Digital Commons Network^™

Membrane Translocation Process Revealed By In Situ Structures Of Type Ii Secretion System Secretins, Zhili Yu, Yaoming Wu, Muyuan Chen, Tong Huo, Wei Zheng, Steven J Ludtke, Xiaodong Shi, Zhao Wang

Faculty, Staff and Students Publications

The GspD secretin is the outer membrane channel of the bacterial type II secretion system (T2SS) which secrets diverse toxins that cause severe diseases such as diarrhea and cholera. GspD needs to translocate from the inner to the outer membrane to exert its function, and this process is an essential step for T2SS to assemble. Here, we investigate two types of secretins discovered so far in Escherichia coli, GspDα, and GspDβ. By electron cryotomography subtomogram averaging, we determine in situ structures of key intermediate states of GspDα and GspDβ in the translocation process, with resolution ranging from 9 Å …

Reasonable Tax Rules: Advancing Process Values With Remedial Restraint, James M. Puckett

Florida Tax Review

The tax administration is at risk of an overcorrection with respect to its rulemaking process. Tax practitioners increasingly are mining the Administrative Procedure Act (APA) as well as chipping away at barriers to pre-enforcement review of tax rules. Tax rules include regulations, revenue rulings, revenue procedures, and more informal guidance to the public. APA-based challenges to tax rules have gained traction in the courts, typically alleging inadequate explanation or timing irregularities involving notice and comment. Such claims potentially pose major challenges for fair and efficient tax administration.

This Article integrates administrative law scholarship calling for a rule of reason with …

Implications Of Denmark's Water Price Reform For Reverine And Coastal Surface Water Quality, Massimo Pizzol, Maria Molinos-Senante, Hans Thodsen, Mikael Skou Andersen

Florida Tax Review

Article 9 of the EU’s Water Framework Directive suggests that Member States should provide “adequate incentives” for efficient use of water resources. Although the Directive is mainly about protecting the ecological quality of water bodies, control of quantity serves as an “ancillary element” in delivering on the objectives. Despite their financial difficulties, Member States have been slow to bring their policies on water pricing up to the wording and 2010 deadline of the Directive’s article 9.

This Article explores the significance of water pricing reform for the ecological quality objectives for surface waters and, as a stepping stone in this …

Medical School Watercooler Newsletter - July 6, 2023, Lindsey Lyle

Watercooler Newsletter

This is the July 6, 2023 edition of the Frederick P. Whiddon College of Medicine's newsletter - Watercooler.

Contents include:

• Pathology residents present research at annual forum
• Basic medical sciences student wins travel award to national conference
• Fellowship-trained gastroenterologist joins internal medicine faculty
• Neurology resident elected to roles at national and state level

Lutein And Β-Carotene Characterization In Free And Nanodispersion Forms In Terms Of Antioxidant Activity And Cytotoxicity, Nourhan S. Elkholy, Mohamad Louai M. Hariri, Haitham S. Mohammed, Medhat W. Shafaa

Faculty Journal Articles

No abstract provided.

Gbmdeconvoluter Accurately Infers Proportions Of Neoplastic And Immune Cell Populations From Bulk Glioblastoma Transcriptomics Data., Shoaib Ajaib, Disha Lodha, Steven Pollock, Gemma Hemmings, Martina A Finetti, Arief Gusnanto, Aruna Chakrabarty, Azzam Ismail, Erica Wilson, Frederick S Varn, Bethany Hunter, Andrew Filby, Asa A Brockman, David Mcdonald, Roel G W Verhaak, Rebecca A Ihrie, Lucy F Stead

Faculty Research 2023

BACKGROUND: Characterizing and quantifying cell types within glioblastoma (GBM) tumors at scale will facilitate a better understanding of the association between the cellular landscape and tumor phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumor microenvironment from bulk RNA sequencing data.

