Digital Commons Network^™

Co-Targeting Bcl-Xl And Bcl-2 By Protac 753b Eliminates Leukemia Cells And Enhances Efficacy Of Chemotherapy By Targeting Senescent Cells, Yannan Jia, Lina Han, Cassandra L Ramage, Zhe Wang, Connie C Weng, Lei Yang, Simona Colla, Helen Ma, Weiguo Zhang, Michael Andreeff, Naval Daver, Nitin Jain, Naveen Pemmaraju, Kapil Bhalla, Satu Mustjoki, Peiyi Zhang, Guangrong Zheng, Daohong Zhou, Qi Zhang, Marina Konopleva

Faculty, Staff and Student Publications

BCL-XL and BCL-2 are key anti-apoptotic proteins and validated cancer targets. 753B is a novel BCL-XL/BCL-2 proteolysis targeting chimera (PROTAC) that targets both BCL-XL and BCL-2 to the von Hippel-Lindau (VHL) E3 ligase, leading to BCLX L/BCL-2 ubiquitination and degradation selectively in cells expressing VHL. Because platelets lack VHL expression, 753B spares on-target platelet toxicity caused by the first-generation dual BCL-XL/BCL-2 inhibitor navitoclax (ABT-263). Here, we report pre-clinical single-agent activity of 753B against different leukemia subsets. 753B effectively reduced cell viability and induced dose-dependent degradation of BCL-XL and BCL-2 in a subset of hematopoietic cell lines, acute myeloid leukemia (AML) …

Rational Design For The Recombinant Expression Of The Receptor Binding Domain Of Sars-Cov-2 Spike Glycoprotein, Luis Mario Rodriguez, Mario Alberto Rodriguez, Hugo A. Barrera-Saldaña, Rocio Marisol Martinez, Daniela Rodriguez

Research Symposium

Background: COVID-19 represents a significant threat to global human health. SARS-CoV-2, the etiologic viral agent, needs to be under-covered at the structural biology level to facilitate the rational design of diagnostic tests and vaccine candidates. SARS-CoV-2 Receptor Binding Domain of Spike protein (RBD-S) acts as the key to open the gate, to enter the cells during infection. Thus, it is a stronger candidate for designing effective antigens for vaccines and diagnostics. Here, we relied on the viral DNA codifying to RBD-S to use synthetic biology for optimizing the recombinant expression of this (rRBD-S) as a proof of concept of rational …

Icvd Polymer Thin Film Bio-Interface-Performance For Fibroblasts, Cancer-Cells, And Viruses Connected To Their Functional Groups And In Silico Studies, Torge Hartig, Asmaa T. Mohamed, Nasra F. Abdel Fattah, Aydin Gülses, Tim Tjardts, Esther Afiba Kangah, Kwing Pak Gabriel Chan, Salih Salih Veziroglu, Yahya Acil, Oral Cenk Aktas, Jörg Jörg Wiltfang, Samah A. Loutfy, Thomas Strunskus, Franz Faupel, Amal Amin, Stefan Schröder

Nanotechnology Research Centre

Thin polymer coatings are used to improve the interface between biological species and functional materials. Their interaction is significantly influenced by the functional groups and roughness of the polymer film and prediction of the interaction is thus of great interest. However, for conventional polymer films, this cannot be examined independently because of the interplay of defects, residual solvent molecules, roughness, and functional groups. Solvent-free polymer films prepared by initiated chemical vapor deposition (iCVD) exhibit conformal, defect-free characteristics and enable precise tailoring of the functional groups. This facilitates to isolate the contribution of functional groups on the bio-interface performance. Consequently, in …

Evolutionary Action-Machine Learning Model Identifies Candidate Genes Associated With Early-Onset Coronary Artery Disease, Dillon Shapiro, Kwanghyuk Lee, Jennifer Asmussen, Thomas Bourquard, Olivier Lichtarge

Faculty, Staff and Students Publications

Background Coronary artery disease is a primary cause of death around the world, with both genetic and environmental risk factors. Although genome-wide association studies have linked >100 unique loci to its genetic basis, these only explain a fraction of disease heritability. Methods and Results To find additional gene drivers of coronary artery disease, we applied machine learning to quantitative evolutionary information on the impact of coding variants in whole exomes from the Myocardial Infarction Genetics Consortium. Using ensemble-based supervised learning, the Evolutionary Action-Machine Learning framework ranked each gene's ability to classify case and control samples and identified 79 significant associations. …

