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Has Regional Hospital Autonomy Achieved Its Goals? Lessons Learned From Indonesia: A Systematic Review, Masyitoh Basabih, Indriaswari Widhakuswara Aug 2025

Has Regional Hospital Autonomy Achieved Its Goals? Lessons Learned From Indonesia: A Systematic Review, Masyitoh Basabih, Indriaswari Widhakuswara

Kesmas

This study examined the impact of hospital autonomy implementation on the performance of regional public hospitals in Indonesia, particularly in terms of efficiency, effectiveness, and governance. A systematic review of 32 peer-reviewed studies published between June 12 and September 6, 2023, was conducted using Garba Rujukan Digital and Google Scholar, following PRISMA guidelines. Studies addressing financial performance, service outcomes, and challenges related to implementing autonomy were included. The findings indicated that while autonomy led to improvements in infrastructure, service types, visit volumes, and hospital revenues, it had only a marginal impact on improving key health performance outcomes, such as service …


Opiate Addiction Crisis In The United States, Autumn Joy Collins Aug 2025

Opiate Addiction Crisis In The United States, Autumn Joy Collins

Doctoral Dissertations and Projects

This research investigates how fentanyl has influenced drug trafficking trends and the corresponding response from law enforcement in New York State. It aims to explore the changes in drug trafficking pathways, organizational structures, and methods in this region since fentanyl's emergence and how state law enforcement has adjusted to this new challenge. The study uses a quantitative methodology, analyzing various data from law enforcement records, court documents, and state government reports. The focus is on fentanyl-related drug trafficking cases in New York State over five years. Methods include examining case records and analyzing trafficking patterns statistically. The study will assess …


Nadph Oxidase Isoforms (Nox-2 And Nox-4) In Myocardial Ischemia/Reperfusion Injury: Platelet Rich Plasma (Prp) As A Therapeutic Agent, Barbara Y. Hargrave, Frank Lattanzio Aug 2025

Nadph Oxidase Isoforms (Nox-2 And Nox-4) In Myocardial Ischemia/Reperfusion Injury: Platelet Rich Plasma (Prp) As A Therapeutic Agent, Barbara Y. Hargrave, Frank Lattanzio

Cardiovascular Research Symposium

Introduction: Blood flow restoration to ischemic cardiac tissue is a critical and necessary intervention that has an associated downside: reperfusion injury. Reperfusion injury is a complicated process mediated in part by a pathological increase in reactive oxygen species (ROS). Although extremely elevated levels of ROS can cause cell damage, a minimum level of ROS is necessary for activation of Hydroxylated-HIF-1a (HIF-1a) and inhibition of Peroxisome Proliferator-Activated Receptor-alpha (PPARa) during myocardial ischemic reperfusion injury (MIRI). MIRI clinical manifestations include arrhythmias, myocardial stunning, decreased ventricular contractility and no-reflow. Platelet rich plasma (PRP) has improved left ventricular (LV) function after MIRI in …


Dna Double-Stranded Breaks, A Hallmark Of Aging, Defined At The Nucleotide Resolution, Are Increased And Associated With Transcription In The Cardiac Myocytes In Lmna-Cardiomyopathy, Benjamin Cathcart, Sirisha M Cheedipudi, Leila Rouhi, Zhongming Zhao, Priyatansh Gurha, Ali J Marian Aug 2025

Dna Double-Stranded Breaks, A Hallmark Of Aging, Defined At The Nucleotide Resolution, Are Increased And Associated With Transcription In The Cardiac Myocytes In Lmna-Cardiomyopathy, Benjamin Cathcart, Sirisha M Cheedipudi, Leila Rouhi, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

Aims: An intrinsic feature of gene transcription is the formation of DNA superhelices near the transcription bubble, which are resolved upon induction of transient double-stranded breaks (DSBs) by topoisomerases. Unrepaired DSBs are pathogenic as they lead to cell cycle arrest, senescence, inflammation, and organ dysfunction. We posit that DSBs would be more prevalent at the genomic sites that are associated with gene expression. The objectives were to identify and characterize genome-wide DSBs at the nucleotide resolution and determine the association of DSBs with transcription in cardiac myocytes.

Methods and results: We identified the genome-wide DSBs in ∼1 million cardiac myocytes …


Rampes: Unveiling The Ideal Counselor Traits In The Sanghyang Siksakandang Karesian Manuscript, Ade Hidayat, Mamat Supriatna Aug 2025

Rampes: Unveiling The Ideal Counselor Traits In The Sanghyang Siksakandang Karesian Manuscript, Ade Hidayat, Mamat Supriatna

Jurnal Kajian Bimbingan dan Konseling

This study aims to describe the ideal characteristics of a counselor based on the values contained in the Sanghyang Siksakandang Karesian (SSK) manuscript. A hermeneutic approach was employed to interpret the meaning of the text from the perspective of guidance and counseling grounded in local wisdom. The findings indicate that the concept of Rampes, mentioned 24 times in the manuscript, serves as the foundation for shaping a counselor’s professional, moral, and integrative character. This concept comprises three dimensions: (1) Bakti, which reflects religious awareness as a creature of God as well as a commitment to ethical behavior; (2) Wastu Siwong, …


