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Articles 6901 - 6930 of 10811

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Cell Type Composition And Circuit Organization Of Clonally Related Excitatory Neurons In The Juvenile Mouse Neocortex, Cathryn R Cadwell, Federico Scala, Paul G Fahey, Dmitry Kobak, Shalaka Mulherkar, Fabian H Sinz, Stelios Papadopoulos, Zheng H Tan, Per Johnsson, Leonard Hartmanis, Shuang Li, Ronald J Cotton, Kimberley F Tolias, Rickard Sandberg, Philipp Berens, Xiaolong Jiang, Andreas Savas Tolias Mar 2020

Cell Type Composition And Circuit Organization Of Clonally Related Excitatory Neurons In The Juvenile Mouse Neocortex, Cathryn R Cadwell, Federico Scala, Paul G Fahey, Dmitry Kobak, Shalaka Mulherkar, Fabian H Sinz, Stelios Papadopoulos, Zheng H Tan, Per Johnsson, Leonard Hartmanis, Shuang Li, Ronald J Cotton, Kimberley F Tolias, Rickard Sandberg, Philipp Berens, Xiaolong Jiang, Andreas Savas Tolias

Faculty, Staff and Students Publications

Clones of excitatory neurons derived from a common progenitor have been proposed to serve as elementary information processing modules in the neocortex. To characterize the cell types and circuit diagram of clonally related excitatory neurons, we performed multi-cell patch clamp recordings and Patch-seq on neurons derived from Nestin-positive progenitors labeled by tamoxifen induction at embryonic day 10.5. The resulting clones are derived from two radial glia on average, span cortical layers 2–6, and are composed of a random sampling of transcriptomic cell types. We find an interaction between shared lineage and connection type: related neurons are more likely to …


The Figure Of The Animal In Modern And Contemporary Poetry By Michael Malay, Brian Bartlett Mar 2020

The Figure Of The Animal In Modern And Contemporary Poetry By Michael Malay, Brian Bartlett

The Goose

Review of Michael Malay's The Figure of the Animal in Modern and Contemporary Poetry


Polr1b And Neural Crest Cell Anomalies In Treacher Collins Syndrome Type 4, Elodie Sanchez, Tomi L Toler, Walton Nephi, Marcia Willing, Et Al. Mar 2020

Polr1b And Neural Crest Cell Anomalies In Treacher Collins Syndrome Type 4, Elodie Sanchez, Tomi L Toler, Walton Nephi, Marcia Willing, Et Al.

2020-Current year OA Pubs

PURPOSE: Treacher Collins syndrome (TCS) is a rare autosomal dominant mandibulofacial dysostosis, with a prevalence of 0.2-1/10,000. Features include bilateral and symmetrical malar and mandibular hypoplasia and facial abnormalities due to abnormal neural crest cell (NCC) migration and differentiation. To date, three genes have been identified: TCOF1, POLR1C, and POLR1D. Despite a large number of patients with a molecular diagnosis, some remain without a known genetic anomaly.

METHODS: We performed exome sequencing for four individuals with TCS but who were negative for pathogenic variants in the known causative genes. The effect of the pathogenic variants was investigated in zebrafish.

RESULTS: …


Methyl-Sensing Nuclear Receptor Liver Receptor Homolog-1 Regulates Mitochondrial Function In Mouse Hepatocytes, Sungwoo Choi, Bingning Dong, Chih-Chun Janet Lin, Mi Jeong Heo, Kang Ho Kim, Zhen Sun, Martin Wagner, Nagireddy Putluri, Jae Myoung Suh, Meng C Wang, David D Moore Mar 2020

Methyl-Sensing Nuclear Receptor Liver Receptor Homolog-1 Regulates Mitochondrial Function In Mouse Hepatocytes, Sungwoo Choi, Bingning Dong, Chih-Chun Janet Lin, Mi Jeong Heo, Kang Ho Kim, Zhen Sun, Martin Wagner, Nagireddy Putluri, Jae Myoung Suh, Meng C Wang, David D Moore

Faculty, Staff and Students Publications

Liver receptor homologue-1 (LRH-1; NR5A2) is a nuclear receptor that regulates metabolic homeostasis in the liver. Previous studies identified phosphatidylcholines as potential endogenous agonist ligands for LRH-1. In the liver, distinct subsets of phosphatidylcholine species are generated by two different pathways: choline addition to phosphatidic acid via the Kennedy pathway, or trimethylation of phosphatidylethanolamine via Phosphatidylethanolamine N-methyl Transferase (PEMT). Here we report that a PEMT - LRH-1 pathway specifically couples methyl metabolism and mitochondrial activities in hepatocytes. We show that the loss of Lrh-1 reduces mitochondrial number, basal respiration, beta-oxidation and ATP production in hepatocytes, and decreases expression of mitochondrial …


