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Allopregnanolone Effects On Inhibition In Hippocampal Parvalbumin Interneurons, Xinguo Lu, Peter Lambert, Ann Benz, Charles F. Zorumski, Steven J. Mennerick Mar 2023

Allopregnanolone Effects On Inhibition In Hippocampal Parvalbumin Interneurons, Xinguo Lu, Peter Lambert, Ann Benz, Charles F. Zorumski, Steven J. Mennerick

2020-Current year OA Pubs

Allopregnanolone (AlloP) is a neurosteroid that potentiates ionotropic GABAergic (GABA


Mechanism Of Kmt5b Haploinsufficiency In Neurodevelopment In Humans And Mice, Sarah E Sheppard, Marisa Andrews, Dustin Baldridge, John Constantino, Et Al. Mar 2023

Mechanism Of Kmt5b Haploinsufficiency In Neurodevelopment In Humans And Mice, Sarah E Sheppard, Marisa Andrews, Dustin Baldridge, John Constantino, Et Al.

2020-Current year OA Pubs

Pathogenic variants in


Eus-Guided Vascular Interventions, Michelle Baliss, Devan Patel, Mahmoud Y Madi, Ahmad Najdat Bazarbashi Mar 2023

Eus-Guided Vascular Interventions, Michelle Baliss, Devan Patel, Mahmoud Y Madi, Ahmad Najdat Bazarbashi

2020-Current year OA Pubs

Endoscopic ultrasound (EUS) has numerous advanced applications as a diagnostic and therapeutic modality in contemporary medicine. Through intraluminal placement, EUS offers a real-time Doppler-guided endoscopic visualization and access to intra-abdominal vasculature, which were previously inaccessible using historical methods. We aim to provide a comprehensive review of key studies on both current and future EUS-guided vascular applications. This review details EUS-based vascular diagnostic techniques of portal pressure measurements in the prognostication of liver disease and portal venous sampling for obtaining circulating tumor cells in the diagnosis of cancer. From an interventional perspective, we describe effective EUS-guided treatments via coiling and cyanoacrylate …


Neurofibromatosis Type 1-Dependent Alterations In Mouse Microglia Function Are Not Cell-Intrinsic, Francesca Logiacco, Laura Cathleen Grzegorzek, Elizabeth C Cordell, Oliver Popp, Philipp Mertins, David H Gutmann, Helmut Kettenmann, Marcus Semtner Mar 2023

Neurofibromatosis Type 1-Dependent Alterations In Mouse Microglia Function Are Not Cell-Intrinsic, Francesca Logiacco, Laura Cathleen Grzegorzek, Elizabeth C Cordell, Oliver Popp, Philipp Mertins, David H Gutmann, Helmut Kettenmann, Marcus Semtner

2020-Current year OA Pubs

We previously discovered a sex-by-genotype defect in microglia function using a heterozygous germline knockout mouse model of Neurofibromatosis type 1 (Nf1 ± mice), in which only microglia from male Nf1 ± mice exhibited defects in purinergic signaling. Herein, we leveraged an unbiased proteomic approach to demonstrate that male, but not female, heterozygous Nf1 ± microglia exhibit differences in protein expression, which largely reflect pathways involved in cytoskeletal organization. In keeping with these predicted defects in cytoskeletal function, only male Nf1 ± microglia had reduced process arborization and surveillance capacity. To determine whether these microglial defects were cell autonomous or reflected …


Role Of Klotho And Age/Rage-Wnt/Β-Catenin Signalling Pathway On The Development Of Cardiac And Renal Fibrosis In Diabetes, Beatriz Martín-Carro, Julia Martín-Vírgala, Sara Fernández-Villabrille, Alejandra Fernández-Fernández, Marcos Pérez-Basterrechea, Juan F Navarro-González, Javier Donate-Correa, Carmen Mora-Fernández, Adriana S Dusso, Natalia Carrillo-López, Sara Panizo, Manuel Naves-Díaz, José L Fernández-Martín, Jorge B Cannata-Andía, Cristina Alonso-Montes Mar 2023