METHODS: We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T-cells, NK-cells, microglia, tumor associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal progenitor-like and mesenchymal GBM cancer cells …

Specialized Late Cingulo-Opercular Network Activation Elucidates The Mechanisms Underlying Decisions About Ambiguity, Jordan E. Pierce, Nathan M. Petro, Elizabeth Clancy, Caterina Gratton, Steven E. Petersen, Maital Neta

Center for Brain, Biology, and Behavior: Faculty Publications

Cortical task control networks, including the cingulo-opercular (CO) network play a key role in decision-making across a variety of functional domains. In particular, the CO network functions in a performance reporting capacity that supports successful task performance, especially in response to errors and ambiguity. In two studies testing the contribution of the CO network to ambiguity processing, we presented a valence bias task in which masked clearly and ambiguously valenced emotional expressions were slowly revealed over several seconds. This slow reveal task design provides a window into the decision-making mechanisms as they unfold over the course of a trial. In …

High-Performing Conductive Hydrogels For Wearable Applications., Hossein Omidian, Sumana Dey Chowdhury

HPD Articles

Conductive hydrogels have gained significant attention for their extensive applications in healthcare monitoring, wearable sensors, electronic devices, soft robotics, energy storage, and human-machine interfaces. To address the limitations of conductive hydrogels, researchers are focused on enhancing properties such as sensitivity, mechanical strength, electrical performance at low temperatures, stability, antibacterial properties, and conductivity. Composite materials, including nanoparticles, nanowires, polymers, and ionic liquids, are incorporated to improve the conductivity and mechanical strength. Biocompatibility and biosafety are emphasized for safe integration with biological tissues. Conductive hydrogels exhibit unique properties such as stretchability, self-healing, wet adhesion, anti-freezing, transparency, UV-shielding, and adjustable mechanical properties, making …

Sharing Innovative Projects, July 6, 2023, Tisa Mason Ed.D.

Heart of a Tiger Columns

No abstract provided.

Eight Gardner-Webb Students Receive Grants For Focused Research, Office Of University Communications, Brandon Richmond

Gardner-Webb NewsCenter Archive

Eight new scholars received grants from the Summer Undergraduate Research Scholars Program (https://gardner-webb.edu/academics/enrichment-programs/summer-research-scholars/), one of Gardner-Webb University’s academic enrichment opportunities. Every year, the initiative allows a student to spend 40 hours a week working on a project for five weeks with the assistance of a Gardner-Webb professor. The students learn more in their fields and help advance the field itself. They also tap into the professors’ knowledge and experience on how to conduct and complete a scholarly project.

Assessing The Impact Of Spatial Resolution Of Uas-Based Remote Sensing And Spectral Resolution Of Proximal Sensing On Crop Nitrogen Retrieval Accuracy, Kianoosh Hassani, Hamed Gholizadeh, Saleh Taghvaeian, Victoria Natalie, Jonathan Carpenter, Jamey Jacob

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Foliar nitrogen (N) plays a central role in photosynthetic machinery of plants, regulating their growth rates. However, field-based methods for monitoring plant N concentration are costly and limited in their ability to cover large spatial extents. In this study, we had two objectives: (1) assess the capability of unoccupied aerial system (UAS) and non-imaging spectroscopic data in estimating sorghum and corn N concentration and (2) determine the impact of spatial and spectral resolution of reflectance data on estimating sorghum and corn N concentration. We used a UAS and an ASD spectroradiometer to collect canopy- and leaf-level spectral data from sorghum …

Book Review: Derviš M. Korkut: A Biography—Rescuer Of The Sarajevo Haggadah, Ehlimana Memišević

Genocide Studies and Prevention: An International Journal

At the beginning of 2020, the Sarajevo-based publishing house El-Kalem, released a biography of Derviš M. Korkut, a Bosniak hero, to whom Yad Vashem posthumously awarded Righteous among the Nations on December 14, 1994.

Winston Churchill's words, with which the author begins the biography—that the Balkans produce more history than they can handle—best describe the difficult times in which Korkut lived. For Korkut and his fellow Bosnians, these difficult times lasted from the beginning of the 20th century to its very end.