Regenerating Zebrafish Fin Epigenome Is Characterized By Stable Lineage-Specific Dna Methylation And Dynamic Chromatin Accessibility, Hyung Joo Lee, Yiran Hou, Yujie Chen, Zea Z Dailey, Aiyana Riddihough, Hyo Sik Jang, Ting Wang, Stephen L Johnson Feb 2020

Regenerating Zebrafish Fin Epigenome Is Characterized By Stable Lineage-Specific Dna Methylation And Dynamic Chromatin Accessibility, Hyung Joo Lee, Yiran Hou, Yujie Chen, Zea Z Dailey, Aiyana Riddihough, Hyo Sik Jang, Ting Wang, Stephen L Johnson

2020-Current year OA Pubs

BACKGROUND: Zebrafish can faithfully regenerate injured fins through the formation of a blastema, a mass of proliferative cells that can grow and develop into the lost body part. After amputation, various cell types contribute to blastema formation, where each cell type retains fate restriction and exclusively contributes to regeneration of its own lineage. Epigenetic changes that are associated with lineage restriction during regeneration remain underexplored.

RESULTS: We produce epigenome maps, including DNA methylation and chromatin accessibility, as well as transcriptomes, of osteoblasts and other cells in uninjured and regenerating fins. This effort reveals regeneration as a process of highly dynamic …


Proteogenomic Characterization Of Endometrial Carcinoma, Yongchao Dou, Daniel Cui Zhou, Alla Karpova, Yige Wu, Song Cao, Matthew A Wyczalkowski, Qingsong Gao, Sunantha Sethuraman, David Mutch, Katherine Fuh, Li Ding, Et Al Feb 2020

Proteogenomic Characterization Of Endometrial Carcinoma, Yongchao Dou, Daniel Cui Zhou, Alla Karpova, Yige Wu, Song Cao, Matthew A Wyczalkowski, Qingsong Gao, Sunantha Sethuraman, David Mutch, Katherine Fuh, Li Ding, Et Al

Open Access Publications

We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/β-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new information about proteomic markers of clinical and genomic tumor subgroups, including relationships to known druggable pathways. An extensive genome-wide acetylation survey yielded insights into regulatory mechanisms linking Wnt signaling and histone acetylation. We also characterized aspects of the tumor immune landscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immune microenvironment, all of …


Immune Checkpoint Modulation Enhances Hiv-1 Antibody Induction., Todd Bradley, Masayuki Kuraoka, Chen-Hao Yeh, Ming Tian, Huan Chen, Derek W Cain, Xuejun Chen, Cheng Cheng, Ali H Ellebedy, Robert Parks, Maggie Barr, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Hilary Bouton-Verville, Sampa Santra, Kevin Wiehe, Mark G. Lewis, Ane Ogbe, Persephone Borrow, David Montefiori, Mattia Bonsignori, M Anthony Moody, Laurent Verkoczy, Kevin O. Saunders, Rafi Ahmed, John R. Mascola, Garnett Kelsoe, Frederick W. Alt, Barton F. Haynes Feb 2020

Immune Checkpoint Modulation Enhances Hiv-1 Antibody Induction., Todd Bradley, Masayuki Kuraoka, Chen-Hao Yeh, Ming Tian, Huan Chen, Derek W Cain, Xuejun Chen, Cheng Cheng, Ali H Ellebedy, Robert Parks, Maggie Barr, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Hilary Bouton-Verville, Sampa Santra, Kevin Wiehe, Mark G. Lewis, Ane Ogbe, Persephone Borrow, David Montefiori, Mattia Bonsignori, M Anthony Moody, Laurent Verkoczy, Kevin O. Saunders, Rafi Ahmed, John R. Mascola, Garnett Kelsoe, Frederick W. Alt, Barton F. Haynes

Manuscripts, Articles, Book Chapters and Other Papers

Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent naive B cell precursors and with unusual genetic features that may be subject to host regulatory control. Here, we administer antibodies targeting immune cell regulatory receptors CTLA-4, PD-1 or OX40 along with HIV envelope (Env) vaccines to rhesus macaques and bnAb immunoglobulin knock-in (KI) mice expressing diverse precursors of CD4 binding site HIV-1 bnAbs. CTLA-4 blockade augments HIV-1 Env …


Dynamic Imaging Of Ldh Inhibition In Tumors Reveals Rapid In Vivo Metabolic Rewiring And Vulnerability To Combination Therapy, Nobu Oshima, Ryo Ishida, Shun Kishimoto, Kristin Beebe, Jeffrey R. Brender, Kazutoshi Yamamoto, Daniel Urban, Ganesha Rai, Michelle S. Johnson, Gloria Benavides, Giuseppe L. Squadrito, Dan Crooks, Joseph Jackson, Abhinav Joshi, Bryan T. Mott, Jonathan H. Shrimp, Michael A. Moses, Min-Jung Lee, Akira Yuno, Tobie D. Lee, Xin Hu, Tamara Anderson, Donna Kusewitt, Helen H. Hathaway, Ajit Jadhav, Didier Picard, Jane B. Trepel, James B. Mitchell, Gordon M. Stott, William Moore, Anton Simeonov, Larry A. Sklar, Jeffrey P Norenberg, W Marston Linehan, David J. Maloney, Chi V. Dang, Alex G. Waterson, Matthew Hall, Victor M. Darley-Usmar, Murali C. Krishna, Leonard M. Neckers Feb 2020

