Digital Commons Network^™

Lipid Nanodisc Scaffold And Size Alter The Structure Of A Pentameric Ligand-Gated Ion Channel, Vikram Dalal, Mark J Arcario, John T Petroff 2nd, Brandon K Tan, Noah M Dietzen, Michael J Rau, James A J Fitzpatrick, Grace Brannigan, Wayland W L Cheng

2020-Current year OA Pubs

Lipid nanodiscs have become a standard tool for studying membrane proteins, including using single particle cryo-electron microscopy (cryo-EM). We find that reconstituting the pentameric ligand-gated ion channel (pLGIC), Erwinia ligand-gated ion channel (ELIC), in different nanodiscs produces distinct structures by cryo-EM. The effect of the nanodisc on ELIC structure extends to the extracellular domain and agonist binding site. Additionally, molecular dynamic simulations indicate that nanodiscs of different size impact ELIC structure and that the nanodisc scaffold directly interacts with ELIC. These findings suggest that the nanodisc plays a crucial role in determining the structure of pLGICs, and that reconstitution of …

Fatty Acid Synthesis Suppresses Dietary Polyunsaturated Fatty Acid Use, Anna Worthmann, Sangeeta Adak, Clay F Semenkovich, Et Al.

2020-Current year OA Pubs

Dietary polyunsaturated fatty acids (PUFA) are increasingly recognized for their health benefits, whereas a high production of endogenous fatty acids - a process called de novo lipogenesis (DNL) - is closely linked to metabolic diseases. Determinants of PUFA incorporation into complex lipids are insufficiently understood and may influence the onset and progression of metabolic diseases. Here we show that fatty acid synthase (FASN), the key enzyme of DNL, critically determines the use of dietary PUFA in mice and humans. Moreover, the combination of FASN inhibition and PUFA-supplementation decreases liver triacylglycerols (TAG) in mice fed with high-fat diet. Mechanistically, FASN inhibition …

Genome-Wide And Targeted Crispr Screens Identify Rnf213 As A Mediator Of Interferon Gamma-Dependent Pathogen Restriction In Human Cells, Sumit K Matta, Hinissan P Kohio, Pallavi Chandra, Adam Brown, John G Doench, Jennifer A Philips, Siyuan Ding, L David Sibley

2020-Current year OA Pubs

To define cellular immunity to the intracellular pathogen

A Dataset Of Digital Holograms Of Normal And Thalassemic Cells, Vahid Abbasian, Arash Darafsheh

2020-Current year OA Pubs

Digital holographic microscopy (DHM) is an intriguing medical diagnostic tool due to its label-free and quantitative nature, providing high-contrast images of phase samples. By capturing both intensity and phase information, DHM enables the numerical reconstruction of quantitative phase images. However, the lateral resolution is limited by the diffraction limit, which prompted the recent suggestion of microsphere-assisted DHM to enhance the DHM resolution straightforwardly. The use of such a technique as a medical diagnostic tool requires testing and validation of the proposed assays to prove their feasibility and viability. This paper publishes 760 and 609 microsphere-assisted DHM images of normal and …

Pacs Viewbook 2024-2025, Program In Audiology And Communication Sciences

PACS News

No abstract provided.

Clinical Research Coordinator Orientation Manual With Accompanying New Employee Checklist For Managers, Kaitlin Moore, Jean Flanagan, Tarisa Mantia, Kristin Geile, Kelly Koogler, Sarah Fowler-Dixon

HRPO Publications

No abstract provided.

Washington University Magazine, August 2024

Washington University Magazine

No abstract provided.

Washington University Magazine, April 2024

Washington University Magazine

No abstract provided.

The Molecular Landscape Of Sepsis Severity In Infants: Enhanced Coagulation, Innate Immunity, And T Cell Repression, Susie Shih Yin Huang, Mohammed Toufiq, Pirooz Eghtesady, Nicholas Van Panhuys, Mathieu Garand

2020-Current year OA Pubs

INTRODUCTION: Sepsis remains a major cause of mortality and morbidity in infants. In recent years, several gene marker strategies for the early identification of sepsis have been proposed but only a few have been independently validated for adult cohorts and applicability to infant sepsis remains unclear. Biomarkers to assess disease severity and risks of shock also represent an important unmet need.

