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Articles 1651 - 1680 of 20211

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Identification Of Lysosomal Lipolysis As An Essential Noncanonical Mediator Of Adipocyte Fasting And Cold-Induced Lipolysis, Yu-Sheng Yeh, Trent D. Evans, Mari Iwase, Se-Jin Jeong, Arick Park, Ali Ghasemian, Borna Dianati, Ali Javaheri, Et Al. Mar 2025

Identification Of Lysosomal Lipolysis As An Essential Noncanonical Mediator Of Adipocyte Fasting And Cold-Induced Lipolysis, Yu-Sheng Yeh, Trent D. Evans, Mari Iwase, Se-Jin Jeong, Arick Park, Ali Ghasemian, Borna Dianati, Ali Javaheri, Et Al.

2020-Current year OA Pubs

Adipose tissue lipolysis is the process by which triglycerides in lipid stores are hydrolyzed into free fatty acids (FFAs), serving as fuel during fasting or cold-induced thermogenesis. Although cytosolic lipases are considered the predominant mechanism of liberating FFAs, lipolysis also occurs in lysosomes via lysosomal acid lipase (LIPA), albeit with unclear roles in lipid storage and whole-body metabolism. We found that adipocyte LIPA expression increased in adipose tissue of mice when lipolysis was stimulated during fasting, cold exposure, or β-adrenergic agonism. This was functionally important, as inhibition of LIPA genetically or pharmacologically resulted in lower plasma FFAs under lipolytic conditions. …


The Gain-Of-Function Ube3aq588e Variant Causes Angelman-Like Neurodevelopmental Phenotypes In Mice, Kellan P Weston, Anna M Gunelson, Susan E Maloney, Xia Ge, Jalin A Stelzer, Kwang-Soo Kim, Shylyn Collier, Marissa M Mindt, Megan J Agajanian, Michael B Major, Dennis Goldfarb, Kevin K Noguchi, Jason J Yi Mar 2025

The Gain-Of-Function Ube3aq588e Variant Causes Angelman-Like Neurodevelopmental Phenotypes In Mice, Kellan P Weston, Anna M Gunelson, Susan E Maloney, Xia Ge, Jalin A Stelzer, Kwang-Soo Kim, Shylyn Collier, Marissa M Mindt, Megan J Agajanian, Michael B Major, Dennis Goldfarb, Kevin K Noguchi, Jason J Yi

2020-Current year OA Pubs

Mutations in the E3 ubiquitin ligase UBE3A that cause enzymatic gain-of-function result in disease phenotypes which differ from classic Angelman syndrome. However, these phenotypes are highly heterogeneous raising questions about the mechanistic basis of such phenotypic diversity. Here, we characterize a mouse model harboring a Ube3a


Matrix Metalloproteinases Accelerate Pericellular Matrix Breakdown And Disrupt Mechanotransduction In Osteoarthritis, Jule Nieuwstraten, Rosa Riester, Ulf Krister Hofmann, Farshid Guilak, Marina Danalache Mar 2025

Matrix Metalloproteinases Accelerate Pericellular Matrix Breakdown And Disrupt Mechanotransduction In Osteoarthritis, Jule Nieuwstraten, Rosa Riester, Ulf Krister Hofmann, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

The pericellular matrix (PCM) is a specialized, narrow matrix surrounding each chondrocyte in articular cartilage, together constituting the chondron - the fundamental metabolic and functional unit of cartilage. The PCM plays a vital role in mediating biomechanical and biochemical signals essential for chondrocyte function. In osteoarthritis (OA), a chronic joint disorder characterized by progressive cartilage degradation, the PCM is one of the earliest sites of catabolic degradation, primarily driven by matrix metalloproteinases (MMPs). This study aims to investigate the functional relationship between PCM degradation and chondrocyte mechanosignaling, with an emphasis on MMP-driven changes in mechanotransduction in osteoarthritic cartilage. Human chondrons …


Apc/C-Mediated Ubiquitylation Of Extranucleosomal Histone Complexes Lacking Canonical Degrons, Aleksandra Skrajna, Kyle M Lapak, Anh Nguyen, Dennis Goldfarb, Et Al. Mar 2025

Apc/C-Mediated Ubiquitylation Of Extranucleosomal Histone Complexes Lacking Canonical Degrons, Aleksandra Skrajna, Kyle M Lapak, Anh Nguyen, Dennis Goldfarb, Et Al.