Adams Contribute To Triple Negative Breast Cancer Via Mtorc1 Pathway: Targeting Adam-Mtor Axis Improves Efficacy, Shuying Liu, Huiqin Chen, Mihai Gagea, Lorenzo Federico, Fan Zhang, Javier Gomez, Kim-Anh Do, William F Symmans, Gabriel N Hortobagyi, Gordon B Mills, Ana M Gonzalez-Angulo, Debasish Tripathy Aug 2025

Adams Contribute To Triple Negative Breast Cancer Via Mtorc1 Pathway: Targeting Adam-Mtor Axis Improves Efficacy, Shuying Liu, Huiqin Chen, Mihai Gagea, Lorenzo Federico, Fan Zhang, Javier Gomez, Kim-Anh Do, William F Symmans, Gabriel N Hortobagyi, Gordon B Mills, Ana M Gonzalez-Angulo, Debasish Tripathy

Faculty, Staff and Student Publications

Breast cancer is the most frequently diagnosed cancer globally and the second leading cause of cancer-related deaths in American women. Triple-negative breast cancer (TNBC) lacks estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Thus, fewer targeting therapies are available for this most aggressive subtype. The A Disintegrin and Metalloproteinase (ADAM) family plays a vital role in cancer pathophysiology. Previous studies focused on single ADAM members. However, none of these have entered into the clinical arena as diagnostics or therapeutics for breast cancer. In this study, we demonstrate the upregulation of a panel of ADAM members in TNBC, …


Bi-5756 Reduces Graft-Versus-Host Disease Through Cb1-Mediated Treg Upregulation, Sena Kim, Abdul-Jalil Dania, Sora Lim, Jaebok Choi Aug 2025

Bi-5756 Reduces Graft-Versus-Host Disease Through Cb1-Mediated Treg Upregulation, Sena Kim, Abdul-Jalil Dania, Sora Lim, Jaebok Choi

2020-Current year OA Pubs

Cannabinoid receptor 1 (CB1) has been implicated in multiple inflammatory diseases by regulating pro-inflammatory mediators or altering immune cell polarization. However, the expression and direct functional role of CB1 in T cells remain largely unexplored. Here, we demonstrate that primary murine T cells express CB1 and that its novel agonist, BI-5756, directly increases the frequencies of regulatory T cells (Tregs) in primary murine pan T cells after activation. In addition, BI-5756 exhibits an in vivo protective effect against graft-versus-host disease (GvHD), an allogeneic T cell-mediated inflammatory complication after allogeneic hematopoietic cell transplantation (allo-HCT), resulting in an improved overall survival with …


A Protective Role Of Src-1 Against Aging Associated Cognitive Decline, Hesong Liu, Yongjie Yang, Jonathan C Bean, Yang He, Hailan Liu, Rambabu Majji, Chen Liang, Nan Zhang, Meng Yu, Longlong Tu, Qingzhuo Liu, Yue Deng, Kristine M Conde, Na Yin, Mengjie Wang, Yongxiang Li, Junying Han, Sanika Vattakuzhiyil Jossy, Megan Elyse Burt, Hari Krishna Yalamanchili, Chunmei Wang Aug 2025

A Protective Role Of Src-1 Against Aging Associated Cognitive Decline, Hesong Liu, Yongjie Yang, Jonathan C Bean, Yang He, Hailan Liu, Rambabu Majji, Chen Liang, Nan Zhang, Meng Yu, Longlong Tu, Qingzhuo Liu, Yue Deng, Kristine M Conde, Na Yin, Mengjie Wang, Yongxiang Li, Junying Han, Sanika Vattakuzhiyil Jossy, Megan Elyse Burt, Hari Krishna Yalamanchili, Chunmei Wang

Duncan NRI Faculty and Staff Publications

Introduction: Research indicates a strong correlation between obesity and the risk of dementia, both are linked to steroid receptor coactivator-1 (SRC-1), a transcriptional coactivator.

Methods: We used RNA sequencing analysis (RNA-Seq) to investigate the transcriptome of SRC-1-KO mice, and identified S100 calcium-binding protein A6 (S100A6), an AD associated gene, as one target of SRC-1. We tested cognitive behaviors in SRC-1-KO mice and mice with a humanized SRC-1 mutation (SRC-1L1376P), and performed promoter luciferase assays on S100A6.