Dynamic Imaging Of Ldh Inhibition In Tumors Reveals Rapid In Vivo Metabolic Rewiring And Vulnerability To Combination Therapy, Nobu Oshima, Ryo Ishida, Shun Kishimoto, Kristin Beebe, Jeffrey R. Brender, Kazutoshi Yamamoto, Daniel Urban, Ganesha Rai, Michelle S. Johnson, Gloria Benavides, Giuseppe L. Squadrito, Dan Crooks, Joseph Jackson, Abhinav Joshi, Bryan T. Mott, Jonathan H. Shrimp, Michael A. Moses, Min-Jung Lee, Akira Yuno, Tobie D. Lee, Xin Hu, Tamara Anderson, Donna Kusewitt, Helen H. Hathaway, Ajit Jadhav, Didier Picard, Jane B. Trepel, James B. Mitchell, Gordon M. Stott, William Moore, Anton Simeonov, Larry A. Sklar, Jeffrey P Norenberg, W Marston Linehan, David J. Maloney, Chi V. Dang, Alex G. Waterson, Matthew Hall, Victor M. Darley-Usmar, Murali C. Krishna, Leonard M. Neckers

Pathology Research and Scholarship

The reliance of many cancers on aerobic glycolysis has stimulated efforts to develop lactate dehydrogenase (LDH) inhibitors. However, despite significant efforts, LDH inhibitors (LDHi) with sufficient specificity and in vivo activity to determine whether LDH is a feasible drug target are lacking. We describe an LDHi with potent, on-target, in vivo activity. Using hyperpolarized magnetic resonance spectroscopic imaging (HP-MRSI), we demonstrate in vivo LDH inhibition in two glycolytic cancer models, MIA PaCa-2 and HT29, and we correlate depth and duration of LDH inhibition with direct anti-tumor activity. HP-MRSI also reveals a metabolic rewiring that occurs in vivo within 30 min …


Synthetic And Genomic Regulatory Elements Reveal Aspects Of Cis-Regulatory Grammar In Mouse Embryonic Stem Cells, Dana M King, Clarice Kit Yee Hong, James L Shepherdson, David M Granas, Brett B Maricque, Barak A Cohen Feb 2020

Synthetic And Genomic Regulatory Elements Reveal Aspects Of Cis-Regulatory Grammar In Mouse Embryonic Stem Cells, Dana M King, Clarice Kit Yee Hong, James L Shepherdson, David M Granas, Brett B Maricque, Barak A Cohen

2020-Current year OA Pubs

In embryonic stem cells (ESCs), a core transcription factor (TF) network establishes the gene expression program necessary for pluripotency. To address how interactions between four key TFs contribute to


What We Can Learn From A Genetic Rodent Model About Autism., Dorit Möhrle, Marta Fernández, Olga Peñagarikano, Andreas Frick, Brian Allman, Susanne Schmid Feb 2020

What We Can Learn From A Genetic Rodent Model About Autism., Dorit Möhrle, Marta Fernández, Olga Peñagarikano, Andreas Frick, Brian Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders that are caused by genetic and/or environmental impacts, often probably by the interaction of both. They are characterised by deficits in social communication and interaction and by restricted and repetitive behaviours and interests from early childhood on, causing significant impairment. While it is clear that no animal model captures the full complexity of ASD in humans, genetic models are extremely useful for studying specific symptoms associated with ASD and the underlying cellular and molecular mechanisms. In this review we summarize the behavioral paradigms used in rodents to model ASD symptoms as they …


Insights Image For "Evidence Of Increased Hypoxia Signalling In Fetal Liver From Maternal Nutrient Restriction In Mice"., Bethany N Radford, Victor K M Han Feb 2020

Insights Image For "Evidence Of Increased Hypoxia Signalling In Fetal Liver From Maternal Nutrient Restriction In Mice"., Bethany N Radford, Victor K M Han

Paediatrics Publications

No abstract provided.


Evidence Of Increased Hypoxia Signaling In Fetal Liver From Maternal Nutrient Restriction In Mice., Bethany N Radford, Victor K M Han Feb 2020

Evidence Of Increased Hypoxia Signaling In Fetal Liver From Maternal Nutrient Restriction In Mice., Bethany N Radford, Victor K M Han

Paediatrics Publications

BACKGROUND: Intrauterine growth restriction (IUGR) is a pregnancy condition where fetal growth is reduced, and offspring from IUGR pregnancies are at increased risk for type II diabetes as adults. The liver is susceptible to fetal undernutrition experienced by IUGR infants and animal models of growth restriction. This study aimed to examine hepatic expression changes in a maternal nutrient restriction (MNR) mouse model of IUGR to understand fetal adaptations that influence adult metabolism.

