Digital Commons Network^™

Enhancing History Education With Google Notebooklm: Case Study Of Mary Easton Sibley’S Diary For Multimedia Content And Podcast Creation, Paul Huffman, James Hutson

Faculty Scholarship

This article explores new features of Google’s NotebookLM, an AI-powered tool designed for advanced document analysis and educational content generation. Tested on the 92-page transcribed diary of Mary Easton Sibley, the founder of Lindenwood University, NotebookLM effectively generated FAQs, a study guide, a table of contents, a briefing document, and an audio overview in podcast format. By transforming static historical documents into dynamic learning materials, the document-based AI model provides a user-friendly interface for educators and students, especially those without experience in audio editing or podcasting. While successful in creating study guides and audio formats, the tool faced challenges in …

Pigments: The Bridge Of Disciplines, Candace Gwyther

Postgraduate

This practice-based research explores the intersection of oil painting and ceramics, highlighting the shared techniques and methods that bridge these two disciplines. By using common pigments and integrating cross-disciplinary approaches, this study demonstrates how each discipline can inform and enhance the other, leading to the creation of an innovative and adaptable medium that seamlessly functions within both ceramics and painting. This interdisciplinary approach challenges traditional boundaries, opening new pathways for creative expression where technical material manipulation intersects with the broader narrative of my artistic practice. Grounded in foundational theories such as path making, meshwork, play, and bricolage, the research culminates …

Reformed Worship (Rw) 153 - Advent / Christmas (September 2024), Reformed Worship Editors

Reformed Worship Magazine

Editorial: The Bending-Down God by Joyce Borger....2

Advent and Mission by Kevin Schutte....3

Worship Series: Reckless Inclusivity by Ruth Ann Schuringa....7

The Plan by Bethany Besteman....13

A Case for Intergenerational Worship by Lindsey Goetz....19

Q&A: Why Sing? by Paul Ryan....23

Songs for the Season: Building Bridges through Congregational Song by James MacMillan....25

Reflections for Timket by Vince Bantu....30

The Troubles by Karen Campbell....33

A Litany for a Sad Church by Johnathan Scott Sumner....38

For Pastors: The Christmas Mission by Scott Hoezee....39

Worship Series: The Gifts of Christmas by Kyle …

Analysis And Conservation Of A 19th Century Automaton, Elisse D. Brautigam

Art Conservation Master's Projects

A late 19th century automaton, Madame La Doll, in the collections of the Buffalo History Museum ceased functioning recently, with the only recorded documentation of the object in motion stored on a DVD. Research was undertaken to provide provenance and authentication of museum records. Examination, digital photographic, and video documentation were done. Materials analysis using ultraviolet induced visible fluorescence, digital capture X-radiography, transmission Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), and FFMPEG were undertaken to characterize all object and video materials employed, identify alterations and repairs as well as provide information relevant to the study and display of …

Not So Cavalier: Technical Study And Conservation Treatment Of A Potential 17th Century Anglo-Dutch Military Portrait Painting, Josephine Ren

Art Conservation Master's Projects

A potential 17^th century Anglo-Dutch military portrait painting from the Memorial Art Gallery at the University of Rochester in Rochester, New York arrived at the Garman Art Conservation Department at Buffalo State University for conservation research and treatment in 2022. The painting’s title, date, and artist were unknown and the subject was initially referred to as a “17^th Century Dutch Cavalier.” Little information existed on the provenance and history of the artwork. The painting was in a state of structural instability and aesthetic disfigurement and showed evidence of a past restoration campaign. This master’s project attempted to broadly …

Weak-Willed Legislatures And Statutory Interpretation, Helen Zhao

University of Chicago Law Review

Not all statutes are created equal. Contributing to the literature on “super statutes,” I suggest that an analogy to the philosophical concept of weakness of will can illuminate circumstances under which some statutes ought to stand above others. Analogizing to philosopher Richard Holton’s account of weak will, I develop an account in which some statutes express long-term commitments, are intended to foreclose future deliberation, and enact reasons into the law. Such statutes have the status of what Holton calls “resolutions.” Like an individual resolving to stop eating meat, yet finding themself unable to resist, Congress can be weak willed when …