Results: Loss of SRC-1 caused alterations in gene signatures that are commonly associated with neurodegenerative diseases, including AD, and diminished the neural plasticity of …


The 9th Annual Lafora Science Symposium: A Rare Epilepsy Community Makes Progress Towards Clinical Readiness, Meredith I. Williams, Katherine J. Donahue, Pascual Sanz, Souad Messahel, Jose M. Serratosa, Jordi Duran, Roberto Michelucci, Lorenzo Muccioli, Antonio Delgado-Escueta, Viet-Hong Nguyen, Berge A. Minassian, Matthew S. Gentry Aug 2025

The 9th Annual Lafora Science Symposium: A Rare Epilepsy Community Makes Progress Towards Clinical Readiness, Meredith I. Williams, Katherine J. Donahue, Pascual Sanz, Souad Messahel, Jose M. Serratosa, Jordi Duran, Roberto Michelucci, Lorenzo Muccioli, Antonio Delgado-Escueta, Viet-Hong Nguyen, Berge A. Minassian, Matthew S. Gentry

Pharmacy Faculty Articles and Research

Lafora disease (LD) is a fatal childhood progressive myoclonus epilepsy and glycogen storage disease that is caused by recessive mutations in either EPM2A or EPM2B. The hallmarks of LD are cytoplasmic, aberrant glycogen-like aggregates, called Lafora bodies (LBs), that drive disease progression. The 9th Annual Lafora Science Symposium was held in San Diego, California and brought together over 70 researchers, clinicians, academic trainees, and friends and family members of patients with LD and 80 attendees joined virtually. This symposium focused primarily on international collaborations for therapeutic development and biomarker identification and strategies for preparing the Lafora community for upcoming …


Loss Of Dihydroceramide Desaturase Drives Neurodegeneration By Disrupting Endoplasmic Reticulum And Lipid Droplet Homeostasis In Glial Cells, Yuqing Zhu, Kevin Cho, Haluk Lacin, Yi Zhu, Jose T Dipaola, Beth A Wilson, Gary Patti, James B Skeath Aug 2025

Loss Of Dihydroceramide Desaturase Drives Neurodegeneration By Disrupting Endoplasmic Reticulum And Lipid Droplet Homeostasis In Glial Cells, Yuqing Zhu, Kevin Cho, Haluk Lacin, Yi Zhu, Jose T Dipaola, Beth A Wilson, Gary Patti, James B Skeath

2020-Current year OA Pubs

Dihydroceramide desaturases convert dihydroceramides to ceramides, the precursors of all complex sphingolipids. Reduction of DEGS1 dihydroceramide desaturase function causes pediatric neurodegenerative disorder hypomyelinating leukodystrophy-18 (HLD-18). We discovered that


Nf1-Depleted Er+ Breast Cancers Are Differentially Sensitive To Cdk4/6 Inhibitors, Ze-Yi Zheng, Anran Chen, Eric J Jaehnig, Meenakshi Anurag, Jonathan T Lei, Long Feng, Chenwei Wang, Diana Fandino, Purba Singh, Hilda Kennedy, Ghazal Yadav, Craig T Vollert, Jill Tsai, Xi Chen, Yi Li, Bora Lim, Alastair Thompson, Shunqiang Li, Charles E Foulds, Bing Zhang, Matthew J Ellis, Eric C Chang Aug 2025

Nf1-Depleted Er+ Breast Cancers Are Differentially Sensitive To Cdk4/6 Inhibitors, Ze-Yi Zheng, Anran Chen, Eric J Jaehnig, Meenakshi Anurag, Jonathan T Lei, Long Feng, Chenwei Wang, Diana Fandino, Purba Singh, Hilda Kennedy, Ghazal Yadav, Craig T Vollert, Jill Tsai, Xi Chen, Yi Li, Bora Lim, Alastair Thompson, Shunqiang Li, Charles E Foulds, Bing Zhang, Matthew J Ellis, Eric C Chang

Faculty, Staff and Students Publications

Neurofibromin/NF1 is a RAS (rat sarcoma virus) GTPase activating protein and estrogen receptor (ER) transcriptional corepressor. NF1low status, identified by copy number loss or low mRNA/protein expression is associated with endocrine therapy resistance in approximately 20% of ER+/HER2− (human epidermal growth factor receptor 2) early-stage breast cancers. The identification of targeted treatments for NF1low ER+/HER2− breast cancer is therefore a priority. In this study proteogenomic analysis of ER+/HER2− breast cancer demonstrated that NF1low tumors exhibited elevated cyclin-dependent kinase 4/6 (CDK4/6) activity. In cell lines, NF1-deletion had a dual effect on CDK4 activity. First, by promoting ER recruitment to CCND1 …


Heterozygous Variants In Plcg1 Affect Hearing, Vision, Cardiac, And Immune Function, Mengqi Ma, Yiming Zheng, Mingxi Deng, Shenzhao Lu, Xueyang Pan, Xi Luo, Michelle Etoundi, David Li-Kroeger, Kim C Worley, Lindsay C Burrage, Lauren S Blieden, Aimee Allworth, Wei-Liang Chen, Giuseppe Merla, Barbara Mandriani, Catherine E Otten, Pierre Blanc, Jill A Rosenfeld, Debdeep Dutta, Shinya Yamamoto, Michael F Wangler, Ian A Glass, Jingheng Chen, Elizabeth Blue, Paolo Prontera, Jeremie Rosain, Sandrine Marlin, Seema R Lalani, Hugo J Bellen, Undiagnosed Diseases Network Aug 2025