The book is based on exhaustive archival research and reconstructs Korkut’s life very precisely, while the concise overview …

Cancer Cell-Specific Cgas/Sting Signaling Pathway In The Era Of Advancing Cancer Cell Biology, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Pattern-recognition receptors (PRRs) are critical to recognizing endogenous and exogenous threats to mount a protective proinflammatory innate immune response. PRRs may be located on the outer cell membrane, cytosol, and nucleus. The cGAS/STING signaling pathway is a cytosolic PRR system. Notably, cGAS is also present in the nucleus. The cGAS-mediated recognition of cytosolic dsDNA and its cleavage into cGAMP activates STING. Furthermore, STING activation through its downstream signaling triggers different interferon-stimulating genes (ISGs), initiating the release of type 1 interferons (IFNs) and NF-κB-mediated release of proinflammatory cytokines and molecules. Activating cGAS/STING generates type 1 IFN, which may prevent cellular transformation …

Controlling Soil Erosion After Wildfire And Guiding Recovery In Southern Utah, Kristina Young, Kara Dohrenwend, Matt Mcettrick, Henry Grover

All Current Publications

Wildfire is a natural part of many ecosystems in the Four Corners region (Southern Utah, Northern Arizona, Southwest Colorado, and Northwest New Mexico). However, after decades of fire suppression, the intensity and size of wildfires is increasing. This fact sheet is intended to help those in dry, monsoonal regions understand what happens to land after a wildfire and explains the processes of soil erosion. It outlines factors that influence how wildfire can affect soils and plants and provides suggestions for reducing soil erosion when necessary. The information presented is relevant to both private landowners and public lands managers whose landscapes …

Acceptability And Feasibility Of A Multicultural Orientation-Informed Focused Acceptance And Commitment Therapy For Caregivers Of Adolescent Bariatric Surgery Candidates, Jessica L. Cook

Electronic Theses and Dissertations Archive

Objective: The current study developed and assessed caregiver perspectives of acceptability and feasibility of a family-based multicultural-orientation Focused Acceptance and Commitment Therapy (FACT) intervention for use with adolescents with obesity pursuing bariatric surgery and their caregivers. The intervention aimed to increase adolescent and caregiver psychological flexibility specific to adolescent implementation and caregiver support of health and related values-consistent behaviors. The intervention was iteratively refined to enhance acceptability among families of diverse sociocultural identities while ensuring feasibility of its implementation during routine interdisciplinary pediatric weight-management clinic visits. Method: Adolescent-caregiver dyads were recruited to participate in two intervention sessions during routine pre-operative …

Exploring The Heterogeneity Of Dopamine Signaling In The Rat Striatum, Rebecca Louise Chicosky

Theses and Dissertations

Dopamine (DA) is a neurotransmitter critical for locomotion, motivation, and reward learning and has implications in the neuropathologies of Parkinson’s disease, schizophrenia, and substance use disorder. The rat striatum, which receives the densest DA innervation in the entire rat brain, shows distinct heterogeneity at different anatomical levels, e.g., dorsal and ventral subregions, patch and matrix compartments, and microdomains. The previous use of carbon-fiber microelectrodes (CFM), a single site microsensor coupled to fast-scan cyclic voltammetry (FSCV), has limited the ability to view and characterize this DA heterogeneity. Furthermore, studies examining the effects of amphetamine (AMPH), a psychostimulant with clinical efficacy and …

Exploring The Impact Of Eddies On Southern Ocean Biogeochemical Structure Using Bgc-Argo Float Observations, Nicola J. Guisewhite

USF Tampa Graduate Theses and Dissertations

The Southern Ocean plays a crucial role in global ocean circulation, and global heat and nutrient transport. However, this region is both distant and dangerous and is therefore largely under-sampled and understudied. Methods to fill in biogeochemical data-gaps include using limited in-situ data in models to output biogeochemical property estimates, but a number of recent studies have raised concerns about how most Southern Ocean models do not resolve eddies. Eddies are known to impact biogeochemistry around the globe but little is known about their impact in the Southern Ocean. This study examines temperature, salinity, oxygen, nitrate, and dissolved inorganic carbon …

The Impact Of The Blended Learning Approach On Sustainable Efl Learning In An Egyptian Context, Wesam Khairy Morsi

English Language and Literature

The blended learning approach (BLA) is a popular trend in higher education because it combines the merits of traditional, face-to-face (FTF) learning, and online learning. This research aims to investigate the effect of implementing the BLA via eLearning on Egyptian undergraduates’ EFL reading and writing achievement compared to their peers’ achievement who only received FTF instruction. The study is qu- asi experimental. A total of 55 freshmen at a private university in Egypt were divided into two experi- mental (study) groups and one control (FTF) group. Students had a reading and writing pre-test before the treatment, and after the treatment, …