Inhibition Of The Interaction Between Hippo/Yap And Akt Signaling With Ursolic Acid And 3’3-Diindolylmethane Suppresses Esophageal Cancer Tumorigenesis, Ruo Yu Meng, Cong Shan Li, Dan Hu, Soon-Gu Kwon, Hua Jin, Ok Hee Chai, Ju-Seog Lee, Soo Mi Kim

Faculty, Staff and Student Publications

Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3'3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of …

Paradoxes Of Cellular Sumoylation Regulation: A Role Of Biomolecular Condensates?, Xiaodong Cheng, Wenli Yang, Wei Lin, Fang Mei

Faculty, Staff and Student Publications

Protein SUMOylation is a major post-translational modification essential for maintaining cellular homeostasis. SUMOylation has long been associated with stress responses as a diverse array of cellular stress signals are known to trigger rapid alternations in global protein SUMOylation. In addition, while there are large families of ubiquitination enzymes, all small ubiquitin-like modifiers (SUMOs) are conjugated by a set of enzymatic machinery comprising one heterodimeric SUMO-activating enzyme, a single SUMO-conjugating enzyme, and a small number of SUMO protein ligases and SUMO-specific proteases. How a few SUMOylation enzymes specifically modify thousands of functional targets in response to diverse cellular stresses remains an …

Kdm5b As A Potential Epigenetic Regulator Of Cardiomyocyte Regeneration And Cell Cycle Activation., Dana Hammouri

Electronic Theses and Dissertations

The limited regenerative capacity of adult cardiomyocytes (CMs) is manifested in prevalent morbidity and mortality associated with ischemic heart disease. We previously demonstrated that a combination of four cell cycle factors (4F) promotes efficient cell division in differentiated CMs. The temporal transcriptional reprogramming in the 4F-transduced CMs indicates that epigenetic modifications mediate the cell cycle progression. Through small molecule screening, we evaluated the epigenetic impact on CM’s response in the 4F-transduced CMs. We identified the histone demethylase 5B (KDM5B), which through in vitro and ex vivo genetic knockdown and overexpression studies, exhibited a modulative effect on CM’s cell cycle plasticity …

Polymorphisms In The Nonhomologous End-Joining Dna Repair Pathway Are Associated With Hpv Integration In Cervical Dysplasia, Jennifer M Geris, E Susan Amirian, Deborah A Marquez-Do, Martial Guillaud, Laura M Dillon, Michele Follen, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

Previous evidence indicates that HPV integration status may be associated with cervical cancer development and progression. However, host genetic variation within genes that may play important roles in the viral integration process is understudied. The aim of this study was to examine the association between HPV16 and HPV18 viral integration status and single nucleotide polymorphisms (SNPs) in non-homologous end-joining (NHEJ) DNA repair pathway genes on cervical dysplasia. Women enrolled in two large trials of optical technologies for cervical cancer detection and positive for HPV16 or HPV18 were selected for HPV integration analysis and genotyping. Associations between SNPs and cytology (normal, …

Pediatric Phase 2 Trial Of A Wee1 Inhibitor, Adavosertib (Azd1775), And Irinotecan For Relapsed Neuroblastoma, Medulloblastoma, And Rhabdomyosarcoma, Kristina A Cole, Heba Ijaz, Lea F Surrey, Mariarita Santi, Xiaowei Liu, Charles G Minard, John M Maris, Stephan Voss, Joel M Reid, Elizabeth Fox, Brenda J Weigel

Faculty, Staff and Students Publications

BACKGROUND: Inhibition of the WEE1 kinase by adavosertib (AZD1775) potentiates replicative stress from genomic instability or chemotherapy. This study reports the pediatric solid tumor phase 2 results of the ADVL1312 trial combining irinotecan and adavosertib.