METHODS: To elucidate characteristics driving sepsis in infants, we assembled a multi-transcriptomic dataset from public microarray datasets originating from five independent studies pertaining to bacterial sepsis in infant < 6-months of age (total n=335). We utilized a COmbat co-normalization strategy to enable comparative evaluation across multiple studies while preserving the relationship between cases and controls.

RESULTS: We found good concordance with only two out of seven …

Plasma Mirna Expression Profile In Pediatric Pineal Pure Germinomas, Mona Fakhry, Moatasem Elayadi, Mariam G Elzayat, Omar Samir, Eslam Maher, Hala Taha, Mohamed El-Beltagy, Amal Refaat, Manal Zamzam, Mohamed S Abdelbaki, Ahmed A Sayed, Mark Kieran, Alaa Elhaddad

2020-Current year OA Pubs

BACKGROUND: Pure germinomas account for 40% of pineal tumors and are characterized by the lack of appreciable tumor markers, thus requiring a tumor biopsy for diagnosis. MicroRNAs (miRNA) have emerged as potential non-invasive biomarkers for germ cell tumors and may facilitate the non-invasive diagnosis of pure pineal germinomas.

MATERIAL AND METHODS: A retrospective chart review was performed on all patients treated at the Children's Cancer Hospital Egypt diagnosed with a pineal region tumor between June 2013 and March 2021 for whom a research blood sample was available. Plasma samples were profiled for miRNA expression, and DESeq2 was used to compare …

Incidence And Risk Factors For Bone Metastases At Presentation In Solid Tumors, Brendan J Knapp, Giordano F Cittolin-Santos, Mary E Flanagan, Nikhil Grandhi, Feng Gao, Pamela P Samson, Ramaswamy Govindan, Daniel Morgensztern

2020-Current year OA Pubs

INTRODUCTION: Bone metastases are associated with increased morbidity and decreased quality of life in patients with solid tumors. Identifying patients at increased risk of bone metastases at diagnosis could lead to earlier interventions. We sought to retrospectively identify the incidence and predictive factors for bone metastases at initial diagnosis in a large population-based dataset.

METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients 18 years-old or older diagnosed with solid cancers from 2010 to 2019. Patients with hematologic malignancies and primary tumors of the bone were excluded. We calculated the incidence and predictive factors for …

Membrane Potential Hyperpolarization: A Critical Factor In Acrosomal Exocytosis And Fertilization In Sperm Within The Female Reproductive Tract, Paula A Balestrini, Valeria Sulzyk, Martina Jabloñski, Liza J Schiavi-Ehrenhaus, Soledad N González, Juan J Ferreira, Matías D Gómez-Elías, Pablo Pomata, Guillermina M Luque, Dario Krapf, Patricia S Cuasnicu, Celia M Santi, Mariano G Buffone

2020-Current year OA Pubs

Hyperpolarization of the membrane potential (Em), a phenomenon regulated by SLO3 channels, stands as a central feature in sperm capacitation-a crucial process conferring upon sperm the ability to fertilize the oocyte.

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S Gross, Deanna M. Barch, Andrew C. Heath, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …

Non-Invasive Auricular Vagus Nerve Stimulation For Subarachnoid Hemorrhage (Navsah): Protocol For A Prospective, Triple-Blinded, Randomized Controlled Trial, Anna Huguenard, Gansheng Tan, Gabrielle Johnson, Markus Adamek, Andrew Coxon, Terrance Kummer, Joshua Osbun, Ananth Vellimana, David Limbrick, Gregory Zipfel, Peter Brunner, Eric Leuthardt

2020-Current year OA Pubs

BACKGROUND: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive …

Disruption Of The Nascent Polypeptide-Associated Complex Leads To Reduced Polyglutamine Aggregation And Toxicity, Leeran B. Dublin-Ryan, Ankan K. Bhadra, Heather L. True

