students Publications

Background: Soilage of the surgical endoscope occurs frequently during minimally invasive surgery. The resultant impairment of visualization of the surgical field compromises patient safety, prolongs operative times, and frustrates surgeons. The standard practice for cleaning the surgical camera involves a disruption in the conduct of surgery by completely removing the endoscope from the field, manually cleaning its lens, treating it with a surfactant, and reinserting it into the patient; after which the surgeon resumes the procedure.

Methods: We developed an automated solution for in vivo endoscope cleaning in minimally invasive surgery- a port that detects the position of the endoscope …

Individual Disruption Of 12 Testis-Enriched Genes Via The Crispr/Cas9 System Does Not Affect The Fertility Of Male Mice, Akira Suzuki, Norikazu Yabuta, Keisuke Shimada, Daisuke Mashiko, Keizo Tokuhiro, Yuki Oyama, Haruhiko Miyata, Thomas X Garcia, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

More than 1200 genes have been shown in the database to be expressed predominantly in the mouse testes. Advances in genome editing technologies such as the CRISPR/Cas9 system have made it possible to create genetically engineered mice more rapidly and efficiently than with conventional methods, which can be utilized to screen genes essential for male fertility by knocking out testis-enriched genes. Finding such genes related to male fertility would not only help us understand the etiology of human infertility but also lead to the development of male contraceptives. In this study, we generated knockout mice for 12 genes (Acrv1, Adgrf3, …

Serum Extracellular Vesicle Protein Profiling For Prediction Of Corneal Transplant Rejection, Hyun Ju Lee, Eun-Hye Bae, Jong Min Choi, Hyemee Kim, Hyeon Ji Kim, Heather Barreda, Sung Yun Jung, Joo Youn Oh, Ryang Hwa Lee

Faculty, Staff and Students Publications

Background: Corneal transplantation is the most common transplant procedure worldwide. Despite immune and angiogenic privilege of the cornea, 50% to 70% of corneal transplants fail in high-risk recipients, primarily because of immune rejection. Therefore, it is crucial to identify predictive biomarkers of rejection to improve transplant survival.

Methods: In search for predictive biomarkers, we performed proteomics analysis of serum extracellular vesicles (EVs) in a fully major histocompatibility complex-mismatched (C57BL/6-to-BALB/c) murine corneal transplantation model, wherein 50% of transplants undergo rejection by day 28 following transplantation.

Results: Our time course study revealed a decrease in the number of serum EVs on day …

Generation Of A Humanized Mace2 And A Conditional Hace2 Mouse Models Permissive To Sars-Cov-2 Infection, I-Wen Song, Megan Washington, Carolina Leynes, Jason Hsu, Kempaiah Rayavara, Yangjin Bae, Nele Haelterman, Yuqing Chen, Ming-Ming Jiang, Aleksandra Drelich, Vivian Tat, Denise G Lanza, Isabel Lorenzo, Jason D Heaney, Chien-Te Kent Tseng, Brendan Lee, Ronit Marom

Faculty, Staff and Students Publications

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains a public health concern and a subject of active research effort. Development of pre-clinical animal models is critical to study viral-host interaction, tissue tropism, disease mechanisms, therapeutic approaches, and long-term sequelae of infection. Here, we report two mouse models for studying SARS-CoV-2: A knock-in mAce2F83Y,H353K mouse that expresses a mouse-human hybrid form of the angiotensin-converting enzyme 2 (ACE2) receptor under the endogenous mouse Ace2 promoter, and a Rosa26 conditional knock-in mouse carrying the human ACE2 allele (Rosa26hACE2). Although the mAce2F83Y,H353K mice were susceptible to …

Cadherin-11 Targeted Cell-Specific Liposomes Enabled Skin Fibrosis Treatment By Inducing Apoptosis, Himanshu N Bhatt, Rimpy Diwan, Igor L Estevao, Rui Dong, Jennifer Smith, Chuan Xiao, Sandeep K Agarwal, Md Nurunnabi

Faculty, Staff and Students Publications

Continuous and aberrant activation of myofibroblasts is the hallmark of pathological fibrosis (e.g., abnormal wound healing). The deposition of excessive extracellular matrix (ECM) components alters or increases the stiffness of tissue and primarily accounts for multiple organ dysfunctions. Among various proteins, Cadherin-11 (CDH11) has been reported to be overexpressed on myofibroblasts in fibrotic tissues. Anti-apoptotic proteins such as (B cell lymphoma-2) (BCL-2) are also upregulated on myofibroblasts. Therefore, we hypothesize that CDH11 could be a targeted domain for cell-specific drug delivery and targeted inhibition of BCL-2 to ameliorate the development of fibrosis in the skin. To prove our hypothesis, we …