Behind Armor Blunt Trauma: Liver Injuries Using A Live Animal Model, Narayan Yoganandan, Alok Shah, Brian D. Stemper, Lewis Somber, Valeta Carol Chancey, Joseph Mcentire

Biomedical Engineering Faculty Research and Publications

Introduction

While the 44-mm clay penetration criterion was developed in the 1970s for soft body armor applications, and the researchers acknowledged the need to conduct additional tests, the same behind the armor blunt trauma displacement limit is used for both soft and hard body armor evaluations and design considerations. Because the human thoraco-abdominal contents are heterogeneous, have different skeletal coverage, and have different functional requirements, the same level of penetration limit does not imply the same level of protection. It is important to determine the regional responses of different thoraco-abdominal organs to better describe human tolerance and improve the current …

Noise Leads To The Perceived Increase In Evolutionary Rates Over Short Time Scales, Brian C. O'Meara, Jeremy M. Beaulieu

Biological Sciences Faculty Publications and Presentations

Across a variety of biological datasets, from genomes to conservation to the fossil record, evolutionary rates appear to increase toward the present or over short time scales. This has long been seen as an indication of processes operating differently at different time scales, even potentially as an indicator of a need for new theory connecting macroevolution and microevolution. Here we introduce a set of models that assess the relationship between rate and time and demonstrate that these patterns are statistical artifacts of time-independent errors present across ecological and evolutionary datasets, which produce hyperbolic patterns of rates through time. We show …

Diverse Origins Of Near-Identical Antifreeze Proteins In Unrelated Fish Lineages Provide Insights Into Evolutionary Mechanisms Of New Gene Birth And Protein Sequence Convergence, Nathan Rives, Vinita Lamba, C.H. Christina Cheng, Xuan Zhuang

Biological Sciences Faculty Publications and Presentations

Determining the origins of novel genes and the mechanisms driving the emergence of new functions is challenging yet crucial for understanding evolutionary innovations. Recently evolved fish antifreeze proteins (AFPs) offer a unique opportunity to explore these processes, particularly the near-identical type I AFP (AFPI) found in four phylogenetically divergent fish taxa. This study tested the hypothesis of protein sequence convergence beyond functional convergence in three unrelated AFPI-bearing fish lineages. Through comprehensive comparative analyses of newly sequenced genomes of winter flounder and grubby sculpin, along with available high-quality genomes of cunner and 14 other related species, the study revealed that near-identical …

Dominant Missense Variants In Srebf2 Are Associated With Complex Dermatological, Neurological, And Skeletal Abnormalities, Matthew J Moulton, Kristhen Atala, Yiming Zheng, Debdeep Dutta, Dorothy K Grange, Wen-Wen Lin, Daniel J Wegner, Jennifer A Wambach, Angela L Duker, Michael B Bober, Lisa Kratz, Carol A Wise, Ila Oxendine, Anas Khanshour, Undiagnosed Diseases Network, Michael F Wangler, Shinya Yamamoto, F Sessions Cole, Jonathan Rios, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Purpose: We identified 2 individuals with de novo variants in SREBF2 that disrupt a conserved site 1 protease (S1P) cleavage motif required for processing SREBP2 into its mature transcription factor. These individuals exhibit complex phenotypic manifestations that partially overlap with sterol regulatory element binding proteins (SREBP) pathway-related disease phenotypes, but SREBF2-related disease has not been previously reported. Thus, we set out to assess the effects of SREBF2 variants on SREBP pathway activation.

Methods: We undertook ultrastructure and gene expression analyses using fibroblasts from an affected individual and utilized a fly model of lipid droplet (LD) formation to investigate the consequences …

The Cerebellum Modulates Thirst, Ila Mishra, Bing Feng, Bijoya Basu, Amanda M Brown, Linda H Kim, Tao Lin, Mir Abbas Raza, Amelia Moore, Abigayle Hahn, Samantha Bailey, Alaina Sharp, Juan C Bournat, Claire Poulton, Brian Kim, Amos Langsner, Aaron Sathyanesan, Roy V Sillitoe, Yanlin He, Atul R Chopra

Duncan NRI Faculty and Staff Publications

The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin's dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by …