METHODS: Pediatric patients with recurrent neuroblastoma (part B), medulloblastoma/central nervous system embryonal tumors (part C), or rhabdomyosarcoma (part D) were treated with irinotecan and adavosertib orally for 5 days every 21 days. The combination was considered effective if there were at least three of 20 responses in parts B and D or six of 19 responses in part C. Tumor tissue was analyzed for alternative …

When A Calorie Is Not Just A Calorie: Diet Quality And Timing As Mediators Of Metabolism And Healthy Aging, Maria M Mihaylova, Amandine Chaix, Mirela Delibegovic, Jon J Ramsey, Joseph Bass, Girish Melkani, Rajat Singh, Zheng Chen, William W Ja, Michele Shirasu-Hiza, Mary N Latimer, Julie A Mattison, Anna E Thalacker-Mercer, Vishwa Deep Dixit, Satchidananda Panda, Dudley W Lamming

Faculty, Staff and Student Publications

An epidemic of obesity has affected large portions of the world, increasing the risk of developing many different age-associated diseases, including cancer, cardiovascular disease, and diabetes. In contrast with the prevailing notion that "a calorie is just a calorie," there are clear differences, within and between individuals, in the metabolic response to different macronutrient sources. Recent findings challenge this oversimplification; calories from different macronutrient sources or consumed at different times of day have metabolic effects beyond their value as fuel. Here, we summarize discussions conducted at a recent NIH workshop that brought together experts in calorie restriction, macronutrient composition, and …

Targeting Gbm With An Oncolytic Picornavirus Svv-001 Alone And In Combination With Fractionated Radiation In A Novel Panel Of Orthotopic Pdx Models, Huiyuan Zhang, Yuchen Du, Lin Qi, Sophie Xiao, Frank K Braun, Mari Kogiso, Yulun Huang, Frank Huang, Aalaa Abdallah, Milagros Suarez, Sekar Karthick, Nabil M Ahmed, Vita S Salsman, Patricia A Baxter, Jack M Su, Daniel J Brat, Paul L Hellenbeck, Wan-Yee Teo, Akash J Patel, Xiao-Nan Li

Faculty, Staff and Students Publications

BACKGROUND: Animal models representing different molecular subtypes of glioblastoma multiforme (GBM) is desired for developing new therapies. SVV-001 is an oncolytic virus selectively targeting cancer cells. It's capacity of passing through the blood brain barrier makes is an attractive novel approach for GBM.

MATERIALS AND METHODS: 23 patient tumor samples were implanted into the brains of NOD/SCID mice (1 × 105 cells/mouse). Tumor histology, gene expression (RNAseq), and growth rate of the developed patient-derived orthotopic xenograft (PDOX) models were compared with the originating patient tumors during serial subtransplantations. Anti-tumor activities of SVV-001 were examined in vivo; and therapeutic efficacy validated …

Assessment Of Antimicrobial Competence Of Epiphytes And Endophytes From Osmium Basilicum And Trigonella Foenum Graecum, Iram Asim, Atia Iqbal, Muhammad Ikrama Tanveer

Journal of Bioresource Management

Plant-associated bacteria are an unexplored group of microorganisms that has enormous potential. These bacteria are the source of finding new antimicrobial substances. The present study aimed to isolate and characterize the epiphytes and endophytes from Osmium basilicum and Trigonella foenum graecum plants and to determine their antimicrobial potential against pathogenic bacteria from Nishtar Hospital Multan, Pakistan. The sum of 18 stems and roots along leaf specimens were assembled as of the plant's Osmium basilicum plus Trigonella foenum graecum as of the distinct locales of the Multan city. Overall 73 bacterial strains were isolated and their colony morphology, gram staining, spore …

The Prevalence Of Electronic Cigarette Use Among College Students Of Taibah University And Symptoms Of Cardiovascular Disease, Talal Alzahrani, Marwan Fahad Alhazmi, Ahmed Naji Alharbi, Feras Talal Alahmadi, Amer Nasser Alhubayshi, Bader Ahmed Alzahrani

Journal of the Saudi Heart Association

Background: Electronic cigarettes (e-cigarettes) have been increasing in popularity among young adults due to the misconception about the safety of e-cigarettes. Our study aims to identify the prevalence rate of e-cigarette use among college students, the reason behind their use, and the relationship between the use of electronic cigarettes and cardiovascular symptoms among college students. Methods: An online questionnaire was sent to students of Taibah University between 2021 and 2022. Data from this survey were analyzed to obtain the prevalence of e-cigarette use among Taibah University students and to compare the demographic and health characteristics differences between e-cigarette users and …