Role Of Klotho And Age/Rage-Wnt/Β-Catenin Signalling Pathway On The Development Of Cardiac And Renal Fibrosis In Diabetes, Beatriz Martín-Carro, Julia Martín-Vírgala, Sara Fernández-Villabrille, Alejandra Fernández-Fernández, Marcos Pérez-Basterrechea, Juan F Navarro-González, Javier Donate-Correa, Carmen Mora-Fernández, Adriana S Dusso, Natalia Carrillo-López, Sara Panizo, Manuel Naves-Díaz, José L Fernández-Martín, Jorge B Cannata-Andía, Cristina Alonso-Montes

2020-Current year OA Pubs

Fibrosis plays an important role in the pathogenesis of long-term diabetic complications and contributes to the development of cardiac and renal dysfunction. The aim of this experimental study, performed in a long-term rat model, which resembles type 1 diabetes mellitus, was to investigate the role of soluble Klotho (sKlotho), advanced glycation end products (AGEs)/receptor for AGEs (RAGE), fibrotic Wnt/β-catenin pathway, and pro-fibrotic pathways in kidney and heart. Diabetes was induced by streptozotocin. Glycaemia was maintained by insulin administration for 24 weeks. Serum and urine sKlotho, AGEs, soluble RAGE (sRAGE) and biochemical markers were studied. The levels of Klotho, RAGEs, ADAM10, …


Adipose-Targeted Swell1 Deletion Exacerbates Obesity- And Age-Related Nonalcoholic Fatty Liver Disease, Susheel K. Gunasekar, John Heebink, Danielle H Carpenter, Ashutosh Kumar, Litao Xie, Haixia Zhang, Joel D. Schilling, Rajan Sah Mar 2023

Adipose-Targeted Swell1 Deletion Exacerbates Obesity- And Age-Related Nonalcoholic Fatty Liver Disease, Susheel K. Gunasekar, John Heebink, Danielle H Carpenter, Ashutosh Kumar, Litao Xie, Haixia Zhang, Joel D. Schilling, Rajan Sah

2020-Current year OA Pubs

Healthy expansion of adipose tissue is critical for the maintenance of metabolic health, providing an optimized reservoir for energy storage in the form of triacylglycerol-rich lipoproteins. Dysfunctional adipocytes that are unable to efficiently store lipid can result in lipodystrophy and contribute to nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. Leucine-rich repeat containing protein 8a/SWELL1 functionally encodes the volume-regulated anion channel complex in adipocytes, is induced in early obesity, and is required for normal adipocyte expansion during high-fat feeding. Adipose-specific SWELL1 ablation (Adipo KO) leads to insulin resistance and hyperglycemia during caloric excess, both of which are associated with NAFLD. …


Charge-Voltage Curves Of Shaker Potassium Channel Are Not Hysteretic At Steady State, John Cowgill, Baron Chanda Mar 2023

Charge-Voltage Curves Of Shaker Potassium Channel Are Not Hysteretic At Steady State, John Cowgill, Baron Chanda

2020-Current year OA Pubs

Charge-voltage curves of many voltage-gated ion channels exhibit hysteresis but such curves are also a direct measure of free energy of channel gating and, hence, should be path-independent. Here, we identify conditions to measure steady-state charge-voltage curves and show that these are curves are not hysteretic. Charged residues in transmembrane segments of voltage-gated ion channels (VGICs) sense and respond to changes in the electric field. The movement of these gating charges underpins voltage-dependent activation and is also a direct metric of the net free-energy of channel activation. However, for most voltage-gated ion channels, the charge-voltage (Q-V) curves appear to be …


Insights Into Pulmonary Phosphate Homeostasis And Osteoclastogenesis Emerge From The Study Of Pulmonary Alveolar Microlithiasis, Yasuaki Uehara, Steven L Teitelbaum, Et Al. Mar 2023

Insights Into Pulmonary Phosphate Homeostasis And Osteoclastogenesis Emerge From The Study Of Pulmonary Alveolar Microlithiasis, Yasuaki Uehara, Steven L Teitelbaum, Et Al.

2020-Current year OA Pubs

Pulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a pulmonary alveolar microlithiasis lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes and other proteins suggested a role for osteoclast-like cells in the host response to microliths. While investigating the mechanisms of microlith clearance, we found …


Frequent First-Trimester Pregnancy Loss In Rhesus Macaques Infected With African-Lineage Zika Virus, Jenna R. Rosinski, Kevin K. Noguchi, Et Al. Mar 2023

Frequent First-Trimester Pregnancy Loss In Rhesus Macaques Infected With African-Lineage Zika Virus, Jenna R. Rosinski, Kevin K. Noguchi, Et Al.