The Timid Invasion: Behavioural Adjustments And Range Expansion In A Non-Native Rodent, Jana A. Eccard, Valeria Mazza, Celia Holland, Peter Stuart

Publications

Animal behaviour can moderate biological invasion processes, and the native fauna's ability to adapt. The importance and nature of behavioural traits favouring colonization success remain debated. We investigated behavioural responses associated with risk-taking and exploration, both in non-native bank voles (Myodes glareolus, N = 225) accidentally introduced to Ireland a century ago, and in native wood mice (Apodemus sylvaticus, N = 189), that decline in numbers with vole expansion. We repeatedly sampled behavioural responses in three colonization zones: established bank vole populations for greater than 80 years (2 sites), expansion edge vole populations present for 1–4 …

Deep Sea Nature-Based Solutions To Climate Change, Nathalie Hilmi, Michael Sutherland, Shekoofeh Farahmand, Gunnar Haraldsson, Erik Van Doorn, Ekkehard Ernst, Mary S. Wisz, Astrid Claudel Rusin, Laura G. Elsler, Lisa A. Levin

Articles

The deep sea (below 200 m depth) is the largest carbon sink on Earth. It hosts abundant biodiversity that underpins the carbon cycle and provides provisioning, supporting, regulating and cultural ecosystem services. There is growing attention to climate-regulating ocean ecosystem services from the scientific, business and political sectors. In this essay we synthesize the unique biophysical, socioeconomic and governance characteristics of the deep sea to critically assess opportunities for deep-sea blue carbon to mitigate climate change. Deep-sea blue carbon consists of carbon fluxes and storage including carbon transferred from the atmosphere by the inorganic and organic carbon pumps to deep …

Evaluating Approaches For Constructing Polygenic Risk Scores For Prostate Cancer In Men Of African And European Ancestry, Burcu F Darst, Jiayi Shen, Ravi K Madduri, Alexis A Rodriguez, Yukai Xiao, Xin Sheng, Edward J Saunders, Tokhir Dadaev, Mark N Brook, Thomas J Hoffmann, Kenneth Muir, Peggy Wan, Loic Le Marchand, Lynne Wilkens, Ying Wang, Johanna Schleutker, Robert J Macinnis, Cezary Cybulski, David E Neal, Børge G Nordestgaard, Sune F Nielsen, Jyotsna Batra, Judith A Clements, Australian Prostate Cancer Bioresource, Henrik Grönberg, Nora Pashayan, Ruth C Travis, Jong Y Park, Demetrius Albanes, Stephanie Weinstein, Lorelei A Mucci, David J Hunter, Kathryn L Penney, Catherine M Tangen, Robert J Hamilton, Marie-Élise Parent, Janet L Stanford, Stella Koutros, Alicja Wolk, Karina D Sørensen, William J Blot, Edward D Yeboah, James E Mensah, Yong-Jie Lu, Daniel J Schaid, Stephen N Thibodeau, Catharine M West, Christiane Maier, Adam S Kibel, Géraldine Cancel-Tassin, Florence Menegaux, Esther M John, Eli Marie Grindedal, Kay-Tee Khaw, Sue A Ingles, Ana Vega, Barry S Rosenstein, Manuel R Teixeira, Nc-La Pcap Investigators, Manolis Kogevinas, Lisa Cannon-Albright, Chad Huff, Luc Multigner, Radka Kaneva, Robin J Leach, Hermann Brenner, Ann W Hsing, Rick A Kittles, Adam B Murphy, Christopher J Logothetis, Susan L Neuhausen, William B Isaacs, Barbara Nemesure, Anselm J Hennis, John Carpten, Hardev Pandha, Kim De Ruyck, Jianfeng Xu, Azad Razack, Soo-Hwang Teo, Canary Pass Investigators, Lisa F Newcomb, Jay H Fowke, Christine Neslund-Dudas, Benjamin A Rybicki, Marija Gamulin, Nawaid Usmani, Frank Claessens, Manuela Gago-Dominguez, Jose Esteban Castelao, Paul A Townsend, Dana C Crawford, Gyorgy Petrovics, Graham Casey, Monique J Roobol, Jennifer F Hu, Sonja I Berndt, Stephen K Van Den Eeden, Douglas F Easton, Stephen J Chanock, Michael B Cook, Fredrik Wiklund, John S Witte, Rosalind A Eeles, Zsofia Kote-Jarai, Stephen Watya, John M Gaziano, Amy C Justice, David V Conti, Christopher A Haiman

