Digital Commons Network^™

Bi-Allelic Kics2 Mutations Impair Kicstor Complex-Mediated Mtorc1 Regulation, Causing Intellectual Disability And Epilepsy, Rebecca Buchert, Martin D Burkhalter, Chrisovalantou Huridou, Linda Sofan, Timo Roser, Kirsten Cremer, Javeria Raza Alvi, Stephanie Efthymiou, Tawfiq Froukh, Sughra Gulieva, Ulviyya Guliyeva, Moath Hamdallah, Muriel Holder-Espinasse, Rauan Kaiyrzhanov, Doreen Klingler, Mahmoud Koko, Lars Matthies, Joohyun Park, Marc Sturm, Ana Velic, Stephanie Spranger, Tipu Sultan, Hartmut Engels, Holger Lerche, Henry Houlden, Alistair T Pagnamenta, Ingo Borggraefe, Yvonne Weber, Penelope E Bonnen, Reza Maroofian, Olaf Riess, Jonasz J Weber, Melanie Philipp, Tobias B Haack

Faculty, Staff and Students Publications

Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy. These variants partly affected KICS2 stability, compromised KICSTOR complex formation, and demonstrated a deleterious impact on nutrient-dependent mTORC1 regulation of 4EBP1 and S6K. Phosphoproteome analyses extended these findings to show that KICS2 variants changed the mTORC1 proteome, affecting proteins that function in translation, splicing, and …

“Burned Through”: Performing Social Justice In The Academy, Matthew P. Bejar, Saemi Lee, Terilyn C. Shigeno, Leslie K. Larsen

Faculty Research, Scholarly, and Creative Activity

In this chapter, we discuss and interrogate our experiences of infusing social justice into our research, teaching, and service amidst sexism, racism, and other intersectional forms of oppression that are prevalent within the academy and how this tension has tended to elicit performative social justice. First, we situate this chapter by summarizing our individual journeys with social justice in sport and exercise psychology (SEP). Second, we describe our collective journey as former graduate students and early career professionals. Third, we discuss the challenges that we encountered with respect to our social justice work. Fourth, we share the ways that we …

Bio-Primed Machine Learning To Enhance Discovery Of Relevant Biomarkers, David M Henke, Alexander Renwick, Joseph R Zoeller, Jitendra K Meena, Nicholas J Neill, Elizabeth A Bowling, Kristen L Meerbrey, Thomas F Westbrook, Lukas M Simon

Faculty, Staff and Students Publications

Precision medicine relies on identifying reliable biomarkers for gene dependencies to tailor individualized therapeutic strategies. The advent of high-throughput technologies presents unprecedented opportunities to explore molecular disease mechanisms but also challenges due to high dimensionality and collinearity among features. Traditional statistical methods often fall short in this context, necessitating novel computational approaches that harness the full potential of big data in bioinformatics. Here, we introduce a novel machine learning approach extending the Least Absolute Shrinkage and Selection Operator (LASSO) regression framework to incorporate biological knowledge, such as protein-protein interaction databases, into the regularization process. This bio-primed approach prioritizes variables that …

Starting Vegetable Seeds Indoors: I. Planning, Wesley Crump, Taun Beddes, Michael Caron, Milena Oliveira

All Current Publications

For many Utah gardeners, starting vegetable seeds indoors offers both an exciting opportunity to experiment with new varieties and a practical necessity for ensuring the successful growth and production of certain crops in their unique environmental conditions. Vegetable gardening involves inherent risks, particularly for the plants, with weather being a significant and largely uncontrollable factor. Because of this, many gardeners are unsure about when to start certain crops and whether the crops should be started indoors or sown directly in the garden. This fact sheet, the first in a series of four, discusses planning considerations when starting seeds indoors.

