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Articles 3301 - 3330 of 10802
Full-Text Articles in Entire DC Network
Type 2 Cannabinoid Receptor Expression On Microglial Cells Regulates Neuroinflammation During Graft-Versus-Host Disease, Alison Moe, Aditya Rayasam, Garrett Sauber, Ravi K. Shah, Ashley Doherty, Cheng-Yin Yuan, Aniko Szabo, Bob M. Moore Ii, Marco Colonna, Weiguo Cui, Julian Romero, Anthony E. Zamora, Cecilia J Hillard, William R. Drobyski
Type 2 Cannabinoid Receptor Expression On Microglial Cells Regulates Neuroinflammation During Graft-Versus-Host Disease, Alison Moe, Aditya Rayasam, Garrett Sauber, Ravi K. Shah, Ashley Doherty, Cheng-Yin Yuan, Aniko Szabo, Bob M. Moore Ii, Marco Colonna, Weiguo Cui, Julian Romero, Anthony E. Zamora, Cecilia J Hillard, William R. Drobyski
2020-Current year OA Pubs
Neuroinflammation is a recognized complication of immunotherapeutic approaches such as immune checkpoint inhibitor treatment, chimeric antigen receptor therapy, and graft versus host disease (GVHD) occurring after allogeneic hematopoietic stem cell transplantation. While T cells and inflammatory cytokines play a role in this process, the precise interplay between the adaptive and innate arms of the immune system that propagates inflammation in the central nervous system remains incompletely understood. Using a murine model of GVHD, we demonstrate that type 2 cannabinoid receptor (CB2R) signaling plays a critical role in the pathophysiology of neuroinflammation. In these studies, we identify that CB2R expression on …
The Swi/Snf Atp-Dependent Chromatin Remodeling Complex In Cell Lineage Priming And Early Development, Dhurjhoti Saha, Srinivas Animireddy, Blaine Bartholomew
The Swi/Snf Atp-Dependent Chromatin Remodeling Complex In Cell Lineage Priming And Early Development, Dhurjhoti Saha, Srinivas Animireddy, Blaine Bartholomew
Faculty, Staff and Student Publications
ATP dependent chromatin remodelers have pivotal roles in transcription, DNA replication and repair, and maintaining genome integrity. SWI/SNF remodelers were first discovered in yeast genetic screens for factors involved in mating type switching or for using alternative energy sources therefore termed SWI/SNF complex (short for SWItch/Sucrose NonFermentable). The SWI/SNF complexes utilize energy from ATP hydrolysis to disrupt histone-DNA interactions and shift, eject, or reposition nucleosomes making the underlying DNA more accessible to specific transcription factors and other regulatory proteins. In development, SWI/SNF orchestrates the precise activation and repression of genes at different stages, safe guards the formation of specific cell …
An Update On Implant-Associated Malignancies And Their Biocompatibility, Grace C Keane Tahmaseb, Alexandra M Keane, Jose A Foppiani, Terence M Myckatyn
An Update On Implant-Associated Malignancies And Their Biocompatibility, Grace C Keane Tahmaseb, Alexandra M Keane, Jose A Foppiani, Terence M Myckatyn
2020-Current year OA Pubs
Implanted medical devices are widely used across various medical specialties for numerous applications, ranging from cardiovascular supports to orthopedic prostheses and cosmetic enhancements. However, recent observations have raised concerns about the potential of these implants to induce malignancies in the tissues surrounding them. There have been several case reports documenting the occurrence of cancers adjacent to these devices, prompting a closer examination of their safety. This review delves into the epidemiology, clinical presentations, pathological findings, and hypothesized mechanisms of carcinogenesis related to implanted devices. It also explores how the surgical domain and the intrinsic properties and biocompatibility of the implants …
Inhibitory G Proteins Play Multiple Roles To Polarize Sensory Hair Cell Morphogenesis., Amandine Jarysta, Abby Tadenev, Matthew Day, Barry Krawchuk, Benjamin E. Low, Michael V. Wiles, Basile Tarchini
Inhibitory G Proteins Play Multiple Roles To Polarize Sensory Hair Cell Morphogenesis., Amandine Jarysta, Abby Tadenev, Matthew Day, Barry Krawchuk, Benjamin E. Low, Michael V. Wiles, Basile Tarchini
Faculty Research 2024
Inhibitory G alpha (GNAI or Gαi) proteins are critical for the polarized morphogenesis of sensory hair cells and for hearing. The extent and nature of their actual contributions remains unclear, however, as previous studies did not investigate all GNAI proteins and included non-physiological approaches. Pertussis toxin can downregulate functionally redundant GNAI1, GNAI2, GNAI3, and GNAO proteins, but may also induce unrelated defects. Here, we directly and systematically determine the role(s) of each individual GNAI protein in mouse auditory hair cells. GNAI2 and GNAI3 are similarly polarized at the hair cell apex with their binding partner G protein signaling modulator 2 …