Targeting Energy Intake And Circadian Biology To Engage Mechanisms Of Aging In Older Adults With Obesity: Calorie Restriction And Time-Restricted Eating, Satchidananda Panda, Geraldine Maier, Dennis T Villareal

Faculty, Staff and Students Publications

With the rise in obesity across age groups, it has been a hindrance to engaging in physical activity and mobility in older adults. Daily calorie restriction (CR) up to 25% has been the cornerstone of obesity management even though the safety in older adults remains incompletely understood. Although some adults can follow CR with clinically significant weight loss and improved health metrics, CR faces 2 obstacles-many fail to adopt CR and even among those who can adopt it short term, long-term compliance can be difficult. Furthermore, there is a continuing debate about the net benefits of CR-induced weight loss in …

Workers With Suspected Diagnosis Of Silicosis: A Case Study Of Sarcoidosis Versus Siderosis, Diemen Delgado-García, Patricio Miranda-Astorga, Ashley Delgado-Cano, Juan Gómez-Salgado, Carlos Ruiz-Frutos

School of Medicine Publications

Silicosis is one of the most important occupational respiratory diseases worldwide, hence the importance of making a correct diagnosis. Diagnosis is commonly based on radiological findings according to the ILO International Classification of Radiographs of Pneumoconioses and occupational exposure. High-resolution computed tomography is indicated for differential diagnosis. This article presents two cases with an initial diagnosis of silicosis that ended up being diagnosed as sarcoidosis and siderosis, respectively. The first case was a 42-year-old male who worked as a crushing operator in an underground copper and molybdenum mine for 22 years. He had a history of exposure to silicon dioxide …

A Guide To The Brain Initiative Cell Census Network Data Ecosystem, Michael Hawrylycz, Maryann E Martone, Giorgio A Ascoli, Jan G Bjaalie, Hong-Wei Dong, Satrajit S Ghosh, Jesse Gillis, Ronna Hertzano, David R Haynor, Patrick R Hof, Yongsoo Kim, Ed Lein, Yufeng Liu, Jeremy A Miller, Partha P Mitra, Eran Mukamel, Lydia Ng, David Osumi-Sutherland, Hanchuan Peng, Patrick L Ray, Raymond Sanchez, Aviv Regev, Alex Ropelewski, Richard H Scheuermann, Shawn Zheng Kai Tan, Carol L Thompson, Timothy Tickle, Hagen Tilgner, Merina Varghese, Brock Wester, Owen White, Hongkui Zeng, Brian Aevermann, David Allemang, Seth Ament, Thomas L Athey, Cody Baker, Katherine S Baker, Pamela M Baker, Anita Bandrowski, Samik Banerjee, Prajal Bishwakarma, Ambrose Carr, Min Chen, Roni Choudhury, Jonah Cool, Heather Creasy, Florence D'Orazi, Kylee Degatano, Benjamin Dichter, Song-Lin Ding, Tim Dolbeare, Joseph R Ecker, Rongxin Fang, Jean-Christophe Fillion-Robin, Timothy P Fliss, James Gee, Tom Gillespie, Nathan Gouwens, Guo-Qiang Zhang, Yaroslav O Halchenko, Nomi L Harris, Brian R Herb, Houri Hintiryan, Gregory Hood, Sam Horvath, Bingxing Huo, Dorota Jarecka, Shengdian Jiang, Farzaneh Khajouei, Elizabeth A Kiernan, Huseyin Kir, Lauren Kruse, Changkyu Lee, Boudewijn Lelieveldt, Yang Li, Hanqing Liu, Lijuan Liu, Anup Markuhar, James Mathews, Kaylee L Mathews, Chris Mezias, Michael I Miller, Tyler Mollenkopf, Shoaib Mufti, Christopher J Mungall, Joshua Orvis, Maja A Puchades, Lei Qu, Joseph P Receveur, Bing Ren, Nathan Sjoquist, Brian Staats, Daniel Tward, Cindy T J Van Velthoven, Quanxin Wang, Fangming Xie, Hua Xu, Zizhen Yao, Zhixi Yun, Yun Renee Zhang, W Jim Zheng, Brian Zingg

