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Animals

2022

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Full-Text Articles in Medicine and Health Sciences

Clonally Related, Notch-Differentiated Spinal Neurons Integrate Into Distinct Circuits, Saul Bello-Rojas, Martha W Bagnall Dec 2022

Clonally Related, Notch-Differentiated Spinal Neurons Integrate Into Distinct Circuits, Saul Bello-Rojas, Martha W Bagnall

2020-Current year OA Pubs

Shared lineage has diverse effects on patterns of neuronal connectivity. In mammalian cortex, excitatory sister neurons assemble into shared microcircuits. In


Diverse Monogenic Subforms Of Human Spermatogenic Failure, Liina Nagirnaja, Wu-Lin Charng, Christina A Gurnett, Kenan R Omurtag, Et Al. Dec 2022

Diverse Monogenic Subforms Of Human Spermatogenic Failure, Liina Nagirnaja, Wu-Lin Charng, Christina A Gurnett, Kenan R Omurtag, Et Al.

2020-Current year OA Pubs

Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining the genetic basis of NOA has proven challenging, and the most advanced classification of NOA subforms is not based on genetics, but simple description of testis histology. In this study, we exome-sequenced over 1000 clinically diagnosed NOA cases and identified a plausible recessive Mendelian cause in 20%. We find further support for 21 genes in a 2-stage burden test with 2072 cases and 11,587 fertile controls. The disrupted genes are primarily on the autosomes, enriched for undescribed human "knockouts", and, for the most part, have …


Deciphering The Role Of Rna Structure In Translation Efficiency., Jianan Lin, Yang Chen, Yuping Zhang, Haifan Lin, Zhengqing Ouyang Dec 2022

Deciphering The Role Of Rna Structure In Translation Efficiency., Jianan Lin, Yang Chen, Yuping Zhang, Haifan Lin, Zhengqing Ouyang

Faculty Research 2022

BACKGROUND: RNA secondary structure has broad impact on the fate of RNA metabolism. The reduced stability of secondary structures near the translation initiation site/start codon of the coding region promotes the efficiency of translation in both prokaryotic and eukaryotic species. However, the inaccuracy of in silico folding and the focus on the coding region limit our understanding of the global relationship between the whole mRNA structure and translation efficiency. Leveraging high-throughput RNA structure probing data in the transcriptome, we aim to systematically investigate the role of RNA structure in regulating translation efficiency.

RESULTS: Here, we analyze the influences of hundreds …


Trem2 Dependent And Independent Functions Of Microglia In Alzheimer's Disease, Jinchao Hou, Yun Chen, Gary Grajales-Reyes, Marco Colonna Dec 2022

Trem2 Dependent And Independent Functions Of Microglia In Alzheimer's Disease, Jinchao Hou, Yun Chen, Gary Grajales-Reyes, Marco Colonna

2020-Current year OA Pubs

Microglia are central players in brain innate immunity and have been the subject of extensive research in Alzheimer's disease (AD). In this review, we aim to summarize the genetic and functional discoveries that have advanced our understanding of microglia reactivity to AD pathology. Given the heightened AD risk posed by rare variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2), we will focus on the studies addressing the impact of this receptor on microglia responses to amyloid plaques, tauopathy and demyelination pathologies in mouse and human. Finally, we will discuss the implications of recent discoveries on microglia …


Myocardial Contractility Pattern Characterization In Radiation-Induced Cardiotoxicity Using Magnetic Resonance Imaging: A Pilot Study With Contractix, El-Sayed H Ibrahim, Antonio Sosa, Sherry-Ann Brown, Dayeong An, Slade Klawikowski, John Baker, Carmen Bergom Dec 2022

Myocardial Contractility Pattern Characterization In Radiation-Induced Cardiotoxicity Using Magnetic Resonance Imaging: A Pilot Study With Contractix, El-Sayed H Ibrahim, Antonio Sosa, Sherry-Ann Brown, Dayeong An, Slade Klawikowski, John Baker, Carmen Bergom

2020-Current year OA Pubs

Radiation therapy (RT) plays an integral role in treating thoracic cancers, despite the risk of radiation-induced cardiotoxicity. We hypothesize that our newly developed magnetic resonance imaging (MRI)-based contractility index (ContractiX) is a sensitive marker for early detection of RT-induced cardiotoxicity in a preclinical rat model of thoracic cancer RT. Adult salt-sensitive rats received image-guided heart RT and were imaged with MRI at 8 weeks and 10 weeks post-RT or sham. The MRI exam included cine and tagging sequences to measure left-ventricular ejection fraction (LVEF), mass, myocardial strain, and ContractiX. Furthermore, ventricular torsion, diastolic strain rate, and mechanical dyssynchrony were measured. …


