Digital Commons Network^™

Mecp2 Interacts With The Super Elongation Complex To Regulate Transcription, Jun Young Sonn, Wonho Kim, Marta Iwanaszko, Yuki Aoi, Yan Li, Guantong Qi, Luke Parkitny, Janice L Brissette, Lorin Weiner, Juan Botas, Ismael Al-Ramahi, Ali Shilatifard, Huda Y Zoghbi

Faculty, Staff and Students Publications

Loss-of-function mutations in methyl-CpG binding protein 2 (MECP2) cause Rett syndrome. While we know that MeCP2 binds to methylated cytosines on DNA, the full breadth of the molecular mechanisms by which MeCP2 regulates gene expression remains incompletely understood. Here, using a genetic modifier screen, we identify the super elongation complex, a P-TEFb–containing elongation factor that releases promoter-proximally paused RNA polymerase II, as a genetic interactor of MECP2. MeCP2 physically interacts with SEC subunits and directly binds AFF4, the scaffold of the SEC, via the transcriptional repression domain. Furthermore, MeCP2 facilitates the binding of AFF4 on a subset …

Dose-Dependent Benefits Of Dietary Yeast Cell Wall Supplementation On The Growth Performance And Stress Resilience Of The European Seabass (Dicentrarchus Labrax), Camille Houdelet, Ana Teresa Goncalves, Jorge Dias, Mark Rawling, Eric Leclercq

School of Biological and Marine Sciences

Preventive health management is central to modern aquaculture practices, within which functional feed additives are a key tool to optimising fish robustness and disease resilience. Despite being well documented, only few studies have assessed the dose–effect of graded levels of S. cerevisiae yeast cell wall (YCW) on fish performance and mucosal barrier immunity. A 9-week trial was conducted to assess the impact of graded levels of YCW on the performance and mucosal barriers of the European seabass under period: (1) non-challenge (43 days) then (2) with an applied husbandry stressors (20 days) in the form of high stocking density, low …

How Experiencing Eudaimonic Emotions Through Music Shapes Prosocial And Altruistic Behavior: Introducing A Unified Model Of Music-Listening-Induced Eudaimonia (Ummie), Rebecca Tukachinsky Forster, Daniel H. Spitz, Tal-Chen Rabinowitch, Roni Granot

Communication Faculty Articles and Research

This paper introduces the Unified Model of Music-Listening Induced Eudaimonia (UMMIE), which offers an integrated novel theoretical framework to explain how music listening promotes prosocial and altruistic outcomes. Drawing on communication and psychology research, UMMIE maintains that elicitation of eudaimonic emotions can be appraised inwards, towards oneself, and thus contribute to the individual's personal growth, wellbeing, and development, or outwards, by connecting to something bigger than oneself, to humanity in general, which could possibly then lead to enhanced prosocial and altruistic attitudes and behaviors. The model specifies musical, situational, and individual variables that serve as moderators and increase the likelihood …

Transdisciplinary Perspectives On Ai: The Fourth Annual Conference Of The European Culture And Technology Laboratory, Connell Vaughan, Ioana Madalina Moldovan, Silivan Moldovan, Noel Fitzpatrick

Books/Book Chapters

The fourth annual conference of the ECT Lab+ was hosted by Technical University of Cluj-Napoca over two days in October 2024 at the Cluj Innovation Park. The conference brought together experts from the Arts, Humanities, Social Sciences, Technology, and other fields to discuss and reflect on the advent of Artificial Intelligence and how the associated technologies are transforming how we live, work and study. Under the title Transdisciplinary perspectives on AI: Alternative Histories, Current Practices and Possible Futures the conference moved beyond simplistic technophila and technophobia to consider whether we can co-evolve with these new technologies which combine machine learning …