2020-Current year OA Pubs

In the 2016 Zika virus (ZIKV) pandemic, a previously unrecognized risk of birth defects surfaced in babies whose mothers were infected with Asian-lineage ZIKV during pregnancy. Less is known about the impacts of gestational African-lineage ZIKV infections. Given high human immunodeficiency virus (HIV) burdens in regions where African-lineage ZIKV circulates, we evaluated whether pregnant rhesus macaques infected with simian immunodeficiency virus (SIV) have a higher risk of African-lineage ZIKV-associated birth defects. Remarkably, in both SIV+ and SIV- animals, ZIKV infection early in the first trimester caused a high incidence (78%) of spontaneous pregnancy loss within 20 days. These findings suggest …


Hiv Increases The Risk Of Cigarette Smoke-Induced Emphysema Through Mmp-9, Bashar S. Staitieh, Simran Malik, Sara C. Auld, Gregory W. Wigger, Xian Fan, Andrew T. Roth, Tanima Chatterjee, Itika Arora, S. Vamsee Raju, Sonya Heath, Saurabh Aggrawal Mar 2023

Hiv Increases The Risk Of Cigarette Smoke-Induced Emphysema Through Mmp-9, Bashar S. Staitieh, Simran Malik, Sara C. Auld, Gregory W. Wigger, Xian Fan, Andrew T. Roth, Tanima Chatterjee, Itika Arora, S. Vamsee Raju, Sonya Heath, Saurabh Aggrawal

2020-Current year OA Pubs

BACKGROUND: HIV is associated with an increased risk for emphysema. Matrix metalloproteinase 9 (MMP-9) is a lung tissue remodeling enzyme associated with emphysema. We previously found MMP-9 activity increases with increases in oxidative stress and that HIV increases alveolar oxidative stress. We hypothesized that HIV proteins would increase the risk of cigarette smoke-induced emphysema due to MMP-9.

METHODS: HIV-1 transgenic rats and wild-type littermates were exposed to cigarette smoke or sham for 8 weeks. Lung compliance and histology were assessed. Bronchoalveolar lavage (BAL), primary alveolar macrophages (AM), and serum samples were obtained. A rat alveolar macrophage cell line was exposed …


Building The Foundation For A Community-Generated National Research Blueprint For Inherited Bleeding Disorders: Research Priorities For Mucocutaneous Bleeding Disorders, Robert F Sidonio Jr, Jorge Di Paola, Et Al. Mar 2023

Building The Foundation For A Community-Generated National Research Blueprint For Inherited Bleeding Disorders: Research Priorities For Mucocutaneous Bleeding Disorders, Robert F Sidonio Jr, Jorge Di Paola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Excessive or abnormal mucocutaneous bleeding (MCB) may impact all aspects of the physical and psychosocial wellbeing of those who live with it (PWMCB). The evidence base for the optimal diagnosis and management of disorders such as inherited platelet disorders, hereditary hemorrhagic telangiectasia (HHT), hypermobility spectrum disorders (HSD), Ehlers-Danlos syndromes (EDS), and von Willebrand disease (VWD) remains thin with enormous potential for targeted research.

RESEARCH DESIGN AND METHODS: National Hemophilia Foundation and American Thrombosis and Hemostasis Network initiated the development of a National Research Blueprint for Inherited Bleeding Disorders with extensive all-stakeholder consultations to identify the priorities of people with …


Targeted Deletion Of Fgf9 In Tendon Disrupts Mineralization Of The Developing Enthesis, Elahe Ganji, Connor Leek, William Duncan, Debabrata Patra, David M Ornitz, Megan L Killian Mar 2023

Targeted Deletion Of Fgf9 In Tendon Disrupts Mineralization Of The Developing Enthesis, Elahe Ganji, Connor Leek, William Duncan, Debabrata Patra, David M Ornitz, Megan L Killian

2020-Current year OA Pubs

The enthesis is a transitional tissue between tendon and bone that matures postnatally. The development and maturation of the enthesis involve cellular processes likened to an arrested growth plate. In this study, we explored the role of fibroblast growth factor 9 (Fgf9), a known regulator of chondrogenesis and vascularization during bone development, on the structure and function of the postnatal enthesis. First, we confirmed spatial expression of Fgf9 in the tendon and enthesis using in situ hybridization. We then used Cre-lox recombinase to conditionally knockout Fgf9 in mouse tendon and enthesis (Scx-Cre) and characterized enthesis morphology as well as mechanical …