Mondoa And Aki And Aki-To-Ckd Transition, Shihomi Maeda, Shinsuke Sakai, Yoshitsugu Takabatake, Takeshi Yamamoto, Satoshi Minami, Jun Nakamura, Tomoko Namba-Hamano, Atsushi Takahashi, Jun Matsuda, Hiroaki Yonishi, Sho Matsui, Atsuhiro Imai, Ryuya Edahiro, Hitomi Yamamoto-Imoto, Isao Matsui, Seiji Takashima, Ryoichi Imamura, Norio Nonomura, Motoko Yanagita, Yukinori Okada, Andrea Ballabio, Shuhei Nakamura, Tamotsu Yoshimori, Yoshitaka Isaka

Duncan NRI Faculty and Staff Publications

Key Points:

1. The expression of MondoA was decreased in the renal tubules of patients with CKD.

2. Genetic ablation of MondoA in proximal tubules inhibited autophagy and increased vulnerability to AKI through increased expression of Rubicon.

3. MondoA ablation during the recovery phase after ischemia-reperfusion aggravated kidney injury through downregulation of the transcription factor EB-peroxisome proliferator-activated receptor-γ coactivator-1α axis.

Background: Elderly individuals and patients with CKD are at a higher risk of AKI. The transcription factor MondoA is downregulated in the kidneys of aged individuals or patients with AKI; however, its roles in AKI development and the AKI-to-CKD transition remain …

Insights Into The Biocompatibility Of Biodegradable Metallic Molybdenum For Cardiovascular Applications-A Critical Review, Janina Mayers, Brianna Hofman, Indie Sobiech, Maria Kwesiga

Open Access Publishing Support Funded Articles

Atherosclerotic cardiovascular disease (ACD) is the leading cause of death worldwide. The gold standard of treatment is the implantation of a permanent stent implant that is often associated with complications such as thrombus formation, vascular neointimal response, and stent fracture, which altogether decrease the long-term safety and efficacy of the stent. Biodegradable metallic materials have become an attractive alternative because of the ability to facilitate a more physiological healing response while the metal degrades. Recently, Molybdenum (Mo) has been considered as a potential candidate due to its excellent mechanical and medical imaging properties. Moreover, the biomedical research studies performed to …

Consequences Of Local Conspecific Density Effects For Plant Diversity And Community Dynamics, Joseph A. Lamanna, Stefan A. Schnitzer

Biological Sciences Faculty Research and Publications

Conspecific density dependence (CDD) in plant populations is widespread, most likely caused by local-scale biotic interactions, and has potentially important implications for biodiversity, community composition, and ecosystem processes. However, progress in this important area of ecology has been hindered by differing viewpoints on CDD across subfields in ecology, lack of synthesis across CDD-related frameworks, and misunderstandings about how empirical measurements of local CDD fit within the context of broader ecological theories on community assembly and diversity maintenance. Here, we propose a conceptual synthesis of local-scale CDD and its causes, including species-specific antagonistic and mutualistic interactions. First, we compare and clarify …

Targeting Nuclear Receptor Coactivator Src-1 Prevents Colorectal Cancer Immune Escape By Reducing Transcription And Protein Stability Of Pd-L1, Yilin Hong, Qiang Chen, Zinan Wang, Yong Zhang, Bei Li, Hanshi Guo, Chuanzhong Huang, Xu Kong, Pingli Mo, Nengming Xiao, Jianming Xu, Yunbin Ye, Chundong Yu

Faculty, Staff and Students Publications

Programmed death-ligand 1 (PD-L1) is overexpressed in multiple cancers and critical for their immune escape. It has previously shown that the nuclear coactivator SRC-1 promoted colorectal cancer (CRC) progression by enhancing CRC cell viability, yet its role in CRC immune escape is unclear. Here, we demonstrate that SRC-1 is positively correlated with PD-L1 in human CRC specimens. SRC-1 deficiency significantly inhibits PD-L1 expression in CRC cells and retards murine CRC growth in subcutaneous grafts by enhancing CRC immune escape via increasing tumor infiltration of CD8