Characterizing Features Affecting Local Ancestry Inference Performance In Admixed Populations, Jessica Honorato-Mauer, Nirav N Shah, Adam X Maihofer, Clement C Zai, Sintia Belangero, Caroline M Nievergelt, Marcos Santoro, Elizabeth G Atkinson

Faculty, Staff and Students Publications

In recent years, significant efforts have been made to improve methods for genomic studies of admixed populations using local ancestry inference (LAI). Accurate LAI is crucial to ensure that downstream analyses accurately reflect the genetic ancestry of research participants. Here, we test analytic strategies for LAI to provide guidelines for optimal accuracy, focusing on admixed populations reflective of Latin America's primary continental ancestries-African (AFR), Amerindigenous (AMR), and European (EUR). Simulating linkage-disequilibrium-informed admixed haplotypes under a variety of 2- and 3-way admixture models, we implemented a standard LAI pipeline, testing the impact of reference panel composition, DNA data type, demography, and …

Dna-Binding Affinity And Specificity Determine The Phenotypic Diversity In Bcl11b-Related Disorders, Ivana Lessel, Anja Baresic, Ivan K Chinn, Jonathan May, Anu Goenka, Kate E Chandler, Jennifer E Posey, Alexandra Afenjar, Luisa Averdunk, Maria Francesca Bedeschi, Thomas Besnard, Rae Brager, Lauren Brick, Melanie Brugger, Theresa Brunet, Susan Byrne, Oscar De La Calle-Martín, Valeria Capra, Paul Cardenas, Céline Chappé, Hey J Chong, Benjamin Cogne, Erin Conboy, Heidi Cope, Thomas Courtin, Wallid Deb, Robertino Dilena, Christèle Dubourg, Magdeldin Elgizouli, Erica Fernandes, Kristi K Fitzgerald, Silvana Gangi, Jaya K George-Abraham, Muge Gucsavas-Calikoglu, Tobias B Haack, Medard Hadonou, Britta Hanker, Irina Hüning, Maria Iascone, Bertrand Isidor, Irma Järvelä, Jay J Jin, Alexander A L Jorge, Dragana Josifova, Ruta Kalinauskiene, Erik-Jan Kamsteeg, Boris Keren, Elena Kessler, Heike Kölbel, Mariya Kozenko, Christian Kubisch, Alma Kuechler, Suzanne M Leal, Juha Leppälä, Sharon M Luu, Gholson J Lyon, Suneeta Madan-Khetarpal, Margherita Mancardi, Elaine Marchi, Lakshmi Mehta, Beatriz Menendez, Chantal F Morel, Sue Moyer Harasink, Dayna-Lynn Nevay, Vincenzo Nigro, Sylvie Odent, Renske Oegema, John Pappas, Matthew T Pastore, Yezmin Perilla-Young, Konrad Platzer, Nina Powell-Hamilton, Rachel Rabin, Aisha Rekab, Raissa C Rezende, Leema Robert, Ferruccio Romano, Marcello Scala, Karin Poths, Isabelle Schrauwen, Jessica Sebastian, John Short, Richard Sidlow, Jennifer Sullivan, Katalin Szakszon, Queenie K G Tan, Undiagnosed Diseases Network, Matias Wagner, Dagmar Wieczorek, Bo Yuan, Nicole Maeding, Dirk Strunk, Amber Begtrup, Siddharth Banka, James R Lupski, Eva Tolosa, Davor Lessel

Faculty, Staff and Students Publications

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive. To dissect these, we performed genotype-phenotype correlations of 92 affected individuals harboring a pathogenic or likely pathogenic BCL11B variant, followed by immune phenotyping, analysis of chromatin immunoprecipitation DNA-sequencing data, dual-luciferase reporter assays, and molecular modeling. These integrative analyses enabled us to define three clinical subtypes of BCL11B-related disorders. …

Design And Implementation Of An Action Plan For Justice, Equity, Diversity, And Inclusion Within The Clinical Genome Resource, Alice B Popejoy, Deborah I Ritter, Danielle Azzariti, Jonathan S Berg, Joanna E Bulkley, Mildred Cho, Claudia Gonzaga-Jauregui, Teri E Klein, Daphne O Martschenko, Akinyemi Oni-Orisan, Erin M Ramos, Heidi L Rehm, Erin R Riggs, Matthew W Wright, Michael Yudell, Sharon E Plon, Joannella Morales

Faculty, Staff and Students Publications

How might members of a large, multi-institutional research and resource consortium foster justice, equity, diversity, and inclusion as central to its mission, goals, governance, and culture? These four principles, often referred to as JEDI, can be aspirational-but to be operationalized, they must be supported by concrete actions, investments, and a persistent long-term commitment to the principles themselves, which often requires self-reflection and course correction. We present here the iterative design process implemented across the Clinical Genome Resource (ClinGen) that led to the development of an action plan to operationalize JEDI principles across three major domains, with specific deliverables and commitments …