Large-Scale Annotated Dataset For Cochlear Hair Cell Detection And Classification., Christopher J Buswinka, David B Rosenberg, Rubina G Simikyan, Richard T Osgood, Katharine Fernandez, Hidetomi Nitta, Yushi Hayashi, Leslie W Liberman, Emily Nguyen, Erdem Yildiz, Jinkyung Kim, Amandine Jarysta, Justine Renauld, Ella Wesson, Haobing Wang, Punam Thapa, Pierrick Bordiga, Noah Mcmurtry, Juan Llamas, Siân R Kitcher, Ana I López-Porras, Runjia Cui, Ghazaleh Behnammanesh, Jonathan E Bird, Angela Ballesteros, A Catalina Vélez-Ortega, Albert S B Edge, Michael R Deans, Ksenia Gnedeva, Brikha R Shrestha, Uri Manor, Bo Zhao, Anthony J Ricci, Basile Tarchini, Martín L Basch, Ruben Stepanyan, Lukas D Landegger, Mark A Rutherford, M Charles Liberman, Bradley J Walters, Corné J Kros, Guy P Richardson, Lisa L Cunningham, Artur A Indzhykulian
Large-Scale Annotated Dataset For Cochlear Hair Cell Detection And Classification., Christopher J Buswinka, David B Rosenberg, Rubina G Simikyan, Richard T Osgood, Katharine Fernandez, Hidetomi Nitta, Yushi Hayashi, Leslie W Liberman, Emily Nguyen, Erdem Yildiz, Jinkyung Kim, Amandine Jarysta, Justine Renauld, Ella Wesson, Haobing Wang, Punam Thapa, Pierrick Bordiga, Noah Mcmurtry, Juan Llamas, Siân R Kitcher, Ana I López-Porras, Runjia Cui, Ghazaleh Behnammanesh, Jonathan E Bird, Angela Ballesteros, A Catalina Vélez-Ortega, Albert S B Edge, Michael R Deans, Ksenia Gnedeva, Brikha R Shrestha, Uri Manor, Bo Zhao, Anthony J Ricci, Basile Tarchini, Martín L Basch, Ruben Stepanyan, Lukas D Landegger, Mark A Rutherford, M Charles Liberman, Bradley J Walters, Corné J Kros, Guy P Richardson, Lisa L Cunningham, Artur A Indzhykulian
Faculty Research 2024
Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. …
Dopamine Release Neuroenergetics In Mouse Striatal Slices, Msema Msackyi, Yuanxin Chen, Wangchen Tsering, Ninghan Wang, Hui Zhang
Dopamine Release Neuroenergetics In Mouse Striatal Slices, Msema Msackyi, Yuanxin Chen, Wangchen Tsering, Ninghan Wang, Hui Zhang
Department of Neuroscience Faculty Papers
Parkinson's disease (PD) is the second most common neurodegenerative disorder. Dopamine (DA) neurons in the substantia nigra pars compacta, which have axonal projections to the dorsal striatum (dSTR), degenerate in PD. In contrast, DA neurons in the ventral tegmental area, with axonal projections to the ventral striatum, including the nucleus accumbens (NAcc) shell, are largely spared. This study aims to uncover the relative contributions of glycolysis and oxidative phosphorylation (OxPhos) to DA release in the striatum. We measured evoked DA release in mouse striatal brain slices using fast-scan cyclic voltammetry applied every two minutes. Blocking OxPhos resulted in a greater …
Evolution Of Chromosome-Arm Aberrations In Breast Cancer Through Genetic Network Rewiring, Elena Kuzmin, Toby M Baker, Tom Lesluyes, Jean Monlong, Kento T Abe, Paula P Coelho, Michael Schwartz, Joseph Del Corpo, Dongmei Zou, Genevieve Morin, Alain Pacis, Yang Yang, Constanza Martinez, Jarrett Barber, Hellen Kuasne, Rui Li, Mathieu Bourgey, Anne-Marie Fortier, Peter G Davison, Atilla Omeroglu, Marie-Christine Guiot, Quaid Morris, Claudia L Kleinman, Sidong Huang, Anne-Claude Gingras, Jiannis Ragoussis, Guillaume Bourque, Peter Van Loo, Morag Park
Evolution Of Chromosome-Arm Aberrations In Breast Cancer Through Genetic Network Rewiring, Elena Kuzmin, Toby M Baker, Tom Lesluyes, Jean Monlong, Kento T Abe, Paula P Coelho, Michael Schwartz, Joseph Del Corpo, Dongmei Zou, Genevieve Morin, Alain Pacis, Yang Yang, Constanza Martinez, Jarrett Barber, Hellen Kuasne, Rui Li, Mathieu Bourgey, Anne-Marie Fortier, Peter G Davison, Atilla Omeroglu, Marie-Christine Guiot, Quaid Morris, Claudia L Kleinman, Sidong Huang, Anne-Claude Gingras, Jiannis Ragoussis, Guillaume Bourque, Peter Van Loo, Morag Park
Faculty, Staff and Student Publications
The basal breast cancer subtype is enriched for triple-negative breast cancer (TNBC) and displays consistent large chromosomal deletions. Here, we characterize evolution and maintenance of chromosome 4p (chr4p) loss in basal breast cancer. Analysis of The Cancer Genome Atlas data shows recurrent deletion of chr4p in basal breast cancer. Phylogenetic analysis of a panel of 23 primary tumor/patient-derived xenograft basal breast cancers reveals early evolution of chr4p deletion. Mechanistically we show that chr4p loss is associated with enhanced proliferation. Gene function studies identify an unknown gene, C4orf19, within chr4p, which suppresses proliferation when overexpressed-a member of the PDCD10-GCKIII kinase module …