METHODS: Liver samples of male offspring from MNR (70% of ad libitum starting at E6.5) or control pregnancies were obtained at E18.5 and differential expression was assessed by …


Role Of Dendritic Cell-Mediated Immune Response In Oral Homeostasis: A New Mechanism Of Osteonecrosis Of The Jaw, Ranya Elsayed, Zoya Kurago, Christopher W Cutler, Roger M Arce, Jennifer Gerber, Esteban Celis, Hussein Sultan, Mahmoud Elashiry, Mohamed Meghil, Christina Sun, Caroline M Auersvald, Mohamed E Awad, Rana Zeitoun, Riham Elsayed, Mohey Eldin M Elshikh, Carlos Isales, Mohammed E Elsalanty Feb 2020

Role Of Dendritic Cell-Mediated Immune Response In Oral Homeostasis: A New Mechanism Of Osteonecrosis Of The Jaw, Ranya Elsayed, Zoya Kurago, Christopher W Cutler, Roger M Arce, Jennifer Gerber, Esteban Celis, Hussein Sultan, Mahmoud Elashiry, Mohamed Meghil, Christina Sun, Caroline M Auersvald, Mohamed E Awad, Rana Zeitoun, Riham Elsayed, Mohey Eldin M Elshikh, Carlos Isales, Mohammed E Elsalanty

Faculty, Staff and Student Publications

Dendritic cells are an important link between innate and adaptive immune response. The role of dendritic cells in bone homeostasis, however, is not understood. Osteoporosis medications that inhibit osteoclasts have been associated with osteonecrosis, a condition limited to the jawbone, thus called medication-related osteonecrosis of the jaw. We propose that disruption of the local immune response renders the oral microenvironment conducive to osteonecrosis. We tested whether zoledronate (Zol) treatment impaired dendritic cell (DC) functions and increased bacterial load in alveolar bone in vivo and whether DC inhibition alone predisposed the animals to osteonecrosis. We also analyzed the role of Zol …


Impaired Meningeal Lymphatic Vessel Development Worsens Stroke Outcome, Pavel Yanev, Katherine Poinsatte, Devon Hominick, Noor Khurana, Kielen R. Zuurbier, Marcus Berndt, Erik J. Plautz, Michael T. Dellinger, Ann M. Stowe Feb 2020

Impaired Meningeal Lymphatic Vessel Development Worsens Stroke Outcome, Pavel Yanev, Katherine Poinsatte, Devon Hominick, Noor Khurana, Kielen R. Zuurbier, Marcus Berndt, Erik J. Plautz, Michael T. Dellinger, Ann M. Stowe

Neurology Faculty Publications

The discovery of meningeal lymphatic vessels (LVs) has sparked interest in identifying their role in diseases of the central nervous system. Similar to peripheral LVs, meningeal LVs depend on vascular endothelial growth factor receptor-3 (VEGFR3) signaling for development. Here we characterize the effect of stroke on meningeal LVs, and the impact of meningeal lymphatic hypoplasia on post-stroke outcomes. We show that photothrombosis (PT), but not transient middle cerebral artery occlusion (tMCAo), induces meningeal lymphangiogenesis in young male C57Bl/J6 mice. We also show that Vegfr3wt/mut mice develop significantly fewer meningeal LVs than Vegfr3wt/wt mice. Again, meningeal lymphangiogenesis occurs in …


Rtk Signaling Requires C3ar1/C5ar1 And Il-6r Joint Signaling To Repress Dominant Pten, Socs1/3 And Phlpp Restraint, Michael G. Strainic, Elliot Pohlmann, Christopher C. Valley, Ajay Sammeta, Wasim Hussain, Diane S. Lidke, M Edward Medof Feb 2020

Rtk Signaling Requires C3ar1/C5ar1 And Il-6r Joint Signaling To Repress Dominant Pten, Socs1/3 And Phlpp Restraint, Michael G. Strainic, Elliot Pohlmann, Christopher C. Valley, Ajay Sammeta, Wasim Hussain, Diane S. Lidke, M Edward Medof

Pathology Research and Scholarship

How receptor tyrosine kinase (RTK) growth signaling is controlled physiologically is incompletely understood. We have previously provided evidence that the survival and mitotic activities of vascular endothelial cell growth factor receptor-2 (VEGFR2) signaling are dependent on C3a/C5a receptor (C3ar1/C5ar1) and IL-6 receptor (IL-6R)-gp130 joint signaling in a physically interactive platform. Herein, we document that the platelet derived and epidermal growth factor receptors (PDGFR and EGFR) are regulated by the same interconnection and clarify the mechanism underlying the dependence. We show that the joint signaling is required to overcome dominant restraint on RTK function by the combined repression of tonically activated …