Aging And Obesity Prime The Methylome And Transcriptome Of Adipose Stem Cells For Disease And Dysfunction, Shaojun Xie, Sulbha Choudhari, Chia-Lung Wu, Karen Abramson, David Corcoran, Simon G Gregory, Jyothi Thimmapuram, Farshid Guilak, Dianne Little Mar 2023

Aging And Obesity Prime The Methylome And Transcriptome Of Adipose Stem Cells For Disease And Dysfunction, Shaojun Xie, Sulbha Choudhari, Chia-Lung Wu, Karen Abramson, David Corcoran, Simon G Gregory, Jyothi Thimmapuram, Farshid Guilak, Dianne Little

2020-Current year OA Pubs

The epigenome of stem cells occupies a critical interface between genes and environment, serving to regulate expression through modification by intrinsic and extrinsic factors. We hypothesized that aging and obesity, which represent major risk factors for a variety of diseases, synergistically modify the epigenome of adult adipose stem cells (ASCs). Using integrated RNA- and targeted bisulfite-sequencing in murine ASCs from lean and obese mice at 5- and 12-months of age, we identified global DNA hypomethylation with either aging or obesity, and a synergistic effect of aging combined with obesity. The transcriptome of ASCs in lean mice was relatively stable to …


Resolution Of Hepatic Fibrosis After Zfn-Mediated Gene Editing In The Piz Mouse Model Of Human Α1-Antitrypsin Deficiency, Yanfeng Li, Chandan Guha, Patrik Asp, Xia Wang, Tatyana L. Tchaikovskya, Kenneth Kim, Matthew Mendel, Gregory J. Cost, David H. Perlmutter, Namita Roy-Chowdhury, Ira J. Fox, Anthony Conway, Jayanta Roy-Chowdhury Mar 2023

Resolution Of Hepatic Fibrosis After Zfn-Mediated Gene Editing In The Piz Mouse Model Of Human Α1-Antitrypsin Deficiency, Yanfeng Li, Chandan Guha, Patrik Asp, Xia Wang, Tatyana L. Tchaikovskya, Kenneth Kim, Matthew Mendel, Gregory J. Cost, David H. Perlmutter, Namita Roy-Chowdhury, Ira J. Fox, Anthony Conway, Jayanta Roy-Chowdhury

2020-Current year OA Pubs

BACKGROUND: α1-antitrypsin deficiency is most commonly caused by a mutation in exon-7 of SERPINA1 (SA1-ATZ), resulting in hepatocellular accumulation of a misfolded variant (ATZ). Human SA1-ATZ-transgenic (PiZ) mice exhibit hepatocellular ATZ accumulation and liver fibrosis. We hypothesized that disrupting the SA1-ATZ transgene in PiZ mice by in vivo genome editing would confer a proliferative advantage to the genome-edited hepatocytes, enabling them to repopulate the liver.

METHODS: To create a targeted DNA break in exon-7 of the SA1-ATZ transgene, we generated 2 recombinant adeno-associated viruses (rAAV) expressing a zinc-finger nuclease pair (rAAV-ZFN), and another rAAV for gene correction by targeted insertion …


A New Mouse Model Of Elastin Haploinsufficiency Highlights The Importance Of Elastin To Vascular Development And Blood Pressure Regulation, Bridget M Brengle, Michelle Lin, Robyn A Roth, Kara D Jones, Jessica E Wagenseil, Robert P Mecham, Carmen M Halabi Mar 2023

A New Mouse Model Of Elastin Haploinsufficiency Highlights The Importance Of Elastin To Vascular Development And Blood Pressure Regulation, Bridget M Brengle, Michelle Lin, Robyn A Roth, Kara D Jones, Jessica E Wagenseil, Robert P Mecham, Carmen M Halabi

2020-Current year OA Pubs

Supravalvular aortic stenosis (SVAS) is an autosomal dominant disease resulting from elastin (ELN) haploinsufficiency. Individuals with SVAS typically develop a thickened arterial media with an increased number of elastic lamellae and smooth muscle cell (SMC) layers and stenosis superior to the aortic valve. A mouse model of SVAS (Eln