Faculty, Staff and Student Publications

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization. Emphasis of the BICCN is on the whole mouse brain with demonstration of prototype feasibility for human and nonhuman …

Migratory Material: Epigenetics & Weaving At The Us-Mexico Border, Valerie Navarrete

Masters Theses

Discourse often sutures the body shut, disallowing representations of identity to outgrow sociopolitical interests. This issue may originate from borders, but also from the unnamable pathology that generational colonial trauma transmits to the mind, body, and environment. Without a direct form of translatability, this thesis proposes a new materialism that deviates from any object-oriented ontology. Untethered and intra-active, epigenetics and weaving represent objects that transform typical ways of knowing and seeing. Their sensitivity to the environment, in addition to their mobility across generations of time, broaden the spatiotemporal loci of the body and its embodiment. Proposing new materials that expand …

Mapping The Functional Interactions At The Tumor-Immune Checkpoint Interface, Behnaz Bozorgui, Elisabeth K Kong, Augustin Luna, Anil Korkut

Faculty, Staff and Student Publications

The interactions between tumor intrinsic processes and immune checkpoints can mediate immune evasion by cancer cells and responses to immunotherapy. It is, however, challenging to identify functional interactions due to the prohibitively complex molecular landscape of the tumor-immune interfaces. We address this challenge with a statistical analysis framework, immuno-oncology gene interaction maps (ImogiMap). ImogiMap quantifies and statistically validates tumor-immune checkpoint interactions based on their co-associations with immune-associated phenotypes. The outcome is a catalog of tumor-immune checkpoint interaction maps for diverse immune-associated phenotypes. Applications of ImogiMap recapitulate the interaction of SERPINB9 and immune checkpoints with interferon gamma (IFNγ) expression. Our analyses …

Advances In Mass Spectrometry On Membrane Proteins, Hsin-Chieh Yang, Weikai Li, Jie Sun, Michael L Gross

2020-Current year OA Pubs

Understanding the higher-order structure of membrane proteins (MPs), which are vital for numerous biological processes, is crucial for comprehending their function. Although several biophysical approaches have been used to study the structure of MPs, limitations exist owing to the proteins' dynamic nature and heterogeneity. Mass spectrometry (MS) is emerging as a powerful tool for investigating membrane protein structure and dynamics. Studying MPs using MS, however, must meet several challenges including the lack of stability and solubility of MPs, the complexity of the protein-membrane system, and the difficulty of digestion and detection. To meet these challenges, recent advances in MS have …

Synthetic Errα/Β/Γ Agonist Induces An Errα-Dependent Acute Aerobic Exercise Response And Enhances Exercise Capacity, Cyrielle Billon, Sadichha Sitaula, Subhashis Banerjee, Ryan Welch, Bahaa Elgendy, Lamees Hegazy, Tae Gyu Oh, Melissa Kazantzis, Arindam Chatterjee, John Chrivia, Matthew E Hayes, Weiyi Xu, Angelica Hamilton, Janice M Huss, Lilei Zhang, John K Walker, Michael Downes, Ronald M Evans, Thomas P Burris

Faculty, Staff and Students Publications

Repetitive physical exercise induces physiological adaptations in skeletal muscle that improves exercise performance and is effective for the prevention and treatment of several diseases. Genetic evidence indicates that the orphan nuclear receptors estrogen receptor-related receptors (ERRs) play an important role in skeletal muscle exercise capacity. Three ERR subtypes exist (ERRα, β, and γ), and although ERRβ/γ agonists have been designed, there have been significant difficulties in designing compounds with ERRα agonist activity. Additionally, there are limited synthetic agonists that can be used to target ERRs in vivo. Here, we report the …

Spike-Phase Coupling Patterns Reveal Laminar Identity In Primate Cortex, Zachary W Davis, Nicholas M Dotson, Tom P Franken, Lyle Muller, John H Reynolds