Periodontal Inflammation: Integrating Genes And Dysbiosis, Shaoping Zhang, Ning Yu, Roger M Arce Feb 2020

Periodontal Inflammation: Integrating Genes And Dysbiosis, Shaoping Zhang, Ning Yu, Roger M Arce

Faculty, Staff and Student Publications

Biofilm bacteria co-evolve and reach a symbiosis with the host on the gingival surface. The disruption of the homeostatic relationship between plaque bacteria and the host can initiate and promote periodontal disease progression. Recent advances in sequencing technologies allow researchers to profile disease-associated microbial communities and quantify microbial metabolic activities and host transcriptional responses. In addition to confirming the findings from previous studies, new putative pathogens and novel genes that have not previously been associated with periodontitis, emerge. For example, multiple studies have reported that Synergistetes bacteria are associated with periodontitis. Genes involved in epithelial barrier defense were downregulated in …


Assessing Lymphatic Route Of Csf Outflow And Peripheral Lymphatic Contractile Activity During Head-Down Tilt Using Near-Infrared Fluorescence Imaging, John C Rasmussen, Sunkuk Kwon, Amanda Pinal, Alexander Bareis, Fred C Velasquez, Christopher F Janssen, John R Morrow, Caroline E Fife, Ron J Karni, Eva M Sevick-Muraca Feb 2020

Assessing Lymphatic Route Of Csf Outflow And Peripheral Lymphatic Contractile Activity During Head-Down Tilt Using Near-Infrared Fluorescence Imaging, John C Rasmussen, Sunkuk Kwon, Amanda Pinal, Alexander Bareis, Fred C Velasquez, Christopher F Janssen, John R Morrow, Caroline E Fife, Ron J Karni, Eva M Sevick-Muraca

Faculty, Staff and Student Publications

Evidence overwhelmingly suggests that the lymphatics play a critical role in the clearance of cerebrospinal fluid (CSF) from the cranial space. Impairment of CSF outflow into the lymphatics is associated with a number of pathological conditions including spaceflight-associated neuro-ocular syndrome (SANS), a problem that limits long-duration spaceflight. We used near-infrared fluorescence lymphatic imaging (NIRFLI) to dynamically visualize the deep lymphatic drainage pathways shared by CSF outflow and disrupted during head-down tilt (HDT), a method used to mimic the cephalad fluid shift that occurs in microgravity. After validating CSF clearance into the lymph nodes of the neck in swine, a pilot …


Glopid-R Report On Chikungunya, O'Nyong-Nyong And Mayaro Virus, Part 5: Entomological Aspects, L. Pezzi, M. S. Diamond, Et Al. Feb 2020

Glopid-R Report On Chikungunya, O'Nyong-Nyong And Mayaro Virus, Part 5: Entomological Aspects, L. Pezzi, M. S. Diamond, Et Al.

2020-Current year OA Pubs

The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) chikungunya (CHIKV), o'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group has been established to investigate natural history, epidemiology and clinical aspects of infection by these viruses. Here, we present a report dedicated to entomological aspects of CHIKV, ONNV and MAYV. Recent global expansion of chikungunya virus has been possible because CHIKV established a transmission cycle in urban settings using anthropophilic vectors such as Aedes albopictus and Aedes aegypti. MAYV and ONNV have a more limited geographic distribution, being confined to Africa (ONNV) and central-southern America (MAYV). ONNV is probably maintained through …


Hypothalamic Orexin And Mechanistic Target Of Rapamycin Activation Mediate Sleep Dysfunction In A Mouse Model Of Tuberous Sclerosis Complex, Bo Zhang, Dongjun Guo, Lirong Han, Nicholas Rensing, Akiko Satoh, Michael Wong Feb 2020

Hypothalamic Orexin And Mechanistic Target Of Rapamycin Activation Mediate Sleep Dysfunction In A Mouse Model Of Tuberous Sclerosis Complex, Bo Zhang, Dongjun Guo, Lirong Han, Nicholas Rensing, Akiko Satoh, Michael Wong

2020-Current year OA Pubs

Tuberous sclerosis complex (TSC) is a genetic disease related to hyperactivation of the mechanistic target of rapamycin (mTOR) pathway and manifested by neurological symptoms, such as epilepsy and sleep disorders. The pathophysiology of sleep dysfunction is poorly understood and is likely multifactorial, but may involve intrinsic biological regulators in the brain. Here, we characterized a mouse model of sleep disorders in TSC and investigated mechanisms of sleep dysfunction in this conditional knockout model involving inactivation of the Tsc1 gene in neurons and astrocytes (Tsc1