2020-Current year OA Pubs

Non-degradative histone ubiquitylation plays a myriad of well-defined roles in the regulation of gene expression and choreographing DNA damage repair pathways. In contrast, the contributions of degradative histone ubiquitylation on genomic processes has remained elusive. Recently, the APC/C has been shown to ubiquitylate histones to regulate gene expression in pluripotent cells, but the molecular mechanism is unclear. Here we show that despite directly binding to the nucleosome through subunit APC3, the APC/C is unable to ubiquitylate nucleosomal histones. In contrast, extranucleosomal H2A/H2B and H3/H4 complexes are broadly ubiquitylated by the APC/C in an unexpected manner. Using a combination of cryo-electron …


Reprogramming Aerobic Metabolism Mitigates Streptococcus Pyogenes Tissue Damage In A Mouse Necrotizing Skin Infection Model, Wei Xu, Tara R Bradstreet, Zongsen Zou, Suzanne Hickerson, Yuan Zhou, Hongwu He, Brian T Edelson, Michael G Caparon Mar 2025

Reprogramming Aerobic Metabolism Mitigates Streptococcus Pyogenes Tissue Damage In A Mouse Necrotizing Skin Infection Model, Wei Xu, Tara R Bradstreet, Zongsen Zou, Suzanne Hickerson, Yuan Zhou, Hongwu He, Brian T Edelson, Michael G Caparon

2020-Current year OA Pubs

Disease tolerance is a host response to infection that limits collateral damage to host tissues while having a neutral effect on pathogen fitness. Previously, we found that the pathogenic lactic acid bacterium Streptococcus pyogenes manipulates disease tolerance using its aerobic mixed-acid fermentation pathway via the enzyme pyruvate dehydrogenase, but the microbe-derived molecules that mediate communication with the host's disease tolerance pathways remain elusive. Here we show in a murine model that aerobic mixed-acid fermentation inhibits the accumulation of inflammatory cells including neutrophils and macrophages, reduces the immunosuppressive cytokine interleukin-10, and delays bacterial clearance and wound healing. In infected macrophages, the …


High-Throughput Repurposing Screen Reveals Compounds With Activity Against Toxoplasma Gondii Bradyzoites, Taher Uddin, Jing Xia, Yong Fu, Case W Mcnamara, Arnab K Chatterjee, L David Sibley Mar 2025

High-Throughput Repurposing Screen Reveals Compounds With Activity Against Toxoplasma Gondii Bradyzoites, Taher Uddin, Jing Xia, Yong Fu, Case W Mcnamara, Arnab K Chatterjee, L David Sibley

2020-Current year OA Pubs

No abstract provided.


Proteome-Wide Analysis Of Autoantibodies In Open-Angle Glaucoma In Japanese Population: A Pilot Study, Naoko Takada, Yukitoshi Izumi, Charles F Zorumski, Et Al. Mar 2025

Proteome-Wide Analysis Of Autoantibodies In Open-Angle Glaucoma In Japanese Population: A Pilot Study, Naoko Takada, Yukitoshi Izumi, Charles F Zorumski, Et Al.

2020-Current year OA Pubs

No abstract provided.


Altered Joint Forces Found In Symptomatic Dysplastic Hips In Women During Sport-Specific Activities, Molly C Shepherd, Rannon Huo, John C Clohisy, Jeffrey J Nepple, Michael Harris Mar 2025

Altered Joint Forces Found In Symptomatic Dysplastic Hips In Women During Sport-Specific Activities, Molly C Shepherd, Rannon Huo, John C Clohisy, Jeffrey J Nepple, Michael Harris

2020-Current year OA Pubs

BACKGROUND: Many patients with developmental dysplasia of the hip (DDH) are young and highly active but often become limited by activity-induced pain. Characterizing how the abnormal bony geometry of DDH affects hip joint loading and multiplanar kinematics during sport-specific motions relevant to active patients may provide insight into injury mechanisms and inform optimal treatment options.