Non-Invasive Ultrasonic Neuromodulation Of The Human Nucleus Accumbens Impacts Reward Sensitivity, Siti N Yaakub, John Eraifej, Nadège Bault, Mathilde Lojkiewiez, Elouan Bellec, Jamie Roberts, Noah S Philip, Amir Puyan Divanbeighi Zand, Alexander L Green, Matthew F S Rushworth, Elsa F Fouragnan

School of Psychology

Precisely neuromodulating deep brain regions could bring transformative advancements in both neuroscience and treatment. We demonstrate that non-invasive transcranial ultrasound stimulation (TUS) can selectively modulate deep brain activity and affect learning and decision making, comparable to deep brain stimulation (DBS). We tested whether TUS could causally influence neural and behavioural responses by targeting the nucleus accumbens (NAcc) using a reinforcement learning task. Twenty-six healthy adults completed a within-subject TUS-fMRI experiment with three conditions: TUS to the NAcc, dorsal anterior cingulate cortex (dACC), or Sham. After TUS, participants performed a probabilistic learning task during fMRI. TUS-NAcc altered BOLD responses to reward …

The Gastrointestinal Endothelin System: Receptors, Cellular Actions, And Involvement In Gastrointestinal Disorders, Arjun Singh, Rajvir Singh

Department of Medicine Faculty Papers

The gastrointestinal endothelin system regulates vital processes including motility, secretion, sensation, and inflammation. Endothelin-1 acts via endothelin A and B receptors expressed on diverse intestinal cells. Dysregulation of endothelin signaling underlies common gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome. Aberrant endothelin-1 production and endothelin A receptor activation contribute to the inflammation, pain hypersensitivity, impaired epithelial function, and smooth muscle hypercontractility characteristic of these diseases. Endothelin receptor antagonists may provide therapies for managing related symptoms. However, knowledge gaps exist regarding cell-specific signaling pathways, regulatory factors, and precise roles in intestinal pathologies. Elucidating these details and translating insights …

Rewilding Gender: Toward Relational Understandings Of ‘The Wild’, Kim Ward

School of Geography, Earth and Environmental Sciences

This commentary reframes gender and rewilding through a relational understanding of wildness. Moving beyond a binary lens of ‘the wild’, it examines how gendered relations shape rewilding's material, emotional, and epistemic dimensions. Centring relational wildness exposes how rewilding challenges masculine imaginaries of control and ownership while opening space for more equitable multispecies relations.

Mucosal Melanoma: Mechanisms Of Its Etiology, Progression, Resistance And Therapy, Sofie-Yasmin Hassan, Thomas W. Flanagan, Sarah-Lilly Hassan, Sybille Facca, Youssef Haikel, Mohamed Hassan

School of Graduate Studies Faculty Publications

Mucosal melanoma (MM) is a rare, aggressive cancer whose incidence has increased continuously over the years. This subtype of melanoma arises from melanocytes on hairless surfaces, typically in the respiratory tract, gastrointestinal (GI) tract, and urogenital tract. The most common sites of occurrence include the head and neck, the anorectal region, and the vulvovaginal region, while the rare sites of MM are the urinary tract and the upper and lower GI tract, including the esophagus, duodenum and the gallbladder. MM arises in melanocytes of the ectodermal mucosa that originate from neural crest cells and migrate through embryonic mesenchyme to their …

Red Midge Larvae Are An Invertebrate Alternative Diet To Beef Liver For Planarian Husbandry, Jonah Pacis , '25, Danielle Ireland, Evangeline Coffinas, Jerome Sheehan, Kate Sun , '27, Eva-Maria S. Collins

Biology Faculty Works

Freshwater planarians are an emerging model for toxicology and neuroscience because of their amenability to rapid behavioral screening and remarkable ability to regenerate a cephalized nervous system. As invertebrates, planarians can help reduce the use of vertebrates in research; however, laboratories typically maintain planarians on diets of homogenized organic beef or chicken liver, raising ethical concerns with feeding a vertebrate diet. Organic liver is difficult to obtain, and preparation methods vary, introducing intra- and interlaboratory variability. Here, we show that Dugesia japonica planarians can be maintained for over a year on commercially available red midge larvae (RML), a natural prey …