Losartan Rescues Inflammation-Related Mucociliary Dysfunction In Relevant Models Of Cystic Fibrosis, Michael D Kim, Nathalie Baumlin, Makoto Yoshida, Deepika Polineni, Sebastian F Salathe, Joseph K David, Charles A Peloquin, Adam Wanner, John S Dennis, Juliette Sailland, Philip Whitney, Frank T Horrigan, Juan R Sabater, William M Abraham, Matthias Salathe Feb 2020

Losartan Rescues Inflammation-Related Mucociliary Dysfunction In Relevant Models Of Cystic Fibrosis, Michael D Kim, Nathalie Baumlin, Makoto Yoshida, Deepika Polineni, Sebastian F Salathe, Joseph K David, Charles A Peloquin, Adam Wanner, John S Dennis, Juliette Sailland, Philip Whitney, Frank T Horrigan, Juan R Sabater, William M Abraham, Matthias Salathe

Faculty, Staff and Students Publications

Rationale: Despite therapeutic progress in treating cystic fibrosis (CF) airway disease, airway inflammation with associated mucociliary dysfunction remains largely unaddressed. Inflammation reduces the activity of apically expressed large-conductance Ca2+-activated and voltage-dependent K+ (BK) channels, critical for mucociliary function in the absence of CFTR (CF transmembrane conductance regulator).

Objectives: To test losartan as an antiinflammatory therapy in CF using CF human bronchial epithelial cells and an ovine model of CF-like airway disease.

Methods: Losartan’s antiinflammatory effectiveness to rescue BK activity and thus mucociliary function was tested in vitro using primary, fully redifferentiated human airway epithelial cells homozygous for …


Short-Chain Fatty Acids Improve Poststroke Recovery Via Immunological Mechanisms, Rebecca Sadler, Julia V. Cramer, Steffanie Heindl, Sarantos Kostidis, Dene Betz, Kielen R. Zuurbier, Bernd H. Northoff, Marieke Heijink, Mark P. Goldberg, Erik J. Plautz, Stefan Roth, Rainer Malik, Martin Dichgans, Lesca M. Holdt, Corinne Benakis, Martin Giera, Ann M. Stowe, Arthur Liesz Jan 2020

Short-Chain Fatty Acids Improve Poststroke Recovery Via Immunological Mechanisms, Rebecca Sadler, Julia V. Cramer, Steffanie Heindl, Sarantos Kostidis, Dene Betz, Kielen R. Zuurbier, Bernd H. Northoff, Marieke Heijink, Mark P. Goldberg, Erik J. Plautz, Stefan Roth, Rainer Malik, Martin Dichgans, Lesca M. Holdt, Corinne Benakis, Martin Giera, Ann M. Stowe, Arthur Liesz

Neurology Faculty Publications

Recovery after stroke is a multicellular process encompassing neurons, resident immune cells, and brain-invading cells. Stroke alters the gut microbiome, which in turn has considerable impact on stroke outcome. However, the mechanisms underlying gut–brain interaction and implications for long-term recovery are largely elusive. Here, we tested the hypothesis that short-chain fatty acids (SCFAs), key bioactive microbial metabolites, are the missing link along the gut–brain axis and might be able to modulate recovery after experimental stroke. SCFA supplementation in the drinking water of male mice significantly improved recovery of affected limb motor function. Using in vivo wide-field calcium imaging, we observed …


Metabolic Dysregulation In The Atp7b-/- Wilson's Disease Mouse Model, Clavia Ruth Wooton-Kee, Matthew Robertson, Ying Zhou, Bingning Dong, Zhen Sun, Kang Ho Kim, Hailan Liu, Yong Xu, Nagireddy Putluri, Pradip Saha, Cristian Coarfa, David D Moore, Alli M Nuotio-Antar Jan 2020

Metabolic Dysregulation In The Atp7b-/- Wilson's Disease Mouse Model, Clavia Ruth Wooton-Kee, Matthew Robertson, Ying Zhou, Bingning Dong, Zhen Sun, Kang Ho Kim, Hailan Liu, Yong Xu, Nagireddy Putluri, Pradip Saha, Cristian Coarfa, David D Moore, Alli M Nuotio-Antar

Faculty, Staff and Students Publications

Inactivating mutations in the copper transporter Atp7b result in Wilson’s disease. The Atp7b−/− mouse develops hallmarks of Wilson’s disease. The activity of several nuclear receptors decreased in Atp7b−/− mice, and nuclear receptors are critical for maintaining metabolic homeostasis. Therefore, we anticipated that Atp7b−/− mice would exhibit altered progression of diet-induced obesity, fatty liver, and insulin resistance. Following 10 wk on a chow or Western-type diet (40% kcal fat), parameters of glucose and lipid homeostasis were measured. Hepatic metabolites were measured by liquid chromatography–mass spectrometry and correlated with transcriptomic data. Atp7b−/− mice fed a chow diet presented …