Death-Associated Protein Kinase 3 Modulates Migration And Invasion Of Triple-Negative Breast Cancer Cells, Junkai Wang, Anh M Tran-Huynh, Beom-Jun Kim, Doug W Chan, Matthew V Holt, Diana Fandino, Xin Yu, Xiaoli Qi, Jin Wang, Weijie Zhang, Yi-Hsuan Wu, Meenakshi Anurag, Xiang H F Zhang, Bing Zhang, Chonghui Cheng, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Sixteen patient-derived xenografts (PDXs) were analyzed using a mass spectrometry (MS)-based kinase inhibitor pull-down assay (KIPA), leading to the observation that death-associated protein kinase 3 (DAPK3) is significantly and specifically overexpressed in the triple-negative breast cancer (TNBC) models. Validation studies confirmed enrichment of DAPK3 protein, in both TNBC cell lines and tumors, independent of mRNA levels. Genomic knockout of DAPK3 in TNBC cell lines inhibited in vitro migration and invasion, along with down-regulation of an epithelial–mesenchymal transition (EMT) signature, which was confirmed in vivo. The kinase and leucine-zipper domains within DAPK3 were shown by a mutational analysis to be essential …

Local Anesthetic Systemic Toxicity In Pregnancy: A Retrospective Cohort Analysis, Micah K De Valle, Michael Adkison, Ruhi Maredia, Cooper Stevenson, Shobana Murugan

Faculty, Staff and Students Publications

Introduction: Local anesthetic systemic toxicity (LAST) is a rare complication of regional anesthesia. Pregnancy is a risk factor due to gestational physiologic changes. Labor and disorders of pregnancy can mask or delay symptoms of LAST, slowing appropriate intervention. This study examines LAST within a larger cohort and identifies features that help distinguish LAST in pregnant women from LAST in nonpregnant patients.

Methods: The TriNetX database was used to compare pregnant and nonpregnant patients with LAST from 2013 to 2023. Cohorts were matched on age, race, obesity status, diabetes, metabolic disorders, local anesthetic type, and cardiovascular, liver, kidney, and respiratory disease. …

Repeat Modules And N-Linked Glycans Define Structure And Antigenicity Of A Critical Enterotoxigenic E. Coli Adhesin, Zachary T. Berndsen, Marjahan Akhtar, Mahima Thapa, Tim J. Vickers, Aaron Schmitz, Pardeep Kumar, Nazia Khatoon, Alaullah Sheikh, Melissa Hamrick, Jackson S. Turner, Ali H. Ellebedy, James M. Fleckenstein, Et Al.

2020-Current year OA Pubs

Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of cases of infectious diarrhea annually, predominantly in children from low-middle income regions. Notably, in children, as well as volunteers challenged with ETEC, diarrheal severity is significantly increased in blood group A (bgA) individuals. EtpA, is a secreted glycoprotein adhesin that functions as a blood group A lectin to promote critical interactions between ETEC and blood group A glycans on intestinal epithelia for effective bacterial adhesion and toxin delivery. EtpA is highly immunogenic resulting in robust antibody responses following natural infection and experimental challenge of volunteers with ETEC. To understand how EtpA …

Spatial Single-Cell Isotope Tracing Reveals Heterogeneity Of De Novo Fatty Acid Synthesis In Cancer, Elena Buglakova, Måns Ekelöf, Michaela Schwaiger-Haber, Lisa Schlicker, Martijn R Molenaar, Mohammed Shahraz, Lachlan Stuart, Andreas Eisenbarth, Volker Hilsenstein, Gary J Patti, Almut Schulze, Marteinn T Snaebjornsson, Theodore Alexandrov

2020-Current year OA Pubs

While heterogeneity is a key feature of cancer, understanding metabolic heterogeneity at the single-cell level remains a challenge. Here we present

Rhesus Rotavirus Nsp1 Mediates Extra-Intestinal Infection And Is A Contributing Factor For Biliary Obstruction, Enkai Li, Ningguo Feng, Qiru Zeng, Liliana Sanchez-Tacuba, Takahiro Kawagishi, Grace Branham, Gaopeng Hou, Zemin Wang, Harry B. Greenberg, Siyuan Ding

2020-Current year OA Pubs

We previously demonstrated that in Ifnar1-/-Ifngr1-/- or Stat1-/- suckling mice lacking intact type I and type II interferon (IFN) signaling, rhesus rotavirus (RRV) infection causes a lethal disease with clinical manifestations similar to biliary atresia, including acholic stools, oily fur, growth retardation, and excess mortality. Elevated levels of viral RNA are detected in the bile ducts and liver of diseased pups together with severe inflammatory responses in these tissues. However, the viral determinants and the molecular mechanisms driving this process remain incompletely understood. Using an optimized rotavirus (RV) reverse genetics system, we generated a panel of recombinant RVs that encode …