Impact Of Cd4 T Cells On Intratumoral Cd8 T-Cell Exhaustion And Responsiveness To Pd-1 Blockade Therapy In Mouse Brain Tumors, Saad M. Khan, Rupen Desai, Andrew Coxon, Alexandra Livingstone, Gavin P Dunn, Allegra Petti, Tanner M Johanns Dec 2022

Impact Of Cd4 T Cells On Intratumoral Cd8 T-Cell Exhaustion And Responsiveness To Pd-1 Blockade Therapy In Mouse Brain Tumors, Saad M. Khan, Rupen Desai, Andrew Coxon, Alexandra Livingstone, Gavin P Dunn, Allegra Petti, Tanner M Johanns

2020-Current year OA Pubs

BACKGROUND: Glioblastoma is a fatal disease despite aggressive multimodal therapy. PD-1 blockade, a therapy that reinvigorates hypofunctional exhausted CD8 T cells (T

METHODS: Single-cell RNA sequencing was performed on flow sorted tumor-infiltrating lymphocytes from female C57/BL6 mice implanted with each model, with and without PD-1 blockade therapy. CD8

RESULTS: The CD8 T-cell compartment of the models is composed of heterogenous CD8 T

CONCLUSIONS: Here, we describe that dysfunctional CD4 T cells are associated with terminal CD8 T-cell exhaustion, suggesting CD4 T cells impact PD-1 blockade efficacy by controlling the severity of exhaustion. Given that CD4 lymphopenia is frequently observed in …


Morphologic Design Of Nanostructures For Enhanced Antimicrobial Activity, Fatma Al-Zahraa Sayed, Noura G Eissa, Yidan Shen, David A Hunstad, Karen L Wooley, Mahmoud Elsabahy Dec 2022

Morphologic Design Of Nanostructures For Enhanced Antimicrobial Activity, Fatma Al-Zahraa Sayed, Noura G Eissa, Yidan Shen, David A Hunstad, Karen L Wooley, Mahmoud Elsabahy

2020-Current year OA Pubs

Despite significant progress in synthetic polymer chemistry and in control over tuning the structures and morphologies of nanoparticles, studies on morphologic design of nanomaterials for the purpose of optimizing antimicrobial activity have yielded mixed results. When designing antimicrobial materials, it is important to consider two distinctly different modes and mechanisms of activity-those that involve direct interactions with bacterial cells, and those that promote the entry of nanomaterials into infected host cells to gain access to intracellular pathogens. Antibacterial activity of nanoparticles may involve direct interactions with organisms and/or release of antibacterial cargo, and these activities depend on attractive interactions and …


Restoring Mitochondrial Cardiolipin Homeostasis Reduces Cell Death And Promotes Recovery After Spinal Cord Injury, Nai-Kui Liu, Chunyan Wang, Et Al. Dec 2022

Restoring Mitochondrial Cardiolipin Homeostasis Reduces Cell Death And Promotes Recovery After Spinal Cord Injury, Nai-Kui Liu, Chunyan Wang, Et Al.

2020-Current year OA Pubs

Alterations in phospholipids have long been associated with spinal cord injury (SCI). However, their specific roles and signaling cascades in mediating cell death and tissue repair remain unclear. Here we investigated whether alterations of cardiolipin (CL), a family of mitochondrion-specific phospholipids, play a crucial role in mitochondrial dysfunction and neuronal death following SCI. Lipidomic analysis was used to determine the profile of CL alteration in the adult rat spinal cord following a moderate contusive SCI at the 10th thoracic (T10) level. Cellular, molecular, and genetic assessments were performed to determine whether CL alterations mediate mitochondrial dysfunction and neuronal death after …


Type Iv Pili Are A Critical Virulence Factor In Clinical Isolates Of Paenibacillus Thiaminolyticus, Christine Hehnly, Petra Erdmann Gilmore, R. Reid Townsend, David D. Limbrick, Et Al. Dec 2022

Type Iv Pili Are A Critical Virulence Factor In Clinical Isolates Of Paenibacillus Thiaminolyticus, Christine Hehnly, Petra Erdmann Gilmore, R. Reid Townsend, David D. Limbrick, Et Al.