Design And Implementation Of An Action Plan For Justice, Equity, Diversity, And Inclusion Within The Clinical Genome Resource, Alice B Popejoy, Deborah I Ritter, Danielle Azzariti, Jonathan S Berg, Joanna E Bulkley, Mildred Cho, Claudia Gonzaga-Jauregui, Teri E Klein, Daphne O Martschenko, Akinyemi Oni-Orisan, Erin M Ramos, Heidi L Rehm, Erin R Riggs, Matthew W Wright, Michael Yudell, Sharon E Plon, Joannella Morales

Faculty, Staff and Students Publications

How might members of a large, multi-institutional research and resource consortium foster justice, equity, diversity, and inclusion as central to its mission, goals, governance, and culture? These four principles, often referred to as JEDI, can be aspirational-but to be operationalized, they must be supported by concrete actions, investments, and a persistent long-term commitment to the principles themselves, which often requires self-reflection and course correction. We present here the iterative design process implemented across the Clinical Genome Resource (ClinGen) that led to the development of an action plan to operationalize JEDI principles across three major domains, with specific deliverables and commitments …

Retracted: A Review Of Breast Cancer Histological Image Classification: Challenges And Limitations, Israa Faisal Jassam, Abdulrahman Abbas Mukhlif, Ahmed Adil Nafea, Mustafa Adnan Tharthar, Ahmed Isam Khudhair

Iraqi Journal for Computer Science and Mathematics

This paper comprehensively reviews the classification of breast cancer histological images. The paper discusses the research objectives, methodologies used, and conclusions drawn, as well as suggestions for the future. The study is based on the ICIAR 2018 database, which is considered one of the largest databases available to support this research. The paper also addresses major challenges such as lack of data, variation in tissue preparation, class imbalance, and computational requirements. Advanced techniques such as deep learning (DL), transfer learning and data augmentation are explored, along with innovative models such as convolutional neural networks (CNNs) and generative adversarial networks (GANs). …

Antidiabetic Properties Of Prickly Pear (Opuntia Ficus-Indica) Fruit Extract, Kenzy Aidan Joseph Mckay

The Undergraduate Research Journal

Diabetes mellitus is a metabolic disorder that claims 1.5 million lives annually. Opuntia ficus-indica, commonly known as the prickly pear, has been commonly used in traditional folk medicine for its hypoglycemic properties. It has been claimed that it has antimicrobial and antioxidant properties as well. The plant is native to Mexico and is commonly found in the middle east and India and folk medicine from all of these areas have been using prickly pear medicinally for years. To test these claims an extract of locally sourced Opuntia ficus-indica was prepared using the flesh and seeds of the fruit. The …

Reflections On Using A Strength-Based Culturally Sensitive Community Psychology Approach To Promoting Sexual Health Of Egyptian Women And Girls, Salma Elhabashi, Farida Elrefaie, Zeina M. Shahine

The Undergraduate Research Journal

Navigating the intricate landscape of sexual and reproductive health (SRH) poses considerable challenges, especially within societies where the discourse is shaped by deeply rooted traditions and cultural norms. This paper examines a research project aimed at addressing the critical gap in dialogue surrounding women's SRH in Egypt. Adopting a community psychology framework, this project has two components: a mother-daughter communication guidebook and a comprehensive needs assessment survey. The guidebook was designed to facilitate discussions during the critical transitional phase of puberty, and the needs assessment survey aimed to understand the distinct needs of Egyptian women using a strengths-based approach. By …

Mechanisms Of Inflammation And Regeneration In The Eye, Yiming Zhang

Arts & Sciences Electronic Theses and Dissertations

Fasting and caloric restriction are effective to treat patients with pre-diabetes or metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), but intensive lifestyle changes are difficult for many to implement and sustain. Therefore, by identifying and studying fasting-mediated signals, we hope to elicit and convey the therapeutic effects of fasting against MASLD without actual physiological fasting. We discovered a key pathway in the liver through unbiased transcriptomic screening in fasted mice, a novel glucose fasting-activated effector: the amino acid hydrolase, arginase 2 (ARG2). Our previously published data demonstrates that forced hepatocyte-specific Arg2 overexpression is …

Local Baptist Leader, Jason Ballard, Featured Speaker For Gardner-Webb Greene Lectureship, Office Of University Communications

Gardner-Webb NewsCenter Archive

Jason Ballard, associational mission strategist for the Greater Cleveland County Baptist Association (GCCBA) in Shelby, N.C., is the speaker for the C.O. and Eliza Greene Endowed Lectureship on Tuesday, March 4, at Gardner-Webb University. His topic is “Leading Change in the Local Church.”