Cmpk2 Is A Host Restriction Factor That Inhibits Infection Of Multiple Coronaviruses In A Cell-Intrinsic Manner, Mingjun Zhu, Jiahuang Lv, Wei Wang, Rongli Guo, Chunyan Zhong, Avan Antia, Qiru Zeng, Jizong Li, Qingtao Liu, Jinzhu Zhou, Xuejiao Zhu, Baochao Fan, Siyuan Ding, Bin Li Mar 2023

Cmpk2 Is A Host Restriction Factor That Inhibits Infection Of Multiple Coronaviruses In A Cell-Intrinsic Manner, Mingjun Zhu, Jiahuang Lv, Wei Wang, Rongli Guo, Chunyan Zhong, Avan Antia, Qiru Zeng, Jizong Li, Qingtao Liu, Jinzhu Zhou, Xuejiao Zhu, Baochao Fan, Siyuan Ding, Bin Li

2020-Current year OA Pubs

Coronaviruses (CoVs) comprise a group of important human and animal pathogens. Despite extensive research in the past 3 years, the host innate immune defense mechanisms against CoVs remain incompletely understood, limiting the development of effective antivirals and non-antibody-based therapeutics. Here, we performed an integrated transcriptomic analysis of porcine jejunal epithelial cells infected with porcine epidemic diarrhea virus (PEDV) and identified cytidine/uridine monophosphate kinase 2 (CMPK2) as a potential host restriction factor. CMPK2 exhibited modest antiviral activity against PEDV infection in multiple cell types. CMPK2 transcription was regulated by interferon-dependent and interferon regulatory factor 1 (IRF1)-dependent pathways post-PEDV infection. We demonstrated …


An Open Label Randomized Controlled Trial Of Ivermectin Plus Favipiravir-Based Standard Of Care Versus Favipiravir-Based Standard Of Care For Treatment Of Moderate Covid-19 In Thailand, Phahol Sarojvisut, Anucha Apisarnthanarak, Kittiya Jantarathaneewat, Ornnicha Sathitakorn, Thanus Pienthong, Chatchai Mingmalairak, David K. Warren, David J. Weber Mar 2023

An Open Label Randomized Controlled Trial Of Ivermectin Plus Favipiravir-Based Standard Of Care Versus Favipiravir-Based Standard Of Care For Treatment Of Moderate Covid-19 In Thailand, Phahol Sarojvisut, Anucha Apisarnthanarak, Kittiya Jantarathaneewat, Ornnicha Sathitakorn, Thanus Pienthong, Chatchai Mingmalairak, David K. Warren, David J. Weber

2020-Current year OA Pubs

BACKGROUND: The role of ivermectin in the treatment of moderate coronavirus disease 2019 (COVID-19) is controversial. We performed an open label randomized controlled trial to evaluate the role of ivermectin plus favipiravir-based standard of care versus favipiravir-based standard of care for the treatment of moderate COVID-19 infection.

MATERIALS AND METHODS: An open-label randomized control trial was performed at Thammasat Field Hospital and Thammasat University Hospital from October 1st, 2021 to May 31st, 2022. Patients with moderate COVID-19 infections were randomized to the intervention (ivermectin plus favipiravir-based standard of care) or control group (favipiravir-based standard of care alone). Patients were followed …


The Menin Inhibitor Revumenib In Kmt2a-Rearranged Or Npm1-Mutant Leukaemia, Ghayas C Issa, John Dipersio, Shalini Shenoy, Et Al. Mar 2023

The Menin Inhibitor Revumenib In Kmt2a-Rearranged Or Npm1-Mutant Leukaemia, Ghayas C Issa, John Dipersio, Shalini Shenoy, Et Al.

2020-Current year OA Pubs

Targeting critical epigenetic regulators reverses aberrant transcription in cancer, thereby restoring normal tissue function


A Trpv4-Dependent Neuroimmune Axis In The Spinal Cord Promotes Neuropathic Pain, Xueming Hu, Lixia Du, Shenbin Liu, Zhou Lan, Kaikai Zang, Jing Feng, Yonghui Zhao, Xingliang Yang, Zili Xie, Peter L. Wang, Aaron M. Ver Heul, Lvyi Chen, Vijay K. Samineni, Yan-Qing Wang, Kory J. Lavine, Robert W. Gereau, Gregory F. Wu, Hongzhen Hu Mar 2023