Heterozygous Variants In Plcg1 Affect Hearing, Vision, Cardiac, And Immune Function, Mengqi Ma, Yiming Zheng, Mingxi Deng, Shenzhao Lu, Xueyang Pan, Xi Luo, Michelle Etoundi, David Li-Kroeger, Kim C Worley, Lindsay C Burrage, Lauren S Blieden, Aimee Allworth, Wei-Liang Chen, Giuseppe Merla, Barbara Mandriani, Catherine E Otten, Pierre Blanc, Jill A Rosenfeld, Debdeep Dutta, Shinya Yamamoto, Michael F Wangler, Ian A Glass, Jingheng Chen, Elizabeth Blue, Paolo Prontera, Jeremie Rosain, Sandrine Marlin, Seema R Lalani, Hugo J Bellen, Undiagnosed Diseases Network

Duncan NRI Faculty and Staff Publications

Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), important signaling molecules involved in many cellular processes including Ca2+ release from the endoplasmic reticulum (ER). PLCG1 encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of PLCG1 are observed in multiple cancers, but only one germline variant has been reported. Here, we describe seven individuals with heterozygous missense variants in PLCG1 [p.(Asp1019Gly), p.(His380Arg), p.(Asp1165Gly), and p.(Leu597Phe)] who present with hearing impairment (5/7), ocular pathology (4/7), cardiac septal defects (3/6), and various immunological issues (5/7). To model these …


Suppression Of Cardiac Allograft Vasculopathy By A Macrophage Efferocytosis Receptor, Sahil Shah, Aparnaa Ananthakrishnan, Matthew Deberge, Kristofor Glinton, Rebecca T L Jones, Mallory Filipp, Ivana Shen, Joey Lockhart, Connor W Lantz, Edward B Thorp Aug 2025

Suppression Of Cardiac Allograft Vasculopathy By A Macrophage Efferocytosis Receptor, Sahil Shah, Aparnaa Ananthakrishnan, Matthew Deberge, Kristofor Glinton, Rebecca T L Jones, Mallory Filipp, Ivana Shen, Joey Lockhart, Connor W Lantz, Edward B Thorp

Faculty, Staff and Student Publications

Cardiac allograft vasculopathy remains a major cause of late morbidity following heart transplantation. While accumulating evidence implicates innate macrophages in the inflammatory progression of CAV, the underlying mechanisms remain incompletely understood. In murine models of CAV, we identified proteolytic cleavage of MERTK, a key anti-inflammatory receptor on macrophages, as a contributing factor to CAV progression. In a model of CAV, MERTK deficiency accelerated allograft rejection and increased intimal leukocyte infiltration. In contrast, mice expressing a genetically cleavage-resistant form of MERTK (MertkCR/CR) exhibited prolonged graft survival, reduced intimal thickening, diminished immune cell infiltration, and decreased circulating effector T cells. …


The Role Of Recruited Adipose Stromal Cells And Their Fibroblastic Differentiation In Cancer, Lingyi Cai, Mikhail G Kolonin, Dimitris Anastassiou Aug 2025

The Role Of Recruited Adipose Stromal Cells And Their Fibroblastic Differentiation In Cancer, Lingyi Cai, Mikhail G Kolonin, Dimitris Anastassiou

Faculty, Staff and Student Publications

Adipose stromal cells (ASCs) are perivascular mesenchymal progenitors of adipose tissue. In cancer patients, ASCs can mobilize and migrate to the tumor, where they subsequently play an important role in cancer progression. This biological process involves the conversion of recruited ASCs into cancer-associated fibroblasts (CAFs). ASC-derived CAFs influence the tumor microenvironment through extracellular matrix remodeling, vascularization, and immunomodulation. These and other processes mediated by secreted paracrine factors also affect gene expression in carcinoma cells to promote the epithelial-mesenchymal transition (EMT), metabolic adaptation, survival, and invasiveness of cancer cells. ASC-derived CAFs can enhance tumor aggressiveness, accounting in part for the link …


Ifit3 Activation Significantly Contributes To Hiv-1-Associated Neurodegenerative Disorder-Mediated Neuroinflammation, Ranjit Kumar Das, Nirakar Sahoo, Deepa Roy, Chun Xu, Jose Galarza, Maria Camila Mejia Garza, Hansapani Rodrigo, Asim K. Duttaroy, Upal Roy Aug 2025

Ifit3 Activation Significantly Contributes To Hiv-1-Associated Neurodegenerative Disorder-Mediated Neuroinflammation, Ranjit Kumar Das, Nirakar Sahoo, Deepa Roy, Chun Xu, Jose Galarza, Maria Camila Mejia Garza, Hansapani Rodrigo, Asim K. Duttaroy, Upal Roy

Health & Biomedical Sciences Faculty Publications

Introduction: The advent of effective combination antiretroviral therapy (cART) has significantly improved HIV-1 treatment, saving millions of lives. However, HAND remains a concern, particularly among aging individuals with HIV-1. The mechanisms underlying HAND are not well understood.