2020-Current year OA Pubs

Hydrocephalus, the leading indication for childhood neurosurgery worldwide, is particularly prevalent in low- and middle-income countries. Hydrocephalus preceded by an infection, or postinfectious hydrocephalus, accounts for up to 60% of hydrocephalus in these areas. Since many children with hydrocephalus suffer poor long-term outcomes despite surgical intervention, prevention of hydrocephalus remains paramount. Our previous studies implicated a novel bacterial pathogen, Paenibacillus thiaminolyticus, as a causal agent of neonatal sepsis and postinfectious hydrocephalus in Uganda. Here, we report the isolation of three


Self-Hybridization In Leishmania Major, Tiago R Ferreira, Ehud Inbar, Jahangheer Shaik, Brendan M Jeffrey, Kashinath Ghosh, Deborah E. Dobson, Stephen M. Beverley, David Sacks Dec 2022

Self-Hybridization In Leishmania Major, Tiago R Ferreira, Ehud Inbar, Jahangheer Shaik, Brendan M Jeffrey, Kashinath Ghosh, Deborah E. Dobson, Stephen M. Beverley, David Sacks

2020-Current year OA Pubs

Genetic exchange between different


The Impact Of Vitamin A Deficiency On Tuberculosis Progression, Brendan K Podell, Omowunmi Aibana, Chuan-Chin Huang, James E Dilisio, Macallister C Harris, David F Ackart, Kody Armann, Alexander Grover, Patrice Severe, Marc Antoine Jean Juste, Kathryn Dupnik, Randall J Basaraba, Megan B Murray Dec 2022

The Impact Of Vitamin A Deficiency On Tuberculosis Progression, Brendan K Podell, Omowunmi Aibana, Chuan-Chin Huang, James E Dilisio, Macallister C Harris, David F Ackart, Kody Armann, Alexander Grover, Patrice Severe, Marc Antoine Jean Juste, Kathryn Dupnik, Randall J Basaraba, Megan B Murray

Journal Articles

BACKGROUND: Although previous studies have shown that vitamin A deficiency is associated with incident tuberculosis (TB) disease, the direction of the association has not been established. We investigated the impact of vitamin A deficiency on TB disease progression.

METHODS: We conducted a longitudinal cohort study nested within a randomized clinical trial among HIV-infected patients in Haiti. We compared serial vitamin A levels in individuals who developed TB disease to controls matched on age, gender, follow-up time, and time to antiretroviral therapy initiation. We also evaluated histopathology, bacterial load, and immune outcomes in TB infection in a guinea pig model of …


Multiplex Immunofluorescence-Guided Laser Capture Microdissection For Spatial Transcriptomics Of Metastatic Melanoma Tissues., Jan Martinek, Te-Chia Wu, Lili Sun, Jianan Lin, Kyung In Kim, Florentina Marches, Paul Robson, Joshy George, Karolina Palucka Dec 2022

Multiplex Immunofluorescence-Guided Laser Capture Microdissection For Spatial Transcriptomics Of Metastatic Melanoma Tissues., Jan Martinek, Te-Chia Wu, Lili Sun, Jianan Lin, Kyung In Kim, Florentina Marches, Paul Robson, Joshy George, Karolina Palucka

Faculty Research 2022

We describe a pipeline for optimized and streamlined multiplexed immunofluorescence-guided laser capture microdissection allowing the harvest of individual cells based on their phenotype and tissue localization for transcriptomic analysis with next-generation RNA sequencing. Here, we analyze transcriptomes of CD3+ T cells, CD14+ monocytes/macrophages, and melanoma cells in non-dissociated metastatic melanoma tissue. While this protocol is described for melanoma tissues, we successfully applied it to human tonsil, skin, and breast cancer tissues as well as mouse lung tissues. For complete details on the use and execution of this protocol, please refer to Martinek et al. (2022).


Evaluation Of Mtorc1 Signaling In Mouse Atherosclerotic Macrophages By Flow Cytometry And Immunofluorescence, Xiangyu Zhang, Jeremiah Stitham, Astrid Rodriguez-Velez, Se-Jin Jeong, Arick Park, Yu-Sheng Yeh, Divya Kapoor, Bettina Mittendorfer, Babak Razani Dec 2022

Evaluation Of Mtorc1 Signaling In Mouse Atherosclerotic Macrophages By Flow Cytometry And Immunofluorescence, Xiangyu Zhang, Jeremiah Stitham, Astrid Rodriguez-Velez, Se-Jin Jeong, Arick Park, Yu-Sheng Yeh, Divya Kapoor, Bettina Mittendorfer, Babak Razani

2020-Current year OA Pubs

Previous studies have demonstrated that a high-protein diet leads to increased atherosclerosis in mice, and that this adverse effect is caused by activation of macrophage mTORC1 signaling. Here, we provide a detailed protocol for the evaluation of diet-induced mTORC1 signaling in plaque macrophages in atherosclerosis-prone apolipoprotein E (ApoE) knockout (KO) mice. This protocol includes flow cytometry and immunofluorescence analysis of atherosclerotic macrophages that can be used to study the atherogenic potential of a variety of mTORC1 modulators. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2020).