A Trpv4-Dependent Neuroimmune Axis In The Spinal Cord Promotes Neuropathic Pain, Xueming Hu, Lixia Du, Shenbin Liu, Zhou Lan, Kaikai Zang, Jing Feng, Yonghui Zhao, Xingliang Yang, Zili Xie, Peter L. Wang, Aaron M. Ver Heul, Lvyi Chen, Vijay K. Samineni, Yan-Qing Wang, Kory J. Lavine, Robert W. Gereau, Gregory F. Wu, Hongzhen Hu

2020-Current year OA Pubs

Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood. Here, we show that genetic ablation or pharmacological blockade of transient receptor potential vanilloid type 4 (TRPV4) markedly attenuated neuropathic pain-like behaviors in a mouse model of spared nerve injury. Mechanistically, microglia-expressed TRPV4 mediated microglial activation and proliferation and promoted functional and structural plasticity of excitatory spinal neurons through release of lipocalin-2. Our results suggest …


Cnih3 Deletion Dysregulates Dorsal Hippocampal Transcription Across The Estrous Cycle, Bernard Mulvey, Hannah E. Frye, Tania Lintz, Stuart Fass, Eric Tycksen, Elliot C. Nelson, Jose A. Morón, Joseph D. Dougherty Mar 2023

Cnih3 Deletion Dysregulates Dorsal Hippocampal Transcription Across The Estrous Cycle, Bernard Mulvey, Hannah E. Frye, Tania Lintz, Stuart Fass, Eric Tycksen, Elliot C. Nelson, Jose A. Morón, Joseph D. Dougherty

2020-Current year OA Pubs

In females, the hippocampus, a critical brain region for coordination of learning, memory, and behavior, displays altered physiology and behavioral output across the estrous or menstrual cycle. However, the molecular effectors and cell types underlying these observed cyclic changes have only been partially characterized to date. Recently, profiling of mice null for the AMPA receptor trafficking gene


Association Of Hospital Resource Utilization With Neurodevelopmental Outcomes In Neonates With Hypoxic-Ischemic Encephalopathy, Vilmaris Quinones Cardona, Rakesh Rao, Amy Distler, Et Al. Mar 2023

Association Of Hospital Resource Utilization With Neurodevelopmental Outcomes In Neonates With Hypoxic-Ischemic Encephalopathy, Vilmaris Quinones Cardona, Rakesh Rao, Amy Distler, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Intercenter variation exists in the management of hypoxic-ischemic encephalopathy (HIE). It is unclear whether increased resource utilization translates into improved neurodevelopmental outcomes.

OBJECTIVE: To determine if higher resource utilization during the first 4 days of age, quantified by hospital costs, is associated with survival without neurodevelopmental impairment (NDI) among infants with HIE.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort analysis of neonates with HIE who underwent therapeutic hypothermia (TH) at US children's hospitals participating in the Children's Hospitals Neonatal Database between 2010 and 2016. Data were analyzed from December 2021 to December 2022.

EXPOSURES: Infants who survived to 4 days …


Harmonization And Standardization Of Nucleus Pulposus Cell Extraction And Culture Methods, Shaghayegh Basatvat, Liufang Jing, Lori Setton, Xiaohong Tan, Et Al. Mar 2023

Harmonization And Standardization Of Nucleus Pulposus Cell Extraction And Culture Methods, Shaghayegh Basatvat, Liufang Jing, Lori Setton, Xiaohong Tan, Et Al.

2020-Current year OA Pubs

BACKGROUND: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources.

METHODS: The most commonly applied methods for NP cell extraction, expansion, and re-differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, …


Tnk2/Ack1-Mediated Phosphorylation Of Atp5f1a (Atp Synthase F1 Subunit Alpha) Selectively Augments Survival Of Prostate Cancer While Engendering Mitochondrial Vulnerability, Surbhi Chouhan, Mithila Sawant, Cody Weimholt, Jingqin Luo, Robert W Sprung, Mailyn Terrado, David M Mueller, H Shelton Earp, Nupam P. Mahajan Mar 2023

Tnk2/Ack1-Mediated Phosphorylation Of Atp5f1a (Atp Synthase F1 Subunit Alpha) Selectively Augments Survival Of Prostate Cancer While Engendering Mitochondrial Vulnerability, Surbhi Chouhan, Mithila Sawant, Cody Weimholt, Jingqin Luo, Robert W Sprung, Mailyn Terrado, David M Mueller, H Shelton Earp, Nupam P. Mahajan