Socioeconomic Determinants Of Health And Well-Being In A Low Resource Setting: A Case Of Older Adults Living In A Rural Setting In Northwestern Cambodia, Kakada Kuy

Brown School Graduate Student Theses and Dissertations

This dissertation examines the associations between socioeconomic factors, and physical and psychological well-being among older adults in Cambodia. Focusing on subjective and objective socioeconomic status (SES) and the mediating roles of social and welfare support, this dissertation consists of three interrelated chapters that address different facets of the relationships. Paper 1 (Chapter 2) investigates the demographic characteristics, socioeconomic factors, and social support structures among older Cambodians. Findings reveal significant gender and age disparities, with women and the oldest adults more likely to experience lower socioeconomic status and weaker social support. Paper 2 (Chapter 3) explores the associations between subjective and …

February 5, 2025 Faculty Senate Minutes, University Of South Carolina

Faculty Senate

No abstract provided.

Future Scenarios Of Adoption Sustainable Materials By Construction Firms In The United Arab Emirates, Mona Albeshr

Theses

The construction industry accounts for 39% of greenhouse gas emissions, and change is required, especially with the Net Zero initiative. UAE construction companies must evaluate their current positions and update their strategies to support government regulations. Building futuristic communities is crucial for expanding the built environment within the country; however, the types of materials used should account for two aspects: sustainability and climate resilience, and both must be considered whenever these construction companies formulate their strategic response. Hence, scenario planning significantly provides valuable insights to decision-makers in construction companies’ strategic departments to envision four plausible scenarios of the external environment …

The Lumberjack, February 05, 2025

Cal Poly Humboldt's Student Newspaper

The student newspaper of Humboldt State University.

Comparing In-Person, Standard Telehealth, And Remote Musculoskeletal Examination With A Novel Augmented Reality Exercise Game System: Pilot Cross-Sectional Comparison Study, Richard Wu, Keerthana Chakka, Sara Belko, Ninad Khargonkar, Kevin Desai, Balakrishnan Prabhakaran, Thiru Annaswamy

SKMC Student Presentations and Publications

BACKGROUND: Current telemedicine technologies are not fully optimized for conducting physical examinations. The Virtual Remote Tele-Physical Examination (VIRTEPEX) system, a novel proprietary technology platform using a Microsoft Kinect-based augmented reality game system to track motion and estimate force, has the potential to assist with conducting asynchronous, remote musculoskeletal examinations.

OBJECTIVE: This pilot study evaluated the feasibility of the VIRTEPEX system as a supplement to telehealth musculoskeletal strength assessments.

METHODS: In this cross-sectional pilot study, 12 study participants with upper extremity pain and/or weakness underwent strength evaluations for four upper extremity movements using in-person, telehealth, VIRTEPEX, and composite (telehealth plus VIRTEPEX) …

Advances In Pyrazolo[1,5-A]Pyrimidines: Synthesis And Their Role As Protein Kinase Inhibitors In Cancer Treatment, Terungwa H. Iorkula, Osasere Jude Kelly Osayawe, Daniel A. Odogwu, Latifat Oluwatobi Ganiyu, Emmanuel Faderin, Raymond Femi Awoyemi, Busayo Odunayo Akodu, Ikhazuagbe Hilary Ifijen, Omowunmi Rebecca Aworinde, Peter Agyemang, Odo Lovelyn Onyinyechi

Michigan Tech Publications

Pyrazolo[1,5-a]pyrimidines are a notable class of heterocyclic compounds with potent protein kinase inhibitor (PKI) activity, playing a critical role in targeted cancer therapy. Protein kinases, key regulators in cellular signalling, are frequently disrupted in cancers, making them important targets for small-molecule inhibitors. This review explores recent advances in pyrazolo[1,5-a]pyrimidine synthesis and their application as PKIs, with emphasis on inhibiting kinases such as CK2, EGFR, B-Raf, MEK, PDE4, BCL6, DRAK1, CDK1 and CDK2, Pim-1, among others. Several synthetic strategies have been developed for the efficient synthesis of pyrazolo[1,5-a]pyrimidines, including cyclization, condensation, three-component reactions, microwave-assisted methods, and green chemistry approaches. Palladium-catalyzed crosscoupling …