Xpo1 Blockade With Kpt-330 Promotes Apoptosis In Cutaneous T-Cell Lymphoma By Activating The P53-P21 And P27 Pathways, Nitin Chakravarti, Amy Boles, Rachel Burzinski, Paola Sindaco, Colleen Isabelle, Kathleen Mcconnell, Anjali Mishra, Pierluigi Porcu
Xpo1 Blockade With Kpt-330 Promotes Apoptosis In Cutaneous T-Cell Lymphoma By Activating The P53-P21 And P27 Pathways, Nitin Chakravarti, Amy Boles, Rachel Burzinski, Paola Sindaco, Colleen Isabelle, Kathleen Mcconnell, Anjali Mishra, Pierluigi Porcu
Kimmel Cancer Center Faculty Papers
Dysregulated nuclear-cytoplasmic trafficking has been shown to play a role in oncogenesis in several types of solid tumors and hematological malignancies. Exportin 1 (XPO1) is responsible for the nuclear export of several proteins and RNA species, mainly tumor suppressors. KPT-330, a small molecule inhibitor of XPO1, is approved for treating relapsed multiple myeloma and diffuse large B-cell lymphoma. Cutaneous T-cell lymphoma (CTCL) is an extranodal non-Hodgkin lymphoma with an adverse prognosis and limited treatment options in advanced stages. The effect of therapeutically targeting XPO1 with KPT-330 in CTCL has not been established. We report that XPO1 expression is upregulated in …
Ccr2+ Monocytes Replenish Border-Associated Macrophages In The Diseased Mouse Brain, Lingxiao Wang, Jiaying Zheng, Shunyi Zhao, Yushan Wan, Meijie Wang, Dale B Bosco, Chia-Yi Kuan, Jason R Richardson, Long-Jun Wu
Ccr2+ Monocytes Replenish Border-Associated Macrophages In The Diseased Mouse Brain, Lingxiao Wang, Jiaying Zheng, Shunyi Zhao, Yushan Wan, Meijie Wang, Dale B Bosco, Chia-Yi Kuan, Jason R Richardson, Long-Jun Wu
Faculty, Staff and Student Publications
Border-associated macrophages (BAMs) are tissue-resident macrophages that reside at the border of the central nervous system (CNS). Since BAMs originate from yolk sac progenitors that do not persist after birth, the means by which this population of cells is maintained is not well understood. Using two-photon microscopy and multiple lineage-tracing strategies, we determine that CCR2+ monocytes are significant contributors to BAM populations following disruptions of CNS homeostasis in adult mice. After BAM depletion, while the residual BAMs possess partial self-repopulation capability, the CCR2+ monocytes are a critical source of the repopulated BAMs. In addition, we demonstrate the existence of CCR2+ …
Topographical And Cell Type-Specific Connectivity Of Rostral And Caudal Forelimb Corticospinal Neuron Populations, Lina Marcela Carmona, Eric D Thomas, Kimberly Smith, Bosiljka Tasic, Rui M Costa, Anders Nelson
Topographical And Cell Type-Specific Connectivity Of Rostral And Caudal Forelimb Corticospinal Neuron Populations, Lina Marcela Carmona, Eric D Thomas, Kimberly Smith, Bosiljka Tasic, Rui M Costa, Anders Nelson
Faculty, Staff and Student Publications
Corticospinal neurons (CSNs) synapse directly on spinal neurons, a diverse assortment of cells with unique structural and functional properties necessary for body movements. CSNs modulating forelimb behavior fractionate into caudal forelimb area (CFA) and rostral forelimb area (RFA) motor cortical populations. Despite their prominence, the full diversity of spinal neurons targeted by CFA and RFA CSNs is uncharted. Here, we use anatomical and RNA sequencing methods to show that CSNs synapse onto a remarkably selective group of spinal cell types, favoring inhibitory populations that regulate motoneuron activity and gate sensory feedback. CFA and RFA CSNs target similar spinal neuron types, …
Functional Organization Of Posterior Parietal Cortex Circuitry Based On Inferred Information Flow, Jung Uk Kang, Eric Mooshagian, Lawrence H Snyder
Functional Organization Of Posterior Parietal Cortex Circuitry Based On Inferred Information Flow, Jung Uk Kang, Eric Mooshagian, Lawrence H Snyder
2020-Current year OA Pubs
Many studies infer the role of neurons by asking what information can be decoded from their activity or by observing the consequences of perturbing their activity. An alternative approach is to consider information flow between neurons. We applied this approach to the parietal reach region (PRR) and the lateral intraparietal area (LIP) in posterior parietal cortex. Two complementary methods imply that across a range of reaching tasks, information flows primarily from PRR to LIP. This indicates that during a coordinated reach task, LIP has minimal influence on PRR and rules out the idea that LIP forms a general purpose spatial …
Large-Scale Annotated Dataset For Cochlear Hair Cell Detection And Classification, Christopher J Buswinka, Jinkyung Kim, Anthony J Ricci, Mark A Rutherford, Et Al.