Tissue-Specific Features Of Innate Lymphoid Cells In Antiviral Defense, Sytse J Piersma

2020-Current year OA Pubs

Innate lymphocytes (ILCs) rapidly respond to and protect against invading pathogens and cancer. ILCs include natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer (LTi) cells and include type I, type II, and type III immune cells. While NK cells have been well recognized for their role in antiviral immunity, other ILC subtypes are emerging as players in antiviral defense. Each ILC subset has specialized functions that uniquely impact the antiviral immunity and health of the host depending on the tissue microenvironment. This review focuses on the specialized functions of each ILC subtype and their roles in antiviral …

A Novel Antigen Biomarker For Detection Of High-Level Of Loa Loa Microfilaremia, Sarah E Greene, Yuefang Huang, Kerstin Fischer, Bruce A. Rosa, John Martin, Makedonka Mitreva, Devyn Yates, Samuel Wanji, Joseph Kamgno, Philip J. Budge, Gary J. Weil, Peter U. Fischer

2020-Current year OA Pubs

BACKGROUND: Loiasis is a disease caused by the nematode Loa loa. Serious adverse events sometimes occur in people with heavy L. loa microfilaremia after ivermectin treatment. In regions of Central Africa where loiasis is endemic, this significantly impedes global elimination programs for lymphatic filariasis and onchocerciasis that use mass distribution of ivermectin. Improved diagnostic tests to identify individuals at increased risk of serious adverse events could facilitate efforts to eliminate lymphatic filariasis and onchocerciasis in this region.

METHODS AND FINDINGS: We previously identified the L. loa protein Ll-Bhp-1 in loiasis patient sera. Here, we further characterize Ll-Bhp-1 and report development …

Reclaiming Healing Spaces: A Phenomenological Study On The Transformative Power Of Outdoor Therapy From The Lived Experiences Of Black Clinicians Working With Black Clients, Lynn Murphy

Dissertations

This phenomenological study involved assessing the experiences of Black therapists who engaged Black clients in outdoor therapeutic contexts. The study was founded on the existing literature that shows the quality of the therapeutic relationship is pivotal for client retention and the Western standards that have historically favored treatment within indoor environments. To contextualize this research, a comprehensive literature review was commenced, covering topics such as the decolonization of therapy, the historical and present-day relationship between Blacks and the outdoors in the United States, sedentary lifestyles, the psychological benefits of time spent in nature, various types of outdoor therapy, and the …

Iron Accumulation And Metabolic Alterations In Aneurysmal Subarachnoid Hemorrhage, Gardenia Pacheco, Joao A Gomes, Kevin Cho, Daniel L Morris, Maddison I Segal, Kayla R Adkins-Travis, Ethan Stancliffe, Gary J Patti, Christopher J Ziegler, Leah P Shriver

2020-Current year OA Pubs

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of stroke that is associated with poor outcome. A subset of patients with aSAH will develop secondary complications, most notably delayed cerebral ischemia (DCI), which potentiates neurological injury. In this study, we investigate the relationship between cerebrospinal fluid (CSF) iron accumulation, brain metabolism, and neuronal injury in patients with aSAH with or without DCI.

METHODS: We collected longitudinal CSF samples of patients immediately after hospitalization and 5 to 8 days after onset of ictus. CSF was analyzed with electron paramagnetic resonance spectroscopy and metabolomics to determine the presence of redox-active iron …

Reduced Guanidinoacetate In Plasma Of Patients With Autosomal Dominant Fanconi Syndrome Due To Heterozygous P341l Gatm Variant And Study Of Organoids Towards Treatment, Ignacio Portales-Castillo, Rhea Singal, Jong Hee Song, Minsoo Son, Young Ah Goo, Ariella Coler-Reilly, Benjamin D Humphreys, Roberto Civitelli, Et Al.