Mouse Kidney Nuclear Isolation And Library Preparation For Single-Cell Combinatorial Indexing Rna Sequencing, Haikuo Li, Benjamin D. Humphreys Dec 2022

Mouse Kidney Nuclear Isolation And Library Preparation For Single-Cell Combinatorial Indexing Rna Sequencing, Haikuo Li, Benjamin D. Humphreys

2020-Current year OA Pubs

Single-cell combinatorial indexing RNA sequencing (sci-RNA-seq3) enables high-throughput single-nucleus transcriptomic profiling of multiple samples in one experiment. Here, we describe an optimized protocol of mouse kidney nuclei isolation and sci-RNA-seq3 library preparation. The use of a dounce tissue homogenizer enables nuclei extraction with high yield. Fixed nuclei are processed for sci-RNA-seq3, and self-loaded transposome Tn5 is used for tagmentation in library generation. The step-by-step protocol allows researchers to generate scalable single-cell transcriptomic data with common laboratory supplies at low cost. For complete details on the use and execution of this protocol, please refer to Li et al. (2022).


Human Nk Cells Confer Protection Against Hiv-1 Infection In Humanized Mice, Can M. Sungur, Qiankun Wang, Ayşe N. Ozantürk, Hongbo Gao, Aaron J. Schmitz, Marina Cella, Wayne M. Yokoyama, Liang Shan Dec 2022

Human Nk Cells Confer Protection Against Hiv-1 Infection In Humanized Mice, Can M. Sungur, Qiankun Wang, Ayşe N. Ozantürk, Hongbo Gao, Aaron J. Schmitz, Marina Cella, Wayne M. Yokoyama, Liang Shan

2020-Current year OA Pubs

The role of NK cells against HIV-1 infections remains to be elucidated in vivo. While humanized mouse models potentially could be used to directly evaluate human NK cell responses during HIV-1 infection, improved functional development of human NK cells in these hosts is needed. Here, we report the humanized MISTRG-6-15 mouse model, in which NK cells were quick to expand and exhibit degranulation, cytotoxicity, and proinflammatory cytokine production in nonlymphoid organs upon HIV-1 infection but had reduced functionality in lymphoid organs. Although HIV-1 infection induced functional impairment of NK cells, antiretroviral therapy reinvigorated NK cells in response to HIV-1 rebound …


Social Attention During Object Engagement: Toward A Cross-Species Measure Of Preferential Social Orienting, Claire Weichselbaum, Nicole Hendrix, Jordan Albright, Joseph D Dougherty, Kelly N Botteron, John N Constantino, Natasha Marrus Dec 2022

Social Attention During Object Engagement: Toward A Cross-Species Measure Of Preferential Social Orienting, Claire Weichselbaum, Nicole Hendrix, Jordan Albright, Joseph D Dougherty, Kelly N Botteron, John N Constantino, Natasha Marrus

2020-Current year OA Pubs

BACKGROUND: A central challenge in preclinical research investigating the biology of autism spectrum disorder (ASD) is the translation of ASD-related social phenotypes across humans and animal models. Social orienting, an observable, evolutionarily conserved behavior, represents a promising cross-species ASD phenotype given that disrupted social orienting is an early-emerging ASD feature with evidence for predicting familial recurrence. Here, we adapt a competing-stimulus social orienting task from domesticated dogs to naturalistic play behavior in human toddlers and test whether this approach indexes decreased social orienting in ASD.

METHODS: Play behavior was coded from the Autism Diagnostic Observation Schedule (ADOS) in two samples …


Gata1 Controls Numbers Of Hematopoietic Progenitors And Their Response To Autoimmune Neuroinflammation, Daniel Hwang, Larissa Ishikawa, Maryam S. Seyedsadr, Elisabeth R. Mari, Ezgi Kasimoglu, Ziver Sahin, Alexandra Boehm, Soohwa Jang, Javad Rasouli, Courtney Vaccaro, Michael Gonzalez, Hakon Hakonarson, Mohamad Rostami, Guang-Xian Zhang, Bogoljub Ciric Dec 2022