Digital Neuropsychology And Social Anxiety: The Effect Of Observer Presence And Personality On Stress And Cognition, Ava M. Dixon

Master's Theses

This study examined how observer presence and social anxiety influence stress and cognitive performance during neuropsychological assessments, focusing on the potential benefits of unsupervised digital testing environments. Eighty university students were randomly assigned to observed or unobserved digital neuropsychological conditions and completed assessments of social cognition and executive functioning and questionnaires of social anxiety and personality. Participants also completed measures of state anxiety and heart rate variability at baseline and after cognitive tests. The findings indicated that observation led to higher subjective anxiety, but it did not produce significant interactions with social anxiety on stress or cognitive performance. Post-hoc analyses …

Crispr Disruption Of Scarna1 Reduces Pseudouridylation In Spliceosomal Rna U2 At U89 And Perturbs The Transcriptome In Hek293t Cells, Amanda Gardner-Kay, Lynndy Le, Michael Filla, Nataliya Kibiryeva, James E. O'Brien Jr., Douglas C. Bittel

Student Publications

Small Cajal body-associated RNAs (scaRNAs) are essential for biochemical modification of spliceosomal RNAs and spliceosome function. Changes in scaRNA expression level have been associated with developmental issues, including cancer and congenital heart defects (CHDs), although the mechanism remains unclear. Small Cajal body-associated RNA 1 (scaRNA1) guides pseudouridylation at uridine 89 (Ψ89) of the spliceosomal RNA U2, a highly conserved modification that may be critical for spliceosome function. To investigate the role of scaRNA1 in splicing regulation, CRISPR-Cas9 genome editing was used to introduce targeted deletions in the scaRNA1 locus in HEK293T cells. Edited clones were identified by T7 endonuclease I …

Met Overexpression Is Associated With Superior Immunotherapy Benefit In Advanced Non-Small Cell Lung Cancer, Hui Li, Lingzhi Hong, Pedro Rocha, Rafael Bach, Luisa M Solis Soto, Waree Rinsurongkawong, Bingnan Zhang, Haniel A Araujo, Yasir Y Elamin, Mehmet Altan, Claudio A Arrechedera, Jianling Zhou, Khaja B Khan, Wei Lu, Elliana Young, Carl M Gay, Tina Cascone, Lauren A Byers, Ferdinandos Skoulidis, George Blumenschein, Frank V Fossella, Anne Tsao, Marcelo V Negrao, Natalie Vokes, Jia Wu, Hai T Tran, Ignacio I Wistuba, J Jack Lee, Don L Gibbons, Ara A Vaporciyan, John V Heymach, Xiuning Le, Jianjun Zhang

Faculty, Staff and Student Publications

Background/objectives: MET overexpression is common in non-small cell lung cancer (NSCLC). The correlation between MET overexpression and immune checkpoint inhibitor (ICI) efficacy in NSCLC is underexplored.

Methods: In this retrospective observational cohort study, we curated a dataset of 279 stage IV NSCLC patients who received ICI treatment and had MET expression assessed by CLIA-certified immunohistochemistry (IHC) assay. MET expression was graded on a scale from 0 to 3+, with overexpression defined as 2+ or 3+. Clinicopathological features associated with MET expression were assessed using logistic regression. Overall survival (OS) and progression-free survival (PFS) were evaluated via Kaplan-Meier analysis and the …

Crispr Disruption Of Scarna1 Reduces Pseudouridylation In Spliceosomal Rna U2 At U89 And Perturbs The Transcriptome In Hek293t Cells., Amanda Gardner-Kay, Lynndy Le, Michael Filla, Nataliya Kibiryeva, James O'Brien, Douglas C. Bittel