Large-Scale Annotated Dataset For Cochlear Hair Cell Detection And Classification, Christopher J Buswinka, Jinkyung Kim, Anthony J Ricci, Mark A Rutherford, Et Al.
2020-Current year OA Pubs
Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. …
Single-Cell T-Cell Receptor Repertoire Profiling In Dogs, My H Hoang, Zachary L Skidmore, Hans Rindt, Shirley Chu, Bryan Fisk, Jennifer A Foltz, Catrina Fronick, Robert Fulton, Mingyi Zhou, Nathan J Bivens, Carol N Reinero, Todd A Fehniger, Malachi Griffith, Jeffrey N Bryan, Obi L Griffith
Single-Cell T-Cell Receptor Repertoire Profiling In Dogs, My H Hoang, Zachary L Skidmore, Hans Rindt, Shirley Chu, Bryan Fisk, Jennifer A Foltz, Catrina Fronick, Robert Fulton, Mingyi Zhou, Nathan J Bivens, Carol N Reinero, Todd A Fehniger, Malachi Griffith, Jeffrey N Bryan, Obi L Griffith
2020-Current year OA Pubs
Spontaneous cancers in companion dogs are robust models of human disease. Tracking tumor-specific immune responses in these models requires reagents to perform species-specific single cell T cell receptor sequencing (scTCRseq). scTCRseq and integration with scRNA data have not been demonstrated on companion dogs with cancer. Here, five healthy dogs, two dogs with T cell lymphoma and four dogs with melanoma are selected to demonstrate applicability of scTCRseq in a cancer immunotherapy setting. Single-cell suspensions of PBMCs or lymph node aspirates are profiled using scRNA and dog-specific scTCRseq primers. In total, 77,809 V(D)J-expressing cells are detected, with an average of 3498 …
An Estrogen Receptor Α-Derived Peptide Improves Glucose Homeostasis During Obesity, Wanbao Yang, Wen Jiang, Wang Liao, Hui Yan, Weiqi Ai, Quan Pan, Wesley A Brashear, Yong Xu, Ling He, Shaodong Guo
An Estrogen Receptor Α-Derived Peptide Improves Glucose Homeostasis During Obesity, Wanbao Yang, Wen Jiang, Wang Liao, Hui Yan, Weiqi Ai, Quan Pan, Wesley A Brashear, Yong Xu, Ling He, Shaodong Guo
Faculty, Staff and Students Publications
Estrogen receptor α (ERα) plays a crucial role in regulating glucose and energy homeostasis during type 2 diabetes mellitus (T2DM). However, the underlying mechanisms remain incompletely understood. Here we find a ligand-independent effect of ERα on the regulation of glucose homeostasis. Deficiency of ERα in the liver impairs glucose homeostasis in male, female, and ovariectomized (OVX) female mice. Mechanistic studies reveal that ERα promotes hepatic insulin sensitivity by suppressing ubiquitination-induced IRS1 degradation. The ERα 1-280 domain mediates the ligand-independent effect of ERα on insulin sensitivity. Furthermore, we identify a peptide based on ERα 1-280 domain and find that ERα-derived peptide …
L-Nac And L-Nac Methyl Ester Prevent And Overcome Physical Dependence To Fentanyl In Male Rats., James N Bates, Santhosh M Baby, Paulina M Getsy, Gregory A Coffee, Yee-Hsee Hsieh, Zackery T Knauss, Albert Dahan, Jason A. Bubier, Peter M Macfarlane, Devin Mueller, Stephen J Lewis
L-Nac And L-Nac Methyl Ester Prevent And Overcome Physical Dependence To Fentanyl In Male Rats., James N Bates, Santhosh M Baby, Paulina M Getsy, Gregory A Coffee, Yee-Hsee Hsieh, Zackery T Knauss, Albert Dahan, Jason A. Bubier, Peter M Macfarlane, Devin Mueller, Stephen J Lewis
Faculty Research 2024
N-acetyl-L-cysteine (L-NAC) is a proposed therapeutic for opioid use disorder. This study determined whether co-injections of L-NAC (500 μmol/kg, IV) or its highly cell-penetrant analogue, L-NAC methyl ester (L-NACme, 500 μmol/kg, IV), prevent acquisition of acute physical dependence induced by twice-daily injections of fentanyl (125 μg/kg, IV), and overcome acquired dependence to these injections in freely-moving male Sprague Dawley rats. The injection of the opioid receptor antagonist, naloxone HCl (NLX; 1.5 mg/kg, IV), elicited a series of withdrawal phenomena (i.e. behavioral and cardiorespiratory responses, hypothermia and body weight loss) in rats that received 5 or 10 injections of fentanyl and …
Bioresorbable, Wireless, Passive Sensors For Continuous Ph Measurements And Early Detection Of Gastric Leakage, Shuo Li, Yameng Xu, Ying Yan, Jorge Zárate Rodriguez, Mitchell A Pet, Chet W Hammill, Matthew R Macewan, Wilson Z Ray, Et Al.