Efemp1 Haploinsufficiency Causes A Marfan-Like Hereditary Connective Tissue Disorder, Irman Forghani, Steven H Lang, Matthew J Rodier, Stephanie A Bivona, Alejo A Morales, Stephan Zuchner, Guney Bademci, Mustafa Tekin

Faculty, Staff and Students Publications

Phenotypic features of a hereditary connective tissue disorder, including craniofacial characteristics, hyperextensible skin, joint laxity, kyphoscoliosis, arachnodactyly, inguinal hernia, and diverticulosis associated with biallelic pathogenic variants in EFEMP1 have been previously described in four patients. Genome sequencing on a proband and her mother with comparable phenotypic features revealed that both patients were heterozygous for a stop-gain variant c.1084C>T (p.Arg362*). Complementary RNA-seq on fibroblasts revealed significantly reduced levels of mutant EFEMP1 transcript. Considering the absence of other molecular explanations, we extrapolated that EFEMP1 could be the cause of the patient's phenotypes. Furthermore, nonsense-mediated decay was demonstrated for the mutant allele …

Genetic Evaluation For Monogenic Disorders Of Low Bone Mass And Increased Bone Fragility: What Clinicians Need To Know, Emily Busse, Brendan Lee, Sandesh C S Nagamani

Faculty, Staff and Students Publications

Purpose of review: The purpose of this review is to outline the principles of clinical genetic testing and to provide practical guidance to clinicians in navigating genetic testing for patients with suspected monogenic forms of osteoporosis.

Recent findings: Heritability assessments and genome-wide association studies have clearly shown the significant contributions of genetic variations to the pathogenesis of osteoporosis. Currently, over 50 monogenic disorders that present primarily with low bone mass and increased risk of fractures have been described. The widespread availability of clinical genetic testing offers a valuable opportunity to correctly diagnose individuals with monogenic forms of osteoporosis, thus instituting …

Kcnk1 Promotes Proliferation And Metastasis Of Breast Cancer Cells By Activating Lactate Dehydrogenase A (Ldha) And Up-Regulating H3k18 Lactylation, Xiangchan Hou, Jiawei Ouyang, Le Tang, Pan Wu, Xiangying Deng, Qijia Yan, Lei Shi, Songqing Fan, Chunmei Fan, Can Guo, Qianjin Liao, Yong Li, Wei Xiong, Guiyuan Li, Zhaoyang Zeng, Fuyan Wang

Faculty, Staff and Students Publications

Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in …

Hyperkinetic Movement Disorder Caused By The Recurrent C892c>T Nacc1 Variant, Jonna Komulainen-Ebrahim, Salla M Kangas, Estrella López-Martín, Timothy Feyma, Fernando Scaglia, Beatriz Martínez-Delgado, Outi Kuismin, Maria Suo-Palosaari, Lucinda Carr, Reetta Hinttala, Manju A Kurian, Johanna Uusimaa

Faculty, Staff and Students Publications

BACKGROUND: Genetic syndromes of hyperkinetic movement disorders associated with epileptic encephalopathy and intellectual disability are becoming increasingly recognized. Recently, a de novo heterozygous NACC1 (nucleus accumbens-associated 1) missense variant was described in a patient cohort including one patient with a combined mitochondrial oxidative phosphorylation (OXPHOS) deficiency.

OBJECTIVES: The objective is to characterize the movement disorder in affected patients with the recurrent c.892C>T NACC1 variant and study the NACC1 protein and mitochondrial function at the cellular level.

METHODS: The movement disorder was analyzed on four patients with the NACC1 c.892C>T (p.Arg298Trp) variant. Studies on NACC1 protein and mitochondrial function …

Intravascular Imaging-Guided Versus Coronary Angiography-Guided Complex Pci: A Meta-Analysis Of Randomized Controlled Trials, Mohamed Hamed, Sheref Mohamed, Mohamed Mahmoud, Jonathan Kahan, Amr Mohsen, Faisal Rahman, Waleed Kayani, Fernando Alfonso, Emmanuel S Brilakis, Islam Y Elgendy, Mamas A Mamas, Ayman Elbadawi

Faculty, Staff and Students Publications

INTRODUCTION: Trials evaluating the role of intravascular imaging in percutaneous coronary intervention (PCI) for complex coronary artery disease have yielded mixed results. This study aimed to compare the outcomes of intravascular imaging specifically intravascular ultrasound (IVUS) with those from conventional coronary angiography in complex PCI.