Manuscripts, Articles, Book Chapters and Other Papers

Small Cajal body-associated RNAs (scaRNAs) are essential for biochemical modification of spliceosomal RNAs and spliceosome function. Changes in scaRNA expression level have been associated with developmental issues, including cancer and congenital heart defects (CHDs), although the mechanism remains unclear. Small Cajal body-associated RNA 1 (scaRNA1) guides pseudouridylation at uridine 89 (Ψ89) of the spliceosomal RNA U2, a highly conserved modification that may be critical for spliceosome function. To investigate the role of scaRNA1 in splicing regulation, CRISPR-Cas9 genome editing was used to introduce targeted deletions in the scaRNA1 locus in HEK293T cells. Edited clones were identified by T7 endonuclease I …

Microrna Profiling Identifies Diagnostic And Prognostic Markers In Pediatric Sarcoma., Terrie Flatt, Leonid M. Yermakov, Shreeram Akilesh, Eleanor Y. Chen, Elizabeth Gonzalez, Alejandro Parrales, Marta Zapata-Tarres, Rocio Cardenas-Cardos, Liliana Velasco-Hidalgo, Celso Corcuera-Delgado, Rodolfo Rodriguez-Jurado, Lillia García-Rodríguez, Midhat S. Farooqi, Atif Ali Ahmed

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: MicroRNAs (miRNAs) function as post-transcriptional gene expression regulators and influence the development and progression of several cancers, yet their roles in pediatric sarcomas remain poorly defined.

METHODS: RNA extracted from formalin-fixed paraffin-embedded tumor tissue scrolls of 108 pediatric tumors, including 32 osteosarcoma (OS), 26 Ewing's sarcoma (EWS), and 50 rhabdomyosarcoma (RMS) cases, were analyzed for microRNA expression using the NanoString multiplex nCounter platform that yielded information on 827 human miRNAs. The expression of candidate miRNAs was validated with in situ hybridization (miRNA-ISH) and QuPath quantification on tissue microarray slides comprising an independent set of 48 OS, 17 EWS, and …

The 23rd International Medical, Pharmaceutical, Cosmeceutical And Health Science Symposium (Impachs), Sultan Qaboos University

Sultan Qaboos University Medical Journal

No abstract provided.

Clinical Characteristics And Risk Factors Associated With Acute Kidney Injury Among Hospitalized Primary Covid-19 Infected Patients, Monchai Siribamrungwong, Kamontip Chaikomon

Chulalongkorn Medical Journal

Background: Coronavirus disease 19 (COVID-19) mainly affects to respiratory system from mild to severe symptoms. Additionally, acute kidney injury (AKI) is an important complication causing substantially high morbidity and mortality. During the pandemic of COVID-19, Public health care in Thailand experienced many cases and complications.

Objectives: This study demonstrated an incidence, clinical characteristic, independent risk factors of AKI and mortality in hospitalized COVID-19 patients with AKI and non-AKI patients.

Methods: A retrospective, observational study was performed in Lesdsin Hospital from August 2021 to August 2022. A total of 576 hospitalized patients with diagnosis of COVID-19 infection were analyzed. AKI was …

Knowledge, Attitude And Practice Of Butchers Regarding Crimean Congo Hemorrhagic Fever In An Endemic Area Of Iran, Mohammad Amin Gorouhi, Abbas Aghaei Afshar, Najmeh Mansoori, Parya Jangipour Afshar, Leila Shirani-Bidabadi, Ismaeil Alizadeh, Nariman Shahhosseini

Chulalongkorn Medical Journal

Background: In endemic countries, Crimean-Congo hemorrhagic fever (CCHF) is an important zoonotic disease with significant public health implications. Previous studies in Iran suggests that CCHF poses a significant health risk to slaughterhouse workers and butchers. The main objecive of this study was to investigate the knowledge, attitude, and practice of butchers regarding CCHF at their workplace in an endemic area in southeastern Iran.