Methods: This study investigated the role of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) and its upstream regulator, signal transducer, and activator of transcription 1 (STAT1), in HAND pathology. Using the SH-SY5Y neuroblastoma cell line and HIV-infected humanized mice, we examined the effects of the cART drugs, HIV Tat protein, and HIV-1 virus on STAT1 and IFIT3 expression.

Results: The results showed that …


Dissection Of Surface Area-Dependent Lipolysis At A Single Organelle Level, Chengxin Ma, Yan Liang, Xinmeng Che, Yuqi Li, Jin Wu, Li Xu, Hongyuan Yang, Tong-Jin Zhao, Feng-Jung Chen, Peng Li Aug 2025

Dissection Of Surface Area-Dependent Lipolysis At A Single Organelle Level, Chengxin Ma, Yan Liang, Xinmeng Che, Yuqi Li, Jin Wu, Li Xu, Hongyuan Yang, Tong-Jin Zhao, Feng-Jung Chen, Peng Li

Faculty, Staff and Student Publications

Lipid droplets are dynamic organelles whose size and number signify their role in energy. However, owing to cellular heterogeneity and technological limitations, the relationship between the lipolytic ability and lipid droplet morphology is unclear. Here, we developed a live-cell imaging assay using geometric analysis to quantify cellular lipolysis at a single organelle level, designated imaging lipolysis. Using imaging lipolysis and super-resolution imaging, we found that lipolysis is controlled by both lipase-accessible lipid droplet surface area and lipase activity. Moreover, lipid droplet fusion regulatory proteins CLSTN3β/CIDEs promote lipolysis by increasing the total lipid droplet surface area-to-volume ratio in biophysical regulation. We …


Danicamtiv Reduces Myosin's Working Stroke But Activates The Thin Filament By Accelerating Actomyosin Attachment, Brent Scott, Lina Greenberg, Caterina Squarci, Kenneth S Campbell, Michael J Greenberg Aug 2025

Danicamtiv Reduces Myosin's Working Stroke But Activates The Thin Filament By Accelerating Actomyosin Attachment, Brent Scott, Lina Greenberg, Caterina Squarci, Kenneth S Campbell, Michael J Greenberg

2020-Current year OA Pubs

Heart failure is a leading cause of death worldwide, and even with current treatments, the 5-y transplant-free survival rate is only ~50 to 70%. As such, there is a need to develop new treatments for patients that improve survival and quality of life. Recently, there have been efforts to develop small molecules for heart failure that directly target components of the sarcomere, including cardiac myosin. Danicamtiv is one of these molecules; however, its direct effects on myosin's single molecule mechanics and kinetics are not well understood. Using optical trapping techniques, stopped flow transient kinetics, and in vitro reconstitution assays, we …


Artificial Intelligence In Ocular Transcriptomics: Applications Of Unsupervised And Supervised Learning, Catherine Lalman, Yimin Yang, Janice L. Walker Aug 2025

Artificial Intelligence In Ocular Transcriptomics: Applications Of Unsupervised And Supervised Learning, Catherine Lalman, Yimin Yang, Janice L. Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Transcriptomic profiling is a powerful tool for dissecting the cellular and molecular complexity of ocular tissues, providing insights into retinal development, corneal disease, macular degeneration, and glaucoma. With the expansion of microarray, bulk RNA sequencing (RNA-seq), and single-cell RNA-seq technologies, artificial intelligence (AI) has emerged as a key strategy for analyzing high-dimensional gene expression data. This review synthesizes AI-enabled transcriptomic studies in ophthalmology from 2019 to 2025, highlighting how supervised and unsupervised machine learning (ML) methods have advanced biomarker discovery, cell type classification, and eye development and ocular disease modeling. Here, we discuss unsupervised techniques, such as principal component analysis …


Signaling By Intracellular Β2-Adrenergic Receptors Regulates Ampa Receptor Trafficking And Synaptic Plasticity, Boram Lee, Xiaomin Xing, Kyle E. Ireton, Bing Xu, Paul J. Gasser, Johannes W. Hell Aug 2025

Signaling By Intracellular Β2-Adrenergic Receptors Regulates Ampa Receptor Trafficking And Synaptic Plasticity, Boram Lee, Xiaomin Xing, Kyle E. Ireton, Bing Xu, Paul J. Gasser, Johannes W. Hell

