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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


Clinical Outcomes After Reverse Shoulder Arthroplasty In Patients 60 Years Old And Younger; Medium-Term Results, Aaron M Chamberlain, Alexander W Aleem, Julianne A Sefko, Karen Steger-May, Jay D Keener Mar 2023

Clinical Outcomes After Reverse Shoulder Arthroplasty In Patients 60 Years Old And Younger; Medium-Term Results, Aaron M Chamberlain, Alexander W Aleem, Julianne A Sefko, Karen Steger-May, Jay D Keener

2020-Current year OA Pubs

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) has been well-described as a surgical solution to manage rotator cuff tear arthropathy in elderly, low demand paitents. As experience has increased along with improvements in technique and implant design, RTSA has become increasingly used to manage more varied pathologic conditions of the shoulder in younger, more active patients. This study evaluates outcomes in a consecutive series of patients aged 60 years old and younger after undergoing RTSA.

METHODS: There were 94 shoulders in 89 patients enrolled. Mean age of the cohort was 54.8 (range 18-60 years). Surgical indications included rotator cuff tear arthropathy, …


Computational Modeling Of The N-Back Task In The Abcd Study: Associations Of Drift Diffusion Model Parameters To Polygenic Scores Of Mental Disorders And Cardiometabolic Diseases, Mads L Pedersen, Dag Alnæs, Dennis Van Der Meer, Sara Fernandez-Cabello, Pierre Berthet, Andreas Dahl, Rikka Kjelkenes, Emanuel Schwarz, Wesley K Thompson, Deanna M Barch, Ole A Andreassen, Lars T Westlye Mar 2023

Computational Modeling Of The N-Back Task In The Abcd Study: Associations Of Drift Diffusion Model Parameters To Polygenic Scores Of Mental Disorders And Cardiometabolic Diseases, Mads L Pedersen, Dag Alnæs, Dennis Van Der Meer, Sara Fernandez-Cabello, Pierre Berthet, Andreas Dahl, Rikka Kjelkenes, Emanuel Schwarz, Wesley K Thompson, Deanna M Barch, Ole A Andreassen, Lars T Westlye

2020-Current year OA Pubs

BACKGROUND: Cognitive dysfunction is common in mental disorders and represents a potential risk factor in childhood. The nature and extent of associations between childhood cognitive function and polygenic risk for mental disorders is unclear. We applied computational modeling to gain insight into mechanistic processes underlying decision making and working memory in childhood and their associations with polygenic risk scores (PRSs) for mental disorders and comorbid cardiometabolic diseases.

METHODS: We used the drift diffusion model to infer latent computational processes underlying decision making and working memory during the n-back task in 3707 children ages 9 to 10 years from the Adolescent …


Aberrant Right Gastric Vein Mimicking Hepatic Spread Of Prostate Cancer On Psma-Pet/Ct, Genevieve C Muñoz, Tyler J Fraum Mar 2023

Aberrant Right Gastric Vein Mimicking Hepatic Spread Of Prostate Cancer On Psma-Pet/Ct, Genevieve C Muñoz, Tyler J Fraum

2020-Current year OA Pubs

Hepatic vasculature can exhibit a wide variety of variants, some of which may resemble pathologic findings. In this case, a 53-year-old man presenting for staging of biochemically recurrent prostatic adenocarcinoma was found to have focally increased prostate-specific membrane antigen (PSMA) tracer uptake on positron emission tomography (PET) imaging in hepatic segment IV. This finding was initially concerning for hepatic metastasis of the patient's primary prostate adenocarcinoma. However, the area of radiotracer uptake was not associated with a discrete lesion on CT, and the geographic morphology of the uptake raised the possibility of a vascular etiology. Magnetic resonance imaging (MRI) of …


Genomic Patterns Of Malignant Peripheral Nerve Sheath Tumor (Mpnst) Evolution Correlate With Clinical Outcome And Are Detectable In Cell-Free Dna, Isidro Cortes-Ciriano, Dana C Borcherding, Jeffrey J Szymanski, Angela C Hirbe, Et Al. Mar 2023