Methods: A descriptive cross-sectional study was conducted from January to March 2022 in Zarand city. In total, 60 butchers were included in the city. Statistical analysis was performed using SPSS version 22.

Results: The average scores of …

Impact Of The Rs1050757 C>T Variant In The 3'Utr Of The G6pd Gene On Mrna Structure And Mirna Binding In G6pd Deficiency: A Nanopore Minion Sequencing Study, Lawrence Billy Vasco Djama, Vorthon Sawaswong Ph.D., Prangwalai Chanchaem, Punchalee Mungkalasut Ph.D., Thanaporn Pimpakan, Poonlarp Cheepsunthorn Ph.D., Sunchai Payungporn Ph.D., Chalisa L. Cheepsunthorn Ph.D.

Chulalongkorn Medical Journal

Background: Glucose 6-phosphate dehydrogenase (G6PD) deficiency is a genetic disorder caused by impaired enzyme function or instability due to mutations in the G6PD gene, resulting in reduced enzyme activity. This study aimed to investigate mutations in the regulatory regions of the G6PD gene using Nanopore MinION sequencing to explore the potential impact of non-coding variants on G6PD activity.

Methods: Blood samples from 19 males (13 adults, 6 neonates) with G6PD deficiency or intermediate enzyme activity but unidentified coding sequence mutations were analysed. Genomic DNA was amplified using degenerate oligonucleotide-primed PCR (DOP-PCR) and sequenced with the Oxford Nanopore MinION platform. Bioinformatic …

Nickel Toxicity To Safflower Seed Germination And Seedling Morphoanatomy, Uğurcan Baran, Sude Tanik, Mert Can Vardar, Güray Ülger, Ahmet Aksoy

Turkish Journal of Botany

The safflowers (Carthamus tinctorius L. cv Olas) grown hydroponically under nickel (Ni) stress were examined in this study. T he effects of 0, 0.75, 1, 3, 5, 10, and 15 mM Ni on seed germination rate, protein, and pigment content of germinating seeds were investigated. Also, the toxicity of 0.75 mM Ni on plant growth, malondialdehyde (MDA) amount, and anatomy of 21-day-old safflower seedlings were studied. Ni adversely affected the germination rate, radicle length, protein, and pigment content of safflower seeds, particularly when higher than 3 mM. It also negatively affected the biomass production, plant length, leaf number, and MDA …

Habitat Determines The Effects Of Wild Ungulate Grazing On Soils: Case Studies From The Iberian Peninsula, Jennifer Adams Krumins, Shih-Chieh Chien, Ramon Perea, Emmanuel Antonio Serrano Ferron, Elena Baraza Ruiz, The Incremento Consortium

Department of Biology Faculty Scholarship and Creative Works

Background and Aims

The bidirectional relationship between plants and their soils can be disrupted by the influence of ungulate grazers. Indeed, herbivores affect plant productivity and above-ground community structure, and plants affect soil health and below-ground community structure. However, the effects of herbivory can be subtle and challenging to address experimentally, even in the case of relatively large ungulate grazers. We attempt to resolve this paradox and experimentally test effects of ungulate grazers in two case studies on the Spanish Iberian Peninsula.

Methods

At the two locations, we experimentally enclosed red deer (Cervus elaphus) at high and hyper …

Protective Role Of Salicylic Acid Against Abiotic Stresses In Horticultural Crops: A Review, Faisal Hayat, Xiaoyun Zhang, Mohammed Alyafei, Fareeha Shireen, Ummara Khan, Sumeera Asghar, Sezai̇ Erci̇şli̇, Karthishwaran Kandhan, Mohamed S. Sheteiwy, Yali Zhang, Xiaoyan Lu