Gata1 Controls Numbers Of Hematopoietic Progenitors And Their Response To Autoimmune Neuroinflammation, Daniel Hwang, Larissa Ishikawa, Maryam S. Seyedsadr, Elisabeth R. Mari, Ezgi Kasimoglu, Ziver Sahin, Alexandra Boehm, Soohwa Jang, Javad Rasouli, Courtney Vaccaro, Michael Gonzalez, Hakon Hakonarson, Mohamad Rostami, Guang-Xian Zhang, Bogoljub Ciric

Department of Neurology Faculty Papers

GATA-binding factor 1 (GATA1) is a transcription factor that governs the development and function of multiple hematopoietic cell lineages. GATA1 is expressed in hematopoietic stem and progenitor cells (HSPCs) and is essential for erythroid lineage commitment; however, whether it plays a role in hematopoietic stem cell (HSC) biology and the development of myeloid cells, and what that role might be, remains unclear. We initially set out to test the role of eosinophils in experimental autoimmune encephalomyelitis (EAE), a model of central nervous system autoimmunity, using mice lacking a double GATA-site (ΔdblGATA), which lacks eosinophils due to the deletion of the …


Stat3 Gain-Of-Function Mutations Connect Leukemia With Autoimmune Disease By Pathological Nkg2dhi Cd8+ T Cell Dysregulation And Accumulation, Etienne Masle-Farquhar, Megan A Cooper, Tiphanie P Vogel, Et Al. Dec 2022

Stat3 Gain-Of-Function Mutations Connect Leukemia With Autoimmune Disease By Pathological Nkg2dhi Cd8+ T Cell Dysregulation And Accumulation, Etienne Masle-Farquhar, Megan A Cooper, Tiphanie P Vogel, Et Al.

2020-Current year OA Pubs

The association between cancer and autoimmune disease is unexplained, exemplified by T cell large granular lymphocytic leukemia (T-LGL) where gain-of-function (GOF) somatic STAT3 mutations correlate with co-existing autoimmunity. To investigate whether these mutations are the cause or consequence of CD8


Tenotomy-Induced Muscle Atrophy Is Sex-Specific And Independent Of Nfκb, Gretchen A Meyer, Stavros Thomopoulos, Yousef Abu-Amer, Karen C Shen Dec 2022

Tenotomy-Induced Muscle Atrophy Is Sex-Specific And Independent Of Nfκb, Gretchen A Meyer, Stavros Thomopoulos, Yousef Abu-Amer, Karen C Shen

2020-Current year OA Pubs

The nuclear factor-κB (NFκB) pathway is a major thoroughfare for skeletal muscle atrophy and is driven by diverse stimuli. Targeted inhibition of NFκB through its canonical mediator IKKβ effectively mitigates loss of muscle mass across many conditions, from denervation to unloading to cancer. In this study, we used gain- and loss-of-function mouse models to examine the role of NFκB in muscle atrophy following rotator cuff tenotomy - a model of chronic rotator cuff tear. IKKβ was knocked down or constitutively activated in muscle-specific inducible transgenic mice to elicit a twofold gain or loss of NFκB signaling. Surprisingly, neither knockdown of …


Loss Of Pex1 In Inner Ear Hair Cells Contributes To Cochlear Synaptopathy And Hearing Loss., Stephanie A Mauriac, Thibault Peineau, Aamir Zuberi, Cathleen Lutz, Gwénaëlle S G Géléoc Dec 2022

Loss Of Pex1 In Inner Ear Hair Cells Contributes To Cochlear Synaptopathy And Hearing Loss., Stephanie A Mauriac, Thibault Peineau, Aamir Zuberi, Cathleen Lutz, Gwénaëlle S G Géléoc

Faculty Research 2022

Peroxisome Biogenesis Disorders (PBD) and Zellweger syndrome spectrum disorders (ZSD) are rare genetic multisystem disorders that include hearing impairment and are associated with defects in peroxisome assembly, function, or both. Mutations in 13 peroxin (PEX) genes have been found to cause PBD-ZSD with ~70% of patients harboring mutations in PEX1. Limited research has focused on the impact of peroxisomal disorders on auditory function. As sensory hair cells are particularly vulnerable to metabolic changes, we hypothesize that mutations in PEX1 lead to oxidative stress affecting hair cells of the inner ear, subsequently resulting in hair cell degeneration and hearing loss. Global …


Acetyl-Coa-Mediated Autoacetylation Of Fatty Acid Synthase As A Metabolic Switch Of De Novo Lipogenesis In Drosophila, Ting Miao, Jinoh Kim, Ping Kang, Hideji Fujiwara, Fong-Fu Hsu, Hua Bai Dec 2022

Acetyl-Coa-Mediated Autoacetylation Of Fatty Acid Synthase As A Metabolic Switch Of De Novo Lipogenesis In Drosophila, Ting Miao, Jinoh Kim, Ping Kang, Hideji Fujiwara, Fong-Fu Hsu, Hua Bai