Genomic Patterns Of Malignant Peripheral Nerve Sheath Tumor (Mpnst) Evolution Correlate With Clinical Outcome And Are Detectable In Cell-Free Dna, Isidro Cortes-Ciriano, Dana C Borcherding, Jeffrey J Szymanski, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

UNLABELLED: Malignant peripheral nerve sheath tumor (MPNST), an aggressive soft-tissue sarcoma, occurs in people with neurofibromatosis type 1 (NF1) and sporadically. Whole-genome and multiregional exome sequencing, transcriptomic, and methylation profiling of 95 tumor samples revealed the order of genomic events in tumor evolution. Following biallelic inactivation of NF1, loss of CDKN2A or TP53 with or without inactivation of polycomb repressive complex 2 (PRC2) leads to extensive somatic copy-number aberrations (SCNA). Distinct pathways of tumor evolution are associated with inactivation of PRC2 genes and H3K27 trimethylation (H3K27me3) status. Tumors with H3K27me3 loss evolve through extensive chromosomal losses followed by whole-genome doubling …


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 …


Surgical Results Of The Lung Cancer Mutation Consortium 3 Trial: A Phase Ii Multicenter Single-Arm Study To Investigate The Efficacy And Safety Of Atezolizumab As Neoadjuvant Therapy In Patients With Stages Ib-Select Iiib Resectable Non-Small Cell Lung Cancer, Valerie W Rusch, G Alexander Patterson, Salama N Waqar, Et Al. Mar 2023

Surgical Results Of The Lung Cancer Mutation Consortium 3 Trial: A Phase Ii Multicenter Single-Arm Study To Investigate The Efficacy And Safety Of Atezolizumab As Neoadjuvant Therapy In Patients With Stages Ib-Select Iiib Resectable Non-Small Cell Lung Cancer, Valerie W Rusch, G Alexander Patterson, Salama N Waqar, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Multimodality treatment for resectable non-small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non-small cell lung cancer and promising preoperatively in small clinical trials for resectable non-small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery.

METHODS: Patients with stage IB to select IIIB resectable non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was …


Molecular Phenotyping Of Single Pancreatic Islet Leader Beta Cells By "Flash-Seq", Pauline Chabosseau, Fiona Yong, Luis F Delgadillo-Silva, Eun Young Lee, Rana Melhem, Shiying Li, Nidhi Gandhi, Jules Wastin, Livia Lopez Noriega, Isabelle Leclerc, Yusuf Ali, Jing W Hughes, Robert Sladek, Aida Martinez-Sanchez, Guy A Rutter Mar 2023

Molecular Phenotyping Of Single Pancreatic Islet Leader Beta Cells By "Flash-Seq", Pauline Chabosseau, Fiona Yong, Luis F Delgadillo-Silva, Eun Young Lee, Rana Melhem, Shiying Li, Nidhi Gandhi, Jules Wastin, Livia Lopez Noriega, Isabelle Leclerc, Yusuf Ali, Jing W Hughes, Robert Sladek, Aida Martinez-Sanchez, Guy A Rutter

2020-Current year OA Pubs

AIMS: Spatially-organized increases in cytosolic Ca

MAIN METHODS: High speed confocal Ca

KEY FINDINGS: Distinct Ca

SIGNIFICANCE: The existence of both a discrete transcriptome and unique localisation implies a role for these features in defining the specialized function of leaders. These data also raise the possibility that localised signalling between delta and leader cells contributes to the initiation and propagation of islet Ca


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 …


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 …


Selective Dorsal Rhizotomy For Treatment Of Spasticity After Hemispherectomy In Children: A Case Report, Ts Park, Susan Joh, Matthew D. Smyth, Nicole L. Meyer, Deanna M. Walter Mar 2023

Selective Dorsal Rhizotomy For Treatment Of Spasticity After Hemispherectomy In Children: A Case Report, Ts Park, Susan Joh, Matthew D. Smyth, Nicole L. Meyer, Deanna M. Walter

2020-Current year OA Pubs

Performing a hemispherotomy or hemispherectomy is known to treat medically intractable epilepsy successfully, yet contralateral hemiparesis and increased muscle tone follow the epilepsy surgery. Spasticity and coexisting dystonia presumably cause the increased muscle tone in the lower extremity on the opposite side of epilepsy surgery. However, the extent of the role of spasticity and dystonia in high muscle tone is unknown. A selective dorsal rhizotomy is performed to reduce spasticity. If a selective dorsal rhizotomy is performed in the affected patient and muscle tone is reduced, the high muscle tone is not due to dystonia. Two children, who previously underwent …