Preparing Students For Civic Engagement: Cultivating Critical Dialogue In Stem Classrooms, Bryan Dewsbury, Carrie Diaz Eaton

All Faculty Scholarship

Thriving democracies require engaged citizens who possess skills pertaining to critical thinking, respectful discourse, and an appreciation of the value of difference. In this chapter, we discuss ways in which we cultivate these skills in STEM classrooms at two demographically different institutions of higher education and course types. Leaning on scholarship that shows the positive impacts of creating community and belonging, we make the case that civic participation is a critical value that should be agnostic to course type. Suggestions for transferability and institution-specific considerations will also be discussed.

Reforming Grading At The University Of Mississippi, Josh Eyler

Events

We are currently in the midst of one of the most fruitful, effective periods of grading reform in our country's history, both in K-12 and in higher ed. At many institutions, including our own, faculty are experimenting with a variety of alternative grading strategies and are having success, but many are eager to see more widespread change at the department and institutional levels. This session provides attendees with research-based tools for advancing grading reform initiatives at scale and provides participants with strategies for moving the conversation forward. Lunch will be provided for registered participants.

Single Amino Acid Changes Impact The Ability Of Drosophila Melanogaster Cecropins To Inhibit Growth Of Providencia Pathogens, Sarah Smith, Marla Forfar, Christopher Feudale, Lauren Shaffer, Grace Ginder, Marion Duval, Quinn Smith, Moria C. Chambers

Faculty Journal Articles

As antibiotic-resistant bacteria spread worldwide, the need to develop novel antimicrobial agents is urgent. One rich source of potential antimicrobials is the insect immune system, as insects produce a wide range of antimicrobial peptides (AMPs) with diverse sequences and structures. Insects also encounter many bacterial pathogens, some of which are closely related to pathogens of clinical relevance. However, despite interest in AMPs as therapeutics, the relationships between the amino acid sequence, biophysical properties, antimicrobial activity, and specificity are still not generalizable. To improve our understanding of these relationships, we assessed how single amino acid changes in cecropin AMPs produced by …

A Critical Appraisal Of The Evidence On Racial Disproportionality In Special Education, Rachel E. Fish, Kenneth Shores, Joào M. Souto Maior

Education and Child Study: Faculty Publications

This essay provides a two-pronged critical assessment of a subset of the literature on racial disproportionality in special education: that which aims to estimate racial disparities among otherwise similar children. This body of research has shown that Black students are less likely than comparable White students to receive special education, and has been interpreted by many to mean that current policies meant to reduce Black over-representation may be exacerbating inequality. Our essay argues that this subset of research has fundamental limitations in its covariate adjustment practices and its data quality, making “under-representation” findings questionable. We argue that caution and further …

The Bg News February 5, 2025, Bowling Green State University

BG News (Student Newspaper)

The BGSU campus student newspaper. February 5, 2025. Volume 104-Issue 16.

An Open-Label Study To Determine The Maximum Tolerated Dose Of Oral Esk-440 Administered As A Single Agent In Patients With Advanced Or Metastatic Solid Tumors, Russell J. Schilder, Drew Rasco, Manish R. Sharma

Kimmel Cancer Center Faculty Papers

PURPOSE: Anaplastic lymphoma kinase (ALK) dysregulation is implicated in numerous cancers. Tyrosine kinase inhibitors (TKIs) targeting ALK have improved disease outcomes, but resistance mechanisms are common. This first-in-human trial evaluates ESK-440, a dual inhibitor of ALK and focal adhesion kinase, as a novel strategy for cancers with resistance to ALK-targeting TKIs.

METHODS: This phase 1, open-label, dose-finding study evaluated the maximum tolerated dose (MTD), safety, efficacy, and pharmacokinetics of ESK-440 in participants with advanced or metastatic solid tumors (ClinicalTrials.gov: NCT01922752). A 3 + 3 dose-escalation design, with daily doses ranging from 25 to 700 mg/day of ESK-440 for each 28-day …

Factors Related To Employment Of Previously Incarcerated Individuals, Toni Victoria Lewis

Walden Dissertations and Doctoral Studies

Employment amongst previously incarcerated individuals is a concern of the criminal justice system because being employed is considered a mitigator of reincarceration. While there is research about the stigma of incarceration in gaining employment, little is known about the factors associated with individuals being able to find employment. The purpose of this quantitative, correlational study was to identify whether there is a direct correlation between individual demographic features and employment status of individuals after 1 year or more of previously being incarcerated in North Carolina. General strain theory was the theoretical framework. The key research question focused on how release …