Biomedical Sciences Faculty Research and Publications

Signaling by norepinephrine (NE) via adrenergic receptors (ARs) mediates attention, yet the underlying molecular mechanisms are largely unknown. AMPA receptors (AMPARs) form a complex with β2ARs, Gs, adenylyl cyclase, and protein kinase A (PKA) to augment AMPAR phosphorylation and, thereby, surface expression. We show that signaling by intracellular β2ARs is required for these effects and two different forms of long-term potentiation (LTP) that depend on β2AR signaling and phosphorylation of the AMPAR GluA1 subunit on S845. Inhibition of two NE transporters, the organic cation transporter 3 (OCT3) and the plasma membrane monoamine transporter (PMAT), impairs phosphorylation of the AMPAR GluA1 …


Multiplex Imaging Mass Cytometry Reveals Prognostic Immunosuppressive Subpopulations And Macrophage-Driven Metastasis In Osteosarcoma, Benjamin B Gyau, Junyan Wang, Weiguo Wu, Brooks Scull, Angela M Major, Weidong Jin, Justin M M Cates, John Hicks, Tsz-Kwong Man Aug 2025

Multiplex Imaging Mass Cytometry Reveals Prognostic Immunosuppressive Subpopulations And Macrophage-Driven Metastasis In Osteosarcoma, Benjamin B Gyau, Junyan Wang, Weiguo Wu, Brooks Scull, Angela M Major, Weidong Jin, Justin M M Cates, John Hicks, Tsz-Kwong Man

Faculty, Staff and Students Publications

Osteosarcoma is a type of bone cancer that mostly affects kids and teens. The biggest danger is when the cancer spreads to the lungs, and current treatments do not work well for those cases. Immunotherapy, which helps the body’s immune system fight cancer, has worked for other cancers but is limited for osteosarcoma because we do not fully understand the environment around the tumor. Our research looked at various cells around the tumor to study why patients have worse outcomes. We found that certain cells, called M2 macrophages (M2) and myeloid-derived suppressor cells (MDSC), which weaken the immune system, are …


Cathartocytosis: Jettisoning Of Cellular Material During Reprogramming Of Differentiated Cells, Jeffrey W Brown, Xiaobo Lin, Gabriel Anthony Nicolazzi, Xuemei Liu, Thanh Nguyen, Megan D Radyk, Joseph Burclaff, Jason C Mills Aug 2025

Cathartocytosis: Jettisoning Of Cellular Material During Reprogramming Of Differentiated Cells, Jeffrey W Brown, Xiaobo Lin, Gabriel Anthony Nicolazzi, Xuemei Liu, Thanh Nguyen, Megan D Radyk, Joseph Burclaff, Jason C Mills

Faculty, Staff and Students Publications

Injury causes differentiated cells to undergo massive reprogramming to become proliferative and repair tissue via paligenosis. Gastric chief cells use paligenosis to reprogram into progenitor-like spasmolytic-polypeptide-expressing metaplasia (SPEM) cells. Stage 1 of paligenosis is the downscaling of mature cell architecture via a process involving lysosomes. Here, we notice that sulfated glycoproteins are not only digested during paligenosis but also excreted into the gland. Various genetic and pharmacological approaches show that endoplasmic reticulum membranes and secretory granule cargo are also excreted and that the process proceeds in parallel with but is mechanistically independent of autophagy. Three-dimensional light and electron microscopy demonstrated …


Mrna Vaccines Encoding Variant Forms Of Sm-Tsp-2 Confer Protective Immunity Against Schistosoma Mansoni, Athos Silva Oliveira, Sevan Alwan, Philip T Loverde, Ramiz Shaheed, Pranav Mandyam, Rakesh Adhikari, Peter Hotez, Maria Elena Bottazzi, Jeroen Pollet Aug 2025

Mrna Vaccines Encoding Variant Forms Of Sm-Tsp-2 Confer Protective Immunity Against Schistosoma Mansoni, Athos Silva Oliveira, Sevan Alwan, Philip T Loverde, Ramiz Shaheed, Pranav Mandyam, Rakesh Adhikari, Peter Hotez, Maria Elena Bottazzi, Jeroen Pollet

Faculty, Staff and Students Publications

Despite the global burden of helminth infections, no human vaccines have yet been licensed against these parasites. This study explored the development and evaluation of mRNA vaccine candidates targeting Schistosoma mansoni tetraspanin-2 (Sm-TSP-2), an antigen currently under evaluation as a protein vaccine. We designed constructs encoding either full-length Sm-TSP-2, or its large extracellular loop (EC2) domain in secretory, membrane-anchored, or cytosolic forms. In a murine challenge model, the secreted and membrane-anchored versions of Sm-TSP-2-EC2 induced the highest of antigen-specific antibody titers. These two construct designs, along with full-length Sm-TSP-2 mRNA, also significantly reduced adult worm …