2020-Current year OA Pubs

The challenge of rapid macromolecular synthesis enforces the energy-hungry cancer cell mitochondria to switch their metabolic phenotypes, accomplished by activation of oncogenic tyrosine kinases. Precisely how kinase activity is directly exploited by cancer cell mitochondria to meet high-energy demand, remains to be deciphered. Here we show that a non-receptor tyrosine kinase, TNK2/ACK1 (tyrosine kinase non receptor 2), phosphorylated ATP5F1A (ATP synthase F1 subunit alpha) at Tyr243 and Tyr246 (Tyr200 and 203 in the mature protein, respectively) that not only increased the stability of complex V, but also increased mitochondrial energy output in cancer cells. Further, phospho-ATP5F1A (p-Y-ATP5F1A) prevented its binding …


The Er Protein Translocation Channel Subunit Sbh1 Controls Virulence Of Cryptococcus Neoformans, Felipe H. Santiago-Tirado, Thomas Hurtaux, Jennifer Geddes-Mcalister, Duy Nguyen, Volkhard Helms, Tamara L Doering, Karin Römisch Feb 2023

The Er Protein Translocation Channel Subunit Sbh1 Controls Virulence Of Cryptococcus Neoformans, Felipe H. Santiago-Tirado, Thomas Hurtaux, Jennifer Geddes-Mcalister, Duy Nguyen, Volkhard Helms, Tamara L Doering, Karin Römisch

2020-Current year OA Pubs

The fungal pathogen Cryptococcus neoformans is distinguished by a cell-wall-anchored polysaccharide capsule that is critical for virulence. Biogenesis of both cell wall and capsule relies on the secretory pathway. Protein secretion begins with polypeptide translocation across the endoplasmic reticulum (ER) membrane through a highly conserved channel formed by three proteins: Sec61, Sbh1, and Sss1. Sbh1, the most divergent, contains multiple phosphorylation sites, which may allow it to regulate entry into the secretory pathway in a species- and protein-specific manner. Absence of


Apical Secretory Glycoprotein Complex Contributes To Cell Attachment And Entry By Cryptosporidium Parvum, Marianna E. Akey, Rui Xu, Soumya Ravindran, Lisa Funkhouser-Jones, L. David Sibley Feb 2023

Apical Secretory Glycoprotein Complex Contributes To Cell Attachment And Entry By Cryptosporidium Parvum, Marianna E. Akey, Rui Xu, Soumya Ravindran, Lisa Funkhouser-Jones, L. David Sibley

2020-Current year OA Pubs

Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. Compared with those of related apicomplexan parasites, the processes of host cell attachment and invasion by C. parvum are poorly understood. The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. Here, we identified the antigens recognized by monoclonal antibody (MAb) 1A5, which stains the apical end of sporozoites and mature merozoites. Immunoprecipitation with MAb 1A5 followed by mass spectrometry …


Network Analysis Of Large-Scale Immgen And Tabula Muris Datasets Highlights Metabolic Diversity Of Tissue Mononuclear Phagocytes, Anastasiia Gainullina, Denis A Mogilenko, Li-Hao Huang, Ki-Wook Kim, Karen Krchma, Jun Wu, Geetika Bajpai, Peter Wang, Kyunghee Choi, Kory Lavine, Gwendalyn J Randolph, Alexey Sergushichev, Maxim N Artyomov, Et Al. Feb 2023

Network Analysis Of Large-Scale Immgen And Tabula Muris Datasets Highlights Metabolic Diversity Of Tissue Mononuclear Phagocytes, Anastasiia Gainullina, Denis A Mogilenko, Li-Hao Huang, Ki-Wook Kim, Karen Krchma, Jun Wu, Geetika Bajpai, Peter Wang, Kyunghee Choi, Kory Lavine, Gwendalyn J Randolph, Alexey Sergushichev, Maxim N Artyomov, Et Al.