Turkish Journal of Botany

Environmental stressors such as drought, floods, salinity, extreme temperatures, and heavy metal toxicity are major threats to horticultural plants because they disrupt plant physiological mechanisms, leading to reduced yield and quality. Salicylic acid (SA) is a plant hormone that regulates various physiological and biochemical functions in plants. Moreover, it regulates hormonal balance, enhances the absorption of essential nutrients, promotes photosynthesis and the production of antistress compounds, and improves stress resistance. This comprehensive review explains several physiological and biochemical activities that are affected by SA under stressful conditions, such as stomatal regulation, antioxidant defense systems, osmotic adjustment and gene expression regulation. …

Biochar Derived From Different Sources Ameliorates The Phytochemical And Physiological Characteristics Of Foxtail Millet (Setaria Italica) Under Water Stress, Mohammad Keshavarz, Ehsan Bijanzadeh, Hamid Reza Boostani

Turkish Journal of Botany

Organic material, such as biochar, can improve soil fertility and crop yield under water stress. A pot experiment was conducted to consider the effects of biochar on the pigment content, enzyme activity, physiological characteristics, and nutrient uptake of foxtail millet under water stress. Plants were tested under normal, mild, and severe irrigation regimes (100%, 75%, and 50% field capacity, respectively) using different biochar sources (licorice root biochar (LRB), cow manure biochar (CMB), cotton residue biochar (CRB), and municipal waste biochar (MWB)) and a control without fertilizer. Under severe water stress, the chlorophyll a content and total chlorophyll increased by 137.3% …

Enhancing Community Health Workers' Knowledge On Childhood Tuberculosis Screening In Nigeria, Rashidat A. Jolaoluwa

Biennial Convention (CONV)

Tuberculosis (TB) poses a significant global health challenge, especially in developing countries like Nigeria, where it disproportionately affects children. This Doctor of Nursing Practice (DNP) study seeks to enhance the knowledge of Community Health Workers (CHWs) and Community Health Extension Worker Students (CHEWs) in screening for childhood TB. Given the urgent need for early detection and intervention, the research focused on equipping CHWs and CHEWs with targeted educational resources. A pretest/posttest design was employed to evaluate changes in knowledge related to childhood TB screening among the participants. Statistical data analysis was conducted to assess improvements and ensure the reliability of …

Accelerating The Degradation Of Biodegradable Mulch Films In Soil And Compost Environments, Harshal Jayesh Kansara

Theses

The incomplete degradation of biodegradable mulch films (BMFs) in agricultural soils poses environmental challenges, with persistent plastic residues impacting soil health. This dissertation investigates the use of bioaugmentation with P. guariconensis to enhance BMF degradation under laboratory, raised bed, and field conditions. The research focuses on optimizing microbial delivery methods, evaluating the efficacy of drip and spray bioaugmentation techniques, and assessing mass loss as a primary metric for degradation. Laboratory experiments established proof-of-concept by demonstrating enhanced carbon mineralization, weight loss, and fragmentation of BMFs under bioaugmented conditions. These findings were translated to field-scale trials, where bioaugmentation treatments consistently outperformed untreated …

Flash Effect Is Diminished By Daily Fractionation Of Electron Rt In Mouse Skin, Aleksandra Ilina, William S. Thomas, Xu Cao, Matthew S. Reed, Kendall Jarvis, Albert Van Der Kogel, Nathaniel Van Asselt, Wesley S. Culberson, Brian W. Pogue

Dartmouth Scholarship

Objective. While FLASH radiotherapy is known to reduce skin damage in vivo from ultra-high dose rate (UHDR) irradiation relative to conventional dose rates (CDR), it is not clear whether this sparing is preserved when delivered as fractionated. This study was designed to directly assess whether three daily fractions would maintain the sparing effects in murine leg models and preserve the murine skin sparing with single fraction treatments. Approach. C57Bl/6j female mice were irradiated with 9 MeV UHDR and CDR beams from a FLASH-capable Mobetron system, in a dose escalation study with doses ranging from single dose 22–30 Gy in a …