Faculty, Staff and Student Publications

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and …

Changes In Outcomes And Factors Associated With Survival In Melanoma Patients With Brain Metastases, Merve Hasanov, Denái R Milton, Alicia Bea Davies, Elizabeth Sirmans, Chantal Saberian, Eliza L Posada, Sylvia Opusunju, Jeffrey E Gershenwald, Carlos A Torres-Cabala, Elizabeth M Burton, Rivka R Colen, Jason T Huse, Isabella C Glitza Oliva, Caroline Chung, Mary Frances Mcaleer, Susan L Mcgovern, Debra N Yeboa, Betty Y S Kim, Sujit S Prabhu, Ian E Mccutcheon, Jeffrey S Weinberg, Frederick F Lang, Hussein A Tawbi, Jing Li, Lauren E Haydu, Michael A Davies, Sherise D Ferguson

Faculty, Staff and Student Publications

BACKGROUND: Treatment options for patients with melanoma brain metastasis (MBM) have changed significantly in the last decade. Few studies have evaluated changes in outcomes and factors associated with survival in MBM patients over time. The aim of this study is to evaluate changes in clinical features and overall survival (OS) for MBM patients.

METHODS: Patients diagnosed with MBMs from 1/1/2009 to 12/31/2013 (Prior Era; PE) and 1/1/2014 to 12/31/2018 (Current Era; CE) at The University of Texas MD Anderson Cancer Center were included in this retrospective analysis. The primary outcome measure was OS. Log-rank test assessed differences between groups; multivariable …

Apoe Gene Associated With Dementia-Related Traits, Depression, And Anxiety In The Hispanic Population, Chun Xu, Victoria Padilla, Stephanie Lozano, Daniela Gamez, Brenda Bin Su, Xuan Wang, Gladys Maestre, Kesheng Wang

Health & Biomedical Sciences Faculty Publications

Alzheimer's disease (AD), a main cause of dementia, is commonly seen in aging populations with a strong genetic component. AD is one of the most common neurodegenerative disorders; it is a genetically and clinically heterogeneous disease. Specific demographic factors and genetic variants have been identified in non-Hispanic populations; however, limited studies have observed the Hispanic population. Therefore, we focused on investigating a known gene, APOE, associated with AD-related phenotypes and two psychiatric diseases (depression and anxiety) within the U.S. Hispanic population in our current study. A total of 1382 subjects were studied based on data collected from the Texas Alzheimer's …

Exploring The Complex Relationship Between Social Needs And Health, Rachel Catherine Garg

Brown School Graduate Student Theses and Dissertations

Over the past two decades, the healthcare sector has increasingly sought to assess and address patients’ health-related social needs with the dual aim of health improvement and cost reduction. However, evidence for the health impact of social needs interventions is mixed. Most interventions are not guided by theories or conceptual models that specify causal pathways or mechanisms for how unmet social needs impact health. It is also currently unknown how social needs change over time and the timeframe over which social needs impact health outcomes. This dissertation seeks to fill these gaps by (1) critically reviewing existing conceptual models proposing …

Mesoporous Particle Embedded Nanofibrous Scaffolds Sustain Biological Factors For Tendon Tissue Engineering, Chiara Rinoldi, Ewa KijeńSka-GawrońSka, Marcin Heljak, Jakub Jaroszewicz, Artur KamińSki, Ali Khademhosseini, Ali Tamayol, Wojciech Swieszkowski