2020-Current year OA Pubs

The nascent polypeptide-associate complex (NAC) is a heterodimeric chaperone complex that binds near the ribosome exit tunnel and is the first point of chaperone contact for newly synthesized proteins. Deletion of the NAC induces embryonic lethality in many multi-cellular organisms. Previous work has shown that the deletion of the NAC rescues cells from prion-induced cytotoxicity. This counterintuitive result led us to hypothesize that NAC disruption would improve viability in cells expressing human misfolding proteins. Here, we show that NAC disruption improves viability in cells expressing expanded polyglutamine and also leads to delayed and reduced aggregation of expanded polyglutamine and changes …

Performance Of The Lumipulse Plasma Aβ42/40 And Ptau181 Immunoassays In The Detection Of Amyloid Pathology, Daniel J Figdore, Heather J Wiste, Joshua A Bornhorst, Randall J Bateman, Yan Li, Jonathan Graff-Radford, David S Knopman, Prashanthi Vemuri, Val J Lowe, Clifford R Jack Jr, Ronald C Petersen, Alicia Algeciras-Schimnich

2020-Current year OA Pubs

INTRODUCTION: This study evaluated the performance of the Lumipulse plasma beta-amyloid (Aβ) 42/40 and pTau181 compared to other assays to detect an abnormal amyloid-positron emission tomography (PET).

METHODS: Plasma samples from cognitively unimpaired (

RESULTS: Lumipulse and IP-MS Aβ42/40 exhibited the highest diagnostic accuracy for detecting an abnormal amyloid-PET (areas under the curve [AUCs] of 0.81 and 0.84, respectively). The Lumipulse and Simoa pTau181 assays exhibited lower performance (AUCs of 0.74 and 0.72, respectively). The Simoa Aβ42/40 assay demonstrated the lowest diagnostic accuracy (AUC 0.57). Combining Aβ42/40 and pTau181 did not significantly improve performance over Aβ42/40 alone for Lumipulse (AUC …

An Internet Mantram Repetition Program To Promote Well-Being In Breast Cancer Survivors: A Feasibility Randomized Controlled Trial, Jennifer M Hulett, An-Lin Cheng, Jill E Bormann, Allison B Anbari, Jane M Armer, Brooke M Hartman, B Ann Bettencourt, Leeanne B Sherwin, Edie L Sperling, Natsayakarn Narkthong, Carol Reinero, Hans Rindt, Kathy Schreiber, Lindsay L Peterson, Emily Albright

2020-Current year OA Pubs

No abstract provided.

Sc2menetdrug: A Computational Tool To Uncover Inter-Cell Signaling Targets And Identify Relevant Drugs Based On Single Cell Rna-Seq Data, Jiarui Feng, S. Peter Goedegebuure, Amanda Zeng, Ye Bi, Ting Wang, Philip Payne, Li Ding, David Denardo, William Hawkins, Ryan C. Fields, Fuhai Li

2020-Current year OA Pubs

Single-cell RNA sequencing (scRNA-seq) is a powerful technology to investigate the transcriptional programs in stromal, immune, and disease cells, like tumor cells or neurons within the Alzheimer's Disease (AD) brain or tumor microenvironment (ME) or niche. Cell-cell communications within ME play important roles in disease progression and immunotherapy response and are novel and critical therapeutic targets. Though many tools of scRNA-seq analysis have been developed to investigate the heterogeneity and sub-populations of cells, few were designed for uncovering cell-cell communications of ME and predicting the potentially effective drugs to inhibit the communications. Moreover, the data analysis processes of discovering signaling …

The Forkhead Transcription Factor Foxj1 Controls Vertebrate Olfactory Cilia Biogenesis And Sensory Neuron Differentiation, Dheeraj Rayamajhi, Steven L. Brody, Et Al.