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 …


Nitric Oxide-Driven Modifications Of Lipoic Arm Inhibit Α-Ketoacid Dehydrogenases, Gretchen L Seim, Steven V John, Nicholas L Arp, Zixiang Fang, David J Pagliarini, Jing Fan Mar 2023

Nitric Oxide-Driven Modifications Of Lipoic Arm Inhibit Α-Ketoacid Dehydrogenases, Gretchen L Seim, Steven V John, Nicholas L Arp, Zixiang Fang, David J Pagliarini, Jing Fan

2020-Current year OA Pubs

Pyruvate dehydrogenase complex (PDHC) and oxoglutarate dehydrogenase complex (OGDC), which belong to the mitochondrial α-ketoacid dehydrogenase family, play crucial roles in cellular metabolism. These multi-subunit enzyme complexes use lipoic arms covalently attached to their E2 subunits to transfer an acyl group to coenzyme A (CoA). Here, we report a novel mechanism capable of substantially inhibiting PDHC and OGDC: reactive nitrogen species (RNS) can covalently modify the thiols on their lipoic arms, generating a series of adducts that block catalytic activity. S-Nitroso-CoA, a product between RNS and the E2 subunit's natural substrate, CoA, can efficiently deliver these modifications onto the lipoic …


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 …


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, …


Zika Virus Spreads Through Infection Of Lymph Node-Resident Macrophages, Glennys V Reynoso, Autumn C Holmes, Yael Alippe, Michael S Diamond, Et Al. Feb 2023

Zika Virus Spreads Through Infection Of Lymph Node-Resident Macrophages, Glennys V Reynoso, Autumn C Holmes, Yael Alippe, Michael S Diamond, Et Al.

2020-Current year OA Pubs

To disseminate through the body, Zika virus (ZIKV) is thought to exploit the mobility of myeloid cells, in particular monocytes and dendritic cells. However, the timing and mechanisms underlying shuttling of the virus by immune cells remains unclear. To understand the early steps in ZIKV transit from the skin, at different time points, we spatially mapped ZIKV infection in lymph nodes (LNs), an intermediary site en route to the blood. Contrary to prevailing hypotheses, migratory immune cells are not required for the virus to reach the LNs or blood. Instead, ZIKV rapidly infects a subset of sessile CD169


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 …


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 …


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


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. …


Engineering A Modular 44ti/44sc Generator: Eluate Evaluation In Preclinical Models And Estimation Of Human Radiation Dosimetry, Nadia Benabdallah, Hanwen Zhang, Ryan Unnerstall, Amanda Fears, Lucy Summer, Michael Fassbender, Buck E Rodgers, Diane Abou, Valery Radchenko, Daniel L J Thorek Feb 2023

Engineering A Modular 44ti/44sc Generator: Eluate Evaluation In Preclinical Models And Estimation Of Human Radiation Dosimetry, Nadia Benabdallah, Hanwen Zhang, Ryan Unnerstall, Amanda Fears, Lucy Summer, Michael Fassbender, Buck E Rodgers, Diane Abou, Valery Radchenko, Daniel L J Thorek

2020-Current year OA Pubs

BACKGROUND:

METHODS:

RESULTS:

CONCLUSIONS: A clinical-scale


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


Care Of Bullet-Related Injuries: A Cross-Sectional Study Of Instructions And Prescriptions Provided On Discharge From The Emergency Department, Jane M. Hayes, L J. Punch, Kristen L. Mueller Feb 2023

Care Of Bullet-Related Injuries: A Cross-Sectional Study Of Instructions And Prescriptions Provided On Discharge From The Emergency Department, Jane M. Hayes, L J. Punch, Kristen L. Mueller

2020-Current year OA Pubs

INTRODUCTION: There are more than 80,000 emergency department (ED) visits for non-fatal bullet-related injuries (BRI) per year in the United States. Approximately half of these patients are discharged home from the ED. Our objective in this study was to characterize the discharge instructions, prescriptions, and follow-up plans provided to patients discharged from the ED after BRI.