PURPOSE/HYPOTHESIS: The purpose of this study was to determine how hip joint loading and kinematics are altered in DDH during 2 common sport activities: running and multidirectional hop-cutting. It was hypothesized that superior and medial joint-reaction forces (JRFs) would be elevated during running and that …


C10-Benzoate Esters Of Anhydrotetracycline Inhibit Tetracycline Destructases And Recover Tetracycline Antibacterial Activity, Emily E Williford, Yao-Peng Xue, Wai Kwan Tang, Ruihao Li, Katherine V Jones, Kevin S Blake, Helen C Blaine, Xiang Lian, Christina L Stallings, Niraj H Tolia, Gautam Dantas, Timothy A Wencewicz Mar 2025

C10-Benzoate Esters Of Anhydrotetracycline Inhibit Tetracycline Destructases And Recover Tetracycline Antibacterial Activity, Emily E Williford, Yao-Peng Xue, Wai Kwan Tang, Ruihao Li, Katherine V Jones, Kevin S Blake, Helen C Blaine, Xiang Lian, Christina L Stallings, Niraj H Tolia, Gautam Dantas, Timothy A Wencewicz

2020-Current year OA Pubs

Tetracyclines (TCs) are an important class of antibiotics threatened by enzymatic inactivation. These tetracycline-inactivating enzymes, also known as tetracycline destructases (TDases), are a subfamily of class A flavin monooxygenases (FMOs) that catalyze hydroxyl group transfer and oxygen insertion (Baeyer-Villiger type) reactions on TC substrate scaffolds. Semisynthetic modification of TCs (e.g., tigecycline, omadacycline, eravacycline, and sarecycline) has proven effective in evading certain resistance mechanisms, such as ribosomal protection and efflux, but does not protect against TDase-mediated resistance. Here, we report the design, synthesis, and evaluation of a new series of 22 semisynthetic TDase inhibitors that explore D-ring substitution of anhydrotetracycline (aTC) …


Expression Of A Single Inhibitory Member Of The Ly49 Receptor Family Is Sufficient To License Nk Cells For Effector Functions, Sytse J Piersma, Shasha Li, Pamela Wong, Michael D Bern, Jennifer Poursine-Laurent, Li-Ping Yang, Diana L Beckman, Bijal A Parikh, Wayne M Yokoyama Mar 2025

Expression Of A Single Inhibitory Member Of The Ly49 Receptor Family Is Sufficient To License Nk Cells For Effector Functions, Sytse J Piersma, Shasha Li, Pamela Wong, Michael D Bern, Jennifer Poursine-Laurent, Li-Ping Yang, Diana L Beckman, Bijal A Parikh, Wayne M Yokoyama

2020-Current year OA Pubs

Natural killer (NK) cells recognize target cells through germline-encoded activation and inhibitory receptors enabling effective immunity against viruses and cancer. The Ly49 receptor family in the mouse and killer immunoglobin-like receptor family in humans play a central role in NK cell immunity through recognition of major histocompatibility complex class I (MHC-I) and related molecules. Functionally, these receptor families are involved in the licensing and rejection of MHC-I-deficient cells through missing-self. The Ly49 family is highly polymorphic, making it challenging to detail the contributions of individual Ly49 receptors to NK cell function. Herein, we showed mice lacking expression of all Ly49s …


Developing A Novel Index For Individual-Level Social Determinants And Cardiovascular Diseases In The Coronary Artery Risk Development In Young Adults (Cardia) Study, Tao Gao, Yinan Zheng, Brian Joyce, Lei Liu, Lili Liu, Catarina Kiefe, Sarah Forrester, Bing Yu, Ankeet Bhatt, Penny Gordon-Larsen, Donald Lloyd-Jones, Kai Zhang, Lifang Hou Mar 2025

Developing A Novel Index For Individual-Level Social Determinants And Cardiovascular Diseases In The Coronary Artery Risk Development In Young Adults (Cardia) Study, Tao Gao, Yinan Zheng, Brian Joyce, Lei Liu, Lili Liu, Catarina Kiefe, Sarah Forrester, Bing Yu, Ankeet Bhatt, Penny Gordon-Larsen, Donald Lloyd-Jones, Kai Zhang, Lifang Hou

2020-Current year OA Pubs

BACKGROUND: Social determinants of health (SDH) have been found to contribute to cardiovascular risk and the development of cardiovascular disease (CVD). However, few studies have examined early-life exposure to SDH and the combined effect of multiple SDH measures on CVD. There is an urgent need to develop an SDH index for use in practice and clinical settings.