2020-Current year OA Pubs

In vertebrates, olfactory receptors localize on multiple cilia elaborated on dendritic knobs of olfactory sensory neurons (OSNs). Although olfactory cilia dysfunction can cause anosmia, how their differentiation is programmed at the transcriptional level has remained largely unexplored. We discovered in zebrafish and mice that Foxj1, a forkhead domain-containing transcription factor traditionally linked with motile cilia biogenesis, is expressed in OSNs and required for olfactory epithelium (OE) formation. In keeping with the immotile nature of olfactory cilia, we observed that ciliary motility genes are repressed in zebrafish, mouse, and human OSNs. Strikingly, we also found that besides ciliogenesis, Foxj1 controls the …

Transcription Factor Interactions Explain The Context-Dependent Activity Of Crx Binding Sites, Kaiser J. Loell, Ryan Z. Friedman, Connie A. Myers, Joseph C. Corbo, Barak A. Cohen, Michael A. White

2020-Current year OA Pubs

The effects of transcription factor binding sites (TFBSs) on the activity of a cis-regulatory element (CRE) depend on the local sequence context. In rod photoreceptors, binding sites for the transcription factor (TF) Cone-rod homeobox (CRX) occur in both enhancers and silencers, but the sequence context that determines whether CRX binding sites contribute to activation or repression of transcription is not understood. To investigate the context-dependent activity of CRX sites, we fit neural network-based models to the activities of synthetic CREs composed of photoreceptor TFBSs. The models revealed that CRX binding sites consistently make positive, independent contributions to CRE activity, while …

Control Intervention Design For Preclinical And Clinical Trials: Consensus-Based Core Recommendations From The Third Stroke Recovery And Rehabilitation Roundtable, Kathryn S Hayward, Emily J Dalton, Jessica Barth, Marian Brady, Leora R Cherney, Leonid Churilov, Andrew N Clarkson, Jesse Dawson, Sean P Dukelow, Peter Feys, Maree Hackett, Steve R Zeiler, Catherine E Lang

2020-Current year OA Pubs

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was …

Examining Associations Between Genetic And Neural Risk For Externalizing Behaviors In Adolescence And Early Adulthood, Sarah J Brislin, Andrey P Anokhin, Et Al.

2020-Current year OA Pubs

BACKGROUND: Researchers have identified genetic and neural risk factors for externalizing behaviors. However, it has not yet been determined if genetic liability is conferred in part through associations with more proximal neurophysiological risk markers.

METHODS: Participants from the Collaborative Study on the Genetics of Alcoholism, a large, family-based study of alcohol use disorders were genotyped and polygenic scores for externalizing (EXT PGS) were calculated. Associations with target P3 amplitude from a visual oddball task (P3) and broad endorsement of externalizing behaviors (indexed via self-report of alcohol and cannabis use, and antisocial behavior) were assessed in participants of European (EA;

RESULTS: …

The Cousa Objective: A Long-Working Distance Air Objective For Multiphoton Imaging In Vivo, Che-Hang Yu, Jinkyung Kim, Et Al.

2020-Current year OA Pubs

Multiphoton microscopy can resolve fluorescent structures and dynamics deep in scattering tissue and has transformed neural imaging, but applying this technique in vivo can be limited by the mechanical and optical constraints of conventional objectives. Short working distance objectives can collide with compact surgical windows or other instrumentation and preclude imaging. Here we present an ultra-long working distance (20 mm) air objective called the Cousa objective. It is optimized for performance across multiphoton imaging wavelengths, offers a more than 4 mm

Overall And Non- Lung Cancer Incidence And Mortality In The National Lung Screening Trial: Opportunities For Multi-Cancer Early Detection, Alpa V. Patel, Ellen T. Chang, Allan Hackshaw, Sam M. Janes, Diana S.M. Buist, Earl Hubbell, Christina A. Clarke, Graham A. Colditz

2020-Current year OA Pubs

No abstract provided.