Fenugreek Counters The Effects Of High Fat Diet On Gut Microbiota In Mice: Links To Metabolic Benefit, Annadora J. Bruce-Keller, Allison J. Richard, Sun-Ok Fernandez-Kim, David M. Ribnicky, J Michael Salbaum, Susan Newman Phd, Rn, Crrn, Faan, Richard Carmouche, Jacqueline M. Stephens Jan 2020

Fenugreek Counters The Effects Of High Fat Diet On Gut Microbiota In Mice: Links To Metabolic Benefit, Annadora J. Bruce-Keller, Allison J. Richard, Sun-Ok Fernandez-Kim, David M. Ribnicky, J Michael Salbaum, Susan Newman Phd, Rn, Crrn, Faan, Richard Carmouche, Jacqueline M. Stephens

Publications

Fenugreek (Trigonella foenum-graecum) is an annual herbaceous plant and a staple of traditional health remedies for metabolic conditions including high cholesterol and diabetes. While the mechanisms of the beneficial actions of fenugreek remain unknown, a role for intestinal microbiota in metabolic homeostasis is likely. To determine if fenugreek utilizes intestinal bacteria to offset the adverse effects of high fat diets, C57BL/6J mice were fed control/low fat (CD) or high fat (HFD) diets each supplemented with or without 2% (w/w) fenugreek for 16 weeks. The effects of fenugreek and HFD on gut microbiota were comprehensively mapped and then statistically assessed in …


Deficient Histone H3 Propionylation By Brpf1-Kat6 Complexes In Neurodevelopmental Disorders And Cancer., Kezhi Yan, Justine Rousseau, Keren Machol, Laura A. Cross, Katherine E. Agre, Cynthia Forster Gibson, Anne Goverde, Kendra Engleman, Hannah Verdin, Elfride De Baere, Lorraine Potocki, Dihong Zhou, Maxime Cadieux-Dion, Gary A. Bellus, Monisa D. Wagner, Rebecca J. Hale, Natacha Esber, Alan F. Riley, Benjamin D. Solomon, Megan T. Cho, Kirsty Mcwalter, Roy Eyal, Meagan K. Hainlen, Bryce A. Mendelsohn, Hillary M. Porter, Brendan C. Lanpher, Andrea M. Lewis, Juliann Savatt, Isabelle Thiffault, Bert Callewaert, Philippe M. Campeau, Xiang-Jiao Yang Jan 2020

Deficient Histone H3 Propionylation By Brpf1-Kat6 Complexes In Neurodevelopmental Disorders And Cancer., Kezhi Yan, Justine Rousseau, Keren Machol, Laura A. Cross, Katherine E. Agre, Cynthia Forster Gibson, Anne Goverde, Kendra Engleman, Hannah Verdin, Elfride De Baere, Lorraine Potocki, Dihong Zhou, Maxime Cadieux-Dion, Gary A. Bellus, Monisa D. Wagner, Rebecca J. Hale, Natacha Esber, Alan F. Riley, Benjamin D. Solomon, Megan T. Cho, Kirsty Mcwalter, Roy Eyal, Meagan K. Hainlen, Bryce A. Mendelsohn, Hillary M. Porter, Brendan C. Lanpher, Andrea M. Lewis, Juliann Savatt, Isabelle Thiffault, Bert Callewaert, Philippe M. Campeau, Xiang-Jiao Yang

Manuscripts, Articles, Book Chapters and Other Papers

Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylation in vitro and in vivo. Immunofluorescence microscopy and ATAC-See revealed the association of this modification with active chromatin. Brpf1 deletion obliterates the acylation in mouse embryos and fibroblasts. Moreover, we identify BRPF1 variants in 12 previously unidentified cases of syndromic intellectual disability and demonstrate that these cases and known BRPF1 variants impair H3K23 propionylation. Cardiac anomalies are present in a subset of the …


Rhoa-Rock Signaling As A Therapeutic Target In Traumatic Brain Injury, Shalaka Mulherkar, Kimberley F Tolias Jan 2020

Rhoa-Rock Signaling As A Therapeutic Target In Traumatic Brain Injury, Shalaka Mulherkar, Kimberley F Tolias

Faculty, Staff and Students Publications

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. TBIs, which range in severity from mild to severe, occur when a traumatic event, such as a fall, a traffic accident, or a blow, causes the brain to move rapidly within the skull, resulting in damage. Long-term consequences of TBI can include motor and cognitive deficits and emotional disturbances that result in a reduced quality of life and work productivity. Recovery from TBI can be challenging due to a lack of effective treatment options for repairing TBI-induced neural damage and alleviating functional impairments. Central nervous system (CNS) …


An Artificial Habitat Increases The Reproductive Fitness Of A Range-Shifting Species Within A Newly Colonized Ecosystem, Zachary J. Cannizzo, Susan Q. Lang, Bryan Benitez-Nelson, Blaine D. Griffen Jan 2020