2020-Current year OA Pubs

Autosomal dominant Fanconi syndrome due to a

Shareholder Agreements In India: An Unsettled Jurisprudence., Vikramaditya S. Khanna

Book Chapters

Shareholder agreements (SAs) are becoming more common around the world as the ownership of companies become more concentrated. Larger investors— in particular, private equity investors— often document their understandings about their investments in increasingly sophisticated SAs. India has also witnessed a rise in SAs, usually with foreign private equity players, which reflects a level of sophistication and formality in contract negotiations that was not always present when such agreements were between family or affinity groups. This has placed increasing pressure on Indian case law to evolve in response to these agreements.

This chapter explores that response and finds that it …

Tauroursodeoxycholic Acid Ameliorates Renal Injury Induced By Col4a3 Mutation, Shuwen Yu, Teija Suhas, Meei-Hua Lin, Jeffrey H Miner, Et Al.

2020-Current year OA Pubs

COL4A3/A4/A5 mutations have been identified as critical causes of Alport syndrome and other genetic chronic kidney diseases. However, the underlying pathogenesis remains unclear, and specific treatments are lacking. Here, we constructed a transgenic Alport syndrome mouse model by generating a mutation (Col4a3 p.G799R) identified previously from one large Alport syndrome family into mice. We observed that the mutation caused a pathological decrease in intracellular and secreted collagen IV α3α4α5 heterotrimers. The mutant collagen IV α3 chains abnormally accumulated in the endoplasmic reticulum and exhibited defective secretion, leading to persistent endoplasmic reticulum stress in vivo and in vitro. RNA-seq analysis revealed …

Mutant Nrf2e79q Enhances The Promotion And Progression Of A Subset Of Oncogenic Ras Keratinocytes And Skin Tumors, John G Witherspoon, Jonathan R Hall, Dereje Jima, Hannah M Atkins, Nathan T Wamsley, Michael B Major, Bernard E Weissman, Robert C Smart

2020-Current year OA Pubs

Squamous cell carcinomas (SCCs), including lung, head & neck, bladder, and skin SCCs often display constitutive activation of the KEAP1-NRF2 pathway. Constitutive activation is achieved through multiple mechanisms, including activating mutations in NFE2L2 (NRF2). To determine the functional consequences of Nrf2 activation on skin SCC development, we assessed the effects of mutant Nrf2

An Interpretable Machine Learning-Based Cerebrospinal Fluid Proteomics Clock For Predicting Age Reveals Novel Insights Into Brain Aging, Justin Melendez, Yun Ju Sung, Miranda Orr, Andrew Yoo, Suzanne Schindler, Carlos Cruchaga, Randall Bateman

2020-Current year OA Pubs

Machine learning can be used to create "biologic clocks" that predict age. However, organs, tissues, and biofluids may age at different rates from the organism as a whole. We sought to understand how cerebrospinal fluid (CSF) changes with age to inform the development of brain aging-related disease mechanisms and identify potential anti-aging therapeutic targets. Several epigenetic clocks exist based on plasma and neuronal tissues; however, plasma may not reflect brain aging specifically and tissue-based clocks require samples that are difficult to obtain from living participants. To address these problems, we developed a machine learning clock that uses CSF proteomics to …

A Damaging Col6a3 Variant Alters The Mir31hg-Regulated Response Of Chondrocytes In Neocartilage Organoids To Hyperphysiologic Mechanical Loading, Niek Gc Bloks, Zainab Harissa, Giorgia Mazzini, Shaunak S Adkar, Amanda R Dicks, Ghazaleh Hajmousa, Nancy Steward, Roman I Koning, Aat Mulder, Berend B R De Koning, Margreet Kloppenburg, Rodrigo Coutinho De Almeida, Yolande Fm Ramos, Farshid Guilak, Ingrid Meulenbelt

2020-Current year OA Pubs

The pericellular matrix (PCM), with its hallmark proteins collagen type VI (COLVI) and fibronectin (FN), surrounds chondrocytes and is critical in transducing the biomechanical cues. To identify genetic variants that change protein function, exome sequencing is performed in a patient with symptomatic OA at multiple joint sites. A predicted damaging variant in COL6A3 is identified and introduced by CRISPR-Cas9 genome engineering in two established human induced pluripotent stem cell-derived in-vitro neocartilage organoid models. The downstream effects of the COL6A3 variant on the chondrocyte phenotypic state are studied by a multi-omics (mRNA and lncRNA) approach in interaction with hyper-physiological mechanical loading …