Bioresorbable, Wireless, Passive Sensors For Continuous Ph Measurements And Early Detection Of Gastric Leakage, Shuo Li, Yameng Xu, Ying Yan, Jorge Zárate Rodriguez, Mitchell A Pet, Chet W Hammill, Matthew R Macewan, Wilson Z Ray, Et Al.
2020-Current year OA Pubs
Continuous monitoring of biomarkers at locations adjacent to targeted internal organs can provide actionable information about postoperative status beyond conventional diagnostic methods. As an example, changes in pH in the intra-abdominal space after gastric surgeries can serve as direct indicators of potentially life-threatening leakage events, in contrast to symptomatic reactions that may delay treatment. Here, we report a bioresorbable, wireless, passive sensor that addresses this clinical need, designed to locally monitor pH for early detection of gastric leakage. A pH-responsive hydrogel serves as a transducer that couples to a mechanically optimized inductor-capacitor circuit for wireless readout. This platform enables real-time …
Advanced Nano-Drug Delivery Systems In The Treatment Of Ischemic Stroke, Jiajie Zhang, Zhong Chen, Qi Chen
Advanced Nano-Drug Delivery Systems In The Treatment Of Ischemic Stroke, Jiajie Zhang, Zhong Chen, Qi Chen
Faculty, Staff and Student Publications
In recent years, the frequency of strokes has been on the rise year by year and has become the second leading cause of death around the world, which is characterized by a high mortality rate, high recurrence rate, and high disability rate. Ischemic strokes account for a large percentage of strokes. A reperfusion injury in ischemic strokes is a complex cascade of oxidative stress, neuroinflammation, immune infiltration, and mitochondrial damage. Conventional treatments are ineffective, and the presence of the blood-brain barrier (BBB) leads to inefficient drug delivery utilization, so researchers are turning their attention to nano-drug delivery systems. Functionalized nano-drug …
Transposable Elements Regulate Thymus Development And Function, Jean-David Larouche, Céline M Laumont, Assya Trofimov, Krystel Vincent, Leslie Hesnard, Sylvie Brochu, Caroline Côté, Juliette F Humeau, Éric Bonneil, Joel Lanoix, Chantal Durette, Patrick Gendron, Jean-Philippe Laverdure, Ellen R Richie, Sébastien Lemieux, Pierre Thibault, Claude Perreault
Transposable Elements Regulate Thymus Development And Function, Jean-David Larouche, Céline M Laumont, Assya Trofimov, Krystel Vincent, Leslie Hesnard, Sylvie Brochu, Caroline Côté, Juliette F Humeau, Éric Bonneil, Joel Lanoix, Chantal Durette, Patrick Gendron, Jean-Philippe Laverdure, Ellen R Richie, Sébastien Lemieux, Pierre Thibault, Claude Perreault
Faculty, Staff and Student Publications
Transposable elements (TEs) are repetitive sequences representing ~45% of the human and mouse genomes and are highly expressed by medullary thymic epithelial cells (mTECs). In this study, we investigated the role of TEs on T-cell development in the thymus. We performed multiomic analyses of TEs in human and mouse thymic cells to elucidate their role in T-cell development. We report that TE expression in the human thymus is high and shows extensive age- and cell lineage-related variations. TE expression correlates with multiple transcription factors in all cell types of the human thymus. Two cell types express particularly broad TE repertoires: …
Cdk8/Cdk19 Promotes Mitochondrial Fission Through Drp1 Phosphorylation And Can Phenotypically Suppress Pink1 Deficiency In Drosophila, Jenny Zhe Liao, Hyung-Lok Chung, Claire Shih, Kenneth Kin Lam Wong, Debdeep Dutta, Zelha Nil, Catherine Grace Burns, Oguz Kanca, Ye-Jin Park, Zhongyuan Zuo, Paul C Marcogliese, Katherine Sew, Hugo J Bellen, Esther M Verheyen
Cdk8/Cdk19 Promotes Mitochondrial Fission Through Drp1 Phosphorylation And Can Phenotypically Suppress Pink1 Deficiency In Drosophila, Jenny Zhe Liao, Hyung-Lok Chung, Claire Shih, Kenneth Kin Lam Wong, Debdeep Dutta, Zelha Nil, Catherine Grace Burns, Oguz Kanca, Ye-Jin Park, Zhongyuan Zuo, Paul C Marcogliese, Katherine Sew, Hugo J Bellen, Esther M Verheyen
Faculty, Staff and Students Publications