Department of Mechanical and Materials Engineering: Faculty Publications

In recent years, fiber-based systems have been explored in the frame of tissue engineering due to their robustness in recapitulating the architecture and mechanical properties of native tissues. Such scaffolds offer anisotropic architecture capable of reproducing the native collagen fibers’ orientation and distribution. Moreover, fibrous constructs might provide a biomimetic environment for cell encapsulation and proliferation as well as influence their orientation and distribution. In this work, we combine two fiber fabrication techniques, such as electrospinning and wet-spinning, in order to obtain novel cell-laden 3D fibrous layered scaffolds which can simultaneously provide: (i) mechanical support; (ii) suitable microenvironment for 3D …

Individualized Therapeutic Composition As A Method Of Improving Sleep Quality In College Students, Nicholas Lanz

Theses and Dissertations

The life of a college student is often bombarded with circumstances, emotions, and decisions that produce stress and anxiety, affecting sleep quality and daily function. Listening to music designed for relaxation has the potential to decrease stress and improve factors of healthy sleep quality. The purpose of this study was to explore the effects of listening to music uniquely composed for each individual on stress relief and sleep quality in college students. The music therapy intervention utilized in this study was individual composition sessions. The researcher met with each participant individually to compose an instrumental piece of music that was …

The Development Of An Effective Synthetic Pathway To The Hiv Protease Inhibitor Darunavir And Its Structural Derivatives For Sar Studies Via An Asymmetric Glycolate Aldol Addition Reaction Approach, Emmanuel Ayim

Theses and Dissertations

The Centers for disease control and Prevention (CDC) published an article describing the disease that would later become known as HIV/AIDS in 1981. There were no treatments for this new disease, and by the time patients began exhibiting detectable symptoms, it would be too late to provide any meaningful treatments. Through the efforts made by the scientific community and social activism, new classes of drugs appeared for the treatment of this disease. These drugs are highly effective when combined with other therapeutic agents that suppress the proliferation of the virus. These combined therapies have helped alleviate the previously insurmountable risks …

Affect Variability And Physical Health: The Moderating Role Of Mean Affect, Brooke N. Jenkins, Lydia Q. Ong, Hee Youn (Helen) Lee, Anthony D. Ong, Julia K. Boehm

Psychology Faculty Articles and Research

Research has only begun to explore how affect variability relates to physical health and has typically not assessed long-term associations nor considered the moderating role of mean affect. Therefore, we used data from the Midlife in the United States Study waves 2 (N = 1512) and 3 (N = 1499) to test how affect variability predicted concurrent and long-term physical health while also testing the moderating role of mean affect. Results indicated that greater negative affect variability was associated concurrently with a greater number of chronic conditions (p = .03) and longitudinally with worse self-rated physical health (p …

Extracellular Cytochrome Nanowires Appear To Be Ubiquitous In Microbes, Public Relations

Browse All News

No abstract provided.

A Functional Link Between Lariat Debranching Enzyme And The Intron-Binding Complex Is Defective In Non-Photosensitive Trichothiodystrophy, Brittany A Townley, Luke Buerer, Ning Tsao, Albino Bacolla, Fadhel Mansoori, Timur Rusanov, Nathanial Clark, Negar Goodarzi, Nicolas Schmidt, Sridhar Nonavinkere Srivatsan, Hua Sun, Reilly A Sample, Joshua R Brickner, Drew Mcdonald, Miaw-Sheue Tsai, Matthew J Walter, David F Wozniak, Alex S Holehouse, Vladimir Pena, John A Tainer, William G Fairbrother, Nima Mosammaparast

Faculty, Staff and Student Publications

The pre-mRNA life cycle requires intron processing; yet, how intron-processing defects influence splicing and gene expression is unclear. Here, we find that TTDN1/MPLKIP, which is encoded by a gene implicated in non-photosensitive trichothiodystrophy (NP-TTD), functionally links intron lariat processing to spliceosomal function. The conserved TTDN1 C-terminal region directly binds lariat debranching enzyme DBR1, whereas its N-terminal intrinsically disordered region (IDR) binds the intron-binding complex (IBC). TTDN1 loss, or a mutated IDR, causes significant intron lariat accumulation, as well as splicing and gene expression defects, mirroring phenotypes observed in NP-TTD patient cells. A Ttdn1-deficient mouse model recapitulates intron-processing defects and certain …