METHODS: A total of 3189 participants from the CARDIA Study who had chest CT scans at the year-25 (Y25) visit were included in this study. Personal and parental SDH measures, including education, occupation, income, financial strain, and childhood family environment, were obtained through …


Differences In Plasma Metabolome Between Non-Hispanic White And Non-Hispanic Black Women, Ghazaleh Pourali, Liang Li, Myung Sik Jeon, Jingqin Luo, Chongliang Luo, Adetunji T Toriola Mar 2025

Differences In Plasma Metabolome Between Non-Hispanic White And Non-Hispanic Black Women, Ghazaleh Pourali, Liang Li, Myung Sik Jeon, Jingqin Luo, Chongliang Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: To understand potential racial differences in disease susceptibility and develop targeted prevention strategies, it is essential to establish biological differences between racial groups in healthy individuals. However, knowledge about how race impacts metabolites is limited. We therefore performed a cross-sectional study using comprehensive metabolomics analysis to investigate racial differences in metabolites among 506 non-Hispanic White (NHW) women and 163 non-Hispanic Black (NHB) women.

METHODS: We performed untargeted plasma metabolomic profiling using Metabolon's platform (Durham, NC®) and identified 1074 metabolites in 9 super-pathways. We used multivariable linear regression models, adjusted for confounders, to identify associations between race and metabolites. We …


Antibodies To Recombinant Human Alpha-L-Iduronidase Prevent Disease Correction In Cortical Bone In Mps I Mice, Sarah C Hurt, Steven Q Le, Shih-Hsin Kan, Quang D Bui, Michael D Brodt, Patricia I Dickson Mar 2025

Antibodies To Recombinant Human Alpha-L-Iduronidase Prevent Disease Correction In Cortical Bone In Mps I Mice, Sarah C Hurt, Steven Q Le, Shih-Hsin Kan, Quang D Bui, Michael D Brodt, Patricia I Dickson

2020-Current year OA Pubs

Mucopolysaccharidosis I (MPS I) is a lysosomal storage disorder caused by deficiency of the enzyme α-l-iduronidase (IDUA). Failure of enzyme replacement therapy (ERT) to treat skeletal disease may be due to development of anti-IDUA antibodies, found previously to alter tissue distribution of ERT in animal models. To test this hypothesis, immunocompromised (non-obese diabetic [NOD]-severe combined immunodeficiency [SCID]) MPS I mice were treated with weekly ERT from birth (ERT alone). Some mice also received weekly injections of rabbit immunoglobulin G (IgG) against IDUA (immunized rabbit immune globulin [IRIG]) concomitant with ERT, imitating antibodies developed in patients (ERT+IRIG). Mice treated with ERT+IRIG …


Structure-Guided Design Of Partial Agonists At An Opioid Receptor, Balazs R Varga, Sarah M Bernhard, Amal El Daibani, Jhoan Aguilar, Kevin Appourchaux, Alexa Kouvelis, Amynah Pradhan, Susruta Majumdar, Tao Che, Et Al. Mar 2025

Structure-Guided Design Of Partial Agonists At An Opioid Receptor, Balazs R Varga, Sarah M Bernhard, Amal El Daibani, Jhoan Aguilar, Kevin Appourchaux, Alexa Kouvelis, Amynah Pradhan, Susruta Majumdar, Tao Che, Et Al.

2020-Current year OA Pubs

Chronic pain and opioid overdose deaths highlight the need for non-addictive analgesics with novel mechanisms. The δ opioid receptor (δOR) is a promising target, as it lacks the respiratory depression associated with µ opioid receptor (µOR) agonists. However, early δOR full agonists caused seizures, limiting their clinical use. Partial δOR agonists may offer more controlled receptor activation than full agonists, but their development has been hindered by uncertainty regarding the molecular mechanism of partial agonism. Here we show that C6-Quino, a bitopic ligand developed through structure-based design, acts as a selective δOR partial agonist. Functional studies reveal that C6-Quino shows …


Comprehensive Cross-Sectional And Longitudinal Comparisons Of Plasma Glial Fibrillary Acidic Protein And Neurofilament Light Across Ftd Spectrum Disorders, Udit Sheth, Nupur Ghoshal, Et Al. Mar 2025

Comprehensive Cross-Sectional And Longitudinal Comparisons Of Plasma Glial Fibrillary Acidic Protein And Neurofilament Light Across Ftd Spectrum Disorders, Udit Sheth, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

BACKGROUND: Therapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood glial fibrillary acidic protein (GFAP) has garnered attention as a FTD biomarker. However, investigations of GFAP in FTD have been hampered by symptomatic and histopathologic heterogeneity and small cohort sizes contributing to inconsistent findings. Therefore, we evaluated plasma GFAP as a FTD biomarker and compared its performance to that of neurofilament light (NfL) protein, a leading FTD biomarker.