Cdk8 in Drosophila is the orthologue of vertebrate CDK8 and CDK19. These proteins have been shown to modulate transcriptional control by RNA polymerase II. We found that neuronal loss of Cdk8 severely reduces fly lifespan and causes bang sensitivity. Remarkably, these defects can be rescued by expression of human CDK19, found in the cytoplasm of neurons, suggesting a non-nuclear function of CDK19/Cdk8. Here we show that Cdk8 plays a critical role in the cytoplasm, with its loss causing elongated mitochondria in both muscles and neurons. We find that endogenous GFP-tagged Cdk8 can be found in both the cytoplasm and nucleus. …
Ml241 Antagonizes Erk 1/2 Activation And Inhibits Rotavirus Proliferation, Jinlan Wang, Xiaoqing Hu, Jinyuan Wu, Xiaochen Lin, Rong Chen, Chenxing Lu, Xiaopeng Song, Qingmei Leng, Yan Li, Xiangjing Kuang, Jinmei Li, Lida Yao, Xianqiong Tang, Jun Ye, Guangming Zhang, Maosheng Sun, Yan Zhou, Hongjun Li
Ml241 Antagonizes Erk 1/2 Activation And Inhibits Rotavirus Proliferation, Jinlan Wang, Xiaoqing Hu, Jinyuan Wu, Xiaochen Lin, Rong Chen, Chenxing Lu, Xiaopeng Song, Qingmei Leng, Yan Li, Xiangjing Kuang, Jinmei Li, Lida Yao, Xianqiong Tang, Jun Ye, Guangming Zhang, Maosheng Sun, Yan Zhou, Hongjun Li
Faculty, Staff and Student Publications
Rotavirus (RV) is the main pathogen that causes severe diarrhea in infants and children under 5 years of age. No specific antiviral therapies or licensed anti-rotavirus drugs are available. It is crucial to develop effective and low-toxicity anti-rotavirus small-molecule drugs that act on novel host targets. In this study, a new anti-rotavirus compound was selected by ELISA, and cell activity was detected from 453 small-molecule compounds. The anti-RV effects and underlying mechanisms of the screened compounds were explored. In vitro experimental results showed that the small-molecule compound ML241 has a good effect on inhibiting rotavirus proliferation and has low cytotoxicity …
Linear And Nonlinear Behaviors Of The Photoreceptor Coupled Network, Ji-Jie Pang, Xiaolong Jiang, Samuel M Wu
Linear And Nonlinear Behaviors Of The Photoreceptor Coupled Network, Ji-Jie Pang, Xiaolong Jiang, Samuel M Wu
Faculty, Staff and Students Publications
Photoreceptors are electrically coupled to one another, and the spatiotemporal properties of electrical synapses in a two-dimensional retinal network are still not well studied, because of the limitation of the single electrode or pair recording techniques which do not allow simultaneously measuring responses of multiple photoreceptors at various locations in the retina. A multiple electrode recording system is needed. In this study, we investigate the network properties of the two-dimensional rod coupled array of the salamander retina (both sexes were used) by using the newly available multiple patch electrode system that allows simultaneous recordings from up to eight cells and …
Characterization Of Early Markers Of Disease In The Mouse Model Of Mucopolysaccharidosis Iiib, Katherine B Mccullough, Amanda Titus, Kate Reardon, Sara Conyers, Joseph D Dougherty, Xia Ge, Joel R Garbow, Patricia Dickson, Carla M Yuede, Susan E Maloney
Characterization Of Early Markers Of Disease In The Mouse Model Of Mucopolysaccharidosis Iiib, Katherine B Mccullough, Amanda Titus, Kate Reardon, Sara Conyers, Joseph D Dougherty, Xia Ge, Joel R Garbow, Patricia Dickson, Carla M Yuede, Susan E Maloney
2020-Current year OA Pubs
BACKGROUND: Mucopolysaccharidosis (MPS) IIIB, also known as Sanfilippo Syndrome B, is a devastating childhood disease. Unfortunately, there are currently no available treatments for MPS IIIB patients. Yet, animal models of lysosomal storage diseases have been valuable tools in identifying promising avenues of treatment. Enzyme replacement therapy, gene therapy, and bone marrow transplant have all shown efficacy in the MPS IIIB model systems. A ubiquitous finding across rodent models of lysosomal storage diseases is that the best treatment outcomes resulted from intervention prior to symptom onset. Therefore, the aim of the current study was to identify early markers of disease in …
Self-Assembled Sting-Activating Coordination Nanoparticles For Cancer Immunotherapy And Vaccine Applications, Xiaoqi Sun, Xuehui Huang, Kyung Soo Park, Xingwu Zhou, Andrew A Kennedy, Carla D Pretto, Qi Wu, Ziye Wan, Yao Xu, Wang Gong, Jonathan Z Sexton, Andrew W Tai, Yu Leo Lei, James J Moon