High-Speed Voltage Imaging Of Action Potentials In Molecular Layer Interneurons Reveals Sensory-Driven Synchrony That Augments Movement, Spencer T Brown, Meghana R Holla, Michelle A Land, Shuyuan Yang, Alex J Mcdonald, François St-Pierre, Indira M Raman Aug 2025

High-Speed Voltage Imaging Of Action Potentials In Molecular Layer Interneurons Reveals Sensory-Driven Synchrony That Augments Movement, Spencer T Brown, Meghana R Holla, Michelle A Land, Shuyuan Yang, Alex J Mcdonald, François St-Pierre, Indira M Raman

Faculty, Staff and Students Publications

Testing whether the synchrony of action potential firing is a cerebellar coding mechanism requires simultaneous recording, with high temporal fidelity, from populations of identified neurons. Here, we used targeted one-photon voltage imaging at 2–4 kHz to record action potentials from groups of ~10–300 molecular layer interneurons (MLIs) expressing a positively tuned, genetically encoded voltage indicator, FORCE1f or pAce. In awake resting mice, crus I MLIs fired brief (~1-ms) spikes at 20–60 spikes/s. Sensory stimuli of air puffs to the whiskers evoked short-latency (< 10 ms) increases in spiking probability. In most trials, >50% of MLIs fired synchronously with 4-ms temporal precision. The magnitude of puff-evoked whisks correlated tightly with …


Pfkfb3 Activates Cad To Enhance De Novo Pyrimidine Synthesis For Cell Growth, Qingen Da, Yongfeng Cai, Qian Ma, Qiuhua Yang, Yapeng Cao, Yaqi Zhou, Dingwei Zhao, Zhiping Liu, Jiean Xu, Junming Quan, Liang Zhang, Rui Wang, Xuejun Jiang, Xiao Liu, Kunfu Ouyang, Zhen Han, Jikui Liu, Tao Wang, Chunxiang Zhang, Neal L Weintraub, David J R Fulton, Jun Zhao, Mei Hong, Zigang Li, Yuqing Huo Aug 2025

Pfkfb3 Activates Cad To Enhance De Novo Pyrimidine Synthesis For Cell Growth, Qingen Da, Yongfeng Cai, Qian Ma, Qiuhua Yang, Yapeng Cao, Yaqi Zhou, Dingwei Zhao, Zhiping Liu, Jiean Xu, Junming Quan, Liang Zhang, Rui Wang, Xuejun Jiang, Xiao Liu, Kunfu Ouyang, Zhen Han, Jikui Liu, Tao Wang, Chunxiang Zhang, Neal L Weintraub, David J R Fulton, Jun Zhao, Mei Hong, Zigang Li, Yuqing Huo

Faculty, Staff and Students Publications

Aerobic glycolysis, termed the Warburg effect, is one of the aberrant metabolic pathways in highly proliferating cells. Glycolysis provides glycolytic metabolites to support the generation of biomass, such as nucleotides, amino acids, and lipids. Research on the direct interactions between glycolysis and other metabolic pathways is an emerging field that has garnered significant interest. Phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) activates glycolysis by synthesizing fructose-2,6-bisphosphate (F2,6BP), which allosterically activates the rate-limiting enzyme 6-phosphofructo-1-kinase (PFK-1). In this study, we found that PFKFB3 directly interacts with and regulates the phosphorylation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), the enzyme catalyzing the first three …


Molecular Mechanisms Of Iron Metabolism And Overload, Aditi Tayal, Jasmeen Kaur, Robert W. Maitta Aug 2025

Molecular Mechanisms Of Iron Metabolism And Overload, Aditi Tayal, Jasmeen Kaur, Robert W. Maitta

Faculty Scholarship

Iron represents an essential element required for normal physiologic processes throughout organ systems. A vast network of transporters is involved not only in uptake of this element but in processing, oxidation, and recycling to maintain it in a tight balance to avoid excess storage. This complex network of transporters, including heme and ferroportin, among many others, are responsible for facilitating inter-organ tissue iron exchange and availability, contributing to overall heme homeostasis. However, exposure to high levels of iron can overwhelm compensatory mechanisms that result in its accumulation and toxicity. This is the case of patients with genetic diseases such as …


Are Orthopaedic Trauma Surgeons At Risk Of Occupational Noise-Induced Hearing Loss?, Vincent W. Lau, Stephanie A. Kwan, Jack Graham, Gregory K. Deirmengian Aug 2025

Are Orthopaedic Trauma Surgeons At Risk Of Occupational Noise-Induced Hearing Loss?, Vincent W. Lau, Stephanie A. Kwan, Jack Graham, Gregory K. Deirmengian

Rothman Institute Papers

OBJECTIVES: Orthopaedic surgeons are at risk of occupational, noise-induced hearing loss due to exposure to instruments in the operating room. The primary objective of this study was to determine whether orthopaedic trauma procedures exceed recommended decibel (dB) limits. The secondary objective was to demonstrate which actions during a case create the highest sound levels.