Streamlined Production, Protection, And Purification Of Enzyme Biocatalysts Using Virus-Like Particles And A Cell-Free Protein Synthesis System, Seung O. Yang, Joseph P. Talley, Gregory H. Nielsen, Kristen M. Wilding, Bradley Charles Bundy

Faculty Publications

Enzymes play an essential role in many different industries; however, their operating conditions are limited due to the loss of enzyme activity in the presence of proteases and at temperatures significantly above physiological conditions. One way to improve the stability of these enzymes against high temperatures and proteases is to encapsulate them in protective shells or virus-like particles. This work presents a streamlined, three-step, cell-free protein synthesis (CFPS) procedure that enables rapid in vitro enzyme production, targeted encapsulation in protective virus-like particles (VLPs), and facile purification using a 6× His-tag fused to the VLP coat protein. This process is performed …

Advanced External Beam Stereotactic Radiotherapy For Skull Base Reirradiation, He Wang, Fahed M Alsanea, Dong Joo Rhee, Xiaodong Zhang, Wei Liu, Jinzhong Yang, Zhifei Wen, Yao Zhao, Tyler D Williamson, Rachel A Hunter, Peter A Balter, Tina M Briere, Ronald X Zhu, Anna Lee, Amy C Moreno, Jay P Reddy, Adam S Garden, David I Rosenthal, Gary B Gunn, Jack Phan

Faculty, Staff and Student Publications

Background/objectives: Stereotactic body radiation therapy (SBRT) for skull base reirradiation is particularly challenging, as patients have already received substantial radiation doses to the region, and nearby normal organs may have approached their tolerance limit from prior treatments. In this study, we reviewed the characteristics and capabilities of four advanced external beam radiation delivery systems and four modern treatment planning systems and evaluated the treatment plan quality of each technique using skull base reirradiation patient cases.

Methods: SBRT plans were generated for sixteen skull base reirradiation patients using four modalities: the GK plan for the Elekta Leksell Gamma Knife Perfexion/ICON, the …

Brd7 Loss Reawakens Dormant Metastasis Initiating Cells In Lung By Forging An Immunosuppressive Niche, Jayanta Mondal, Junfeng Zhang, Feng Qing, Shunping Li, Dhiraj Kumar, Jason T Huse, Filippo G Giancotti

Faculty, Staff and Student Publications

Metastasis in cancer is influenced by epigenetic factors. Using an in vivo screen, we demonstrate that several subunits of the polybromo-associated BAF (PBAF) chromatin remodeling complex, particularly Brd7, are required for maintaining breast cancer metastatic dormancy in the lungs of female mice. Brd7 loss induces metastatic reawakening, along with modifications in epigenomic landscapes and upregulated oncogenic signaling. Breast cancer cells harboring Brd7 inactivation also reprogram the surrounding immune microenvironment by downregulating MHC-1 expression and promoting a pro-metastatic cytokine profile. Flow cytometric and single-cell analyses reveal increased levels of pro-tumorigenic inflammatory and transitional neutrophils, CD8+ exhausted T cells, and CD4+ stress …

Acute Mecp2 Loss In Adult Mice Reveals Transcriptional And Chromatin Changes That Precede Neurological Dysfunction And Inform Pathogenesis, Sameer S Bajikar, Jian Zhou, Ryan O'Hara, Harini P Tirumala, Mark A Durham, Alexander J Trostle, Michelle Dias, Yingyao Shao, Hu Chen, Wei Wang, Hari Krishna Yalamanchili, Ying-Wooi Wan, Laura A Banaszynski, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene cause Rett syndrome, a severe childhood neurological disorder. MeCP2 is a well-established transcriptional repressor, yet upon its loss, hundreds of genes are dysregulated in both directions. To understand what drives such dysregulation, we deleted Mecp2 in adult mice, circumventing developmental contributions and secondary pathogenesis. We performed time series transcriptional, chromatin, and phenotypic analyses of the hippocampus to determine the immediate consequences of MeCP2 loss and the cascade of pathogenesis. We find that loss of MeCP2 causes immediate and bidirectional progressive dysregulation of the transcriptome. To understand what drives gene downregulation, we …