Self-Assembled Sting-Activating Coordination Nanoparticles For Cancer Immunotherapy And Vaccine Applications, Xiaoqi Sun, Xuehui Huang, Kyung Soo Park, Xingwu Zhou, Andrew A Kennedy, Carla D Pretto, Qi Wu, Ziye Wan, Yao Xu, Wang Gong, Jonathan Z Sexton, Andrew W Tai, Yu Leo Lei, James J Moon
Faculty, Staff and Student Publications
The cGAS-STING pathway plays a crucial role in innate immune activation against cancer and infections, and STING agonists based on cyclic dinucleotides (CDN) have garnered attention for their potential use in cancer immunotherapy and vaccines. However, the limited drug-like properties of CDN necessitate an efficient delivery system to the immune system. To address these challenges, we developed an immunostimulatory delivery system for STING agonists. Here, we have examined aqueous coordination interactions between CDN and metal ions and report that CDN mixed with Zn2+ and Mn2+ formed distinctive crystal structures. Further pharmaceutical engineering led to the development of a functional coordination …
Host Response During Unresolved Urinary Tract Infection Alters Female Mammary Tissue Homeostasis Through Collagen Deposition And Timp1, Samantha Henry, Xue-Yan He, Et Al.
Host Response During Unresolved Urinary Tract Infection Alters Female Mammary Tissue Homeostasis Through Collagen Deposition And Timp1, Samantha Henry, Xue-Yan He, Et Al.
2020-Current year OA Pubs
Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explore how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell transcriptomics, and flow cytometry, we identify that mammary tissue from UTI-bearing mice displays collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition. Bacterial cells are absent in the mammary tissue and blood of UTI-bearing mice, therefore, alterations to the distal mammary tissue are mediated by the systemic host response to local infection. Furthermore, broad …
Novel Jak Inhibitors To Reduce Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation In A Preclinical Mouse Model, Sena Kim, Peter Ruminski, Megh Singh, Karl Staser, Kidist Ashami, Julie Ritchey, Sora Lim, John F Dipersio, Jaebok Choi
Novel Jak Inhibitors To Reduce Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation In A Preclinical Mouse Model, Sena Kim, Peter Ruminski, Megh Singh, Karl Staser, Kidist Ashami, Julie Ritchey, Sora Lim, John F Dipersio, Jaebok Choi
2020-Current year OA Pubs
Allogeneic hematopoietic cell transplantation (allo-HCT) is a highly effective, well-established treatment for patients with various hematologic malignancies and non-malignant diseases. The therapeutic benefits of allo-HCT are mediated by alloreactive T cells in donor grafts. However, there is a significant risk of graft-versus-host disease (GvHD), in which the donor T cells recognize recipient cells as foreign and attack healthy organs in addition to malignancies. We previously demonstrated that targeting JAK1/JAK2, mediators of interferon-gamma receptor (IFNGR) and IL-6 receptor signaling, in donor T cells using baricitinib and ruxolitinib results in a significant reduction in GvHD after allo-HCT. Furthermore, we showed that balanced …
Acetaminophen Influences Musculoskeletal Signaling But Not Adaptations To Endurance Exercise Training, Brandon Roberts, Alyssa Geddis, Alexandra Ciuciu, Marinaliz Reynoso, Nikhil Mehta, Alyssa Varanoske, Alyssa Kelley, Raymond Walker, Rigoberto Munoz, Alexander Kolb, Jeffery Staab, Marshall Naimo, Ryan Tomlinson
Acetaminophen Influences Musculoskeletal Signaling But Not Adaptations To Endurance Exercise Training, Brandon Roberts, Alyssa Geddis, Alexandra Ciuciu, Marinaliz Reynoso, Nikhil Mehta, Alyssa Varanoske, Alyssa Kelley, Raymond Walker, Rigoberto Munoz, Alexander Kolb, Jeffery Staab, Marshall Naimo, Ryan Tomlinson
Department of Orthopaedic Surgery Faculty Papers
Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats. Nine-week-old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% …
Vhl Governs M6a Modification And Pik3r3 Mrna Stability In Clear Cell Renal Cell Carcinomas, Hyemin Lee, Li Zhuang, Boyi Gan
Vhl Governs M6a Modification And Pik3r3 Mrna Stability In Clear Cell Renal Cell Carcinomas, Hyemin Lee, Li Zhuang, Boyi Gan