2020-Current year OA Pubs

De novo lipogenesis is a highly regulated metabolic process, which is known to be activated through transcriptional regulation of lipogenic genes, including fatty acid synthase (FASN). Unexpectedly, we find that the expression of FASN protein remains unchanged during


Taxonomic Assessment Of Two Wild House Mouse Subspecies Using Whole-Genome Sequencing., Raman Akinyanju Lawal, Verity L Mathis, Mary Barter, Jeremy R. Charette, Alexis Garretson, Beth L Dumont Dec 2022

Taxonomic Assessment Of Two Wild House Mouse Subspecies Using Whole-Genome Sequencing., Raman Akinyanju Lawal, Verity L Mathis, Mary Barter, Jeremy R. Charette, Alexis Garretson, Beth L Dumont

Faculty Research 2022

The house mouse species complex (Mus musculus) is comprised of three primary subspecies. A large number of secondary subspecies have also been suggested on the basis of divergent morphology and molecular variation at limited numbers of markers. While the phylogenetic relationships among the primary M. musculus subspecies are well-defined, relationships among secondary subspecies and between secondary and primary subspecies remain less clear. Here, we integrate de novo genome sequencing of museum-stored specimens of house mice from one secondary subspecies (M. m. bactrianus) and publicly available genome sequences of house mice previously characterized as M. m. helgolandicus, with whole genome sequences …


Distinct Tumor Necrosis Factor Alpha Receptors Dictate Stem Cell Fitness Versus Lineage Output In Dnmt3a-Mutant Clonal Hematopoiesis., Jennifer M. Sanmiguel, Elizabeth Eudy, Matthew A. Loberg, Kira Young, Jayna J. Mistry, Kristina D. Mujica, Logan S. Schwartz, Timothy M. Stearns, Grant A Challen, Jennifer J. Trowbridge Dec 2022

Distinct Tumor Necrosis Factor Alpha Receptors Dictate Stem Cell Fitness Versus Lineage Output In Dnmt3a-Mutant Clonal Hematopoiesis., Jennifer M. Sanmiguel, Elizabeth Eudy, Matthew A. Loberg, Kira Young, Jayna J. Mistry, Kristina D. Mujica, Logan S. Schwartz, Timothy M. Stearns, Grant A Challen, Jennifer J. Trowbridge

Faculty Research 2022

Clonal hematopoiesis resulting from the enhanced fitness of mutant hematopoietic stem cells (HSC) associates with both favorable and unfavorable health outcomes related to the types of mature mutant blood cells produced, but how this lineage output is regulated is unclear. Using a mouse model of a clonal hematopoiesis-associated mutation, DNMT3AR882/+ (Dnmt3aR878H/+), we found that aging-induced TNFα signaling promoted the selective advantage of mutant HSCs and stimulated the production of mutant B lymphoid cells. The genetic loss of the TNFα receptor TNFR1 ablated the selective advantage of mutant HSCs without altering their lineage output, whereas the loss of TNFR2 resulted in …


Distinct Tumor Necrosis Factor Alpha Receptors Dictate Stem Cell Fitness Versus Lineage Output In Dnmt3a-Mutant Clonal Hematopoiesis, Jennifer M Sanmiguel, Elizabeth Eudy, Matthew A Loberg, Kira A Young, Jayna J Mistry, Kristina D Mujica, Logan S Schwartz, Timothy M Stearns, Grant A Challen, Jennifer J Trowbridge Dec 2022

Distinct Tumor Necrosis Factor Alpha Receptors Dictate Stem Cell Fitness Versus Lineage Output In Dnmt3a-Mutant Clonal Hematopoiesis, Jennifer M Sanmiguel, Elizabeth Eudy, Matthew A Loberg, Kira A Young, Jayna J Mistry, Kristina D Mujica, Logan S Schwartz, Timothy M Stearns, Grant A Challen, Jennifer J Trowbridge

2020-Current year OA Pubs

UNLABELLED: Clonal hematopoiesis resulting from the enhanced fitness of mutant hematopoietic stem cells (HSC) associates with both favorable and unfavorable health outcomes related to the types of mature mutant blood cells produced, but how this lineage output is regulated is unclear. Using a mouse model of a clonal hematopoiesis-associated mutation, DNMT3AR882/+ (Dnmt3aR878H/+), we found that aging-induced TNFα signaling promoted the selective advantage of mutant HSCs and stimulated the production of mutant B lymphoid cells. The genetic loss of the TNFα receptor TNFR1 ablated the selective advantage of mutant HSCs without altering their lineage output, whereas the loss of TNFR2 resulted …