2020-Current year OA Pubs

The cortical column is one of the fundamental computational circuits in the brain. In order to understand the role neurons in different layers of this circuit play in cortical function it is necessary to identify the boundaries that separate the laminar compartments. While histological approaches can reveal ground truth they are not a practical means of identifying cortical layers in vivo. The gold standard for identifying laminar compartments in electrophysiological recordings is current-source density (CSD) analysis. However, laminar CSD analysis requires averaging across reliably evoked responses that target the input layer in cortex, which may be difficult to generate in …

Molecular Mechanisms Of Immune Escape Of Sars-Cov-2 Omicron Variants: A Computational Biology Study, Disha A, Nikhil Pathak, Nirmal Mazumdar

Manipal Research Colloquium - 2023

Manipal Research Colloquium- 2023 aims to bring students, scholars, and scientists to this forum where discussion on a diverse range of topics from various streams (Health Sciences, Technical Sciences, Basic & Applied Sciences, Humanities & Social Sciences, and Management Sciences) will be taking place.

Scar Formation In The Presence Of Mitomycin C And The Anti-Fibrotic Antibody In A Rabbit Model Of Glaucoma Microsurgery: A Pilot Study, Aakriti Garg Shukla, Tatyana Milman, Jolanta Fertala, Andrzej Steplewski, Andrzej Fertala

Wills Eye Hospital Papers

Purpose: This study aimed to evaluate the utility of a rationally engineered antibody that directly blocks collagen fibrillogenesis to reduce scar tissue formation associated with subconjunctival glaucoma surgery.

Material and methods: Fourteen eyes of 7 adult rabbits underwent glaucoma filtering surgery using XEN 45 Gel Stent. The rabbits’ eyes were divided randomly into three treatment groups: (i) treated with the antibody, (ii) treated with mitomycin C, and (iii) treated with the antibody and mitomycin C. Following surgeries, the intraocular pressure and bleb appearance were evaluated in vivo. The rabbits were sacrificed 8 weeks after the surgery, and their eyes were …

Perinucleolar Compartment (Pnc) Prevalence As An Independent Prognostic Factor In Pediatric Ewing Sarcoma: A Multi-Institutional Study., Elizabeth Gonzalez, Atif A. Ahmed, Laura Mccarthy, Katherine Chastain, Sahibu Sultan M Habeebu, Marta Zapata-Tarres, Rocio Cardenas-Cardos, Liliana Velasco-Hidalgo, Celso Corcuera-Delgado, Rodolfo Rodriguez-Jurado, Lilia García-Rodríguez, Alejandro Parrales, Tomoo Iwakuma, Midhat S. Farooqi, Brian R. Lee, Scott J. Weir, Terrie Flatt

Manuscripts, Articles, Book Chapters and Other Papers

The perinucleolar compartment (PNC) is a small nuclear body that plays important role in tumorigenesis. PNC prevalence correlates with poor prognosis and cancer metastasis. Its expression in pediatric Ewing sarcoma (EWS) has not previously been documented. In this study, we analyzed 40 EWS tumor cases from Caucasian and Hispanic patients for PNC prevalence by immunohistochemical detection of polypyrimidine tract binding protein and correlated the prevalence with dysregulated microRNA profiles. EWS cases showed staining ranging from 0 to 100%, which were categorized as diffuse (≥77%, n = 9, high PNC) or not diffuse (p= 0.017) and in patients who relapsed with …

A Distinct Pattern Of Growth And Rac1 Signaling In Melanoma Brain Metastasis Cells, Ioana Stejerean-Todoran, Phyllis A Gimotty, Andrea Watters, Patricia Brafford, Clemens Krepler, Tetiana Godok, Haiyin Li, Zuriñe Bonilla Del Rio, Anke Zieseniss, Dörthe M Katschinski, Sinem M Sertel, Silvio O Rizzoli, Bradley Garman, Katherine L Nathanson, Xiaowei Xu, Qing Chen, Jack H Oswald, Michal Lotem, Gordon B Mills, Michael A Davies, Michael P Schön, Ivan Bogeski, Meenhard Herlyn, Adina Vultur

Faculty, Staff and Student Publications

Background: Melanoma, the deadliest of skin cancers, has a high propensity to form brain metastases that are associated with a markedly worsened prognosis. In spite of recent therapeutic advances, melanoma brain lesions remain a clinical challenge, biomarkers predicting brain dissemination are not clear and differences with other metastatic sites are poorly understood.