METHODS: We availed ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources to conduct a comprehensive cross-sectional and …


Factors Influencing Cyanoacrylate Tissue Adhesive Outcomes For Corneal Thinning And Perforation, Anjali Om, Anjali Badami, Yuqing Wang, Xiangqin Cui, Soroosh Behshad, Joung Kim, Praneetha Thulasi Mar 2025

Factors Influencing Cyanoacrylate Tissue Adhesive Outcomes For Corneal Thinning And Perforation, Anjali Om, Anjali Badami, Yuqing Wang, Xiangqin Cui, Soroosh Behshad, Joung Kim, Praneetha Thulasi

2020-Current year OA Pubs

No abstract provided.


Innate Immune Sensing Of Rotavirus By Intestinal Epithelial Cells Leads To Diarrhea, Gaopeng Hou, Juhee Son, Maria Florencia Gomez Castro, Takahiro Kawagishi, Avan Antia, Qiru Zeng, Anna L Deveaux, Hinissan P Kohio, Megan T Baldridge, Siyuan Ding, Et Al. Mar 2025

Innate Immune Sensing Of Rotavirus By Intestinal Epithelial Cells Leads To Diarrhea, Gaopeng Hou, Juhee Son, Maria Florencia Gomez Castro, Takahiro Kawagishi, Avan Antia, Qiru Zeng, Anna L Deveaux, Hinissan P Kohio, Megan T Baldridge, Siyuan Ding, Et Al.

2020-Current year OA Pubs

Diarrhea is the predominant symptom of acute gastroenteritis resulting from enteric infections and a leading cause of death in infants and young children. However, the role of the host response in diarrhea pathogenesis is unclear. Using rotavirus and neonatal mice as a model, we found that oral inoculation of UV-inactivated replication-defective rotavirus consistently induced watery diarrhea by robust activation of cytosolic double-stranded RNA sensing pathways and type III interferon (IFN-λ) secretion. Diarrhea was significantly diminished in mice lacking the IFN-λ receptor. Mechanistically, IFN-λ signaling downregulates the expression of Dra, a chloride and bicarbonate exchanger, which contributes to reduced water absorption. …


Late Adverse Event Reporting From Medical Device Manufacturers To The Us Food And Drug Administration: Cross Sectional Study, Alexander O Everhart, Pinar Karaca-Mandic, Rita F Redberg, Joseph S Ross, Sanket S Dhruva Mar 2025

Late Adverse Event Reporting From Medical Device Manufacturers To The Us Food And Drug Administration: Cross Sectional Study, Alexander O Everhart, Pinar Karaca-Mandic, Rita F Redberg, Joseph S Ross, Sanket S Dhruva

2020-Current year OA Pubs

OBJECTIVE: To describe the extent of late adverse event reporting by manufacturers to the US Food and Drug Administration's (FDA) Manufacturer And User Facility Device Experience (MAUDE) database as well as the distribution of late reporting among manufacturers and associations with device characteristics.

DESIGN: Cross sectional study.

SETTING: The FDA MAUDE database, a central postmarket safety surveillance tool for US medical devices, from 1 September 2019 to 31 December 2022.

PARTICIPANTS: Medical device manufacturers that submitted initial adverse event reports to the FDA between 1 September 2019 and 31 December 2022.

MAIN OUTCOME MEASURES: Time in days between date manufacturer …


Structural Mapping Of Polyclonal Igg Responses To Ha After Influenza Virus Vaccination Or Infection, André Nicolás León, Alesandra J Rodriguez, Sara T Richey, Alba Torrents De La Pena, Rachael M Wolters, Abigail M Jackson, Katherine Webb, C Buddy Creech, Sandra Yoder, Philip A Mudd, James E Crowe, Julianna Han, Andrew B Ward Mar 2025

Structural Mapping Of Polyclonal Igg Responses To Ha After Influenza Virus Vaccination Or Infection, André Nicolás León, Alesandra J Rodriguez, Sara T Richey, Alba Torrents De La Pena, Rachael M Wolters, Abigail M Jackson, Katherine Webb, C Buddy Creech, Sandra Yoder, Philip A Mudd, James E Crowe, Julianna Han, Andrew B Ward