METHODS: This was a single-center, cross-sectional study of the first 100 consecutive patients who presented to an urban, academic, Level I trauma center ED with an acute BRI beginning on January 1, 2020. We queried the electronic health record for patient demographics, insurance status, …


Long-Term Intensive Endurance Exercise Training Is Associated To Reduced Markers Of Cellular Senescence In The Colon Mucosa Of Older Adults, Marco Demaria, Beatrice Bertozzi, Nicola Veronese, Francesco Spelta, Edda Cava, Valeria Tosti, Laura Piccio, Dayna S Early, Luigi Fontana Feb 2023

Long-Term Intensive Endurance Exercise Training Is Associated To Reduced Markers Of Cellular Senescence In The Colon Mucosa Of Older Adults, Marco Demaria, Beatrice Bertozzi, Nicola Veronese, Francesco Spelta, Edda Cava, Valeria Tosti, Laura Piccio, Dayna S Early, Luigi Fontana

2020-Current year OA Pubs

Regular endurance exercise training is an effective intervention for the maintenance of metabolic health and the prevention of many age-associated chronic diseases. Several metabolic and inflammatory factors are involved in the health-promoting effects of exercise training, but regulatory mechanisms remain poorly understood. Cellular senescence-a state of irreversible growth arrest-is considered a basic mechanism of aging. Senescent cells accumulate over time and promote a variety of age-related pathologies from neurodegenerative disorders to cancer. Whether long-term intensive exercise training affect the accumulation of age-associated cellular senescence is still unclear. Here, we show that the classical senescence markers p16 and IL-6 were markedly …


Orthodenticle Homeobox 2 Is Transported To Lysosomes By Nuclear Budding Vesicles, Jun Woo Park, Eun Jung Lee, Eunyoung Moon, Hong-Lim Kim, In-Beom Kim, Didier Hodzic, Namsuk Kim, Hee-Seok Kweon, Jin Woo Kim Feb 2023

Orthodenticle Homeobox 2 Is Transported To Lysosomes By Nuclear Budding Vesicles, Jun Woo Park, Eun Jung Lee, Eunyoung Moon, Hong-Lim Kim, In-Beom Kim, Didier Hodzic, Namsuk Kim, Hee-Seok Kweon, Jin Woo Kim

2020-Current year OA Pubs

Transcription factors (TFs) are transported from the cytoplasm to the nucleus and disappear from the nucleus after they regulate gene expression. Here, we discover an unconventional nuclear export of the TF, orthodenticle homeobox 2 (OTX2), in nuclear budding vesicles, which transport OTX2 to the lysosome. We further find that torsin1a (Tor1a) is responsible for scission of the inner nuclear vesicle, which captures OTX2 using the LINC complex. Consistent with this, in cells expressing an ATPase-inactive Tor1aΔE mutant and the LINC (linker of nucleoskeleton and cytoskeleton) breaker KASH2, OTX2 accumulated and formed aggregates in the nucleus. Consequently, in the mice expressing …


Trpv1-Mediated Sonogenetic Neuromodulation Of Motor Cortex In Freely Moving Mice, Kevin Xu, Yaoheng Yang, Zhongtao Hu, Yimei Yue, Yan Gong, Jianmin Cui, Joseph P Culver, Michael R Bruchas, Hong Chen Feb 2023

Trpv1-Mediated Sonogenetic Neuromodulation Of Motor Cortex In Freely Moving Mice, Kevin Xu, Yaoheng Yang, Zhongtao Hu, Yimei Yue, Yan Gong, Jianmin Cui, Joseph P Culver, Michael R Bruchas, Hong Chen

2020-Current year OA Pubs

No abstract provided.