2020-Current year OA Pubs

The diversity of mononuclear phagocyte (MNP) subpopulations across tissues is one of the key physiological characteristics of the immune system. Here, we focus on understanding the metabolic variability of MNPs through metabolic network analysis applied to three large-scale transcriptional datasets: we introduce (1) an ImmGen MNP open-source dataset of 337 samples across 26 tissues; (2) a myeloid subset of ImmGen Phase I dataset (202 MNP samples); and (3) a myeloid mouse single-cell RNA sequencing (scRNA-seq) dataset (51,364 cells) assembled based on Tabula Muris Senis. To analyze such large-scale datasets, we develop a network-based computational approach, genes and metabolites (GAM) clustering, …


A Fetal Tumor Suppressor Axis Abrogates Mll-Fusion-Driven Acute Myeloid Leukemia, Mohamed Eldeeb, Ouyang Yuan, Nicola Guzzi, Phuong Cao Thi Ngoc, Anna Konturek-Ciesla, Trine A Kristiansen, Sowndarya Muthukumar, Jeffrey Magee, Cristian Bellodi, Joan Yuan, David Bryder Feb 2023

A Fetal Tumor Suppressor Axis Abrogates Mll-Fusion-Driven Acute Myeloid Leukemia, Mohamed Eldeeb, Ouyang Yuan, Nicola Guzzi, Phuong Cao Thi Ngoc, Anna Konturek-Ciesla, Trine A Kristiansen, Sowndarya Muthukumar, Jeffrey Magee, Cristian Bellodi, Joan Yuan, David Bryder

2020-Current year OA Pubs

MLL-rearrangements (MLL-r) are recurrent genetic events in acute myeloid leukemia (AML) and frequently associate with poor prognosis. In infants, MLL-r can be sufficient to drive transformation. However, despite the prenatal origin of MLL-r in these patients, congenital leukemia is very rare with transformation usually occurring postnatally. The influence of prenatal signals on leukemogenesis, such as those mediated by the fetal-specific protein LIN28B, remains controversial. Here, using a dual-transgenic mouse model that co-expresses MLL-ENL and LIN28B, we investigate the impact of LIN28B on AML. LIN28B impedes the progression of MLL-r AML through compromised leukemia-initiating cell activity and suppression of MYB signaling. …


Mucosal And Systemic Neutralizing Antibodies To Norovirus Induced In Infant Mice Orally Inoculated With Recombinant Rotaviruses, Takahiro Kawagishi, Liliana Sánchez-Tacuba, Ningguo Feng, Veronica P Costantini, Ming Tan, Xi Jiang, Kim Y Green, Jan Vinjé, Siyuan Ding, Harry B Greenberg Feb 2023

Mucosal And Systemic Neutralizing Antibodies To Norovirus Induced In Infant Mice Orally Inoculated With Recombinant Rotaviruses, Takahiro Kawagishi, Liliana Sánchez-Tacuba, Ningguo Feng, Veronica P Costantini, Ming Tan, Xi Jiang, Kim Y Green, Jan Vinjé, Siyuan Ding, Harry B Greenberg

2020-Current year OA Pubs

Rotaviruses (RVs) preferentially replicate in the small intestine and frequently cause severe diarrheal disease, and the following enteric infection generally induces variable levels of protective systemic and mucosal immune responses in humans and other animals. Rhesus rotavirus (RRV) is a simian RV that was previously used as a human RV vaccine and has been extensively studied in mice. Although RRV replicates poorly in the suckling mouse intestine, infection induces a robust and protective antibody response. The recent availability of plasmid only-based RV reverse genetics systems has enabled the generation of recombinant RVs expressing foreign proteins. However, recombinant RVs have not …


Virology Under The Microscope-A Call For Rational Discourse, Felicia Goodrum, Carolina Lopez, Sean Whelan, Et Al. Feb 2023

Virology Under The Microscope-A Call For Rational Discourse, Felicia Goodrum, Carolina Lopez, Sean Whelan, Et Al.

2020-Current year OA Pubs

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled …


Single Cell Preparations Of Mycobacterium Tuberculosis Damage The Mycobacterial Envelope And Disrupt Macrophage Interactions, Ekansh Mittal, Andrew T Roth, Anushree Seth, Srikanth Singamaneni, Wandy Beatty, Jennifer A Philips Feb 2023

Single Cell Preparations Of Mycobacterium Tuberculosis Damage The Mycobacterial Envelope And Disrupt Macrophage Interactions, Ekansh Mittal, Andrew T Roth, Anushree Seth, Srikanth Singamaneni, Wandy Beatty, Jennifer A Philips

2020-Current year OA Pubs

For decades, investigators have studied the interaction of