2020-Current year OA Pubs

Cellular and molecular characterization of immune responses elicited by influenza virus infection and seasonal vaccination have informed efforts to improve vaccine efficacy, breadth, and longevity. Here, we use negative stain electron microscopy polyclonal epitope mapping (nsEMPEM) to structurally characterize the humoral IgG antibody responses to hemagglutinin (HA) from human patients vaccinated with a seasonal quadrivalent flu vaccine or infected with influenza A viruses. Our data show that both vaccinated and infected patients had humoral IgGs targeting highly conserved regions on both H1 and H3 subtype HAs, including the stem and anchor, which are targets for universal influenza vaccine design. Responses …


Identifying Distinct Prognostic And Predictive Contributions Of Tumor Epithelium Versus Tumor Microenvironment In Colorectal Cancer, Mingli Yang, Moh'd Khushman, Et Al. Mar 2025

Identifying Distinct Prognostic And Predictive Contributions Of Tumor Epithelium Versus Tumor Microenvironment In Colorectal Cancer, Mingli Yang, Moh'd Khushman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Accumulating evidence has suggested that cancer progression and therapeutic response depend on both tumor epithelium (EPI) and tumor microenvironment (TME). However, the dependency of clinical outcomes on the tumor EPI vs. the TME has neither been clearly defined nor quantified.

METHODS: We classified 2373 colorectal cancer (CRC) tumors into the consensus molecular subtypes (CMS1-4) and generated the 10-gene TME

RESULTS: The TME

CONCLUSIONS: Here we identified a pair of new, distinct 10-gene signatures (the EPI


Outcomes After Isolated Medial Meniscus Posterior Root Repairs Using An Anatomic Transtibial Pullout Technique In Patients Older Than 60 Years: A Matched Cohort Study, Garrett R Jackson, Derrick M Knapik, Zeeshan A Khan, Harkirat Jawanda, Obianuju A Obioha, Daniel J Kaplan, Johnathon R Mccormick, Joan Sugrañes, Anjay Batra, Enzo S Mameri, Nikhil N Verma, Jorge Chahla Mar 2025

Outcomes After Isolated Medial Meniscus Posterior Root Repairs Using An Anatomic Transtibial Pullout Technique In Patients Older Than 60 Years: A Matched Cohort Study, Garrett R Jackson, Derrick M Knapik, Zeeshan A Khan, Harkirat Jawanda, Obianuju A Obioha, Daniel J Kaplan, Johnathon R Mccormick, Joan Sugrañes, Anjay Batra, Enzo S Mameri, Nikhil N Verma, Jorge Chahla

2020-Current year OA Pubs

BACKGROUND: Management of isolated medial meniscus posterior root (MMPR) tears is challenging, especially in older patients, where indications for repair must be weighed against potential repair failure and osteoarthritic progression.

PURPOSE: To compare patient-reported outcomes and incidence of failure after anatomic transtibial pullout repair for isolated MMPR tears in patients >60 versus ≤60 years of age.

STUDY DESIGN: Cohort study; Level of evidence, 3.

METHODS: Included in the study were patients aged ≥18 years who underwent isolated anatomic transtibial pullout repair using either the single- or double-tunnel technique for MMPR tears at a single institution between January 2016 and September …


Transcriptome Complexity Disentangled: A Regulatory Molecules Approach, Amir Asiaee, Zachary B Abrams, Heather H Pua, Kevin R Coombes Mar 2025

Transcriptome Complexity Disentangled: A Regulatory Molecules Approach, Amir Asiaee, Zachary B Abrams, Heather H Pua, Kevin R Coombes

2020-Current year OA Pubs

Transcription factors (TFs) and microRNAs (miRNAs) are fundamental regulators of gene expression, cell state, and biological processes. This study investigated whether a small subset of TFs and miRNAs could accurately predict genome-wide gene expression. We analyzed 8895 samples across 31 cancer types from The Cancer Genome Atlas and identified 28 miRNA and 28 TF clusters using unsupervised learning. Medoids of these clusters could differentiate tissues of origin with 92.8% accuracy, demonstrating their biological relevance. We developed Tissue-Agnostic and Tissue-Aware models to predict 20,000 gene expressions using the 56 selected medoid miRNAs and TFs. The Tissue-Aware model attained an R2 of …


Resilience And Its Association With Hopelessness, Depression, Loneliness, Post-Traumatic Stress Disorder (Ptsd) And Suicidal Ideations And Behavior In A Cohort In The Nairobi Metropolitan, David M Ndetei, Victoria Mutiso, Christine Musyimi, Eric Jeremiah, Pascalyne Nyamai, Samuel Walusaka, Veronica Onyango, Kamaldeep Bhui, Daniel Mamah Mar 2025