Genome-Edited Zebrafish Model Of Abcc8 Loss-Of-Function Disease, Jennifer M Ikle, Robert C Tryon, Soma S Singareddy, Nathaniel W York, Maria S Remedi, Colin G Nichols Dec 2022

Genome-Edited Zebrafish Model Of Abcc8 Loss-Of-Function Disease, Jennifer M Ikle, Robert C Tryon, Soma S Singareddy, Nathaniel W York, Maria S Remedi, Colin G Nichols

2020-Current year OA Pubs

ATP-sensitive potassium channel (K


Research Note: Association Of Single Nucleotide Polymorphism Of Akt3 With Egg Production Traits In White Muscovy Ducks (Cairina Moschata)., Semiu Folaniyi Bello, Haiping Xu, Kan Li, Lijin Guo, Siyu Zhang, Ridwan Olawale Ahmed, Endashaw Jebessa Bekele, Ming Zheng, Mingjian Xian, Bahareldin Ali Abdalla, Adeniyi Charles Adeola, Adeyinka Abiola Adetula, Raman Akinyanju Lawal, Weijian Zhu, Dexiang Zhang, Xiquan Zhang, Congliang Ji, Qinghua Nie Dec 2022

Research Note: Association Of Single Nucleotide Polymorphism Of Akt3 With Egg Production Traits In White Muscovy Ducks (Cairina Moschata)., Semiu Folaniyi Bello, Haiping Xu, Kan Li, Lijin Guo, Siyu Zhang, Ridwan Olawale Ahmed, Endashaw Jebessa Bekele, Ming Zheng, Mingjian Xian, Bahareldin Ali Abdalla, Adeniyi Charles Adeola, Adeyinka Abiola Adetula, Raman Akinyanju Lawal, Weijian Zhu, Dexiang Zhang, Xiquan Zhang, Congliang Ji, Qinghua Nie

Faculty Research 2022

Prior studies on transcriptomes of hypothalamus and ovary revealed that AKT3 is one of the candidate genes that might affect egg production in White Muscovy ducks. The role of AKT3 in the uterus during reproductive processes cannot be overemphasized. However, functional role of this gene in the tissues and on egg production traits of Muscovy ducks remains unknown. To identify the relationship between AKT3 and egg production traits in ducks, relative expression profile was first examined prior to identifying the variants within AKT3 that may underscore egg production traits [age at first egg (AFE), number of eggs at 300 d …


Analysis Of Genome-Wide Knockout Mouse Database Identifies Candidate Ciliopathy Genes., Kendall Higgins, Bret A Moore, Zorana Berberovic, Hibret A Adissu, Mohammad Eskandarian, Ann M Flenniken, Andy Shao, Denise M Imai, Dave Clary, Louise Lanoue, Susan Newbigging, Lauryl M J Nutter, David J Adams, Fatima Bosch, Robert Schneider, Steve D M Brown, Mary E Dickinson, Michael Dobbie, Paul Flicek, Xiang Gao, Sanjeev Galande, Anne Grobler, Jason D Heaney, Yann Herault, Martin Hrabe De Angelis, Hsian-Jean Genie Chin, Fabio Mammano, Chuan Qin, Toshihiko Shiroishi, Radislav Sedlacek, J-K Seong, Ying Xu, K C Kent Lloyd, Colin Mckerlie, Ala Moshiri Dec 2022

Analysis Of Genome-Wide Knockout Mouse Database Identifies Candidate Ciliopathy Genes., Kendall Higgins, Bret A Moore, Zorana Berberovic, Hibret A Adissu, Mohammad Eskandarian, Ann M Flenniken, Andy Shao, Denise M Imai, Dave Clary, Louise Lanoue, Susan Newbigging, Lauryl M J Nutter, David J Adams, Fatima Bosch, Robert Schneider, Steve D M Brown, Mary E Dickinson, Michael Dobbie, Paul Flicek, Xiang Gao, Sanjeev Galande, Anne Grobler, Jason D Heaney, Yann Herault, Martin Hrabe De Angelis, Hsian-Jean Genie Chin, Fabio Mammano, Chuan Qin, Toshihiko Shiroishi, Radislav Sedlacek, J-K Seong, Ying Xu, K C Kent Lloyd, Colin Mckerlie, Ala Moshiri