METHODS: Intraoperative recordings were taken during orthopaedic trauma surgeries and classified into open reduction internal fixation (ORIF), intramedullary nailing, closed reduction percutaneous pinning, external fixation, soft tissue procedures, or a combination thereof. Recordings were taken of drilling, screw insertion, suctioning, saw use, and mallet striking. Decibel …


Progressive Respiratory Failure In A Term Neonate With Abca3 Surfactant Deficiency: Beyond The Common Causes Of Respiratory Distress, Andrew M Beverstock, Hillary C Lee, David S Moreno Mcneill, Morcos Hanna Aug 2025

Progressive Respiratory Failure In A Term Neonate With Abca3 Surfactant Deficiency: Beyond The Common Causes Of Respiratory Distress, Andrew M Beverstock, Hillary C Lee, David S Moreno Mcneill, Morcos Hanna

Faculty, Staff and Students Publications

Background

Most cases of respiratory distress in term neonates are due to transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), or air leak syndromes. Genetic surfactant deficiencies are rare causes of respiratory distress. Among these, mutations in the ABCA3 gene disrupt surfactant metabolism and can lead to severe, treatment-refractory respiratory failure. While commonly considered in preterm infants, surfactant dysfunction should also be considered in term infants with unexplained and persistent hypoxemia.

Case

We present a case of a 38-weeks term female infant with fetal growth restriction who developed respiratory distress shortly after birth. She initially responded to continuous …


Astrocytes Expressing Mutant Hnrnpa1 Induce Non-Cell-Autonomous Motor Neuron Death, Qinxue Wu, Xionghao Liu, Tingting Zhang, Shiquan Cui, Bo Huang, Cao Huang, Qilin Cao, Xu-Gang Xia, Hongxia Zhou Aug 2025

Astrocytes Expressing Mutant Hnrnpa1 Induce Non-Cell-Autonomous Motor Neuron Death, Qinxue Wu, Xionghao Liu, Tingting Zhang, Shiquan Cui, Bo Huang, Cao Huang, Qilin Cao, Xu-Gang Xia, Hongxia Zhou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pathogenic mutation of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is causative to amyotrophic lateral sclerosis (ALS). Neuron death resulting from pathogenic hnRNPA1 may not require its presence across all pertinent cells types, including neurons, glia, and muscles. Rather, the exclusive presence of pathogenic hnRNPA1 in a specific cell type, such as astrocytes, may suffice to substantially alter cellular functions. Consequently, this alteration initiates abnormal interaction within intricate neuron-glia networks, culminating in non-cell-autonomous motor neuron death. To investigate the pivotal role of non-cell-autonomous neuron death in hnRNPA1-associated ALS, we developed transgenic rats overexpressing mutant hnRNPA1 in specifically astrocytes. The confined overexpression of …


Dolutegravir Developmental Toxicity Is Mitigated By Magnesium And Folate In Zebrafish Embryos, Robert M Cabrera, Ahmed Mohamed, Ryoko Minowa, Katheryn A Neugebauer, Daniel A Gorelick Aug 2025

Dolutegravir Developmental Toxicity Is Mitigated By Magnesium And Folate In Zebrafish Embryos, Robert M Cabrera, Ahmed Mohamed, Ryoko Minowa, Katheryn A Neugebauer, Daniel A Gorelick

Faculty, Staff and Students Publications

Integrase-strand-transfer inhibitors have transformed HIV therapy, yet the widely prescribed drug dolutegravir (DTG) has been linked to developmental toxicity and its teratogenic mechanism remains uncertain. Here we use zebrafish to dissect DTG toxicity during early vertebrate development. DTG exposure from 2-4 h post-fertilization (hpf) to 24 hpf produced high mortality and abnormal morphology; co-treatment with folic acid or 5-methyltetrahydrofolate partially restored normal morphology, whereas calcium had no effect. Strikingly, supplementation with magnesium (Mg) rescued DTG-exposed embryos almost as effectively as folate, implicating magnesium availability in protection. In competitive binding assays, Mg increased binding of folate to purified folate receptor (FOLR1) …


Sleep, Emotion Regulation, And Relationship Satisfaction: A Moderation Analysis, Lakyn Boone Aug 2025

Sleep, Emotion Regulation, And Relationship Satisfaction: A Moderation Analysis, Lakyn Boone

Doctoral Dissertations

Sleep plays a pivotal role in overall health and well-being, influencing mental health, cognitive abilities, memory, emotional balance, and physical well-being (Luyster et al., 2012; Mukherjee et al., 2015). Emotions constitute a natural and indispensable element of human existence but necessitate proper regulation, as any disruption in emotion control has been associated with various mental health disorders (Gross & Jazaieri, 2014; Kring & Gordon, 1998; Phelps, 2006). Furthermore, human connections and relationships are fundamental aspects of the human experience, contributing to emotional support, personal growth, a sense of belonging, and even influencing one's physical health outcomes (Baumeister & Leary, 1995; …