Membrane Phospholipids Control Gating Of The Mechanosensitive Potassium Leak Channel Trek1, Philipp A M Schmidpeter, John T Petroff 2nd, Leila Khajoueinejad, Aboubacar Wague, Cheryl Frankfater, Wayland W L Cheng, Crina M Nimigean, Paul M Riegelhaupt Feb 2023

Membrane Phospholipids Control Gating Of The Mechanosensitive Potassium Leak Channel Trek1, Philipp A M Schmidpeter, John T Petroff 2nd, Leila Khajoueinejad, Aboubacar Wague, Cheryl Frankfater, Wayland W L Cheng, Crina M Nimigean, Paul M Riegelhaupt

2020-Current year OA Pubs

Tandem pore domain (K2P) potassium channels modulate resting membrane potentials and shape cellular excitability. For the mechanosensitive subfamily of K2Ps, the composition of phospholipids within the bilayer strongly influences channel activity. To examine the molecular details of K2P lipid modulation, we solved cryo-EM structures of the TREK1 K2P channel bound to either the anionic lipid phosphatidic acid (PA) or the zwitterionic lipid phosphatidylethanolamine (PE). At the extracellular face of TREK1, a PA lipid inserts its hydrocarbon tail into a pocket behind the selectivity filter, causing a structural rearrangement that recapitulates mutations and pharmacology known to activate TREK1. At the cytoplasmic …


Mitochondrial Phosphatidylethanolamine Modulates Ucp1 To Promote Brown Adipose Thermogenesis, Jordan M Johnson, Irfan J Lodhi, Et Al. Feb 2023

Mitochondrial Phosphatidylethanolamine Modulates Ucp1 To Promote Brown Adipose Thermogenesis, Jordan M Johnson, Irfan J Lodhi, Et Al.

2020-Current year OA Pubs

Thermogenesis by uncoupling protein 1 (UCP1) is one of the primary mechanisms by which brown adipose tissue (BAT) increases energy expenditure. UCP1 resides in the inner mitochondrial membrane (IMM), where it dissipates membrane potential independent of adenosine triphosphate (ATP) synthase. Here, we provide evidence that phosphatidylethanolamine (PE) modulates UCP1-dependent proton conductance across the IMM to modulate thermogenesis. Mitochondrial lipidomic analyses revealed PE as a signature molecule whose abundance bidirectionally responds to changes in thermogenic burden. Reduction in mitochondrial PE by deletion of phosphatidylserine decarboxylase (PSD) made mice cold intolerant and insensitive to β3 adrenergic receptor agonist-induced increase in whole-body oxygen …


[18f]Tosyl Fluoride As A Versatile [18f]Fluoride Source For The Preparation Of 18f-Labeled Radiopharmaceuticals, Dong Zhou, Wenhua Chu, Jinbin Xu, Sally Schwarz, John A Katzenellenbogen Feb 2023

[18f]Tosyl Fluoride As A Versatile [18f]Fluoride Source For The Preparation Of 18f-Labeled Radiopharmaceuticals, Dong Zhou, Wenhua Chu, Jinbin Xu, Sally Schwarz, John A Katzenellenbogen

2020-Current year OA Pubs

Positron emission tomography (PET) is an in vivo imaging technology that utilizes positron-emitting radioisotope-labeled compounds as PET radiotracers that are commonly used in clinic and in various research areas, including oncology, cardiology, and neurology. Fluorine-18 is the most widely used PET-radionuclide and commonly produced by proton bombardment of


Child Adult Relationship Enhancement In Primary Care (Pricare): Study Design/Protocol For A Randomized Trial Of A Primary Care-Based Group Parenting Intervention To Prevent Child Maltreatment, Samantha Schilling, Byron J Powell, Paul W Stewart, Joanne N Wood Feb 2023

Child Adult Relationship Enhancement In Primary Care (Pricare): Study Design/Protocol For A Randomized Trial Of A Primary Care-Based Group Parenting Intervention To Prevent Child Maltreatment, Samantha Schilling, Byron J Powell, Paul W Stewart, Joanne N Wood

2020-Current year OA Pubs

BACKGROUND: Child maltreatment (CM) is a pervasive public health problem and there is a critical need for brief, effective, scalable prevention programs. Problematic parent-child relationships lie at the heart of CM. Parents who maltreat their children are more likely to have punitive parenting styles characterized by high rates of negative interaction and ineffective discipline strategies with over-reliance on punishment. Thus, parenting interventions that strengthen parent-child relationships, teach positive discipline techniques, decrease harsh parenting, and decrease child behavioral problems hold promise as CM prevention strategies. Challenges in engaging parents, particularly low-income and minority parents, and a lack of knowledge regarding effective …