Multimodal Cardiac Imaging Of Immune-Mediated Complications Post Heart Transplantation: A Contemporary Review, Bruno Bezerra Lima, Tam T Doan, Atilla Feher, James C Wilkinson, Marvin W Kronenberg, Chloe Carr, Malek Nayfeh, Tania Ruiz, Luke L Laws, Melissa Lou Silva, John A Wells, Leandro Slipczuk, Emily T Lippincott, John J Carr, Kaushik Amancherla, Cameron Henry, David Parra, Kelly Schlendorf, Quinn S Wells, Sean G Hughes, Jonathan Soslow

Faculty, Staff and Students Publications

Heart transplantation significantly enhances survival and quality of life for patients with end-stage heart failure. Despite advances in surgical and postoperative care, immune-mediated complications, acute graft rejection and cardiac allograft vasculopathy (CAV), remain major barriers to long-term success. Acute rejection predominantly affects early posttransplant survival, whereas CAV becomes a leading cause of mortality in later years. The gold standards for diagnosis, endomyocardial biopsy for rejection and coronary angiography for CAV, are invasive and imperfect. Noninvasive multimodality imaging is increasingly used to complement or, in selected scenarios, defer invasive testing. Echocardiography with strain detects early myocardial dysfunction when ejection fraction is …

Investigating The Neuronal Role Of The Proteasomal Atpase Subunit Gene Psmc5 In Neurodevelopmental Proteasomopathies, Sébastien Küry, Janelle E Stanton, Geeske M Van Woerden, Amélie Bosc-Rosati, Tzung-Chien Hsieh, Lise Bray, Marielle Oloudé, Cory Rosenfelt, Marie Pier Scott-Boyer, Victoria Most, Tianyun Wang, Jonas J Papendorf, Charlotte De Konink, Wallid Deb, Virginie Vignard, Maja Studencka-Turski, Thomas Besnard, Anna M Hajdukowicz, Franziska G Thiel, Sophie Wolfgramm, Laëtitia Florenceau, Silvestre Cuinat, Sylvain Marsac, Yann Verrès, Audrey Dangoumau, Léa Poirier, Ingrid M Wentzensen, Annabelle Tuttle, Cara Forster, Johanna Striesow, Richard Golnik, Damara Ortiz, Laura Jenkins, Jill A Rosenfeld, Alban Ziegler, Clara Houdayer, Dominique Bonneau, Erin Torti, Amber Begtrup, Kristin G Monaghan, Sureni V Mullegama, Catharina M L Nienke Volker-Touw, Koen L I Van Gassen, Renske Oegema, Mirjam S De Pagter, Katharina Steindl, Anita Rauch, Ivan Ivanovski, Kimberly Mcdonald, Emily Boothe, Andrew Dauber, Janice Baker, Noelle Andrea V Fabie, Raphael A Bernier, Tychele N Turner, Siddharth Srivastava, Kira A Dies, Lindsay C Swanson, Carrie Costin, Alali Abdulrazak, Rebekah K Jobling, John Pappas, Rachel Rabin, Dmitriy Niyazov, Anne Chun-Hui Tsai, Karen Kovak, David B Beck, May Christine V Malicdan, David R Adams, Lynne Wolfe, Rebecca D Ganetzky, Colleen C Muraresku, Davit Babikyan, Zdeněk Sedláček, Miroslava Hančárová, Andrew T Timberlake, Hind Al Saif, Berkley Nestler, Kayla King, M J Hajianpour, Gregory Costain, D'Arcy Prendergast, Chumei Li, David Geneviève, Antonio Vitobello, Arthur Sorlin, Christophe Philippe, Tamar Harel, Ori Toker, Ataf Sabir, Derek Lim, Mark J Hamilton, Lisa J Bryson, Elaine Cleary, Sacha Weber, Trevor L Hoffman, Anna M Cueto-González, Eduardo F Tizzano, David Gómez-Andrés, Marta Codina-Solà, Athina Ververi, Efterpi Pavlidou, Alexandros Lambropoulos, Kyriakos Garganis, Marlène Rio, Jonathan Levy, Sarah J Langas, Anne M Mcrae, Mathieu K Lessard, Maria Daniela D'Agostino, Isabelle De Bie, Meret Wegler, Rami Abou Jamra, Susanne B Kamphausen, Viktoria Bothe, Lorraine Potocki, Eric Olinger, Yves Sznajer, Elsa Wiame, Michelle L Thompson, Molly C Schroeder, Catherine Gooch, Raphael A Smith, Arti Pandya, Larissa M Busch, Uwe Völker, Elke Hammer, Kristian Wende, Benjamin Cogné, Bertrand Isidor, Jens Meiler, Clémentine Ripoll, Stéphanie Bigou, Frédéric Laumonnier, Peter W Hildebrand, Evan E Eichler, Kirsty Mcwalter, Peter M Krawitz, Florence Roux-Dalvai, Ype Elgersma, Julien Marcoux, Marie-Pierre Bousquet, Arnaud Droit, Jeremie Poschmann, Andreas M Grabrucker, Francois V Bolduc, Stéphane Bézieau, Frédéric Ebstein, Elke Krüger