Faculty, Staff and Student Publications
N6-Methyladenosine (m6A), a prevalent posttranscriptional modification, plays an important role in cancer progression. Clear cell renal cell carcinoma (ccRCC) is chiefly associated with the loss of the von Hippel-Lindau (VHL) gene, encoding a component of the E3 ubiquitin ligase complex. In this issue of the JCI, Zhang and colleagues unveiled a function of VHL beyond its canonical role as an E3 ubiquitin ligase in regulating hypoxia-inducible factors (HIFs). It also governed m6A modification by orchestrating the assembly of m6A writer proteins METTL3 and METTL14, thereby stabilizing PIK3R3 mRNA. Mechanistically, PIK3R3 contributed to p85 ubiquitination, which restrained PI3K/AKT signaling and consequently …
Vitamin A Status Modulates Epithelial Mesenchymal Transition In The Lung: The Role Of Furin, M Teresa Cabezuelo, Luis Torres, Elena Ortiz-Zapater, Gerardo López-Rodas, M Pilar Marín, Joaquín Timoneda, Juan R Viña, Rosa Zaragozá, Teresa Barber
Vitamin A Status Modulates Epithelial Mesenchymal Transition In The Lung: The Role Of Furin, M Teresa Cabezuelo, Luis Torres, Elena Ortiz-Zapater, Gerardo López-Rodas, M Pilar Marín, Joaquín Timoneda, Juan R Viña, Rosa Zaragozá, Teresa Barber
Faculty, Staff and Student Publications
Vitamin A deficiency (VAD) induced TGF-β hyperactivation and reduced expression of cell adhesion proteins in the lung, suggesting that the disruption of retinoic acid (RA) signaling leads to epithelial-mesenchymal transition (EMT). To elucidate the role of lung vitamin A status in EMT, several EMT markers and the expression of the proprotein convertase furin, which activates TGF-β, were analyzed in two experimental models. Our in vivo model included control rats, VAD rats, and both control rats and VAD rats, treated with RA. For the in vitro studies, human bronchoalveolar epithelial cells treated with RA were used. Our data show that EMT …
Hammerhead-Type Fxr Agonists Induce An Enhancer Rna Fincor That Ameliorates Nonalcoholic Steatohepatitis In Mice, Jinjing Chen, Ruoyu Wang, Feng Xiong, Hao Sun, Byron Kemper, Wenbo Li, Jongsook Kemper
Hammerhead-Type Fxr Agonists Induce An Enhancer Rna Fincor That Ameliorates Nonalcoholic Steatohepatitis In Mice, Jinjing Chen, Ruoyu Wang, Feng Xiong, Hao Sun, Byron Kemper, Wenbo Li, Jongsook Kemper
Faculty, Staff and Student Publications
The nuclear receptor, farnesoid X receptor (FXR/NR1H4), is increasingly recognized as a promising drug target for metabolic diseases, including nonalcoholic steatohepatitis (NASH). Protein-coding genes regulated by FXR are well known, but whether FXR also acts through regulation of long non-coding RNAs (lncRNAs), which vastly outnumber protein-coding genes, remains unknown. Utilizing RNA-seq and global run-on sequencing (GRO-seq) analyses in mouse liver, we found that FXR activation affects the expression of many RNA transcripts from chromatin regions bearing enhancer features. Among these we discovered a previously unannotated liver-enriched enhancer-derived lncRNA (eRNA), termed FXR-induced non-coding RNA (
Combined Deletion Of Men1, Atrx And Pten Triggers Development Of High-Grade Pancreatic Neuroendocrine Tumors In Mice, Mary Esmeralda Fuentes, Xiaoyin Lu, Natasha M Flores, Simone Hausmann, Pawel K Mazur
Combined Deletion Of Men1, Atrx And Pten Triggers Development Of High-Grade Pancreatic Neuroendocrine Tumors In Mice, Mary Esmeralda Fuentes, Xiaoyin Lu, Natasha M Flores, Simone Hausmann, Pawel K Mazur
Faculty, Staff and Student Publications
Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of tumors that exhibit an unpredictable and broad spectrum of clinical presentations and biological aggressiveness. Surgical resection is still the only curative therapeutic option for localized PanNET, but the majority of patients are diagnosed at an advanced and metastatic stage with limited therapeutic options. Key factors limiting the development of new therapeutics are the extensive heterogeneity of PanNETs and the lack of appropriate clinically relevant models. In that context, genomic sequencing of human PanNETs revealed recurrent mutations and structural alterations in several tumor suppressors. Here, we demonstrated that combined loss of MEN1, …