Traversing The Bench To Bedside Journey For Inkt Cell Therapies, Julie O'Neal, Melissa Mavers, Reyka G Jayasinghe, John F Dipersio

2020-Current year OA Pubs

Invariant natural killer T (iNKT) cells are immune cells that harness properties of both the innate and adaptive immune system and exert multiple functions critical for the control of various diseases. Prevention of graft-versus-host disease (GVHD) by iNKT cells has been demonstrated in mouse models and in correlative human studies in which high iNKT cell content in the donor graft is associated with reduced GVHD in the setting of allogeneic hematopoietic stem cell transplants. This suggests that approaches to increase the number of iNKT cells in the setting of an allogeneic transplant may reduce GVHD. iNKT cells can also induce …

Elevating Voices, Addressing Depression, Toxic Stress, And Equity Through Group Prenatal Care: A Pilot Study, Shannon N Lenze, Kelly Mckay-Gist, Rachel Paul, Melissa Tepe, Katherine Mathews, Sara Kornfield, Cheron Phillips, Richelle Smith, Amanda Stoermer, Ebony B Carter

2020-Current year OA Pubs

INTRODUCTION: Elevating Voices, Addressing Depression, Toxic Stress and Equity (EleVATE) is a group prenatal care (GC) model designed to improve pregnancy outcomes and promote health equity for Black birthing people. This article outlines the foundational community-engaged process to develop EleVATE GC and pilot study results.

METHODS: We used community-based participatory research principles and the Ferguson Commission Report to guide creation of EleVATE GC. The intervention, designed by and for Black birthing people, centers trauma-informed care, antiracism, and integrates behavioral health strategies into group prenatal care to address unmet mental health needs. Using a convenience sample of patients seeking care at …

Neurosteroids: Mechanistic Considerations And Clinical Prospects, Jamie L Maguire, Steven Mennerick

2020-Current year OA Pubs

Like other classes of treatments described in this issue's section, neuroactive steroids have been studied for decades but have risen as a new class of rapid-acting, durable antidepressants with a distinct mechanism of action from previous antidepressant treatments and from other compounds covered in this issue. Neuroactive steroids are natural derivatives of progesterone but are proving effective as exogenous treatments. The best understood mechanism is that of positive allosteric modulation of GABA

The Type Ii Raf Inhibitor Tovorafenib In Relapsed/Refractory Pediatric Low-Grade Glioma: The Phase 2 Firefly-1 Trial, Lindsay B Kilburn, Mohamed S Abdelbaki, Et Al.

2020-Current year OA Pubs

BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 (n = 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system-penetrant, type II RAF inhibitor tovorafenib (420 mg m

A Global Multicohort Study To Map Subcortical Brain Development And Cognition In Infancy And Early Childhood, Ann M Alex, Kelly Botteron, Et Al.

2020-Current year OA Pubs

The human brain grows quickly during infancy and early childhood, but factors influencing brain maturation in this period remain poorly understood. To address this gap, we harmonized data from eight diverse cohorts, creating one of the largest pediatric neuroimaging datasets to date focused on birth to 6 years of age. We mapped the developmental trajectory of intracranial and subcortical volumes in ∼2,000 children and studied how sociodemographic factors and adverse birth outcomes influence brain structure and cognition. The amygdala was the first subcortical volume to mature, whereas the thalamus exhibited protracted development. Males had larger brain volumes than females, and …

Development, Usability, And Preliminary Efficacy Of A Virtual Reality Experience To Promote Healthy Lifestyle Behaviors In Children: Pilot Randomized Controlled Trial, Lauren A. Fowler, Melissa M. Vázquez, Bianca Depietro, Denise E. Wilfley, Ellen E. Fitzsimmons-Craft

2020-Current year OA Pubs

BACKGROUND: Virtual reality (VR) shows promise for supporting behavior change in children. This study used user-centered design to translate key tenets of behavioral health interventions into VR for children aged 6-12 years and their caregivers and examined the feasibility, acceptability, and preliminary efficacy of the VR experience in a pilot parallel, two-group randomized controlled trial (RCT).

METHODS: The VR experience incorporates psychoeducational content from evidence-based behavioral health interventions using voiceover and an interactive go-kart game related to the concepts of "food as fuel" and nutrition guidelines. Study 1 involved usability testing with n=5 child-caregiver dyads, which informed technical and content …