An Artificial Habitat Increases The Reproductive Fitness Of A Range-Shifting Species Within A Newly Colonized Ecosystem, Zachary J. Cannizzo, Susan Q. Lang, Bryan Benitez-Nelson, Blaine D. Griffen

Faculty Publications

When a range-shifting species colonizes an ecosystem it has not previously inhabited, it may experience suboptimal conditions that challenge its continued persistence and expansion. Some impacts may be partially mitigated by artificial habitat analogues: artificial habitats that more closely resemble a species' historic ecosystem than the surrounding habitat. If conditions provided by such habitats increase reproductive success, they could be vital to the expansion and persistence of range-shifting species. We investigated the reproduction of the mangrove tree crab Aratus pisonii in its historic mangrove habitat, the suboptimal colonized salt marsh ecosystem, and on docks within the marsh, an artificial mangrove …


Natural Sources And Bioactivities Of 2,4-Di-Tert-Butylphenol And Its Analogs, Fuqiang Zhao, Ping Wang, Rima D. Lucardi, Zushang Su, Shiyou Li Jan 2020

Natural Sources And Bioactivities Of 2,4-Di-Tert-Butylphenol And Its Analogs, Fuqiang Zhao, Ping Wang, Rima D. Lucardi, Zushang Su, Shiyou Li

NCPC Publications and Patents

2,4-Di-tert-butylphenol or 2,4-bis(1,1-dimethylethyl)-phenol (2,4-DTBP) is a common toxic secondary metabolite produced by various groups of organisms. The biosources and bioactivities of 2,4-DTBP have been well investigated, but the phenol has not been systematically reviewed. This article provides a comprehensive review of 2,4-DTBP and its analogs with emphasis on natural sources and bioactivities. 2,4-DTBP has been found in at least 169 species of bacteria (16 species, 10 families), fungi (11 species, eight families), diatom (one species, one family), liverwort (one species, one family), pteridiphyta (two species, two families), gymnosperms (four species, one family), dicots (107 species, 58 families), monocots (22 species, …


In The Loveland Aquarium, Sam Niven Jan 2020

In The Loveland Aquarium, Sam Niven

Inscape

No abstract provided.


Evaluation Of The Therapeutic Efficacy Of Praziquantel Against Schistosomes In Seven Countries With Ongoing Large-Scale Deworming Programs, B. Levecke, J. Vlaminck, L. Andriamaro, S. Ame, V. Belizario, Abraham Degarege, D. Engels, B. Erko, A. D. Garba, G. M. Kaatano, Z. Mekonnen, A. Montresor, P. Olliaro, O. S. Pieri, M. Sacko, S. O. Sam-Wobo, L. A. Tchuem Tchuenté, J. P. Webster, J. Vercruysse Jan 2020

Evaluation Of The Therapeutic Efficacy Of Praziquantel Against Schistosomes In Seven Countries With Ongoing Large-Scale Deworming Programs, B. Levecke, J. Vlaminck, L. Andriamaro, S. Ame, V. Belizario, Abraham Degarege, D. Engels, B. Erko, A. D. Garba, G. M. Kaatano, Z. Mekonnen, A. Montresor, P. Olliaro, O. S. Pieri, M. Sacko, S. O. Sam-Wobo, L. A. Tchuem Tchuenté, J. P. Webster, J. Vercruysse

Journal Articles: Epidemiology

The World Health Organization (WHO) recommends periodic assessment of the therapeutic efficacy of praziquantel (PZQ) to detect reduced efficacy that may arise from drug resistance in schistosomes. In this multi-country study (2014), we assessed the therapeutic efficacy of a single oral dose of PZQ (40 mg/kg) against Schistosoma mansoni (Brazil, Cameroon, Ethiopia, Mali, Madagascar and Tanzania), S. haematobium (Cameroon, Ethiopia, Mali, Tanzania and Zanzibar) and S. japonicum (the Philippines) infections in school-aged children, across a total of 12 different trials. Each trial was performed according to the standardized methodology for evaluating PZQ efficacy as described by the WHO. Overall, therapeutic …


Integrative Qtl Analysis Of Gene Expression And Chromatin Accessibility Identifies Multi-Tissue Patterns Of Genetic Regulation., Gregory R Keele, Bryan C Quach, Jennifer W Israel, Grace A Chappell, Lauren Lewis, Alexias Safi, Jeremy M Simon, Paul Cotney, Gregory E Crawford, William Valdar, Ivan Rusyn, Terrence S Furey Jan 2020

Integrative Qtl Analysis Of Gene Expression And Chromatin Accessibility Identifies Multi-Tissue Patterns Of Genetic Regulation., Gregory R Keele, Bryan C Quach, Jennifer W Israel, Grace A Chappell, Lauren Lewis, Alexias Safi, Jeremy M Simon, Paul Cotney, Gregory E Crawford, William Valdar, Ivan Rusyn, Terrence S Furey

Faculty Research 2020

Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues-liver, lung, and kidney-in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 …