Faculty, Staff and Students Publications

Neurodevelopmental proteasomopathies are a group of disorders caused by variants in proteasome subunit genes, that disrupt protein homeostasis and brain development through poorly characterized mechanisms. Here, we report 26 distinct variants in PSMC5, encoding the AAA⁺ ATPase subunit PSMC5/RPT6, in individuals with syndromic neurodevelopmental conditions. Combining genetic, multi-omics and biochemical approaches across cellular models and Drosophila, we unveil the essential role of proteasomes in sustaining key cellular processes. Loss of PSMC5/RPT6 function impairs proteasome activity, leading to protein aggregation, disruption of mitochondrial homeostasis, and dysregulation of lipid metabolism and immune signaling. It also compromises synaptic balance, neuritogenesis, and neural progenitor …

Transcription-Replication Collisions Trigger High-Fidelity Replication Reset, Matthew B Cooke, Kobie T Welch, Laura Deus Ramirez, Katelin M Hagstrom, Alice X Wen, Jennifer A Halliday, Susan M Rosenberg, Christophe Herman

Faculty, Staff and Students Publications

Double-stranded DNA ends arise from external agents or cellular processes like transcription-replication collisions (TRCs), threatening genome stability. Here, we performed genomic CRISPRi screens to uncover DNA end formation factors in Escherichia coli. We discovered that translation-transcription decoupling causes DNA end formation through a TRC-dependent pathway, which is lethal when DNA end processing by RecBCD is disrupted, but not when recombination is disrupted. We find that TRCs cause replisome stalling followed by "rear-ending" from trailing replisomes which generates free DNA ends, rather than strand breaks. Surprisingly, these DNA ends are resolved through a process we call "replication reset", where the stalled …

Dna Extrusion Size Determines Pathway Choice During Cag Repeat Expansion, Mayuri Bhatia, Ashutosh S. Phadte, Anna Lakhina, Anthony R. Monte Carloi Iii, Sarah Barndt, Anna Pluciennik

Department of Biochemistry and Molecular Biology Faculty Papers

DNA triplet repeat expansion causes several primarly neurological disorders like Huntington's disease, myotonic dystrophy type 1, and fragile-X related disorders. There is general consensus that recognition of extrahelical extrusions or hairpin-loop structures (formed by strand slippage) by the DNA mismatch repair protein MutSβ leads to repeat expansion by a mutagenic process. By contrast, the FAN1 nuclease attenuates triplet repeat expansion, the molecular basis of which was explained by our recent finding that FAN1 nuclease cleaves and initiates removal of extrahelical extrusions. Here we show that extrusions containing two or more triplet repeats are subject to recognition and processing by either …

Cover And Conents

Turkish Journal of Botany

No abstract provided.