METHODS: Comprehensive electronic search of MEDLINE, EMBASE, and Cochrane databases was performed until March 2023 for randomized clinical trials (RCTs) comparing intravascular imaging with coronary angiography in patients undergoing complex PCI. Complex PCI was defined per each study, and included PCI for American College of Cardiology/American Heart Association (ACC/AHA) type B2/C lesions, unprotected left main …

Myocardial Infarction Suppresses Protein Synthesis And Causes Decoupling Of Transcription And Translation, Shijie Liu, Vaibhav Deshmukh, Fangfei Wang, Jie Liang, Jenna Cusick, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Gene expression involves transcription, translation, and mRNA and protein degradation. Advanced RNA sequencing measures mRNA levels for cell state assessment, but mRNA level does not fully reflect protein level. Identifying heart cell proteomes and their stress response is crucial. Using a cardiomyocyte-specific mouse model, we tracked protein synthesis after myocardial infarction. Our results showed that myocardial infarction suppresses protein synthesis and unveils a decoupling of translation and transcription regulation in cardiomyocytes.

Challenges And Implications For Substance Use And Mental Healthcare Among Under-Resourced Women In The Covid-19 Era, Maria C Mejia, Alicia Kowalchuk, Sandra J Gonzalez, Muktha Nair, Lisa Webb, Nadine Scamp

Faculty, Staff and Students Publications

BACKGROUND: The COVID-19 pandemic exacerbated disparities in mental healthcare and substance use disorder (SUD) treatment access, especially in under-resourced communities. This study aimed to comprehend the experiences of under-resourced women with SUD during the pandemic, their knowledge and attitudes toward it, and its impact on substance use and treatment access.

METHODS: A cross-sectional study included 66 under-resourced women receiving medically managed withdrawal treatment at a community residential SUD center. Data collection occurred between November 2021 and August 2022, utilizing a 75-item instrument covering COVID-19 exposure and its impact on health, substance use, treatment access, vaccination status, beliefs, and knowledge. Descriptive …

Nk Cells As Powerful Therapeutic Tool In Cancer Immunotherapy, Mao Huang, Yixuan Liu, Qijia Yan, Miao Peng, Junshang Ge, Yongzhen Mo, Yumin Wang, Fuyan Wang, Zhaoyang Zeng, Yong Li, Chunmei Fan, Wei Xiong

Faculty, Staff and Students Publications

Background: Natural killer (NK) cells have gained considerable attention and hold great potential for their application in tumor immunotherapy. This is mainly due to their MHC-unrestricted and pan-specific recognition capabilities, as well as their ability to rapidly respond to and eliminate target cells. To artificially generate therapeutic NK cells, various materials can be utilized, such as peripheral blood mononuclear cells (PBMCs), umbilical cord blood (UCB), induced pluripotent stem cells (iPSCs), and NK cell lines. Exploiting the therapeutic potential of NK cells to treat tumors through in vivo and in vitro therapeutic modalities has yielded positive therapeutic results.

Conclusion: This review …

The Kat Module Of The Saga Complex Maintains The Oncogenic Gene Expression Program In Mycn- Amplified Neuroblastoma, Clare F Malone, Nathaniel W Mabe, Alexandra B Forman, Gabriela Alexe, Kathleen L Engel, Ying-Jiun C Chen, Melinda Soeung, Silvi Salhotra, Allen Basanthakumar, Bin Liu, Sharon Y R Dent, Kimberly Stegmaier

Faculty, Staff and Student Publications

Pediatric cancers are frequently driven by genomic alterations that result in aberrant transcription factor activity. Here, we used functional genomic screens to identify multiple genes within the transcriptional coactivator Spt-Ada-Gcn5-acetyltransferase (SAGA) complex as selective dependencies for MYCN-amplified neuroblastoma, a disease of dysregulated development driven by an aberrant oncogenic transcriptional program. We characterized the DNA recruitment sites of the SAGA complex in neuroblastoma and the consequences of loss of SAGA complex lysine acetyltransferase (KAT) activity on histone acetylation and gene expression. We demonstrate that loss of SAGA complex KAT activity is associated with reduced MYCN binding on chromatin, suppression of …

Presynaptic Nanoscale Components Of Retrograde Synaptic Signaling, Benjámin Barti, Barna Dudok, Kata Kenesei, Miklós Zöldi, Vivien Miczán, Gyula Y Balla, Diana Zala, Mariana Tasso, Claudia Sagheddu, Máté Kisfali, Blanka Tóth, Marco Ledri, E Sylvester Vizi, Miriam Melis, László Barna, Zsolt Lenkei, Iván Soltész, István Katona