Resilience And Its Association With Hopelessness, Depression, Loneliness, Post-Traumatic Stress Disorder (Ptsd) And Suicidal Ideations And Behavior In A Cohort In The Nairobi Metropolitan, David M Ndetei, Victoria Mutiso, Christine Musyimi, Eric Jeremiah, Pascalyne Nyamai, Samuel Walusaka, Veronica Onyango, Kamaldeep Bhui, Daniel Mamah

2020-Current year OA Pubs

Comprehending resilience in the face of mental health issues is important, especially for young people who deal with a variety of psychological pressures. This study aims to investigate the co-occurrence of several mental health conditions and the role of resilience as a potential intervention in youth 14-25 years in the Nairobi metropolitan area. We recruited 1,972 youths. The following self-administered instruments were used: resilience (ARM-R), hopelessness (BHS), depression (BDI, PHQ-9), PTSD (HTQ), loneliness (UCLA Loneliness Scale) and suicidality (C-SSRS). Descriptive statistics, Pearson correlation and hierarchical multiple regression analyses were conducted on the data. The key findings are that depression and …


Tracking And Mitigating Imprint Erasure During Induction Of Naive Human Pluripotency At Single-Cell Resolution, Laura A Fischer, Brittany Meyer, Monica Reyes, Joseph E Zemke, Jessica K Harrison, Kyoung-Mi Park, Ting Wang, Harald Jüppner, Sabine Dietmann, Thorold W Theunissen Mar 2025

Tracking And Mitigating Imprint Erasure During Induction Of Naive Human Pluripotency At Single-Cell Resolution, Laura A Fischer, Brittany Meyer, Monica Reyes, Joseph E Zemke, Jessica K Harrison, Kyoung-Mi Park, Ting Wang, Harald Jüppner, Sabine Dietmann, Thorold W Theunissen

2020-Current year OA Pubs

Naive human pluripotent stem cells (hPSCs) model the pre-implantation epiblast. However, parent-specific epigenetic marks (imprints) are eroded in naive hPSCs, which represents an important deviation from the epiblast in vivo. To track the dynamics of imprint erasure during naive resetting in real time, we established a dual-colored fluorescent reporter at both alleles of the imprinted SNRPN locus. During primed-to-naive resetting, SNRPN expression becomes biallelic in most naive cells, and biallelic SNRPN expression is irreversible upon re-priming. We utilized this live-cell reporter to evaluate chemical and genetic strategies to minimize imprint erasure. Decreasing the level of MEK/ERK inhibition or overexpressing the …


Treatment Patterns And Outcomes In Follicular Lymphoma With Pod24: An Analysis From The Leo Consortium, Jonathan R Day, Brad S Kahl, Et Al. Mar 2025

Treatment Patterns And Outcomes In Follicular Lymphoma With Pod24: An Analysis From The Leo Consortium, Jonathan R Day, Brad S Kahl, Et Al.

2020-Current year OA Pubs

Progression of disease within 24 months of initial immunochemotherapy (POD24) is a negative prognostic factor for patients with follicular lymphoma (FL). There is no standard treatment after POD24. Assembling an academic-based cohort from the Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence, we evaluated patterns of care and outcomes for 220 patients with FL with POD24 and retained FL histology. Therapy after POD24 was heterogeneous, with no treatment category accounting for >25% of the total. Among patients initially treated with bendamustine-rituximab, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) was the predominant second-line choice (48%). Among patients initially treated with R-CHOP, …


Ibrutinib For Therapy Of Steroid-Refractory Chronic Graft-Versus-Host Disease: A Multicenter Real-World Analysis, Joseph Pidala, Iskra Pusic, Et Al. Mar 2025

Ibrutinib For Therapy Of Steroid-Refractory Chronic Graft-Versus-Host Disease: A Multicenter Real-World Analysis, Joseph Pidala, Iskra Pusic, Et Al.