Methods: We examined a genetically diverse panel of human-derived melanoma brain metastasis (MBM) and extracranial cell lines using targeted sequencing, a Reverse Phase Protein Array, protein expression analyses, and functional studies in vitro and in vivo.

Results: Brain-specific genetic alterations were not detected; however, MBM cells in vitro …

Molecular Function And Contribution Of Tbx4 In Development And Disease, Justyna A Karolak, Carrie L Welch, Christian Mosimann, Katarzyna Bzdęga, James D West, David Montani, Mélanie Eyries, Mary P Mullen, Steven H Abman, Matina Prapa, Stefan Gräf, Nicholas W Morrell, Anna R Hemnes, Frédéric Perros, Rizwan Hamid, Malcolm P O Logan, Jeffrey Whitsett, Csaba Galambos, Paweł Stankiewicz, Wendy K Chung, Eric D Austin

Faculty, Staff and Students Publications

Over the past decade, recognition of the profound impact of the TBX4 (T-box 4) gene, which encodes a member of the evolutionarily conserved family of T-box–containing transcription factors, on respiratory diseases has emerged. The developmental importance of TBX4 is emphasized by the association of TBX4 variants with congenital disorders involving respiratory and skeletal structures; however, the exact role of TBX4 in human development remains incompletely understood. Here, we discuss the developmental, tissue-specific, and pathological TBX4 functions identified through human and animal studies and review the published TBX4 variants resulting in variable disease phenotypes. We also outline future research …

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 …

A New Era Of Morphological Investigations: Reviewing Methods For Comparative Anatomical Studies, K. L. Ford, J. S. Albert, A. P. Summers, B. P. Hedrick, E. R. Schachner, A. S. Jones, K. Evans, P. Chakrabarty

School of Medicine Faculty Publications

The increased use of imaging technology in biological research has drastically altered morphological studies in recent decades and allowed for the preservation of important collection specimens alongside detailed visualization of bony and soft-tissue structures. Despite the benefits associated with these newer imaging techniques, there remains a need for more "tra- ditional"methods of morphological examination in many comparative studies. In this paper, we describe the costs and benefits of the various methods of visualizing, examining, and comparing morphological structures. There are significant differences not only in the costs associated with these different methods (monetary, time, equipment, and software), but also in …

Magnetized Chitosan Hydrogel And Silk Fibroin, Reinforced With Pva: A Novel Nanobiocomposite For Biomedical And Hyperthermia Applications, Reza Eivazzadeh-Keihan, Zeinab Pajoum, Hooman Aghamirza Moghim Aliabadi, Adibeh Mohammadi, Amir Kashtiaray, Milad Salimi Bani, Banafshe Pishva, Ali Maleki, Majid M Heravi, Mohammad Mahdavi, Elaheh Ziaei Ziabari

Department of Orthopaedic Surgery Faculty Papers

Herein, a multifunctional nanobiocomposite was designed for biological application, amongst which hyperthermia cancer therapy application was specifically investigated. This nanobiocomposite was fabricated based on chitosan hydrogel (CS), silk fibroin (SF), water-soluble polymer polyvinyl alcohol (PVA) and iron oxide magnetic nanoparticles (Fe₃O₄ MNPs). CS and SF as natural compounds were used to improve the biocompatibility, biodegradability, adhesion and cell growth properties of the nanobiocomposite that can prepare this nanocomposite for the other biological applications such as wound healing and tissue engineering. Since the mechanical properties are very important in biological applications, PVA polymer was used to increase the …

The Microbiome And Its Impact On Allogeneic Hematopoietic Cell Transplantation, Florent Malard, Robert R Jenq

Faculty, Staff and Student Publications

Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for a variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk for complications with potentially life-threatening toxicities, including a variety of opportunistic infections as well as acute and chronic manifestations of graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to the patient. With recent advances, including newer conditioning regimens, advances in viral and fungal infection prophylaxis, and novel GVHD prophylactic and treatment strategies, improvements in clinical outcomes have steadily improved. One modality with great potential that has yet to …