Faculty, Staff and Students Publications

While our understanding of the nanoscale architecture of anterograde synaptic transmission is rapidly expanding, the qualitative and quantitative molecular principles underlying distinct mechanisms of retrograde synaptic communication remain elusive. We show that a particular form of tonic cannabinoid signaling is essential for setting target cell–dependent synaptic variability. It does not require the activity of the two major endocannabinoid-producing enzymes. Instead, by developing a workflow for physiological, anatomical, and molecular measurements at the same unitary synapse, we demonstrate that the nanoscale stoichiometric ratio of type 1 cannabinoid receptors (CB1Rs) to the release machinery is sufficient to predict synapse-specific release probability. Accordingly, …

Multifactoral Immune Modulation Potentiates Durable Remission In Multiple Models Of Aggressive Malignancy, Matthew M Halpert, Briana A Burns, Spencer R Rosario, Henry G Withers, Akshar J Trivedi, Colby J Hofferek, Benjamin D Gephart, Haotong Wang, Jonathan Vazquez-Perez, Sharon B Amanya, Sean T Hyslop, Jianhua Yang, Jan O Kemnade, Vlad C Sandulache, Vanaja Konduri, William K Decker

Faculty, Staff and Students Publications

Tumors typically lack canonical danger signals required to activate adaptive immunity and also frequently employ substantial immunomodulatory mechanisms that downregulate adaptive responses and contribute to escape from immune surveillance. Given the variety of mechanisms involved in shielding tumors from immune recognition, it is not surprising that single-agent immunomodulatory approaches have been largely unsuccessful in generating durable antitumor responses. Here we report a unique combination of immunomodulatory and cytostatic agents that recondition the tumor microenvironment and eliminate complex and/or poor-prognosis tumor types including the non-immunogenic 4T-1 model of TNBC, the aggressive MOC-2 model of HNSCC, and the high-risk MYCN-amplified model of …

A Review Of Image Sensors Used In Near-Infrared And Shortwave Infrared Fluorescence Imaging, Banghe Zhu, Henry Jonathan

The Brown Foundation: Institute of Molecular Medicine

To translate near-infrared (NIR) and shortwave infrared (SWIR) fluorescence imaging into the clinic, the paired imaging device needs to detect trace doses of fluorescent imaging agents. Except for the filtration scheme and excitation light source, the image sensor used will finally determine the detection limitations of NIR and SWIR fluorescence imaging systems. In this review, we investigate the current state-of-the-art image sensors used in NIR and SWIR fluorescence imaging systems and discuss the advantages and limitations of their characteristics, such as readout architecture and noise factors. Finally, the imaging performance of these image sensors is evaluated and compared.

Risk Factors For Pediatric Ischemic Stroke And Intracranial Hemorrhage: A National Electronic Health Record Based Study, Stuart Fraser, Samantha M Levy, Amee Moreno, Gen Zhu, Sean Savitz, Alicia Zha, Hulin Wu

Faculty, Staff and Student Publications

BACKGROUND: Stroke is an important cause of morbidity in pediatrics. Large studies are needed to better understand the epidemiology, pathogenesis and risk factors associated with pediatric stroke. Large administrative datasets can provide information on risk factors in perinatal and childhood stroke at low cost. The aim of this hypothesis-generating study was to use a large administrative dataset to assess for prevalence and odds-ratios of rare exposures associated with pediatric stroke.

METHODS: The data for patients aged 0-18 with a diagnosis of either ischemic stroke or intracranial hemorrhage were extracted from the Cerner Health Facts EMR Database from 2000 to 2018. …

Neurorehabilitation With Vagus Nerve Stimulation: A Systematic Review, Radha Korupolu, Alyssa Miller, Andrew Park, Nuray Yozbatiran

Faculty, Staff and Student Publications

OBJECTIVE: To systematically review vagus nerve stimulation (VNS) studies to present data on the safety and efficacy on motor recovery following stroke, traumatic brain injury (TBI), and spinal cord injury (SCI).

METHODS: Data sources: PubMed, EMBASE, SCOPUS, and Cochrane.

STUDY SELECTION: Clinical trials of VNS in animal models and humans with TBI and SCI were included to evaluate the effects of pairing VNS with rehabilitation therapy on motor recovery.

DATA EXTRACTION: Two reviewers independently assessed articles according to the evaluation criteria and extracted relevant data electronically.

DATA SYNTHESIS: Twenty-nine studies were included; 11 were animal models of stroke, TBI, and …