2020-Current year OA Pubs

To examine the activity of ibrutinib in steroid-refractory chronic graft-versus-host disease (SR-cGVHD) after the US Food and Drug Administration approval, we conducted a multicenter retrospective study. Data were standardly collected (N = 270 from 19 centers). Involved organs included skin (75%), eye (61%), mouth (54%), joint/fascia (47%), gastrointestinal (GI) (26%), lung (27%), liver (19%), genital (7%), and others (4.4%). The National Institutes of Health (NIH) severity was mild in 5.7%, moderate 42%, and severe 53%. Thirty-nine percent had overlap subtype. Karnofsky performance status (KPS) was ≥80% in 72%. The median prednisone was 0.21 mg/kg (0-2.27). Ibrutinib was started at a …


Recessive Genetic Contribution To Congenital Heart Disease In 5,424 Probands, Weilai Dong, Sheng Chih Jin, Et Al. Mar 2025

Recessive Genetic Contribution To Congenital Heart Disease In 5,424 Probands, Weilai Dong, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Variants with large effect contribute to congenital heart disease (CHD). To date, recessive genotypes (RGs) have commonly been implicated through anecdotal ascertainment of consanguineous families and candidate gene-based analysis; the recessive contribution to the broad range of CHD phenotypes has been limited. We analyzed whole exome sequences of 5,424 CHD probands. Rare damaging RGs were estimated to contribute to at least 2.2% of CHD, with greater enrichment among laterality phenotypes (5.4%) versus other subsets (1.4%). Among 108 curated human recessive CHD genes, there were 66 RGs, with 54 in 11 genes with >1 RG, 12 genes with 1 RG, and …


Structural Basis For Dimerization And Activation Of Uvrd-Family Helicases, Ankita Chadda, Binh Nguyen, Timothy M Lohman, Eric A Galburt Mar 2025

Structural Basis For Dimerization And Activation Of Uvrd-Family Helicases, Ankita Chadda, Binh Nguyen, Timothy M Lohman, Eric A Galburt

2020-Current year OA Pubs

UvrD-family helicases are superfamily 1A motor proteins that function during DNA replication, recombination, repair, and transcription. UvrD family monomers translocate along single-stranded (ss) DNA but need to be activated by dimerization to unwind DNA in the absence of force or accessory factors. However, prior structural studies have only revealed monomeric complexes. Here, we report the first structures of a dimeric UvrD-family helicase,


Autism- And Intellectual Disability-Associated Myt1l Mutation Alters Human Cortical Interneuron Differentiation, Maturation, And Physiology, Ramachandran Prakasam, Julianna Determan, Gareth Chapman, Mishka Narasimhan, Renata Shen, Maamoon Saleh, Komal Kaushik, Paul Gontarz, Kesavan Meganathan, Bilal Hakim, Bo Zhang, James E Huettner, Kristen L Kroll Mar 2025

Autism- And Intellectual Disability-Associated Myt1l Mutation Alters Human Cortical Interneuron Differentiation, Maturation, And Physiology, Ramachandran Prakasam, Julianna Determan, Gareth Chapman, Mishka Narasimhan, Renata Shen, Maamoon Saleh, Komal Kaushik, Paul Gontarz, Kesavan Meganathan, Bilal Hakim, Bo Zhang, James E Huettner, Kristen L Kroll

2020-Current year OA Pubs

Myelin transcription factor 1 like (MYT1L) is a neuronal transcription factor highly expressed in the developing and adult brain, and, while pathogenic MYT1L mutations cause neurodevelopmental disorders, these have not been characterized in human models of neurodevelopment. Here, we modeled the consequences of pathogenic MYT1L mutation using human stem cell-derived cortical neurons, demonstrating that MYT1L mutation alters the differentiation trajectory, increasing neuronal gene expression, morphological complexity, and synapse production. We also examined consequences of MYT1L mutation in mature cortical interneurons, identifying hallmarks of impaired neuronal identity and maturation and correspondingly altered channel expression and electrophysiological properties. Finally, by defining MYT1L …


Augmented Expression Of Superoxide Dismutase 2 Mitigates Progression And Rupture Of Experimental Abdominal Aortic Aneurysm, Huimin Yan, Ying Hu, Yang Lyu, Antonina Akk, Angela C Hirbe, Samuel A Wickline, Hua Pan, Elisha D O Roberson, Christine T N Pham Mar 2025

Augmented Expression Of Superoxide Dismutase 2 Mitigates Progression And Rupture Of Experimental Abdominal Aortic Aneurysm, Huimin Yan, Ying Hu, Yang Lyu, Antonina Akk, Angela C Hirbe, Samuel A Wickline, Hua Pan, Elisha D O Roberson, Christine T N Pham

2020-Current year OA Pubs

No abstract provided.