Faculty Research 2022

We searched a database of single-gene knockout (KO) mice produced by the International Mouse Phenotyping Consortium (IMPC) to identify candidate ciliopathy genes. We first screened for phenotypes in mouse lines with both ocular and renal or reproductive trait abnormalities. The STRING protein interaction tool was used to identify interactions between known cilia gene products and those encoded by the genes in individual knockout mouse strains in order to generate a list of "candidate ciliopathy genes." From this list, 32 genes encoded proteins predicted to interact with known ciliopathy proteins. Of these, 25 had no previously described roles in ciliary pathobiology. …


Lifespan Benefits For The Combination Of Rapamycin Plus Acarbose And For Captopril In Genetically Heterogeneous Mice., Randy Strong, Richard A Miller, Catherine J Cheng, James F Nelson, Jonathan Gelfond, Shailaja Kesaraju Allani, Vivian Diaz, Angela Olsen Dorigatti, Jonathan Dorigatti, Elizabeth Fernandez, Andrzej Galecki, Brett Ginsburg, Karyn L Hamilton, Martin A Javors, Kerry Kornfeld, Matt Kaeberlein, Suja Kumar, David B Lombard, Marisa Lopez-Cruzan, Benjamin F Miller, Peter Rabinovitch, Peter C. Reifsnyder, Nadia Rosenthal, Molly A. Bogue, Adam B Salmon, Yousin Suh, Eric Verdin, Herbert Weissbach, John Newman, Francesca Maccchiarini, David E. Harrison Dec 2022

Lifespan Benefits For The Combination Of Rapamycin Plus Acarbose And For Captopril In Genetically Heterogeneous Mice., Randy Strong, Richard A Miller, Catherine J Cheng, James F Nelson, Jonathan Gelfond, Shailaja Kesaraju Allani, Vivian Diaz, Angela Olsen Dorigatti, Jonathan Dorigatti, Elizabeth Fernandez, Andrzej Galecki, Brett Ginsburg, Karyn L Hamilton, Martin A Javors, Kerry Kornfeld, Matt Kaeberlein, Suja Kumar, David B Lombard, Marisa Lopez-Cruzan, Benjamin F Miller, Peter Rabinovitch, Peter C. Reifsnyder, Nadia Rosenthal, Molly A. Bogue, Adam B Salmon, Yousin Suh, Eric Verdin, Herbert Weissbach, John Newman, Francesca Maccchiarini, David E. Harrison

Faculty Research 2022

Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone. In females, lifespan in mice …


Expression And Localization Of Nrf2/Keap1 Signalling Pathway Genes In Mouse Preimplantation Embryos Exposed To Free Fatty Acids., Grace Dionne, Michele D. Calder, Dean H Betts, Basim Abu Rafea, Andrew J Watson Dec 2022

Expression And Localization Of Nrf2/Keap1 Signalling Pathway Genes In Mouse Preimplantation Embryos Exposed To Free Fatty Acids., Grace Dionne, Michele D. Calder, Dean H Betts, Basim Abu Rafea, Andrew J Watson

Obstetrics & Gynaecology Publications

Obese women experience greater incidence of infertility, with reproductive tracts exposing preimplantation embryos to elevated free fatty acids (FFA) such as palmitic acid (PA) and oleic acid (OA). PA treatment impairs mouse preimplantation development in vitro, while OA co-treatment rescues blastocyst development of PA treated embryos. In the present study, we investigated the effects of PA and OA treatment on NRF2/Keap1 localization, and relative antioxidant enzyme (Glutathione peroxidase; Gpx1, Catalase; Cat, Superoxide dismutase; Sod1 and γ-Glutamylcysteine ligase catalytic unit; Gclc) mRNA levels, during in vitro mouse preimplantation embryo development. Female mice were superovulated, mated, and embryos cultured in the presence …


Management Of Mammalian Bites To The External Genitalia: A Scoping Review., Sagar R Patel, Pratik Kanabur, Harlee E Possoit, Austin Kinley, Beatriz Varman, Michael Coburn, Shyam Sukumar Dec 2022

Management Of Mammalian Bites To The External Genitalia: A Scoping Review., Sagar R Patel, Pratik Kanabur, Harlee E Possoit, Austin Kinley, Beatriz Varman, Michael Coburn, Shyam Sukumar

Library Staff Publications

OBJECTIVE: To review existing publications to determine the approaches for the medical and operative management of mammalian bites to the external genitalia.

MATERIALS AND METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Review guidelines were followed. Four databases were searched. Articles were independently screened and analysed by two reviewers. Publications were included if detailed summaries of genitalia bites and management were documented. Discrepancies were resolved by a third reviewer. Data were extracted from the final article cohort.

RESULTS: A total of 42 articles were included in this scoping review with 67 cases of mammalian bites to …